NEWS ITEMS FOR THE YEAR 1999


Genetic Analysis in the Plant Kingdom

December 15, 1999. For the first time, chromosomes from a member of the plant kingdom have been analyzed -- a major step toward developing improved crops. Researchers unraveled the genetic structure of two chromosomes from Arabidopsis thaliana, a member of the mustard family. Click for more details.


First Cross Species Implantation in New Orleans

December 14, 1999. Click for more details.


Emory University Uses Cord Blood Stem Cells for SickleCell Anemia

December 13, 1999. Click for more details.


Porcine Pituitary Growth Hormone Secretagogue Discovered

December 8, 1999. See "Gene Therapy Plumps Pigs, Study Says: Technique Stimulates Growth Hormones -- Makes Hogs Grow 40 Percent Larger and Faster," The Los Angeles Times, p. A29 (December 8, 1999) and Nature Biotechnology, p. 1179, Vol. 17, No. 12 (December 1999). Click for more details .


Artificial Chromosomes Inherited in Mice

December 8, 1999. Click for more details .


Gene Therapy Death at the University of Pennsylvania -- More Details on Our October 11th Story Below

December 3, 1999. Click for more details .


Sequence Complete for Chromosome 22

December 2, 1999. An international team of scientists have now fully sequenced the second-smallest human chromosome. Dr. Francis Collins of NIH said "It's like seeing an ocean liner emerge out of the fog for the first time, rather than a bunch of row boats." The raw data has been published on the web at The Sanger Center in England or alternatively at The University of Oklahoma . See The Wall Street Journal , p. A1 (December 2, 1999) or Paul Jacobs, "Researchers Break Code on Chromosome," The Los Angeles Times , p. A1, 42 (December 2, 1999). Details are published in the current issue of Nature . Click for the Abstract...
Nature Dec. 99

This news gave a sharp boost today to most biotechnology stocks on Wall Street . Of course, regular readers of this website already knew that this news was coming, even if Wall Street considered it a surprise! [c.f. news item below dated October 21, 1999]. Click for more details .


Administration Proposes Strict Guidelines to Fund NIH-Sponsored Research on Human Embryonic Stem Cells

December 2, 1999. The recommended change in rules governing the proposed funding was published in the Federal Register today for a 60-day "public comment period.." Dr. Harold E. Varmus, Director of NIH, said that "We need to pursue this incredibly-promising lead within the current legal limits [set by recent legislation]. Ethical concerns [by Congress] cut both ways -- and we [at NIH] have to be concerned with the health of the [100 million] Americans who would ultimately benefit from this research if it were successful." In direct opposition, a coalition of over 70 members of Congress have already expressed their displeasure at the prospect of such a funding plan. Although analysts do not expect these opponents to have sufficient votes to be able to overturn the new rules by legislation, this is such an emotional issue, they are likely to try. Stay tuned for breaking developments in the next two months. See Chris Adams, "NIH Proposes Guides to Fund Research on Stem Cells from Human Embryos," The Wall Street Journal , p. A1, B2 (December 2, 1999) and Thomas H. Maugh, II, "U.S. to Fund Research on Stem Cells from Human Embroys," The Los Angeles Times, p. A1, 31 (December 2, 1999). See Guidelines for a complete listing of the newly proposed rules.


Human Genome Project Reports Progress

November 24, 1999. Government scientists have identified, sequenced, and published data on one-third of the 3 GBP (Giga [billion] base pairs) comprising the human genome. A draft version of the complete 3 GBP map is due in the Spring. See The Wall Street Journal , p. A1 (November 24, 1999). Click for more details .


Italian Researchers Extend Lifespan of Mice

November 18, 1999. Click for more details from the Associated Press. Click for the Abstract from Nature .


More Exercise Than Thought May Be Needed to Keep Weight Off

November 15, 1999. See The Los Angeles Times , p. A14 (November 16, 1999). Click for more details .


Telomere Defects May Explain Mental Retardation

November 14, 1999. Click for more details .


Genetics of Colon Cancer Uncovered

November 14, 1999. Click for more details .


NIH and Celera May Join Forces

November 14, 1999. Click for more details .


British Medical Journal Predicts the Shape of Medicine in the Next Millennium

November 11, 1999. Click for more details .


U.S. Congress Probes Sales of Fetal Tissues

November 8, 1999. Click for more details .


Proof that Diet and Life Style Decisions Can Extend Life

November 8, 1999. See Terence Monmaney, "Healthy Habits Cut Women's Heart Disease Up to 82%," The Los Angeles Times , p. A1, A22 (November 9, 1999). Click for more details . Editorial Remark: What took us so long to figure this out?


Tissue-Engineering of Heart Valves for Sheep

November 8, 1999. See "Heart Valves Grown in Lab Offer Hope of Replacement, The Los Angeles Times , p. A9 (November 9, 1999). Click for more details .


Monastrol Blocks Cell Division

October 29, 1999. Click for more details .


Amgen Says, "Beta-Secretase Antagonists May Reverse Alzheimer's Disease"

October 22, 1999. Elizabeth Pennisi, "Enzymes Point Way to Potential Alzheimer's Therapies"

Researchers are now isolating the enzymes that make beta-amyloid, a small protein that builds up in the brains of Alzheimer's patients, where it may kill neurons and thereby drive the relentless neurological degeneration of the disease. In Friday's issue of Science, molecular biologists describe a new candidate for beta-secretase, an elusive enzyme that is needed to free one end of beta-amyloid from its larger precursor protein. A second beta-secretase candidate is due to be reported at this week's annual meeting of the Society for Neuroscience in Miami. [Editor's Note: Bristol-Myers plans to bring an amyloid-blocking drug into human tests in several months. This drug will target a second enzyme, gamma- secretase, which is also involved in releasing amyloid.] If amyloid is the destructive agent in Alzheimer's, drugs that target its production could slow or even reverse the disease's course. Refs: Robert Langreth, "A New Finding in Drug Search for Alzheimer's," The Wall Street Journal, A1, B1,4 (October 22, 1999), Paul Jacobs, "Finding on Alzheimer's May Be Key," The Los Angeles Times p. A1, 31 (October 22, 1999), and Steve Sternberg, "A Culprit Identified in Alzheimer's Disease: Frustration Turns to Optimism that a Remedy is Closer," USA Today, p. 8D (October 25,1999).

Robert Vassar, Brian D. Bennett, Safura Babu-Khan, Steve Kahn, Elizabeth A. Mendiaz, Paul Denis, David B. Teplow, Sandra Ross, Patricia Amarante, Richard Loeloff, Yi Luo, Seth Fisher, Janis Fuller, Steven Edenson, Jackson Lile, Mark A. Jarosinski, Anja Leona Biere, Eileen Curran, Teresa Burgess, Jean-Claude Louis, Frank Collins, James Treanor, Gary Rogers, and Martin Citron, "Beta-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE," Science, Vol. 286, No. 5440, pp. 735-741 (October 22, 1999).

ABSTRACT

Cerebral deposition of amyloid peptide (A) is an early and critical feature of Alzheimer's disease. A generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.

Click for more details .


Hypomitochondriosis May Be Secondary to Mutations in Control mtDNA

October 21, 1999. Elizabeth Pennisi, "Do Mitochondrial Mutations Dim the Fire of Life?"

A team of geneticists reports in Friday's issue of Science that some of the first hard evidence that the cellular power plants called mitochondria deteriorate as people age. The team found that mutations in the 16,500-base mitochondrial genome accumulate with time and in a particularly important region: a 1000-base segment that controls the genome's replication. Although some scientists are not convinced that mitochondrial changes bring about aging by themselves, the new results have researchers on aging taking a fresh look at mitochondria.

Yuichi Michikawa, Franca Mazzucchelli, Nereo Bresolin, Guglielmo Scarlato, and Giuseppe Attardi [E-mail: attardig@seqaxp.bio.caltech.edu ], "Aging-Dependent Large Accumulation of Point Mutations in the Human mtDNA Control Region for Replication," Science, Vol. 286, No. 5440, pp.774-779 (October 22, 1999).

ABSTRACT

Progressive damage to mitochondrial DNA (mtDNA) during life is thought to contribute to aging processes. However, this idea has been difficult to reconcile with the small fraction of mtDNA so far found to be altered. Here, examination of mtDNA revealed high copy point mutations at specific positions in the control region for replication of human fibroblast mtDNA from normal old, but not young, individuals. Furthermore, in longitudinal studies, one or more mutations appeared in an individual only at an advanced age. Some mutations appeared in more than one individual. Most strikingly, a T414G transversion was found, in a generally high proportion (up to 50 percent) of mtDNA molecules, in 8 of 14 individuals above 65 years of age (57 percent) but was absent in 13 younger individuals.

Ref. Sylvai Pagan Westphal, "Mutations inCells Are Linked to Aging: CalTech Researchers Say Findings Support Theory that Genetic Changes in Mitochondria Cause Cells to Lose Energy and Essentially 'Run Out of Steam'," The Los Angeles Times , p. A2, 30 (October 22, 1999). Click for more details .


Milestone in Human Genomics: Chromosome 22

October 21, 1999. Click for more details .


Interleukin-10 Given to Rats with Induced Spinal-Cord Injury Heals Better than Steroids Given to Controls

October 17, 1999. Rats recovered quickly from spinal-cord injury when treated with Interleukin-10, a substance pumped out by immune T-cells, than steroids -- the standard anti- inflammatory treatment protocol, as reported by researchers in Miami in the October issue of the Journal of Neurotrauma . Ref. The Wall Street Journal , p. A1 (October 18, 1999). Click for more details .


Mature Primate Brains Regenerate Neurons

October 14, 1999. According to Princeton researchers, the long-held belief that "cerebral growth ends in adulthood" is called further into question. These findings point a path toward treating brain injuries and dementias, such as Alzheimers Disease, Parkinson's Disease, or ALS. Refs. The Wall Street Journal , p. A1 (October 15, 1999) and Elizabeth Gould [E-mail: goulde@princeton.edu ], Alison J. Reeves, Michael S. A. Graziano, and Charles G. Gross [Department of Psychology, Princeton University, Princeton, NJ 08544, USA],"Neurogenesis in the Neocortex of Adult Primates", Science , Vol. 286, No. 5439 [The Genome Issue], pp. 548-552 (October 15, 1999).

ABSTRACT:

In primates, prefrontal, inferior temporal, and posterior parietal cortex are important for cognitive function. It is shown that in adult macaques, new neurons are added to these three neocortical association areas, but not to a primary sensory area (striate cortex). The new neurons appeared to originate in the subventricular zone and to migrate through the white matter to the neocortex, where they extended axons. These new neurons, which are continually added in adulthood, may play a role in the functions of association neocortex.

Click for more details .


Mouse Genome Added to Sequencing Effort

October 14, 1999. Even as the largest academic genome sequencing centers scramble to generate a rough draft of the Human Genome by March 2000, they have taken on another monumental task -- producing a preliminary sequence of the Mouse Genome by 2003, followed by a high-quality version two years later. Ref: Elizabeth Pennisi, Science , Vol 286, No. 5438, p. 210 (October 8, 1999).


Thymic Tissue Implant Helps DiGeorge Syndrome Children

October 14, 1999. DiGeorge Syndrome, a rare disorder occurring in one out of 2,000 births is characterized by a flawed T-cell Immune System, leaving these children defenseless against viral infections. Using tissue from the thymus normally thrown away after heart surgery, researchers at Duke University Medical Center have implanted this tissue in the thighs of five patients when they were infants. As reported in today's New England Journal of Medicine, two of the children, age 1 and 6, are still alive and their immune systems are functioning normally. Ref. The Los Angeles Times , p. B2 (October 14, 1999).


New Statistics on U.S. Longevity from the CDC

October 13, 1999. Click for more details on the demographics.


Nobel Prize in Medicine Goes to Rockefeller Cell Biologist Guenter Blobel

October 11, 1999. The Nobel Prize for Medicine went to Dr. Guenter Blobel of The Rockefeller University in New York today for pioneering research on the inner workings of the cell, particular with regard to mechanisms of protein transport and signaling within the cytoplasm. Blobel's discoveries have shed new light on diseases such as Cystic Fibrosis, and laid the foundation for bioengineered drugs such as insulin and growth hormone. Refs. Thomas H. Maugh, II, "Nobel Prize Awarded for Work on Protein Functions: New York Researcher's Discovery Has Led to Breakthroughs in Understanding Several Genetic Diseases," The Los Angeles Times , p A1,16 (October 12, 1999); "In a Series of Discoveries Beginning in the 1970s, Dr. Blobel Showed How Proteins Locate their Proper Places in Cells and How Mistakes Lead to Diseases," The Wall Street Journal, p. A1 (October 12, 1999); and Lawrence K. Altman, "Rockefeller University Biologist, 63, Wins Nobel Prize for Protein Cell Research," The New York Times , p. A29 (October 12, 1999). Click for more details .


Cystic Fibrosis Therapy with Fatty Acid Leads to Reversal of Symptoms in Mice

October 10, 1999; The ratio of DocosaHexaenoic Acid (DHA) to Arachidonic Acid (AA) is crucial to the mechanism of Cystic Fibrosis, according to Boston researchers reporting at a Conference in Seattle. Treatment with high levels of a purified form of DHA, available without a doctor's prescription in health food stores, could reverse symptoms in 30,000 patients afflicted with this fatal disease. The cost of treatment would be negligible in comparison with what is being spent to support these patients today. Nothing in any of the news articles published so far explains "What took us so long?" Refs. Thomas H. Maugh, II, "Cystic Fibrosis Remedy Shows Promise in Tests on Mice," The Los Angeles Times (p.A1, 32; October 10, 1999); Laura Johannes, "Cystic Fibrosis Is Reversed in Mice by Fatty Acid DHA," The Wall Street Journal (p. A1, B14, October 11, 1999); and CNN Health .

Click for more details and see also the Cystic Fibrosis Foundation website.


Significant Progress in Fetal/Stem Cell Therapy for Human Neurodegenerative Disease

October 6, 1999. Fetal pig cells are becoming a method of choice to treat certain neurodegenerative disorders, such as Parkinson's Disease, Huntington's Disease, Focal Epilepsy, and Stroke, as well as Chronic Intractable Pain, Spinal Cord Injury, Macular Degeneration, and even Acute Liver Failure, according to Diacrin, Inc. of Charlestown, Massachusetts. Their website is www.diacrin.com . Click for a three-page essay obtained from The Boston Globe .


Obesity Proven to be Harmful to Longevity

October 6, 1999; Overweight people die younger, according to a study of more than one million Americans by the American Cancer Society. It found a clear link with heart disease and cancer rates, even among non-smokers who, thought overweight, are otherwise healthy. Ref. The Wall Street Journal (p. A1, October 7, 1999).

An article in The New England Journal of Medicine reports that obesity increases the risk of death at all ages. The study, conducted by the American Cancer Society, followed more than 1 million Americans from 1982 through 1996 and showed conclusively that obesity led to an increased risk of both heart disease and cancer. "The evidence is now compelling and irrefutable," said Dr. JoAnn Manson of Harvard University. "Obesity is ... the second-leading preventible cause of death in the United States after cigarette smoking, so it is a very serious problem." An estimated 55 percent of Americans weigh more than they should. Ref. (p. B2, October 7, 1999); Click for more details .


Stem Cells to the Rescue

Prof. David J. Anderson, Department of Biology at CalTech will give an Earnest C. Watson Lecture on the topic "Stem Cells to the Rescue" on October 20th at 7:30 PM in the Beckman Auditorium.

Stem cells are primitive, undifferentiated cells that can self-propagate and produce differentiated cell types such as nerve, muscle, or blood. The ability to isolate, grow, and manipulate these cells has opened up the prospect of using them to repair or replace diseased or damaged tissues. Transplants of adult blood stem cells are already used to regenerate the immune systems of high-dose chemotherapy patients. But is there an "all-purpose" stem cell, or do we need different kinds of stem cells for different tissues? How realistic are the prospects for using stem cells in so-called regenerative medicine? Come and hear the answers.

For future reference: Mr. Robert Lee Hotz, Senior Science Writer for The Los Angeles Times will host a Biology Forum on February 24, 2000, including David J. Anderson, CalTech; Jeremy Brockes, University College of London ("Stem Cells in Limb Regeneration"); and Barbara Wold of CalTech ("Using Stem Cells to Make Muscle and Organs").


Harvard Researchers Modify Vein Genetically

October 5, 1999; Bypass surgeons may have a new technique to stop veins from reclogging. Click for more details .


Professor Hopes to Clone a Mammoth

October 2, 1999; Flagstaff, AZ. Prof. Larry Agenbroad, a geologist from Northern Arizona University with an international team of scientists, aims to excavate and clone a woolly mammoth from a sample of its DNA.

Click for more details .


Negative hTERT (Anti-Telomerase) Blocks Cancer In Vitro

September 28, 1999. In the latest issue of Nature Medicine Prof. Robert Weinberg of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts has just published that an anti-telomerase compound successfully blocks cancer in tissue culture. See
W C Hahn, S A Stewart, M W Brooks, S G York, E Eaton, A Kurachi, R L Beijersbergen, J H M Knoll, M Meyerson, and R A Weinberg, "Inhibition of Telomerase Limits the Growth of Human Cancer Cells," Vol. 5, No. 10, pp 1164 - 1170, Nature Medicine (October 1999).

Click for more details .


Boy Dies at University of Pennsylvania After Undergoing Gene Therapy

October 11, 1999. The FDA has temporarily suspended human testing of Schering-Plough Corp.'s gene therapy for colorectal and liver cancer. Ref. Robert Langreth, "Gene Therapy Is Dealt a Setback by the FDA," p. B1, The Wall Street Journal (October 11, 1999).

September 29, 1999. Click for more details .


The World's Oldest Person Reaches 119

September 25, 1999. Mrs. Sarah Knauss of Allentown, Pennsylvania reached the age of 119 on Saturday. However, she did not make it to the next millennium after all, having passed away on December 30, 1999 .

Click for more details from The Morning Call.


One Gene Controls Cell Size in Fruit Flies

September 23, 1999. Swiss researchers have now identified a single gene that controls the size of cells in Drosphila.

Jacques Montagne, Mary J. Stewart, Hugo Stocker, Ernst Hafen, Sara C. Kozma, George Thomas, "Drosophila S6 Kinase: A Regulator of Cell Size," Science, Vol. 285, No. 5436, pp. 2126-2129 (September 24, 1999).

Friedrich Miescher Institute; Maulbeerstrasse 66; 4058 Basel, Switzerland, Zoology Institute, University of Zurich; Winterthurerstrasse 190; 8057 Zurich, Switzerland, and Department of Zoology; North Dakota State University; Fargo, ND 58105. E-mail: gthomas@fmi.ch

ABSTRACT:

Cell proliferation requires cell growth; that is, cells only divide after they reach a critical size. However, the mechanisms by which cells grow and maintain their appropriate size have remained elusive. Drosophila deficient in the S6 kinase gene (dS6K) exhibited an extreme delay in development and a severe reduction in body size. These flies had smaller cells rather than fewer cells. The effect was cell-autonomous, displayed throughout larval development, and distinct from that of ribosomal protein mutants (Minutes). Thus, the dS6K gene product regulates cell size in a cell-autonomous manner without impinging on cell number.

Click for more details from Associated Press.


New Gene Therapy for Muscular Dystrophy

September 23, 1999. Boston Children's Hospital researchers reported in today's issue of Nature that bone marrow stem cells can insert a missing protein into muscles in mice with muscular dystrophy. But the risks from this procedure as it now stands (including radiation therapy to destroy the mouse's natural bone marrow cells) are far greater than any potential benefits. Particularly, since the concentration of dystrophin genes introduced into the muscle was not sufficient to be therapeutically beneficial. See Thomas H. Maugh, II, "New Gene Therapy Method for Muscular Dystrophy Uncovered," The Los Angeles Times, p. B2 (September 23, 1999). Click for more details from Associated Press.


National Commission Submits Report on Embryonic Stem Cell Policy

September 14, 1999. As we reported in our stories on May 23rd and July 14th, NBAC (National Bioethics Advisory Commission) has finally submitted its long-awaited report (originally due by the end of August) to President Clinton (who requested it last November). See Marlene Cimons, "Panel Urges Embryo Study Funding, The Los Angeles Times, P. A16 (September 14, 1999). President Clinton replied while attending a summit conference in Aukland, New Zealand, "The issues addressed by the NBAC's recommendations are complex and difficult. The Commissioners are to be commended for the thoroughness with which they engaged in this discussion and the national dialogue that they facilitated, seeking the views and opinions of virtually every segment of our society, including scientists, patients, scholars from most of the major religions in the United States, lawyers, philosophers, ethicists and the public."

As with the earlier drafts, this final report urges an end to the current ban on federal funds for research using human embryos, saying such research would enable scientists to more easily study stem cells -- the earliest cells form which body organs are developed. The legislative implications of this report are still unclear at this moment, and the US Congress will probably wish to have the last word before all is said and done. Check out the NBAC website at their new location www.bioethics.gov . The full report is currently available in manuscript form and can be obtained by calling Ms. Patricia Norris at 301-402-4242. A final version is expected to be posted on the above website in October. However, the 15-page Executive Summary of the Report with its 13 Recommendations is now available here. Click for more details from Associated Press.


Multiperous Birth Statistics Increasing in US

September 14, 1999. The rate of twining, tripleting, etc. has increased markedly in the last 20 years as a result of infertility treatments and a shift in the time of first pregnancy to older ages. Click for more details .


Genetic Engineering Restores Brain Cells in Old Monkeys

September 14, 1999. In a study to appear in today's issue of the Proceedings of the National Academy of Sciences researchers at UCSD describe the use of Nerve Growth Factor (NGF) gene therapy in old monkeys that restores their brains to an almost youthful appearance. In a related story in today's issue of The Wall Street Journal (Page A1), NGF gene therapy may soon be tested in humans with Alzheimer's Disease. Click for more details .


Celera Completes Genome Sequence for Drosophila melanogaster

September 9, 1999. Dr. J. Craig Venter, President and COO of Celera Genomics of Rockville, Maryland, announced this afternoon the completion of the genetic sequence for the fruit fly -- over 1.8 Mbp (million base pairs) or between 12 and 20 thousand genes. The final assembly and analysis of the sequence must now be accomplished. The company expects to complete this task by the end of December 1999. Click for more details at CNN .

Between now and the end of the year, the company expects to turn its attention to sequencing the human genome. It will have completed 70 percent of the sequence by January 1st and 90 percent by early Spring 2000.


September Nature Genetics Reports Dolly's mtDNA is Exclusively Derived from Enucleated Egg

September 5, 1999. Scientists have inspected Dolly's mtDNA and found no trace of the genetic mother's contribution at all. "That's a surprise, and it suggests the egg destroyed the ewe's mtDNA," said Eric Schon of the Columbia University College of Physicians and Surgeons in New York. Co-authors include Dolly cloner Dr. Ian Wilmut of the Roslin Institute in Scotland. They got the same result with the mtDNA of nine other sheep cloned from fetal cells. Schon said this work has major implications for attempts to study diseases caused by flaws in mitochondrial DNA.

Click for more details .


Calf Cloned from Oldest Donor Ever

8:18 AM PST; Friday, September 3, 1999; CBS-TV Morning News; Ms. Hattie Kauffman interviewed Jonathan Hill, Researcher with the College of Veterinary Medicine; Texas A&M University; College Station, Texas. The nucleus extracted from an epithelial cell taken from a 21- year-old Brahman Bull named Chance was injected into an enucleated cow egg and stimulated to divide mitotically for seven days in a proper medium into a 100-cell embryo that was subsequently implanted into a surrogate cow. After consecutive 188 failures, a healthy baby calf named 2nd Chance was born nine months later and is now three weeks old at the time of the interview. As with Dolly the sheep's offspring, they expect to perform chromosomal investigations soon to find out whether Chance's presumably shorter telomere lengths are inherited as well, and, if so, whether this will have any life-shortening implications for the calf.

Footnote: A two-year effort to clone a dog at Texas A&M is progressing well, but there are no results to report at this moment. (See below for more details on the Missyplicity Project.)


First Gene Therapy for Muscular Dystrophy Attempted in Ohio

September 2, 1999. Click for more details .


Scientists at Princeton University Create Smarter Mice

September 1, 1999. As published in Thursday's issue of Nature , Neurobiologist Joseph Z. Tsien and his colleagues have identified a gene called NR2B that biologists believe is a key switch that controls the brain's ability to form synapses. See also, Robert Langreth, "Gene Scientists Create Strain of Smarter Mice," The Wall Street Journal, p. B12 (September 2, 1999) and Thomas H. Maugh, II, "Scientists Create Smarter Mice by Adding Gene," The Los Angeles Times, p. A1, 25 (September 2, 1999). Click for more details .


The University of Wisconsin Reveals the Molecular Basis for Life Extension in Caloric Restriction -- Only 100 Genes of first 6,000 in Mice

August 27, 1999. Using Affymetrix, Inc. of Santa Clara, California GeneChip Technology, researchers at the University of Wisconsin in Madison have reported in Today's issue of Science that, so far, 100 genes appear to be involved in the mechanisms for life-extension in calorically-restricted mice. This may represent 5 to 10 percent of the complete mouse genome. See Cheol-Koo Lee, Roger G. Klopp, Richard Weindruch, Tomas A. Prolla, "Gene Expression Profile of Aging and Its Retardation by Caloric Restriction," Science, Vol. 285, No. 5432, pp.1390-93 (August 27, 1999).

ABSTRACT:


The gene expression profile of the aging process was analyzed in skeletal muscle of mice. Use of high-density oligonucleotide arrays representing 6,347 genes revealed that aging resulted in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes. Most alterations were either completely or partially prevented by caloric restriction, the only intervention known to retard aging in mammals. Transcriptional patterns of calorie-restricted animals suggest that caloric restriction retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage.

See also Michael Waldholz, "New Gene-Scanning Techniques Reveal Biochemical Clues to Aging Process," The Wall Street Journal , Page B6 (August 27, 1999), Terence Monmaney, "Gene Chip Helps Unlock Aging's Secrets," The Los Angeles Times , Page A1, 31 (August 27, 1999), and Nicholas Wade, "New Study Hints at Way to Prevent Aging," The New York Times, p. A16 (August 27, 1999). Mitos, Inc., a new start-up company from Carlsbad, California, is expected to fund future work in Wisconsin, according to Kameron Maxwell, CEO. Click for more details from Associated Press .


Human Genome Sciences of Rockville, Maryland

Dr. William Haseltine of Human Genome Sciences, Inc. (HGS) of Rockville, Maryland was quoted in the latest issue of Science (Vol. 285, p. 999, August 13, 1999) as saying "I am looking forward to an era when older tissues can be transformed into young ones by setting back their genetic clocks; I think we can get to a stage, perhaps in 100 years from now, when we can keep people young and dramatically extend human life."


International Symposium on the Endocrinology of Aging

October 27-30, 1999 in Tempe, Arizona. Barry B. Bercu, M.D., Michael Fossel, M.D., Ph.D., Johannes D. Veldhuis, M.D., Marc R. Blackman, M.D., Caleb E. Finch, Ph.D., Leonard Hayflick, Ph.D., and many others will present papers. Contact: Dr. Leslie Nies, President, Endocrinology of Aging, Serono Symposia USA, Inc.; Norwell, Massachusetts. $500.00 for full registration. FAX your request to: 781-982-9481; 18 credit hours Category I CME.


US Bioethics Commission Reports to the President Soon

July 13-14, 1999. President Clinton's top advisors on bioethics are finalizing their recommendations that Federal law be changed to allow the government to finance research on Embryonic Stem Cells. However, the White House and the Congress are likely to disagree before a compromise is finally reached. Click for more details .


Cloned Cows Reach One Year in Japan

July 5, 1999; Tokyo -- The world's first clones from cells of an adult cow turned one-year- old on Monday, and scientists report that Noto and Kaga are doing fine. They were the second adult-animal clones after Dolly . Click for more details .


Immortal Genes Found by Science

July 4, 1999; The Times of London -- Prof. Michael Rose of the University of California at Irvine explained that his latest generation of fruit flies can live for 130 days, nearly three times the normal span of wild-type controls. Click for more details .


Dr. Richard Seed Joins Forces with a Start-up Called Clonaid, the First Company in the World to Offer Human-Cloning Services

Predictably, French scientist Brigitte Boisselier, Ph.D., Scientific Director of Clonaid, sees no ethical problems associated with cloning humans. She said, "Parents have the right to have a baby who will bear the genetic code of only one of them." Since it is now technically feasible for a mother to give birth to a baby using IVF and the frozen sperm of a now dead father, "imagine the joy of a widow raising a child who grew up to look exactly like her beloved deceased husband." However, prospective parent(s) had better be wealthy, since the starting price-of-admission is advertised to be $200,000 US. Furthermore, the actual laboratory work may not be carried out in The Bahamas, the location of their headquarters, but in a third, off-shore country, to be determined -- one that does not legally prohibit human cloning.

By the way, one of the Founders of Clonaid believes that all human life on Earth was created not by God but by an alien race in a "laboratory" [1]. Also, they claim that cloning will enable mankind to achieve immortality as follows: "The next step [after conventional human cloning is perfected], will be to clone an adult person without having to go through the process of [embryogenesis]. Then, we will transfer memory [plus personality] directly into this [cloned body]. Lastly, we will wake up [after death] in a brand new body, just like after [having had] a good night's sleep!" The founders intend no humor on their website but convey a strong sense of religious conviction. Click for more details .

_____________________
Constance Holden, Ed., "Clone Rangers," p. 2083, Vol. 284, No. 5423, Science (June 25, 1999).


EXTRO 4 Meeting Planned for August

The Fourth Extropy Conference will be devoted to the topic of "Life Extension and Genetic Engineering." The meeting will be held at the University of California at Berkeley on the weekend of August 7-8, 1999. Planned speakers include Cal Harley of Geron, Roy Walford, Greg Stock, and John Campbell of UCLA, Chris Heward of Kronos, Cynthia Kenyon of UCSF, Judith Campisi of Berkeley, and many others. Click for more details
Dynamic DNA about the Conference.


Great Britain Bans Cloning of Human Embryos for Research

June 24, 1999. Unfortunately, the British Government has decided to reject the advice of its own scientists and banned the cloning of human embryos for any kind of medical research, at least for the time being. Click for details .


Stealing Time: The New Science of Anti-Aging

Check out the PBS Television Series now available on three VHS video tapes for $49.98 (TRT = 3 hours). The companion book by Isadore Rosenfeld may be preordered from Amazon.com under our "Resources" section, but the release date for this book has been pushed back by the publisher until July 30th.


Retraction by Geron Corp.

June 15, 1999. The Washington Post reported on June 14th that both Geron Corp. of Menlo Park, California and Advanced Cell Technology of Worcester, Massachusetts are attempting to clone human embryos [as reprinted in The Los Angeles Times on the same day]. However, the very next day The New York Times reported that both companies denied any such thing! [Nicholas Wade, "Company Denies Research Seeks to Clone Human Embyos," p. A21] In particular, Geron stated, "At no stage in the process [of embryonic stem cell research], as it has been described, would a human embryo be created. Although human embryonic stem cells can generate all the tissues of the body [pleuripotent], the tissues are not formed in an orderly fashion unless they are inside a ... hollow sphere known as a trophoblast, [which we are not doing]." Wade goes on to say that "scientists are highly skeptical of ACT's approach [which involves the insertion of a human nucleus into an enucleated bovine egg], since cow-egg mitochondria would not work compatibly with a human nucleus [and any attempt to exchange bovine mitochondria with human mitochondria is fraught with peril]."


Dr. Koop Raises $84.4 million in IPO

June 9, 1999. Wednesday's Wall Street Journal story by Ann Carrns [p. B6] and The Los Angeles Times story by Ashley Dunn [p. C1] both report that Dr. C. Everett Koop, former Surgeon General during the Reagan Administration [1981-89], has raised $84.4 million in an Initial Public Offering (IPO) underwritten by Bear, Stearns & Co. for his website at drkoop.com . Interestingly, the Austin, Texas-based company's NASDAQ Ticker Symbol is "KOOP." Trading opened at $12.25 a share well above the IPO price of $9.00 and closed at $16.44 a share. Media Metrix ranks drkoop.com as the No. 1 Internet health network with more than 280,000 registered users. Dr. Koop's major competitors include, WebMD, Inc., Medscape, Inc., and HealthGate Data Corp..

We wish Dr. Koop well in his new endeavors.


New Drug Helps Bone Marrow Transplants

June 3, 1999. Thursday's New England Journal of Medicine reports that a new drug called CTLA4-Ig made by Repligen Corp. of Needham, Massachusetts may help prevent immune rejection and graft vs. host disease. Click for details.


Mice Cloned from Tail Cells

May 31, 1999. Scientists in Hawaii have cloned a trio of identical mice using ordinary cells rather than DNA extracted from the female reproductive system. Click for details.


Dolly has Shortened Telomeres

May 26, 1999. As some of us in the LA-GRG predicted in 1997, Dolly has now been shown to have shortened telomeres. Her daughter, Bonnie, however, appears fully normal. Click for more details.

The Los Angeles Times now has a special web site devoted to the topic of cloning.


Government Panel Recommends in Favor of Embryo Research

May 24, 1999. Click for more details.


Rat Stem Cells Used to Make New Liver Tissue

May 14, 1999; Washington, D.C. (AP) - In today's issue of Science special bone marrow cells have been shown to convert into basic liver tissue, raising the possibility that one day a patient's own marrow could be used to repair a failing liver. In laboratory rat studies at the University of Pittsburgh Medical Center, researchers found in the bone marrow a stem cell that, under special conditions, can differentiate into functioning liver tissue cells. Dr. Bryon Petersen, lead author of the study said, "This work is the first step toward learning how to repair failing livers by using the body's own stem cells." Click for more details .


C. elegans Enzyme Extends Life

In the May 13th issue of the journal Nature , a cytosolic catalase enzyme appears to be responsible for long life in nematodes (microscopic worms). Click for more details.


Bone Strength Lingers in Late Years

May 9, 1999. Click for more details.


Menlo Park, May 5, 1999: Geron Corp. seeks to acquire Roslin Bio-Med of Edinburgh, a spinoff of the Scottish Institute that cloned Dolly. See details below.


Genzyme Affiliate Clones Three Goats Altered Genetically

Scientists at Genzyme Transgenics Corp. of Framingham, Massachusetts have produced three identical cloned goats, each genetically altered to produce the human blood-clot- dissolving-medication antithrombin in their milk. A transgenic herd increases one's yield of any pharmaceutical. Natural methods would produce goats that were half male -- a dead loss from the point of view of getting milk -- and "of the females produced, only half of them might produce the desired active ingredient," said Dr. Sandra Nusinoff Lehrman, CEO. "Using cloning technology, 100 percent of the animals would be medicine-producing females. This will shave a year off the 18-36 months it would take to create a production herd."

Ref. Laura Johannes, p. B15, The Wall Street Journal (April 27, 1999).
Click for more details .


Health Benefits of Vitamin C Revealed

AP Press Release: Wednesday, April 21, 1999. Click for details.


Functional Pig Arteries Grown from Cells In Vitro at Duke University

Friday, April 16, 1999 Report in Science. Click for details.


Four Male Whales Have Now Been Identified As Being Older Than 100 Years!

This is quite a surprise, considering that whales are not fish but mammals like us. Ref. John C. George, Jeffrey Bada, Judith Zeh, Laura Scott, Stephen E. Brown, Todd O'Hara, Robert Suydam, "Age and Growth Estimates of Bowhead Wales (Balamena mysticetus) via Aspartic Acid Racemization," Canadian Journal of Zoology (in press).

"Analysis of annual rings in whale ear plugs indicates that some species may live beyond 100 years: blue whales, sibbaldus are the largest mammal at more than 108 grams; balanoptera are slightly smaller. Data on the racemization of amino acids in dentine and other non-replicated proteins also indicate very long life spans." Ref. pp. 152-153, Caleb E. Finch, Longevity, Senescence, and the Genome (University of Chicago Press; 1990).


NIH Proposes Rules for Embryonic Stem Cell Research

Bethesda, MD, April 8, 1999 (AP) -- Government advisers drew up proposed rules Thursday to control Federal financing of research on "master cells" obtained from human embryos - a promising area of science that has raised serious ethical questions. A 13-member Committee drafted a proposal that would permit NIH to pay for ES-cell studies only if researchers adhered to strict guidelines that would control how the cells were obtained. These cells, also called pluripotent stem cells, are the building blocks for nearly all of the tissues in the body. They are capable of growing virtually any human tissue. Researchers believe they can learn how to use the cells to make body parts or to correct some disorders, such as Parkinson's Disease or Diabetes. But the cells can only be obtained from human embryos (or from very early fetuses).

Federal law currently bans Government funding of embryo research and severely restricts fetal research. At least 75 members of Congress have said stem cells taken from human embryos are covered by the ban. Some religious organizations also are opposed to the research.

See Davor Solter and John Gearhart, "Putting Stem Cells to Work," Science, Vol. 283, pp. 1468-70 (March 5, 1999). Solter is from The Max Planck Institute of Immunology in Germany and Gearhart is from The Johns Hopkins University School of Medicine (OB/GYN) in Baltimore, Maryland.


Mesenchymal Stem Cell Isolated by Osiris Therapeutics

Researchers at Osiris Therapeutics of Baltimore, Maryland have reported in the April 2nd issue of Science that they have isolated a Mesenchymal Stem Cell that can produce bone, cartilage, or fat. Click for details . Also, see Laura Johannes, "Adult Sem Cells Have Advantage Battling Disease," The Wall Street Journal, Page B1 (April 13, 1999) for further information about Ontogeny, Inc. of Cambridge, MA; Biogen, Inc.; Cytotherapeutics, Inc. of Lincoln, RI; Creative BioMolecules, Inc. of Hopkinton, MA; and Stryker Corp. of Kalamazoo, MI.


New Date for Human Genome Project is Spring 2K!

Small Animated DNA

Announced on the Ides of March, the date to complete the first draft of the human genome project (all 3 Bbps) is now set for Spring 2000, according to Dr. Francis Collins and the publicly-financed consortium sponsoring the work. Sources: "Academic Sequencers Challenge Celera in a Sprint to the Finish" pp. 1822-3, Vol. 283, Science (March 19, 1999); Nicholas Wade, "Who'll Sequence Human Genome First? It's up to Phred" The New York Times Page D2 (March 23, 1999); Nicholas Wade, "One of Two Teams in Genome-Map Race Sets an Earlier Deadline," The New York Times , Page A15 (March 16, 1999); Robert Langreth, "US, Private Gene-Sequencing Race Heats Up," The Wall Street Journal , Page B8 (March 16, 1999). In a related development, Dr. J. Craig Venter, CEO, Celera Corp. of Rockville, Maryland said that he is still on track to complete the sequence by the end of 2001 (Venter-Hunkapiller Initiative). They hope to compete the full sequence of Drosophila in just 3 to 6 months.

If you believe that these new forecasts represent such a significant development that it warrants reducing the GRG Clock (see below) somewhat, please E-mail us at scoles@grg.org.


Both Watson and Crick Interviewed on CBS-TV

CBS News briefly interviewed both Drs. James Watson and Francis Crick (one of the rare occasions in which they are seen together nowadays) during a program on "Significant Accomplishments of this Century" in connection with their joint work on DNA. The narrator, Bill Bradley, addressing Watson said "I know that you are in favor of genetic interventions to eliminate human disease, but what if a potential mother came to you and asked if you could ensure that her child would have blue eyes?" Watson replied with his eyes twinkling, "But what's wrong with blue eyes. I rather like blue eyes." Nevertheless, we believe that the question is serious, and we must ask what the implications of accurate prenatal diagnosis, genetic engineering, and cloning will be for human eugenics and the future of our species?


Canadian Scientists Mass Produce Artificial Chromosomes

Dr. Gyula Hadlaczky of Hungary and Chromos Molecular Systems, Inc. of Vancouver, British Columbia have modified both murine and human chromosomes to serve as vectors for research in genetic engineering. Each chromosome consists of (1) a gene-cassette with several copies of the active gene in order to express the desired protein in quantity; (2) upstream control genes for switching synthesis on or off; (3) a large amount of neutral (silent) satellite DNA for bulk; and (4) those structural components required for stability and replication in mitotically active cells: a centromere, origins of replication, pairs of "p" and "q" arms, and four telomeres at the tips.

Initial experiments demonstrated that these chromosomes were non-toxic post-insertion into the cell nucleus. Now they have been shown to be inherited in cell culture across many replicative generations along side the cells' normal chromosomes. HACs (Human Artificial Chromosomes) potentially have a much larger payload than the interior volume of a viral capsid and, in principle, are easier to manipulate. Cells containing HACs could be programmed to synthesize complex biopharmaceuticals or hormones on cue (e.g., indexed to diurnal rhythm or another type of on/off switch like "fever *and* rapamycin") which couldn't be easily mass produced using today's technology. Please click here to check out their web site.


UCLA Roundtable on Critical Future Milestones in Aging Research (February19-20, 1999)

Click UCLA
Round Table for more details. See Gina Kolata's article in today's New York Times (Tuesday, March 9th; Page D1) "Pushing the Limits of the Human Life Span: After Designing Long-Lived Worms and Flies, Experts Turn to People," which reviews this meeting. Click here to login to their site and do a search for "Gina Kolata Aging" to find it.


Cold Spring Harbor Meeting on Telomeres and Telomerase in New York on March 25-28th (See Meetings for more details)


Genetic Engineering at the University of Penn

Researchers at the University of Pennsylvania Medical School said last Thursday, December 31st, that they have developed a genetic engineering technique for switching genes on or off through the use of a drug called rapamycin that worked in both mice and rhesus monkeys over a period of three to six months. For your interest, we include the Abstract below...

Xuehai Ye, Victor M. Rivera, Philip Zoltick, Franklin Cerasoli Jr., Michael A. Schnell,
Guang-ping Gao, Joseph V. Hughes, Michael Gilman, James M. Wilson,
"Regulated Delivery of Therapeutic Proteins After in Vivo Somatic Cell Gene Transfer,"
Science , Vol. 283, pp. 88-91 (January 1, 1999).

Stable delivery of a therapeutic protein under pharmacologic control was achieved through in vivo somatic gene transfer. This system was based on the expression of two chimeric, human-derived proteins that were reconstituted by rapamycin into a transcription factor complex. A mixture of two adeno-associated virus vectors, one expressing the transcription factor chimeras and one containing erythropoietin (Epo) under the control of a promoter responsive to the transcription factor, was injected into skeletal muscle of immune-competent mice. Administration of rapamycin resulted in 200-fold induction of plasma Epo. Stable engraftment of this humanized system in immune-competent mice was achieved for 6 months with similar results for at least 3 months in a rhesus monkey.

X. Ye, P. Zoltick, M. A. Schnell, G.-p. Gao, J. V. Hughes, J. M. Wilson, Institute for Human Gene Therapy and Departments of Molecular and Cellular Engineering and of Medicine, University of Pennsylvania, and the Wistar Institute, Philadelphia, PA 19104, USA.
V. M. Rivera, F. Cerasoli Jr., M. Gilman, ARIAD Pharmaceuticals, Cambridge, MA 02139, USA


New Conference on the Genetics of Aging

A new conference on Aging: Genetic and Environmental Influences on Life Span was held February 2-7, 1999 at the Sheraton Tamarron Resort in Durango, Colorado. For further details, see Item 6 of "Other Meetings of Interest" under "Meetings."


Click for News Items from 1998.