BREAKING NEWS ITEMS [2005]


Japan's Population Now in Decline

December 23, 2005; Tokyo, JAPAN (WSJ, p. A1) - Japan's Ministry of Health said that "the long-predicted decline in population has started." It reported the number of 2005 deaths will exceed births.


U.S. Life Expectancy Hits 77.6 Years

December 9, 2005; Atlanta, GA (AP) - According to the latest data from the National Center for Health Statistics, U.S. life expectancy has hit another record high -- of 77.6 years, while deaths due to heart disease, cancer, and stroke continue to drop. Still, there is a worrisome turn: Half of Americans in the [55 - 64] cohort - including the oldest of the so called "baby boomers" -- - have high blood pressure, and two in five are considered obese. That means that they are in worse shape in some respects than Americans born a decade earlier were, when they were the same age.

The health of this large group of the near-elderly is of major concern to American taxpayers because they are soon becoming eligible for Medicare and Social Security. "What happens to this group is very important because it's going to affect every other cohort below them," said Amy Bernstein a co-author of the latest government report. The [55 - 64] age group is expected to rise from 29 million Americans in 2004 to 40 million in 2014.


New "Oldest Living Person in the World" Is from Ecuador

Sra. Maria Esther Capovilla, 116

December 8, 2005; Sra. Maria Esther Capovilla, born September 14, 1889, has recently been confirmed by The Guinness Book of World Records to be 116 years old. Click on her photo for more details.


Donor Egg Ethics Scandal in Seoul

Prof. Hwang Woo Suk
November 24, 2005; Prof. Hwang Woo Suk of Seoul National University, the first scientist to clone a dog [See our story of Snuppy dated August 3rd below], has now confessed to lying to the media (with mitigating circumstances having to do with patient privacy and not as a result of suspected coercion of two female lab workers). He has subsequently resigned his South Korean Government post, presumably as a form of atonement for his role. Click on the photo for more details. This saga is further continued in the news item for January 10, 2006.


President Bush Announces $7.1 Billion Avian Flu Emergency Plan

President Bush at NIH
November 1, 2005; Click on the photo for details.


New Human HapMap Published in Nature

October 27, 2005; Dr. Francis Collins, M.D., Ph.D., Director of the National Human Genome Research Institute at NIH, said regarding the recent publication in today's issue of Nature, "We expect to see an outpouring of discovery in the in the next two to three years."

Refs.:

1. AP, "DNA Map Targets Genetic Diseases," CNN (October 26, 2005).
2. Thomas H. Maugh, II, "Disease Hunters Get a New Genetic Map," The Los Angeles Times, pp. A2, 20 (October 27, 2005).
3. "Finding Genes for Common Illnesses," The Wall Street Journal, pp. A1, D1, 5 (October 27, 2005).
4. Nature (October 27, 2005).
5. Jennifer Couzin, "Genomics: New Haplotype Map May Overhaul Gene Hunting," Science, Vol. 310, No. 5748. p. 601 (October 28, 2005).


Panel: The Promise and Pitfalls of Stem-Cell Research

Panelists

Panelists from L. to R.: Dr. Irving Weissman, M.D.; Dr. Ted Peters, Pastor; Prof. Geoffrey Cowan, Moderator; California State Sen. Deborah Ortiz; and Dr. Lawrence S. B. Goldstein, Ph.D.

September 24, 2005; The California Science Center in Los Angeles has launched a new speakers program entitled Science Matters with the aim of exploring challenging current science issues at the forefront of public concern. The first meeting, Introduced by former- California Gov. George Deukmejian, was held today on the topic of Stem-Cell Research . There was an audience of nearly 900 attendees on a Saturday afternoon! Click on the photo for more details about the panel.


California Stem-Cell Training Grants Issued by CIRM

September 9, 2005; California's stem-cell-research agency awarded the first of a planned $3 billion in grants today to help organize programs to train scientists. CIRM announced that a little less than $39 million would be awarded to the following institutions: UCLA, UC Irvine, UC San Francisco, UC San Diego, UC Santa Cruz, UC Berkeley, UC Davis, the La Jolla-based Burnham Institute for Cancer Research, Childrens Hospital Los Angeles; the Scripps Research Institute in La Jolla; the J. Gladstone Institutes, affiliated with UC San Francisco; the Salk Institute for Biological Studies in La Jolla, Stanford University, the California Institute of Technology, and the University of Southern California.

Not everyone was happy with this announcement however. Mr. Jesse Reynolds, a Program Director on Biotechnology Accountability of the Center for Genetics and Society, located in the San Francisco Bay Area, said "CIRM should have delayed all funding decisions until the legal issues were resolved. It's irresponsible for anyone to promise something you're not sure you can deliver."

Refs.:

1. Alex Raksin,"Stem-Cell Agency Awards $39 Million," The Los Angeles Times, p. B1 (September 10, 2005).
2. Constance Holden, "Hall Now Named the First Permanent President of the CIRM," Science, Vol. 309, No. 5742, p. 1801 (September 16, 2005).


MIT Researchers Identify Three Human Embryonic Stem-Cell Chemokines with More to Come

September 8, 2005; What exactly makes a stem cell a stem cell? The question may seem circular, but while we know a great deal of what stem cells can do, we still don't understand the molecular processes that afford them such unique plasticity. Now, researchers at Whitehead Institute for Biomedical Research working with human embryonic stem cells have uncovered the process responsible for the single-most tantalizing characteristic of these cells: their ability to differentiate into any type of cell in the body (~220 varieties along three major tissue types), a trait known as pluripotency.

"This is precisely what makes these stem cells so interesting from a therapeutic perspective," says Whitehead Member Richard Young, senior author on the paper which will be published September 8th in the early on-line edition of the journal Cell. "They are wired so they can become almost any part of the body. We've uncovered a key part of the wiring diagram for these cells and can now see how this is accomplished."

Once an embryo is a few days old, the stem cells start to differentiate into particular tissue types, and pluripotency is forever lost. But if stem cells are extracted, researches can keep them in this pluripotent state indefinitely, preserving them as a kind of cellular blank slate. The therapeutic goal then is to take these blank slates and coax them into, say, liver or brain tissue. But in order to guide them out of pluripotency with efficiency, we need to know what keeps them there to begin with.

Researchers in the Whitehead Laboratories of Young, Rudolf Jaenisch, MIT-computer scientist David Gifford, and the Harvard Lab of Douglas Melton focused on three proteins known to be essential for stem cells. These proteins, Oct4, Sox2, and Nanog, are called transcription factors or chemokines, proteins whose job is to regulate gene expression. (Transcription factors are really the genome's primary movers, overseeing, coordinating, and controlling all gene activity.)

These proteins were known to play essential roles in maintaining stem cell identity - if they are disabled, the stem cell immediately begins to differentiate and is thus no longer a stem cell. "But we did not know how these proteins instructed stem cells to be pluripotent," says Laurie Boyer, first author on the paper and a postdoctoral scientist who divides her time between the Jaenisch and Young Labs.

Using a microarray technology invented in the Young lab, Boyer and her colleagues analyzed the entire genome of a human embryonic stem cell and identified the genes regulated by these three transcription factors. The research team discovered that while these transcription factors activate certain genes essential for cell growth, they also repress a key set of genes needed for an embryo to develop.

This key set of repressed genes produce additional transcription factors that are responsible for activating entire networks of genes necessary for generating many different specialized cells and tissues. Thus, Oct4, Sox2, and Nanog are master regulators, silencing genes that are waiting to create the next generation of cells. When Oct4, Sox2, and Nanog are inactivated as the embryo begins to develop, these networks then come to life, and the stem cell ceases to be a stem cell.

The new work provides the first wiring diagram of human embryonic stem-cell regulatory circuitry. "This gives us a framework to further understand how human development is regulated," says Boyer.

"These findings provide the foundation for learning how to modify the circuitry of embryonic stem cells to repair damaged or diseased cells or to make cells for regenerative medicine," says Young. "They also establish the foundation for solving circuitry for all human cells."
_________________________
Contact: David Cameron
Whitehead Institute for Biomedical Research
Voice: 617-324-0460
E-mail: newsroom@wi.mit.edu

This research was funded by the National Human Genome Research Institute and the National Institutes of Health. Richard Young consults for Agilent Technologies, manufacturers of his microarray platform.

[ Editorial Comments: In our view, this is one of the most important papers of the past two months. One of our GRG members, Mr. Robert Bradbury of Seattle, WA asks, "Obviously, the $64,000 question is "What happens if you turn all or some of these genes back on?" "For example, does one then get de-differentiation?" Of these three factors, it appears that Nanog is more fundamental, but it is clear that we need to understand the complete set of chemokine commands (some of which may actually be located in oocyte cytoplasm and become active for the first time following fertilization by a sperm to demethylate nucleotides and deactylate histones along the DNA, so that permanently switched-off genes can be reactivated.) if we are to form "legal sentences" in the Embryonic Stem-Cell Command Language, commands that turn off, as well as turn on, processes of development, lest we recapitulate the cautionary tale of the Sorcerer's Apprentice , where we have to wait for the "Sorcerer" to come home before the "Apprentice" can stop flooding the house with buckets of water simply because he hastily experimented with his incomplete knowledge without having read and understood the entire "Book of Magic" about how to "reboot" the system. During embryogenesis, timing is everything, and we may have to explore thousands of non-coding microRNA molecules (RNAi) that serve as commands for the exquisite temporal monotonic (irreversible) control of gene activation and silencing. Think: Here's a long row of dominos all perfectly lined up, where all one has to do is flick over the first one to activate the entire chain, all falling over at a certain speed, depending on spacing intervals, until the last one falls; furthermore, at no time do the dominos right themselves once they have fallen over, so you can't get a reverberating circular loop, as one can with equilibrium (reversible) chemical reactions. However, branching paths or forks in the road (or even paths that come together) are certainly legal options in the language, and that feature of the logic is probably used constantly to synthesize symmetric (left/right) phenotypes of all creatures.]

Refs.:

1. Laurie A. Boyer, Tong Ihn Lee, Megan F. Cole, Sarah E. Johnstone, Stuart S. Levine, Jacob P. Zucker, Matthew G. Guenther, Roshan M. Kumar, Heather L. Murray, Richard G. Jenner, David K. Gifford, Douglas A. Melton, Rudolf Jaenisch, and Richard A. Young, "Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells," Cell, Vol 122, No. 6 (September 8, 2005).

Abstract:

The transcription factors OCT4, SOX2, and NANOG have essential roles in early development and are required for the propagation of undifferentiated Embryonic Stem (ES) Cells in culture. To gain insights into transcriptional regulation of human ES cells, we have identified OCT4, SOX2, and NANOG target genes using genome-scale location analysis. We found, surprisingly, that OCT4, SOX2, and NANOG co-occupy a substantial portion of their target genes. These target genes frequently encode transcription factors, many of which are developmentally important homeodomain proteins. Our data also indicate that OCT4, SOX2, and NANOG collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops. These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal.

2. "Researchers Discover Key to Human Embryonic Stem-Cell Potential".

3. Nicholas Wade, Senior Science Writer, "Analyzing the Circuitry of Stem Cells" The New York Times, p. D6 (September 13, 2005).


New Data on the Chimp vs. the Human Genome in Nature

Clint, the Chimp at the Yerkes National Primate Research Center

September 1, 2005; Click for more details.

Refs.:

1. Karen Kaplan, "Man, Chimp Separated by Dab of DNA: A New Comparison of Genetic Blueprints Shows That Just a Handful of Mutations Account for the Vast Differences between the Species," The Los Angeles Times, pp. A1, 12 (September 1, 2005).
2. "The Chimp Genome Has Been Cataloged, Researchers Report in the journal Nature, Opening the Door To Finding Just How Close a Cousin the Ape Is," The Wall Street Journal, p. A1 (September 1, 2005).
3. Bruce Bower, "Chimps to People: Apes Show Contrasts in Genetic Makeup," Science News, Vol. 168, No. 10, p. 147 (September 3, 2005).


Hendrikje van Andel-Schipper, World's Oldest Person: [1890 - 2005]

Mrs. Hendrikje van Andel-Schipper, 115

August 30, 2005; Mrs. Hendrikje van Andel-Schipper died today at age 115 in Hoogeveen, Netherlands. She held the title of the world's oldest person for 15 months. Mr. Johan Beijering, Nursing Home Director said that "she was very clear mentally right up to the end... She said, 'It's been nice, but the man upstairs says it's time to go.'" She once said that the automobile was the greatest technological advance in her lifetime, despite the fact that she never learned to drive and preferred riding her bicycle. She agreed to be autopsied by the University of Groningen in The Netherlands to help scientists learn more about longevity. Mrs. Elizabeth Jones Bolden of Memphis, TN, age 115, is her successor as our World's newest Oldest Person.

Refs.:

1. Myrna Oliver, "Obituary: Hendrikje Van Andel-Schipper, 115; Held the Title of the World's Oldest Person for 15 Months," The Los Angeles Times, p. B11 (August 31, 2005).
2. Tribune News Service, "World's Oldest Person Was 115," The Chicago Tribune, Section 2, p. 8 (August 31, 2005).


Klotho Hormone Extends Male Mouse Life Span 30 Percent


Rare milestone: Mice over-expressing the Klotho gene are pictured here on their third birthday.
Credit: H. Kurosu

August 26, 2005; Click on the photo for more details as well as the Abstract from today's on-line issue of Science.

Refs.:

1. Rob Stein, "Hormone Extends Life of Mice: Research Could Lead to Drugs to Boost Human Longevity," The Washington Post (August 26, 2005).
2. Roland Pease, BBC Science Correspondent, "Scientists Probe Anti-Aging Gene," BBC (August 26, 2005).
3. Elizabeth Cohen, "Klotho Gene," CNN-TV Paula Zahn Now (Friday, August 26, 2005; 11:25 PM PDT; TRT = 3:40 min.).
4. Thomas H. Maugh, II, "Hormone Could Lead to a Fountain of Youth Research," The Los Angeles Times, p. A7 (August 27, 2005).
5. Jennifer Couzin, "Physiology: Boosting Gene Extends Mouse Life Span," Science, Vol. 309, No. 5739, pp. 1310-1 (August 26, 2005).
6. "Klotho for Eternal Youth," Science, Vol. 309, No. 5742, p. 1785 (September 16, 2005).


Embryonic Stem Cells and Adult Fibroblasts Fused at Harvard

Stem Cells Fused

August 21, 2005; This announcement could become an important political breakthrough in the log jam in the US Senate next month. Click on the photo for further details.

Refs.:

1. Kathy Wren, "Reprogramming Adult Stem Cells," AAAS (August 22, 2005).
2. "Researchers Report Potential Stem Cell Breakthrough," CNN (August 22, 2005).
3. "Stem Cell Breakthrough Is Reported by Scientists," The Los Angeles Times (August 22, 2005).
4. Rick Weiss, "Skin Cells 'Reprogrammed' to Stem Cells: Scientists' Work Could Clear Moral Hurdle to Embryonic Research," The Washington Post (August 22, 20005).
5. Randolph E. Schmid, "Harvard Researchers Report Potential Stem-Cell Breakthrough," The Boston Globe (August 22, 2005).
6. Antonio Regalado, "Harvard Team Says It Coaxed Skin Cells to Act Like Stem Cells," The Wall Street Journal, pp. A1, D4 (August 23, 2005).
7. Nicholas Wade, "Harvard Scientists Report a Stem-Cell Advance: Therapeutic Cells One Day, Perhaps, without Discarded Embryos," The New York Times, pp. A1, 14 (August 23, 2005).
8. John Roach, "Stem Cell Breakthrough: No More Need to Destroy Embryos?" National Geographic News (August 23, 2005).
9. Dan Vergano, "Science: Fusion Could Open New Door in Stem-Cell Research: 'Hybrid' Technology in Early Stage," USA Today, p. 7D (August 23, 2005).
10. Ira Faltow, NPR-Radio, Day to Day (Thursday, August 25, 2005; TRT=3.45 min.).
11. Christen Brownlee, "Turning Back Time: Embryonic Stem-Cell Rejuvenates Skin Cell," Science News, Vol. 168, No. 9, p. 131 (August 27, 2005).


TERT Grows Hairy Mice at Stanford University

Smooth Mouse
A normal smooth-haired mouse is on the left. The long-haired, fuzzy mouse, pictured on the right, was the result of experiments that led Stanford researchers to discover a technique to switch on Adult Stem Cells at will.

August 18, 2005; Click on the mice for more details.

Ref.:

Lou Bergeron, "Behind Method for Activating Adult Stem Cells, A Shaggy-Mouse Story," Stanford Report (August 24, 2005).


DNA Sequence of Rice Now Completed

August 10, 2005; New York, NY (Malcolm Ritter, Science Writer, AP[3]) -- An international team of scientists has deciphered the genetic code of rice, an advance that should speed improvements in a crop that feeds more than half the world's population. It's the first crop plant to have its genome sequenced, which means scientists identified virtually all the 389 MBP's [millions of base pairs of DNA]. Certain sequences of these building blocks form genes, like letters spelling words. The advance will help breeders produce new rice varieties with traits such as higher yield, improved nutritional content and better resistance to disease and pests, said one of the project's leaders, W. Richard McCombie of Cold Spring Harbor Laboratory in New York. "I would think this is going to help people find genes and probably enhance the crop in well under 10 years," McCombie said.

The work is reported in Thursday's issue of the journal Nature [1] by the International Rice Genome Sequencing Project [2], which was established in 1998 and includes scientists from ten nations. The effort was led by Japanese researchers.

In the Nature report, scientists estimated rice contains 37,544 genes but said that figure will no doubt be revised with further research. Humans, by contrast, have only [20,000 - 25,000] genes. They also said having the genome sequence in hand will be crucial for breeding and biotechnology advances to increase rice yield, noting that by one estimate the world's rice production must increase by 30 percent over the next 20 years to keep up with demand. Besides Japan and the United States, participating scientists came from Brazil, China, France, India, Korea, Taiwan, Thailand, and the United Kingdom.

Pamela Ronald of the University of California, Davis, who studies disease resistance in rice but didn't participate in the project, said the sequencing of the rice genome lets scientists do new experiments to unlock secrets of the plant. "A lot of people are building on this work," she said. For example, her laboratory used data released earlier from the sequencing project to develop a way to identify rice genes that become active when the plant deals with stresses like a germ attack or drought. That can help scientists track down particular genes for targeting in breeding programs, she said.

Refs.:

1. Click for the Abstract.
2. International Rice Genome Sequencing Project.
3. AP (August 10, 2005).
4. Dennis Normile, "Genomics: Painstaking Approach Pays Off for Rice Sequencing Project," Science, Vol 309, No. 5737, p. 997 (August 12, 2005).
5. "Scientists Have Deciphered Rice's Genetic Code, a Step That Could Improve Production of a Crop That Helps Feed More Than Half the World's Population," The Wall Street Journal, p. A1 (August 11, 2005).
6. Robert Lee Hotz, "Genetic Map Completed, New Rice Age Dawns: Rice Data Promise Clues to Other Crops' Heredity," The Los Angeles Times, pp. A1, 8 (August 11, 2005).
7. Alexei Barrionuevo, "Fields of Bio-Engineered Dreams: Can Gene-Altered Rice Help Rescue the Farm Belt?" The New York Times, pp. C1,2 (August 16, 2005).


First Canine Clone Is an Afghan Hound

Snuppy, First Cloned Puppy on Right
Snuppy, the first cloned dog (R), is an identical twin of Tai, the three-year-old male, brindle Afghan Hound (L), whose ear cells were used to clone the puppy. Snuppy was born last April 24th to a surrogate mother bitch, a yellow Labrador Retriever owned by one of Prof. Hwang's students. Photo: Seoul National University. Note: Subsequent investigations have unequivocally demonstrated that Snuppy is a genuine canine clone, so the Nature reference cited below will not be retracted, as have been the Science articles from 2004 and 2005.

Prof. Hwang with Snuppy
"I had already produced many cloned cows and pigs, but when Snuppy was born, it was different... I was so happy. He was very healthy."
- -- Woo Suk Hwang with Snuppy
Seoul National University

Snuppy with Male Donor (Adult Afghan) and Surrogate Mother (Labrador Retriever)

August 3, 2005; Click on the top photo of Snuppy above for more details from [1-4]. One of the more interesting aspects of this extraordinary accomplishment is that this is really the first time we've gotten a reasonable explanation for why dogs are so hard to clone as compared with other mammals. Genetic Savings & Clone, Inc. has been working on this problem for nearly seven years, first at Texas A&M, later in Sausalito, CA, and most recently in Madison, WI with a team of 50 employees and an accumulated budget of over $19 million. And they were beaten out in this "race" by the Hwang Lab (that spent only US$1 million over two-and-a-half years, using 123 female dogs to create 1,095 embryos). GS&C only got to clone a cat, as a "booby prize," as it were.

Starting with 1,095 embryos (from over 100 donors) and transferring [5 - 12] embryos to each of 123 carefully chosen surrogates, the Huang Lab produced only three pregnancies! One was a still-born [a miscarriage or spontaneous abortion]; another was a full-term puppy, who died of pneumonia after only 22 days; and finally, Snuppy, who was a singleton, full-term [61 days], healthy success story [born by C-section]). This success story took a great deal of perseverance and tenacity (including two years to develop an in vitro cell culture medium hospitable to canine embryos), and the Hwang Lab (a 45-member team) should be rightfully proud.

But to attempt to explain very briefly what's so different about canines: First of all, their eggs do not fully mature in the ovary; they mature "down stream," after ovulation into one of the fallopian tubes, and it's much harder to find these eggs at the right time of maturity. They don't seem to naturally ripen on their own in vitro. Eventually, the team discovered, by brute force and trial-and-error, a signature spike in the hormone Progesterone that signaled the onset of ovulation. Therefore, the whole procedure requires a full surgery with general (not local) anesthesia. To make matters worse, bitches come into season (estrus) only once (or maybe twice) a year, and we don't know how to accelerate the process with pharmacological hormone-regulators, like Lupron, as we can with other mammals, including human females. The same constraint is true for the genetically-unrelated surrogate mothers, in that we cannot prepare the uterine lining with hormones to allow easy synchronized implantation of the embryos.

[ Editorial Remark: Gina Kolata of The New York Times[5] interviewed Ms. Tina Vogel, an Afghan breeder from Norwalk, OH, who ostensibly said, "I am opposed to cloning dogs on the grounds that it would be just like cloning a person. If it was meant to be, God would have done it." A cynical translation of this remark into other words, to better expose the underlying logical fallacy, would be to put it in the same equivalence class as my maiden Aunt Tilly's speculation thirty years ago about why we shouldn't have gone to the moon; in particular, she said "We shouldn't have wasted tax-payer money on going to the moon, given that there are still so many problems right here on Earth. Instead, we should have stayed home and watched television the way God intended us to." Further translation: "If God didn't do it already, it was not meant to be."

On the other hand, we do wear clothes to keep warm next to a cozy fire in the Winter (for which we were capriciously expelled from the Garden of Eden by our Judeo/Christian God and for which Prometheus was subsequently punished by Zeus), we should still be shivering somewhere in a cave trying to figure out how to be obedient little hunter/gatherers, so that we could avoid becoming extinct as a species, also known as not being hungry and starving to death or else being eaten by stealthy predators with exquisitely sharp teeth. So it is especially curious that Ms. Vogel was apparently unaware that God did invent cloning before we did. Cloning commonly takes place in plants and in certain species of insects (ants) and lizards as a standard mode of reproduction. So there, Ms. Vogel of Ohio, take that.]

Refs.: (This story made the front page of The New York Times, The Los Angeles Times, The Wall Street Journal, and USA Today, respectively. Video clips appeared several times on CNN-TV as well. This must mean that this story is important, right?)

1. Byeong Chun Lee [1], Min Kyu Kim [1], Goo Jang [1], Hyun Ju Oh [1], Fibrianto Yuda [1], Hye Jin Kim [1], M. Hossein Shamim [1], Jung Ju Kim [1], Sung Keun Kang [1], Gerald Schatten [2], and Woo Suk Hwang [1],
"Dogs Cloned from Adult Somatic Cells,"
Nature, Vol. 436, No. 7041, p. 641 (August 4, 2005)

Abstract:

Several mammals including sheep, mice, cows, goats, pigs, rabbits, cats{1}, a mule{2}, a horse{3} and a litter of three rats{4} have been cloned by transfer of a nucleus from a somatic cell into an egg cell (oocyte) that has had its nucleus removed. This technology has not so far been successful in dogs because of the difficulty of maturing canine oocytes in vitro. Here we describe the cloning of two Afghan Hounds by nuclear transfer from adult skin cells into oocytes that had matured in vivo. Together with detailed sequence information generated by the canine-genome project{5, 6}, the ability to clone dogs by Somatic-Cell Nuclear Transfer should help to determine genetic and environmental contributions to the diverse biological and behavioral traits associated with the many different canine breeds{7, 8}.

[1.] Department of Theriogenology and Biotechnology
College of Veterinary Medicine
Seoul National University, Gwanak-gu
Seoul 151-742; SOUTH KOREA
[2.] Pittsburgh Development Center
Magee-Womens Research Institute
Departments of Obstetrics-Gynecology-Reproductive Sciences and
Cell Biology-Physiology
University of Pittsburgh School of Medicine
Pittsburgh, PA 15213; USA

E-mail correspondence to Dr. Woo Suk Hwang hwangws@snu.ac.kr.

2. CNN "Scientists Clone Man's Best Friend" (August 3, 2005).
3. Joe Palca NPR-Radio, All Things Considered (Wednesday; August 3, 2005; TRT=3:54 min.).
4. Nicholas Zamiska and Antonio Regalado, "In South Korea, Scientists Clone First Canine - 'Snuppy'," The Wall Street Journal, pp. A1, B1,3 (August 4, 2005).
5. Karen Kaplan, "First Cloned Dog Is a One-in-a-Thousand Success," The Los Angeles Times, pp. A1, 18 (August 4, 2005).
6. Gina Kolata, "Beating Hurdles, Scientists Clone a Dog for a First: Feat for South Koreans: Scuccess with Afghan Pup Is Called 'Dry Run' for Debate on Humans," The New York Times, pp. A1,6 (August 4, 2005).
7. Dan Vergano, "Another Cloning 'First': A Dog," USA Today, p. 1A (August 4, 2005).
8. Wayne Pacelle, "The Problem with Cloning Fido," The Los Angeles Times, p. B13 (August 5, 2005).
Wayne Pacelle is President of The Humane Society of the United States and makes a predictably-obtuse plea that cloning of any animal for any reason is not only frivolous or monumentally unnecessary, but an assault on their dignity. Excuse me, Mr. Pacelle, as I recall, any human who is not a vegetarian regularly EATS animals. Is this not an assault on their dignity?
9. Christen Brownlee, "Double Dog: Researchers Produce First Cloned Canine," Science News, Vol. 168, No. 6, p. 83 (August 6, 2005).
10. Editorial, "Dog Ticks," The Los Angeles Times, p. B18 (August 6, 2005).
My only quibble here is that the Editors took a cheap shot at Dr. John G. Sperling, Chairman of the University of Phoenix, without mentioning him by name but referring to him as a "billionaire who wanted to clone his favorite mutt" [he was uniquely the one who financed the creation of a pet-cloning company facetiously called Genetic Savings & Clone, Inc. (which has had dramatic successes and failures of its own over the last five years), with the explicit aim of cloning his own pet dog Missy, now deceased, but presumably with tissue frozen in liquid Nitrogen in some lab.] The "cheap shot" refers to the fact that all billionaires (indeed all rich people including those who are merely multi-millionaires) turn out to be extraordinarily self- indulgent. While they're alive, they like to endow chairs at universities, build buildings with their name on it, or entire museums, if they can afford it. But they also routinely buy $10 million houses in gated communities in different parts of the country, with horse breeding stables, swimming pools, tennis courts, extra houses on the same property for special guests, yachts, airplanes, dozens of antique cars, fine art, treasure their privacy by using lawyers as intermediaries for all public transactions or donations to the candidates from the political party of their choice, etc., etc. None of these behaviors, following great wealth, are necessary for achieving happiness. Furthermore, after they die, they frequently (inadvertently) create Last-Wills-and-Testaments that cause their living relatives (and/or ex-wives) to fight endlessly over the liquidation of their assets. But this is the capitalist way. We've already proven that Marx and Engels were wrong to think that their ideal form of communism could really work in any government in the world in competition with our beloved capitalism. If we attempt to remind the rich that there are children starving in Africa (say Niger), they would say, "Tell me something I don't know. I prefer to let my money "trickle down" to the poor. I have no moral compulsion to do otherwise, do I? So in conclusion, Sperling's self-indulgent behavior is, in principle, no different from any other rich person in this country. If he wants a pet cloned of his choice and he can afford it, so be it. It's not against the law.
And, finally, we do hail Dr. Woo Suk Hwang as the champion cloner for his tour-de-force with Afghan Hound, Snuppy. It's just that we don't believe the rationale about dogs being used in medical research. This is way too expensive a solution to a non-existent problem. It was really a matter of climbing Mt. Everest because it's there. Now that it's been done, hardly anyone will follow that path. Dog pet cloning can probably not be done profitably at $100,000 a clip given all the problems that we now know about, so that door will also be closed for a long time to come. Cloning a mastodon, using a surrogate female elephant, now that's a challenge! Good luck, Woo.
11. "Doggy Dog," Nature Biotechnology, Vol. 23, No. 9, p. 1093 (September 2005).
12. Alice Park, "Dogged Pursuit: First Sheep, Now a Dog - What Next? How a Lab in South Korea Perfected a Cloning Technique That Is Likely To Transform Medical Research Around the World," Time Magazine, Vol. 166, No. 21, pp. 70-3 (November 21, 2005).


Why Don't Identical Twins Reared Together Over a Lifetime Die on the Very Same Day?

July 11, 2005; Answer: Epigentics or Imprinting, the third leg of the three- legged stool of the aging process (the other two, of coursse, are genetics and life-style), is a stochastic process influenced by comic rays and other vagaries of oxidative metabolism over which, so far, we have little control. These random insults attack our genomes as a function of time in the same way the wind and water erode the Egyptian Pyramids over millennia. The longer twins live, the more their genomes diverge. Here is new evidence from the Proceedings of the National Academy of Sciences...

MEDICAL SCIENCES:
"Epigenetic Differences Arise during the Lifetime of Monozygotic Twins,"
Mario F. Fraga *, Esteban Ballestar *, Maria F. Paz *, Santiago Ropero *, Fernando Setien *, Maria L. Ballestar {dagger}, Damia Heine-Su¤er {ddagger}, Juan C. Cigudosa , Miguel Urioste , Javier Benitez , Manuel Boix-Chornet {dagger}, Abel Sanchez-Aguilera {dagger}, Charlotte Ling ||, Emma Carlsson ||, Pernille Poulsen **, Allan Vaag **, Zarko Stephan {dagger}{dagger}, Tim D. Spector {dagger}{dagger}, Yue-Zhong Wu {ddagger}{ddagger}, Christoph Plass {ddagger}{ddagger} and Manel Esteller *, 
PNAS, Vol. 102, No. 30, pp.10604-9 (July 26, 2005).

*Epigenetics, Cytogenetics, and Genetic Laboratories
Spanish National Cancer Center (CNIO)
Melchor Fernandez Almagro 3
28029 Madrid, SPAIN
{dagger} Department of Behavioral Science
University of Valencia
46010 Valencia, SPAIN
{ddagger} Molecular Genetics Laboratory
Genetics Department
Son Dureta Hospital
07014 Palma de Mallorca; SPAIN
||Department of Clinical Sciences
University Hospital Malmö Lund University
S-205 02 Malmö; SWEDEN
**Steno Diabetes Center
2820 Gentofte; DENMARK
{dagger}{dagger}Twin Research and Genetic Epidemiology Unit
St. Thomas' Hospital
London SE1 7EH; UK and
{ddagger}{ddagger}Human Cancer Genetics Program
Department of Molecular Virology, Immunology, and Medical Genetics
Ohio State University
Columbus, OH 43210; USA

Edited by: Stanley M. Gartler
University of Washington
Seattle, WA and approved

May 23, 2005 (received for review January 17, 2005).

Abstract:


Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically-indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.

Key Words: DNA Methylation | Epigenetics | Histones

This paper was submitted directly (Track II) to the PNAS Office.

Abbreviations: AIMS, Amplification of InterMethylated Sites
ESD, Euclidean Squared Distance
5mC, 5-methylcytosine
MZ, MonoZygotic
RLGS, Restriction Landmark Genomic Scanning

 To whom correspondence should be addressed. E-mail: mesteller@cnio.es.


Marion Higgins: Oldest Living Person in California Turns 112

Mrs. Marion Higgins and Horace, 82 Year Old Son Mrs. Marion Higgins, 111

June 25, 2005; Click on either of the photos above to read the full story on the front page Column One of today's (Saturday's) Los Angeles Times by Andrew H. Malcolm; pp. A1,22,23. [Note: Although the photos above are the same as in the hard-copy edition, these, taken from the LA Times website, are in color, while the hard-copy photos were larger (uncropped) but in black-and-white (to save on printing costs).]


Mrs. Margaret C. Russell [1892 - 2005]

Madge Russell, ~100

June 3, 2005; Madge Russell of Los Angeles passed away on Sunday, May 29th at the age of 112 years, 210 days. Click on her photo for Madge Russell's Obituary from today's Los Angeles Times.


Contrary to Its Recent Traditions, the Vatican Has Chosen to Enter into Italian Politics

May 30, 2005; Rome, ITALY; A Referendum, that requires 50 percent of the voters in Italy to pass due to a legal quirk, will be voted in a couple of weeks on June 12-13th. It would repeal the current law introduced by the center-right government of Prime Minister Silvio Berlusconi last December 2003 to overcome some conspicuous abuses that were occurring in a vacuum with no apparent regulations whatsoever. However, the new law was so onerous that many infertile Italian couples were leaving the country to get treatment abroad in Greece and other European countries where conventional IVF procedures were still being practiced. The new law essentially through out the baby with the bath water. What did it say?

1. Life is defined as beginning at conception. (As a side effect, this would opens up a way to make all abortions, for any purpose, illegal);
2. Ban sperm donor programs;
3. Ban egg donor programs;
4. Ban surrogate motherhood;
5. Prohibit all research on human embryos. (This would make all attempts at therapeutic, as well as reproductive cloning, illegal, such as was accomplished in South Korea last week);
6. With regard to IVF as an infertility treatment, only three (3) eggs shall be harvested and fertilized at any one time, and they must be implanted simultaneously. (This procedure would be considered malpractice if carried out in the USA and such an OB/GYN infertility doc would be denied his/her malpractice insurance if not license to practice medicine by the state board with appropriate jurisdiction); 7. No eggs or fertilized embryos are to be frozen (in liquid Nitrogen). (This would make impossible an Itallian so-called "snowflake baby," of the sort that President George W. Bush was happily seen to be kissing in an contrived photo-op on Tuesday, May 24th at the time the House of Representatives was passing HR 810 to relax his arbitrary constraints on the development of new stem-cell lines back in August 2001 (thawed and "adopted" for implantation into a genetically-unrelated surrogate mother).
The Catholic church by way of the Cardinals, the Bishops, and parish Priests has been requesting its faithful to abstain from voting at all. This would lead to an automatic failure of the proposition, resulting in a retention of the current law and would be consistent with the new Pope's Catholic orthodoxy. The Vatican slogan of the Referendum Campaign was "Life cannot be put to a vote: Don't vote."

We wish to confirm that, when the polls closed on Monday afternoon (14 hours Sunday + 8 hours Monday = 14 hours over a two day period) only 12 million voters of the 48 million eligible voters turned out (26 percent), far short of the 50 percent needed. However, for whatever it's worth, of these 12 million, approximately 3/4ths of them were in favor of the Referendum. So Pope Benedict XVI and his Cardinals/Bishops won by default, and the attempt to ease these onerous fertility laws has failed, at least on this particular round.

Refs.:

1. Ian Fisher and Elisabetta Povoledo, "In Political Step, Pope Joins Fray on Fertility Law," The New York Times, pp. A1, 11 (May 31, 2005).
2. Tracy Wilkinson, "Pope Backs Boycott of Fertility Measure," The Los Angeles Times, p A3 (May 31, 2005).
3. "Pope Benedict XVI Backed Efforts To Curb Fertility Procedures, Such As Egg and Sperm Donation, that a Referendum Proposes to Ease," The Wall Street Journal, p. A1 (May 31, 2005).
4. Gretchen Vogel, "Italians Face Vote on Embryo Research," Science, Vo. 308, No. 5727, p. 1393 (June 3, 2005).
5. Tracy Wilkinson, "With Too Few Voting, Effort to Ease Italian Fertility Law Fails: Analysts Are Split on Whether Low Turnout at the Polls Shows the Strength of the Vatican, Which Sought a Boycott of the Referendum," The Los Angeles Times, p. A5 (June 14, 2005).
6. "Italian Voters Failed To Turn Out in Sufficient Numbers To Validate a Referendum on Loosening Assisted-Fertility Curbs, a Victory for the Vatican," The Wall Street Journal, p. A1 (June 14, 2005).
7. Ian Fisher, "Italian Vote to Ease Fertility Law Fails for Want of Voters," The New York Times, pp. A1, 8 (June 14, 2005).
8. Reuters, "Turnout Low for Italy's Embryo Research Vote: Vatican Sought Boycott of the Measure, Which Seeks an End to Curbs on Fertility Treatments," The Los Angeles Times, p. A8 (June 13, 2005).
9. "Italians Voted in a Referendum on Loosening Restrictions on Assisted Fertility and Embryo Research: Turnout Was Low Amid a Vatican Boycott Call," The Wall Street Journal, p. A1 (June 13, 2005).
10. Gretchen Vogel, "Italian Science: Abstentions Scuttle Drive to Liberalize Italy's Embryo Laws," Science, Vol. 308, No. 5739, p. 1722 (June 17, 2005).
11. "Italians Scuttle Embryo Law," Nature Biotechnology, Vol. 23, No. 7, p. 771 (July 2005).


House Bill HR 810, To Fund Stem-Cell Research by the NIH, Passes by a Margin of 238-194

President Bush holds snowflake baby, Trey Jones
Snow flakes at the White House in May?

May 25, 2005; Today, the US House of Representatives passed a Bill to relax the stringent rules on Federal funding of stem-cell research promulgated by President Bush from his ranch at Crawford, TX back in August of 2001. The President stated in prepared remarks in the East Room of the White House, "This Bill would take us across a critical ethical line by creating new incentives for the on-going destruction of emerging human life. Crossing this line would be a great mistake... and I intend to veto it." However, the House Bill did pass and soon will go before the Senate, where its chances are estimated to be reasonably good, in spite of the President's threats to veto this measure. At this point, the availability of the necessary votes needed to override this veto are unclear. Stay tuned.

After delivering his remarks, the President held baby Trey Jones in his arms in a "photo op," as her Mother Tracy Jones glowed adoringly. Click on the President's photo for an icy, flaming GRG Editorial.


South Koreans Report Histocompatible Therapeutic Cloning in Science Magazine

Cloned Egg from South Korea
Click on the image of the egg for the full text of the 11-page article in pdf format. Then, click on the image of Dr. Hwang for an interview by CNN.

[Editor's Note: Click for a silent, three-minute "avi" animated movie of the cloning process developed by the University of Pittsburgh. Scroll down to the bottom of the page and click on "video" to download the file "HwangVideo.avi" which is about 10 MB. If you click on this file, it should then start playing automatically in whatever your default video player application may be. This is a really informative visual explanation of the process that almost anyone, even a high-school student, could understand.]

[ Editor's Warning: December 15, 2005; The paper associated with the following Abstract has been disputed by several of its co-authors and may be retracted by Science Magazine in the coming weeks.
January 10, 2006; Science now reports that all co-authors have agreed to retract this article, and it will be done. See the News Item for this date.]

May 20, 2005; Published in Science On-line on May 19, 2005; Submitted on March 15, 2005; Accepted on May 12, 2005
"Patient-Specific Embryonic Stem Cells Derived from Human SCNT Blastocysts"
Woo Suk Hwang [1*], Sung Il Roh [2], Byeong Chun Lee [3], Sung Keun Kang [3], Dae Kee Kwon [3], Sue Kim [3], Sun Jong Kim [2], Sun Woo Park [3], Hee Sun Kwon [3], Chang Kyu Lee [4], Jung Bok Lee [2], Jin Mee Kim [2], Curie Ahn [5], Sun Ha Paek [5], Sang Sik Chang [6], Jung Jin Koo [6], Hyun Soo Yoon [7], Jung Hye Hwang [7],Youn Young Hwang [7], Ye Soo Park [7], Sun Kyung Oh [5], Hee Sun Kim [5], Jong Hyuk Park [8], Shin Yong Moon [5], Gerald Schatten [8*]
Science, Vol. 308, No. 5729, pp. 1777-83 (June 17, 2005).
__________________________________________
1. College of Veterinary Medicine
Seoul National University
Seoul 151-742, SOUTH KOREA
School of Agricultural Biotechnology Seoul 151-742, SOUTH KOREA
2. Medical Research Center
MizMedi Hospital
Seoul 135-280, SOUTH KOREA
3. College of Veterinary Medicine
Seoul National University
Seoul 151-742, SOUTH KOREA
4. School of Agricultural Biotechnology
Seoul National University
Seoul 151-742, SOUTH KOREA
5. College of Medicine
Seoul National University
Seoul 110-744, SOUTH KOREA
6. Hanna Women's Clinic
Seoul 137-872, SOUTH KOREA
7. School of Medicine
Hanyang University
Seoul 471-701, SOUTH KOREA
8. Pittsburgh Development Center
Magee-Womens Research Institute
Departments of Obstetrics-Gynecology-Reproductive Sciences and
Cell Biology-Physiology
University of Pittsburgh School of Medicine
Pittsburgh, PA 15213; USA

* To whom correspondence should be addressed
Woo Suk Hwang, E-mail: hwangws@snu.ac.kr
Gerald Schatten, E-mail: gschatten@pdc.magee.edu

Abstract:

Patient-specific, immune-matched human Embryonic Stem Cells (hESC) are anticipated to be of great biomedical importance for studies of disease and development, and to advance clinical deliberations for stem cell transplantation. Eleven hESC lines were established by nuclear transfer (SCNT; NT) of skin cells from patients with disease or injury into donated oocytes. These lines (NT-hESCs), grown on human feeders from the same NT-donor or genetically- unrelated individuals, were established at high rates, regardless of NT-donor sex or age. NT- hESCs were pluripotent, chromosomally normal, and match NT-patient's DNA. Major Histocompatibility Complex (MHC) identity of each NT-hESC with the patient's showed immunological compatibility, important for eventual transplantation. With the generation of these NT-hESCs, evaluations of genetic and epigenetic stability can be made. Additional work remains regarding the development of reliable directed differentiation and the elimination of remaining animal components. Prior to clinical use of these cells, preclinical evidence is required to prove that transplantation of differentiated-NT-hESCs can be safe, effective, and tolerated..

Refs.

1. AP, "Scientists Clone Stem Cells Genetically Matched to Patients"); Washington, D.C. CNN (May 19, 2005).
2. Antonio Regalado, "Seoul Team Creates Custom Stem Cells from Cloned Embryos," The Wall Street Journal pp. A1, B1,3 (May 20, 2005).
3. Bernard Wysocki, Jr. and John D. McKinnon, "Stem-Cell Bill Poses a Quandary for Bush: Veto May Be Risky Strategy, as Influential Republicans Back a Measure Likely to Clear House," The Wall Street Journal, p. A4 (May 20, 2005).
4. Sheryl Gay Stolberg, "As Vote Nears, DeLay Attacks Bill Expanding Stem Cell Research," The New York Tims, p. A15 (May 19, 2005).
5. Gina Kolata, "Koreans Report Ease in Cloning for Stem Cells" The New York Times, pp. A1, 22 (May 20, 2005).
"The South Korean team works 365 days a year, except on leap years, when they work 366 days. They have lab meetings at 6:30 AM every morning except on Sunday, when they have their meeting at 8:00 AM," according to Dr. Gerald Schatten, a co-author from Pittsburgh, PA
[ Editorial Remark: We're all shamefully lazy compared with this lab! Will we ever be able to catch up? --- Steve Coles]
6. Dan Vergano, "Koreans Shake Up Stem-Cell Creation: Stunning Research Streamlines Process," USA Today, p. 1A (May 20, 2005).
7. Karen Kaplan, "Cloned Embryos Created to Match Stem Cells, Patients: The Process Could Lead to the Making of Tissues Suitable for Transplant without a Rejection Risk" The Los Angeles Times, pp. A1, 10 (May 20, 2005).
8. Mary Curtius and Peter Wallsten, "Bush Objects to Stem Cell Bill: The President Threatens To Veto Funding for Embryonic Research That Is Gaining Congressional Support. He Criticizes a South Korean Advance," The Los Angeles Times, pp. A1, 18 (May 21, 2005).
9. Karen Kaplan and Megan Garvey, "With Clones Come Complex Concerns," The Los Angeles Times, p. A19 (May 21, 2005).
10. Michael Hiltzik, "Stem-Cell Agency on Errant Fast Track," The Los Angeles Times, p. C1, 2 (May 16, 2005).
This article is a bunch of diatribe and contained no new information.
11. Megan Garvey, "California's Stem Cell Bid Stuck in Neutral," The Los Angeles Times, pp. A1, 12 (May 23, 2005).
12. BBC World News, "Q&A: The US Debate Over Stem Cells," BBC On-Line (May 20, 2005).
13. CNN (May 24, 2005).
14. Rone Tempest, "Stem Cell Dispute Heats Up: Research Institution's Board Voices Opposition to a Proposal That Would Increase State Oversight [SCA-13]," The Los Angeles Times, pp. B1, 9 (May 24, 2005).
It seems that California State Senator Deborah Ortiz (D - Sacramento) has gone over to the "dark side." I suspect that CalTech President David Baltimore, the member of the Board who composed the unanimous resolution opposing the Ortiz Resolution, will cross swords (light sabers) with her again before these delaying tactics are resolved.
15. NPR FM Radio "Which Way LA" on the Science of Stem Cells (with UC Irvine) 7:00 PM PDT (May 24, 2005). 16. Gretchen Vogel, "Cell Biology: Kroean Team Speeds Up Creation of Cloned Human Stem Cells," Science, Vol. 308, No. 5725, pp. 1096-7 (May 20, 2005).
Instead of using a needle to suck out the donor egg's nucleus (a routine procedure for standard enucleation), they made a small tear in the donor egg's cytoplasmic membrane and gently squeezed out the egg's original chromosomes. They then inserted an entire endothelial (skin) cell through the lesion followed by the application of a small electric shock fusing the two cells together in a common cytoplasm (one cell embedded within the other) which in turn triggers the onset of mitotic division of an egg with a diploid nucleus. This is equivalent to the natural electrical discharge that typically precludes polyspermie post fertilization by a single (but not by more than one) sperm (accompanied by a so-called "calcium cascade"). The genetic fingerprint of the resulting blastocyst was that of the donated skin cell, not that of the original oocyte proving that this was definitely not a case of parthenogenesis, in which an unfertilized egg that begins to divide on its own (immaculate conception?). Furthermore, this cell and all its progeny when grown in culture on human feeder cells including differentiation down particular pathways (neuro, myo, epithelial, etc.) would be histocompatible with that of the skin-cell donor and could be transplanted for therapeutic purposes back into this patient. It would not necessarily be histocompatible with the young woman who donated the eggs, except in the peculiar case where they were identical twins.
We should be quick to point out that the value of this approach to preclude a potential massive rejection of transplanted cells, leading to host death, has not yet been proven. There are some unconventional practitioners who have denied that any fetal tissue transplanted into an adult patient would ever be rejected, either by a mechanism of graft-vs.-host or host-vs.-graft, since this, they say, would be impossible in principle on the grounds that the immune system always accepts fetal tissues of any type, so long as they are not xenografts (from another species)! Moreover, it is no guarantee that histocompatible tissues from a identical twin but of a radically different age (10-day embryonic tissue vs. 20,000-day adult tissue) would still not be rejected. Adult immune systems may seek to reject any fetal or embryonic tissues whatsoever, as a defense against what looks to it like a cancer under development. Lastly, a requirement for immunosuppressive drugs either for a short time (or for a lifetime) is rather unclear at this point. Consider the side effects of this. Finally, to make matters worse, there are multiple submechanisms possible for rejection, some of which involve Killer T-cells that trigger apoptosis (anaphylactic shock) and the thymic gland, which is largely involuted by the onset of adulthood, and B-cell antibody defenses that may smolder in the background, and therefore may slowly kill off the new cells. One needs to know if one or the other or both of these mechanisms is operating before one can confidently say that stem-cell administration as a therapy fits in the same simple category as Red Cross style cross-matching a patient for transfusion (four types: A, B, AB, and O). The organ-donation HLA-type-and-cross-match business is exceedingly complex compared with what the blood-banking industry has become today, independently of the obvious supply and demand issues.
16. Christen Brownlee, "Perfect Match: Embryonic Stem Cells Carry Patients' DNA," Science News, Vol. 167, No. 21, p. 323 (May 21, 2005).
11 patients ranged in age from 2 to 56 years. They started with 185 donor eggs and created 31 embryos carrying DNA from 9 of the 11 patients.
17. "Five Letters to the Editor: A Critical Juncture on Stem Cells," The New York Times (May 24, 2005).
18. Mary Curtius, "GOP Senators Join Stem-Cell Dissension: A Bipartisan Group Backs Expanding Federal Funding of Embryo Research, Further Complicating Bush's Opposition to It," The Los Angeles Times, p. A20 (May 26, 2005).
19. Elizabeth Edwardsen, "From Us to Science Three Embryos: Stem-Cell Research: Living between Donation and Outcome," The Los Angeles Times, p. B13 (May 27, 2005).
20. Ryan J. Foley, "Stem Cells Seen As Tool to Test Cardiac Drugs: A Pioneer in the Field Locates His Start-Up in Wisconsin, Despite California's Program to Finance Research," The Los Angeles Times, p. C2 (May 27, 2005).
21. Gretchen Vogel, "Manhattan Showered with Stem-Cell Gifts," Science, Vol. 308, No. 5726, p. 1237 (May 27, 2005).
22. AP, "Massachusetts Governor Vetoes Stem-Cell Bill," The Los Angeles Times, p. A34 (May 28, 2005).
23. Five Letters to the Editor: The Stem-Cell Controversy," The Los Angeles Times, p. B23 (May 28, 2005).
24. James Brooke, "Without Apology, Leaping Ahead in Cloning," The New York Times, pp. D1, 4 (May 31, 2005).
25. AP, "Cloning Pioneer Plans to Open Stem-Cell Bank," The Wall Street Journal, pp. A1, D3 (June 2, 2005).
Dr. Hwang said in an interview that they "hoped to open a stem-cell bank by the end of the year in Seoul to help speed up the quest to grow replacement tissues to treat disease in a custom fashion."
26. Constance Holden, "Embryonic Stem Cells: Spotlight Shifts to Senate after Historic House Vote," Science, Vol. 308, No. 5727, pp. 1388-9 (June 3, 2005).
27. "Four Letters to the Editor: Stem-Cell Research: Question of Definition," The Los Angeles Times, p. B10 (May 31, 2005).
28. Gretchen Vogel, "News Focus: Ready or Not? Human ES Cells Head Toward the Clinic," Science, Vol. 308, No. 5728, pp. 1534-8 (June 10, 2005).
29. Constance Holden, "Stem-Cell Institute Faces Possible Vote," Science, Vol. 308, No. 5728, pp. 1531 (June 10, 2005).
"California legislators were expected to vote this month on a measure that would tighten conflict-of-interest rules for advisory bodies to the state's new Institute for Regenerative Medicine (CIRM). A Committee of overseers at the nascent Stem-Cell Institute moved last week to consider toughening its policies in the hopes of heading off the legislation, seen as potentially limiting the participation of experts. If passed by two-thirds of both houses, the proposed constitutional amendment will go before California voters in November. Meanwhile, amid pending lawsuits and financial uncertainty, CIRM this week received $5 million from San Francisco sound pioneer Raymond Dolby to help it get started. The Institute is also pursing a $100 million loan."
30. Escolar, et al, "Giving Sem Cells a Chance," New England Journal of Medicine, Vol. 352, No. 20 (2005).
A stem-cell study of newborns with Krabbe's Disease, a rare genetic disorder in which the loss of a lysosomal enzyme in cells resident in the CNS allows lipids to accumulate resulting in rapid death, is now underway.


California Stem-Cell Institute for Regenerative Medicine HQ To Be Located in San Francisco

Golden Gate Bridge

May 7, 2005; Fresno, CA; Click for details.

Refs.:

1. Louis Sahagun, "San Francisco Wins Stem Cell Institute: A $17-million Package of Perks Helps Persuade the Biotech Agency to Establish Its Offices in the Bay Area. San Diego, Sacramento Lose Out," The Los Angeles Times, p. A1, B1,8 (May 7, 2005).
2. Lee Romney, "Stem Cells May Help a City Heal: Still Bleeding from the Dot-Com Crash, San Francisco Stakes Future Health on Institute," The Los Angeles Times, pp. B1, 6 (May 10, 2005).
3. AP, "Funding of Stem Cell Agency Is Hampered: State Officials Fight Two Lawsuits That Are Holding Up $3 Billion in Bond Sales for Research," The Los Angeles Times, p. B1, 6 (May 10, 2005).
4. Andrew Pollack, "California Seeks Interim Financing for Stem-Cell Research," The New York Times, p. C4 (May 10, 2005).
5. Constance Holden, "Stem-Cell Research: California Institute Picks City by the Bay," Science, Vol. 308, No. 5724, p. 934 (May 13, 2005).
6. David P. Hamilton, "Stem-Cell Therapy Succeeds in Trial: Method Aaids Spinal Injuries in Rats, But Technique May Not Work in Humans," The Wall Street Journal, pp. A1, D1,4 (May 11, 2005).
7. Rone Tempest, "Stem-Cell Dispute Heats Up: Research Institution's Board Voices Opposition to a Proposal that Would Increase State Oversight: Agency Says Proposal Could Impede Its Work," The Los Angeles Times, p. B1,9 (May 24, 2005).
8. Dan Morain, "Senator Seeks to Delay Stem-Cell Bonds: A Former Backer of the Research Says She Wants To Ensure that Poor People Would Benefit. Her Measure Would Send the Issue Back to the Voters," The Los Angeles Times, p. B3 (June 7, 2005).
Nobel Prize Laureate, CalTech President, Prof. David Baltimore said, as he prepared to meet with legislators, "I don't know what her [California State Sen. Deborah Ortiz (D - Sacramento)] motivation is, but I know the result is extremely dangerous and could undermine the whole reputation of our state as a leader in stem-cell research." Curiously, Ortiz's Bill is backed by Senate Republicans, rather than fellow Democrats, whose endorsement is largely based on ideological opposition to embryonic stem-cell research rather than a disingenuous interest in the poor citizens of California. Joseph Dunn (D. Santa Ana) said, "In my view there are many Republicans who would like to slow [Prop. 71] down and end it as a first choice. That's fine. I respect their view. But this was established by the voters of California, and we need to respect their wishes." "There may be a Senate vote on Thursday," according to Senate President Pro Tem Don Perata (D. Oakland).
[ Editor's Note: How dare Ortiz cross swords with Baltimore? Ortiz couldn't carry water for Baltimore. She must be smoking something. Explanation? As we said before, Ortiz must have gone over to the "Dark Side."]
9. Michael Hiltzik, "A Voice of Balance in Stem-Cell Program," The Los Angeles Times, pp. C1, 5 (July 4, 2005).
10. David P. Hamilton, "California Stem-Cell Agency Gets Off to Inauspicious Start," The Wall Street Journal, pp. A11, 12 (July 5, 2005).
11. Megan Garvey, "New Stem-Cell Agency Takes Shape" Board Tries To Balance Its Sense of Urgency with the Need To Set Stringent Standards As It Prepares To Spend $3 Billion on Controversial Research," The Los Angeles Times, pp. B1, 6 (January 7, 2005).
12. Antonio Regalado and David P. Hamilton, "Venture Will Sell Licenses to Use Cloning Patents: Geron Corp. Is Putting Its Broad Patent Portfolio on [Animal] Cloning Technology into a New Joint Venture," The Wall Street Journal, pp. A1, D4 (April 6, 2005).
Dr. John Sperling, Ph.D. of the University of Phoenix and Exeter Life Sciences, Inc. will hold 49.9 percent of the joint venture. California-based Genetic Savings & Clone, Inc., also owned by Dr. Sperling, will be the principal beneficiary.
13. "Four Letters to the Editor: A Bone To Pick about Cloning," The Los Angeles Times, p. B17 (April 9, 2005).
14. Antonio Regalado, Kathryn Kranhold, and Bernard Wysocki, Jr., "Big Companies Quietly Pursue Research on Embyronic Stem Cells," The Wall Street Journal, pp. A1, 6 (April 12, 2005).
15. Jessica Garrison, "Hahn's Staffers Grilled Over Failed Bid for Stem-Cell Site," The Los Angeles Times, p. B4 (April 15, 2005).
Councilmen Jack Weiss and Martin Ludlow led an hourlong hearing Thursday into what went wrong, much of which focused on wheterh the Mayor's Office did make an irrevocable lease offer. "I Read English. Where does it say that?" asked Weiss, questioning Deputy Mayor Renata Simril on where in the proposal an irrevocable lease offer is spelled out.
16. Gintautas Dumcius, "Cord-Blood Handling Takes Focus: U.S. Is Urged to Coordinate Oversight of Bank Facilities to Widen Stem-Cell Access," The Wall Street Journal, p. A1, B2 (April 15, 2005).
17. Alan Zarembo, "Network Urged for Cord Blood: Federally Coordinated Collection and Storage of the Stem-Cell Resource Would Increase Its Availability, a Study Recommends," The Los Angeles Times (April 15, 2005).


12-Year Delay in Menopause Is a Possibility

Ovarian Stem Cell

May 4, 2005 ( BBC [1]); The scientists looked at cells found on the surface of ovaries. Early stage human eggs have been developed from stem cells for the first time, US researchers have revealed. Researchers from the University of Tennessee claim the laboratory research could help women with premature menopause or fertility problems. And they suggest in Reproductive Biology and Endocrinology that it could lead to the natural menopause being delayed by up to twelve years. But a leading UK expert cautioned the work was still at a very early stage. "This research is at a very early stage and needs to be confirmed," said Dr. Simon Fishel, Director of Care Fertility. Women have around two million egg-producing follicles in their ovaries when they are born. But by the time they reach puberty the number has fallen to about 400,000. The number of follicles continues to fall until her menopause, at which point she will no longer be able to produce a mature egg capable of being fertilized.

'Easily Harvested'

However the Tennessee researchers found ovarian stem cells could develop into new eggs. They took Ovarian Surface Epithelium (OSE) cells from the outside of the ovaries of five women aged [39 - 52]. They were then grown in a lab for five to six days. Some were exposed to a growth-stimulating oestrogen medium called phenol red. Those cells which were cultured without this medium differentiated into immature small cells of various different types. But those exposed to phenol red completed the first stage of the division needed to become mature human eggs, capable of being fertilized and developing into an embryo. The team said that the OSE cells can be easily harvested from the surface of the ovaries, using a laparoscope, a flexible telescope-like instrument. They said the discovery could help those women with poor fertility or who are set to go through an early menopause, who lack follicles in their ovaries, to have a better chance of conceiving through IVF. They predicted that eventually, frozen OSE cells from younger women could be preserved for later production of fresh eggs, potentially preventing the risks linked to pregnancies in older women which naturally have to use mature eggs. And being able to produce new egg and granulosa stem cells may enable the development of new ovarian follicles. The team claim this could lead to a 10- to 12-year delay of the onset of natural menopause.

Possibilities

Prof. Antonin Bukovsky, who led the research and is Editor-in-chief of Reproductive Biology and Endocrinology, wrote: "Development of numerous mature oocytes (eggs) from adult ovarian stem cells in vitro offers new strategies for the egg preservation, IVF utilization, and treatment of female infertility." They added that fertilized laboratory-grown eggs could also provide embryonic stem cells for other medical applications and basic research. Dr Fishel told BBC News On-line: "Other research has shown it's very difficult to get eggs that exist at an immature stage to become viable. And here, we're going back to an enormous stage even before that." But he added, "If it is confirmed, it is possible that it could help pre- menopausal women and women coming up to their menopause having IVF, who currently need to use egg donors. "This could mean they could have a baby using their own genetic material."

"Oogenesis in Cultures Derived from Adult Human Ovaries,"

Antonin Bukovsky, Marta Svetlikova, and Michael R. Caudle,
Reproductive Biology and Endocrinology, Vol. 3, No. 17, pp. 1477-7827 (May 5, 2005).

Abstract (Provisional)[2]:

Ten years ago, we reported that in adult human females the Ovarian Surface Epithelium (OSE) is a source of germ cells. Recently, we also demonstrated that new primary follicles are formed by assembly of oocytes with nests of primitive granulosa cells in the ovarian cortex. The components of the new primary follicles, primitive granulosa, and germ cells, differentiated sequentially from the OSE, which arises from cytokeratin positive mesenchymal progenitor cells residing in the ovarian tunica albuginea. In the present study, we investigated the possibility that the oocytes and granulosa cells may differentiate in cultures derived from adult human ovaries. Cells were scrapped from the surface of ovaries and cultured for 5 to 6 days, in the presence or absence of estrogenic stimuli [Phenol Red (PhR)]. The OSE cells cultured in the medium without PhR differentiated into small (15 micron) cells of granulosa phenotype, and epithelial, neural, and mesenchymal type cells. In contrast, OSE cells cultured in the presence of PhR differentiated directly into large (180 micron) cells of the oocyte phenotype. Such cells exhibited germinal vesicle breakdown, expulsion of the polar body, and surface expression of zona-pellucida proteins, i.e., characteristics of secondary oocytes. These in vitro studies confirm our in vivo observations that in adult human ovaries, the OSE is a bipotent source of oocytes and granulosa cells. Development of numerous mature oocytes from adult ovarian stem cells in vitro offers new strategies for the egg preservation, IVF utilization, and treatment of female infertility. In addition, other clinical applications aiming to utilize stem cells, and basic stem cell research as well, may employ totipotent embryonic stem cells developing from fertilized oocytes.

Refs.:

1. BBC On-Line.
2. Full Paper. Note: This second reference contains some fabulous photos hidden at the end of the paper.


Champion Horse (Gelding) Cloned

Paris Texas

April 28, 2005; Born on March 13th, Paris Texas, the first cloned foal in the US was announced by Texas A&M University researchers at College Park, TX [1]. (A female horse was previously cloned in Italy.) It took over 400 attempts over a six-month period. Six embryos were created, and one of them was successfully brought to term in a surrogate mare named Greta. The pregnancy took 12 1/2 months. (The normal gestation time for horses is 11 months.) Texas A&M had previously cloned pigs, a Boer goat, an Angus bull, a Brahma bull, and a deer.

This month, a French-Italian collaboration announced the successful birth of a foal cloned from a gelding. Now two months old, the foal was produced by the French genetic engineering company Cryozootech and the Italian reproductive technology lab LTR-CIZ. The lab's team, headed by Cesare Galli, has improved on techniques it used two years ago to produce the first horse clone, a mare. From 200 nuclear transfers using skin cells from Pieraz, a retired thoroughbred Arabian endurance champion, the researchers got 34 embryos and three pregnancies, one of them successful. [2]

Galli has predicted that cloning will revolutionize the horse-racing industry. But at present, the thoroughbred racing community doesn't even permit artificial insemination, much less cloning. Paul Struthers of Britain's Jockey Club says racers have a very restricted gene pool and "there would be very serious implications for the long-term welfare of the thoroughbred were the gene pool to be reduced further" by breeders all going after the progeny of superachievers. But cloning could have a future with horses intended for show jumping, dressage, or endurance racing events with fewer breeding restrictions. "Over 90 percent of dressage stallions are gelded to make them more manageable," [So, that's why they do it. I could never figure out why anybody would ever want to geld a race horse just by common knowledge from reading the sports pages, since, obviously, I'm not an insider in this particular sandbox.] says Nicolas Robin of Cryozootech: "So imagine how many gene lines are lost." But no longer. The company is preserving cells from some 30 prize stallions and plans to market semen from their clones.

Refs.:

1. AP, "Horse Cloned by U.S., French Research Team: Believed To Be a First in North America -- the Foal Named Paris Texas -- Makes His Debut," The Los Angeles Times, p. A23 (April 28, 2005).
2. Constance Holden, "Champion Racer Cloned," Science, Vol 308, No. 5722, p. 628 (April 29, 2005).


National Academy of Sciences Issues Report on Ethical Guidelines for Research on Embryonic Stem Cells

Greek Centaur c. 530 B.C.
Click on the Centaur to test the depth of your knowledge of chimera (over 60 types documented so far).
NAS/IOM Ethical Guidelines
Click on the cover for the Internet version of this Report.

April 26, 2005; The US National Academy of Sciences and the Institute of Medicine have issued a 131-page Report with Ethical Guidelines for Research using Embryonic Stem Cells. These guidelines will almost certainly be adopted by the Institute on Regenerative Medicine in connection with its own grant process for stem-cell research in California. We expect to prepare an editorial describing our differences with these guidelines, if any, by the end of the week. At a first glance almost all the guidelines would seem to be acceptable to our group with the exception of whether scientists can pay human subjects to donate eggs above and beyond their normal medical expenses (hormones, syringes, ultra sound exams, surgery to harvest eggs from the ovaries, anesthesiology) in connection with the institutionally approved donor egg program.

Refs.:

1. Cover Pages for the Report on Ethical Guidelines for Embryonic Stem Cell Research The National Academy of Sciences (April 26, 2005).
2. Antonio Regalado and Gintautas Dumcius, "Stem Cell Labs To Get Guidance on Ethics Issues," The Wall Street Journal, pp. A1, B1,7 (April 26, 2005).
3. "Group Wants Stem-Cell Ethics Guidelines" CNN (April 26, 2005).
4. Nicholas Wade, Senior Science Writer, and Sheryl Gay Stolberg, "Scientists Draft Rules on Ethics for Stem Cells: Academy Cites Lack of Guidelines by U.S.," New York Times, pp. A1, 16 (April 27, 2005).
5. Karen Kaplan and Megan Garvey, "Stem-Cell Research Standards Offered: Voluntary Guidelines Prohibit Profiling from Embryo Production and Set Limits on Use," The Los Angeles Times, pp. A1, 14 (April 27, 2005).
6. Dan Vergano and Elizabeth Weise, "Panel Urges National Standard to Govern Stem-Cell Research: More Than 30 Guidelines Suggested; Some Strictly Prohibit Experiments," USA Today, p. 6D (April 27, 2005).
7. Nicholas Wade, "Chimeras on the Horizon, But Don't Expect Centaurs," New York Times, pp. D1, 8 (May 3, 2005).
8. L. Stephen Coles, The Compleat Tables of Mythological Chimeras and Alien Creatures (First Edition, c. 1956).
9. Sharon Begley, "Science Journal: Now That Chimeras Exist, What If Some Turn Out Too Human?" The Wall Street Journal, p. B1 (May 6, 2005).
10. Constance Holden and Gretchen Vogel, "National Academies: Panel Would Entrust Stem-Cell Research to Local Oversight," Science, Vol. 308, No. 5722, p. 611 (April 29, 2005).
11. Editorial, "Stem-Cell Research Ethics," The Los Angeles Times, p. B10 (May 9, 2005).
"[Robert Klein, II, Chairman of the Institute for Regenerative Medicine Oversight Committee and his colleagues] should also embrace the detailed set of stem-cell research guidelines that the National Academy of Sciences just fast-tracked into print, six months ahead of schedule, in the hopes of influencing Klein's Agency."
12. David Magnus and Mildred K. Cho, "Ethics: Issues in Oocyte Donation for Stem-Cell Research," Science, Vol. 308, No. 5729, pp. 1747-8 (June 17, 2005).


New USDA Food Pyramid

2005 Food Pyramid

April 20, 2005; The new pyramid is actually 12 different pyramids indexed by age, gender, height, weight, and level of physical exercise on a typical day that needs to be customized for each person at the USDA website If you click on the icon above, you can link to a much larger poster-quality version (in pdf format) that can be printed out on a color printer for wall mounting.

Refs.:

1. Sara Schaefer Munoz, "The Food Pyramid Gets Personalized," The Wall Street Journal, pp. D1,4 (April 20, 2005).
2 Thomas H. Maugh, II, "U.S. Goes for an Even Dozen on Dietary Rules: The Revised Guidelines Stress Exercise and Reflect the Nation's Diverse Lifestyles," The Los Angeles Times, p. A21 (April 20, 2005).
3. Jeanniene Stein, "Scaling the New Pyramid: Food Guide Emphasizes Customization, But Will Americans Actually Find It Useful?" The Los Angeles Times, pp. F1,8 (April 25, 2005).
4. A mock USDA Website that ends in ".org" instead of ".gov" (like the true USDA Federal-Government website) been fabricated as a satirical spoof of the official version by a couple of pranksters in Minneapolis. If one looks carefully, it's called the US Department of Agribusiness (sic) website, and when you go to enter the number of minutes per day that you engage in moderate or vigorous physical activity, one of the choices includes 11 minutes per day getting up to change the channel on your TV, instead of using a remote clicker. Do these people have too much time on their hands?
5. Rosie Mestel, "Mock Pyramid Has a Political Point: It Looks Like the USDA Website, But the Advice Pokes Fun at the New Food Guidelines," The Los Angeles Times, p. F3 (May 2, 2005).


California Institute for Regenerative Medicine HQ Short List

April 12, 2005; San Francisco, San Diego, Sacramento, and Emeryville are the four cities remaining on the short list of finalists for the HQ location of the California Stem Cell Institute for Regenerative Medicine that will spend $3 billion in bond appropriations in the next ten years.

Refs.:

1. Megan Garvey, "Stem Cell HQ Won't Be in L.A.," The Los Angeles Times, pp. B1, 11 (April 13, 2005).
2. Jessica Garrison, "Hahn's Staffers Grilled Over Failed Bid for Stem Cell Site," The Los Angles Times, p B4 (April 15, 2005).
Los Angeles Councilmen Jack Weiss and Martin Ludlow led an hour-long hearing into why the City of Los Angeles bid was rejected on a technicality, particular whether Mayor James K. Hahn's deputies made an 'irrevocable lease offer' for the required office space. "I read English. Where does it say that?" asked Weiss rhetorically, questioning Deputy Mayor Renata Simril on where it was spelled out explicitly. However, the answer that 'the Council's Resolution was equivalent to such an offer, a practice that has been accepted on state bids in the past' was unconvincing. Council members loyal to the Mayor suggested that "the hearing was unnecessary and that nothing useful came out of it." "It was shameful," Tim McOsker said, as he left the meeting. However, Weiss castigated the Mayor's staff: "We lost thousands of jobs, millions of dollars in economic development related to savings countless lives, and at the end-of-the-day they said they 'wouldn't have changed a thing.' That's simply astonishing!"
3. Jessica Garrison and Patrick McGreevy, "Los Angeles Elections: Mayoral Contest Leaves City Hall a House Divided," The Los Angeles Times, pp. B1,8 (April 17, 2005).
4. Antonio Regalado and David P. Hamilton, "Venture Will Sell Licenses to Use Cloning Patents," The Wall Street Journal, pp A1, D4 (April 6, 2005).
The Geron Corp. of Menlo Park, CA patent portfolio recently sold to Exeter Life Sciences of Phoenix, AZ (a holding company that includes Dr. John Sperling's Genetic Savings and Clone, Inc. of Sausalito, CA) appears to be related to animal cloning only. Geron, it seems, will retain the rights to its patents for human cloning technology, and in particular the growing of sterile human stem cells in culture without contamination by animal viruses coming from mouse feeder cells or beef broth.
5. Debra Greenfield, Fellow of the Institute on Biotechnology and the Human Future; Malibu, CA "A Bone to Pick about Cloning," The Los Angeles Times, p. B17 (April 9, 2005). Institute on Biotechnology and the Human Future located in Chicago, IL.
[ Editor's Note: This appears to be a stealth website for the White House evangelical position on human cloning. The home page appears, superficially, to be an objective intellectual society with the goal of bringing us opportunities for "public debate of the issues." We suspect that, on the contrary, they have a hidden agenda. But we will need to do a more careful investigation regarding the background of their supporters, before we can say for sure. Does anyone out there know who they are and what their real motives may be?]
6. Antonio Regalado, Kathryn Kranhold, and Bernard Wysocki, Jr., "Big Companies Quietly Pursue Research on Embryonic Stem Cells," The Wall Street Journal, pp. A1, 6 (April 12, 2005).
It appears that "big pharmas" (large, international, publicly-held companies) are exquisitely sensitive to investor demonstrations suggesting that they may be do something immoral (if not illegal) and its subsequent implications for a tank in their stock price. However, the fact that they are hedging their bets with potentially large capital resources, even if only in small ways, tells us that we're on to something important. It would be a shame if the universities were the pioneers (the one's who get all the arrows in their backs) just so that the pharmas can come behind and take all the credit and glory later on, without sharing in the early-adopter risks.
7. Gintautas Dumcius, "Cord-Blood Handling Takes Focus: U.S. Is Urged to Coordinate Oversight of Bank Facilities to Widen Stem-Cell Access," The Wall Street Journal, pp. A1, B2 (April 15, 2005).
8. Alan Zarembo, "Network Urged for Cord Blood," The Los Angeles Times (April 15, 2005).
9. "The Promise of Stem Cells: Solving the Medical Challenges of Our Day," The New York Times, p. A23 (April 19, 2005).
10. Nancy Vogel, "Bill Would Outlaw Sale of Copied Cats: For $32,000, Anyone Can Have a Favorite Feline Cloned [the price has come down from last year's $50,000], But Foes Say It's Unethical. A Proposed Law Would Bar Sale of Such Pets in California." Los Angeles Times, p. B3 (May 2, 2005).
11. Louis Sahagun, "S.F. Leads in Stem-Cell Agency Race: Sacramento and San Diego Are Runners-Up. Final Pitches Will Be Made Friday," The Los Angeles Times, p. B3 (May 3, 2005).
12. AP, "California: San Francisco Backed as Research Site," The New York Times, p. A20 (May 3, 2005).


U.S. Obesity May Block Longevity Gains in the Future

NEJM

March 17, 2005; According to a new report in the New England Journal of Medicine, the linear rise in U.S. average life expectation over the last century need not follow a linear extrapolation nor look like Moore's Law for inevitable progress in chip technology. Instead it could turn down fairly soon as our children eat themselves to death. Let's head this "wake-up call."

"A Potential Decline in Life Expectancy in the United States in the 21st Century,"
S. Jay Olshansky, Ph.D., Douglas J. Passaro, M.D., Ronald C. Hershow, M.D., Jennifer Layden, M.P.H., Bruce A. Carnes, Ph.D., Jacob Brody, M.D., Leonard Hayflick, Ph.D., Robert N. Butler, M.D., David B. Allison, Ph.D., and David S. Ludwig, M.D., Ph.D.,
NEJM , Vol. 352, No. 11, pp. 1138-45 (March 17, 2005).

Source Information:

From the University of Illinois at Chicago, Chicago (S.J.O., D.J.P., R.C.H., J.L., J.B.);
University of Oklahoma Health Sciences Center, Oklahoma City (B.A.C.);
University of California at San Francisco, San Francisco (L.H.);
International Longevity Center, New York (R.N.B.);
University of Alabama, Birmingham (D.B.A.); and
Children's Hospital, Boston (D.S.L.).

Address reprint requests to Dr. Olshansky:
The University of Illinois
1603 West Taylor Street, Room 885
Chicago, IL 60612, or at
E-mail: sjayo@uic.edu.

Abstract:

Forecasts of life expectancy are an important component of public policy that influence age-based entitlement programs such as Social Security and Medicare. Although the Social Security Administration recently raised its estimates of how long Americans are going to live in the 21st century, current trends in obesity in the United States suggest that these estimates may not be accurate. From our analysis of the effect of obesity on longevity, we conclude that the steady rise in life expectancy during the past two centuries may soon come to an end.

Refs.:

1. Rosie Mestel, "Study Finds Childhood Obesity Could Shorten U.S. Lifespans," The Los Angeles Times (March 17, 2005).
2. Rachel Zimmerman, "Obesity May Shrink U.S. Lifespan," The Wall Street Journal, pp. A1, D1, 6 (March 17, 2005).


Paul Glenn Foundation $5 Million Grant to Harvard University on Molecular Basis of Aging

March 11, 2005; Cambridge, MA; Click for details.


UN General Assembly Votes to Ban All Forms of Human Cloning

Man needs good DNA

March 8, 2005; United Nations; New York City ( UN News Centre) The United Nations General Assembly today approved a non-binding declaration calling on all UN Member States to ban all forms of human cloning, including cloning for medical treatment, as "incompatible with human dignity and the protection of human life." By a vote of 84 in Favor, 34 Against, and 37 Abstentions, with 36 Absent, the Assembly acted on the recommendation of its Legal, or Sixth Committee to adopt the text, called The United Nations Declaration on Human Cloning. But some delegates said they opposed banning therapeutic cloning. The Declaration, negotiated by a Working Group last month, also banned "genetic engineering techniques that may be contrary to human dignity."

Refs.:

1. UN News Service, "General Assembly Approves Declaration Banning All Forms of Cloning" (March 9, 2005).
2. Reuters/CNN "U.N. approves Call for Ban on Human Cloning: Vote a Symbolic Victory for Bush" (March 8, 2005).
3. AP, "U.N. Assembly Urges Cloning Ban," The Los Angeles Times, p. A4 (March 9, 2005).
4. Bernard Siegel, who was mentioned in the Reuters story [2] above, is the Executive Director of the Genetics Policy Institute (GPI) of Coral Gables, FL , but it seems that this website has not been updated in a while; nevertheless, here is an
5. interview with Siegel (Spring 2004).


ACT Avoids Mouse Feeder Cells and Bovine Serum that May Contaminate Human Stem Cell Cultures

March 8, 2005; Worcester, MA; ACT has reported in Lancet a system for growing embryonic stem cells that markedly reduces the risk of contamination with pathogens (particularly murine viruses) that could be transmitted to patients and the population-at-large. The extracellular-matrix-coated plates used in ACT's study proved remarkably stable, and could be easily sterilized using a variety of conventional treatment and sterilization processes. This work also represents a step toward completely animal product-free culture system for the derivation and maintenance of new "clean" embryonic stem cell lines.

"Human Embryonic Stem Cells Derived Without Feeder Cells," Irina Klimanskaya, Young Chung, Lorraine Meisner, Julie Johnson, Michael D West, and Robert Lanza, Lancet, Vol. 365, No. 9463, p. 4997 (March 12, 2005).

Abstract:

Background: Human embryonic stem cells are likely to play an important role in the future of regenerative medicine. However, exposure of existing human embryonic stem-cell lines to live animal cells and serum risks contamination with pathogens that could lead to human health risks. We aimed to derive an embryonic stem-cell line without exposure to cells or serum.

Methods: Frozen cleavage-stage embryos were thawed and cultured to the blastocyst stage. Inner cell masses were isolated by immunosurgery and plated onto extracellular-matrix- coated plates that can be easily sterilized. Six established human embryonic stem-cell lines were also maintained with this serum and feeder-free culture system.

Findings: A new stem-cell line was derived from human embryos under completely cell- and serum-free conditions. The cells maintained normal karyotype and markers of pluripotency, including Octamer-Binding Protein 4 (Oct-4), Stage-Specific Embryonic Antigen (SSEA)-3, SSEA-4, Tumor-Rejection Antigen (TRA)-1-60, TRA-1-81, and Alkaline Phosphatase. After more than six months of undifferentiated proliferation, these cells retained the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem-cell lines.

Interpretation: This system eliminates exposure of human embryonic stem cells and their progeny to animal and human feeder layers, and thus the risk of contamination with pathogenic agents capable of transmitting diseases to patients.

Published on-line: March 8, 2005.

Refs.:

1. "Stem Cells Grown Free of Animal Cells," The Los Angeles Times, p. A23 (March 12, 2005).

2. A.C.T. Holding and Advanced Cell Technology Report," Genetic Engineering News, Vol. 25, No. 7, p. 40 (April 1, 2005).

3. See the news item below dated January 24th.


Dean Hall of the USC School of Medicine to Head California Institute for Regenerative Medicine

Prof. Zach W. Hall, Ph.D.

March 2, 2005; Stanford, CA; Prof. Zach W. Hall, Ph.D., Associate Dean at the Keck School of Medicine at USC has been named interim President of the State's new $3-billion stem- cell agency. The 29-member Public Oversight Committee charged with creating the agency voted unanimously to hire Hall, 67.

Formerly, Hall was President and CEO of Envivo Pharmaceuticals, Inc., a start-up, biotechnology company focused on using simple organisms to discover drugs for neurodegenerative disease. From 1997 to 2001, he was Executive Vice Chancellor at the University of California at San Francisco, where he was responsible for planning the new 43-acre UCSF Mission Bay campus, which is part of a 300 acre public/private biomedical research park. He also oversaw research administration at UCSF, including the Office of Industry and Research Development, dealing with technology transfer and industry relations.

Dr. Hall received his undergraduate degree in English from Yale University and a doctoral degree in Biochemistry (Medical Sciences) from Harvard University. Following a post-doctoral Fellowship at Stanford University, he joined the faculty in the Department of Neurobiology at Harvard in 1968, where he remained until moving to the University of California at San Francisco in 1976. From 1994-97, Hall was Director of the National Institute of Neurological Disorders and Stroke (NINDS) at the NIH, where he presided over a major reorganization of intramural and extramural research programs. NINDS is the leading Federal research agency supporting research on the nervous system and its diseases. At the time Hall was Director, the agency had an annual budget of $780 million and employed over 700 scientists and administrators. Before going to NIH, Hall was Chair of the Department of Physiology at UCSF and Head of the Biomedical Sciences Graduate Program.

Hall has been a member of the Medical Advisory Board of the Howard Hughes Medical Institute and of the Dana Alliance for Brain Initiatives. He is Chair of the Scientific Advisory Committees for the National Neurofibromatosis Foundation and of the Searle Scholars Program. He is an elected member of the Institute of Medicine, the American Academy of Arts and Sciences, and an Honorary Member of the American Neurological Society. He has published more than 100 research papers and reviews, is the author and Editor of the widely used textbook An Introduction to Molecular Neurobiology and served as Founding Editor of Neuron, a leading neurobiological journal.

Refs.:

1. Megan Garvey, "Board Names Head of State's Stem-Cell Agency: In a Unanimous Vote, USC Neuroscientist Zach W. Hall Is Selected To Be Interim President," The Los Angeles Times, p. B3 (March 2, 2005).
2. Constance Holden, "Stem Cell Center Gets Head," Science, Vol. 307, No. 5714, p. 1391 (March 4, 2005).
3. Megan Garvey, "Regional Stem-Cell Labs Urged," The Los Angeles Times, p. B1, 8 (March 16, 2005).
4. Megan Garvey, "Limits on Stem-Cell Agency Proposed," The Los Angeles Times, pp. B1, 9 (March 17, 2005).
5. Louis Sahagun and Michael Finnegan, "L.A. Among Cities Seeking To Be Site of Stem-Cell Agency's Headquarters," The Los Angeles Times, p. B9 (March 17, 2005).


Americans Are Living Longer

March 1, 2005; Here are some new statistical highs for US life expectancy at birth: Today's average = 77.6 years (Females = 80.1 years; Males 74.8 years; delta = 5.3 years).

Internationally, in 2002, Japan had the longest life expectancy at 81.9 years, followed by Monaco, 81.2, San Marino and Switzerland, 80.6, Australia, 80.4, Andorra, 80.3, and Iceland, 80.1. Other countries topping the United States included Austria, Belgium, Canada, Finland, France, Germany, Greece, Israel, Italy, Luxembourg, Malta, Netherlands, New Zealand, Norway, Singapore, Spain, and the United Kingdom. What happened to Sweden that used to rank very high in previous years?

Refs.:

1. Jennifer Corbett Dooren, "Americans' Life Expectancy Rose to Record High in 2003," The Wall Street Journal, pp. A1, D8 (March 1, 2005).
2. AP, "Americans are Living Longer," The New York Times, p. A15 (March 1, 2005).
3. Rosie Mestel, "People in U.S. Living Longer," The Los Angeles Times, p. A12 (March 1, 2005).


The Wall Street Journal Interviews Mrs. Marion Higgins, Age 111 and the GRG

Marion Higgins, 111 L. Stephen Coles

February 25, 2005; Seal Beach, CA; Click her "pixel photo" for the font-page WSJ Interview.

Ref.:

Jeffrey Zaslow, "This Exclusive Club Has One Requirement: 110 Birthday Candles: Gerontology Sleuths Search For 'Supercentenarians'; Disproving False Claims," The Wall Street Journal, pp. A1,14 (February 25, 2005).


Feline Genome May Weigh-in by Summer

Cinnamon
Cinnamon is not just any cat. She comes form a carefully bred colony at the University of Missouri, and her lineage can be traced back for decades.

February 15, 2005; Cats exist on nearly every continent, where they occupy the top of the food chain where ever they live. House cats were first domesticated about 6,000 years ago (dogs about 12,000 years ago). But the Cat Genome Project will be done next, after which come the elephant, the orangutan, the shrew, the hedgehog, the guinea pig, the tenrec, the armadillo, and the rabbit (So, where on this list is the bat, the most numerous mammal on our planet?). The work is to be done by Agencourt Bioscience Corp. of Beverly, MA under contract to the NIH National Human Geonome Research Institute for about $5.5 million and be completed as soon as this Summer but maybe not until the end of the year, depending on how things go. Even though the sequencing is largely automated at every stage, there are still a lot of labor-intensive steps, and there will be more than 100 people involved in the project in one way or another.

Ref.:

Nicholas Bakalar, "With Genetic Mapping, Cats' Mysteries Will Be Unraveled," The New York Times, p. D2 (February 15, 2005).


Inventor Says Immortality Is No More Than 20 Years Away

Dr. Ray Kruzweil
Click on Ray's photo to see the full story from Associated Press.

February 15, 2005; Inventor and author, Dr. Ray Kurzweil, predicts human immortality is no more than 20 years away. He wants to make sure that he's going to be here to take advantage of it when it comes. Wouldn't it be a shame if one missed out by dying just before hand?

Refs.:

1. Jay Lindsay, AP, "Inventor Preserves Self to Witness Immortality," CNN (February 15, 2005).
2. Ray Kurzweil and Terry Grossman, Fantastic Voyage: Live Long Enough to Live Forever ( ISBN: 1579549543; $14.97 on Amazon.com; 452 pages; Rodale Press; Emmaus, PA; 2004).
3. Ray Kurzweil, The Singularity Is Near: When Humans Transcend Biology, ( ISBN: 0670033847; 416 pages; List Price = $25.95; Amazon.com Price = $17.65; Viking Adult; Future Publication Date: September 22, 2005).


Orange County, California Supercentenarian Addresses Kiwanis Club

Mrs. Marion Higgins and her Son Horace, 82

February 10, 2005 The Kiwanis Club of Leisure World met at Noon Thursday in Clubhouse 4. Ms. Darlene Dortch, President, and.The Rev. Howard Fox, Program Chairman, introduced Mrs. Marion Higgins, Leisure World's Supercentenarian, who has had an interesting life for more than 111 years. She discussed her third son, Robert, who was born with a physical handicap. Another of her sons, Horace, 82, interviewed her, discussing her early life in New England, pioneering in Idaho, school, family, singing in a Messiah Choral Group, and the war years. At the age of 102, she wrote a book about the interesting incidents in her life entitled, Ripples on a Quite Stream: The Story of the Life and Times of Marion Bigelow Higgins (122 pages; 2003). Marion, who has a keen mind and a great memory, has participated in several memory walks put on by The Alzheimer's Association in Orange County. Thelma Kramar, Marion's writing teacher, took turn with Horace pushing her wheel chair. They have also participated in the yearly walk-a-thons in support of The Golden Age Foundation. Quilt-making was Marion's hobby, but unfortunately, she had to give it up due to failing eyesight.

Ref.:

Barbara LaBoyteaux, "Marion Higgins Will Be Today's Guest Speaker," Seal Beach Leisure World Golden Rain News, p. 3 (February 10, 2005).


Prof. Leroy Hood, M.D., Ph.D., Presents "Systems Biology, Biotechnology, and the Future of Medicine" at CalTech Seminar in Pasadena

Dr. Leroy Hood
Click on Dr. Hood's photo to view 53 of his PowerPoint slides.

February 10, 2005; Dr. Leroy Hood, former Chairman of the Biology Division at CalTech, is recognized as one of the world's leading scientists in molecular biotechnology and genomics. Dr. Hood along with colleagues developed the DNA Gene Sequencer and Synthesizer, and the Protein Sequencer and Synthesizer - which comprise the technological foundation for contemporary molecular biology. He was also one of the first advocates of and is a key player in the Human Genome Project. Dr. Hood has also played a role in founding numerous biotechnology companies, including Amgen, Applied Biosystems, Systemix, Darwin, Rosetta, and MacroGenics. In 2000, Dr. Hood co-founded the Institute for Systems Biology in Seattle, WA to pioneer systems approaches to biology and medicine. He serves as President of the Institute and continues to actively pursue his interest in biology, medicine, technology, development, and computational biology.

One of our GRG Co-Founders, Dr. Robert Nathan, asked Dr. Hood during the Q&A Session that followed his lecture,
"But what about aging, which you hardly mentioned in your talk?
Shouldn't that receive some special focus of attention in the new Systems Biology?"

Hood replied: "We've made some spectacular progress in aging research using model organisms like C. elegans and Drosphila. Next, we have to apply this knowledge to humans. I predict that, by applying the principles of Systems Biology, in ten years we can expect to see a 10- to 20-year increase in average life expectancy for the general population. In ten years, with the cost of DNA sequencing coming down by another 100,000-fold due to advances in technology, every single person in this room, who wishes, will have their unique DNA sequence routinely placed in a computer data base that will lead to custom therapeutic interventions that are tailored to their individual, idiosyncratic genes."


Proposed Law by Van Nuys Assemblyman Would Ban All Cloned Pets in California

Cloned Cats
Click on the cats to link to the Genetic Savings & Clone website.

February 10, 2005; The cloning of two cats for sale by Genetic Savings & Clone of Sausalito, CA has prompted an outcry by animal-rights activists. Assemblyman Lloyd Levine, (D -- Van Nuys, CA) has taken up their cause with a bill that would outlaw cloned dogs, cats, birds, and fish in California, including those fish that have been genetically modified. Separately, Genetic Savings & Clone has announced that they have opened a new lab near Madison, WI with the aim of cloning a dog within 12 months, the one long-term goal that has so far eluded them. [1]

California Considers Ban on Pet Cloning: Genetic Savings & Clone, Inc. Charges $50,000 to Clone a Cat

February 10, 2005; San Francisco, CA ( Reuters) -- A California lawmaker said on Wednesday he would introduce a bill this week to ban sales of cloned pets, a move that could end a California company's plans to replicate beloved domestic animals. "A ban is necessary because the technology is unregulated and animal shelters are filled to capacity with potential pets," Assembly Member Lloyd Levine said in an interview. "If you were to use animals for experiments, for agriculture, for all sorts of things, there are all sorts of regulations ... Who knows what's going to happen if these things get released into the wild?," Levine said.

The proposal follows the first pet cloning last year from Sausalito, CA-based Genetic Savings & Clone, Inc., which charges $50,000 to clone a cat. The company in December revealed it had cloned a cat -- named Little Nicky after its progenitor Nicky -- for a client in Texas. [Scroll down to see last year's story dated October 10, 2004]. "Why do we need to pay $50,000 for a cat?" Levine said. "We're not banning legitimate scientific research. We're simply banning the exploitation of vulnerable people." The privately-held company says it has four other cat clones in various stages of production and is developing a dog-cloning service.

"The proposed ban is based on myths and science fiction and would neither improve animal welfare nor serve the interests of consumers," said Ben Carlson, a spokesman for Genetic Savings & Clone. "I have the impression Levine is pandering to animal-rights advocates." [2]

[ Editorial Remark: "GloFish" are actually Zebra Fish with an additional gene inserted to make them glow green developed by Yorktown Technologies, L.P. Years ago, I worked for a veterinarian for one year in his clinic, and I have a broad range of experience with cats and dogs, as well as their owners. I bred Afghan Hounds at one time and have owned a cat as well. There are plenty of laws on the books to prevent the abuse of pets, and we don't need any new ones. The holier-than-thou animal-rights activists who are writing these anti-pet-cloning laws are really "slippery-slope anti-technologists" in disguise, and we need to expose their true agenda for what it is. The ASPCA has not yet made a decision on this matter but is expected to do so shortly. Even if you don't live in California, if you are a pet owner, why don't you write to them and take a stand? Also, while you're at it, by way of a show of support and as a protest against the "animal-rights activists," and providing that you don't live in California, why don't you purchase some GloFish yourself by clicking on this GloFish.com link. This link will also lead you to copies of all the scientific analysis by the US FDA and the State of California Department of Fish and Game approving their ownership by fish fanciers and acknowledging their lack of any hypothetical threat to the environment, which was a grave concern by environmentalists a couple of years ago when they were first introduced for sale. - - Steve Coles, News-Section Editor GRG.ORG]

Refs.:

1. Antonio Regalado, "Pet Cloning Sparks Backlash," The Wall Street Journal, pp. A1, D1, 6 (February 10, 2005).
Thank you Antonio for scooping the LA Times on what could have been merely a local California issue.
2. CNN (February 10, 2005).
3. Wade Roush, "Genetic Savings and Clone: No Pet Project: Can It Cash in on Cloned Cats?" MIT Technology Review [keyword = "clone"], Vol. 102, No. 3, pp. 31-2 (March 2005).
4. AP, "Horse Cloned by U.S., French Research Team: Believed To Be a First in North America -- the Foal Named Paris Texas -- Makes His Debut," The Los Angeles Times, p. A23 (April 28, 2005).
Born on March 13th, Paris Texas, the first cloned foal in the US was announced by Texas A&M University researchers at College Park, TX (A horse was cloned previously in Italy.) It took over 400 attempts during a six-month period. Six embryos were created, and one of them was successfully brought to term in a surrogate mare named Greta. The pregnancy took 12 1/2 months. (The normal gestation time for horses is 11 months.) Texas A&M had previously cloned pigs, a Boer goat, an Angus bull, a Brahma bull, and a deer. 5. "Sacramento: Lawmakers Reject Bill Banning Cloning of Pets," The Los Angeles Times, p. B4 (May 4, 2005).
We are pleased to report that California lawmakers on Tuesday rejected a Bill that would have banned the sale of cloned or genetically modified pets in California. ... Members of the Assembly Business and Professions Committee rejected [Lloyd Levine's] Bill, AB1428 on a 2-4 vote. Some lawmakers called the Bill premature or said that "such regulation is best left to the US Congress.


University of Pennsylvania Settles with Gelsinger Family

February 10, 2005; More than one million dollars was spent by the University of Pennsylvania to settle fraud allegations related to the death of a teenager during a gene therapy experiment. Jesse Gelsinger, 18, of Tucson, AZ died in late 1999 after he suffered catastrophic anaphylactic shock following an unexpected massive immune rejection of the viral capsid of the vector used to transport a gene that would have corrected a mutated version that he inherited causing a liver-enzyme failure that blocked his body's ability to process Nitrogen normally ( Ornithine Transcarbamylase Deficiency)[3]. (Other patients had not exhibited this sort of rejection of the vector.) After his death, Gelsinger's family said the teen had not truly given informed consent and was, in fact, misled about the experiment's potential risks. The Children's National Medical Center and the University have maintained that this death was completely unforeseen and that he was properly enrolled in the study based on the best scientific information available at the time. Neither institution was required to acknowledge any wrongdoing as part of the settlement. The family had already settled a "wrongful-death" lawsuit against the teen's doctors and the University of Pennsylvania in the year 2000, the terms of which were never disclosed as part of the settlement. More about the legal decision can be found in [4, 5].

[ Editorial Remark: This tragic story of Jesse Gelsinger's death should have had a different ending. We should be remembering him proudly, as a pioneer, whose example helped to teach us some new science. Instead, we only remember his greedy parents, who helped to crush progress in this nascent field of genetic engineering on the grounds that the attending physicians, working at the cutting edge of medicine, did not do their job of properly enrolling this young boy into their protocol, something that we can't tell from what has been disclosed publicly. Didn't they carefully explain all the attendant risks, including the possible death of the subject? The paperwork was duely signed by him in advance (or they wouldn't have done it), and he was of age to sign on his own behalf, wasn't he? Dr. James Wilson said the fatal reaction was a surprise, and he also denied any financial conflict-of-interest with regard to this experiment. But investigations by The Washington Post and by the Food and Drug Administration during the following months revealed multiple scientific and ethical lapses that undermined those assertions. Among them were unreported deaths of monkeys given similar treatments; the failure to inform the FDA, as required, when patients became so ill from the treatment that, according to FDA rules, the study should have been suspended; and Wilson's failure to disclose that a company in which he had a strong financial interest stood to profit if the treatment was successful. It also came to light that, under the study guidelines, Gelsinger was too sick to get the treatment, but he was treated anyway. Therefore, there were a lot of mitigating circumstances for all parties. But, that's never enough when things don't go your way, and you have good lawyers. Hopefully, now the University can go back to its normal work, after being properly reprimanded.]

Refs.:

1. Peter Loftus, "Hospital, Upenn Reach Settlements Over Gene Therapy," The Wall Street Journal, p. B2 (February 10, 2005).
2. AP, "$1 Million to Be Paid Over Teen's Death in Gene Therapy Study," The Los Angeles Times, p. A23 (February 10, 2005).
3. Alice E. Fugate, "Is Gene Therapy Safe?" (Fugate Publications).
4. The Washington Post (February 9, 2005).
5. Red Nova (February 9, 2005).


Dolly's Creator Gets Human Therapeutic Cloning License for UK

Prof. Ian Wilmut, Ph.D.
February 8, 2005; London and Edinburgh, UK ( AP) -- Prof. Ian Wilmut, the creator of Dolly the sheep has been granted a license to clone human embryos for medical research, authorities in London have announced. Dr. Wilmut of the Roslin Institute in Edinburgh and a team from King's College, London plan to clone embryos to study Motor Neuron Disease. Consent for the cloning to treat the incurable muscle-wasting condition was granted by Britain's Human Fertilization and Embryology Authority (HFEA).

[ Editorial Remark: We are delighted to see that one of the world's recognized figures in the field is getting to do work that will teach us a lot about the presumed promise of this field, even though, in our view, the particular strategy proposed by Drs. Wilmut and Christopher Shaw of the Institute of Psychiatry at King's College London is unlikely to yield a cure for Lou Gehrig's Disease (Amyotrophic Lateral Sclerosis). We suspect that neurons differentiated from Embryonic Stem Cells derived from patients having the disease are more likely to appear perfectly normal compared with controls than to exhibit a pathonomonic marker for the disease. To our knowledge, there is no significant inherited (genetic) component to this debilitating, fatal disease. Nevertheless, we would expect to see many valuable details published about chemokines for differentiating stem cells in vitro that would be extraordinarily important for all future work in this field, and they are clearly laying the ground work in the context of officially-sanctioned Government approval.

One the other hand, there are people out there who are completely misinformed about the medical significance of this work on some sort of moral grounds. One egregious example, is the London-based ProLife Alliance, which has pronounced that "All human cloning is intrinsically wrong and should be outlawed. The creation of cloned human embryos destined for experimentation and subsequent destruction is particularly abhorrent." Well, ladies and gentlemen of the ProLife Alliance, I find your paradoxical view of life to be self-contradictory. It seems to me that your Alliance is distinctly "AntiLife" rather than "ProLife," else how are we to cure diseases in the future? (which you may or may not be in favor of, I'm not sure). Your Manifesto on the Internet [4] (a panopoly of loose thinking) doesn't make this clear. However, I suspect that the real issue is not that you are in favor of disease, but that you subscribe to the discredited notion that human "personhood" begins at conception (and that any deliberate destruction of a fertilized egg constitutes murder, which is a fallacy about which you need to be re-educated, and I challenge you to debate this issue at any time and place of your choosing. Stephen Coles, News Section Editor, GRG.ORG.]

Refs.:

1. CNN (February 8, 2005).
2. AP, "Scientist to Clone Embryos for Stem Cells," The Los Angeles Times, p. A9 (February 9, 2005).
3. "The Scientist Who Created Dolly the Sheep, the First Cloned Mammal, was Granted a License in Britain to Clone Human Embryos for Research on Motor Neuron Disease," The Wall Street Journal, p. A1 (February 9, 2005).
4. ProLife Alliance Manifesto.


The Latest US Toxicology Report Adds 17 Carcinogens That May Cause Cancer

February 1, 2005; Papillomaviruses and heterocyclic-amine compounds, created during the grilling of meat or eggs at high temperatures, have now been added to the official Government List of Carcinogens that can be found in The National Toxicology Program 11th Report.

Refs.:

1. Jennifer Corbett Dooren, "U.S. Expands List of Cancer Causes, Adding 17 Agents," The Wall Street Journal, pp. A1, D1, 4 (February 1, 2005).
2. AP, "Cancer Agent List Expanded," The Los Angeles Times, p. A11 (February 1, 2005).


Burned Out Mitochondria Linked to Aging

Rats

January 27, 2005; Rats bred for low aerobic capacity really seem to suffer from poorly-functioning mitochondria. These rats will die sooner than controls.

Refs.:

1. Jean Marx, "Low-Power Mitochondria May Raise Risk of Cardiovascular Problems," Science, Vol. 307, No. 5708, pp. 334-5 (January 21, 2005).

"Try as we might, only an elite few will ever win the Tour de France or even the local 10-K foot race. People simply vary widely in their ability to perform aerobic exercise. New work with rats now suggests that individuals with a low tolerance for aerobic exercise may have a lot more to worry about than just their inability to run fast and long. The same underlying defect that reduces aerobic capacity may also predispose a person to a witch's brew of medical problems that could increase the possibility of heart attacks and strokes.

Ulrik Wislff of the Norwegian University of Science and Technology in Trondheim, Sonia Najjar of the Medical College of Ohio in Toledo, and Steven Britton of the University of Michigan, Ann Arbor, reports that rats that have been selectively bred to have reduced capacity for aerobic exercise show obesity, resistance to the hormone insulin (a sign of Type-II Diabetes), and high blood pressure, all symptoms of the so-called metabolic syndrome that raises the risk of cardiovascular disease. The researchers also provide evidence that impaired function of the mitochondria, small structures that produce most of a cell's energy, underlies the metabolic problems of the rats with low aerobic capacity.

Previous work had implicated poor mitochondrial function with individual components of metabolic syndrome, but this is the first time researchers have linked it to all of them at once. "This is an incredibly provocative study," says Vamsi Mootha of Massachusetts General Hospital in Boston, whose own work has linked mitochondrial malfunction to Type-II Diabetes. "They linked metabolic syndrome to mitochondria in a way that hasn't been done before."

Running for their lives, these rats, bred to have high aerobic capacity, appear to have fewer cardiovascular risk factors than their couch-potato cousins..."

2. Ulrik Wisloff, et al, "Cardiovascular Risk Factors Emerge after Artificial Selection for Low Aerobic Capacity," Science, Vol. 307, No. 5708, pp. 418-20 (January 21, 2005).


Approved Stem-Cell Lines Shown To Be Contaminated

Stem Cells

January 24, 2005; In the January 30th issue of Nature Medicine (Vol. 11, pp. 228- 32), Prof. Fred Gage of the Salk Institute in La Jolla, CA writes that "whenever a Sialic Acid (in particular, N-glycolylneuraminic Acid or Neu5Gc for short), which is commonly found in other mammals but not in humans, is eaten by way of meat or milk, it is immediately destroyed by host antibodies (as a foreign protein)." This latest work demonstrates that these antibodies, found in human plasma, will, in fact, kill stem-cells from the standard, NIH-approved lines in vitro. It is expected that were these cells injected into humans, the same destruction would occur in vivo. To fix the problem, one could go down one of two hypothetical paths: (1) Start over and develop properly sterile human lines that do not make use of mouse feeder cells or calf blood serum, normally used to facilitate all stem-cell development in vitro; or (2) If you believe, for religious reasons, that developing new embryonic stem-cell lines is tantamount to murder (sic) or if you work outside of California and depend on NIH funding (sigh!), labor to purify the existing lines.
[ Editorial Remark: For those scientists who choose (or must choose) the second alternative, we wish you good luck!]

Refs:

1. Maria J. Martin, Alysson Muotri, Fred Gage, and Ajit Varki, "Human Embryonic Stem Cells Express an Immunogenic Nonhuman Sialic Acid," On-Line Prepublication Copy in PDF Format Nature Medicine, pp. 1-5 (January 30, 2005).
2. AP, "Study: Stem-Cell Lines Contaminated," CNN (Washington, D.C.; January 23, 2005).
3. "Stem-Cell Researchers Say Bush Approved Lines Are Tainted by Non-human Molecules from the Medium Used to Grow Them," The Wall Street Journal, p. A1 (January 24, 2005).
4. Karen Kaplan and Megan Garvey, "Study Says All Stem Cell Lines Tainted," The Los Angeles Times, pp. A1, 11 (January 24, 2005).
5. Karla Gale, Reuters Health, "Contaminant Found in Human Embryonic Stem Cell Lines" (January 24, 2005.

Human Embryonic Stem Cell (HESC) Lines cultured with animal-derived products have become contaminated with N-glycolylneuraminic Acid (Neu5Gc), a Sialic Acid that human cells are genetically unable to make, according to a new report. Because humans normally express antibodies to Neu5Gc, these contaminated cells would be dangerous if used clinically.

All HESC lines currently approved for study under Federal funding in the US have been grown on or derived from a mouse feeder layer. HESC lines grown on mouse-feeder cells and in culture media containing animal products become contaminated through a "Trojan Horse" type of mechanism, Senior Investigator Dr. Ajit Varki, of the University of California San Diego, told Reuters Health. The cells take up Neu5Gc-containing molecules, which are delivered to the lysosome where they are released and delivered to the cellular metabolic machinery.

Writing in the journal Nature Medicine published on-line January 23rd, Dr. Varki and his colleagues note that approximately [6 - 10.5] percent of total Sialic Acids in HESCs are made up of Neu5Gc. Attempts at growing contaminated cells on animal-free feeder systems and in heat-inactivated human serum have failed to remove all traces of Neu5Gc. If used in humans, "there is a significant chance of a deleterious immune reaction and/or rejection of the transplanted cells," Dr. Varki said. "Either more needs to be done to figure out how to eliminate this problem or we have to start over with new stem cell lines" that are never exposed to animal-derived products, the researcher said, an option that "generates a lot of political and policy concerns."

6. Editorial, "Stem-Cell Setbacks," The Los Angeles Times, p. B8 (January 24, 2005).
[ GRG Editorial: For the sake of public accountability, The LA Times Editorial writer complains that there should be still more focus on open meetings by the Institute for Regenerative Medicine and its ICOC regarding ethics and disclosure of potential conflicts-of- interest. We agree. But we must remind them that public meetings were held in four locations in California last week, and ethics was a major topic discussed by Dr. Steven Peckman, M.D., Associate Director for Human Subjects Research at the UCLA David Geffen School of Medicine in downtown Los Angeles last Wednesday, January19th, and no LA Times reporter(s) were present to document the event. Perhaps we should make his PowerPoint slides available at UCLA Office for the Protection of Human Subjects (OPRS) or in the Resources Section of this website and send a letter to the Editor for publication?]
7. Constance Holden, "Stem Cells: California's Bold $3 Billion Initiative Hits the Ground Running," Science, Vol. 307, No.5707, p. 195 (January14, 2005).
The Center for Genetics and Society of Oakland, CA has voiced criticism of the ICOC for its alleged failure to hold open meetings with agendas published with ten-day advance notice, as required by State of California regulations for governmental and quasi-governmental agencies. BTW, the Genetics and Society.org website is also translated into three other languages (Russian, Spanish, and Portuguese)!
8. Leah Rosin, "The Politics of Stem Cells: Multiple Viewpoints," BioProcess International , Vol. 3, No. 1, p. 80 (January 2005).
This editorial in a business magazine mentions Law Prof. R. Alta Charo of Wisconsin, who attended a two-day meeting "Playing God or Playing Politics? How Stem Cells Made It to the Convention Floor" (Northwestern University, Evanston, IL; October 2004).
9. Maisam M. Mitalipova, et al., Letter to the Editor, "Preserving the Genetic Integrity of Human Embryonic Stem Cells," Nature Biotechnology, Vol. 23, No. 1, pp. 19-20 (January 2005).
10. Andy Coglan, "Approved Stem-Cell Lines Contaminated," New Scientist, Vol. 185, No. 2484, p. 9 (January 29, 2005).
11. Helen Pearson, "The Great Divide: A Major Foreign Breakthrough Highlights the Limits Placed on U.S. Stem-Cell Researchers," Popular Science, Vol. 266, No. 1, p. 55 (January 2005).


New Master Oncogene: Pokeman

"Role of the Proto-Oncogene Pokemon in Cellular Transformation and ARF Repression"
TAKAHIRO MAEDA [1,2], ROBIN M. HOBBS [1,2], TAHA MERGHOUB [1,2], ILHEM GUERNAH [1,2], ARTHUR ZELENT [3], CARLOS CORDON-CARDO [2], JULIE TERUYA-FELDSTEIN [2] , and PIER PAOLO PANDOLFI [1,2]
_____________________________
1. Cancer Biology and Genetics Program,
2. Department of Pathology
Memorial Sloan-Kettering Cancer Center
Sloan-Kettering Institute
1275 York Avenue
New York, New York 10021; USA
3. Leukemia Research Fund Center
The Institute of Cancer Research
Chester Beatty Laboratories
Fulham Road
London SW3 6JB, UK

Correspondence and requests for materials should be addressed to P.P.P.
( p-pandolfi@sik.mskcc.org).
__________________________________
Nature, Vol. 433, pp. 278 - 285 (January 20, 2005).

Abstract:

Aberrant transcriptional repression through chromatin remodelling and histone deacetylation has been postulated to represent a driving force underlying tumorigenesis because histone deacetylase inhibitors have been found to be effective in cancer treatment. However, the molecular mechanisms by which transcriptional derepression would be linked to tumor suppression are poorly understood. Here we identify the transcriptional repressor Pokemon (encoded by the Zbtb7 gene) as a critical factor in oncogenesis. Mouse embryonic fibroblasts lacking Zbtb7 are completely refractory to oncogene-mediated cellular transformation. Conversely, Pokemon overexpression leads to overt oncogenic transformation both in vitro and in vivo in transgenic mice. Pokemon can specifically repress the transcription of the tumor suppressor gene ARF through direct binding. We find that Pokemon is aberrantly overexpressed in human cancers and that its expression levels predict biological behavior and clinical outcome. Pokemon's critical role in cellular transformation makes it an attractive target for therapeutic intervention.

______________________________________________________________________

"Scientists Identify a Single 'Master' Gene That Seems to Turn On Cancer"
by
Delthia Ricks
Newsday

An international team of scientists believes it has found cancer's master switch with the discovery of a gene they dubbed "Pokemon." Like the electronic game figures - tiny monsters with bad tempers - the cancer-triggering gene apparently instigates the misbehavior of other cancer-causing genes, leading to tumor formation. In today's issue of the journal Nature, researchers at Memorial Sloan-Kettering Cancer Center in Manhattan, in collaboration with teams in Japan and Britain, announce that the gene plays a key role in starting a malignancy. As a result, scientists now believe they have stumbled upon an important new target for an anti-cancer drug.

Dr. Carlos Cardon-Cardo, a molecular pathologist at the cancer center and a senior author of the research, defined Pokemon as an oncogene, which means it is capable of causing cancer. Dozens of oncogenes have been discovered over the past 25 years. But unlike the others, Cardon-Cardo said Pokemon has a governing role -- it is needed for other genes to function. "Eliminate Pokemon," he said, and "you stop the activity of other cancer-causing genes."


Sherwin Nuland, M.D. and MIT's Technology Review Deliberately Trash Aubrey de Grey

Aubrey de Grey, Ph.D.

January 18, 2005; With a bizarre series of ad hominem arguments and a patronizing tone, the Editors of the otherwise cutting-edge magazine Technology Review, have decided to post Aubrey's photo on their cover like an FBI Most-Wanted Poster and send him off to an institution for the insane on the grounds that "he's nuts." The unflattering close-up cover photo has a caption which asks the provocative question "Is he nuts?" while the Table of Contents on Page 3 presumes to answer this question "... [We] found him brilliant --- but also nuts." Can Aubrey, one of our more energetic spokesmen, really be a "troll," a slovenly dresser, sporting a Rip-van-Winkle beard (I might have said Rasputin), lacks children, drinks too much beer, shows signs of decay at the age of 41, and spends way too much time on his obsession?[1] Sure he can. We always knew that Aubrey had a certain "studied look." But how can he have the arrogance to attempt to "perturb" our assumptions about biological longevity? That's impossible, isn't it?

Refs.:

1. Jason Pontin, "Against Transcendence," Technology Review, Vol. 108, No. 2, p. 10 (February 2005).
2. Sherwin Nuland, "Do You Want to Live Forever? " Technology Review, Vol. 108, No. 2, pp. 36 - 45 (February 2005).
3. Check out Aubrey's Science or click on his photo above.
4. Aubrey Responds to Nuland.
5. GRG Letter to the Editor of Technology Review.


World's Oldest Mother

Adriana Iliescu, Oldest Mother Adriana Iliescu and Daughter
The second photo comes from the 2007 Guinness Book of World Records, p. 64
Adriana Emilia Iliescu (b. May 31, 1938) was 66 years and 230 days old when she gave birth by C-section to her daughter Eliza Maria Bogdana at the Clinical Hospital of Obstetrics and Gynecology in Bucharest, ROMANIA on January 16, 2005.

January 18, 2005; Bucharest, ROMANIA - A 66-year old Romanian professor, who writes children's books, claims to have become the world's oldest woman to give birth, and doctors said she and her day-old daughter were in good condition at Giulesti Maternity Hospital. Doctors said that " Adriana Iliescu, who is single, became pregnant though in vitro fertilization (IVF) using sperm and egg from anonymous donors." They said "she delivered her first child, 3-lb. 4- oz. Eliza Maria, by C-section on Sunday but that a twin sister was stillborn."

________________

January 17, 2005; Bucharest, ROMANIA ( The Times of London) -- A retired professor yesterday became the oldest woman in the world to give birth - at the age of 66. Adriana Iliescu, who was due to have twins next month, had a girl Eliza Maria. Her pregnancy was induced after a[n ultrasound] scan revealed one of the children had died.

Doctors feared for the safety of he second twin but she was born weighing 1.4 Kg (3 lbs.) and 'in perfect health.' "Ms. Iliescu's age was probably unrelated to the other twin's death," said doctors in the Romanian capital, Bucharest. 'The Mother is doing well -- she's saying she has been given a new lease of life,' added hospital staff.

Josephine Quintavalle, for The ProLife Party, said 'a child deserved a mother and father who 'will be around for as long as possible.' Ms. Iliescu had nine years of hormone treatment to delay her menopause before becoming pregnant. The egg was fertilized with donor sperm.

Last month, she said 'I worked so hard in my career that I had no chance to start a family. 'A woman has a right to give birth, and I had to follow my dream - no matter how old I was.'

Previously, the oldest woman to give birth was Satyabhama Mahapatra, a 65-year-old Indian who was impregnated in 2003. The British record is held by hill farmer Liz Buttle. She had a son, Joe, in 1997 at 60 after lying about her age to receive fertility treatment. [2]

Many experts warn of the risks of becoming pregnant after age 50 because of physical stress to the mother and baby.

[ Editor's Note: Dr. Richard Paulson, OB/GYN Infertility Specialist from USC was a speaker to the LA-GRG on July 29, 2003 and was featured on Nova Special covering this topic. One of Dr. Paulson's more famous patients (Mrs. Arceli Keh) deliberately concealed her true age (60), representing herself to USC as 50 years old (the age limit for surrogate mothers receiving donor eggs under the protocol was set at 55). She subsequently became the oldest woman in the world at that time (63), to give birth. Fortunately for everyone concerned, her infant turned out to be a healthy baby girl! [3]]

June 19, 2005; Click for an update on the puzzling hostility from the Romanian Orthodox Catholic Church at the time of daughter Eliza Maria's Baptism.
[ Editorial Remark: One gets the feeling that whenever science and technology dislocate the "normal" pattern of human affairs, there is an inevitable backlash until the public gets familiar with it. After that, today's people wonder how we ever got along before we invented the wheel, penicillin, gun powder, electricity, or whatever, take your pick.]

Refs.:

1. "At 66, a Professor, Writer, and New Mom," The Los Angeles Times, p. A4 (January 18, 2005).
2. Oliver Stallwood, "Woman of 66 Has Baby," Metro, The Times of London (January 17, 2005).
3. PBS-TV Channel 28 in Los Angeles, Nova, "18 Ways to Make a Baby" (Tuesday, June 10, 2003; [8:00 - 9:00] PM PDT).
4. Abby Lippman and Stuart A. Newman, "The Ethics of Deriving Gametes from ES Cells," Letters to Science, Vol. 307, No. 5709, pp. 515-7 (January 28, 2005).
" Assemblages resulting from combining an ES cell-derived egg or sperm with normally produced sperm or egg via in-vitro fertilization (IVF) are entities distanced not only from the physiological reproductive process but from human forebears with any socially prescribed responsibility for them."
Response by Giuseppe Testa and John Harris, "It is not the enabling technology, but the choice of the word "assemblage," in its objectifying power, that distances potential humans generated through [ES-Derived Gametes] from the rest of society. Creatures born through ESDGs would be humans just like anybody else, whether conceived naturally or through [in vitro fertilization]."


LRRK2 Gene Linked to Parkinson's Disease

January 18, 2005; London, UK ( Reuters) -- Three teams of scientists have identified a genetic mutation that is linked to about five percent of inherited cases of Parkinson's Disease. Te fault on the recently discovered LRRK2 gene is one of five genetic defects liked to the progressive nervous-system disorder and could lead to improved diagnosis and the development of a genetic test.

"Our results suggest that the mutation we have studied is the most common cause of Parkinson's Disease identified to date," said Tatiana Foroud, an Associate Professor at Indiana University School of Medicine in Indianapolis. The research is one of three studies by scientists in Britain, The Netherlands, and the U.S. who identified the LRRK2 gene mutation. Their findings are being published in the on-line issue of Lancet today.

Refs.:

1. "Genetic Mutation Tied to Parkinson's," The Wall Street Journal (January 18, 2005).
2. "Genetic Defect Linked to Some Parkinson's Cases," The Los Angeles Times, p. A14 (January 22, 2005).


News Items for 2004

Click for News Items from 2004.