IGF-1 Receptor Mediates ROS in Mice

July 26, 2003; As reported by David E. Duncan, the author of five books, in his article "The Pursuit of Longevity: Long-Lived Worms Tantalize Researchers with the Promise of Extended Life. In the Meantime Though, They Suggest Cures for Chronic Diseases of Old Age," Acumen Journal of Sciences, Vol. 1, No. 2, pp. 40-6 (August/September 2003).

Martin Holzenberger,* Joëlle Dupont,***** Bertrand Ducos,* Patricia Leneuve,* Alain Géloën,*** Patrick C. Even,**** Pascale Cervera,** and Yves Le Bouc,*
"IGF-1 Receptor Regulates Lifespan and Resistance to Oxidative Stress in Mice,"
Nature, Vol. 421, pp.182-7 (January 9, 2003).
_____________________________________________
* Institut National de la Santé et de la Recherche Médicale U515
Hôpital Saint-Antoine
75571 Paris 12, FRANCE
** Service d'Anatomie et de Cytologie Pathologiques
Hôpital Saint-Antoine
75571 Paris 12, FRANCE
***** Institut National de la Recherche Agronomique
37380 Nouzilly, FRANCE
*** Institut National de la Santé et de la Recherche Médicale U352
INSA
69621 Villeurbanne, FRANCE
**** Institut National de la Recherche Agronomique, INA P-G
75231 Paris 5, FRANCE

Correspondence and requests for materials should be addressed to M.H.
E-mail: holzenberger@st- antioine.inserm.fr.

ABSTRACT:

Studies in invertebrates have led to the identification of a number of genes that regulate lifespan, some of which encode components of the insulin or insulin-like signalling pathways. Examples include the related Tyrosine Kinase Receptors InR ( Drosophila melanogaster) and DAF-2 ( Caenorhabditis elegans) that are homologues of the mammalian Insulin-Like Growth Factor Type-1 Receptor (IGF-1R). To investigate whether IGF-1R also controls longevity in mammals, we inactivated the IGF-1R gene in mice (Igf1r). Here, using heterozygous knockout mice because null mutants are not viable, we report that Igf1r+/- mice live on average 26 percent longer than their wild-type littermates (P < 0.02). Female Igf1r+/- mice live 33 percent longer than wild-type females (P < 0.001), whereas the equivalent male mice show an increase in lifespan of 16 percent, which is not statistically significant. Long-lived Igf1r+/- mice do not develop dwarfism, their energy metabolism is normal, and their nutrient uptake, physical activity, fertility and reproduction are unaffected. The Igf1r+/- mice display greater resistance to oxidative stress, a known determinant of aging. These results indicate that the IGF-1 receptor may be a central regulator of mammalian lifespan.

Why Do Social Species Have Different Mortality Curves?

July 25, 2003; Dr. Ronald Lee, a demographer at the University of California at Berkeley has just published a new theory of aging in a recent issue of PNAS that purports to tie together the reduction in post-menopausal mortality (thereby promoting post-reproductive longevity) that uniquely shaped our Homo sapiens Life-History-Survival Curves during our pre-agriculture hunter-gatherer stage. Lee's theory suggests that non-social species have no requirement for a "transfer effect" in their genes to provide with the time needed to invest in children. But in social species, such as ourselves, for whom parity (average number of children per birth) has been fixed and grandparental investment in progeny makes a difference, there is a significant advantage in reducing fertility, "inventing" menopause, and having childhood mortality decline until the onset of puberty.

Refs:

1. Ronald D. Lee, "Social Sciences: Rethinking the Evolutionary Theory of Aging: Transfers, Not Births, Shape Senescence in Social Species," PNAS USA On-Line, Vol. 100, No. 16, pp. 9637-42 (10.1073; 6 pages; August 5, 2003)

Departments of Demography and Economics
University of California
2232 Piedmont Avenue
Berkeley, CA 94720-2120; USA;
E-mail: rlee@dmog.berkeley.edu

Edited by Samuel H. Preston,
University of Pennsylvania
Philadelphia, PA; USA
Approved: June 3, 2003 (received for review January 16, 2003)

ABSTRACT:

The classic evolutionary theory of aging explains why mortality rises with age: As individuals grow older, less lifetime fertility remains, so continued survival contributes less to reproductive fitness. However, successful reproduction often involves intergenerational transfers as well as fertility. In the formal theory offered here, age-specific selective pressure on mortality depends on a weighted average of remaining fertility (the classic effect) and remaining intergenerational transfers to be made to others. For species at the optimal quantity-investment tradeoff for offspring, only the transfer effect shapes mortality, explaining postreproductive survival and why juvenile mortality declines with age. It also explains the evolution of lower fertility, longer life, and increased investments in offspring.

2. Nicholas Wade, "Why We Die, Why We Live: A New Theory on Aging," The New York Times, p. D3 (July 15, 2003).

"XX" Marks the Spot

July 24, 2003; Inactivation of one X chromosome occurs in "XX" female cells to bring about equivalence of X gene-expression with male cells. There are two possibilities: It requires either (1) a counting mechanism that triggers X inactivation in cells with more than one X; or (2) a blocking mechanism that saves a single X from an undiscerning inactivation process acting on all remaining X's. Dr. Laura O'Neill and colleagues from the Chromatin and Gene Expression Group at the University of Birmingham Medical School report that both X Chromosomes are epigenetically marked in female cells, while the autosomes and the single X in male cells are not marked, suggesting that a chromatin-based counting mechanism restricts X inactivation to cells with more than one X chromosome.

O'Neill immunoprecipitated acetylated isoforms of the four core histones in Murine Embryonic Stem (MES) Cells and assayed DNA from bound and unbound fractions for X-linked and autosomal sequences. They revealed a two- to three-fold enhancement of acetylation of X-linked genes in female cells, coordinated in all four histones. Pooling other data consistent with their results revealed hyperacetylation to be a general phenomenon in X-linked genes in both coding and promoter regions. They ruled out effects of differences in ES lines or culture conditions and showed that hyperacetylation was not restricted to only one X. Following differentiation and X inactivation, the active X remained hyperacetyled for several days, while the epigenetic marking on the inactivated X was lost. Similar results were observed for methylation.

"It is suggested that [the modification] provides the two X chromosomes with comparable chromatin structures, and thereby facilitates the subsequent stages that lead ultimately to selective X inactivation... The fact that the mark described here is distributed across the X Chromosome is consistent with its involvement in a chromosome-wide event, such as a spreading of the inactive state," the authors conclude.

Refs:

1. Laura P. O'Neill, et al, Human Molecular Genetics, Vol.12, pp. 1783-90 (August 1, 2003).
2. Cathy Holding, "Epigenetic Modification of Both X Chromosomes in Female Cells Marks Them for X-Inactivation," The Scientist (July 24, 2003).
3. David Bainbridge, The X in Sex: How the X Chromosome Controls Our Lives (Harvard University Press, Cambridge, MA; 2003).

Scientists Will Attempt to Clone a Mammoth

July 19, 2003; Japanese Scientists at the Gifu Prefectural Science and Technology Promotion Center and Kinki University will attempt to clone a wooly mammoth using frozen DNA samples from bone marrow, muscle, and skin that were unearthed in August in the Siberian tundra, where they had been preserved in ice for thousands of years.

Ref:

"Scientists Will Attempt to Clone Mammoth," The Los Angeles Times (July 19, 2003).

70 Percent of All Fertilized Eggs Perish Before Implantation

July 19, 2003; In a recent study, 183 fertilized eggs that were examined carefully using a molecular fluorescent marker (the acronym is called "FISH"). Only 91 percent (167 eggs) began with the correct haploid count of 23 chromosomes. 6 percent (11 eggs) started with polyploidy (46 chromosomes), indicating that they had failed to properly carry out the last step of meiosis; 10 percent had a triploidy (at least one extra chromosome), while 3 percent (5 eggs) had a completely missing chromosome (failed disjunction along the spindle apparatus). Clearly, this is the poorest of quality control (thinking of good engineering-practice standards). And these are not bizarre events for the purpose of exam questions written by fanatical pathologists. These are routine, every-day occurrences.

In another study, 70 percent of the embryos obtained from a 40-year-old woman undergoing IVF exhibited aneuploidy (non-matching chromosomes), as a spontaneous (non-hereditary) abnormality. Dr. Harvey Stern, Head of the Genetics and IVF Institute's PGD (Preimplantation Genetic Diagnosis) Program in Fairfax, VA, said "You see plenty of obviously defective blatocysts, and then you'll see one that is just stone-cold normal. Your think, 'Oh, my God. How does anyone ever get pregnant?'"

Most chromosomal abnormalities result in lethal events for the embryo very early on, so the luxury (or pain) of implantation is never experienced by the potential Mother, who never had a clue that she was potentially pregnant nor that a conception following intercourse had even occurred. Indeed, as described above, 7 out of 10 conceptions fail to implant in the uterus for one reason or another. The female menstrual period conceals a multitude of sins. This explains how easy it is to deceive one's self about the relative perfection of the local events in the process. If you can't see the chaos under the covers, it doesn't mean it's not happening (like the existence of "spots" on the surface of the sun before Galileo was able to demonstrate them; the sun is a "perfect" heavenly body, isn't it?) just because the net effect of the process is so nearly perfect. {Trisomy 21 ( Down's Syndrome), however, is only one example of an abnormality that is not instantly lethal for the offspring and it is known to have an exponentially-rising incidence with increasing maternal age after 35.}

At the level of the germ line, this is not a logical, disciplined layout by a well-trained design engineer. Although the net effective is to propagate our species, it appears to be more like eggs are a mob involved in a chaotic struggle for survival within the ovary than a well-orchestrated sequence of carefully-executed digital events. Think if seven out of every ten births had six fingers (or whatever) instead of five! I could not find the actual frequency of hereditary polydactyly while doing a quick search on the Internet, but it must be less than one in a million.]

Refs:

1. Journal of Human Genetics, p. 488 (September 2002).
2. "FISH Helps Study of Chromosome Abnormalities," Biophotonics International, p. 66 (January/February 2003).
3. Melissa Healy, "Testing for Abnormal Embryos," The Los Angeles Times, p. F8 (July 21, 2003).

Stem-Cell Forum Launched: Twelve Nations Sign Up for Project Designed to Speed Up Research

July 17, 2003; Pat Hagan of The Scientist.com reports that scientists from 12 countries have officially launched a new organization designed to promote collaboration on stem-cell research and to speed up the development of new medical treatments. Called the International Stem-Cell Forum, the new body was sanctioned at a meeting chaired by the UK's Medical Research Council (MRC) in London on July 11th. The launch comes just six months after the MRC announced it was setting up an informal discussion forum to tackle stem-cell research on a global rather than national basis.

The main aim is to produce international scientific benchmarks on the characteristics of new and existing stem-cell lines. This will be achieved by inviting researchers from major institutions in each of the member countries to examine cell lines, using standardized tools and procedures.

Apart from the UK representatives, signatories include the US National Institutes of Health, the National Health and Medical Research Council of Australia, the Canadian Institutes of Health Research, and the Israel Academy of Sciences and Humanities. The other states involved in the collaboration are Germany, France, Japan, Finland, Singapore, the Netherlands, and Sweden.

A new registry of stem cell lines, which will be made available on a dedicated website, is being developed under the leadership of Peter Andrews from the Center for Stem-Cell Biology at the University of Sheffield. One of the underlying concerns has been that in the race to explore new applications for stem-cell technology, teams of scientists around the world could end up working to different criteria or duplicating one another's efforts. The idea behind the forum is to reduce this as much as possible and to speed up research by sharing information. The United Kingdom will take charge of the drive to characterize cell lines, and representatives from Australia and Canada have agreed to explore ethical and patenting issues.

MRC Chief Executive George Radda said in a press statement "International coordination will accelerate progress in this cutting-edge area of research, maximizing health benefits for the global public." James Battey from the US National Institutes of Health said he hoped the initiative would allow US scientists to "harmonize" their research efforts with those elsewhere. He told The Scientist, "A standardized approach to characterizing human embryonic stem-cell lines throughout the international research community will reveal similarities and differences between the properties and potential of lines established at different times under different experimental protocols. Such an effort will undoubtedly accelerate the pace of discovery." According to Andrews, a "task force" of four or five representatives has been formed to establish a program of work for the forum for the next year. "We'll do it in bite-sized chunks because it's such a huge project," he told The Scientist. "It's a question of working on the key parts, such as how to characterize cell lines, how to stop them doing things you don't want them to do, and how to get them to differentiate into cells that you want. "There is a huge amount of promise in stem-cell research but also a huge amount of hype, so we have to be careful what we tell people. It could take [15 - 20] years, but there's a good chance we could produce therapies that are really revolutionary for diseases that cripple a lot of people," said Andrews.

Ref:

"U.S. Should Centralize Stem Cells, Scientists Say," The Los Angeles Times (May 10, 2003).
As reported in the May 9th issue of Science.

NEJM: Congress Must Vote to Approve Legislation for Stem-Cell Therapy

July 17, 2003; Jeffrey M. Drazen, M.D., Editor-in-Chief of The New England Journal of Medicine, has now adopted a strong position against Bills by Sam Brownbeck (R., KS) (S. 245, which has not yet come to a vote on the Senate floor) and David Weldon (R., FL) (HR. 534, "The Human Cloning Prohibition Act of 2003," which passed the House on February 27th by a vote of 241 to 155). (President Bush has already indicated that he would sign a properly reconciled bill into law at the earliest possible date.) The stage is now set for a host of legislative actions at both the Federal and state levels to define permissible bounds for cloning/stem-cell research. The justification for more restrictive legislation hinges in part on scientific perceptions about the versatility and therefore the promise of Adult as compared with Embryonic Stem-Cells, itself a topic of intense scientific disagreement. The debates in the halls of Congress and the scientific laboratories are inextricably intertwined, and "the outcome will profoundly influence the future of regenerative medicine."

"Although the science of creating genetically compatible tissues with the use of Somatic-Cell Nuclear Transfer (SCNT) is in its infancy, as a community of scholars, we know that this approach to treatment is now possible. Since the precedent has been set, there is no question but that SCNT will be used to develop treatments for conditions that are currently incurable. When such treatments have been perfected, patients with these conditions will be offered the prospect of cure... It is reasonable to regulate the technology of SCNT, just as we regulate the use of radioisotopes and recombinant DNA, but it is unreasonable to prohibit research using this technology. No matter what the Congress decides, such treatments will be developed somewhere in the world. Physicians and scientists in the US should be at the center of the action, not on the sidelines. We want to be sure that legislative myopia does not blur scientific insight."

Refs:

1. Jeffrey M. Drazen, "Legislative Myopia on Stem Cells, NEJM, Vol. 349, No. 3, p. 300 (July 17, 2003).

2. George Q. Daley, "Cloning and Stem Cells Handicapping the Political and Scientific Debates," NEJM, Vol. 349, No. 3, pp. 211-2 (July 17, 2003).
Daley, M.D., Ph.D. with the MIT Whitehead Institute says "...A worthy goal of biomedical research is to reprogram an Adult Cell directly, without having it pass through the intermediate stage of the preimplantation embryo."

3. Konrad Hochedlinger and Rudolf Jaenisch, "Nuclear Transplantation, Embyronic Stem Cells, and the Potential for Cell Therapy," NEJM, Vol. 349, No. 3, pp. 275-86 (July 17, 2003).
Prof. Rudy Jaenisch, M.D. with the MIT Whitehead Institute for Biomedical Research in Cambridge, MA, one of the more cautious scientists in the field, and the strongest advocate I know for exposing fraud by pretenders to human cloning, says toward the end of this paper,
"To overcome the ethical and practical limitations of therapeutic cloning, it would be useful to reprogram somatic cells directly into embryonic stem cells without the use of oocytes. An understanding of the factors that have a role in establishing and maintaining pluripotency might make it possible to alter the fate of somatic cells directly. For instance, Oct-4 appears to act as a regulator of pluripotency during development[*]. The manipulation of Oct-4 and related genes in somatic cells might help to reprogram their nuclei to an embryonic state. This could reduce or even circumvent the need for human oocytes. Recently, Hubner, et al., provided evidence of the differentiation of murine embyronic stem cells into oocyte-like cells in vitro." [ Note: See the News Item below dated May 2nd.].
It is exciting to see one of the more conservative scientists in this field lend credibility and legitimacy to an idea that would have been considered to be science fiction just a few years ago!

4. Nadia Rosenthal, "Prometheus's Vulture and the Stem-Cell Promise," NEJM, Vol. 349, No. 3, pp. 267-74 (July 17, 2003).

________________________________

* Manipulating expression of Oct4 could reprogram Adult Cells into a Stem-Cell condition. Expression of the Transcription Factor Oct4, a marker of pluripotency, is a prerequisite for the development of both normal and cloned embryos. In the July 15th issue of Current Biology, James Byrne and colleagues at the Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology report the expression of Oct4 during reprogramming of transferred differentiated nuclei into Xenopus oocytes. Their results indicate a repression of expression of differentiation markers and a rapid and strong induction of the Oct4 transcription factor.

5. James Byrne, et al, Current Biology, Vol. 13, pp. 1206-1213 (July 15, 2003).
6. "Wanted: Stem-Cell Research Papers," Science, Vol. 301, No. 5633, p. 591 (August 1, 2003).
Interestingly, the AAAS Editors chose to comment on an uncharacteristic political swing toward science in one of their more conservative sister publications ( The NEJM), which is not normally known for going out a limb. The Editors, including Donald Kennedy, Editor-and-Chief of Science), are on record for quite some time as strongly supporting stem-cell research. Therefore, the NEJM will also now become "an important gatekeeper for the emerging field of Regenerative Medicine."

Stem Cells Enable Paralyzed Rats to Walk

July 3, 2003; Washington, D.C. Nerve cells derived from human embryonic stem cells and transplanted into paralyzed rats have enabled the animals to walk again. The findings add to a growing number of studies that suggest embryonic stem cells could have a valuable role to play in treating spinal injuries. The researchers, whose work was funded by stem-cell giant Geron Corp. of Menlo Park, CA, say trials on people could start in just two years.

But the first trials are likely to involve patients with recent spinal cord injuries and localized damage. Treating people who have been paralyzed for years or suffer from degenerative nerve diseases would be far more difficult. Ways will also have to be found to prevent people rejecting the stem cells. One possible alternative to immunosuppressant drugs, Geron President Thomas Okarma told the BIO-2003 Conference in Washington, D.C. last week, would be to first give patients bone-marrow stem cells from the same source as the nerve cells. This might trick the patients' immune system into developing tolerance.

Researchers are exploring a number of approaches to repairing damaged spines, including drugs that overcome spinal cells' reluctance to regrow, ways of bridging the gap between severed nerves and transplants of various tissues, including adult stem cells derived from bone marrow and nerve cells from the nose. Human trials of some treatments, such as using nose cells, have already begun.

Serious Limitations

But Okarma thinks adult cells have serious limitations as a mass-market treatment, because not many cells can be grown from a single source. That is not a problem with embryonic stem cells (ESCs). "One cell bank derived from a single embryo produces enough neurons to treat 10 million Parkinson's Disease patients," says Okarma.

What is more, he claims, adult stem cells may not be as versatile. "At this moment, there is very little hard evidence that a bone marrow stem cell can turn into anything but blood or that a skin stem cell can become anything but skin." ESCs, on the other hand, have the potential to develop into practically any type of tissue. But there is also a serious problem with ESCs. "Undifferentiated human embryonic stem cells have a very high probability of forming tumors," says Hans Keirstead at the University of California, Irvine, whose team did the latest research.

To prevent this, his team turned ESCs into specialized cells before transplanting them. They transformed the ESCs into oligodendrocytes, the cells that form the insulating layer of myelin that is vital for conducting nerve impulses. Keirstead's team transplanted the oligodendrocytes into rats with "bruised" spines. After nine weeks, the rats fully regained the ability to walk, he says, whereas rats given no therapy remained paralyzed. The team repeated the experiment on three separate occasions, with the same results.

Wrap Around

Analysis of the rats' spinal cords revealed that the transplanted oligodendrocytes had wrapped themselves around neurons and formed new myelin sheaths. The transplanted cells also secreted growth factors that appear to have stimulated the formation of new neurons.

While many promising spinal repair experiments have proved hard to reproduce, researchers at Johns Hopkins University in Baltimore, MD, also announced similar results last week. The team injected undifferentiated human ESCs into rats with injured spinal cords. After 24 weeks, the treated rats could support their own weight. Team leader Douglas Kerr thinks the animals' recovery was not due to the growth of new cells, but to the secretion of two growth factors ( TGF-alpha and BDNF), which protected damaged neurons and helped them to re-establish connections with other neurons. "The stem cells' magic was really their ability to get into the area of injury and snuggle up to those neurons teetering on the brink of death," says Kerr, whose results will appear in the Journal of Neuroscience.

Okarma hopes the results will help persuade policy makers in Washington not to ban therapeutic cloning, which is one way of obtaining human ESCs, and increase funding for ESC research. "The promise of this technology is beginning to be realized," he says. "That's why we think this battle is worth fighting."

Preregister Today for Biomedical Gerontology Conference

June 27, 2003; "Urgent! July 10th is the new deadline for Abstract Submission and early- discount registration for the Biomedical Gerontology Congress (in Cambridge, England at the end of September). Click for details, and also for more details on registration.

The Y Chromosome Turns Out To Be More Complex Than Was Thought

June 19, 2003; Cambridge, MA; The human male Y-Chromosome has now been sequenced and has been found to contain 78 genes, many of which are repeated in reverse as palindromes, sequences that are mirror images (e.g., "Madam I'm Adam."). This could be a defense mechanism against random lethal point mutations that autosomal chromosomes don't need, since they always come in pairs. Dr. Francis Collins, Director of the National Human Genome Research Institute, commented "to have all its instructions laid out in front of us is a very significant moment in the history of biology."

Refs:

1. Helen Skaletsky*, Tomoko Kurodak-Kawaguchi*, Patrick J. Minx , Holland S. Cordum , Ladeana Hillier , Laura G. Brown*, Sjoerd Repping , Tatayana Pyntikova*, Johar Ali , Tamberlyn Bieri , Asif Chinwalla , Andrew Delehaunty , Kim Delehaunty , Hus Dui Du , Ginger Fewell , Lucinda Fulton , Robert Fulton , Tina Graves , Shun-Fang Hou , Philip Latrielle , Shawan Leonard , Elaine Mardis , Rachel Maupin , John McPherson , Tracie Miner , William Nash , Christine Nguyen , Philip Ozersky , Kymberlie Pepin , Susan Rock , Tracy Rohlfing , Kelsi Scott , Brian Schultz , Cindy Strong , Aye Tin-Wollam , Shiaw-Pyng Yang , Robert H. Waterston , Richard K. Wilson , Steve Rozen*, and David C. Page*, "The Male-Specific Region of the Human Y Chromosome is a Mosaic of Discrete Sequence Classes," Nature, Vol. 423, pp. 825-37 (June 19, 2003).
_________________________________
* Howard Hughes Medical Institute
Department of Biology
MIT Whitehead Institute
9 Cambridge Center
Cambridge, MA 02142, USA

Genome Sequencing Center
Washington University School of Medicine
4444 Forest Park Boulevard
St. Louis, MO 63108, USA

Center for Reproductive Medicine
Department of Obstetrics and Gynecology
Academic Medical Center
Amsterdam 1105 AZ, The Netherlands
_________________________________
Correspondence and requests for materials should be addressed to Dr. David C. Page at
E-mail: page_admin@wi.mit.edu.

ABSTRACT:

The Male-Specific region of the Y chromosome (MSY) differentiates the sexes and comprises 95 percent of the chromosome's length. Here, we report that the MSY is a mosaic of heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X-degenerate, and ampliconic. These classes contain all 156 known transcription units, which include 78 protein-coding genes that collectively encode 27 distinct proteins. The X-transposed sequences exhibit 99 percent identity to the X chromosome. The X-degenerate sequences are remnants of ancient autosomes from which the modern X and Y chromosomes evolved. The ampliconic class includes large regions (about 30 percent of the MSY euchromatin) where sequence pairs show greater than 99.9 percent identity, which is maintained by frequent gene conversion (non-reciprocal transfer). The most prominent features here are eight massive palindromes, at least six of which contain testis genes.

2. Robert Lee Hotz, "Chromosomally, Men Are Not So Simple After All," The Los Angeles Times, pp. A1, 20 (June 19, 2003).

Clock Protein Found in Mouse Retinal Cells

June 16, 2003; Scientists at Johns Hopkins University in Baltimore have recently identified a third type of cell in the retina of the mouse eye. Melanopsin cells are light-sensitive retinal cells, probably in humans as well, that are neither rods nor cones. They appear to make a protein needed to recalibrate the pineal gland secretion of melatonin when darkness descends, and somehow keeps mice (and us) on a diurnal, 24-hour schedule. However, since mice are nocturnal creatures, the interpretation of melatonin by the rest of the brain may be very different in mouse and man.

Refs:

1. AP, CNN (June 16, 2003).
2. King-Wai Yau, et al, Nature On-Line (June 16, 2003).

FDA Warns Michigan Hospital Not To Repeat Stem-Cell Transplant

June 12, 2003; Royal Oaks, MI; A 16-year old Michigan boy who received a pioneering stem-cell transplant in February after suffering a heart attack will have no further treatments for now. Recall from our story of March 6th below that Mr. Dimitri Bonnville was accidentally shot in the heart with a nail gun on a construction site [sigh!], and after surgeons at Beaumont Hospital removed the nail, he had a heart attack that destroyed nearly a third of his heart's muscle cells. As the condition could only worsen with time, he would either need a new heart transplant or an experimental bone-marrow stem-cell transplant directly into the damage heart. The latter was tried and seems to have worked! The day after the doctors disclosed the experiment, the FDA began an inquiry. When the hospital declined to conduct additional requested experiments with animals before further human procedures would be allowed to continue, the FDA ruled that they would not permit further treatment despite the fact that the initial experiment, conducted without any authorization, seems to have worked.

[ Editor's Note: There is an exciting and promising, but contradictory, flood of new data being published on stem-cell treatments, and we believe that much more work needs to be done in laboratory animals before human trials get underway in this country. So we view this move by Federal regulators as a prudent approach, at least for the time being.]

Refs:

1. Antonio Regalado, "FDA Holds Up Hospital's Work with Stem Cells," The Wall Street Journal, pp. A1, B1,4 (June 12, 2003).
2. "Stem Cells Save Boy's Life: FDA Warns Doctors, "Do Not Do It Again," Life Extension Magazine, Vol. 9, No. 10, p. 14 (October 2003).
3. James T. Willerson, et al, "Stem Cells Improve Heart Function of Seriously-Ill Heart-Failure Patients," Circulation: Journal of the American Heart Association (April 22, 2003).

Geron Announces UK Authorization for Stem-Cell Derivation

June 11, 2003; Menlo Park, CA ( Business Wire) Geron Corp. (Nasdaq: GERN) today announced that the Human Fertilization Embryology Authority (HFEA) of the UK has authorized the Roslin Institute to derive new human Embryonic Stem cells (hES cells) from donated excess embryos created as a result of In Vitro Fertilization (IVF) treatment. The Institute's research, funded by and conducted in collaboration with Geron, seeks to establish new hES cell lines as well as to improve the technology to produce and maintain hES cells in culture. The new hES cells lines will be used in research.

The HFEA is charged with licensing and monitoring IVF procedures, donor insemination, and human embryo research in the UK. Any derivation of human embryonic stem cells in the UK requires a license from the HFEA. Before granting a license, the HFEA considers the scientific, ethical, and medical aspects of the project.

"We are pleased that the HFEA has granted a license to enable this important research," said Dr. Jane S. Lebkowski, Ph.D., Geron's Vice President of Regenerative Medicine. "The additional hES cell lines that we expect to derive at Roslin will expand our current resource of six hES cell lines, and increase the genetic diversity of the cell lines we can use for research. We also expect this work to continue our progress in making the derivation and culture of hES cells more efficient."

Human embryonic stem cells are unique cells that can develop into all cells and tissues in the body. Geron is developing hES cell-based approaches to treating spinal cord injury, Parkinson's Disease, heart failure, diabetes, and other diseases. Geron has built an international portfolio of patent applications covering technologies it has developed to enable the scalable growth and differentiation of hES cells, as well as various differentiated cell types that can be produced from hES cells. In addition to the patents it owns, Geron holds licenses under U.S. Patent Nos. 5,843,780 and 6,200,806, including exclusive rights to develop and commercialize neural, cardiomyocyte and islet cells derived from hES cells for therapeutic applications.

Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for applications in oncology and regenerative medicine, and research tools for drug discovery. Geron's product development programs are based upon three patented core technologies: telomerase, human embryonic stem cells, and nuclear transfer.

Refs:

1. Denise Gellene, "Patent News Sends Geron Stock Up 15 Percent," The Los Angeles Times, p. B2 (June 11, 2003).
2. Cynthia Schreiber, "Geron, Ariad, ..." The Wall Street Journal, p. C8 (June 11, 2003).
3. AP, "Geron's Stock Soars on Patent Grant," The Kansas City Star San Francisco, CA (June 10, 2003).
The newly issued patent involves a technology to purify hES cells to increase their potency and covers a method of inserting an "apoptotic gene" into a cell that becomes activated only when the cell does not develop properly. The requirement for this patent is not yet clear to researchers.

Genetic Engineering of Cochlea Hair Cells in the Inner Ear

June 1, 2003; Prof. Yehoash Raphael of the University of Michigan in Ann Arbor published in today's issue of the Journal of Neuroscience a technique for growing new sensory hair cells in guinea pigs, using gene therapy, for the first time. Sharks grow new hair cells throughout their lives, and some birds can too; but no mammals exhibit similar regenerative powers. Loss of hair cells in the inner ear results in the kind of deafness most commonly suffered by the elderly.

Ref:

John Travis, "Getting an Earful," Science News, Vol. 163, No. 23, p. 355 (June 7, 2003).

First Cloned Mule

May 30, 2003;

As reported in today's issue of Science Magazine,

"A Mule Cloned from Fetal Cells by Nuclear Transfer,"
Gordon L. Woods 1*, Kenneth L. White 2, Dirk K. Vanderwall 1, Guang-Peng Li 2,
Kenneth I. Aston 2, Thomas D. Bunch 2, Lora N. Meerdo 2, and Barry J. Pate, 2
Science, Vol. 300, No. 5624 (May 30, 2003).

1. Northwest Equine Reproduction Laboratory, Department of Animal and
Veterinary Science, University of Idaho, Moscow, ID 83844, USA.
2. Center for Developmental and Molecular Biology, Biotechnology Center, Animal,
Dairy and Veterinary Sciences Department, Utah State University, Logan, UT 84322, USA.
* To whom correspondence should be addressed: E-mail: gwoods@uidaho.edu.
______________________________________________

ABSTRACT:

A mule, an animal that is incapable of reproducing naturally, has been successfully cloned.

[ Editor's Note: The pdf file of this Brevia on-line article has a fabulous picture of Idaho Gem.]
____________________________________________________________________
GENETICS:
First Cloned Mule Races to Finish Line
by
Constance Holden (p. 1354)

On May 5th, a mule named Idaho Gem was born after a normal 346-day gestation in the womb of a mare, researchers report on-line in Science this week. He's the first member of the horse family, as well as the first sterile animal to be cloned. He is the clone of Taz, a famous racing mule.

_________________________________________________________________
Refs:

1. Antonio Regalado, "Stubborn Mule Beats Horses in Race to Be First Cloned Equine," The Wall Street Journal, pp. A1, 3 (May 30, 2003).

2. Rosie Mestel, "Still a Crossbreed, But This Baby Mule Is a Full-Blooded Clone," The Los Angeles Times, pp. A2, 22 (May 30, 2003).

3. AP, "Scientists Clone First Mule: Researchers: First Member of the Horse Family Cloned," CNN Friday, May 30, 2003 Posted: 10:19 AM EDT (14:19 GMT).

4. "Cloned Banteng Arrives at Wild Animal Park," The Los Angeles Times (April 26, 2003).

In a related development, a cloned banteng calf born to a domestic cow arrived at the San Diego Wild Animal Park, where scientists will continue to study it. The bull calf is active and eating well, according to officials at Trans Ova Genetics of Iowa, where it was born April 1st. The calf is genetically identical to a male banteng that died at the animal park outside San Diego 23 years ago. Frozen skin cells from that animal had been stored in the San Diego Zoo's "Frozen Zoo," a bank of cells and genetic material from about 100 endangered species. Fewer than 8,000 bantengs remain in the wild, mostly in Southeast Asia.

5. Robin Marantz Henig, "Pandora's Baby: In Vitro Fertilization Was Once Considered by Some to Be a Threat to Our Very Humanity. Cloning Inspires Similar Fears," Scientific American, Vol. 228, No. 6, pp. 62-7 (June 2003).

6. AP, "Coned Mules to Face Off in Race," The Los Angeles Times (May 27, 2006).
Two identical, cloned, three-year old mules, Idaho Star and Idaho Gem will compete in a professional mule race in Winnemucca, NV at the start of the racing season on June 2nd, challenging a set (herd?) of naturally-bred racing mules. The DNA source was the same parents who sired Taz, a champion mule racer in his day. But, the two clones are not likely to finish in a "dead heat." There's a lot more than genes operating in any particular race. Winners get about $5,000 per race and a total of $500,000 in purse money throughout the Summer, so any wins will more than pay off the lease fee of $1,000 per year from the University of Idaho. Kentucky Derby winners do better, of course, but the stringent rules of thoroughbred racing prohibit cloned horses, at least for the moment.
7. James Gorman, "Belmont, Schmelmont. You Ought To See a Cloned Mule Run," The New York Times, p. D2 (June 13, 2006).
The results from the race on June 5th: Our two cloned mules came in third and seventh, respectively. The first and second place winners were made the old-fashioned way by arranging for a male donkey and a female horse to mate and produce a sterile hybrid (no stud fees, gentlemen). So, what's the Nature vs. Nurture trade-off?

The answer lies in the lyrics to the song, "The Erie Canal," praising a stubborn female mule named Sal [for Sally, I guess]...

"A friend of mine once made her sore;
Now he's got a broken jaw.
She let fly with an iron toe,
and kicked him back to Buffalo."

[ Editor's Note: The behind-the-scenes rivalries for who would be first team to successfully clone an equine species appear to have been intense. Prof. Katrin Hinrichs of Texas A&M University reportedly said, "It's a little disappointing that it's a mule. Our own lab has a mare that is now five months pregnant with a clone of Skip Firestorm," a horse ridden by Dr. Hinrichs's nine-year old daughter and is expected in November. An Italian team claims that they have a cloned horse that is expected within just days. One day, this could be a big business. Top jumpers and dressage animals are worth millions. And what about Funny Cide, the gelding who may win the Triple Crown in a few days time in Belmont, New York? Geldings don't make sperm, do they? Why make a gelding anyway? Does it require surgery? Do these horses live longer? They normally don't run faster. Some pedigreed stallions produce sperm at the rate of $50,000 a week! Is it a horse or a bank? I'm obviously not part of the race-horsing cognoscenti community. I don't even know why they measure the length of a race track in furlongs instead of meters (sigh!). Reporters in the sports pages don't ever take you through "Racing 101"; they only tell you the win, place, and show and how much money you made if you bet. I don't even know why it's called "win, place, and show." Help! Can anyone lend an enlightening hand (hoof) here?
We found the answer ourselves by typing in the word "gelding" into the Google.com search engine. The real reason it appears is to calm down an otherwise impossible-to-handle high-strung stallion that may injure either himself or those around him. See the Cherry Hill Ranch of Colorado website for more details than you ever wanted to know about this topic.]

Successful Gene Therapy During Angioplasty

May 26, 2003; As reported in the May 14th on-line edition of Circulation: Journal of the American Heart Association, a team of scientists at the University of Kuopio in Finland have introduced a VEGF (Vascular Endothelial Growth Factor) gene during conventional angioplasty in 103 patients (aged [38 - 75] years) using two different types of vectors: an adenovirus (37 patients) and a liposome (28 patients) (placebo = 38 patients). Although blood flow improved for all three groups, those who received VEGF by adenovirus had significantly improved blood flow. This approach may be superior to that of drug-coated stents and may ultimately obviate the need for coronary artery bypass surgery.

Ref:

Jane E. Allen, "Gene Therapy with Angioplasty May Prevent Bypass: A New Study Finds that the Procedure Increases Oxygen-Carrying Blood to the Heart," The Los Angeles Times, p. F6 (May 26, 20003).

Mice Given Younger Ovaries Live Longer

May 24, 2003; Prof. James Carey of the University of California at Davis has just published in the May 30th issue of the journal Aging Cell that mice implanted with ovaries from much younger mice live to a riper old age.. Ovaries from female mice age 11 months (the equivalent of a 50 year old woman) were replaced by fresh ovaries from two-month-old females. The experimental mice lived 40 percent longer than controls. Click on the picture of the mouse for more details.

Shelley L. Cargill, James R. Carey, Hans-Georg Müller, and Gary Anderson, "Age of Ovary Determines Remaining Life Expectancy in Old Ovariectomized Mice," Aging Cell, Vol. 2, No. 3, p. 185 (June 2003).

ABSTRACT:

We investigated the capacity of young ovaries, transplanted into old ovariectomized CBA mice, to improve remaining life expectancy of the hosts. Donor females were sexually mature two-month-olds; recipients were prepubertally ovariectomized at three weeks and received transplants at 5, 8, or 11 months of age. Relative to ovariectomized control females, life expectancy at 11 months was increased by 60 percent in 11-month recipient females and by 40 percent relative to intact control females. Only 20 percent of the 11-month transplant females died in the 300-day period following ovarian transplantation, whereas nearly 65 percent of the ovariectomized control females died during this same period. The 11-month-old recipient females resumed estrus and continued to cycle up to several months beyond the age of control female reproductive senescence. Across the three recipient age groups, transplantation of young ovaries increased life expectancy in proportion to the relative youth of the ovary. Our results relate to recent findings on the gonadal input upon aging in Caenorhabditis elegans and may suggest how the mammalian gonad, including that of humans, could regulate aging and determine longevity.

[ Editor's Commentary: We consider this paper to be extremely important, since the observation that ovarian tissue matters in determining lifespan is consistent with our hypothesis that the maximum lifespan of any Sexually-Reproductive Species-Specific Life-History Trajectory is more closely correlated with its Onset of Puberty (dictated by a set-point associated with an anterior-hypothalamic/pineal reverberating clock circuit {yet to be identified by neuroanatomists, but similar in architecture, we suppose, to the SA and AV nodes in the Bundle of His in the heart}. This circuit ticks relentlessly with its own time constant {independently of most other genes expressed in the species} and which keeps very careful track of diurnal rhythms, with modulation by lunar/tidal months and seasons). This ultimately stimulates the first synthesis of FSH/LH Releasing Factors in the female, ultimately dictating the interval-of-reproductive-competence {the species' biological-warranty period} by either early- or late-onset, than any other species' parameter that is genetically-determined.]

Refs:

1. Ascribe.org, "Mice Given Younger Ovaries Live Longer," The Los Angeles Times, p. A18 (May 24, 2003).
2. Sorcha McDonagh, "Lease on Life: Old Mice Live Longer When Given Young Ovaries," Science News, Vol. 163, No. 24, pp. 272-3 (June 14, 2003).

Canine Genome Next: Boxer Breed Chosen

May 24, 2003; From a pool of 120 candidate dogs, the MIT/Whitehead Institute for Genome Research will sequence a female boxer ( Tasha) as their first canine species.

[ Editor's Note: Comparative Canine Genomics will be exploited in the future to discover why Great Danes are big and Chihuahuas small. (It would certainly be nice if this computational effort could become as simple as a high-school science project, once ten different canine genomes were placed on the same publically-available parallel-architecture supercomputer programmed with the appropriate homology-scanning {BLAST} software and made available 24-hours-a-day world-wide on the Internet for all students to try their hand. Of course, if it existed, this sort of "OPEN Software" High-School Genetics Consortium, following the LINUX Model, could also be made available for: (i) mouse; (ii) rat; (iii) bat; (iv) whale; (v) chimp; and (vi) human genomes, not to mention Yeast, the Fruit Fly, and C elegans.) Because of deliberate inbreeding for specialization of man's "best friend" (e.g., Blood Hounds for tracking and Gaze Hounds for hunting pheasant where scent is not so important, etc. the genomes of many individual breeds are highly variable. But all breeds are known to descend from a single Asian Gray Wolf about 15,000 years ago (an extremely short time in evolutionary terms), thus the number of idiosyncratic, phenotypic genes/SNIPs that make each breed appear so exquisitely different may actually be very few in number. Of course, why small breeds live systematically longer than large breeds may then fall out of this investigation, as a side benefit ( lambda max ranges form 12 years to 24 years). Sadly, our prehistoric ancestors never cared to breed dogs for longevity the way today's biologists have bred fruit flies to double or triple their lifespans over wild type as a proof- of-concept. The main goal for cave men was not having long-lived pets/companions but a good watch dog to alert us to potential predators during the night while we were asleep or an animal that paid its own way in support of hunting or other economically-useful collaborative activities.]

Also worthy of mention is that sequencing scientists announced this week that they are very close to publishing the Chimpanzee genome. Also, the Honey Bee draft is expected in mid-July, while the Sea Urchin draft, too, is coming along nicely. The draft Chicken genome is expected to be completed by early 2004.

[ Editor's Speculation:

Although they might not admit to it, I believe that gerontologists are a little like drunks searching for their lost keys under a lamp post (because that's where the light is). They are doomed to fail because they are not looking in the right place and complete strangers may find our keys before we do. Sigh!

We spend a great deal of time chasing after Telomeres, Reactive Oxygen Species, and Caloric Restriction, but in reality, we may not find out what we're looking for using these approaches for decades. Others (namely, comparative genomicists) who have little interest in the stated goals of gerontology are more likely to figure out and publish what we need to know before we can. Although they have somewhat of an advantage from funding by pharmaceutical companies' drug discovery programs with access to capital that we don't have, that is not really their major driver. If this hypothesis is true, let's just try to keep up with what our genetics colleagues are doing or else expect to be run over.]

Ref:

Rosie Mestel, "The Boxer Leads the Pack in Genome Project: Sequencing Will Help Scientists Analyze Other Dogs and May Shed Light on Human Diseases," The Los Angeles Times, p. 18 (May 24, 2003).

Gene Count in Human Genome Shrinks Significantly

May 23, 2003; Following the final draft of the human genome published last month, the number of human genes embedded in our estimated 3.1 billion base pairs of DNA (actually 27,322,000 uninterrupted base pairs of high-quality sequence have been published by the National Human Genome Research Institute) have just been reduced from an estimated 31,000 genes to only 25,000 genes or possibly even less! Recall that the original estimates were in the [80 - 140] thousand gene range. What's going on here? It seems that a large number of hypothetical genes were shifted from the "genes" category into the "junk DNA" category after they were found not to be true genes after all. For a relatively simple creature like brewer's yeast, the efficiency of genes embedded in DNA is on the order of 75 percent, whereas for humans, it has now been determined to be less than 1.5 percent! It still is not possible to scan a raw DNA sequence and pick out all the start-points and end-points of genes based on a set of simple "punctuation marks" (known specialized sequences, like STOP codons). Many of these "junk" sequences looked like they were once genes, and maybe they were once-upon-a-time, but then got broken during the course of evolution and are no longer functional ( vestigial genes, so to speak). Since there is no clear editing mechanism to get rid of vestigial genes in mammals, as there may well be in small-volume cells or viruses, where volumetric efficiency may be essential for survival, these non-functional "worthless" genes litter the genome and will keep getting copied for thousands of generations. But wait, the concept of "junk DNA" was invented by us, not by God. May the so-called "junk" is not junk at all. Maybe these sequences are essential for proper embryogenesis. Maybe the length of the junk is what is essential, not the exact sequence. And maybe the "junk" makes valuable control RNA (RNA that never exits the nuclear membrane as mRNA to synthesize proteins in the cytoplasm). By the way, the size of the human proteome (on the order of [150 - 250] thousand proteins) has not been revised, just because the estimated number of genes has been reduced. The one gene ---> one mRNA --> one polypeptide ---> one protein model does not hold for eukaryotic cells. The ratio of proteins:genes may be 10- or 20-to-one as a result of very clever re-splicing of messengers. The number of post polypeptide processing steps (methylations, glycations, etc.) may be as high as 20 or 30 that can operate so as to make a final protein uniquely functional. Anyway, the junk-DNA hypothesis suggests a variety of straightforward experiments to establish the value of "junk" sequences to the organism's survival and whether alterations in junk are typically lethal or of no consequence.

[ Editor's Note: The Cold Spring Harbor, New York, GeneSweepstake Betting Pool established over two years ago, may be completed soon [See next paragraph]. It is rumored that the winner will be announced next week. See the News Item on this website for the date of July 25, 2000 for the original statement of the GeneSweep Challenge.

June 6, 2003; Ewan Birney of the European Bioinformatics Institute near Cambridge, UK who organized the GeneSweep Contest at Cold Spring Harbor three years ago announced last week that Lee Rowen and two of her colleagues from Seattle were declared winners of GeneSweep, having made the best prediction with the lowest bids [4]. The best estimate for the number of human genes is now 24,500, of which 3,000 might actually be pseudo or otherwise broken genes that don't produce proteins and therefore don't really count. However, there's quite a bit of poorly explored DNA sequence dubbed dark matter that may contain a few more genes. So, this number is still just an estimate.]

Refs:

1. Sharon Begley, "Just How Many Genes Does It Take to Make a Human?", The Wall Street Journal, p. B1 (May 23, 2003).
2. AP, "Scientist Says Chimps Belong in Human Genus," The Los Angeles Times, p. A18 (May 24, 2003).
3. " Chimps and Bonobos are so similar to humans that they belong in the genus Homo, a report in The Proceedings of the National Academy of Sciences argues," The Wall Street Journal, p. A1 (May 20, 3003).
Humans and Chimps share 99.4 percent of their DNA (not 98.5 percent [sic], as I was taught for many years by my professors), according to Morris Goodman of the School of Medicine, Wayne State University in Michigan. The only member of the genus Homo not extinct today is Homo Sapien, viz. us. [ Homo neaderthalensis lost out in a competition during which we both cohabited the planet (but did not interbreed, as had been suggested by certain cavalier anthropologists.] Chimps ( troglodytes) and Bonobos ( paniscus) are currently placed in the genus Pan. There is no official Biology Board in charge of placing animals in their various genera, and in some cases there remains a true ambiguity and alternative taxonomies have been proposed with proselytizing commonplace in the narrow community. The important thing for us is to avoid this controversy altogether and realize that our search for genes that determine species maximum lifespan has just gotten simpler.
4. David Malakoff, "Human Genome: A Low Number Wins the GeneSweep Pool," Science, Vol. 300, No. 5625, pp. 1484-5 (June 6, 2003).
5. Wojciech Makalowski, "Genomics: Not Junk After All," Science, Vol. 300, No. 5623, pp. 1246-7 (May 23, 2003).
According to Makalowski's hypothesis regarding the value of "junk DNA," one has to realize that each organism is a dynamic work-in-progress with many genetic experiments-of-Nature going on concurrently within the genome. Nature did not intend for man or even mammals to be the final word. The "purpose" of many or these replicated, broken genes -- that don't appear to be doing anything useful from our point of view then is the result of multiple duplications of a single functional gene followed by random mutation and divergence of the various copies over time (Nature's little evolutionary experiments in progress) the copies don't reveal their etymology to us simply looking at their chromosomal location without some sleuthing, while preserving the essential function of the original gene during the course of experimentation (otherwise, we might achieve a lethal point-mutation for the entire organism).
[ Editor's Note: In computer jargon, this concept is called "reusable code," and experienced human computer programmers regularly utilize this concept of an open subroutine (as distinguished from a closed subroutine [with general-purpose parameters] in an algebraic computer language) as they develop new code in the most efficient manner possible (this technique has recently been called Object-Oriented Design). It makes more sense to modify a copy of a running program and then test it in isolation than either to reinvent such a program from scratch or to "play around" with a running program in such a way as to introduce a "bug" in the Operating System while it's still running. This latter type of bad programming technique might cause not just behavioral anomalies but a catastrophic system crash that would be impossible to debug or recover from!]

Senate Testimony on Proposed New Stem-Cell Lines

May 22, 2003; A US Senate panel heard testimony today by scientists being denied access to new human stem-cell lines, as it weighs legislation to overturn President Bush's curbs.

Refs:

1. Ali H. Brivanlou, Fred H. Gage, Rudolf Jaenisch, Thomas Jessell, Douglas Melton, Janet Roussant, "Perspectives: Setting Standards for Human Embryonic Stem Cells," Science, Vol. 300, No. 5621, pp. 913-6 (May 9, 2003).
2. Elias Zerhouni, Director of NIH, "Stem Cell Programs," Science, Vol. 300, No. 5621, pp. 911-2 (May 9, 2003).
3. Donald Kennedy, Editor-in-Chief, AAAS Science, "Stem Cells: Still Here, Still Waiting: What Concerns the Scientific Community Now Is How Access to New Lines of Stem Cells Can Be Arranged," Science, Vol. 300, No. 5621, p. 865 (May 9, 2003).

Therapeutic Cloning Is Good for America

May 14, 2003; Click for a Wall Street Journal Editorial by Drs. Shirley Tilghman, Ph.D., Molecular Biologist and President of Princeton University and David Baltimore, Ph.D., Nobel Laureate, Molecular Biologist, and President of the California Institute of Technology (February 26, 2003). An righteously indignant letter from a representative of the Family Research Council of Washington, D.C. and a satirical GRG Editorial in response follow.

Additional Reference:

Report of the American Association for the Advancement of Science (AAAS) Workshop held on March 11, 2003, Regulating Human Cloning (April 3, 2003).

Adenovirus Genetically Engineered to Block Gliomas in Mice

May 7, 2003; According to today's issue of The Journal of the National Cancer Institute, scientists at the University of Texas in Houston, have genetically engineered a common-cold virus to penetrate and destroy cells from inoperable, malignant gliomas (a form of brain tumor) in mice. This methodology should easily generalize to humans.

Ref:

CNN and Reuters.

Mouse Stem Cells Differentiate to Eggs

May 2, 2003; In a development that could alter the ethical landscape surrounding human Embryonic Stem (ES) cells, scientists have published in today's issue of Science that mouse ES cells are capable of developing into oocytes in vitro. It is not yet clear whether the cells can be fertilized and develop into embryos. But if so, and if human ES cells turn out to have similar powers, such cells might allow researchers to get around some of the expense and complex ethical questions that arise from using donated eggs for therapeutic cloning experiments [Ref. 4]. This is next on their agenda.

Karin Hubner [1], Guy Fuhrmann [2], Lane K. Christenson [3], James Kehler [1], Rolland Reinbold [1], Rabindranath De La Fuente [4], Jennifer Wood [3], Jerome F. Strauss III [3], Michele Boiani [1], Hans R. Sch”ler [1*], "Derivation of Oocytes from Mouse Embryonic Stem Cells," Science, Vol. 300, pp. 1251-6 (May 2, 2003).
______________________________________________________________
1. Germline Development Group
The School of Veterinary Medicine
University of Pennsylvania, New Bolton Center
382 West Street Road
Kennett Square, PA 19348, USA.
2. Centre de Neurochimie, Laboratoire de Neurobiologie du Developpement et de la Regeneration
FRE 2373 CNRS
5 rue Blaise Pascal
67084 Strasbourg Cedex, FRANCE.
3. Center for Research on Reproduction and Women's Health
The School of Medicine, University of Pennsylvania
1349 Biomedical Research Building 2/3 (6140)
421 Curie Blvd.
Philadelphia, PA 19104; USA.
4. Female Germ Cell Biology Group
Center for Animal Transgenesis and Germ Cell Research
The School of Veterinary Medicine
University of Pennsylvania, New Bolton Center
382 West Street Road
Kennett Square, PA 19348, USA.
_________________________________________________________
* To whom correspondence should be addressed... E-mail: scholer@vet.upenn.edu. _________________________________________________________

ABSTRACT:

[ GRG Editorial on Hermoclones: If we coin the term hermoclone to mean a clone of an individual (an identical twin displaced in time) but of opposite gender (something that does not exist in Nature, since opposite gender twins are always fraternal, never identical), we now have the technology to create a female hermoclone of a man, providing that human cloning could be made to work at all. In other words, a man may ask "what would it be like to raise a child who would be identical to me?" meaning, of course, a boy, but could now legitimately ask what it would be like to raise a copy of myself, but as a girl? (i.e., what would I look like if I were a girl?) This is a somewhat gratuitous question, since the technology is not here yet (we would need to enucleate an egg and 'fertilize' it with two carefully-selected X- Chromosome sperm {polyspermy}, thereby creating a complete diploid "XX" individual {female} that would then be inserted into the womb of a willing surrogate mother). But to my knowledge, no one has ever even thought of this fanciful experiment, even in literature. Readers: Please inform us if you can find a reference to this concept anywhere else.

And while we're at it, why not consider the possibility of a male hermoclone? If a woman were to combine the haploid nuclei of two of her eggs into a heterokaryon, then taking the Y-Chromosome from a selected sperm from one of her male relatives and using it to replace one of her X-Chromosomes (without replacement, you would obtain an XXY {Klinefelter's Syndrome} male child that would likely grow up to be sterile). Note: There's not that much genetic material along the "Y" Chromosome, so a male relative's Y would probably do just as well to get the full effect of a clone, even though it's not 100 percent identical to the index maternal genome. But even identical twins are not really identical. They have different finger prints, for example. They grow up in different parts of the uterine lining even though they share the same placenta and maternal blood supply, and they do exit the womb at different times depending on their location.

So, what's the purpose of putting this information here on a public website. One might ask, if it's such an original idea, why don't you patent it, as a method patent, first? (And by implication, get rich from your invention). Well, my idea is to put it in the public domain, so we can say that it was published here first, and so that nobody else can patent it. Hello. WWW.PTO.GOV: are you listening? All that we would like is for people to start using the term "hermoclone," a new English word, correctly, and give us credit, and we'll be happy.

However, an important additional motivation is to block the patent application of Dr. Norbert Gleicher of the Center for Human Reproduction in Chicago, who said at the Annual Meeting of the European Society for Human Reproduction and Embryology (ESHRE) in Madrid, SPAIN that he plans to patent the technique of developing mixed-gender embryos (chimeras). It is alleged that twelve chimeric embryos were grown to the six-day blastocyst stage before they were destroyed. The work was being pursued on the grounds that it would be a way to repair genetic disorders. However, in our view this work is not only ethically objectionable, it is scientifically and medically questionable, since there are potential long-term health risks and the possibility of congenital defects for any child, were this to be used in a clinical setting. See The Scientist (July 8, 2004).]

Stem Cells, Inc. Devises Treatment for Spinal Cord Injuries

May 2, 2003; New York, NY ( Dow Jones Newswires) -- Tiffany Kary reported that "StemCells Inc. (STEM) shares shot up as much as 204 percent after the company announced that preclinical data could lead to a treatment for spinal-cord injuries."

Refs:

1. University of Pennsylvania (May 2, 2003)
2. Smart Money (May 2, 2003).

GABA Boosts the Brains of Aging Monkeys

May 2, 2003; "Aging brains may be sharpened and, in effect, made young again briefly by increasing the levels of Gamma Amino Butyric Acid. Researchers at the University of Utah in Salt Lake City found that GABA appears to help extremely old rhesus monkeys focus their vision and thinking processes by silencing the interfering static from other neurons. "GABA filters out stray brain signals that may make thinking and seeing difficult in older brains," according to a study published in today's issue of Science.

Refs:

1. "Neurochemical Boosts Aging Brains, Study Says," The Los Angeles Times, p. A20 (May 3, 2003).
2. "Study Suggests Chemical May Help Aging Brains," CNN (May 2, 2003).

Using IVF Could End-Run the Risk of Human Reproductive Cloning

April 29, 2003; Scientists suggested during a discussion on cloning at the Human Genome Organization's Meeting in Cancun, Mexico that "the safety problem inherent in human reproductive cloning might be obviated if cloned human embryos were first used to derive healthy sperm and egg cells that could then be used in a standard in vitro fertilization procedure." "The process of egg and sperm production, called gametogenesis, naturally reprograms cells in readiness for fertilization," said cloning expert Dr. Rudi Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, MA.

Ref:

Helen Pearson, "DNA Re-Write Could Allay Cloning Fears: Extra Step Might Overcome Safety Objections to Reproductive Cloning," Nature (April 29, 2003).

President's Council on Bioethics to Address the Value of Longevity Research

April 28, 2003; "Age-Retardation: Scientific Possibilities and Moral Challenges," will be the title of the next Staff Working Paper of the President's Council on Bioethics chaired by Prof. Leon Kass of the University of Chicago. We expect to keep you informed of any new developments as they are announced.

Ref:

Ronald Bailey, "You Shouldn't Live So Long: Who Wants to Live Forever Anyway?", Reason-Online (April 9, 2003).

New Perspective on SARS: Media Over-Reaction

April 28, 2003; As of this date, approximately 300 persons have died of SARS (Severe Acute Respiratory Syndrome)(with no deaths in the US so far). There is an estimated 4,800 total cases of SARS worldwide. But we ought to strive for a more realistic perspective on the actual dangers of this new epidemic. Despite the existence of an effective Flu Vaccine for many years, 20,000 Americans still die from influenza every year and the media hardly notices. [Even worse, 40,000 Americans die on highways every year, and even worse, 400,000 Americans die of smoking-related diseases every year (lung and other forms of cancer, not to mention persons killed in fires started by smokers who fell asleep while smoking in bed), and the press makes hardly any mention of these statistics.] As Prof. David Baltimore said in an Editorial in today's Wall Street Journal [2], those of us who are professionally devoted to a rational analysis [of SARS], need to do more than wag our finger at the press, as they routinely swell the fear factor toward a level that could itself become a danger." We must be prepared for the possibility that this virus will settle into the human population (sort of like the AIDS virus and many other global viruses have done in the distant past), so that SARS may always be with us from now on, perhaps at a somewhat lower level.

For up-to-date information on the SARS Epidemic and current travel advisories to Asia, see the Centers for Disease Control and Prevention (CDC) website in Atlanta, GA as well as the World Health Organization (WHO) website of the United Nations based in New York. In Los Angeles, one may contact the office of Dr. Jonathan E. Fielding, M.D., M.P.H., Los Angeles County Medical Director and Chief Health Officer, Department of Health Services, the Acute Communicable Disease Control Program, and the Health Alert Network at 213-240-7941. Health warnings in English, Spanish, and Chinese can be obtained from this office as Adobe Acrobat PDF files.

The WHO stated that, as of Tuesday, April 15th, there were 3,235 cases of SARS worldwide [in 25 countries, but especially prevalent in China (Hong Kong, Shanghai, Singapore, and Guangdong Province), Canada (Toronto), USA, Vietnam (Hanoi), and Germany (Frankfurt)] with 154 suspected deaths thus far. Dr. Julie L. Gerberding, Director of the CDC said that Canadian researchers at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia (Dr. Marco Marra) had completed the DNA sequence for the SARS-Associated Coronavirus (distinct from other known viruses in this family [and it was not a picornavirus nor the H5N1 Avian Flu Virus nor a paramyxovirus as first suspected]) in record time. Twelve different labs participated in the global sequencing effort (including Erasmus University in Rotterdam, The Netherlands, The National Microbiology Laboratory in Winnipeg, Manitoba, Queen Mary Hospital in Hong Kong, French Hospital in Hanoi, and Joseph DeRisi's lab at the University of California in San Francisco using a 1,000-virus microarray gene-chip) and finished it in weeks instead of months. This will set a new standard for "future pandemics of infectious disease," said a report last week in The New England Journal of Medicine.

Refs:

1. Click for instructions on how to download (from Genbank) and inspect the SARS Coronavirus Genome Assembly itself... Release 2 Sequence of 29,763 Base Pairs.
2. Prof. David Baltimore, Ph.D., President of CalTech and Nobel Laureate in Medicine, "The SARS Epidemic: Severe Acute Media Syndrome?" The Wall Street Journal, pp. A1, 12 (April 28, 3003).
3. Tim Rutten, "Regarding Media: A Plea for Careful SARS Coverage," The Los Angeles Times, pp. E1, 10 (April 30, 2003).
4. Joshua Lederberg, "An Inner Peace: In Battling Disease, We Have to Settle for a Truce with the Microbes Inside Us," The Los Angeles Times, p. B17 (April 24, 2003).
5. Alexander Batalin, Correspondent, "The Atypical Pneumonia Virus Has Been Created Artificially Says Scientist Sergei Kolesnikov," RIA Novosti.
April 10, 2003; Irkutsk, Siberia; RUSSIA The virus of Atypical Pneumonia has been created artificially, possibly as a bacteriological weapon, believes Professor Sergei Kolesnikov, Academician of the Russian Academy of Medical Sciences. He expressed this opinion at a news conference on Thursday. According to him, "the virus of Atypical Pneumonia is a synthesis of two viruses (of Measles and Infectious Parotiditis or Mumps), a natural compound of which is impossible." This could be carried out only in a laboratory, the Academician is convinced. He also said that in creating bacteriological weapons a protective anti-viral vaccine is, as a rule, worked out at the same time. Therefore, the scientist believes, an antidote for Atypical Pneumonia may soon appear. He does not exclude that the spread of the virus could have begun accidentally, as a result of an unsanctioned leakage from some [Chinese?] laboratory. Click on Dr. Patricia A. Doyle's website for more details.
[ Editor's Note: We do not accept this alleged hypothesis to be true. It has the flavor of the now discredited searches for Big Foot, the UFO aliens who created British Crop Circles during the night, or the Loc Ness Monster in Scotland. Since when is Nature no longer capable of synthesizing a new virus on her own and without our permission?]
6. "SARS And Genetic Engineering?" published by the London-based Institute for Science in Society (April 27, 2003).
7. David P. Hamilton, "Will New Kind of Drug Work Against SARS?" The Wall Street Journal, pp. B1, 5 (April 30, 2003).
A 20-Oligo Anti-Sense-RNA Drug based on a Polyprotein detected in the SARS Viral Sequence developed by Dr. Patrick Iversen, Chief Scientist of AVI BioPharma, Inc. of Portland, OR, will be tested soon in a Biosafety Level-3 Lab to be provided by NIH.

8. Thomas H. Maugh, II, "Animals Sold as Delicacy in China May Transmit Virus to Humans," The Los Angeles Times, pp. A12-13 (May 24, 2003).
9. Matt Pottinger, "Link to Animals Solves One Riddle: Discovery Can Help Design Strategies Against SARS; Cultural Issues Remain," The Wall Street Journal, p. A1, D8 (May 27, 2003).
Masked-Palm Civet Cats are not cats at all, but look more like weasels or mongooses. They are typically butchered under unsanitary conditions and eaten in China as a delicacy. The Civet form of the coronovirus appears to be identical to the human form except for the existence of a small additional segment on one end of its RNA sequence. Experts speculate that the loss of that segment might have allowed the virus to jump from its animal reservoir to humans. The animals do not appear to get ill from their native form, but do have anti-bodies in their blood. Therefore, anyone coming into contact with civet feces or saliva might be at risk for contracting SARS.

April 17, 2003; Washington, D.C. According to Dr. Francis Collins, "researchers led by a team of scientists at the National Human Genome Research Institute have identified a gene ( LMNA = 25,000 BP) on Chromosome 1 (a single-point mutation of Cytosine [C] to Thymine [T]) responsible for Hutchinson Gilford Syndrome," a rare (only 100 cases observed throughout the world), non-inherited ( de novo) condition that affects young children, causing them to die at a very early age (average age of 13 years). It could be passed to the embryo through a flaw in the genes of the father's sperm. There is a missing stretch of 50 amino acids near one of the ends of the protein that appears to cause instability in the nuclear membranes of cells when they are put under stress. Finally, even though it is called progeria, Prof. Calib E. Finch of the Andrus Gerontology Center at USC has called this condition a "cartoon of aging," since those afflicted exhibit only some but not all of the manifestations of aging.

Refs:

1. NIH News Release, "Researchers Identify Gene for Premature Aging Disorder: Progeria Gene Discovery May Help Solve Mysteries of Normal Aging," National Human Genome Research Institute (April 16, 2003).
2. Annachiara De Sandre-Giovannoli [1], Rafaelle Bernard [2], Pierre Cau [3], Claire Navarro [1], Jeanne Amiel [4], Irene Boccaccio [1], Stanislas Lyonnet [4], Colin L. Stewart [5], Arnold Munnich [4], Martine Le Merrer [4], Nicolas Levy [6]*, "Lamin A Truncation in Hutchinson-Gilford Progeria," Science, Vol. 300, p. 1205 (April 17, 2003).
A rare premature aging syndrome is caused by a mutation in the gene for a protein that coats and organizes the interior surface of the nuclear envelope.
_______________________________________
1. Inserm U491: "Genetique Medicale et Developpement", Faculte de Medecine Timone, Marseille, FRANCE.
2. Departement de Genetique Medicale, Hopital la Timone, Marseille, FRANCE.
3. Inserm U491: "Genetique Medicale et Developpement", Faculte de Medecine Timone, Marseille, FRANCE;
Laboratoire de Biologie Cellulaire, Hopital Conception, Marseille, FRANCE.
4. Inserm U393, Hopital Necker, Paris, FRANCE.
5. Cancer and Developmental Biology Laboratory, NCI-Frederick, Frederick, Maryland, USA.
6. Inserm U491: "Genetique Medicale et Developpement", Faculte de Medecine Timone, Marseille, France; Departement de Genetique Medicale, Hopital la Timone, Marseille, FRANCE.
* To whom correspondence should be addressed: E-mail: Nicholas.Levy@medicine.univ- mrs.fr.
_______________________________________
3. Maria Eriksson [1], W. Ted Brown [2], Leslie B. Gordon [3], Michael W. Glynn [7], Joel Singer [5], Laura Scott [5], Michael R. Erdos [1], Christiane M. Robbins [1], Tracy Y. Moses [1], Peter Berglund [4], Amalia Dutra [1], Evgenia Pak [1], Sandra Durkin [7], Antaonei B. Csoka [6], Michael Boehnke [5], Thomas W. Glover [7], and Francis S. Collins [1], "Recurrent De Novo Point Mutations in Lamin-A Cause Hutchinson Gilford Progeria Syndrome," Letter to Nature, Vol. 423, pp. 293-8 and pp. 298-301 (April 25, 2003).
_______________________________________
1. and 4. National Human Genome Research Institute, and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
2. Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
3. Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, and Department of Pediatrics, Rhode Island Hospital, Providence, RI 02903, USA
5. Department of Human Genetics, and Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
6. Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA

Correspondence and requests for materials should be addressed to Dr. Francis S. Collins, M.D., Ph.D. at NIH [ E-mail: fc23a@nih.gov].

ABSTRACT:

Hutchinson Gilford Progeria Syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. Here, we present evidence of mutations in Lamin-A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to Chromosome 1q by observing two cases of uniparental isodisomy of 1q the inheritance of both copies of this material from one parent -- and one case with a 6-Mega Base paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harbored an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G (GGC > GGT), within Exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within Exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against Lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human aging.
_______________________________________
4. "Gene Is Discovered for Rapid Aging in Children," CNN (April 17, 2003).
5. AP, "Accelerated Aging Disorder Linked to a Genetic Mutation," The Los Angeles Times, p. A28 (April 17, 2003).
6. "Gene Scientists Have Identififed the Mutation behind Hutchinson-Gilford Progeria, or Very Premature Old Age...," The Wall Street Journal, p. A1 (April 17, 2003).
7. Leslie B. Gordon, M.D., Scott Burns, M.D., and Sam (their 7 year-old son with HGPS), "Family Crisis Becomes Scientific Quest," Science, Vol. 300, No. 5621, p. 899 (May 9, 2003).
8. "Aging Too Fast: Progeria Linked to Spontaneous Gene Mutations," Acumen Journal of Sciences, Vol. 1, No. 2, p. 98 (August/September 2003).

Stem Cells Repair Damage in Mouse Model of Multiple Sclerosis

April 17, 2003 ( AP) Researchers from Milan, Italy have injected stem cells into mice to repair damage and sharply reduce symptoms from an experimental form of MS.

Refs:

1. The Wall Street Journal, p. A1 (April 17, 2003).
2. "Study: Stem Cells Fix Damage in Experimental MS," CNN (April 17, 2003).

Milestone: Completion of the Human Genome Sequence

April 14, 2003; London, UK and Bethesda, MD, USA ( Reuters and AP) -- As had been planned by The International Human Genome Sequencing Consortium (US, England, Germany, France, Japan, and China) and The US Human Genome Research Institute for the occasion of the Golden (50th) Anniversary of the discovery of the double-helix shape of DNA --- for which Drs. Francis Crick and James Watson subsequently won the Nobel Prize --- the full sequence of human DNA has now been completed and has been posted on the Internet. Further details will be published in this week's issue of Nature.

Recall that a "Rough or Working Draft" has been available since June 2000. However, it covered only 90 percent of the genome, whereas this final version covers 99 percent of the 3.1 billion base pairs. The earlier draft had an error rate of 1:1,000 with 150,000 gaps, while the final version has an error rate of only 1:10,000 with only 400 gaps. Many of these gaps still remain, however. For unknown reasons, some of the sequences are difficult to replicate in bacteria (they may be toxic) and other parts express highly repetitive sequences (like the telomeres and centromeres at the ends of middle of our 23 pairs of chromosomes, respectively) and are known not to contain genes. The total number of estimated genes still remains in the neighborhood of 30,000, the vast majority of whose functions are still unknown. The "scientist bet" at the Long Island, New York Cold Spring Harbor Laboratory on who proves to be closest to the final number is still ongoing. On the other hand, the identification of disease-related genes has exploded from less than 100 in 1990 to more than 1,400 such genes today. Many parts of the genome don't appear to encode for genes at all but may nevertheless be vitally important for control of downstream gene expression. In other words, some sequences may not encode for mRNAs that are subsequently translated to proteins in the cytoplasm, but up to 255 microRNAs (nearly 1 percent) may remain in the nucleus to serve for subsequent gene expression control. [See Science (March 7, 2003)].

Serious Comparative Genomics among humans, chimpanzees, monkeys, rats, bats, whales, dogs, cats, cows, and other mammals has really yet to begin. A windfall of clinically-useful information regarding transformation of genotype-to-phenotype, secondary to communication by growth factors among embryonic stem cells, is expected to result from this work in the next four or five years..

The number of DNA sites containing SNPs (Single Nucleotide Polymorphisms) has grown to 10 million. This is the part of the DNA that helps us distinguish one human individual from another (extremely useful for forensic identification). The HapMap Project, announced in October, is intended to pinpoint the 100,000 variations deemed most useful for tracking down genetic traits and predisposition to disease. The effort is expected to take another three years. The newly-formed ENCODE Project (ENCyclOpedia of DNA Elements) will re-analyze 1 percent of the genome in much greater detail to identify every functioning element. It aims to tease out all the myriad of functions throughout a tiny sliver of the genome. ENCODE will examine regions known to contain genes-of-interest and others regions selected randomly.

Refs:

1. CNN (April 14, 2003).
2. CNN (April 15, 2003).
3. Rosie Mestel, "Human Genome Is Completed Now Comes the Hard Part," The Los Angeles Times, p. A18 (April 15, 2003).
4. AP, "Human Genetic Map Is Done," The Wall Street Journal, pp. A1, D5 (April 15, 2003).
5. Nicholas Wade, "Once Again, Scientists Say Human Genome Is Complete," The New York Times, pp. D1,4 (April 15, 2003).
6. Britain's Wellcome Trust offers a excellent primer on genome research and its potential impact on medicine and society. The Genome Browser profiles each chromosome and highlights its important genes. Visitors can read news updates and features on topics ranging from gene therapy to the origin of red hair. Helpful backgrounders explore the ethical implications of genome research.
7. Malcolm Campbell, Genome Consortium for Active Teaching (GCAT).
8. A. Malcolm Campbell, Genomics, Proteomics, and Bioinformatics, Course based on his textbook with Laurie J. Heyer, Discovering Genomics, Proteomics, and Bioinformatics (This course comes on CD-ROM published by Benjamin/Cummings, New York; 2003; $70.60 on Amazon.com).
9. Jackson Laboratory, Bar Harbor, ME, annotated Gene Expression Database describing thousands of mouse genes activated during different stages of murine embryogenesis, Science, Vol. 300, No. 5621, p. 973 (May 9, 2003).
10. Elizabeth Pennisi, "Human Genome: Reaching Their Goal Early, Sequencing Labs Celebrate," Science, Vol. 300, No. 5618 , p. 409 (April 18, 2003).

Cloning Primates Is Really Difficult

April 10, 2003; Washington, D.C. ( AP) Cloning humans, or any other primates, may be impossible with today's techniques because of a fundamental molecular obstacle, say scientists trying to understand why attempts to clone monkeys have failed. From the very first step, cloned primate cells don't divide properly, secondary to a deformed spindle apparatus which causes chaotic polyploid chromosomes, too abnormal for pregnancy to even begin, Clavin Simerly and his colleagues at the University of Pittsburgh report in tomorrow's issue of the journal Science. They describe more than 700 futile attempts to clone rhesus monkeys. In other animals, spindle-apparatus proteins aren't as tightly bound to the egg's DNA and remain in the egg after the DNA is removed. On the other hand, it appears that there may be a relatively simple way to sidestep the problem by combining cloning with old-fashioned egg fertilization. More on this idea later.

Refs:

1. Lauran Neergaard, AP Medical Writer, "Studies: Human Cloning May Be Impossible," (April 10, 2003).
2. John Travis, "Egg's Missing Proteins Thwart Primate Cloning," Science News, Vol. 286, No.18, p. 286 (May 3, 2003).
3. Gautam Naik, "Doctor Who First Cloned Sheep Sets Sights on Human Embryo," The Wall Street Journal p. A1 (April 11, 2003).
Dr. Ian Wilmut, Father of Dolly and Joint Head of the Department of Gene Expression and Development at the Roslin Institute in Edinburgh, SCOTLAND, says he will "seek permission this Summer for the cloning of human embryos from the UK Human Fertilization and Embryology Authority to conduct experiments leading to a cure for Lou Gehrig's Disease or ALS (Amyotrophic Lateral Sclerosis), a neurodegenerative disease that afflicts 350,000 people world- wide and kills 100,000 each year.
4. Antonio Regalado, "University of Pittsburgh Group Seeks to 'Humanize' Pig Organs," The Wall Street Journal (April 10, 2003).
An investor group led by the University of Pittsburgh Medical Center has bought out the US operations of PPL Therapeutics, PLC of Blacksburg, VA formed by the Roslin Institute of Scotland. They will continue their research with pigs, attempting to knock out both porcine genes responsible for acute immune rejection of xenotransplanted organs in humans. The pig organs will be tested in monkeys within the next two months. Success in monkeys would be a prerequisite before human transplants could begin.

Europeans Vote to Severely Constrain Use of Embryonic Stem Cells

April 10, 2003; This decision could see the use of Embryonic Stem Cells barred across most of Europe. Click for more details.

Refs:

1. Pat Hagan, "Euro MPs Vote Against Stem-Cell Research," The Scientist (April 20, 2003).
2. PM, "EP Bans Stem-Cell Research," Nature Biotechnology, Vol. 21, No. 5, p. 473 (May 2003).

Dr. Zavos Publishes a Preliminary Experiment in Human Cloning in a Peer-Reviewed Journal

April 9, 2003; Lexington, KY Dr. Panayiotis M. Zavos, Ph.D., Andrologist, and CEO of ZDL, Inc., a supplier of equipment for testing sperm, will soon publish a paper entitled "Human Reproductive Cloning: The Time Is Near," in the British journal Reproductive BioMedicine On-Line in its next issue (Vol. 6, No. 4, June 2003). The journal's Editor-in-Chief, Dr. Robert G. Edwards, was one of two British scientists who produced the world's first "test-tube baby" via in vitro fertilization back in 1978. Dr. Zavos described a single human embryo that had grown to 8 to 10 cells over a period of four days. This work, like that published earlier by scientists at ACT of Worcester, MA, is considered very preliminary, and it is not yet clear whether these first steps are truly on the right track. At least this work will not be called a hoax, as was said of the Clonaid company's announcements with great fanfare that began in December of last year.
[ Editor's Note: Although not illegal in the U.S., it is reported that this work was accomplished abroad.]

Refs:

1. Antonio Regalado, "Human Embryo Is Cloned, Expert to Say in Paper," The Wall Street Journal, pp. D1, 2 (April 9, 2003).
2. Aaron Zitner, "Scientists Clone Banteng in Effort to Save Dying Species," The Los Angeles Times, p. A18 (April 8, 2003).
In an unrelated development, Dr. Robert Lanza and colleagues at ACT have succeeded in cloning two Southeast Asian horned cows called Bantengs on an Iowa farm. Fewer than 8,000 are thought to exist worldwide. Previous attempts to clone endangered species had been attempted with a Gaur and a Mouflon, a Mediterranean sheep.
3. "Another Endangered Species Cloned," Science, Vol. 300, No. 5618, p. 421 (April 18, 2003).
4. KP, "New Life in Banteng Gene Pool," Nature Biotechnology, Vol. 21, No.5, p. 473 (May 2003).
5. Louis M. Guenin, "The Set of Embryo Subjects," Nature Biotechnology, Vol. 21, No.5, pp. 482-3 (May 2003).

Why Do So Many Centenarians Live in Nova Scotia?

April 3, 2003; Halifax, Nova Scotia, CANADA --- The answer, it seems, lies in the genes of the inhabitants --- "the Yarmouth area was settled by only 20 or 30 families, the Acadians, who, after their rough treatment by the English, were not inclined to mix with people from the rest of their Province. Today they still speak French, display the Arcadian flag, while local radio stations play dance music not unlike that played in Louisiana... Thus, the genes that have predisposed them to extreme longevity have been passed down from generation to generation," speculated Dr. Chris MacKnight, who seeks answers to why some of the very old are spry, while others among them are frail. Scientists suspect that there may be a few age-defying genes and hope to discover drugs that mimic their function. To skeptics, that sounds a bit like a futile quest for the fountain of youth. Nevertheless, Dr. Tom Perls, Director of the New England Centenarian Study at Boston University said, "We're not seeking a fountain of youth so much as a fountain of 'aging well'." Centenarians tend to be healthier than one might think 40 percent avoid chronic illnesses until their 85 or older, 20 percent postpone age-related debilities until they're age 100 or more." Longevity-enabling genes might protect Centenarians in the same manner as Caloric Restriction, the only longevity intervention that has been experimentally shown to extend life across many species. Another common element, free-radicals, may spur atherosclerosis and Alzheimer's Disease and could be a key mechanism or root cause in aging of many species. Lifestyle, however, can play a role, in that Centenarians tend to be prudent, rarely smoking, drinking heavily, or becoming obese. "No matter how close we come to discovering gerontic genes, no matter how well we may discern the biological protections that Centenarians share in common, it seems that the-very-old will always be an exceptionally heterogeneous group, each one with a unique story to tell, but without a lot of superficially- obvious easy-to-imitate things in common."

Dr. Perls and his colleagues with Centagenetix, Inc. in Cambridge, MA ^* are examining the DNA from 137 sets of Centenarian Siblings. [ Editor's Note: Centagenetix has recently merged with Elixir Pharmaceuticals of Cambridge, MA. Elixir's stated Mission is "to discover therapeutics to slow aging, forestall the disease and disability that accompany aging, and extend life's most productive period."] By studying the epidemiology and genetics of Centenarians, Centagenetix has focused on Human Chromosome 4, narrowing their search to a few hundred genes. (See the News Item from June 17, 2002 on this Website citing their PNAS paper of June 11, 2002.)

Around Noon time on Saturday, January 18th, while answering questions after a standard talk at the USC Annual Symposium on Animal Species Exhibiting Gradual Senescence [ SOSA-2 (Symposium on Organisms with Slow Aging) -- The focus of this year's Symposium was on the natural life history of aging in long-lived birds and reptiles. Leading gerontological researchers ranging from field biologists and zoological specialists to molecular geneticists presented, with a final Saturday afternoon session devoted to human longevity ], Perls acknowledged that his company had reduced their search down to two SNPs, but he couldn't reveal the name of the gene, as a scientific paper describing their work had been submitted for publication in Nature and was still under review.

Ref:

Mary Duenwald, "Puzzle of the Century: Is It the Fresh Air, the Seafood, or Genes?: Why Do So Many Hardy 100-Year Olds Live in, Yes, Nova Scotia?" Smithsonian Magazine, pp. 75 - 80 (January 2003).

[ Notes from GRG Members:
A few of our GRG members have pointed out that this article is largely a human-interest story (i.e., based on statistically illiteracy).
For example, Mr. Louis Epstein of New York writes, "the density of Centenarians in Nova Scotia (CANADA), is certainly not on the scale of Nuoro Province (ITALY) or Okinawa Prefecture (JAPAN). Indeed, Canadian Supercentenarians have generally not even come from Nova Scotia, but from other Canadian provinces."
Furthermore, Mr. Robert Young of Atlanta writes, "Alina Morton, Laura Rollock, and Rose McDonald all reached 110 years. While the rate of 21 Centenarians-per-100,000 is higher than average, it is not extremely high and is lower than it is for some U.S. states. Many researchers are guilty of selectional bias; they should compare numbers to the Birth Cohort, not the Population-Living-There-Today, because areas with high emigration tend to have distorted numbers of Centenarians. That said, much of the rest of the differences can be attributed to better lifestyles in the rural areas of the U.S. North and in CANADA."
_______________________________
* [ Editor's Note: Tom told me personally that, to preserve his scientific objectivity, he deliberately chose not to hold an equity position in the company, despite the fact that he was one of its co-founders.]

Texas Heart Institute Uses Adult Stem Cells to Restore Heart Muscle Post MI

April 1, 2003; Chicago, IL ( WSJ) Dr. Emerson C. Perin and colleagues from the Texas Heart Institute in Houston reported encouraging early results of efforts to use a patient's own bone-marrow cells to restore heart muscle tissue damaged by a heart attack at the Annual Scientific Meeting of the American College of Cardiology. The researchers "injected immature cells directly into heart muscle tissue in 14 patients. The effort led to improved blood flow to damaged tissue and improved ability to participate in daily activities compared with 7 patients who didn't get the treatment." Further studies are planned.

Ref:

Ron Winslow, "Pharmacia, Guidant Heart Studies Show Progress," The Wall Street Journal, p. D8 (April 1, 2003).

Geron Demonstrates Differentiation of Hepatocytes from Human Embryonic Stem Cells

April 1, 2003; Menlo Park, CA ( Business Wire) -- Geron Corporation announced today the publication of research results that describe the production of hepatocytes --- the basic functional cells of the liver from human Embryonic Stem Cells (hESCs). These studies demonstrate that cells with multiple characteristics of hepatocytes, including drug- metabolizing enzyme activity, can be reproducibly differentiated from hESCs. These cells have potential for widespread use in drug discovery research as well as for transplantation therapy for patients with liver failure.

As published in the March issue of Cell Transplantation, Geron scientists describe protocols that differentiate hESCs into human hepatocytes that express Albumin, Alpha-1- Antitrypsin, Glycogen, and other proteins found in human adult liver cells. Importantly, the cells also express certain Phase-1 and Phase-2 drug-metabolizing enzymes which are responsible for metabolizing most pharmaceuticals.

A reliable source for the production of human hepatocytes with well-characterized and reproducible properties would have a major beneficial impact on the drug discovery process. Currently, drug candidates are tested for toxicity and metabolic effects on the liver late in the discovery process using tools and methods that are inadequate. For example, access to primary human liver tissue is very limited, and hepatocytes isolated from adult liver tissue cannot be propagated in tissue culture. The available rat and mouse models only approximate human metabolism, and biochemical assays based on liver microsomes do not represent the complete physiological environment of liver cells. The widespread availability of standardized, normal human hepatocytes produced on a large scale from hESCs would allow drug metabolism and toxicity studies to be performed earlier in the drug discovery process, enabling the elimination of toxic compounds before undertaking costly human trials.

"This discovery serves as a foundation for the commercialization of hESC-based cell types for drug discovery applications," stated Dr. Thomas B. Okarma, M.D., Ph.D., Geron's President and CEO. "Both large pharmaceutical companies and small biotechs would benefit from the availability of hepatocytes derived from hESCs that can reliably represent a functioning liver. We have already received two U.S. Patents covering hESC-derived hepatocytes and their use as drug screening tools [U.S. Patent Nos. 6,458,589 and 6,506,574]. Our next steps are to complete the characterization of these cells and to develop a high-volume production process. At that point we have a product."

In addition to the hepatocytes described in this publication, Geron has generated six other cell types from hESCs that are being developed into therapeutic productsHematopoietic Progenitors, Dopaminergic Neurons, Oligodendrocytes, Cardiomyocytes, Beta-Islet Cells, and Osteoblasts. All cell types exhibit normal functions expected of that cell type if isolated from adult tissue. The company is currently conducting pre-clinical animal safety and efficacy studies with four of these cell types.

Refs:

1. Tomi Kilgore, "Geron Stock Rallies on Results of Liver-Cell Studies," (April 1, 2003)
2. "Geron Shares Rise 28 Percent on Stem-Cell Research: The Biotech Company Says It May Be Able to Help Scientists Test Drugs for Liver Toxicity," The Los Angeles Times, p. C2 (April 2, 2003).
3. Brief Item under Also, "Geron said that it would raise as much as $24 million through a sale of stock," The Los Angeles Times, p. C3 (April 9, 2003)

Note: See related Geron stories dated March 27th and 19th below.

GDNF for Parkinson's Disease

March 31, 2003; Madison, WI ( AP) As published in the latest issue of Nature Medicine, Clive N. Svendsen of the University of Wisconsin demonstrated that all five patients in the trial testing GDNF (Glial-Cell-Line Derived Neurotrophic Factor), delivered by continuous pump infusion, experienced measurable improvement in their involuntary tremors associated with Parkinson's Disease.

Refs:

1. CNN (March 31, 2003).
2. In Brief, "Drug Shows Promise for Parkinson's Patients," Los Angeles Times (March 31, 2003).
3. Nicholas Wade, "Promising Results Are Seen in Small Parkinson's Trial," The New York Times pp. D1,7 (April 8, 2003).

Cell Fusion May Repair Bad Livers

March 31, 2003; Bone-marrow cells may regenerate the liver by cell fusion not by cellular differentiation. Xin Wang and colleagues at the Oregon Health and Science University in Portland transplanted "Fah-/- deficient"mice with bone-marrow cells from Fanconi Anemia group- C gene (Fancc) homozygous-mutant mice and Fah-wild-type mice. 80 "XXXY" (diploid-to-diploid fusion) and 120 "XXXXYY" (diploid-to-tetraploid fusion) karyotypes indicated a fusion between donor and host cells. Click on the Ref. for more details...

Ref:

Tudor P. Toma, "Cell Fusion Repairs Liver," The Scientist (March 31, 2003).

Bad Economy Has Devastating Effect on Small Biotechnology and Stem-Cell Firms

March 27, 2003; ACT, Geron, PPL Therapeutics, and many others are in trouble. ESI of Australia may be one counterexample. Human Embryonic Stem-Cell (ES Cell) and therapeutic-cloning investments have fallen 50 percent in the last three years, to $50.2 million in 2002, mirroring the plunge in stock prices for the Biotechnology Sector as a whole. It seems that investments in any sort of speculative research are all but over. Analyst Steven Dickman of Techno Venture Management in Boston says, "While the science remains very interesting, from a venture-capital perspective, the bloom is off the rose. Even companies like Geron have to spin their results so that shareholders can see the excitement." ACT has lost three of its four highest-profile scientists (Drs. Tanja Dominko, Tony Perry, and Teruhiko Wakayama) that were recruited with great fanfare. PPL Therapeutics of Edinburgh and Blacksburg, VA announced that it will simply leave the field and try to sell off its "regenerative medicine" assets. Geron laid off 40 of its 90 staff members. Its stock fell from a high of $69 a share in 2000 to $1.70 a share today. But they have two-year's worth of cash in the bank. BresaGen of Athens, Georgia has lost nearly one-third of its staff in the last six months. Their stock fell from more than 90 cents a share in late 2000 to 15 cents last week. They have only one-year's cash reserve in the bank. "There's a lot of intellectual property [patent rights] out there that can be had for very cheap prices," said John Smeaton, CEO of BresaGen.

Refs:

1. Gretchen Vogel, "Stem Cells Lose Market Luster," Science, Vol. 299, No. 5614, pp. 1830-1 (March 21, 2003).
2. Mark Henderson, "EU Curbs Threaten British Stem-Cell Research," British News (March 29, 2003).

ACT Wins Patent Dispute

March 22, 2003; An Appeals Panel at the U.S. Patent and Trademark Office ruled in favor of Advanced Cell Technology of Worcester, MA and against Infigen, Inc. of DeForest, WI in their ownership fight over three key animal cloning patents (based on a technicality). ACT still faces a significant legal challenge from Geron, Inc. of Menlo Park, CA which owns the cloning technology that they acquired from the Roslin Institute of Edinburgh, Scotland.

Refs:

1. ( AP) Biotechnology, "Advanced Cell Prevails in Cloning Dispute," The Los Angeles Times, p. C3 (March 22, 2003).
2. JLF, "ACT Wins Patent Dispute," Nature Biotechnology, Vol. 21, No 5, p. 473 (May 2003).

Geron Proposes Telomerase as Anti-Cancer Vaccine

Note: See item dated April 1st above.

March 19, 2003; Geron Corp. of Menlo Park, CA has published in the current issue of the journal Cancer Gene Therapy research supporting the use of telomerase as an anti-cancer vaccine. The genetically-engineered vaccine helped kill three types of cancer cells, including melanoma and colon cancer in vitro. Many of our colleagues, however, are skeptical about the toxicity of this compound in vivo.

Ref:

( AP) "Geron Soars After Research Backs Cancer Vaccine," The Los Angeles Times, p. C4 (March 19, 2003).

Americans Are Living Longer

March 14, 2003; Atlanta, GA ( AP) The CDC reported today that a dip in some disease deaths has permitted US Life Expectancy Statistics to top 77...

................2000...............2001
Overall:77.0 years..........77.2 years
[ Note: In 1900, life expectancy was around 49; while in 1929, it was 57.1 years]

Demographics by Gender:
Males:....74.3................ 74.4 years
Females: 79.7................ 79.8 years

Drop in deaths from major disease:
Pneumonia: 7 percent
Heart Disease: 4 percent
Cancer: 2 percent.
Stroke: nearly 5 percent

Note: Homicides increased by 17 percent, but this was an anomaly due to the events surrounding September 11th. Without the attacks, the homicide rate would actually have declined by 1.7 percent.

Refs:

1. "CDC: Americans Living Longer Than Ever," CNN (March 14, 2003).
2. "Average Life Expectancy Increased to 77.2 Years in 2001," The Wall Street Journal, p. A1 (March 17, 2003).

Aging Experts Give Silver Fleece Award to Clonaid

Friday, March 14, 2003; Chicago, IL (AP) -- "A group that claims to have cloned the first human babies, and capsules that purport to combat old age, are recipients of tongue-in-cheek awards from three prominent aging experts. The "Silver Fleece" awards announced Thursday were created by Dr. S. Jay Olshansky, a scientist at the University of Illinois at Chicago, aging expert Prof. Leonard Hayflick of the University of California at San Francisco, and Dr. Bruce Carnes, who studies the biology of aging at the National Opinion Research Center in Chicago. The trio contend the Anti-Aging industry's claims aren't backed up by good science.

The selection of Clonaid, the group whose recent cloning claims have been questioned by many scientists, was a "no-brainer," Hayflick said. Clonaid claims on its website that in the eventual cloning of an adult, memories and personality will be transferred into "a brand new body," allowing people to "wake-up after death."

Also winning an award are capsules called Longevity, sold by Urban Nutrition, Inc. as an "Anti-Aging" formula. The recipients "are people who are trying to exploit the fear of death that almost everyone has," Carnes said.

But Thomas Kaenzig, Clonaid's Vice President, said the criticism comes from "backward- oriented scientists" akin to those who said 50 years ago "that we will not be able to go to the moon. Matthew Oden, Urban Nutrition's marketing manager, said Longevity doesn't claim to reverse or stop aging, even though the company calls it an "Anti-Aging" formula. That's "more just a buzz word," he said. "The product is primarily promoted as helping rejuvenate appearance and the immune system," Oden said.

The awards -- "bottles of corn syrup labeled 'Snake Oil'" are modeled after the "Golden Fleece" awards created by former U.S. Sen. William Proxmire to highlight questionable government spending.

Refs: 1. Silver Fleece
2. William M. London, "Longevity, Clonaid Receive Silver Fleece Awards for 2003," Skeptical Inquirer, Vol. 27, No. 4, p. 9 (July/August 2003).
[ Editor's Note: William London is the Program Director and Editor of the NCAHF Newsletter, National Council Against Health Fraud.]

Senate Bans Partial Birth Abortion by 64 to 33

March 13, 2003; The likely scenario is that the House will follow suit sometime this Spring and once President Bush signs the measure into law, which he has vowed to do, having already praised the work of the majority of the Senators, the only way to stop the politicians from looking over the shoulders of the gynecologists is in the courts.

Refs:

1. Richard Simon, "Senate Oks Bill to Curb Abortions," The Los Angeles Times, pp. A1, 28, 29 (March 14, 2003).
2. David G. Savage, "Logic of Debate on Abortion Is Questioned," The Los Angeles Times, p. A16 (March 13, 2003).
3. David Rogers, "Senators Defeat Attempt to Ease Planned Late-Term Abortion Ban," The Wall Street Journal, pp. A1, 4 (March 13, 2003).
4. Editorial, "Hypocrisy in Abortion Vote," The Los Angeles Times, p. B12 (March 19, 2003).

Bovine DNA To Be Sequenced

March 8, 2003 ( Reuters); The National Human Genome Research Institute has approved spending $50 million to sequence all the genes in cattle. The work will be done in Texas at the Baylor College of Medicine in Houston and Texas A&M University. The Maryland- based research institute (at NIH), which has sponsored projects to sequence the human genome as well as the collection of genes in mice, fruit flies, and other animals, said it would put up half the money if the rest could be raised from other sources. Texas Gov. Rick Perry said, "the state would pay $10 million and work to raise an additional $15 million, adding that the project promised benefits for human health and the biotechnology industry, as well as gains for the beef and dairy industries." The bovine genome is similar in size to those of humans and other mammals, with an estimated size of 3 Giga Base Pairs (3 GBP).

"By comparing the human genome with the genomes of different organisms [ Comparative Genomics], we can better understand the structure and function of human genes and thereby develop new strategies in the battle against human disease, said Dr. Francis Collins, the Institute's Director. "The more genomes we have, the more powerful this tool becomes."

Ref:

Reuters, "Genome Institute OKs Funding of Cattle Gene Study," The Los Angeles Times (March 8, 2003).

Bone-Marrow Adult Stem Cell Surprise: Select Monocytes Can Transform to Neurons

March 1, 2003; Dr. Eliezer Huberman of Argonne National Laboratory in Illinois will publish in an upcoming PNAS that different growth factors can switch isolated bone-marrow monocytes into what appear to be liver cells, blood vessel cells, neurons (using Nerve Growth Factor [NGF], and other non-macrophage immune-function cells. The monocyte population that has been identified differs from multipurpose bone-marrow stem cells. Patent applications on the medical use of monocyte stem cells have already been submitted. It is speculated that these may be the cells that travel to damaged organs for purposes of repair. We still need to do two things: (1) Confirm that the transformed cells are functional and (2) whether these adult monocytes lose their potency with age. Check back here for the Abstract in PNAS and for more details as they become available.

First Ref:

John Travis, "Stem Cell Surprise: Blood Cells Form Liver, Nerve Cells," Science News, Vol. 163, No. 9, p. 131 (March 1, 2003).

Autologous Adult Stem Cells Transplanted into Teenager's Damaged Heart

March 6, 2003; Royal Oak, MI (AP) --- An experimental procedure aiming to grow new cardiac muscle and vessels in a damaged heart was tried yesterday at a hospital in Michigan. Private companies, however, have approached the area of cell therapy tentatively. Regalado [2] writes, "although the markets are potentially huge, it hasn't been clear how to establish a successful business model, especially in cases where the product is the patient's own cells. On the other hand, a treatment for heart attacks would present a major breakthrough for the field. G-CSF (Neupogen) from Amgen of Thousand Oaks, CA was used to enrich the number of bone-marrow stem cells in the bloodstream. Then doctors harvested the cells using leukopheresis (with cell sorter). Ten doses of the stem-cell-concentrated solution were injected by catheter into a vessel of the teenager's heart." Within five days, Dimitr's Cardiac Ejection Fraction (quantity of blood pumped out with each beat) rose form 25 to 35 percent. We should know in about three or four months if this treatment is working.

Refs:

1. "Stem Cells Transplanted to Teen's Heart," CNN (March 6, 2003).
[ Editor's Note: There is a stunningly beautiful animation on the CNN website called "Embryonic Stem Cell Research" that can be gotten to by a single mouse click from the story above. It's worth the price of admission just for that.]
2. Antonio Regalado, "Doctors Use Teen's Stem Cells in Procedure to Repair His Heart," The Wall Street Journal, pp. A1,9 (March 6, 2003).
3. Thomas H. Maugh, II, "Stem-Cell Procedure May Let Teen Live Normally: Michigan Boy Has the Experimental Transplant after a Nail Gun Pierced His Heart," The Los Angeles Times, p. A21 (March 6, 2003).

House Passes Weldon-Stupak Bill Banning All Forms of Human Cloning

February 28, 2003; Washington, D.C. Two years ago the US House of Representatives approved a comprehensive ban on human cloning by a vote of [265:162]. However, the measure has never been taken up by the Senate. Yesterday, Rep. David Weldon (R- FL) submitted The Human Cloning Prohibition Act of 2003 [HR 534] that would set up a prison term of up to 10 years in jail and civil fines of $1 million or more for anyone who performed (or tried to perform) human cloning for any purpose whatsoever. This Bill passed decisively by [241:155]. largely along party lines, but with a number of crossover votes going both ways.

Rep. Susan Wilkins Myrick ( R-NC) argued, "Cloning would be the most ghoulish and dangerous enterprise in human history." Later, Rep. Todd W. Akin ( R-MO) spun it as "some sort of Brave New World that none of us wants to find ourselves in ... a world in which parts of human beings are stored like parts in a junkyard."

[ Editorial Comment: This statement is in the same truth-value equivalence-class as the statement, "I've never seen or heard of any man living forever, so I might as well die now and get it over with." This, in turn, is equivalent c. 1000 A.D. to "I've never seen or heard of a man who could fly, so men can never fly." But just in case, let's pass a law against attempts to fly and put the Wright Brothers in jail, if we ever were to locate them before they were successful. By the way, if only the imagined "junkyard" existed, I would sign myself up immediately and be the first one on line. How could it be that there are educated, seemingly-intelligent adult human beings who are seeking to criminalize what I myself am deliberately trying to do? I always thought of myself as a nice guy.:-)

More seriously, why did the House repeat, yesterday, this shameless exercise of two years ago? Answer: Because they could. And, of course, to perpetrate the illusion of momentum in the minds of the American public in favor of themselves as enemies of "murderers of human babies." By the way, they regularly put in a plug for research on adult stem cells, but I haven't seen any big pot of money thrown at this problem either.

On the other hand, the Senate is still too sophisticated for the White House Staffers and Religious Fundamentalists to crack; so, for the moment, we are stuck. The dispute over research cloning is so sharp that no Bill may pass Congress this year, leaving the US as one of the few developed nations with no ban on reproductive cloning! Talk about "throwing out the baby with the bath water." (Forgive the pun.)

There must be a lot of behind-the-scenes jockeying for position among religious fundamentalists, women's rights groups, the National Right-to-Life Committee, and various anti-abortion groups allied with the White House, who are all pushing for an agenda that insists on any form of human cloning as "tantamount to killing a baby for the sake of research." However, on the other side are patient-groups lobbying for particular diseases, medical scientists trying to understand what's going on, and the biotechnology industry as a whole.

But, sadly, both alliances seem to be equally impotent. The conservatives don't appear to have the 60 votes they need for cloture in the Senate to officially criminalize what they don't like about what they think we might be able to do someday, while the medical establishment, on the other hand, doesn't yet know how to do what it is they are accusing us of trying to do. Nevertheless, both sides are willing to fight-to-the-death over things that, today, are merely hypothetical speculations.

The Weldon bill is neither a repeat of the July 2001 bill that passed nor of last year's Brownback bill that was withdrawn before a Senate vote could be taken. The Weldon bill is so draconian, it would not only prohibit patients traveling abroad to receive embryonic stem-cell treatments, in particular, by requiring them to be arrested upon their return to the US (as in Brownback), it would also prohibit the importation of any medical therapy created from cloned embryos in general, even though the development was legal in the country of origin.

The arrogance of our legislators is breathtaking! They are telling us, "if you want to live in this country, you're going to live under our religious ideological control, whether you like it or not. If you wish to escape from our jurisdiction, for any reason, by going abroad, don't expect to ever return and try and live here again, or we'll send you to jail as a criminal!" This legislation would certainly override a new law governing legal therapeutic cloning in the State of California that was signed last year by Gov. Gray Davis and went into effect on January 1st of this year. Should California secede from the Union over the issue of therapeutic cloning? How else can we prevent conservatives in Washington, D.C. from deciding what constitutes a crime in what should rightfully be our own jurisdiction?

According to Reuters, President Bush has vowed to veto any bill (even the reasonable bills of Kennedy/Hatch/Feinstein/Specter/Harkin) that "does not outlaw all forms of human cloning." I am sure that Sen. Bill Frist (R - TN), Senate Majority Leader and also an M.D. who is looking for a middle ground, knows this too. Can Dr. Frist schedule Dr. Michael West, Ph.D., CEO of ACT to testify at the upcoming Senate Subcommittee hearings? ]

Refs:

1. "House Opens Debate on Cloning," CNN (February 27, 2003).
2. Aaron Zitner, "House Votes to Outlaw Human Cloning: Ban Includes Research," The Los Angeles Times, p. A32 (February 28, 2003).
3. Ted Agres, "House Passes Anti-Cloning Measure: Bill Would Criminalize Research Using Human SCNT," The Scientist (February 28, 2003).
4. Mark Ingebretsen, "Senate Readies for Battle Over Bill to Ban Cloning," The Daily Scan, The On-Line Wall Street Journal (March 3, 2003).
5. A. Scott Loveless, "A Better Cloning Plan," Salt Lake Tribune (March 2, 2003).
6. Norah Vincent, Op-Ed Piece, "Ethics Must Trump Mindless Technology," The Los Angeles Times, p. B17 (March 6, 2003).
[ Editorial Remark: Ms. Vincent, a columnist in Yardley, PA and frequent editorial writer, is passionately concerned with what she sees as "blind technological advance" and "the juggernaut of scientific progress." But the speed of a train depends on whether the background is standing still. For those of us who are interested in science and technology, the train seems to be hardly moving at all! [Yet, it does move.] Ms. Vincent cites the work of ACT in November 2001 with parthenogenesis as her "end run" from the ethical dilemma created by the possibility of all forms of cloning, not just reproductive but also therapeutic cloning. She equates disposing of pre-implantation viable human embryos with abortion. But, she warns, therapeutic cloning is even worse than abortion, because it is premeditated at conception. At least some abortions have moral purpose if, for example, they followed a rape or incest that were outside of our control. Deliberate harvesting of embryos, for her, results in "gruesome test-tube fodder." It's amazing, to me, how conservatives, who are so passionately adverse to abortion, are willing to offer unsolicited advice about "adult" stem-cell technology without offering us any evidence that it works. In fact, as far as I know, there is little evidence that embryonic stem cells work, since the data is so sparse. The few positive experiments we have have not been faithfully and routinely reproduced in other labs. We are at the Wright-Brothers stage of aeronautical engineering. We need a huge set of controlled experiments with mice that compare murine adult stem cells with embryonic stem cells in both old and young mice to see what really works. It will cost a lot of money (but not that much, maybe $10 million) and it will take a long time (but not that long, maybe two to three years), but it's all doable by NIA/NIH if we get started. Will Ms. Vincent aggressively support the research needed to figure out whether adult stem cells work? Most interestingly, if they can be shown to work, can they be stimulated with growth factors in situ to replenish tissues that are shriveling up or thinning out as we age?]
7. Editorial, "The Good Kind of Cloning," The Los Angeles Times, p. B12 (March 12, 2003).
Bill S. 245 (Sen Sam Brownback ( R - Kan)) proposes to ban all forms of human cloning (and criminalize even unsuccessful attempts to conduct therapeutic cloning by medical scientists within the jurisdiction of US law enforcement) by subjecting convicted suspects to up-to-ten-years-in-prison and fines of up-to-$1-million. I think you have my attention Senator. On the other hand, a competing bill, S.303 (Sen. Orrin G. Hatch ( R - UT)), proposes to prohibit reproductive cloning but allow for the possibility of legal therapeutic [or research] cloning. S.303 would also adopt strict regulations modeled after a successful oversight system put into effect two years ago in Great Britain. The Times Editorial clearly favors Hatch over Brownback, calling the latter a "sledgehammer." Voting in the Senate is expected to take place next week. Stay tuned for the details.

By the way, does anybody know how passage will affect the current law that went into effect here in California on January 1st? Is it true that there is no grandfather provision for earlier state laws that conflict with a newly-minted federal law? Please E-mail us if you know the answer to this question.

8. Steve Coles, "Therapeutic Cloning Should Not Be Banned," The Los Angeles Times, p. B10 (March 17, 2003).
9. Don C. Reed, "Let Hope Grow in a Petri Dish," The Los Angeles Times, p. M5 (March 16, 2003).
Mr. Reed is Chairman of a lobbying group that raised $4.8 million for California legislation to promote therapeutic cloning known as Californians for Cure. Mr. Reed's son, Roman, is paralyzed and much in need of stem- cell therapy.
10. One-Page Letter-to-Science by LeRoy Walters, Kennedy Institute of Ethics at Georgetown University in Washington, D.C., "Research Cloning, Ethics, and Public Policy," Science, Vol. 299, No. 5613, p. 1661 (March 14, 2003).
11. Two Letters to the Editor, "Stem-Cell Research Should Stay in U.S.," The Los Angeles Times, p. B16 (March 20, 2003).
12. Editorial, "Get Real," Scientific American, Vol. 288, No. 4, p. 10 (April 2003).
[ Editor's Remarks: This Editorial is clearly pro Therapeutic Cloning. The Editors of Scientific American attack technocynics like Drs. Francis Fukuyama and Bill Joy while promoting one of our own members, Prof. Greg Stock of UCLA. They go on to cite the poet, Henry David Thoreau [1817 - 1862] as "regarding trains, telegraphs, newspapers, and even the delivery of mail as dehumanizing." But our biggest danger is not that science will run ahead of ethics concerns, but the exact opposite: that ethical hair triggers will paralyze truly worthy research. "We should deal with actual rather than imaginary problems." Just because there are a small group of literary intellectuals who can imagine them, doesn't mean that all potential problems merit immediate action, just that one ought to be aware of them. No technology has ever conferred unalloyed bliss on its beneficiaries. However, side-effect problems are usually corrected by refinements to the technology or legislation on its use. Driving your automobile on a freeway will always be a more-or-less dangerous activity depending on the traffic and weather conditions. But do you want to give up cars? In similar fashion, just because the satirist Jonathan Swift could imagine the problem of the Struldbruggs (a race of people who figured out how to ask for immortality but forgot to ask for youthfulness, and therefore suffered the problem of getting perpetually older but were never allowed to die; you know, the problem of the Sorcerer's Apprentice or "Be careful what you ask for, because you just might get it.") in his (political) children's story Gulliver's Travels doesn't mean that we ought to terminate our scientific quest for immortality, since, under certain circumstances, it might lead us down a slippery slope or cause us to make an "unnatural bargain with the devil." We can admire Swift for the cleverness of his cautionary tale --- he was a smart guy, but that's all. It does means that we need to think about what we're doing, while we're doing it, but not to stop doing it out of fear of side effects. Cars do bring other problems with them... traffic lights that don't work all the time or air bags that might go off when they shouldn't. "To stop research would be to give up trying to make the world a better place. Such would deny human nature ostensibly to save it."]
13. Michael Shermer, Publisher of Skeptic Magazine and General Editor of The Skeptical Encyclopedia of Pseudoscience, "I, Clone: The Three Laws of Cloning Will Protect Clones and Advance Science," Scientific American, Vol. 288, No. 4, p. 38 (April 2003).
The Three Laws of Cloning (based loosely on "The Three Laws of Robotics" so well articulated in Isaac Asimov's I, Robot science-fiction stories, but without the self- referencial recursion) are as follows:
(1) A human clone is a human being no less unique in his or her personhood than an identical twin;
(2) A human clone shall have all the rights and privileges that accompany this legal and moral status;
(3) A human clone is to be accorded the same dignity and respect as would be due to any other member of our species.
Prof. Shermer goes on to refute various myths about cloning ranging from "Identical Personhood," and "Playing God," to "Human Dignity," many of which are based on pure ignorance of the scientific issues. It is unclear, however, that he is doing anything here other than "preaching to the choir." Let's revisit the problem after it's been done.
14. The Human Cloning Foundation of Georgia claims to be an official site in support of human cloning technology. They have at least five very good books advertised on the right-hand frame of their site. [ Note: HCF has been determined to be a 501(c)3 non-profit organization and, therefore, all donations are tax-deductible to the extent permitted by law.]
15. Bill McKibben, Op-Ed Piece, "Keep Us Human: If We're Truly Smart, We'll Refuse to Foolishly Tamper with Our DNA," The Los Angeles Times, p. B11 (April 14, 2003).
Based on his newly published book, Enough: Staying Human in an Engineered Age (Times Books, New York; 2003).

Mr. John I. McMorran [1889 - 2003]

February 25, 2003; Lakeland, FL; We are sad to report that Mr. John I. McMorran, born June 19, 1889, died on Monday, February 24th at the age of 113 years, 250 days, of heart failure and complications related to pneumonia. We have been tracking John as the Oldest Living American Male for many years, and a video clip of him at age 111 is available on the Centenarian portion of this website. Mr. Michael Bradley, Administrator of the Tandem Health Care Nursing Home at the Socrum Loop Facility in Lakeland, informed us that John's Grandson Robert and his Great Grandson Scott, came to visit John regularly during the 11 years he resided at the nursing home, which was not always true of many other long-term residents. Furthermore, John was very pleased a few years ago to learn that the LA-GRG had officially designated him as Oldest Living Man in America.

John was alert up until the last two weeks of his life, when he declined to eat or drink, and the reason why they decided to hospitalize him during his last few days. When asked "to what if anything he attributed John's extreme longevity?" Robert answered that "His Grandfather worked hard all his life, and he was a kind man who had a great sense of humor." The family decided that an autopsy would not be performed, despite my protest that we would attempt to publish a summary of the findings in a medical journal, and it might be an important contribution to the scientific literature. But, obviously, we respect the privacy of the families of our Supercentenarins as our highest priority. John's funeral was held on Friday, February 28th in Michigan.

For those who are wondering about the name of John's successor, our new Oldest Living American Male is Mr. Fred Hale of New York State. His son, Fred Hale, Jr., reports that, as of this morning, his father, Mr. Hale, Sr., is alive and well. We will keep you posted.

Refs:

1. AP, CNN International (February 25, 2003; 5:37 GMT).
2. Myrna Oliver, "J. McMorran, 113; Oldest Man in U.S., 5th-Oldest Ever," The Los Angeles Times, p. B14 (February 27, 2003).

Rhesus Monkeys To Be Cloned From Embryonic Cells

February 21, 2003; Beaverton, OR ( Science News) --- The birth of Dolly provoked an international furor about the possibility of human cloning. Donald Wolf, of the Oregon Regional Primate Research Center, worries that the world will similarly overreact if he and his colleagues clone an adult nonhuman primate, such as a rhesus monkey. That fear "is a disincentive to continue, but [we] simply can't be intimidated," he says. "There's such a need for genetically identical monkeys, such as for AIDS-vaccine work, that we need to press on."

Several years ago, Wolf's team successfully cloned monkeys by using the nucleus of an embryonic cell. Yet, it hasn't succeeded when starting with the nucleus of a cell from an adult monkey. Indeed, the researchers are still struggling to get such cloned embryos ready for transfer into a surrogate mother.

"Progress has been slow and has been limited. We're trying to establish conditions where we can get [cloned] embryos to grow to the implantation stage. Once we do that with a reasonable degree of regularity, we'll go back to doing embryo transfers to establish pregnancies," Wolf said, "We're on the cusp."

Ref:

John Travis, "Dolly Was Lucky: Scientists Warn that Cloning Is Too Dangerous for People," Science News, Vol. 160, No. 16 (October 20, 2001).

Dolly, the First Cloned Animal, Dead at Age 6

February 14, 2003; Edinburgh, UK ( CNN); Dr. Harry Griffen, Head of the Roslin Institute, said that a decision was taken to euthanize Dolly after she was diagnosed with an irreversible lung disease [ Pulmonary Adenomatosis or Jaagsiekte]. Dolly, named for country-western singer Dolly Parton, was born on July 6, 1996, and therefore lived for 6 years, 222 days. Although Finn-Dorset sheep can live for as much as 11 or 12 years, lung infections are common in older sheep, particularly those housed in-doors. A full post-mortem (autopsy) will be conducted to report any significant findings. Afterward, Dolly's body will be placed on display at the National Museum of Scotland. She is survived by at least three of six healthy lambs, whom she conceived in the conventional manner. Click the photo above for more details.

Refs:

1. Janet Stobart and Rosie Mestel, "Sheep Dolly, 6, Dies; Pioneer Clone's Birth Sparked Debate," The Los Angeles Times, pp. A1, 3 (February 15, 2003).
2. Rosie Mestel, "Dolly's Death Resurrects Debate on Cloning Ethics: Death a Reminder of Cloning's Complexity," The Los Angeles Times, pp. A1, 32 (February 16, 2003).
[ Editor's Note: The best statistics for the affect of cloning on longevity comes from mice. (The data on sheep, cows, goats, rabbits, pigs, cats, and rats are too sparse, while data from dogs and monkeys are virtually non- existent; preliminary data for human cloning obtained by researchers at ACT of Worcester, MA were not encouraging, while data from the Raelian Sect {three alleged cases in the US/Israel, The Netherlands, and South Korea}, unless they are willing to provide some scientific evidence to the contrary, may be nothing more than an elaborate hoax in which the media was victimized into providing free publicity in exchange for a non-existent story.) In particular, with regard to mice, Japanese researchers have found that cloned mice died somewhat earlier than normal mice, dying prematurely from a combination of pneumonia, damaged livers, and tumors. Prof. Rudolf Jaenisch, of the Whitehead Institute for Biomedical Research in Cambridge, MA has examined 10,000 mouse genes in the livers and placentas of cloned mice and found that hundreds of these genes exhibited abnormal patterns of activation (especially associated with "imprinting"). Even the most basic steps in the process of cloning remain exquisitely treacherous, sort of like performing brain surgery with a hammer, a chisel, and a screw driver."]
3. "Dolly the sheep was euthanized on Friday due to lung disease. The first sheep cloned from an adult cell lived just six years, half a normal lifespan," The Wall Street Journal, p. A1 (February 18, 2003).
4. Jim Giles and Jonathan Knight, "Dolly's Death Leaves Researchers Woolly on Clone Aging Issue," Nature, Vol. 421, p. 776 (2003).
Dr. Ian Wilmut, leader of the team that created Dolly at the Roslin Institute in Scotland, said that "the post mortem revealed that she suffered from a virus that caused lung tumors characteristic of the disease. There were no other gross abnormalities, apart from her arthritis, which was diagnosed last year."
[ Editor's Note: Therefore, Dolly's death appears to be unconnected with cloning per se, as the virus that causes this pulmonary infection has afflicted both cloned and normal sheep at this same Institute.]
5. "A Sad Farewell for Dolly the Sheep, the World's First Cloned Mammal," New Scientist, Vol. 177, No. 2383, p. 8 (February 22, 2003).
6.Gretchen Vogel, "Dolly Goes to Greener Pastures," Science, Vol. 299, No. 5610, p. 1163 (February 21, 2003).
"... Wilmut and his colleagues, meanwhile, are continuing to push the frontiers: They are applying for one of the first licenses in the UK to begin nuclear transfer experiments with human cells. Also, the Institute has decided to suspend its livestock cloning program and is concentrating instead on trying to better understand the cloning process in mice."
7. "In Memorium: Good-Bye, Dolly," Scientific American, Vol. 288, No. 4, p. 30 (April 2003).
8. KP, "Dolly, the First Cloned Sheep, Dies," Nature Biotechnology, Vol. 21, p. 349 (April 2003).
[ Editor's Note: This article contains a very nice Table of Cloning Success Rates for goats, mice, cows, sheep, cats, pigs, and rabbits. Cloning Efficiency is defined as the number of live offspring expressed as a percentage of the total number of nuclear transfer oocytes where the DNA donor cell was an adult cell. Roslin Institute.
9. "Dolly is Dead, But Her Legend Lives On," Science, Vol. 300, No. 5618, p. 423 (April 18, 2003).
Dolly went on display last week as a new exhibit at the Royal Museum in Edinburgh. "The embalming involved mounting Dolly's skin on a fiberglass mold of her body and fitting her with glass eyes and resin hooves."

C150T Gene Mutation Prevalent in mtDNA of Italian Centenarians

February 12, 2003; Pasadena, CA ( CNBC) - Prof. Giuseppe Attardi of the Molecular Biology Department at CalTech has published new findings in the February 4th issue of the Proceedings of the National Academy of Sciences on the distribution of mitochondrial mutations in Italian Centenarians. Click for more details.

Zhang J, Asin-Cayuela J, Fish J, Michikawa Y, Bonafe M, Olivieri F, Passarino G, De Benedictis G, Franceschi C, and Attardi G.*, "Strikingly Higher Frequency in Centenarians and Twins of mtDNA Mutation Causing Remodeling of Replication Origin in Leukocytes, Proc. Natl. Acad. Sci. USA, Vol.100, No. 3, pp.1116-21 (February 4, 2003).
____________________
* Division of Biology, California Institute of Technology, Pasadena, CA 91125; USA.

Abstract:

The presence of a genetic component in longevity is well known. Here, the association of a mtDNA mutation with a prolonged life span in humans was investigated. Large-scale screening of the mtDNA main control region in leukocytes from subjects of an Italian population revealed a homoplasmic C150T transition near an origin of heavy mtDNA-strand synthesis in approximately 17% of 52 subjects [99 - 106] years old, but, in contrast, in only 3.4% of 117 younger individuals (P = 0.0035). Evidence was obtained for the contribution of somatic events, under probable nuclear genetic control, to the striking selective accumulation of the mutation in centenarians. In another study, among leukocyte mtDNA samples from 20 monozygotic and 18 dizygotic twins, 60-75 years old, 30% (P = 0.0007) and 22% (P = 0.011), respectively, of the individuals involved exhibited the homoplasmic C150T mutation. In a different system, i.e., in five human fibroblast longitudinal studies, convincing evidence for the aging-related somatic expansion of the C150T mutation, up to homoplasmy, was obtained. Most significantly, 5'-end analysis of nascent heavy mtDNA strands consistently revealed a new replication origin at position 149, substituting for that at 151, only in C150T mutation-carrying samples of fibroblasts or immortalized lymphocytes. Considering the aging-related health risks that the centenarians have survived and the developmental risks of twin gestations, it is proposed that selection for a remodeled replication origin, inherited or somatically acquired, provides a survival advantage and underlies the observed high incidence of the C150T mutation in centenarians and twins.

Ref:

"People Over 100 Share Genetic Mutation, Study Says," The Los Angeles Times, p. A26 (February 15, 2003).

Homologous Recombination Used to Create Knockout Mice and Disease-Gene Deletion in Human Embryonic Stem Cells

February 9, 2003; Madison, WI ( Reuters) Drs. James Thomson and Thomas Zwaka of the University of Wisconsin have deleted a disease gene from human embryonic stem cells. They are currently working on Lesch-Nyhan Disease, a rare type of mental retardation caused by a single mutation that affects boys.

Refs:

1. "Scientists Replace Human Stem Cell Genes," CNN (February 10, 2003).
2. Eithan Galun, "Gene Therapy Has Vast Potential Despite Setbacks; Push On with Human Trials," The Los Angeles Times, Op-Ed Piece, p. B13 (February 18, 2003).
3. John Travis, "Mining the Mouse: A Rodent's DNA Sheds Light on the Human Genome," Science News, Vol. 163, No. 8, pp. 122-3 (February 22, 2003).

US Senate Bill S.303 Will Allow Human Therapeutic Cloning, While Banning Reproductive Cloning

February 7, 2003; Click for more details.

Telomere Length Linked to Life Expectancy

January 31, 2003; As published in today's issue of The Lancet [1], Dr. Richard Cawthon and colleagues of the University of Utah in Salt Lake City have analyzed the telomere lengths of chromosomes from blood samples taken from 143 men and women aged 60 years or older (originally drawn for a different reason back in the time period [1982 - 1986]). The shortest quarter had a mortality rate from infectious disease (pneumonia) that was 8 times higher than those with the longest telomeres. Also, patients with telomere lengths in the shorter half had a 3 x higher morality rate from heart disease. Dr. Elizabeth Blackburn, a molecular biologist and telomere expert from UC San Francisco said that "this was the first such association with mortality that she had seen in the literature." "This does not mean that telomere shortening is necessarily a cause of aging. However, it could be statistically associated as a side effect of aging," she said.

Abstract:

During normal aging, the gradual loss of telomeric DNA in dividing somatic cells can contribute to replicative senescence, apoptosis, and/or neoplastic transformation. In the genetic disorder Dyskeratosis Congenita, telomere shortening is accelerated, and patients have premature onset of many age-related diseases and early death.

We aimed to assess an association between telomere length and mortality in 143 normal unrelated individuals over the age of 60 years. Those with shorter telomeres in blood DNA had poorer survival, attributable in part to a 3.18-fold higher mortality rate from heart disease [95% Confidence Interval: [1.36 7.45], P = 0.0079], and an 8.54-fold higher mortality rate from infectious disease [1.52 47.9]; P = 0.015. These results lend support to the hypothesis that telomere shortening in human beings contributes to mortality in many age-related diseases.

Refs:

1. Richard M. Cawthon, Ken R. Smith, Elizabeth O'Briend, Anna Sivatchenkoc, and Richard A. Kerberc, "Association between Telomere Length in Blood and Mortality in People Aged 60 Years or Older," The Lancet, Vol. 361, No. 9355, pp. 393-5 (February 1, 2003).
2. Rosie Mestel, "DNA Structure Linked to Lifespan: A New Study Suggests the Length of Telomeres, 'Caps' at the End of Chromosomes, Offer Clues to Life Expectancy," The Los Angeles Times, p. A17 (January 31, 2003).

Saturday, February 1, 2003; Noon PDT; We share the grief of the families of the seven astronauts who perished when the Space Shuttle Columbia disintegrated upon reentry early this morning (5:53 AM PST - 7:59 AM CST] and fell from the sky ~40 miles above North Eastern Texas, USA. There is no better way to honor their memory than by continuing their work.

GRG Editorial: President Asks for a Ban on All Human Cloning

Tuesday, January 28, 2003; President Bush's delicately-worded statement in his State-of-the-Union Address seeking to criminalize all human cloning, not just reproductive cloning [with which we strongly agree], but also therapeutic cloning [with which we strongly disagree], with the support of the US Senate was impeccably crafted as follows:

"And because no human life should be started or ended as the object of an experiment, I ask you to set a high standard for humanity and pass a law against all human cloning." [applause]

We believe that the presuppositional logic in above sentence is a rhetorical masterpiece. "A+" to the White House speech-writer who wrote it and probably burned the midnight oil seeking to articulate in this speech means to advance the Administration's religious agenda without alienating ordinary, middle-of-the-road American viewers. But we believe that it is the GRG's job to expose this sort of sophistry for what it is... striving to make an inherently wrong idea palatable to ordinary folks before they know what they've signed up to. Indeed, the State of California legislation passed last year and that went into effect on January 1st with the aim of funding therapeutic cloning is likely to be overruled if the US Senate were to pass newer legislation and the California law was inconsistent with Federal law.

A full GRG Editorial on the subtleties of human cloning will be posted on this website if we can ever get any of the groups that are striving to accomplish reproductive cloning to provide us with scientific evidence of their alleged success rather than a flimsy press conference touting their claims. Don't forget the boy "who cried wolf." Someone might actually do it quietly off shore. Who knows?

Refs:

1. "President Delivers the State-of-the-Union," U.S. Capitol, www.whitehouse.gov (January 28, 2003; 9:01 PM EST).
2. State-of-the-Union Address, The Los Angeles Times, p. A12 (January 29, 2003).

UC Scientists Switch Bird Beaks

January 24, 2003; In today's issue of Science University of California San Francisco scientists report that they have swapped neural crest cells, using a very fine needle into the eggs, at the 36-hour stage of avian embryogenesis, so that live ducks were born with the pointy beak of a quail, while live quail were born with the flat bill normally found on ducks. These chimera may ultimately lead to a better understanding of facial birth defects in humans, like cleft palate.

" Qucks," " Duails," and Beak Morphology

Vertebrates have been remarkably successful at adapting to new environments, and the evolution of complex head and face features is considered fundamental to their origins and diversity. Their developmental flexibility is particularly evident in the bird beak, whose morphology has undergone dramatic diversification and specialization over time. In a report in the ( January 24th issue of Science, Schneider and Helms revealed some of the cellular and molecular mechanisms that underlie this remarkable variability. In an elegant set of experiments, they exchanged neural crest cells -- which produce skeletal and connective tissue in the head and face-- between the beak-developing regions of growing quail and duck embryos. Normal ducks have long, flat bills, while quails typically have shorter, narrower ones. But in the transplant recipients, the resulting beak shapes were characteristic of the donor species, and not of the host into which the donor cells were transplanted. In other words, transplanting duck cells into a quail yielded a duck-billed quail, and vice versa. This suggests that neural crest cells control beak development in a species-specific manner. Furthermore, genetic analysis demonstrated that these cells pattern beak development by maintaining their own molecular programs and by regulating gene expression in adjacent host tissues.

Ref:

Paul Trainor, "Development: The Bills of Qucks and Duails," Science, Vol. 299, No. 5606, p. 523 (January 24, 2003).

Now a Dutch Couple Is Said to Have a Clone?

January 4, 2003; Amsterdam; NETHERLANDS ( MS-NBC) Clonaid, the company that claims to have produced the first human clone last week, said today that a second cloned baby girl has been born yesterday at 10:00 PM local time to a Dutch lesbian couple (the surrogate mother was also the egg donor and the nuclear-transfer provider, so she gave birth, as in the case of the American Mother of Eve, to her genetically-identical twin; she was said to be 32 years old). But neither baby has been confirmed to be a clone by genetic testing, and mainstream scientists are skeptical of the company's claims.

[ Editor's Note: As of this hour, the location of the baby has not been revealed (maybe in Northern Europe, but not Holland). Give us a break! Is this a hoax intended to produce free publicity for the Raelian Sect? Hello!]

Where in the USA does Eve's Mother live? Where in Europe was "Eve2" born? We cannot continue to cut slack for this group indefinitely. Privacy can be maintained if there is a credible third-party who can serve as a witness without any financial ties to the principals. It is rumored that Clonaid expects to charge more than $200,000 per procedure. Dr. Guillen is rumored to have a conflict-of-interest in that he sought to sell a TV documentary on the Raelians to a half-dozen media companies several months ago, and he is no longer affiliated as a science journalist with ABC-TV News.

Refs:

Stem Cells Offer Hope to Heart-Attack Victims

January 3, 2003; London, UK ( Reuters) --- "Stem cells may help patients recover from heart attacks by triggering new cell growth in damaged tissue," scientists said on Friday. Click for more details.

News Items for 2002

Click for News Items from 2002.

FDA Warns Michigan Hospital Not To Repeat Stem-Cell Transplant

June 12, 2003; Royal Oaks, MI; A 16-year old Michigan boy who received a pioneering stem-cell transplant in February after suffering a heart attack will have no further treatments for now. Recall from our story of March 6th below that Mr. Dimitri Bonnville was accidentally shot in the heart with a nail gun on a construction site [sigh!], and after surgeons at Beaumont Hospital removed the nail, he had a heart attack that destroyed nearly a third of his heart's muscle cells. As the condition could only worsen with time, he would either need a new heart transplant or an experimental bone-marrow stem-cell transplant directly into the damage heart. The latter was tried and seems to have worked! The day after the doctors disclosed the experiment, the FDA began an inquiry. When the hospital declined to conduct additional requested experiments with animals before further human procedures would be allowed to continue, the FDA ruled that they would not permit further treatment despite the fact that the initial experiment, conducted without any authorization, seems to have worked.

[ Editor's Note: There is an exciting and promising, but contradictory, flood of new data being published on stem-cell treatments, and we believe that much more work needs to be done in laboratory animals before human trials get underway in this country. So we view this move by Federal regulators as a prudent approach, at least for the time being.]

Ref:

Antonio Regalado, "FDA Holds Up Hospital's Work with Stem Cells," The Wall Street Journal, pp. A1, B1,4 (June 12, 2003).

Geron Announces UK Authorization for Stem-Cell Derivation

June 11, 2003; Menlo Park, CA ( Business Wire) Geron Corp. (Nasdaq: GERN) today announced that the Human Fertilization Embryology Authority (HFEA) of the UK has authorized the Roslin Institute to derive new human Embryonic Stem cells (hES cells) from donated excess embryos created as a result of In Vitro Fertilization (IVF) treatment. The Institute's research, funded by and conducted in collaboration with Geron, seeks to establish new hES cell lines as well as to improve the technology to produce and maintain hES cells in culture. The new hES cells lines will be used in research.

The HFEA is charged with licensing and monitoring IVF procedures, donor insemination, and human embryo research in the UK. Any derivation of human embryonic stem cells in the UK requires a license from the HFEA. Before granting a license, the HFEA considers the scientific, ethical, and medical aspects of the project.

"We are pleased that the HFEA has granted a license to enable this important research," said Dr. Jane S. Lebkowski, Ph.D., Geron's Vice President of Regenerative Medicine. "The additional hES cell lines that we expect to derive at Roslin will expand our current resource of six hES cell lines, and increase the genetic diversity of the cell lines we can use for research. We also expect this work to continue our progress in making the derivation and culture of hES cells more efficient."

Human embryonic stem cells are unique cells that can develop into all cells and tissues in the body. Geron is developing hES cell-based approaches to treating spinal cord injury, Parkinson's Disease, heart failure, diabetes, and other diseases. Geron has built an international portfolio of patent applications covering technologies it has developed to enable the scalable growth and differentiation of hES cells, as well as various differentiated cell types that can be produced from hES cells. In addition to the patents it owns, Geron holds licenses under U.S. Patent Nos. 5,843,780 and 6,200,806, including exclusive rights to develop and commercialize neural, cardiomyocyte and islet cells derived from hES cells for therapeutic applications.

Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for applications in oncology and regenerative medicine, and research tools for drug discovery. Geron's product development programs are based upon three patented core technologies: telomerase, human embryonic stem cells, and nuclear transfer.

Refs:

1. Denise Gellene, "Patent News Sends Geron Stock Up 15 Percent," The Los Angeles Times, p. B2 (June 11, 2003).
2. Cynthia Schreiber, "Geron, Ariad, ..." The Wall Street Journal, p. C8 (June 11, 2003).
3. AP, "Geron's Stock Soars on Patent Grant," The Kansas City Star San Francisco, CA (June 10, 2003).
The newly issued patent involves a technology to purify hES cells to increase their potency and covers a method of inserting an "apoptotic gene" into a cell that becomes activated only when the cell does not develop properly. The requirement for this patent is not yet clear to researchers.

Genetic Engineering of Cochlea Hair Cells in the Inner Ear

June 1, 2003; Prof. Yehoash Raphael of the University of Michigan in Ann Arbor published in today's issue of the Journal of Neuroscience a technique for growing new sensory hair cells in guinea pigs, using gene therapy, for the first time. Sharks grow new hair cells throughout their lives, and some birds can too; but no mammals exhibit similar regenerative powers. Loss of hair cells in the inner ear results in the kind of deafness most commonly suffered by the elderly.

Ref:

John Travis, "Getting an Earful," Science News, Vol. 163, No. 23, p. 355 (June 7, 2003).

First Cloned Mule

May 30, 2003;

As reported in today's issue of Science Magazine,

"A Mule Cloned from Fetal Cells by Nuclear Transfer,"
Gordon L. Woods 1*, Kenneth L. White 2, Dirk K. Vanderwall 1, Guang-Peng Li 2,
Kenneth I. Aston 2, Thomas D. Bunch 2, Lora N. Meerdo 2, and Barry J. Pate, 2
Science, Vol. 300, No. 5624 (May 30, 2003).

1. Northwest Equine Reproduction Laboratory, Department of Animal and
Veterinary Science, University of Idaho, Moscow, ID 83844, USA.
2. Center for Developmental and Molecular Biology, Biotechnology Center, Animal,
Dairy and Veterinary Sciences Department, Utah State University, Logan, UT 84322, USA.
* To whom correspondence should be addressed: E-mail: gwoods@uidaho.edu.
______________________________________________

ABSTRACT:

A mule, an animal that is incapable of reproducing naturally, has been successfully cloned.

[ Editor's Note: The pdf file of this Brevia on-line article has a fabulous picture of Idaho Gem.]
____________________________________________________________________
GENETICS:
First Cloned Mule Races to Finish Line
by
Constance Holden (p. 1354)

On May 5th, a mule named Idaho Gem was born after a normal 346-day gestation in the womb of a mare, researchers report on-line in Science this week. He's the first member of the horse family, as well as the first sterile animal to be cloned.

_________________________________________________________________
Refs:

1. Antonio Regalado, "Stubborn Mule Beats Horses in Race to Be First Cloned Equine," The Wall Street Journal, pp. A1, 3 (May 30, 2003).
2. Rosie Mestel, "Still a Crossbreed, But This Baby Mule Is a Full-Blooded Clone," The Los Angeles Times, pp. A2, 22 (May 30, 2003).
3. AP, "Scientists Clone First Mule: Researchers: First Member of the Horse Family Cloned," CNN Friday, May 30, 2003 Posted: 10:19 AM EDT (14:19 GMT).
4. Robin Marantz Henig, "Pandora's Baby: In Vitro Fertilization Was Once Considered by Some to Be a Threat to Our Very Humanity. Cloning Inspires Similar Fears," Scientific American, Vol. 228, No. 6, pp. 62-7 (June 2003).

[ Editor's Note: The behind-the-scenes rivalries for who would be first team to successfully clone an equine species appear to have been intense. Prof. Katrin Hinrichs of Texas A&M University reportedly said, "It's a little disappointing that it's a mule. Our own lab has a mare that is now five months pregnant with a clone of Skip Firestorm," a horse ridden by Dr. Hinrichs's nine-year old daughter and is expected in November. An Italian team claims that they have a cloned horse that is expected within just days. One day, this could be a big business. Top jumpers and dressage animals are worth millions. And what about Funny Cide, the gelding who may win the Triple Crown in a few days time in Belmont, New York? Geldings don't make sperm, do they? Why make a gelding anyway? Does it require surgery? Do these horses live longer? They normally don't run faster. Some pedigreed stallions produce sperm at the rate of $50,000 a week! Is it a horse or a bank? I'm obviously not part of the race-horsing cognoscenti community. I don't even know why they measure the length of a race track in furlongs instead of meters (sigh!). Reporters in the sports pages don't ever take you through "Racing 101"; they only tell you the win, place, and show and how much money you made if you bet. I don't even know why it's called "win, place, and show." Help! Can anyone lend an enlightening hand (hoof) here?
We found the answer ourselves by typing in the word "gelding" into the Google.com search engine. The real reason is to calm down an otherwise impossible-to-handle high-strung stallion that may injure either himself or those around him.]

Successful Gene Therapy During Angioplasty

May 26, 2003; As reported in the May 14th on-line edition of Circulation: Journal of the American Heart Association, a team of scientists at the University of Kuopio in Finland have introduced a VEGF (Vascular Endothelial Growth Factor) gene during conventional angioplasty in 103 patients (aged [38 - 75] years) using two different types of vectors: an adenovirus (37 patients) and a liposome (28 patients) (placebo = 38 patients). Although blood flow improved for all three groups, those who received VEGF by adenovirus had significantly improved blood flow. This approach may be superior to that of drug-coated stents and may ultimately obviate the need for coronary artery bypass surgery.

Ref:

Jane E. Allen, "Gene Therapy with Angioplasty May Prevent Bypass: A New Study Finds that the Procedure Increases Oxygen-Carrying Blood to the Heart," The Los Angeles Times, p. F6 (May 26, 20003).

Mice Given Younger Ovaries Live Longer

May 24, 2003; Prof. James Carey of the University of California at Davis has just published in the May 30th issue of the journal Aging Cell that mice implanted with ovaries from much younger mice live to a riper old age.. Ovaries from female mice age 11 months (the equivalent of a 50 year old woman) were replaced by fresh ovaries from two-month-old females. The experimental mice lived 40 percent longer than controls. Click on the picture of the mouse for more details.

[ Editor's Commentary: I consider this paper to be extremely important, even though it's not out in the journal yet, since the observation that ovarian tissue matters in determining lifespan is consistent with our hypothesis that the maximum lifespan of any Sexually- Reproductive Species-Specific Life-History Chart is more closely correlated with it's Onset of Puberty (dictated by a set-point associated with an anterior-hypothalamic/pineal reverberating clock circuit {yet to be identified by neuroanatomists, but similar in architecture, we suppose, to the SA and AV nodes in the Bundle of His in the heart} ticking relentlessly with its own time constant {independently of most other genes expressed in the species} and which keeps very careful track of diurnal rhythms, with modulation by lunar/tidal months and seasons) which ultimately stimulates the first synthesis of FSH/LH Releasing Factors in the female, ultimately dictating the interval-of-reproductive-competence {the species' biological-warranty period} by either early- or late-onset, than any other species' genetically-determined parameter. I apologize that the previous sentence was so long. Sigh! Sometime in the future I will figure out how to make break it up into shorter sentences.]

Ref:

Ascribe.org, "Mice Given Younger Ovaries Live Longer," The Los Angeles Times, p. A18 (May 24, 2003).

Canine Genome Next: Boxer Breed Chosen

May 24, 2003; From a pool of 120 candidate dogs, the MIT/Whitehead Institute for Genome Research will sequence a female boxer ( Tasha) as their first canine species.

[ Editor's Note: Comparative Canine Genomics will be exploited in the future to discover why Great Danes are big and Chihuahuas small. (It would certainly be nice if this computational effort could become as simple as a high-school science project, once ten different canine genomes were placed on the same publically-available parallel-architecture supercomputer programmed with the appropriate homology-scanning {BLAST} software and made available 24-hours-a-day world-wide on the Internet for all students to try their hand. Of course, if it existed, this sort of "OPEN Software" High-School Genetics Consortium, following the LINUX Model, could also be made available for: (i) mouse; (ii) rat; (iii) bat; (iv) whale; (v) chimp; and (vi) human genomes, not to mention Yeast, the Fruit Fly, and C elegans.) Because of deliberate inbreeding for specialization of man's "best friend" (e.g., Blood Hounds for tracking and Gaze Hounds for hunting pheasant where scent is not so important, etc. the genomes of many individual breeds are highly variable. But all breeds are known to descend from a single Asian Gray Wolf about 15,000 years ago (an extremely short time in evolutionary terms), thus the number of idiosyncratic, phenotypic genes/SNIPs that make each breed appear so exquisitely different may actually be very few in number. Of course, why small breeds live systematically longer than large breeds may then fall out of this investigation, as a side benefit ( lambda max ranges form 12 years to 24 years). Sadly, our prehistoric ancestors never cared to breed dogs for longevity the way today's biologists have bred fruit flies to double or triple their lifespans over wild type as a proof- of-concept. The main goal for cave men was not having long-lived pets/companions but a good watch dog to alert us to potential predators during the night while we were asleep or an animal that paid its own way in support of hunting or other economically-useful collaborative activities.]

Also worthy of mention is that sequencing scientists announced this week that they are very close to publishing the Chimpanzee genome. Also, the Honey Bee draft is expected in mid-July, while the Sea Urchin draft, too, is coming along nicely. The draft Chicken genome is expected to be completed by early 2004.

[ Editor's Speculation:

Although they might not admit to it, I believe that gerontologists are a little like drunks searching for their lost keys under a lamp post (because that's where the light is). They are doomed to fail because they are not looking in the right place and complete strangers may find our keys before we do. Sigh!

We spend a great deal of time chasing after Telomeres, Reactive Oxygen Species, and Caloric Restriction, but in reality, we may not find out what we're looking for using these approaches for decades. Others (namely, comparative genomicists) who have little interest in the stated goals of gerontology are more likely to figure out and publish what we need to know before we can. Although they have somewhat of an advantage from funding by pharmaceutical companies' drug discovery programs with access to capital that we don't have, that is not really their major driver. If this hypothesis is true, let's just try to keep up with what our genetics colleagues are doing or else expect to be run over.]

Ref:

Rosie Mestel, "The Boxer Leads the Pack in Genome Project: Sequencing Will Help Scientists Analyze Other Dogs and May Shed Light on Human Diseases," The Los Angeles Times, p. 18 (May 24, 2003).

Gene Count in Human Genome Shrinks Significantly

May 23, 2003; Following the final draft of the human genome published last month, the number of human genes embedded in our estimated 3.1 billion base pairs of DNA (actually 27,322,000 uninterrupted base pairs of high-quality sequence have been published by the National Human Genome Research Institute) have just been reduced from an estimated 31,000 genes to only 25,000 genes or possibly even less! Recall that the original estimates were in the [80 - 140] thousand gene range. What's going on here? It seems that a large number of hypothetical genes were shifted from the "genes" category into the "junk DNA" category after they were found not to be true genes after all. For a relatively simple creature like brewer's yeast, the efficiency of genes embedded in DNA is on the order of 75 percent, whereas for humans, it has now been determined to be less than 1.5 percent! It still is not possible to scan a raw DNA sequence and pick out all the start-points and end-points of genes based on a set of simple "punctuation marks" (known specialized sequences, like STOP codons). Many of these "junk" sequences looked like they were once genes, and maybe they were once-upon-a-time, but then got broken during the course of evolution and are no longer functional ( vestigial genes, so to speak). Since there is no clear editing mechanism to get rid of vestigial genes in mammals, as there may well be in small-volume cells or viruses, where volumetric efficiency may be essential for survival, these non-functional "worthless" genes litter the genome and will keep getting copied for thousands of generations. But wait, the concept of "junk DNA" was invented by us, not by God. May the so-called "junk" is not junk at all. Maybe these sequences are essential for proper embryogenesis. Maybe the length of the junk is what is essential, not the exact sequence. And maybe the "junk" makes valuable control RNA (RNA that never exits the nuclear membrane as mRNA to synthesize proteins in the cytoplasm). By the way, the size of the human proteome (on the order of [150 - 250] thousand proteins) has not been revised, just because the estimated number of genes has been reduced. The one gene ---> one mRNA --> one polypeptide ---> one protein model does not hold for eukaryotic cells. The ratio of proteins:genes may be 10- or 20-to-one as a result of very clever re-splicing of messengers. The number of post polypeptide processing steps (methylations, glycations, etc.) may be as high as 20 or 30 that can operate so as to make a final protein uniquely functional. Anyway, the junk-DNA hypothesis suggests a variety of straightforward experiments to establish the value of "junk" sequences to the organism's survival and whether alterations in junk are typically lethal or of no consequence.

[ Editor's Note: The Cold Spring Harbor, New York, GeneSweepstake Betting Pool established over two years ago, may be completed soon [See next paragraph]. It is rumored that the winner will be announced next week. See the News Item on this website for the date of July 25, 2000 for the original statement of the GeneSweep Challenge.

June 6, 2003; Ewan Birney of the European Bioinformatics Institute near Cambridge, UK who organized the GeneSweep Contest at Cold Spring Harbor three years ago announced last week that Lee Rowen and two of her colleagues from Seattle were declared winners of GeneSweep, having made the best prediction with the lowest bids [4]. The best estimate for the number of human genes is now 24,500, of which 3,000 might actually be pseudo or otherwise broken genes that don't produce proteins and therefore don't really count. However, there's quite a bit of poorly explored DNA sequence dubbed dark matter that may contain a few more genes. So, this number is still just an estimate.]

Refs:

1. Sharon Begley, "Just How Many Genes Does It Take to Make a Human?", The Wall Street Journal, p. B1 (May 23, 2003).
2. AP, "Scientist Says Chimps Belong in Human Genus," The Los Angeles Times, p. A18 (May 24, 2003).
3. " Chimps and Bonobos are so similar to humans that they belong in the genus Homo, a report in The Proceedings of the National Academy of Sciences argues," The Wall Street Journal, p. A1 (May 20, 3003).
Humans and Chimps share 99.4 percent of their DNA (not 98.5 percent [sic], as I was taught for many years by my professors), according to Morris Goodman of the School of Medicine, Wayne State University in Michigan. The only member of the genus Homo not extinct today is Homo Sapien, viz. us. [ Homo neaderthalensis lost out in a competition during which we both cohabited the planet (but did not interbreed, as had been suggested by certain cavalier anthropologists.] Chimps ( troglodytes) and Bonobos ( paniscus) are currently placed in the genus Pan. There is no official Biology Board in charge of placing animals in their various genera, and in some cases there remains a true ambiguity and alternative taxonomies have been proposed with proselytizing commonplace in the narrow community. The important thing for us is to avoid this controversy altogether and realize that our search for genes that determine species maximum lifespan has just gotten simpler.
4. David Malakoff, "Human Genome: A Low Number Wins the GeneSweep Pool," Science, Vol. 300, No. 5625, pp. 1484-5 (June 6, 2003).
5. Wojciech Makalowski, "Genomics: Not Junk After All," Science, Vol. 300, No. 5623, pp. 1246-7 (May 23, 2003).
According to Makalowski's hypothesis regarding the value of "junk DNA," one has to realize that each organism is a dynamic work-in-progress with many genetic experiments-of-Nature going on concurrently within the genome. Nature did not intend for man or even mammals to be the final word. The "purpose" of many or these replicated, broken genes -- that don't appear to be doing anything useful from our point of view then is the result of multiple duplications of a single functional gene followed by random mutation and divergence of the various copies over time (Nature's little evolutionary experiments in progress) the copies don't reveal their etymology to us simply looking at their chromosomal location without some sleuthing, while preserving the essential function of the original gene during the course of experimentation (otherwise, we might achieve a lethal point-mutation for the entire organism).
[ Editor's Note: In computer jargon, this concept is called "reusable code," and experienced human computer programmers regularly utilize this concept of an open subroutine (as distinguished from a closed subroutine [with general-purpose parameters] in an algebraic computer language) as they develop new code in the most efficient manner possible (this technique has recently been called Object-Oriented Design). It makes more sense to modify a copy of a running program and then test it in isolation than either to reinvent such a program from scratch or to "play around" with a running program in such a way as to introduce a "bug" in the Operating System while it's still running. This latter type of bad programming technique might cause not just behavioral anomalies but a catastrophic system crash that would be impossible to debug or recover from!]

Senate Testimony on Proposed New Stem-Cell Lines

May 22, 2003; A US Senate panel heard testimony today by scientists being denied access to new human stem-cell lines, as it weighs legislation to overturn President Bush's curbs.

Refs:

1. Ali H. Brivanlou, Fred H. Gage, Rudolf Jaenisch, Thomas Jessell, Douglas Melton, Janet Roussant, "Perspectives: Setting Standards for Human Embryonic Stem Cells," Science, Vol. 300, No. 5621, pp. 913-6 (May 9, 2003).
2. Elias Zerhouni, Director of NIH, "Stem Cell Programs," Science, Vol. 300, No. 5621, pp. 911-2 (May 9, 2003).
3. Donald Kennedy, Editor-in-Chief, AAAS Science, "Stem Cells: Still Here, Still Waiting: What Concerns the Scientific Community Now Is How Access to New Lines of Stem Cells Can Be Arranged," Science, Vol. 300, No. 5621, p. 865 (May 9, 2003).

Therapeutic Cloning Is Good for America

May 14, 2003; Click for a Wall Street Journal Editorial by Drs. Shirley Tilghman, Ph.D., Molecular Biologist and President of Princeton University and David Baltimore, Ph.D., Nobel Laureate, Molecular Biologist, and President of the California Institute of Technology (February 26, 2003). An righteously indignant letter from a representative of the Family Research Council of Washington, D.C. and a satirical GRG Editorial in response follow.

Additional Reference:

Report of the American Association for the Advancement of Science (AAAS) Workshop held on March 11, 2003, Regulating Human Cloning (April 3, 2003).

Adenovirus Genetically Engineered to Block Gliomas in Mice

May 7, 2003; According to today's issue of The Journal of the National Cancer Institute, scientists at the University of Texas in Houston, have genetically engineered a common-cold virus to penetrate and destroy cells from inoperable, malignant gliomas (a form of brain tumor) in mice. This methodology should easily generalize to humans.

Ref:

CNN and Reuters.

Mouse Stem Cells Differentiate to Eggs

May 2, 2003; In a development that could alter the ethical landscape surrounding human Embryonic Stem (ES) cells, scientists have published in today's issue of Science that mouse ES cells are capable of developing into oocytes in vitro. It is not yet clear whether the cells can be fertilized and develop into embryos. But if so, and if human ES cells turn out to have similar powers, such cells might allow researchers to get around some of the expense and complex ethical questions that arise from using donated eggs for therapeutic cloning experiments [Ref. 4]. This is next on their agenda.

Karin Hubner [1], Guy Fuhrmann [2], Lane K. Christenson [3], James Kehler [1], Rolland Reinbold [1], Rabindranath De La Fuente [4], Jennifer Wood [3], Jerome F. Strauss III [3], Michele Boiani [1], Hans R. Sch”ler [1*], "Derivation of Oocytes from Mouse Embryonic Stem Cells," Science (May 2, 2003).
______________________________________________________________
1. Germline Development Group
The School of Veterinary Medicine
University of Pennsylvania, New Bolton Center
382 West Street Road
Kennett Square, PA 19348, USA.
2. Centre de Neurochimie, Laboratoire de Neurobiologie du Developpement et de la Regeneration
FRE 2373 CNRS
5 rue Blaise Pascal
67084 Strasbourg Cedex, FRANCE.
3. Center for Research on Reproduction and Women's Health
The School of Medicine, University of Pennsylvania
1349 Biomedical Research Building 2/3 (6140)
421 Curie Blvd.
Philadelphia, PA 19104; USA.
4. Female Germ Cell Biology Group
Center for Animal Transgenesis and Germ Cell Research
The School of Veterinary Medicine
University of Pennsylvania, New Bolton Center
382 West Street Road
Kennett Square, PA 19348, USA.
_________________________________________________________
* To whom correspondence should be addressed... E-mail: scholer@vet.upenn.edu. _________________________________________________________

ABSTRACT:

[ GRG Editorial on Hermoclones: If we coin the term hermoclone to mean a clone of an individual (an identical twin displaced in time) but of opposite gender (something that does not exist in Nature, since opposite gender twins are always fraternal, never identical), we now have the technology to create a female hermoclone of a man, providing that human cloning could be made to work at all. In other words, a man may ask "what would it be like to raise a child who would be identical to me?" meaning, of course, a boy, but could now legitimately ask what it would be like to raise a copy of myself, but as a girl? (i.e., what would I look like if I were a girl?) This is a somewhat gratuitous question, since the technology is not here yet (we would need to enucleate an egg and 'fertilize' it with two carefully-selected X- Chromosome sperm {polyspermy}, thereby creating a complete diploid "XX" individual {female} that would then be inserted into the womb of a willing surrogate mother). But to my knowledge, no one has ever even thought of this fanciful experiment, even in literature. Readers: Please inform us if you can find a reference to this concept anywhere else.

And while we're at it, why not consider the possibility of a male hermoclone? If a woman were to combine the haploid nuclei of two of her eggs into a heterokaryon, then taking the Y-Chromosome from a selected sperm from one of her male relatives and using it to replace one of her X-Chromosomes (without replacement, you would obtain an XXY {Klinefelter's Syndrome} male child that would likely grow up to be sterile). Note: There's not that much genetic material along the "Y" Chromosome, so a male relative's Y would probably do just as well to get the full effect of a clone, even though it's not 100 percent identical to the index maternal genome. But even identical twins are not really identical. They have different finger prints, for example. They grow up in different parts of the uterine lining even though they share the same placenta and maternal blood supply, and they do exit the womb at different times depending on their location.

So, what's the purpose of putting this information here on a public website. One might ask, if it's such an original idea, why don't you patent it, as a method patent, first? (And by implication, get rich from your invention). Well, my idea is to put it in the public domain, so we can say that it was published here first, and so that nobody else can patent it. Hello. WWW.PTO.GOV: are you listening? All that we would like is for people to start using the term "hermoclone," a new English word, correctly, and give us credit, and we'll be happy.

However, an important additional motivation is to block the patent application of Dr. Norbert Gleicher of the Center for Human Reproduction in Chicago, who said at the Annual Meeting of the European Society for Human Reproduction and Embryology (ESHRE) in Madrid, SPAIN that he plans to patent the technique of developing mixed-gender embryos (chimeras). It is alleged that twelve chimeric embryos were grown to the six-day blastocyst stage before they were destroyed. The work was being pursued on the grounds that it would be a way to repair genetic disorders. However, in our view this work is not only ethically objectionable, it is scientifically and medically questionable, since there are potential long-term health risks and the possibility of congenital defects for any child, were this to be used in a clinical setting. See The Scientist (July 8, 2004).]

Stem Cells, Inc. Devises Treatment for Spinal Cord Injuries

May 2, 2003; New York, NY ( Dow Jones Newswires) -- Tiffany Kary reported that "StemCells Inc. (STEM) shares shot up as much as 204 percent after the company announced that preclinical data could lead to a treatment for spinal-cord injuries."

Refs:

1. University of Pennsylvania (May 2, 2003)
2. Smart Money (May 2, 2003).

GABA Boosts the Brains of Aging Monkeys

May 2, 2003; "Aging brains may be sharpened and, in effect, made young again briefly by increasing the levels of Gamma Amino Butyric Acid. Researchers at the University of Utah in Salt Lake City found that GABA appears to help extremely old rhesus monkeys focus their vision and thinking processes by silencing the interfering static from other neurons. "GABA filters out stray brain signals that may make thinking and seeing difficult in older brains," according to a study published in today's issue of Science.

Refs:

1. "Neurochemical Boosts Aging Brains, Study Says," The Los Angeles Times, p. A20 (May 3, 2003).
2. "Study Suggests Chemical May Help Aging Brains," CNN (May 2, 2003).

Using IVF Could End-Run the Risk of Human Reproductive Cloning

April 29, 2003; Scientists suggested during a discussion on cloning at the Human Genome Organization's Meeting in Cancun, Mexico that "the safety problem inherent in human reproductive cloning might be obviated if cloned human embryos were first used to derive healthy sperm and egg cells that could then be used in a standard in vitro fertilization procedure." "The process of egg and sperm production, called gametogenesis, naturally reprograms cells in readiness for fertilization," said cloning expert Dr. Rudi Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, MA.

Ref:

Helen Pearson, "DNA Re-Write Could Allay Cloning Fears: Extra Step Might Overcome Safety Objections to Reproductive Cloning," Nature (April 29, 2003)

President's Council on Bioethics to Address the Value of Longevity Research

April 28, 2003; "Age-Retardation: Scientific Possibilities and Moral Challenges," will be the title of the next Staff Working Paper of the President's Council on Bioethics chaired by Prof. Leon Kass of the University of Chicago. We expect to keep you informed of any new developments as they are announced.

Ref:

Ronald Bailey, "You Shouldn't Live So Long: Who Wants to Live Forever Anyway?", Reason-Online (April 9, 2003).

New Perspective on SARS: Media Over-Reaction

April 28, 2003; As of this date, approximately 300 persons have died of SARS (Severe Acute Respiratory Syndrome)(with no deaths in the US so far). There is an estimated 4,800 total cases of SARS worldwide. But we ought to strive for a more realistic perspective on the actual dangers of this new epidemic. Despite the existence of an effective Flu Vaccine for many years, 20,000 Americans still die from influenza every year and the media hardly notices. [Even worse, 40,000 Americans die on highways every year, and even worse, 400,000 Americans die of smoking-related diseases every year (lung and other forms of cancer, not to mention persons killed in fires started by smokers who fell asleep while smoking in bed), and the press makes hardly any mention of these statistics.] As Prof. David Baltimore said in an Editorial in today's Wall Street Journal [2], those of us who are professionally devoted to a rational analysis [of SARS], need to do more than wag our finger at the press, as they routinely swell the fear factor toward a level that could itself become a danger." We must be prepared for the possibility that this virus will settle into the human population (sort of like the AIDS virus and many other global viruses have done in the distant past), so that SARS may always be with us from now on, perhaps at a somewhat lower level.

For up-to-date information on the SARS Epidemic and current travel advisories to Asia, see the Centers for Disease Control and Prevention (CDC) website in Atlanta, GA as well as the World Health Organization (WHO) website of the United Nations based in New York. In Los Angeles, one may contact the office of Dr. Jonathan E. Fielding, M.D., M.P.H., Los Angeles County Medical Director and Chief Health Officer, Department of Health Services, the Acute Communicable Disease Control Program, and the Health Alert Network at 213-240-7941. Health warnings in English, Spanish, and Chinese can be obtained from this office as Adobe Acrobat PDF files.

The WHO stated that, as of Tuesday, April 15th, there were 3,235 cases of SARS worldwide [in 25 countries, but especially prevalent in China (Hong Kong, Shanghai, Singapore, and Guangdong Province), Canada (Toronto), USA, Vietnam (Hanoi), and Germany (Frankfurt)] with 154 suspected deaths thus far. Dr. Julie L. Gerberding, Director of the CDC said that Canadian researchers at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia (Dr. Marco Marra) had completed the DNA sequence for the SARS-Associated Coronavirus (distinct from other known viruses in this family [and it was not a picornavirus nor the H5N1 Avian Flu Virus nor a paramyxovirus as first suspected]) in record time. Twelve different labs participated in the global sequencing effort (including Erasmus University in Rotterdam, The Netherlands, The National Microbiology Laboratory in Winnipeg, Manitoba, Queen Mary Hospital in Hong Kong, French Hospital in Hanoi, and Joseph DeRisi's lab at the University of California in San Francisco using a 1,000-virus microarray gene-chip) and finished it in weeks instead of months. This will set a new standard for "future pandemics of infectious disease," said a report last week in The New England Journal of Medicine.

Refs:

1. Click for instructions on how to download (from Genbank) and inspect the SARS Coronavirus Genome Assembly itself... Release 2 Sequence of 29,763 Base Pairs.
2. Prof. David Baltimore, Ph.D., President of CalTech and Nobel Laureate in Medicine, "The SARS Epidemic: Severe Acute Media Syndrome?" The Wall Street Journal, pp. A1, 12 (April 28, 3003).
3. Tim Rutten, "Regarding Media: A Plea for Careful SARS Coverage," The Los Angeles Times, pp. E1, 10 (April 30, 2003).
4. Joshua Lederberg, "An Inner Peace: In Battling Disease, We Have to Settle for a Truce with the Microbes Inside Us," The Los Angeles Times, p. B17 (April 24, 2003).
5. Alexander Batalin, Correspondent, "The Atypical Pneumonia Virus Has Been Created Artificially Says Scientist Sergei Kolesnikov," RIA Novosti.
April 10, 2003; Irkutsk, Siberia; RUSSIA The virus of Atypical Pneumonia has been created artificially, possibly as a bacteriological weapon, believes Professor Sergei Kolesnikov, Academician of the Russian Academy of Medical Sciences. He expressed this opinion at a news conference on Thursday. According to him, "the virus of Atypical Pneumonia is a synthesis of two viruses (of Measles and Infectious Parotiditis or Mumps), a natural compound of which is impossible." This could be carried out only in a laboratory, the Academician is convinced. He also said that in creating bacteriological weapons a protective anti-viral vaccine is, as a rule, worked out at the same time. Therefore, the scientist believes, an antidote for Atypical Pneumonia may soon appear. He does not exclude that the spread of the virus could have begun accidentally, as a result of an unsanctioned leakage from some [Chinese?] laboratory. Click on Dr. Patricia A. Doyle's website for more details.
[ Editor's Note: We do not accept this alleged hypothesis to be true. It has the flavor of the now discredited searches for Big Foot, the UFO aliens who created British Crop Circles during the night, or the Loc Ness Monster in Scotland. Since when is Nature no longer capable of synthesizing a new virus on her own and without our permission?]
6. "SARS And Genetic Engineering?" published by the London-based Institute for Science in Society (April 27, 2003).
7. David P. Hamilton, "Will New Kind of Drug Work Against SARS?" The Wall Street Journal, pp. B1, 5 (April 30, 2003).
A 20-Oligo Anti-Sense-RNA Drug based on a Polyprotein detected in the SARS Viral Sequence developed by Dr. Patrick Iversen, Chief Scientist of AVI BioPharma, Inc. of Portland, OR, will be tested soon in a Biosafety Level-3 Lab to be provided by NIH.

8. Thomas H. Maugh, II, "Animals Sold as Delicacy in China May Transmit Virus to Humans," The Los Angeles Times, pp. A12-13 (May 24, 2003).
9. Matt Pottinger, "Link to Animals Solves One Riddle: Discovery Can Help Design Strategies Against SARS; Cultural Issues Remain," The Wall Street Journal, p. A1, D8 (May 27, 2003).
Masked-Palm Civet Cats are not cats at all, but look more like weasels or mongooses. They are typically butchered under unsanitary conditions and eaten in China as a delicacy. The Civet form of the coronovirus appears to be identical to the human form except for the existence of a small additional segment on one end of its RNA sequence. Experts speculate that the loss of that segment might have allowed the virus to jump from its animal reservoir to humans. The animals do not appear to get ill from their native form, but do have anti-bodies in their blood. Therefore, anyone coming into contact with civet feces or saliva might be at risk for contracting SARS.

April 17, 2003; Washington, D.C. According to Dr. Francis Collins, "researchers led by a team of scientists at the National Human Genome Research Institute have identified a gene ( LMNA = 25,000 BP) on Chromosome 1 (a single-point mutation of Cytosine [C] to Thymine [T]) responsible for Hutchinson Gilford Syndrome," a rare (only 100 cases observed throughout the world), non-inherited ( de novo) condition that affects young children, causing them to die at a very early age (average age of 13 years). It could be passed to the embryo through a flaw in the genes of the father's sperm. There is a missing stretch of 50 amino acids near one of the ends of the protein that appears to cause instability in the nuclear membranes of cells when they are put under stress. Finally, even though it is called progeria, Prof. Calib E. Finch of the Andrus Gerontology Center at USC has called this condition a "cartoon of aging," since those afflicted exhibit only some but not all of the manifestations of aging.

Refs:

1. NIH News Release, "Researchers Identify Gene for Premature Aging Disorder: Progeria Gene Discovery May Help Solve Mysteries of Normal Aging," National Human Genome Research Institute (April 16, 2003).
2. Annachiara De Sandre-Giovannoli [1], Rafaelle Bernard [2], Pierre Cau [3], Claire Navarro [1], Jeanne Amiel [4], Irene Boccaccio [1], Stanislas Lyonnet [4], Colin L. Stewart [5], Arnold Munnich [4], Martine Le Merrer [4], Nicolas Levy [6]*, "Lamin A Truncation in Hutchinson-Gilford Progeria," Science (April 17, 2003).
A rare premature aging syndrome is caused by a mutation in the gene for a protein that coats and organizes the interior surface of the nuclear envelope.
_______________________________________
1. Inserm U491: "Genetique Medicale et Developpement", Faculte de Medecine Timone, Marseille, FRANCE.
2. Departement de Genetique Medicale, Hopital la Timone, Marseille, FRANCE.
3. Inserm U491: "Genetique Medicale et Developpement", Faculte de Medecine Timone, Marseille, FRANCE;
Laboratoire de Biologie Cellulaire, Hopital Conception, Marseille, FRANCE.
4. Inserm U393, Hopital Necker, Paris, FRANCE.
5. Cancer and Developmental Biology Laboratory, NCI-Frederick, Frederick, Maryland, USA.
6. Inserm U491: "Genetique Medicale et Developpement", Faculte de Medecine Timone, Marseille, France; Departement de Genetique Medicale, Hopital la Timone, Marseille, FRANCE.
* To whom correspondence should be addressed: E-mail: Nicholas.Levy@medicine.univ- mrs.fr.
_______________________________________
3. Maria Eriksson [1], W. Ted Brown [2], Leslie B. Gordon [3], Michael W. Glynn [7], Joel Singer [5], Laura Scott [5], Michael R. Erdos [1], Christiane M. Robbins [1], Tracy Y. Moses [1], Peter Berglund [4], Amalia Dutra [1], Evgenia Pak [1], Sandra Durkin [7], Antaonei B. Csoka [6], Michael Boehnke [5], Thomas W. Glover [7], and Francis S. Collins [1], "Recurrent De Novo Point Mutations in Lamin-A Cause Hutchinson Gilford Progeria Syndrome," Letter to Nature (April 25, 2003).
_______________________________________
1. and 4. National Human Genome Research Institute, and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
2. Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
3. Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, and Department of Pediatrics, Rhode Island Hospital, Providence, RI 02903, USA
5. Department of Human Genetics, and Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
6. Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA

Correspondence and requests for materials should be addressed to Dr. Francis S. Collins, M.D., Ph.D. at NIH [ E-mail: fc23a@nih.gov].

ABSTRACT:

Hutchinson Gilford Progeria Syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. Here, we present evidence of mutations in Lamin-A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to Chromosome 1q by observing two cases of uniparental isodisomy of 1q the inheritance of both copies of this material from one parent -- and one case with a 6-Mega Base paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harbored an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G (GGC > GGT), within Exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within Exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against Lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human aging.
_______________________________________
4. "Gene Is Discovered for Rapid Aging in Children," CNN (April 17, 2003).
5. AP, "Accelerated Aging Disorder Linked to a Genetic Mutation," The Los Angeles Times, p. A28 (April 17, 2003).
6. "Gene Scientists Have Identififed the Mutation behind Hutchinson-Gilford Progeria, or Very Premature Old Age...," The Wall Street Journal, p. A1 (April 17, 2003).
7. Leslie B. Gordon, M.D., Scott Burns, M.D., and Sam (their 7 year-old son with HGPS), "Family Crisis Becomes Scientific Quest," Science, Vol. 300, No. 5621, p. 899 (May 9, 2003).

Stem Cells Repair Damage in Mouse Model of Multiple Sclerosis

April 17, 2003 ( AP) Researchers from Milan, Italy have injected stem cells into mice to repair damage and sharply reduce symptoms from an experimental form of MS.

Refs:

1. The Wall Street Journal, p. A1 (April 17, 2003).
2. "Study: Stem Cells Fix Damage in Experimental MS," CNN (April 17, 2003).

Milestone: Completion of the Human Genome Sequence

April 14, 2003; London, UK and Bethesda, MD, USA ( Reuters and AP) -- As had been planned by The International Human Genome Sequencing Consortium (US, England, Germany, France, Japan, and China) and The US Human Genome Research Institute for the occasion of the Golden (50th) Anniversary of the discovery of the double-helix shape of DNA --- for which Drs. Francis Crick and James Watson subsequently won the Nobel Prize --- the full sequence of human DNA has now been completed and has been posted on the Internet. Further details will be published in this week's issue of Nature.

Recall that a "Rough or Working Draft" has been available since June 2000. However, it covered only 90 percent of the genome, whereas this final version covers 99 percent of the 3.1 billion base pairs. The earlier draft had an error rate of 1:1,000 with 150,000 gaps, while the final version has an error rate of only 1:10,000 with only 400 gaps. Many of these gaps still remain, however. For unknown reasons, some of the sequences are difficult to replicate in bacteria (they may be toxic) and other parts express highly repetitive sequences (like the telomeres and centromeres at the ends of middle of our 23 pairs of chromosomes, respectively) and are known not to contain genes. The total number of estimated genes still remains in the neighborhood of 30,000, the vast majority of whose functions are still unknown. The "scientist bet" at the Long Island, New York Cold Spring Harbor Laboratory on who proves to be closest to the final number is still ongoing. On the other hand, the identification of disease-related genes has exploded from less than 100 in 1990 to more than 1,400 such genes today. Many parts of the genome don't appear to encode for genes at all but may nevertheless be vitally important for control of downstream gene expression. In other words, some sequences may not encode for mRNAs that are subsequently translated to proteins in the cytoplasm, but up to 255 microRNAs (nearly 1 percent) may remain in the nucleus to serve for subsequent gene expression control. [See Science (March 7, 2003)].

Serious Comparative Genomics among humans, chimpanzees, monkeys, rats, bats, whales, dogs, cats, cows, and other mammals has really yet to begin. A windfall of clinically-useful information regarding transformation of genotype-to-phenotype, secondary to communication by growth factors among embryonic stem cells, is expected to result from this work in the next four or five years..

The number of DNA sites containing SNPs (Single Nucleotide Polymorphisms) has grown to 10 million. This is the part of the DNA that helps us distinguish one human individual from another (extremely useful for forensic identification). The HapMap Project, announced in October, is intended to pinpoint the 100,000 variations deemed most useful for tracking down genetic traits and predisposition to disease. The effort is expected to take another three years. The newly-formed ENCODE Project (ENCyclOpedia of DNA Elements) will re-analyze 1 percent of the genome in much greater detail to identify every functioning element. It aims to tease out all the myriad of functions throughout a tiny sliver of the genome. ENCODE will examine regions known to contain genes-of-interest and others regions selected randomly.

Refs:

1. CNN (April 14, 2003).
2. CNN (April 15, 2003).
3. Rosie Mestel, "Human Genome Is Completed Now Comes the Hard Part," The Los Angeles Times, p. A18 (April 15, 2003).
4. AP, "Human Genetic Map Is Done," The Wall Street Journal, pp. A1, D5 (April 15, 2003).
5. Nicholas Wade, "Once Again, Scientists Say Human Genome Is Complete," The New York Times, pp. D1,4 (April 15, 2003).
6. Britain's Wellcome Trust offers a excellent primer on genome research and its potential impact on medicine and society. The Genome Browser profiles each chromosome and highlights its important genes. Visitors can read news updates and features on topics ranging from gene therapy to the origin of red hair. Helpful backgrounders explore the ethical implications of genome research.
7. Malcolm Campbell, Genome Consortium for Active Teaching (GCAT).
8. A. Malcolm Campbell, Genomics, Proteomics, and Bioinformatics, Course based on his textbook with Laurie J. Heyer, Discovering Genomics, Proteomics, and Bioinformatics (This course comes on CD-ROM published by Benjamin/Cummings, New York; 2003; $70.60 on Amazon.com).
9. Jackson Laboratory, Bar Harbor, ME, annotated Gene Expression Database describing thousands of mouse genes activated during different stages of murine embryogenesis, Science, Vol. 300, No. 5621, p. 973 (May 9, 2003).
10. Elizabeth Pennisi, "Human Genome: Reaching Their Goal Early, Sequencing Labs Celebrate," Science, Vol. 300, No. 5618 , p. 409 (April 18, 2003).

Cloning Primates Is Really Difficult

April 10, 2003; Washington, D.C. ( AP) Cloning humans, or any other primates, may be impossible with today's techniques because of a fundamental molecular obstacle, say scientists trying to understand why attempts to clone monkeys have failed. From the very first step, cloned primate cells don't divide properly, secondary to a deformed spindle apparatus and causing a chaotic polyploid chromosomes, too abnormal for pregnancy to even begin, University of Pittsburgh researchers reported today in the journal Science. On the other hand, it appears that there may be a relatively simple way to sidestep the problem by combining cloning with old-fashioned egg fertilization. More later.

Refs:

1. Lauran Neergaard, AP Medical Writer, "Studies: Human Cloning May Be Impossible," (April 10, 2003).
2. Gautam Naik, "Doctor Who First Cloned Sheep Sets Sights on Human Embryo," The Wall Street Journal p. A1 (April 11, 2003).
Dr. Ian Wilmut, Father of Dolly and Joint Head of the Department of Gene Expression and Development at the Roslin Institute in Edinburgh, SCOTLAND, says he will "seek permission this Summer for the cloning of human embryos from the UK Human Fertilization and Embryology Authority to conduct experiments leading to a cure for Lou Gehrig's Disease or ALS (Amyotrophic Lateral Sclerosis), a neurodegenerative disease that afflicts 350,000 people world- wide and kills 100,000 each year.
3. Antonio Regalado, "University of Pittsburgh Group Seeks to 'Humanize' Pig Organs," The Wall Street Journal (April 10, 2003).
An investor group led by the University of Pittsburgh Medical Center has bought out the US operations of PPL Therapeutics, PLC of Blacksburg, VA formed by the Roslin Institute of Scotland. They will continue their research with pigs, attempting to knock out both porcine genes responsible for acute immune rejection of xenotransplanted organs in humans. The pig organs will be tested in monkeys within the next two months. Success in monkeys would be a prerequisite before human transplants could begin.

Europeans Vote to Severely Constrain Use of Embryonic Stem Cells

April 10, 2003; This decision could see the use of Embryonic Stem Cells barred across most of Europe. Click for more details.

Refs:

1. Pat Hagan, "Euro MPs Vote Against Stem-Cell Research," The Scientist (April 20, 2003).
2. PM, "EP Bans Stem-Cell Research," Nature Biotechnology, Vol. 21, No. 5, p. 473 (May 2003).

Dr. Zavos Publishes a Preliminary Experiment in Human Cloning in a Peer-Reviewed Journal

April 9, 2003; Lexington, KY Dr. Panayiotis M. Zavos, Ph.D., Andrologist, and CEO of ZDL, Inc., a supplier of equipment for testing sperm, will soon publish a paper entitled "Human Reproductive Cloning: The Time Is Near," in the British journal Reproductive BioMedicine On-Line in its next issue (Vol. 6, No. 4, June 2003). The journal's Editor-in-Chief, Dr. Robert G. Edwards, was one of two British scientists who produced the world's first "test-tube baby" via in vitro fertilization back in 1978. Dr. Zavos described a single human embryo that had grown to 8 to 10 cells over a period of four days. This work, like that published earlier by scientists at ACT of Worcester, MA, is considered very preliminary, and it is not yet clear whether these first steps are truly on the right track. At least this work will not be called a hoax, as was said of the Clonaid company's announcements with great fanfare that began in December of last year.
[ Editor's Note: Although not illegal in the U.S., it is reported that this work was accomplished abroad.]

Refs:

1. Antonio Regalado, "Human Embryo Is Cloned, Expert to Say in Paper," The Wall Street Journal, pp. D1, 2 (April 9, 2003).
2. Aaron Zitner, "Scientists Clone Banteng in Effort to Save Dying Species," The Los Angeles Times, p. A18 (April 8, 2003).
In an unrelated development, Dr. Robert Lanza and colleagues at ACT have succeeded in cloning two Southeast Asian horned cows called Bantengs on an Iowa farm. Fewer than 8,000 are thought to exist worldwide. Previous attempts to clone endangered species had been attempted with a Gaur and a Mouflon, a Mediterranean sheep.
3. "Another Endangered Species Cloned," Science, Vol. 300, No. 5618, p. 421 (April 18, 2003).
4. KP, "New Life in Banteng Gene Pool," Nature Biotechnology, Vol. 21, No.5, p. 473 (May 2003).
5. Louis M. Guenin, "The Set of Embryo Subjects," Nature Biotechnology, Vol. 21, No.5, pp. 482-3 (May 2003).

Why Do So Many Centenarians Live in Nova Scotia?

April 3, 2003; Halifax, Nova Scotia, CANADA --- The answer, it seems, lies in the genes of the inhabitants --- "the Yarmouth area was settled by only 20 or 30 families, the Acadians, who, after their rough treatment by the English, were not inclined to mix with people from the rest of their Province. Today they still speak French, display the Arcadian flag, while local radio stations play dance music not unlike that played in Louisiana... Thus, the genes that have predisposed them to extreme longevity have been passed down from generation to generation," speculated Dr. Chris MacKnight, who seeks answers to why some of the very old are spry, while others among them are frail. Scientists suspect that there may be a few age-defying genes and hope to discover drugs that mimic their function. To skeptics, that sounds a bit like a futile quest for the fountain of youth. Nevertheless, Dr. Tom Perls, Director of the New England Centenarian Study at Boston University said, "We're not seeking a fountain of youth so much as a fountain of 'aging well'." Centenarians tend to be healthier than one might think 40 percent avoid chronic illnesses until their 85 or older, 20 percent postpone age-related debilities until they're age 100 or more." Longevity-enabling genes might protect Centenarians in the same manner as Caloric Restriction, the only longevity intervention that has been experimentally shown to extend life across many species. Another common element, free-radicals, may spur atherosclerosis and Alzheimer's Disease and could be a key mechanism or root cause in aging of many species. Lifestyle, however, can play a role, in that Centenarians tend to be prudent, rarely smoking, drinking heavily, or becoming obese. "No matter how close we come to discovering gerontic genes, no matter how well we may discern the biological protections that Centenarians share in common, it seems that the-very-old will always be an exceptionally heterogeneous group, each one with a unique story to tell, but without a lot of superficially- obvious easy-to-imitate things in common."

Dr. Perls and his colleagues with Centagenetix, Inc. in Cambridge, MA ^* are examining the DNA from 137 sets of Centenarian Siblings. [ Editor's Note: Centagenetix has recently merged with Elixir Pharmaceuticals of Cambridge, MA. Elixir's stated Mission is "to discover therapeutics to slow aging, forestall the disease and disability that accompany aging, and extend life's most productive period."] By studying the epidemiology and genetics of Centenarians, Centagenetix has focused on Human Chromosome 4, narrowing their search to a few hundred genes. (See the News Item from June 17, 2002 on this Website citing their PNAS paper of June 11, 2002.)

Around Noon time on Saturday, January 18th, while answering questions after a standard talk at the USC Annual Symposium on Animal Species Exhibiting Gradual Senescence [ SOSA-2 (Symposium on Organisms with Slow Aging) -- The focus of this year's Symposium was on the natural life history of aging in long-lived birds and reptiles. Leading gerontological researchers ranging from field biologists and zoological specialists to molecular geneticists presented, with a final Saturday afternoon session devoted to human longevity ], Perls acknowledged that his company had reduced their search down to two SNPs, but he couldn't reveal the name of the gene, as a scientific paper describing their work had been submitted for publication in Nature and was still under review.

Ref:

Mary Duenwald, "Puzzle of the Century: Is It the Fresh Air, the Seafood, or Genes?: Why Do So Many Hardy 100-Year Olds Live in, Yes, Nova Scotia?" Smithsonian Magazine, pp. 75 - 80 (January 2003).

[ Notes from GRG Members:
A few of our GRG members have pointed out that this article is largely a human-interest story (i.e., based on statistically illiteracy).
For example, Mr. Louis Epstein of New York writes, "the density of Centenarians in Nova Scotia (CANADA), is certainly not on the scale of Nuoro Province (ITALY) or Okinawa Prefecture (JAPAN). Indeed, Canadian Supercentenarians have generally not even come from Nova Scotia, but from other Canadian provinces."
Furthermore, Mr. Robert Young of Atlanta writes, "Alina Morton, Laura Rollock, and Rose McDonald all reached 110 years. While the rate of 21 Centenarians-per-100,000 is higher than average, it is not extremely high and is lower than it is for some U.S. states. Many researchers are guilty of selectional bias; they should compare numbers to the Birth Cohort, not the Population-Living-There-Today, because areas with high emigration tend to have distorted numbers of Centenarians. That said, much of the rest of the differences can be attributed to better lifestyles in the rural areas of the U.S. North and in CANADA."
_______________________________
* [ Editor's Note: Tom told me personally that, to preserve his scientific objectivity, he deliberately chose not to hold an equity position in the company, despite the fact that he was one of its co-founders.]

Texas Heart Institute Uses Adult Stem Cells to Restore Heart Muscle Post MI

April 1, 2003; Chicago, IL ( WSJ) Dr. Emerson C. Perin and colleagues from the Texas Heart Institute in Houston reported encouraging early results of efforts to use a patient's own bone-marrow cells to restore heart muscle tissue damaged by a heart attack at the Annual Scientific Meeting of the American College of Cardiology. The researchers "injected immature cells directly into heart muscle tissue in 14 patients. The effort led to improved blood flow to damaged tissue and improved ability to participate in daily activities compared with 7 patients who didn't get the treatment." Further studies are planned.

Ref:

Ron Winslow, "Pharmacia, Guidant Heart Studies Show Progress," The Wall Street Journal, p. D8 (April 1, 2003).

Geron Demonstrates Differentiation of Hepatocytes from Human Embryonic Stem Cells

April 1, 2003; Menlo Park, CA ( Business Wire) -- Geron Corporation announced today the publication of research results that describe the production of hepatocytes --- the basic functional cells of the liver from human Embryonic Stem Cells (hESCs). These studies demonstrate that cells with multiple characteristics of hepatocytes, including drug- metabolizing enzyme activity, can be reproducibly differentiated from hESCs. These cells have potential for widespread use in drug discovery research as well as for transplantation therapy for patients with liver failure.

As published in the March issue of Cell Transplantation, Geron scientists describe protocols that differentiate hESCs into human hepatocytes that express Albumin, Alpha-1- Antitrypsin, Glycogen, and other proteins found in human adult liver cells. Importantly, the cells also express certain Phase-1 and Phase-2 drug-metabolizing enzymes which are responsible for metabolizing most pharmaceuticals.

A reliable source for the production of human hepatocytes with well-characterized and reproducible properties would have a major beneficial impact on the drug discovery process. Currently, drug candidates are tested for toxicity and metabolic effects on the liver late in the discovery process using tools and methods that are inadequate. For example, access to primary human liver tissue is very limited, and hepatocytes isolated from adult liver tissue cannot be propagated in tissue culture. The available rat and mouse models only approximate human metabolism, and biochemical assays based on liver microsomes do not represent the complete physiological environment of liver cells. The widespread availability of standardized, normal human hepatocytes produced on a large scale from hESCs would allow drug metabolism and toxicity studies to be performed earlier in the drug discovery process, enabling the elimination of toxic compounds before undertaking costly human trials.

"This discovery serves as a foundation for the commercialization of hESC-based cell types for drug discovery applications," stated Dr. Thomas B. Okarma, M.D., Ph.D., Geron's President and CEO. "Both large pharmaceutical companies and small biotechs would benefit from the availability of hepatocytes derived from hESCs that can reliably represent a functioning liver. We have already received two U.S. Patents covering hESC-derived hepatocytes and their use as drug screening tools [U.S. Patent Nos. 6,458,589 and 6,506,574]. Our next steps are to complete the characterization of these cells and to develop a high-volume production process. At that point we have a product."

In addition to the hepatocytes described in this publication, Geron has generated six other cell types from hESCs that are being developed into therapeutic productsHematopoietic Progenitors, Dopaminergic Neurons, Oligodendrocytes, Cardiomyocytes, Beta-Islet Cells, and Osteoblasts. All cell types exhibit normal functions expected of that cell type if isolated from adult tissue. The company is currently conducting pre-clinical animal safety and efficacy studies with four of these cell types.

Refs:

1. Tomi Kilgore, "Geron Stock Rallies on Results of Liver-Cell Studies," (April 1, 2003)
2. "Geron Shares Rise 28 Percent on Stem-Cell Research: The Biotech Company Says It May Be Able to Help Scientists Test Drugs for Liver Toxicity," The Los Angeles Times, p. C2 (April 2, 2003).
3. Brief Item under Also, "Geron said that it would raise as much as $24 million through a sale of stock," The Los Angeles Times, p. C3 (April 9, 2003)

Note: See related Geron stories dated March 27th and 19th below.

GDNF for Parkinson's Disease

March 31, 2003; Madison, WI ( AP) As published in the latest issue of Nature Medicine, Clive N. Svendsen of the University of Wisconsin demonstrated that all five patients in the trial testing GDNF (Glial-Cell-Line Derived Neurotrophic Factor), delivered by continuous pump infusion, experienced measurable improvement in their involuntary tremors associated with Parkinson's Disease.

Refs:

1. CNN (March 31, 2003).
2. In Brief, "Drug Shows Promise for Parkinson's Patients," Los Angeles Times (March 31, 2003).
3. Nicholas Wade, "Promising Results Are Seen in Small Parkinson's Trial," The New York Times pp. D1,7 (April 8, 2003).

Cell Fusion May Repair Bad Livers

March 31, 2003; Bone-marrow cells may regenerate the liver by cell fusion not by cellular differentiation. Xin Wang and colleagues at the Oregon Health and Science University in Portland transplanted "Fah-/- deficient"mice with bone-marrow cells from Fanconi Anemia group- C gene (Fancc) homozygous-mutant mice and Fah-wild-type mice. 80 "XXXY" (diploid-to-diploid fusion) and 120 "XXXXYY" (diploid-to-tetraploid fusion) karyotypes indicated a fusion between donor and host cells. Click on the Ref. for more details...

Ref:

Tudor P. Toma, "Cell Fusion Repairs Liver," The Scientist (March 31, 2003).

Bad Economy Has Devastating Effect on Small Biotechnology and Stem-Cell Firms

March 27, 2003; ACT, Geron, PPL Therapeutics, and many others are in trouble. ESI of Australia may be one counterexample. Human Embryonic Stem-Cell (ES Cell) and therapeutic-cloning investments have fallen 50 percent in the last three years, to $50.2 million in 2002, mirroring the plunge in stock prices for the Biotechnology Sector as a whole. It seems that investments in any sort of speculative research are all but over. Analyst Steven Dickman of Techno Venture Management in Boston says, "While the science remains very interesting, from a venture-capital perspective, the bloom is off the rose. Even companies like Geron have to spin their results so that shareholders can see the excitement." ACT has lost three of its four highest-profile scientists (Drs. Tanja Dominko, Tony Perry, and Teruhiko Wakayama) that were recruited with great fanfare. PPL Therapeutics of Edinburgh and Blacksburg, VA announced that it will simply leave the field and try to sell off its "regenerative medicine" assets. Geron laid off 40 of its 90 staff members. Its stock fell from a high of $69 a share in 2000 to $1.70 a share today. But they have two-year's worth of cash in the bank. BresaGen of Athens, Georgia has lost nearly one-third of its staff in the last six months. Their stock fell from more than 90 cents a share in late 2000 to 15 cents last week. They have only one-year's cash reserve in the bank. "There's a lot of intellectual property [patent rights] out there that can be had for very cheap prices," said John Smeaton, CEO of BresaGen.

Refs:

1. Gretchen Vogel, "Stem Cells Lose Market Luster," Science, Vol. 299, No. 5614, pp. 1830-1 (March 21, 2003).
2. Mark Henderson, "EU Curbs Threaten British Stem-Cell Research," British News (March 29, 2003).

ACT Wins Patent Dispute

March 22, 2003; An Appeals Panel at the U.S. Patent and Trademark Office ruled in favor of Advanced Cell Technology of Worcester, MA and against Infigen, Inc. of DeForest, WI in their ownership fight over three key animal cloning patents (based on a technicality). ACT still faces a significant legal challenge from Geron, Inc. of Menlo Park, CA which owns the cloning technology that they acquired from the Roslin Institute of Edinburgh, Scotland.

Refs:

1. ( AP) Biotechnology, "Advanced Cell Prevails in Cloning Dispute," The Los Angeles Times, p. C3 (March 22, 2003).
2. JLF, "ACT Wins Patent Dispute," Nature Biotechnology, Vol. 21, No 5, p. 473 (May 2003).

Geron Proposes Telomerase as Anti-Cancer Vaccine

Note: See item dated April 1st above.

March 19, 2003; Geron Corp. of Menlo Park, CA has published in the current issue of the journal Cancer Gene Therapy research supporting the use of telomerase as an anti-cancer vaccine. The genetically-engineered vaccine helped kill three types of cancer cells, including melanoma and colon cancer in vitro. Many of our colleagues, however, are skeptical about the toxicity of this compound in vivo.

Ref:

( AP) "Geron Soars After Research Backs Cancer Vaccine," The Los Angeles Times, p. C4 (March 19, 2003).

Americans Are Living Longer

March 14, 2003; Atlanta, GA ( AP) The CDC reported today that a dip in some disease deaths has permitted US Life Expectancy Statistics to top 77...

................2000...............2001
Overall:77.0 years..........77.2 years
[ Note: In 1900, life expectancy was around 49; while in 1929, it was 57.1 years]

Demographics by Gender:
Males:....74.3................ 74.4 years
Females: 79.7................ 79.8 years

Drop in deaths from major disease:
Pneumonia: 7 percent
Heart Disease: 4 percent
Cancer: 2 percent.
Stroke: nearly 5 percent

Note: Homicides increased by 17 percent, but this was an anomaly due to the events surrounding September 11th. Without the attacks, the homicide rate would actually have declined by 1.7 percent.

Refs:

1. "CDC: Americans Living Longer Than Ever," CNN (March 14, 2003).
2. "Average Life Expectancy Increased to 77.2 Years in 2001," The Wall Street Journal, p. A1 (March 17, 2003).

Aging Experts Give Silver Fleece Award to Clonaid

Friday, March 14, 2003; Chicago, IL (AP) -- "A group that claims to have cloned the first human babies, and capsules that purport to combat old age, are recipients of tongue-in-cheek awards from three prominent aging experts. The "Silver Fleece" awards announced Thursday were created by Dr. S. Jay Olshansky, a scientist at the University of Illinois at Chicago, aging expert Prof. Leonard Hayflick of the University of California at San Francisco, and Dr. Bruce Carnes, who studies the biology of aging at the National Opinion Research Center in Chicago. The trio contend the Anti-Aging industry's claims aren't backed up by good science.

The selection of Clonaid, the group whose recent cloning claims have been questioned by many scientists, was a "no-brainer," Hayflick said. Clonaid claims on its website that in the eventual cloning of an adult, memories and personality will be transferred into "a brand new body," allowing people to "wake-up after death."

Also winning an award are capsules called Longevity, sold by Urban Nutrition, Inc. as an "Anti-Aging" formula. The recipients "are people who are trying to exploit the fear of death that almost everyone has," Carnes said.

But Thomas Kaenzig, Clonaid's Vice President, said the criticism comes from "backward- oriented scientists" akin to those who said 50 years ago "that we will not be able to go to the moon. Matthew Oden, Urban Nutrition's marketing manager, said Longevity doesn't claim to reverse or stop aging, even though the company calls it an "Anti-Aging" formula. That's "more just a buzz word," he said. "The product is primarily promoted as helping rejuvenate appearance and the immune system," Oden said.

The awards -- "bottles of corn syrup labeled 'Snake Oil'" are modeled after the "Golden Fleece" awards created by former U.S. Sen. William Proxmire to highlight questionable government spending.

Refs: 1. Silver Fleece
2. William M. London, "Longevity, Clonaid Receive Silver Fleece Awards for 2003," Skeptical Inquirer, Vol. 27, No. 4, p. 9 (July/August 2003).
[ Editor's Note: William London is the Program Director and Editor of the NCAHF Newsletter, National Council Against Health Fraud.]

Senate Bans Partial Birth Abortion by 64 to 33

March 13, 2003; The likely scenario is that the House will follow suit sometime this Spring and once President Bush signs the measure into law, which he has vowed to do, having already praised the work of the majority of the Senators, the only way to stop the politicians from looking over the shoulders of the gynecologists is in the courts.

Refs:

1. Richard Simon, "Senate Oks Bill to Curb Abortions," The Los Angeles Times, pp. A1, 28, 29 (March 14, 2003).
2. David G. Savage, "Logic of Debate on Abortion Is Questioned," The Los Angeles Times, p. A16 (March 13, 2003).
3. David Rogers, "Senators Defeat Attempt to Ease Planned Late-Term Abortion Ban," The Wall Street Journal, pp. A1, 4 (March 13, 2003).
4. Editorial, "Hypocrisy in Abortion Vote," The Los Angeles Times, p. B12 (March 19, 2003).

Bovine DNA To Be Sequenced

March 8, 2003 ( Reuters); The National Human Genome Research Institute has approved spending $50 million to sequence all the genes in cattle. The work will be done in Texas at the Baylor College of Medicine in Houston and Texas A&M University. The Maryland- based research institute (at NIH), which has sponsored projects to sequence the human genome as well as the collection of genes in mice, fruit flies, and other animals, said it would put up half the money if the rest could be raised from other sources. Texas Gov. Rick Perry said, "the state would pay $10 million and work to raise an additional $15 million, adding that the project promised benefits for human health and the biotechnology industry, as well as gains for the beef and dairy industries." The bovine genome is similar in size to those of humans and other mammals, with an estimated size of 3 Giga Base Pairs (3 GBP).

"By comparing the human genome with the genomes of different organisms [ Comparative Genomics], we can better understand the structure and function of human genes and thereby develop new strategies in the battle against human disease, said Dr. Francis Collins, the Institute's Director. "The more genomes we have, the more powerful this tool becomes."

Ref:

Reuters, "Genome Institute OKs Funding of Cattle Gene Study," The Los Angeles Times (March 8, 2003).

Bone-Marrow Adult Stem Cell Surprise: Select Monocytes Can Transform to Neurons

March 1, 2003; Dr. Eliezer Huberman of Argonne National Laboratory in Illinois will publish in an upcoming PNAS that different growth factors can switch isolated bone-marrow monocytes into what appear to be liver cells, blood vessel cells, neurons (using Nerve Growth Factor [NGF], and other non-macrophage immune-function cells. The monocyte population that has been identified differs from multipurpose bone-marrow stem cells. Patent applications on the medical use of monocyte stem cells have already been submitted. It is speculated that these may be the cells that travel to damaged organs for purposes of repair. We still need to do two things: (1) Confirm that the transformed cells are functional and (2) whether these adult monocytes lose their potency with age. Check back here for the Abstract in PNAS and for more details as they become available.

First Ref:

John Travis, "Stem Cell Surprise: Blood Cells Form Liver, Nerve Cells," Science News, Vol. 163, No. 9, p. 131 (March 1, 2003).

Autologous Adult Stem Cells Transplanted into Teenager's Damaged Heart

March 6, 2003; Royal Oak, MI (AP) --- An experimental procedure aiming to grow new cardiac muscle and vessels in a damaged heart was tried yesterday at a hospital in Michigan. Private companies, however, have approached the area of cell therapy tentatively. Regalado [2] writes, "although the markets are potentially huge, it hasn't been clear how to establish a successful business model, especially in cases where the product is the patient's own cells. On the other hand, a treatment for heart attacks would present a major breakthrough for the field. G-CSF (Neupogen) from Amgen of Thousand Oaks, CA was used to enrich the number of bone-marrow stem cells in the bloodstream. Then doctors harvested the cells using leukopheresis (with cell sorter). Ten doses of the stem-cell-concentrated solution were injected by catheter into a vessel of the teenager's heart." Within five days, Dimitr's Cardiac Ejection Fraction (quantity of blood pumped out with each beat) rose form 25 to 35 percent. We should know in about three or four months if this treatment is working.

Refs:

1. "Stem Cells Transplanted to Teen's Heart," CNN (March 6, 2003).
[ Editor's Note: There is a stunningly beautiful animation on the CNN website called "Embryonic Stem Cell Research" that can be gotten to by a single mouse click from the story above. It's worth the price of admission just for that.]
2. Antonio Regalado, "Doctors Use Teen's Stem Cells in Procedure to Repair His Heart," The Wall Street Journal, pp. A1,9 (March 6, 2003).
3. Thomas H. Maugh, II, "Stem-Cell Procedure May Let Teen Live Normally: Michigan Boy Has the Experimental Transplant after a Nail Gun Pierced His Heart," The Los Angeles Times, p. A21 (March 6, 2003).

House Passes Weldon-Stupak Bill Banning All Forms of Human Cloning

February 28, 2003; Washington, D.C. Two years ago the US House of Representatives approved a comprehensive ban on human cloning by a vote of [265:162]. However, the measure has never been taken up by the Senate. Yesterday, Rep. David Weldon (R- FL) submitted The Human Cloning Prohibition Act of 2003 [HR 534] that would set up a prison term of up to 10 years in jail and civil fines of $1 million or more for anyone who performed (or tried to perform) human cloning for any purpose whatsoever. This Bill passed decisively by [241:155]. largely along party lines, but with a number of crossover votes going both ways.

Rep. Susan Wilkins Myrick ( R-NC) argued, "Cloning would be the most ghoulish and dangerous enterprise in human history." Later, Rep. Todd W. Akin ( R-MO) spun it as "some sort of Brave New World that none of us wants to find ourselves in ... a world in which parts of human beings are stored like parts in a junkyard."

[ Editorial Comment: This statement is in the same truth-value equivalence-class as the statement, "I've never seen or heard of any man living forever, so I might as well die now and get it over with." This, in turn, is equivalent c. 1000 A.D. to "I've never seen or heard of a man who could fly, so men can never fly." But just in case, let's pass a law against attempts to fly and put the Wright Brothers in jail, if we ever were to locate them before they were successful. By the way, if only the imagined "junkyard" existed, I would sign myself up immediately and be the first one on line. How could it be that there are educated, seemingly-intelligent adult human beings who are seeking to criminalize what I myself am deliberately trying to do? I always thought of myself as a nice guy.:-)

More seriously, why did the House repeat, yesterday, this shameless exercise of two years ago? Answer: Because they could. And, of course, to perpetrate the illusion of momentum in the minds of the American public in favor of themselves as enemies of "murderers of human babies." By the way, they regularly put in a plug for research on adult stem cells, but I haven't seen any big pot of money thrown at this problem either.

On the other hand, the Senate is still too sophisticated for the White House Staffers and Religious Fundamentalists to crack; so, for the moment, we are stuck. The dispute over research cloning is so sharp that no Bill may pass Congress this year, leaving the US as one of the few developed nations with no ban on reproductive cloning! Talk about "throwing out the baby with the bath water." (Forgive the pun.)

There must be a lot of behind-the-scenes jockeying for position among religious fundamentalists, women's rights groups, the National Right-to-Life Committee, and various anti-abortion groups allied with the White House, who are all pushing for an agenda that insists on any form of human cloning as "tantamount to killing a baby for the sake of research." However, on the other side are patient-groups lobbying for particular diseases, medical scientists trying to understand what's going on, and the biotechnology industry as a whole.

But, sadly, both alliances seem to be equally impotent. The conservatives don't appear to have the 60 votes they need for cloture in the Senate to officially criminalize what they don't like about what they think we might be able to do someday, while the medical establishment, on the other hand, doesn't yet know how to do what it is they are accusing us of trying to do. Nevertheless, both sides are willing to fight-to-the-death over things that, today, are merely hypothetical speculations.

The Weldon bill is neither a repeat of the July 2001 bill that passed nor of last year's Brownback bill that was withdrawn before a Senate vote could be taken. The Weldon bill is so draconian, it would not only prohibit patients traveling abroad to receive embryonic stem-cell treatments, in particular, by requiring them to be arrested upon their return to the US (as in Brownback), it would also prohibit the importation of any medical therapy created from cloned embryos in general, even though the development was legal in the country of origin.

The arrogance of our legislators is breathtaking! They are telling us, "if you want to live in this country, you're going to live under our religious ideological control, whether you like it or not. If you wish to escape from our jurisdiction, for any reason, by going abroad, don't expect to ever return and try and live here again, or we'll send you to jail as a criminal!" This legislation would certainly override a new law governing legal therapeutic cloning in the State of California that was signed last year by Gov. Gray Davis and went into effect on January 1st of this year. Should California secede from the Union over the issue of therapeutic cloning? How else can we prevent conservatives in Washington, D.C. from deciding what constitutes a crime in what should rightfully be our own jurisdiction?

According to Reuters, President Bush has vowed to veto any bill (even the reasonable bills of Kennedy/Hatch/Feinstein/Specter/Harkin) that "does not outlaw all forms of human cloning." I am sure that Sen. Bill Frist (R - TN), Senate Majority Leader and also an M.D. who is looking for a middle ground, knows this too. Can Dr. Frist schedule Dr. Michael West, Ph.D., CEO of ACT to testify at the upcoming Senate Subcommittee hearings? ]

Refs:

1. "House Opens Debate on Cloning," CNN (February 27, 2003).
2. Aaron Zitner, "House Votes to Outlaw Human Cloning: Ban Includes Research," The Los Angeles Times, p. A32 (February 28, 2003).
3. Ted Agres, "House Passes Anti-Cloning Measure: Bill Would Criminalize Research Using Human SCNT," The Scientist (February 28, 2003).
4. Mark Ingebretsen, "Senate Readies for Battle Over Bill to Ban Cloning," The Daily Scan, The On-Line Wall Street Journal (March 3, 2003).
5. A. Scott Loveless, "A Better Cloning Plan," Salt Lake Tribune (March 2, 2003).
6. Norah Vincent, Op-Ed Piece, "Ethics Must Trump Mindless Technology," The Los Angeles Times, p. B17 (March 6, 2003).
[ Editorial Remark: Ms. Vincent, a columnist in Yardley, PA and frequent editorial writer, is passionately concerned with what she sees as "blind technological advance" and "the juggernaut of scientific progress." But the speed of a train depends on whether the background is standing still. For those of us who are interested in science and technology, the train seems to be hardly moving at all! [Yet, it does move.] Ms. Vincent cites the work of ACT in November 2001 with parthenogenesis as her "end run" from the ethical dilemma created by the possibility of all forms of cloning, not just reproductive but also therapeutic cloning. She equates disposing of pre-implantation viable human embryos with abortion. But, she warns, therapeutic cloning is even worse than abortion, because it is premeditated at conception. At least some abortions have moral purpose if, for example, they followed a rape or incest that were outside of our control. Deliberate harvesting of embryos, for her, results in "gruesome test-tube fodder." It's amazing, to me, how conservatives, who are so passionately adverse to abortion, are willing to offer unsolicited advice about "adult" stem-cell technology without offering us any evidence that it works. In fact, as far as I know, there is little evidence that embryonic stem cells work, since the data is so sparse. The few positive experiments we have have not been faithfully and routinely reproduced in other labs. We are at the Wright-Brothers stage of aeronautical engineering. We need a huge set of controlled experiments with mice that compare murine adult stem cells with embryonic stem cells in both old and young mice to see what really works. It will cost a lot of money (but not that much, maybe $10 million) and it will take a long time (but not that long, maybe two to three years), but it's all doable by NIA/NIH if we get started. Will Ms. Vincent aggressively support the research needed to figure out whether adult stem cells work? Most interestingly, if they can be shown to work, can they be stimulated with growth factors in situ to replenish tissues that are shriveling up or thinning out as we age?]
7. Editorial, "The Good Kind of Cloning," The Los Angeles Times, p. B12 (March 12, 2003).
Bill S. 245 (Sen Sam Brownback ( R - Kan)) proposes to ban all forms of human cloning (and criminalize even unsuccessful attempts to conduct therapeutic cloning by medical scientists within the jurisdiction of US law enforcement) by subjecting convicted suspects to up-to-ten-years-in-prison and fines of up-to-$1-million. I think you have my attention Senator. On the other hand, a competing bill, S.303 (Sen. Orrin G. Hatch ( R - UT)), proposes to prohibit reproductive cloning but allow for the possibility of legal therapeutic [or research] cloning. S.303 would also adopt strict regulations modeled after a successful oversight system put into effect two years ago in Great Britain. The Times Editorial clearly favors Hatch over Brownback, calling the latter a "sledgehammer." Voting in the Senate is expected to take place next week. Stay tuned for the details.

By the way, does anybody know how passage will affect the current law that went into effect here in California on January 1st? Is it true that there is no grandfather provision for earlier state laws that conflict with a newly-minted federal law? Please E-mail us if you know the answer to this question.

8. Steve Coles, "Therapeutic Cloning Should Not Be Banned," The Los Angeles Times, p. B10 (March 17, 2003).
9. Don C. Reed, "Let Hope Grow in a Petri Dish," The Los Angeles Times, p. M5 (March 16, 2003).
Mr. Reed is Chairman of a lobbying group that raised $4.8 million for California legislation to promote therapeutic cloning known as Californians for Cure. Mr. Reed's son, Roman, is paralyzed and much in need of stem- cell therapy.
10. One-Page Letter-to-Science by LeRoy Walters, Kennedy Institute of Ethics at Georgetown University in Washington, D.C., "Research Cloning, Ethics, and Public Policy," Science, Vol. 299, No. 5613, p. 1661 (March 14, 2003).
11. Two Letters to the Editor, "Stem-Cell Research Should Stay in U.S.," The Los Angeles Times, p. B16 (March 20, 2003).
12. Editorial, "Get Real," Scientific American, Vol. 288, No. 4, p. 10 (April 2003).
[ Editor's Remarks: This Editorial is clearly pro Therapeutic Cloning. The Editors of Scientific American attack technocynics like Drs. Francis Fukuyama and Bill Joy while promoting one of our own members, Prof. Greg Stock of UCLA. They go on to cite the poet, Henry David Thoreau [1817 - 1862] as "regarding trains, telegraphs, newspapers, and even the delivery of mail as dehumanizing." But our biggest danger is not that science will run ahead of ethics concerns, but the exact opposite: that ethical hair triggers will paralyze truly worthy research. "We should deal with actual rather than imaginary problems." Just because there are a small group of literary intellectuals who can imagine them, doesn't mean that all potential problems merit immediate action, just that one ought to be aware of them. No technology has ever conferred unalloyed bliss on its beneficiaries. However, side-effect problems are usually corrected by refinements to the technology or legislation on its use. Driving your automobile on a freeway will always be a more-or-less dangerous activity depending on the traffic and weather conditions. But do you want to give up cars? In similar fashion, just because the satirist Jonathan Swift could imagine the problem of the Struldbruggs (a race of people who figured out how to ask for immortality but forgot to ask for youthfulness, and therefore suffered the problem of getting perpetually older but were never allowed to die; you know, the problem of the Sorcerer's Apprentice or "Be careful what you ask for, because you just might get it.") in his (political) children's story Gulliver's Travels doesn't mean that we ought to terminate our scientific quest for immortality, since, under certain circumstances, it might lead us down a slippery slope or cause us to make an "unnatural bargain with the devil." We can admire Swift for the cleverness of his cautionary tale --- he was a smart guy, but that's all. It does means that we need to think about what we're doing, while we're doing it, but not to stop doing it out of fear of side effects. Cars do bring other problems with them... traffic lights that don't work all the time or air bags that might go off when they shouldn't. "To stop research would be to give up trying to make the world a better place. Such would deny human nature ostensibly to save it."]
13. Michael Shermer, Publisher of Skeptic Magazine and General Editor of The Skeptical Encyclopedia of Pseudoscience, "I, Clone: The Three Laws of Cloning Will Protect Clones and Advance Science," Scientific American, Vol. 288, No. 4, p. 38 (April 2003).
The Three Laws of Cloning (based loosely on "The Three Laws of Robotics" so well articulated in Isaac Asimov's I, Robot science-fiction stories, but without the self- referencial recursion) are as follows:
(1) A human clone is a human being no less unique in his or her personhood than an identical twin;
(2) A human clone shall have all the rights and privileges that accompany this legal and moral status;
(3) A human clone is to be accorded the same dignity and respect as would be due to any other member of our species.
Prof. Shermer goes on to refute various myths about cloning ranging from "Identical Personhood," and "Playing God," to "Human Dignity," many of which are based on pure ignorance of the scientific issues. It is unclear, however, that he is doing anything here other than "preaching to the choir." Let's revisit the problem after it's been done.
14. The Human Cloning Foundation of Georgia claims to be an official site in support of human cloning technology. They have at least five very good books advertised on the right-hand frame of their site. [ Note: HCF has been determined to be a 501(c)3 non-profit organization and, therefore, all donations are tax-deductible to the extent permitted by law.]
15. Bill McKibben, Op-Ed Piece, "Keep Us Human: If We're Truly Smart, We'll Refuse to Foolishly Tamper with Our DNA," The Los Angeles Times, p. B11 (April 14, 2003).
Based on his newly published book, Enough: Staying Human in an Engineered Age (Times Books, New York; 2003).

Mr. John I. McMorran [1889 - 2003]

February 25, 2003; Lakeland, FL; We are sad to report that Mr. John I. McMorran, born June 19, 1889, died on Monday, February 24th at the age of 113 years, 250 days, of heart failure and complications related to pneumonia. We have been tracking John as the Oldest Living American Male for many years, and a video clip of him at age 111 is available on the Centenarian portion of this website. Mr. Michael Bradley, Administrator of the Tandem Health Care Nursing Home at the Socrum Loop Facility in Lakeland, informed us that John's Grandson Robert and his Great Grandson Scott, came to visit John regularly during the 11 years he resided at the nursing home, which was not always true of many other long-term residents. Furthermore, John was very pleased a few years ago to learn that the LA-GRG had officially designated him as Oldest Living Man in America.

John was alert up until the last two weeks of his life, when he declined to eat or drink, and the reason why they decided to hospitalize him during his last few days. When asked "to what if anything he attributed John's extreme longevity?" Robert answered that "His Grandfather worked hard all his life, and he was a kind man who had a great sense of humor." The family decided that an autopsy would not be performed, despite my protest that we would attempt to publish a summary of the findings in a medical journal, and it might be an important contribution to the scientific literature. But, obviously, we respect the privacy of the families of our Supercentenarins as our highest priority. John's funeral was held on Friday, February 28th in Michigan.

For those who are wondering about the name of John's successor, our new Oldest Living American Male is Mr. Fred Hale of New York State. His son, Fred Hale, Jr., reports that, as of this morning, his father, Mr. Hale, Sr., is alive and well. We will keep you posted.

Refs:

1. AP, CNN International (February 25, 2003; 5:37 GMT).
2. Myrna Oliver, "J. McMorran, 113; Oldest Man in U.S., 5th-Oldest Ever," The Los Angeles Times, p. B14 (February 27, 2003).

Rhesus Monkeys To Be Cloned From Embryonic Cells

February 21, 2003; Beaverton, OR ( Science News) --- The birth of Dolly provoked an international furor about the possibility of human cloning. Donald Wolf, of the Oregon Regional Primate Research Center, worries that the world will similarly overreact if he and his colleagues clone an adult nonhuman primate, such as a rhesus monkey. That fear "is a disincentive to continue, but [we] simply can't be intimidated," he says. "There's such a need for genetically identical monkeys, such as for AIDS-vaccine work, that we need to press on."

Several years ago, Wolf's team successfully cloned monkeys by using the nucleus of an embryonic cell. Yet, it hasn't succeeded when starting with the nucleus of a cell from an adult monkey. Indeed, the researchers are still struggling to get such cloned embryos ready for transfer into a surrogate mother.

"Progress has been slow and has been limited. We're trying to establish conditions where we can get [cloned] embryos to grow to the implantation stage. Once we do that with a reasonable degree of regularity, we'll go back to doing embryo transfers to establish pregnancies," Wolf said, "We're on the cusp."

Ref:

John Travis, "Dolly Was Lucky: Scientists Warn that Cloning Is Too Dangerous for People," Science News, Vol. 160, No. 16 (October 20, 2001).

Dolly, the First Cloned Animal, Dead at Age 6

February 14, 2003; Edinburgh, UK ( CNN); Dr. Harry Griffen, Head of the Roslin Institute, said that a decision was taken to euthanize Dolly after she was diagnosed with an irreversible lung disease [ Pulmonary Adenomatosis or Jaagsiekte]. Dolly, named for country-western singer Dolly Parton, was born on July 6, 1996, and therefore lived for 6 years, 222 days. Although Finn-Dorset sheep can live for as much as 11 or 12 years, lung infections are common in older sheep, particularly those housed in-doors. A full post-mortem (autopsy) will be conducted to report any significant findings. Afterward, Dolly's body will be placed on display at the National Museum of Scotland. She is survived by at least three of six healthy lambs, whom she conceived in the conventional manner. Click the photo above for more details.

Refs:

1. Janet Stobart and Rosie Mestel, "Sheep Dolly, 6, Dies; Pioneer Clone's Birth Sparked Debate," The Los Angeles Times, pp. A1, 3 (February 15, 2003).
2. Rosie Mestel, "Dolly's Death Resurrects Debate on Cloning Ethics: Death a Reminder of Cloning's Complexity," The Los Angeles Times, pp. A1, 32 (February 16, 2003).
[ Editor's Note: The best statistics for the affect of cloning on longevity comes from mice. (The data on sheep, cows, goats, rabbits, pigs, cats, and rats are too sparse, while data from dogs and monkeys are virtually non- existent; preliminary data for human cloning obtained by researchers at ACT of Worcester, MA were not encouraging, while data from the Raelian Sect {three alleged cases in the US/Israel, The Netherlands, and South Korea}, unless they are willing to provide some scientific evidence to the contrary, may be nothing more than an elaborate hoax in which the media was victimized into providing free publicity in exchange for a non-existent story.) In particular, with regard to mice, Japanese researchers have found that cloned mice died somewhat earlier than normal mice, dying prematurely from a combination of pneumonia, damaged livers, and tumors. Prof. Rudolf Jaenisch, of the Whitehead Institute for Biomedical Research in Cambridge, MA has examined 10,000 mouse genes in the livers and placentas of cloned mice and found that hundreds of these genes exhibited abnormal patterns of activation (especially associated with "imprinting"). Even the most basic steps in the process of cloning remain exquisitely treacherous, sort of like performing brain surgery with a hammer, a chisel, and a screw driver."]
3. "Dolly the sheep was euthanized on Friday due to lung disease. The first sheep cloned from an adult cell lived just six years, half a normal lifespan," The Wall Street Journal, p. A1 (February 18, 2003).
4. Jim Giles and Jonathan Knight, "Dolly's Death Leaves Researchers Woolly on Clone Aging Issue," Nature, Vol. 421, p. 776 (2003).
Dr. Ian Wilmut, leader of the team that created Dolly at the Roslin Institute in Scotland, said that "the post mortem revealed that she suffered from a virus that caused lung tumors characteristic of the disease. There were no other gross abnormalities, apart from her arthritis, which was diagnosed last year."
[ Editor's Note: Therefore, Dolly's death appears to be unconnected with cloning per se, as the virus that causes this pulmonary infection has afflicted both cloned and normal sheep at this same Institute.]
5. "A Sad Farewell for Dolly the Sheep, the World's First Cloned Mammal," New Scientist, Vol. 177, No. 2383, p. 8 (February 22, 2003).
6.Gretchen Vogel, "Dolly Goes to Greener Pastures," Science, Vol. 299, No. 5610, p. 1163 (February 21, 2003).
"... Wilmut and his colleagues, meanwhile, are continuing to push the frontiers: They are applying for one of the first licenses in the UK to begin nuclear transfer experiments with human cells. Also, the Institute has decided to suspend its livestock cloning program and is concentrating instead on trying to better understand the cloning process in mice."
7. "In Memorium: Good-Bye, Dolly," Scientific American, Vol. 288, No. 4, p. 30 (April 2003).
8. KP, "Dolly, the First Cloned Sheep, Dies," Nature Biotechnology, Vol. 21, p. 349 (April 2003).
[ Editor's Note: This article contains a very nice Table of Cloning Success Rates for goats, mice, cows, sheep, cats, pigs, and rabbits. Cloning Efficiency is defined as the number of live offspring expressed as a percentage of the total number of nuclear transfer oocytes where the DNA donor cell was an adult cell. Roslin Institute.
9. "Dolly is Dead, But Her Legend Lives On," Science, Vol. 300, No. 5618, p. 423 (April 18, 2003).
Dolly went on display last week as a new exhibit at the Royal Museum in Edinburgh. "The embalming involved mounting Dolly's skin on a fiberglass mold of her body and fitting her with glass eyes and resin hooves."

C150T Gene Mutation Prevalent in mtDNA of Italian Centenarians

February 12, 2003; Pasadena, CA ( CNBC) - Prof. Giuseppe Attardi of the Molecular Biology Department at CalTech has published new findings in the February 4th issue of the Proceedings of the National Academy of Sciences on the distribution of mitochondrial mutations in Italian Centenarians. Click for more details.

Zhang J, Asin-Cayuela J, Fish J, Michikawa Y, Bonafe M, Olivieri F, Passarino G, De Benedictis G, Franceschi C, and Attardi G.*, "Strikingly Higher Frequency in Centenarians and Twins of mtDNA Mutation Causing Remodeling of Replication Origin in Leukocytes, Proc. Natl. Acad. Sci. USA, Vol.100, No. 3, pp.1116-21 (February 4, 2003).
____________________
* Division of Biology, California Institute of Technology, Pasadena, CA 91125; USA.

Abstract:

The presence of a genetic component in longevity is well known. Here, the association of a mtDNA mutation with a prolonged life span in humans was investigated. Large-scale screening of the mtDNA main control region in leukocytes from subjects of an Italian population revealed a homoplasmic C150T transition near an origin of heavy mtDNA-strand synthesis in approximately 17% of 52 subjects [99 - 106] years old, but, in contrast, in only 3.4% of 117 younger individuals (P = 0.0035). Evidence was obtained for the contribution of somatic events, under probable nuclear genetic control, to the striking selective accumulation of the mutation in centenarians. In another study, among leukocyte mtDNA samples from 20 monozygotic and 18 dizygotic twins, 60-75 years old, 30% (P = 0.0007) and 22% (P = 0.011), respectively, of the individuals involved exhibited the homoplasmic C150T mutation. In a different system, i.e., in five human fibroblast longitudinal studies, convincing evidence for the aging-related somatic expansion of the C150T mutation, up to homoplasmy, was obtained. Most significantly, 5'-end analysis of nascent heavy mtDNA strands consistently revealed a new replication origin at position 149, substituting for that at 151, only in C150T mutation-carrying samples of fibroblasts or immortalized lymphocytes. Considering the aging-related health risks that the centenarians have survived and the developmental risks of twin gestations, it is proposed that selection for a remodeled replication origin, inherited or somatically acquired, provides a survival advantage and underlies the observed high incidence of the C150T mutation in centenarians and twins.

Ref:

"People Over 100 Share Genetic Mutation, Study Says," The Los Angeles Times, p. A26 (February 15, 2003).

Homologous Recombination Used to Create Knockout Mice and Disease-Gene Deletion in Human Embryonic Stem Cells

February 9, 2003; Madison, WI ( Reuters) Drs. James Thomson and Thomas Zwaka of the University of Wisconsin have deleted a disease gene from human embryonic stem cells. They are currently working on Lesch-Nyhan Disease, a rare type of mental retardation caused by a single mutation that affects boys.

Refs:

1. "Scientists Replace Human Stem Cell Genes," CNN (February 10, 2003).
2. Eithan Galun, "Gene Therapy Has Vast Potential Despite Setbacks; Push On with Human Trials," The Los Angeles Times, Op-Ed Piece, p. B13 (February 18, 2003).
3. John Travis, "Mining the Mouse: A Rodent's DNA Sheds Light on the Human Genome," Science News, Vol. 163, No. 8, pp. 122-3 (February 22, 2003).

US Senate Bill S.303 Will Allow Human Therapeutic Cloning, While Banning Reproductive Cloning

February 7, 2003; Click for more details.

Telomere Length Linked to Life Expectancy

January 31, 2003; As published in today's issue of The Lancet [1], Dr. Richard Cawthon and colleagues of the University of Utah in Salt Lake City have analyzed the telomere lengths of chromosomes from blood samples taken from 143 men and women aged 60 years or older (originally drawn for a different reason back in the time period [1982 - 1986]). The shortest quarter had a mortality rate from infectious disease (pneumonia) that was 8 times higher than those with the longest telomeres. Also, patients with telomere lengths in the shorter half had a 3 x higher morality rate from heart disease. Dr. Elizabeth Blackburn, a molecular biologist and telomere expert from UC San Francisco said that "this was the first such association with mortality that she had seen in the literature." "This does not mean that telomere shortening is necessarily a cause of aging. However, it could be statistically associated as a side effect of aging," she said.

Abstract:

During normal aging, the gradual loss of telomeric DNA in dividing somatic cells can contribute to replicative senescence, apoptosis, and/or neoplastic transformation. In the genetic disorder Dyskeratosis Congenita, telomere shortening is accelerated, and patients have premature onset of many age-related diseases and early death.

We aimed to assess an association between telomere length and mortality in 143 normal unrelated individuals over the age of 60 years. Those with shorter telomeres in blood DNA had poorer survival, attributable in part to a 3.18-fold higher mortality rate from heart disease [95% Confidence Interval: [1.36 7.45], P = 0.0079], and an 8.54-fold higher mortality rate from infectious disease [1.52 47.9]; P = 0.015. These results lend support to the hypothesis that telomere shortening in human beings contributes to mortality in many age-related diseases.

Refs:

1. Richard M. Cawthon, Ken R. Smith, Elizabeth O'Briend, Anna Sivatchenkoc, and Richard A. Kerberc, "Association between Telomere Length in Blood and Mortality in People Aged 60 Years or Older," The Lancet, Vol. 361, No. 9355, pp. 393-5 (February 1, 2003).
2. Rosie Mestel, "DNA Structure Linked to Lifespan: A New Study Suggests the Length of Telomeres, 'Caps' at the End of Chromosomes, Offer Clues to Life Expectancy," The Los Angeles Times, p. A17 (January 31, 2003).

Saturday, February 1, 2003; Noon PDT; We share the grief of the families of the seven astronauts who perished when the Space Shuttle Columbia disintegrated upon reentry early this morning (5:53 AM PST - 7:59 AM CST] and fell from the sky ~40 miles above North Eastern Texas, USA. There is no better way to honor their memory than by continuing their work.

GRG Editorial: President Asks for a Ban on All Human Cloning

Tuesday, January 28, 2003; President Bush's delicately-worded statement in his State-of-the-Union Address seeking to criminalize all human cloning, not just reproductive cloning [with which we strongly agree], but also therapeutic cloning [with which we strongly disagree], with the support of the US Senate was impeccably crafted as follows:

"And because no human life should be started or ended as the object of an experiment, I ask you to set a high standard for humanity and pass a law against all human cloning." [applause]

We believe that the presuppositional logic in above sentence is a rhetorical masterpiece. "A+" to the White House speech-writer who wrote it and probably burned the midnight oil seeking to articulate in this speech means to advance the Administration's religious agenda without alienating ordinary, middle-of-the-road American viewers. But we believe that it is the GRG's job to expose this sort of sophistry for what it is... striving to make an inherently wrong idea palatable to ordinary folks before they know what they've signed up to. Indeed, the State of California legislation passed last year and that went into effect on January 1st with the aim of funding therapeutic cloning is likely to be overruled if the US Senate were to pass newer legislation and the California law was inconsistent with Federal law.

A full GRG Editorial on the subtleties of human cloning will be posted on this website if we can ever get any of the groups that are striving to accomplish reproductive cloning to provide us with scientific evidence of their alleged success rather than a flimsy press conference touting their claims. Don't forget the boy "who cried wolf." Someone might actually do it quietly off shore. Who knows?

Refs:

1. "President Delivers the State-of-the-Union," U.S. Capitol, www.whitehouse.gov (January 28, 2003; 9:01 PM EST).
2. State-of-the-Union Address, The Los Angeles Times, p. A12 (January 29, 2003).

UC Scientists Switch Bird Beaks

January 24, 2003; In today's issue of Science University of California San Francisco scientists report that they have swapped neural crest cells, using a very fine needle into the eggs, at the 36-hour stage of avian embryogenesis, so that live ducks were born with the pointy beak of a quail, while live quail were born with the flat bill normally found on ducks. These chimera may ultimately lead to a better understanding of facial birth defects in humans, like cleft palate.

" Qucks," " Duails," and Beak Morphology

Vertebrates have been remarkably successful at adapting to new environments, and the evolution of complex head and face features is considered fundamental to their origins and diversity. Their developmental flexibility is particularly evident in the bird beak, whose morphology has undergone dramatic diversification and specialization over time. In a report in the ( January 24th issue of Science, Schneider and Helms revealed some of the cellular and molecular mechanisms that underlie this remarkable variability. In an elegant set of experiments, they exchanged neural crest cells -- which produce skeletal and connective tissue in the head and face-- between the beak-developing regions of growing quail and duck embryos. Normal ducks have long, flat bills, while quails typically have shorter, narrower ones. But in the transplant recipients, the resulting beak shapes were characteristic of the donor species, and not of the host into which the donor cells were transplanted. In other words, transplanting duck cells into a quail yielded a duck-billed quail, and vice versa. This suggests that neural crest cells control beak development in a species-specific manner. Furthermore, genetic analysis demonstrated that these cells pattern beak development by maintaining their own molecular programs and by regulating gene expression in adjacent host tissues.

Ref:

Paul Trainor, "Development: The Bills of Qucks and Duails," Science, Vol. 299, No. 5606, p. 523 (January 24, 2003).

Now a Dutch Couple Is Said to Have a Clone?

January 4, 2003; Amsterdam; NETHERLANDS ( MS-NBC) Clonaid, the company that claims to have produced the first human clone last week, said today that a second cloned baby girl has been born yesterday at 10:00 PM local time to a Dutch lesbian couple (the surrogate mother was also the egg donor and the nuclear-transfer provider, so she gave birth, as in the case of the American Mother of Eve, to her genetically-identical twin; she was said to be 32 years old). But neither baby has been confirmed to be a clone by genetic testing, and mainstream scientists are skeptical of the company's claims.

[ Editor's Note: As of this hour, the location of the baby has not been revealed (maybe in Northern Europe, but not Holland). Give us a break! Is this a hoax intended to produce free publicity for the Raelian Sect? Hello!]

Where in the USA does Eve's Mother live? Where in Europe was "Eve2" born? We cannot continue to cut slack for this group indefinitely. Privacy can be maintained if there is a credible third-party who can serve as a witness without any financial ties to the principals. It is rumored that Clonaid expects to charge more than $200,000 per procedure. Dr. Guillen is rumored to have a conflict-of-interest in that he sought to sell a TV documentary on the Raelians to a half-dozen media companies several months ago, and he is no longer affiliated as a science journalist with ABC-TV News.

Refs:

Stem Cells Offer Hope to Heart-Attack Victims

January 3, 2003; London, UK ( Reuters) --- "Stem cells may help patients recover from heart attacks by triggering new cell growth in damaged tissue," scientists said on Friday. Click for more details.

News Items for 2002

Click for News Items from 2002.