BREAKING NEWS ITEMS [2002]

Kidney Precursor Cells Identified in Humans and Pigs

December 28, 2002; As reported in the January 2003 issue of Nature Medicine, Israeli researchers have grown functioning kidneys in mice, a feat that could lead to the production of kidneys in humans, eliminating the need for transplants! The team inserted specific stem cells called, Kidney Precursor Cells from humans and pigs into mice. Both types of tissue grew into "perfectly formed functional kidneys the size of normal mouse kidneys." The kidneys actually produced urine and were sustained by blood vessels.

[ Editor's Note: Does anyone know if there are other organ precursor cells, like lung, heart, liver, etc.?]

Benjamin Dekel[1], Tatyana Burakova[1], Fabian D. Arditti[1], Shlomit Reich-Zeliger[1], Oren Milstein[1], Sarit Aviel-Ronen[3], Gideon Rechavi[3, 4], Nir Friedman[5], Naftali Kaminski[3], Justen H. Passwell[2], and Yair Reisner[1], "Human and Porcine Early Kidney Precursors As a New Source for Transplantation," Nature Medicine (December 23, 2002).

ABSTRACT:

Kidney transplantation has been one of the major medical advances of the past 30 years. However, tissue-availability remains a major obstacle. This can potentially be overcome by the use of undifferentiated or partially-developed kidney precursor cells derived from early embryos and fetal tissue. Here, transplantation in mice reveals the earliest gestational time point at which kidney precursor cells, of both human and pig origin, differentiate into functional nephrons and not into other, non-renal professional cell types. Moreover, successful organogenesis is achieved when using the early kidney precursors, but not later-gestation kidneys. The formed, miniature kidneys are functional, as evidenced by the dilute urine they produce. In addition, decreased immunogenicity of the transplants of early human and pig kidney precursors compared with adult kidney transplants is demonstrated in vivo. Our data pinpoint a window of human and pig kidney organogenesis that may be optimal for transplantation in humans.

1. Department of Immunology, Weizmann Institute of Science, Rehovot, ISRAEL
2. Department of Pediatrics, Sheba Medical Center, Tel Hashomer, ISRAEL
3. Functional Genomics Unit, Molecular Hemato-Oncology and Respiratory Medicine, Sheba Medical Center, Tel Hashomer, ISRAEL
4. Department of Pediatric Hemato-Oncology, Sheba Medical Center, Tel Hashomer, ISRAEL
5. School of Computer Science and Engineering, Hebrew University, Jerusalem, ISRAEL

Correspondence should be addressed to: Y Reisner. E-mail: yair.reisner@weizmann.ac.il.

Refs:

1. Reuters, "Kidneys Grown in Mice from Human Stem Cells," CNN (December 23, 2002).
2. "Israeli Team Grows Kidney in Mice," The Los Angeles Times, p. A18 (December 28, 2002).

Raelian Sect Says It Has Cloned the World's First Human Baby the Day After Christmas: No Evidence Yet

December 27, 2002; Hollywood, FL ( CNN) --- Biochemist, Dr. Brigitte Boisselier, Ph.D., CEO and Scientific Director of Clonaid, Inc. located in The Bahamas (no longer at a formerly secret laboratory in West Virginia after its location was discovered and raided by the FBI), announced at a beachfront hotel press conference in Hollywood, FL (North of Miami) this morning that they have succeeded in cloning the first human baby, and that four more cloned babies are on the way in January or February (one in Northern Europe, two from Asia, and one other from North America). The first is a reportedly healthy 7-pound baby girl born by C-Section at 11:55 AM EST on Thursday, December 26, 2002 and code-named Eve (not her real name, presumably to protect her privacy) at an unknown location (presumably in the Eastern time zone but not in the US or Canada in a clear attempt to evade national or local laws against this practice by remaining outside of their jurisdiction) to a married (husband is said to suffer from a male infertility factor), 31-year-old American woman who effectively delivered her daughter as her genetically-identical twin (displaced in time)! No proof of this claim was provided at this press conference, but it was stated that objective forensic DNA evidence would be forthcoming within nine or ten days. Michael Guillen, Ph.D., has been chosen to provide this service, using two different laboratories simultaneously. Dr. Guillen will not accept any funds from Clonaid or its surrogates.

[ Editor's Speculation: The logistics may prove difficult for any attempt by the parents to gain US Citizenship for their daughter and/or to return with her to the US without being subjected to potential harassment by the INS, and to maintain their privacy while not filing a meretricious Birth Certificate containing the imprimatur of the Health Service of the Country-of-Birth (a genuine female "Clone Birth Certificate," I imagine, would have to list the Mother as "Father" as well as "Mother," no? which would sort of make it stand out in comparison with your garden variety certificate) with a US State Department Visa Application at their local US Embassy/Mission. It would not be surprising if President Bush's Daily Morning Brief in Crawford, TX did not already contain all their full names and their address in the US, since there are at least two different methods the CIA could use (if they were asked) to identify an American family abroad given that citizens always leave an "audit trail" of their travels whenever they legally leave or re-enter the US at an official port-of-entry. And if they were flagged as being "persons-of-interest," they would be immediately subjected to detention and the full force of the law. They could, in principle, risk having all their US assets confiscated, lose their privileges as US citizens, and/or be permanently deported for a felony, if they in fact did anything illegal, like making false statements or forged an official document, or surreptitiously crossed the border with an illegal alien (Jane Doe). I am not a lawyer, but I do know that a number of indigent women, who chose to deliver their baby at home (which is certainly not illegal), brought their newborn child into our hospital the next day or so to have it briefly examined by a pediatrician and to have the birth officially recorded, which was done at no cost to the Mother and essentially as a public service.]

REACTION TO THE NEWS RANGES FROM SKEPTICAL TO RIGHTEOUS INDIGNATION...

Prof. Alta Charo of the University of Wisconsin said it was "medical grandstanding." Dr. Robert Lanza, M.D., of Advanced Cell Technology in Worcester, MA, stated that such attempts are "ethically appalling, scientifically irresponsible, and medically dangerous; a backlash could cripple an area of medical research [ therapeutic cloning] that could serve millions of people." In Rome, fertility doctor Severino Antinori, M.D., OB/GYN, said that the Raelian claim "makes me laugh." [Dr. Antinori will make his own announcement about a male clone in January.] President Bush commented through Deputy White House Press Secretary Scott McClelland that "he believes, like most Americans, that Human cloning is deeply troubling, and he strongly supports legislation banning all human cloning." Religious opponents warn that "human cloning represents an attempt by scientists to put themselves on a par with God." The Catholic Church weighed in with the statement, "This announcement is an expression of a brutal mentality, lacking all ethical and human consideration," Joaquin Navarro-Valls, a Spokesman for the Vatican. Prof. Stanley M. Hauerwas, Department of Theological Ethics at Duke University said, "The very attempt to clone a human being is evil; the assumption that we must do what we can do is fueled by the Promethean desire to be our own creators." The GRG itself will prepare an Editorial on this topic only after the Raelians provide the public with forensic DNA evidence, given that they have no scientific/medical track record in this field, regardless of how one may feel about their theological credibility and/or their outrageous lifestyle. CNN and Fox News TV channels and other media have had a "field day" with this story for the past two days.

December 29, 2002; Prof. Leon Kass, Chairman of the President's Advisory Council on Bioethics, said that "The arguments... go beyond questions of concerns about safety and really add up to a deep and permanent objection to what these Raelians claim to have done." Ms. Claire Buchan, White House spokeswoman, said that "the announcement underscores the need for Congress to act in a bipartisan manner to ban human cloning."

_________________________________
* About 4.5 percent of all IVF or test-tube babies have significant congenital defects in comparison with a comparable sex-matched control group of 4,000 babies. The defects ranged from cleft pallets to life-threatening heart-valve or ventricular foramen abnormalities. One of the newest methods of assisted conception called Intracytoplasmic Sperm Injection (ISI) [in which a single sperm is mechanically injected directly into the egg, secondary to male factor infertility] had a 9 percent rate of congenital defects in a survey of 1,138 infants done in England and Australia.

Refs:

1. Clonaid.com.
This site is viewable in any of five different languages. Curiously, news on the English version is more up to date than the French version. Since Rael's native language is French (Parisian French, not French Canadian), does that tell you something their marketing plan to prospect for future customers?
2. Rael.org .
This website is viewable in 20 different languages! The Raelians claim 55,000 members in 84 countries; however, active members may be substantially fewer than that. The site opens with a wonderful Flash Animation of Rael's first encounter with a four-foot-tall alien while traveling in central France. Curiously, the narrator has a distinctly British accent. There doesn't seem to be a comparable version for this animation (in French) on the French-language site. Presumably the original alien spoke French, but this level of detail is not revealed. Even the creatures from Middle Earth spoke their own neological language (with a well-defined, consistent vocabulary and syntax) in The Lord of the Rings.
3. John-Thor Dahlburg, "Firm Says It Created First Human Clone: Although Skepticism Abounds, Scientists Don't Entirely Reject the Claim that a Religious Group Believing in UFOs May Have Produced 'Eve'," The Los Angeles Times, pp. A1, 13 (December 28, 2002).
4. Michael Ramirez, Political Cartoon, "Six Identical Clowns are Exiting from a Very Small Car with "Clonaid" Written on the Side Door," The Los Angeles Times, p. B23 (December 28, 2002).
5. Times Wire Reports, New York, "Company Hints It Has Produced Human Clone," The Los Angeles Times, p. A17 (December 27, 2002).
6. "Raelian Leader: Cloning First Step to Immortality," CNN (December 28, 2002).
7. Fox News (December 27, 2002).
8. NBC-TV (December 26, 2002).
9. AP, "Expert to Probe Claim of Cloned Human," The New York Times (December 28, 2002).
The attempt at proof [that Eve is a true clone] will be made quickly, promised free-lance TV journalist Dr. Michael Guillen, Ph.D. The former ABC-TV Science Editor said he had chosen an expert who will draw DNA samples from the Newborn and her Mother.
10. Malcom Ritter, Associated Press, "First Cloned Baby? Religious Cult Announces Birth of First Cloned Baby," ABC-TV (December 27, 2002).
11. Gina Kolata, "Experts Are Suspicious of Claim of Cloned Human's Birth," The New York Times (December 28, 2002).
12. "Cloning Claim Prompts Call for Ban," BBC (December 28, 2002).
13. Rick Weiss, Staff Writer, "An Uncertain Year for Cloning Laws," The Washington Post (December 26, 2002).
The first discussion we have seen of Sen. Bill Frist's, M.D. (R -TN), the new Senate Majority Leader replacing Trent Lott, position on cloning and the fact that he went to visit ACT in Worcester, MA personally two weeks ago.
14. AP, "Clerics Denounce Cloned Baby Claim," The Los Angeles Times, p. A14 (December 29, 2002).
15. Antonios Regalado, Laurie McGinley, and Sarah Lueck, "Cloning Claim Spurs Ethics Debate: Claim of Clone by Raelians Provokes Skepticism," The Wall Street Journal, pp. A3, 6 (December 30, 2002).
16. Mark Heinzl and Antonio Regalado, "Clonaid's Claim Raises Doubt, Envy of Rivals," The Wall Street Journal, pp. B1, 3 (December 30, 2002).
17. AP, "Cloned Girl Will Fly to U.S. Today, Firm Says," The Los Angeles Times, p. A15 (December 30, 2002).
The US FDA believes that its charter offers the Agency some jurisdiction over attempts to clone humans in this country (only with its permission, which it has not given) and so "it plans to investigate whether any portion of the Clonaid Project occurred within the U.S. with criminal prosecution as a potential outcome of its probe."
[ Editor's Note: To our knowledge, all Clonaid facilities, but not its clients, are currently located abroad. If this proves to be the case, the FDA's investigation will turn out to have been a waste of time. In any event, this point will soon become moot when the Mother of "Eve" and her husband are interviewed by the media and such FDA suspicions are obviated. Since she is flying [ CNN] into the US today, there will be a feeding frenzy of tabloid reporters and paparazzi waiting there, attempting to purchase an exclusive interview, as soon as the airport is identified, which is probably known to a sufficient number of insiders that it will be purchased and/or leaked in the next few days, if this hasn't happened already. At present, the location of the parents' home is ostensibly still a secret, even though I suspect that the US Government is fully aware of it, and has put the FBI and the Justice Department on notice.]
18. Onora O'Neill, "Reason and Passion in Bioethcis," Science, Vol. 298, No. 5602, p. 2335 (December 20, 2002).
"Prof. Kass, the Chairman of President George W. Bush's Council on Bioethics, offers a passionate polemic against current ways of thinking about reproductive technologies in Reference 19 below."
19. Leon R. Kass, Life, Liberty, and the Defense of Dignity: The Challenge for Bioethics (319 pp.; $26.95; ISBN 1-893554-55-4; Encounter Books, San Francisco, CA; 2002).
20. Wire Services listing of virtually all news about the topic of human cloning.
21. Clone Rights United Front by Mr. Randolfe H.Wicker, who promotes himself as the World's First Pro-Human Cloning Activist, active since 1997.
22. Letters to the Editor, "If This Child Is Truly a Clone...," The New York Times, p. A20 (December 31, 2002).
Prof. Rebecca Dresser's (3rd) Letter, Law and Ethics in Medicine at Washington University in St. Louis, MO (December 28, 2002) was well reasoned. The others either complained that "2 + 2 = 4" or proudly announced that "2 + 2 = 4." For example, "If God hadn't wanted us to clone humans, He wouldn't have given us the power to do it." That counterfactual fallacious presuppositional speculation falls in the same category as my Aunt Tillie's advice: "God never intended for us to go to the moon; we should have stayed home and watched television, like He meant us to." or Donald Duck's advice: "The day before a vacation should be a vacation," presumably to allow for more preparation time, but that makes all recursively-innumerable days vacation days, past and future, doesn't it?
23. December 31, 2002 ( Fox-TV News) Mr. Philip Reeker, spokesman for the US State Department said at a press briefing, "Regarding the hypothetical situation of cloning, this is a new situation." (Reporters could be heard laughing in the background.) "We don't yet know how US law applies to the question of citizenship [which is not automatically granted to a child born abroad just because the parent(s) are US citizens]. However, for the record, all passport applications are confidential," meaning that INS/State was not going to reveal the location of the parents of Eve to the reporters just because they wanted to know.
24. Jane Sutton, "Legal Guardian Sought for Clone in Florida Court," Alert Net; Reuters Foundation (December 31, 2002); Miami, FL -- An attorney has asked a Florida State Court to appoint a legal guardian for the baby girl [Eve] purported to be the first human clone, saying that "the infant is being exploited and may have suffered birth defects."
[ Editor's Note: Talk about a nightmarish jurisdictional problem for a Florida judge if Eve doesn't reside in that state.]
25. Rick Weiss, "Cloning a Previous Hoax?" The Washington Post (December 31, 2002).
David M. Rorvik [previously a science reporter for The New York Times and Time Magazine, so he had some credibility, but his credentials also included wide-eyed articles on psychic and faith healers and a passionate advocacy of the discredited anti-cancer drug Laetrile] wrote a book entitled In His Image: The Cloning of Man (J. B. Lippincott Company, Philadelphia, PA; 1978), which told the tale of an unnamed American millionaire (code-named Max) who presumably hired Mr. Rorvik to set up a lab on an unnamed Pacific island where a team of scientists succeeded in cloning Max after five years of effort, using a paid surrogate mother for the full-term birth. The book represented this story as fact with real names presumably replaced by pseudonyms to protect the innocent and a full scholarly bibliography of references to the scientific literature (of that time) --- not as fiction - but it was subsequently proven to be a fraud and a hoax in 1981 (not by DNA evidence, which didn't exist yet, but by a court-order for evidence in a legal ruling). Experts called the book "a case study in commercial exploitation."
[ Editor's Note: I happen to own an original copy of this now out-of-print book in my collection. What was especially galling was that it quoted one of my Professors at Stanford Medical School, Dr. Joshua Lederberg (Nobel Laureate), as saying (in 1962) that "There is nothing to suggest any particular difficulty about accomplishing [cloning] in mammals or man, though it will rightly be admired as a technical tour de force when it is first accomplished. It places man on the brink of a major evolutionary perturbation." as a way to gain credibility for the book.]
26. James (The Amazing) Randi, a well-known skeptic, professional magician, and debunker of psychics and frauds (Uri Geller, the infamous spoon-bending Israeli prestidigitator, as well as so- called "psychic surgeons" in the Philippines who purportedly performed surgery on patients removing diseased internal organs without breaking the external skin) points out that an "independent chain of custody" of blood and/or skin samples (with coded non-forgeable labels: "A," "B," "C," etc.) from the Mother and Eve need to be guarded scrupulously before being shipped to two independent forensic laboratories (that presumably will provide identical results for samples "A," "B," "C," "D," "E," etc. with other coded dummy samples randomly mixed in).or risk a new round of fraud. If samples are out-of-sight of the investigative team for even a minute, one may expect foul play assuming the perpetrators of fraud hope to succeed by "not getting caught." By the way, Randi apparently has little respect for Dr. Michael Guillen, Ph.D. who has a Doctorate in Physics, Mathematics, and Astronomy from Cornell University and has been designated by Clonaid to be an objective custodian for the validation process and who says that he has no financial connection to either Clonaid or The Raelian Sect. In fact, Randi has dealt with Dr. Guillen before, saying "because of his acceptance of Scientology, cults are right up his alley, and to put him in charge of this investigation is like putting the fox in charge of the hen house." And Guillen has a potential conflict-of-interest, as he is in the process of negotiating a documentary about the sect as an independent producer, even though he denies that this would be a conflict, as such.
26. Matt Ridley [author of Genome: The Autobiography of a Species in 23 Chapters (Harper Collins, New York; 2000)], "Biology's Chernobyl," The Wall Street Journal, p. A14 (December 31, 2002).
27. Michael Shermer [publisher of The Skeptic Magazine and Columnist for Scientific American], "Wake Up, Cloning's Day Has Come," The Los Angeles Times, p. B13 (January 2, 2003).
28. AP, Paris; FRANCE, "Parents of Cloned Baby Undecided on DNA Testing," USA (January 2, 2003).
29. Amanda Onion, "Put to the Test: Genetic Tests Could Resolve Cloned Baby Claim, But Are Not Foolproof," ABC News (January 2, 2003).
30. AP, Paris, FRANCE, "Clonaid Says Parents Balk at DNA Test," The Los Angeles Times, p. A13 (January 3, 2003).
31. Sharon Begley, "Eve May Be Offspring of a Very Long Line of Hoaxes," The Wall Street Journal, p. A7 (January 3, 2003).
32. Paris, FRANCE, "Clone Firm: Second Birth by Sunday," CNN (January 3, 2003).
A Broward County, Florida Circuit Court has set a hearing date of January 22nd for a lawsuit filed by Attorney Bernard Siegel who has asked that the court to appoint a legal guardian for Eve, the alleged clone (does the home of Eve or does the location of the announcement provide the court with jurisdiction?). If the Mother of Eve does not appear at the hearing on that date then the court could conceivably order that the baby be removed from the Mother, a highly-unlikely prospect, and custody given to foster parents, providing that they can find the baby, who may have been sequestered somewhere else by other family members in the mean time.
33.Catherine Bremer, "Second Cloned Baby Said Imminent, But No DNA Tests," Reuters (January 3, 2003).

Raelian Sect Says It Will Deliver the World's First Cloned Baby on Christmas Day

December 24, 2002 Montreal, Quebec, CANADA ( Reuters) The cult that believes in free love and also teaches that all life on Earth was created by intelligent extra-terrestrials said that "it may deliver the world's first cloned baby (a girl) by Christmas Day." Coincidentally, the woman whose cells were used for the purpose of the cloning procedure has also served as surrogate mother, carrying the birth to full term. Therefore, she will literally deliver a genetic copy of herself. Dr. Brigitte Boisselier, Ph.D. biochemist and a Bishop in the Raelian Religion (founded by 56 year-old Mon. Claude Vorilhon (Prophet Rael) French Canadian) and CEO and Scientific Director of their cloning effort through a company called Clonaid, Inc., said that ten human embryos were cloned last Spring with only five miscarriages occurring, leaving the December birth and four other cloned babies to be expected in early 2003. Diagnostic ultrasounds were not mentioned but are presumably being done on a regular basis. The announcement above was greeted with skepticism by experts in the field. See the announcement below by Dr. Severino Antinori, M.D. of Rome (November 26th) that he expects to deliver a cloned boy sometime in January.

Ref:

"Sect Says First Cloned Baby Due Soon," MSNBC News (December 19, 2002).
This web page contains a really superb Flash Animation explaining the difference between therapeutic cloning and reproductive cloning.

U.S. Launches Proteomics Initiative

NIH will spend $157 million over the next seven years to unlock the protein interactions that underlie a spectrum of hear, lung, blood, and sleep disorders.

Ref:

Science Designates siRNAs the Top Story of the Year

December 20, 2002; Molecular switches called small interfering RNAs or siRNA's have the potential to treat such diseases as HIV and cancer, since these molecules could, in principle, instantly shut off selected genes along our chromosomes.

Refs:

1. "Molecular Switches Top Science Story," The Los Angeles Times, p. A14 (December 21, 2002).
2. Jennifer Couzin, "Breakthrough of the Year: Small RNAs Make Big Splash," Science, Vol. 298, pp. 2296-7 (December 20, 2002).
3. Ken Barber, "Prescription RNA," MIT Technology Review, Vol. 105, No. 10, pp. 42- 8 (December 2002, January 2003).

New Stem-Cell Law Passed in Australia

December 13, 2002; Australia's Parliament this week approved a national stem-cell law that will harmonize a jumble of state and territorial rules. Researchers will be able to use existing human embryonic stem-cell lines and create new lines from excess embryos created for IVF prior to April 5, 2002. This gives researchers a sound ethical basis to go forward, said Dr. Martin Pera of Monash University.

Ref:

Stanford University Receives $12 Million Grant for Research on Stem Cells

December 11, 2002; Palo Alto, CA; Prof. Irving Weissman, M.D. who will direct the new Institute for Cancer/Stem-Cell Biology and Medicine at Stanford University Medical School, will use tens of stem cells arising from eggs with nuclear transplants in mice and in humans to investigate the genetics of chronic diseases, such as cancer, diabetes, heart disease, allergies, Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS), and others. Dr. Weissman has campaigned in scientific-journal editorials and through the National Academy of Sciences to achieve consensus on a separate label to distinguish the work he proposes to do from either reproductive or therapeutic cloning. Technically, he is using nuclear transplantation technology to produce a set of embryonic stem-cell lines that exhibit a particular pathology. Under certain conditions, a blastocyst (early embryo) can be formed in culture using 20 or 30 enucleated eggs with a corresponding number of fibroblast (skin cell) nuclei inserted. "If one were to work by itself, you'd call that a clone, while if two or three work together, you ought to call that nuclear transfer."

Refs.:

1. Marilyn Chase, Antonio Regalado, and David Hamilton, "Full Disclosure: Stanford Unveils Stem-Cell Plans," The Wall Street Journal, pp. A1, B1, 3 (December 11, 2002).
2. Aaron Zitner, "Stanford to Create Institute for Embryonic Stem-Cell Research: Scientists Do Not Rule Out Using a Form of Human Embryo Cloning, But Other Ways Will Be Tried," The Los Angeles Times, pp. A1, 14 (December 12, 2002).
3. "Stanford Stem-Cell Project Draws Criticism: Debate Over What Constitutes Cloning," CNN (December 11, 2002).
4. Antonio Regalado and Tom Liskey, "Cloning Pioneer Abandons Project: New Job at Michigan State Wouldn't Permit Research To Create Human Embryos," The Wall Street Journal, p. B4 (November 11, 2002).
Dr. Jose B. Cebelli, 39, Argentine-born researcher with Advanced Cell Technology of Worcester, MA, will leave ACT to accept a faculty position at Michigan State University in East Lansing, MI. Robert Lanza, M.D., VP of ACT said that, "due to a shortage of funds, Dr. Cebelli's Therapeutic Cloning Project had been put 'on hold' since earlier this year." (By the way, this shockingly negative revelation would have not have been known had one not read to the end of the article, since it started off with all this positive spin on Cebelli's career move.) ACT competitor Infigen, Inc. of DeForest, WI has recently reduced its own work force, as has cloning- pioneer PPL Therapeutics. Geron, Inc. of Menlo Park, CA and Celera Genomics, Inc. have likewise fallen on hard times along with the rest of the Biotech Sector.
[ Editorial Remark: What do we have to do to get this promising field moving again? The commercial Therapeutic-Cloning-Research Sector does not appear to be failing, at this point, because of the efforts of its ideological adversaries in the Bush Administration or even the pending adverse regulatory legislation in the US Senate, but because of the failing economy which is hurting everyone. Hopefully, the (anonymous) donor who has promised to fund the Stem-Cell Research Institute at Stanford will hang in there for the long haul (5 - 10 years).]
5. "Cloned Cells May 'Re-Boot the Immune System: Tests on Cows Could Lead to 'Grow-Your- Own' Human Transplants," CNN (December 6, 2002).
Dr. Robert Lanza, M.D., Medical Director of Advanced Cell Technology in Worcester, MA, reported at the Third Annual Conference on Regenerative Medicine held in Washington, D.C. earlier this week that "cattle allowed to live natural lives can survive 24 years and longer. We found the oldest cattle we could, and we cloned them. Stem cells traveled throughout their blood and out-competed their older, native cells. If this approach were to work in humans, it could not only be used to treat cancer and immunodeficiencies, but to 're-boot' the immune system in patients with various autoimmune diseases (Multiple Sclerosis, Rheumatoid Arthritis, Juvenile Diabetes, Systemic Lupus Erythematosis (SLE), Inflammatory Bowel Disease, and others) ." Lanza, along with other scientists working in the field, fears that the US Congress may soon block this sort of research. One of two competing bills would ban all cloning research involving humans, while the second would allow this type of work to go on. But U.S. Federal policy, backed by President Bush, is to ban all Federal funding of such work, which scientists believe will definitely slow it down. "We're all a bit frustrated by the lack of progress We should have been on the verge of clinical trials by now, but we're not." Lanza said.
6. Dr. Michael West, CEO, ACT, "Scientists Rewind Aging Clock in Cells of Cloned Cows, Study Says," CNN (April 27, 2000).
7. "Bush Advisor's Slam Stanford's Stem Cell Research," CNN (December 20, 2002).
8. "Apology in Stem Cell Feud: Stanford Retracts Statement Viewed as Suggesting Presidential Panel Backs Cloning," The Los Angeles Times, p. A14 (December 21, 2002).
Dr. Leon Kass, Chairman of the President's Council on Bioethics, demanded and received a correction, explaining that, contrary to what was stated on Stanford's website regarding the announcement of the creation of a new Institute for Stem-Cell Biology and Medicine, "[The Council] does not endorse cloning for biomedical research, and that Stanford had tried to 'obfuscate' the nature of its potential experiments. It is unfortunate that Stanford and [Prof. Irving] Weissman have clouded the ongoing debate over stem cells by disputing that their work could result in cloned human embryos."
[ Editor's Note: Phrases like "could not result," "should not result," "will not result," or "shall not result" are very tricky in legalistic English. Because Stanford's new Institute intends to use private funding exclusively -- and has no plans to seek grant funding from NIH or other Federal agencies --- its research program would be sanctioned under current law (because there is, at present, no Federal law governing private ventures in this highly entrepreneurial area). However, stay tuned to learn what the newly-constituted US Senate has in store for Stanford and its ilk, when it returns to session in January.]
9. Constance Holden, "Stanford Gets Gift for New Institute," Science, Vol. 298, No. 5602, pp. 2307-8 (December 20, 2002).
Nobelist Prof. Paul Berg says "their goal is to raise $100 million to support research on genetically-based treatments for cancer, Parkinson's Disease, heart disease, and other illnesses."

IBM Builds 6 nm Transistor

December 9, 2002; IBM will announce next week in San Francisco that it has developed a transistor that is one-tenth the size of the smallest such device in use today at six nanometers.

Refs.:

1. IBM, Armonk, NY; "World's Smallest Transistor," The Wall Street Journal (December 9, 2002).
2. David M. Ewalt, "Big Step for Nanotech: IBM Builds Worlds Smallest Transistor, Which Will Lead to More Powerful Chips," Information Week, p. 30 (December 16, 2002).

Rat Genomics Almost Wins the Race

December 7, 2002; The draft rat genome is only a whisker behind the mouse. The International Rat Genome Sequencing Consortium announced on November 25th that it completed its own draft sequence. Dr. Howard Jacob, Director of the Human and Molecular Genetics Center at the Medical College of Wisconsin in Milwaukee said, "I love the mouse, but rats are better models for clinical pharmacology (like diabetes, kidney disease, hypertension, and many other diseases)." "The rat genome hasn't been analyzed yet; however, we do know that it is larger than the mouse genome but smaller than the human genome," said Prof. Richard Gibbbs, Director of the Genome Center at the Baylor College of Medicine in Houston, TX. "Having two rodent genomes and the human genome will be particularly helpful in interpreting and cross-checking the sequences from all three mammalian species."

Ref:

Rosie Mestel, "Research Wins in Genome Rat Race," The Los Angeles Times, p. A24 (December 7, 2002).

Mouse Genome Published on the Internet by the Public Genome Sequencing Consortium

December 5, 2002; According to Dr. Robert Waterston of Washington University in St. Louis, only 300 genes (about 1 percent) are unique to either the mouse or humans (30,000 genes are present in both mammals). The total amount of DNA in a mouse (2.5 Giga Base Pairs) is about 15 percent less than that of humans, not because they have fewer genes but because they have the have less "junk" DNA in which the genes are embedded. Admittedly, we don't know what junk DNA does. Indeed, a significant number of the 300 unique genes on the mouse side turn out to be specific for odors, not for long whiskers or tails, which are present in humans too but just not expressed in the same way. Obviously, smelling is a more critical sense for the survival of rodents than it is for primates. See today's issue of the journal Nature with one of the Abstracts cited below.

[ Editor's Note: Celera Genomics has sold subscriptions to its Mouse Genome Data Base for the last year-and-a-half to its paying customers. However, the public version of the mouse-genome sequence will be available free-of-charge to any investigator on the Internet. It would be of great interest if one of the Celera's customers came forward publically with their view of the value of paying for the privilege of having an early copy. For example, are the two versions nearly the same. The public version is essentially 95 percent complete as I understand. Does one or the other have more annotations that makes it more valuable?]

[ Editorial Remark: In any event, we consider this to be an important milestone for gerontology despite the fact that most of the scientists doing the work don't consider themselves gerontologists (but rather computational geneticists). Nor do most gerontologists even track this aspect of genetics, which they consider a branch of biology outside their field of interest! The conspicuous reason that this is a milestone is that the comparative genomics of all mammals from rodents to bats/dogs/cats/rabbits/pigs/goats/sheep/cows/horses/giraffes/elephants/whales and finally to primates will provide us for the first time with the protein data we need to understand and manipulate the two order-of-magnitude differential longevity phenotype expressed by these various mammalian genomes and anatomically where their annual "clocks" are expressed, presumably in the brain somewhere (maybe the anterior hypothalamus). Just as the SA Node and the AV Node are bundles of reverberating nerve fibers in the heart that clock the (milli-second time-constant) rhythm of the EKG (P-QRS-T) 24 hours-a-day for as long as we live (modulated by the Vegas Nerve and Sympathetic Fibers to allow for a slower heart rate when we're asleep and a faster one when we're running to catch a train, respectively), so must there be a diurnal clocking mechanism (pineal gland) that synchronizes the annual clock(s) that determine the precise onset of puberty (12 +/- 2 years) and andro/menopause (52 +/- 5 years) that ultimately leads to the no-less-real epiphenomena of aging, chronic disease, and death (Average Life Expectancy, as modulated by one's inherited genes, nationality, climate, nutrition, exercise, and life style (peace vs. war time, daily stress level, marriage, occupation, smoking, and other parameters of risk taking)).]

[ Editor's Note: After his talk, we asked our December Speaker, Dr. William A. Goddard, III, Charles and Mary Ferkel Professor of Chemistry, Material Science, and Applied Physics, and Director of the Materials and Process Simulation Center at CalTech to comment on how long he thought it might take us to understand the structure of the biochemical receptors on Embryonic Stem Cells that dictate how it could be that only 150 or so unique genes in mice that are not in humans, less than 1 percent leads them down an embryogenesis pathway to express the phenotype of "whiskers and tails" while we instead with a similar number of unique genes grow up without whiskers and tails but grow up to be six feet tall? He said, "That's a really tough problem (in comparison with what we've done during the last few years). It might take four or five additional years to figure that out!" We answered, "we'll check back with you in five years." ]
+++++++++++++++++++++++++++++++++++++++

The Mouse Genome Sequencing Consortium, "Initial Sequencing and Comparative Analysis of the Mouse Genome," Nature, Vol. 420, pp. 520-562 (December 5, 2002).

ABSTRACT:

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure, and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

Refs:

1. News Roundup, "Genetic Makeup of Mice Presents Insights for People," The Wall Street Journal, p. A1, D10 (December 5, 2002).
2. Rosie Mestel, "Of Mice and Men: We're Quite Similar, Genetically. Scientists Complete Map of the Rodent's Genome, Which Is Hailed As an Essential Research Tool," The Los Angeles Times, p. A1, 19 (December 5, 2002).
3. "Mice and Men Share 99 Percent of Their Genes," CNN (December 4, 2002)
4. Nicholas Wade, "At Genetic Frontier, the House Mouse Serves Humanity," The New York Times, p. D1, 3 (December 10, 2002).
5. For a Mouse Genome Informatics Database that compiles most information about the genetics of the standard laboratory mouse ( C57BL strain) click on The Jackson Laboratory in Bar Harbor, ME. This database has lists of known mouse genes and reports the work of nomenclature committees on how to refer correctly to mouse strains and provides an anatomical dictionary/browser ranging from fetogenesis to adulthood. The Fantom Consortium (Functional Annotation of the Mouse) has captured and decoded 61,000 transcripts (essentially the protein products of all the active genes in mouse cells). The Complex Traits Consortium's goal is to find out how mouse genes act in concert. So far, only about 5,000 genes have been mutated.by the International Mouse Mutagenesis Consortium. They plan to generate mouse strains with mutations in the remaining 25,000 genes soon. Lexicon Genetics, Inc. of Woodland, TX (North of Houston) has coverage for 59 percent of the genes that are active in stem cells. Lexicon is systematically disrupting genes in early embryonic stem cells to find out which embryos can then be grown into full pups and, therefore by complementarity, which mutations are lethal.
6. Elizabeth Pennisi, "Genomics: Sequence Tells Mouse, Human Genome Secrets," Science, Vol. 298, No. 5600, pp. 1863-4 (December 6, 2002).
7. Charley Rose PBS-TV Interview with Dr. Eric Lander, Director of the Whitehead Institute's Center for Genome Research at MIT (Monday, December 9, 2002; 11:30 PM PST).

Craig Venter Proposes to Develop an Artificial Organism

December 4, 2002; Drs. J. Craig Venter Director and Nobel-prize winner Hamilton Smith along with a 25-member team at the Institute for Biological Energy Alternatives in Rockville, MD were awarded a three-year $3 million dollar contract by the US DOE to design a novel form of life. They must produce a useful, self-replicating organism with a completely artificial genome capable of removing unwanted carbon or toxic materials from the environment or producing hydrogen for fuel.

Ref:

Eliot Marshall, "Venter Gets Down to Life's Basics," Science, Vol. 298, No. 5599, p. 1701 (November 29, 2002).

Lack of Stem Cells Slows Brain Repair in Huntington's Disease

November 30, 2002; Dr. Maurice A. Curtis of the University of Auckland in New Zealand has formulated a new hypothesis that there is an ongoing process of neurogenesis in all adult brains, which if not properly maintained leads to a global deficit, like Huntington's Disease. Proliferating Cell Nuclear Antigen (PCNA) which is a hallmark of dividing cells, along with a protein called Class III Beta-Tubulin, which is specific to nerve cells, is important in replenishing dead neurons. In Huntington's the brain apparently cannot generate new nerve cells fast enough to replace the dying ones.

Ref:

John Travis, "Slow Brain Repair Seen in Huntington's," Science News, Vol. 162, No. 21, p. 334 (November 23, 2002).

Upregulated p53 Mice Have Fewer Tumors - Normal Life Spans

November 30, 2002; A third copy of the endogenous p53 gene was inserted into mice who not only demonstrated enhanced activation of a p53 response to DNA damage, they developed significantly fewer tumors after exposure to carcinogens. Contrary to the findings at Baylor University in Houston, TX earlier this year, these super-p53 mice did not exhibit signs of premature aging. A good question would be, why didn't they exhibit a longer lifespan than controls, since mice are known for suffering a large number of tumors just before they die.

Refs:

1. Garcia-Cao, et al, EMBO Journal, Vol 21, No. 6225 (2002).
2. "Is More p53 Better?," Science, Vol. 298, No. 5597, p. 1301 (November 15, 2002).

Mechanism of CR Uncovered at Yale

November 29, 2002; As published in today's issue of Science, Rpd4, a histone deacetylase enzyme, is likely to be a key gene for longevity, according to Prof. Stewart Frankel of Yale University. Drosophila with lower levels of the enzyme lived [33 - 50] percent longer than controls. A CR diet leads to life extension of about 41 percent. The compound Phenylbutyrate is thought to target the Rpd3 enzyme and could be useful as a model for the development of drugs that inhibit this particular enzyme and provide benefits without having to endure the rigors of CR.

Blanka Rogina[1], Stephen L. Helfand[1], and Stewart Frankel[2]*,
"Longevity Regulation by Drosophila Rpd3 Deacetylase and Caloric Restriction,"
Science, Vol. 298, No. 5598, p. 1745 (November 29, 2002).
________________________
[1.] Department of Genetics and Developmental Biology,
School of Medicine,
University of Connecticut Health Center,
Farmington, CT 06030, USA;
[2.] Department of Pediatrics,
Boyer Center for Molecular Medicine,
Yale University School of Medicine,
295 Congress Avenue, New Haven, CT 06536, USA
. * To whom correspondence should be addressed:. E-mail: stewart.frankel@yale.edu.

ABSTRACT:

Genetic studies of single gene mutations are revealing mechanisms and pathways that regulate longevity across distant species (1). One such mechanism is an alteration in histone deacetylase activity. Abolishing expression of the Rpd3 deacetylase (2) or increasing expression of the Sir2 deacetylase (1) increases life-span in yeast; Sir2 mediates increased nematode longevity as well (1). Caloric restriction is an intervention that increases life-span in mammals, insects, nematodes, and yeast (1, 3). Although the molecular pathways underlying the response to caloric restriction are yielding to genetic analysis in yeast (1), there is little information on how this response is regulated in metazoans. We investigated the relationship between histone deacetylases, caloric restriction, and longevity in Drosophila.

Greatly reduced Rpd3 levels are lethal in Drosophila (4), but partial reduction of Rpd3 levels has not been evaluated for its effect on life-span. We found that males heterozygous for either a hypomorphic (partial loss-of-function) or null mutation of rpd3 have life-span extension of 33% and 41 to 47%, respectively (Fig. 1A). Females heterozygous for the hypomorphic allele have a 52% increase in life-span, whereas females carrying the null mutation have only modest changes in life-span (maximum but not median life-spans are increased). The presence of large increases in life-span for males carrying both types of allele indicates that the effect is specific to the rpd3 locus. The different results for females may indicate a greater sensitivity to the predicted lower levels of Rpd3 in individuals carrying the null mutation compared with individuals carrying the hypomorphic allele.

To further explore the parallels between life extension in yeast and Drosophila, we examined the effect of caloric restriction on normal-lived control and long-lived rpd3 mutants. Longevity is increased to approximately the same extent in control flies fed a low-calorie diet and rpd3 mutants fed a normal diet (Fig. 1B). In addition, caloric restriction of the rpd3 mutants shows no further extension of life-span (Fig. 1B). The lack of an additive increase in longevity is not due to a physiological cap for life-span extension, because rpd3 females that were kept as virgins did have a further extension of longevity [see (14) in supporting online material (SOM) (5)]. Furthermore, at least one other mutation in Drosophila, Indy, increases life-span to a greater extent (>90%) (6). It has previously been demonstrated that caloric restriction of flies leads to a moderate but significant down-regulation of Rpd3, analogous to the decreases obtained in heterozygotes carrying rpd3 mutations (7, 8). The data suggest that life-span extension by the rpd3 mutation is within a pathway related to caloric restriction.

Given the evidence connecting histone deacetylases to life-span extension, we wanted to determine whether Drosophila longevity was generally responsive to changes in histone acetylation. Increased acetylation (9) was achieved by mutating an independent locus, Su(var)2-101. This had virtually no effect upon life-span (5). The effects of Rpd3 therefore appear to be specific, mediated by its targeting to particular genes and/or histone residues. The life-span extension obtained by feeding the drug phenylbutyrate to adult Drosophila may operate by a similar mechanism (10).

Studies in yeast have implicated Sir2 as an important element in the life-extending effects of caloric restriction (1). We found that under our two life-extending conditions, rpd3 mutants fed normal food and wild-type flies fed low-calorie food, Sir2 expression was increased twofold (Fig. 1C). Our results highlight the conservation of longevity regulation across distant species boundaries and suggest a genetic pathway that begins with caloric restriction and proceeds to down-regulation of Rpd3, followed by Sir2-independent regulation of longevity effector genes (gene activation) and/or increased Sir2 levels and Sir2-dependent modulation of longevity effector genes (gene silencing).

Other Refs.:

1. CNN (November 27, 2002).
2. Reuters, "Enzyme May Be Key to a Longer Life," The Los Angeles Times, p. A37 (November 29, 2002).

First Human Clone To Be Born in January

November 26, 2002; Rome, ITALY (CNN) --
Dr. Severino Antinori, M.D. announced today that he with others will soon accomplish their goal of being the first to perform human cloning. A surrogate mother carrying a cloned baby is allegedly pregnant with a delivery date sometime next month (early January 2003) presumably in a country where it is not illegal. Three more surrogate mothers are also pregnant, and it is assumed that they will deliver at later dates. However, Dr. Antinori offered no proof for any of these extravagant claims.

Both Prof. Rudolf Janesch, Ph.D., of MIT and Robert Lanza, M.D., Vice President of Medical and Scientific Development of Advanced Cell Technology of Worcester, MA commented saying that Dr. Antinori is considered to be a fringe practitioner who has systematically ignored the warnings of the scientific community by conducting such irresponsible experiments apparently for his own personal edification.

The LA-GRG will prepare a detailed Editorial on the significance of this matter if and when Dr. Antinori and his anonymous colleagues publish their work in a respected, peer-reviewed scientific journal containing definitive DNA evidence to support their claims. The standard of proof for cloning was first established by Dr. Ian Wilmut when Dolly the sheep was cloned and DNA evidence was published in Nature shortly thereafter.

. Refs:

1. ABC-TV Local News, Tuesday, November 26, 2002; 4:00 PM PST.
2. CNN (November 27, 2002).
3. CNN (November 26, 2002).
4. Connie Chung, Interview, CNN (November 29, 2002).
5. Robin Marantz Henig, "Adapting to Our Own Engineering: Clones May Soon Be As Acceptable As Test-Tube Babies," Op-Ed Piece, The New York Times, p. A35 (December 17, 2002).
Antinori, Zavos, and the Raelians (Boisselier) are in a three-way race.

Stem-Cell Reviews in Curent Issue of JuveNews

November 25, 2002; JuveNews, published in the San Francisco Bay Area, provides current summaries on the biology of aging, youth, and rejuvenation. The Managing Editor is Mignon Fogarty, the Senior Science Editor is Dr. Gregory Frank, and the Business Editor is Brian Chiko. Click for more details .

Aging Linked to Apoptosis by Way of Sir-2 Gene

November 25, 2002; Prof. Leonard Guarente of MIT began studying a regulator gene called Sir2 in yeast more than 20 years ago. It is now known that Sir2 together with the vitamin co-factor NAD (strict dependence) deacetylases (removes an acetyl group from) a histone (a protein that binds to DNA) preventing transcription (silencing). Homologs of this gene are conserved in a variety of species from E. coli to C. elegans, to mice, and probably to humans. The NAD component is part of a feedback loop involving cellular mitochondria (metabolic rate). By the way, Caloric Restriction (CR) extends the lifespan of yeast and other organisms only so long as Sir2 products (Sirtuins) and NAD are both present. The human homolog of Sir2 is called Sirt1 and appears to prevent apoptosis in human cells by inhibiting the p53 gene that is heavily implicated in preventing cancer.

Ref:.

Jennifer Fisher Wilson, "Enzyme Role Found for Aging Gene: Two Labs Independently Discover the Mechanism for How Sir2 Extends Lifespan," The Scientist, Vol. 16, No. 22, pp. 36- 37 (November 11, 2002).

Stem Cells Repair Damaged Hearts

November 25, 2002; Experts estimate that 50 persons have received cell transplants in their hearts since the procedure was first attempted about ten months ago. There has been no reported uncorrectable toxicity, and many of the patients have improved significantly. Yet, no cause-and- effect relationship can be attributed to the stem-cell therapy, since these patients are generally very sick (with very low cardiac ejection fractions) and are undergoing a variety of interventions simultaneously, anyone of which could be responsible for their improvement. Dr. Francis Pagani of the University of Michigan, Dr. Philippe Menasche of the Georges Pompidou European Hospital in Paris, and Dr. Nabil Dib of the Arizona Heart Institute in Phoenix are all performing some of these trials on small numbers of patients, all of which leads to anecdotal reports of great promise. However, a major clinical trial must be started soon to gain acceptance for this treatment by the larger cardiology establishment. A planned trial involving 300 patients in Europe and North America will be performed under the direction of Dr. Manasche in Paris cosponsored by Genzyme Biosurgery, which developed the technique for growing the bone- marrow stem cells in culture. Hopefully, we will have some answers in about a year or so.

Ref:

Thomas H. Maugh, II, "For Damaged Hearts, Some Added Muscle," The Los Angeles Times, pp. F1,8 (November 25, 2002).

Human Clinical Trials of Caloric Restriction Planned by NIH

November 25, 2002; Dr. Donald K. Ingram, Acting Chef of the Laboratory of Experimental Gerontology at NIH has announced a multi-center trial of human Caloric Restriction to be conducted at Louisiana State University, Tuffs University in Massachusetts, and Washington University in St. Louis, Missouri Hopefully, we will establish a more rigorous means for determining whether a methodology that works for rodents and monkeys actually does work in people, given all the obvious constraints associated with human subjects in a long-term study. The only other rigorous investigation of human subjects was done by conscientious-objector volunteers during World War II that led us to the conclusion that such subjects become highly irritable and spent most of their time "reading cookbooks planing their meals for when the study would be over!"

Ref:

Bob Rosenblatt, "Eating Less for Longevity," The Los Angeles Times, pp. F1,4 (November 25, 2002).

Aging Well Runs in Families

November 22, 2002; Chicago, IL ( CNN); Children of centenarians are less likely to suffer from a number of cardiovascular diseases, according to a study presented Monday at the annual meeting of the American Heart Association. Click for more details .

VEGF Genetic Engineering for Angina

November 21, 2002; Chicago, IL (American Heart Association); In a clinical trial involving 71 patients with angina, injecting a Vascular Endothelial Growth Factor (VEGF) gene by way of an adenovirus (vector) into the heart muscle prompted patients to grow their own blood vessels and thereby bypass obstructed coronary arteries. However, opening the chest wall is such a traumatic surgical procedure by itself that a much less invasive technique threading a catheter into the heart for administration of the VEGF gene -- will be tried next.

Ref:

Ron Winslow, "Gene Therapy Bolsters Weak Heart," The Wall Street Journal (November 21, 2002).

Significant Side Effects in a Short-Duration Clinical Trial of hGH

November 13, 2002; Drs. Marc Blackman and Mitchell Harman have reported in today's issue of JAMA that Carpal Tunnel Syndrome, joint pain, swollen limbs, Diabetes Mellitus and other disturbances in blood sugar regulation appear at significantly higher rates than was previously expected under the controlled conditions of a 26-week clinical trial. The authors have therefore recommended that, for now, hGH for the elderly be restricted to rigorous clinical trials until more is known. However, Prof. Ronald Swerdloff of Harbor UCLA Medical Center said he has noticed "impressive improvements in the bodies and moods of growth-hormone-deficient patients after administration of hGH injections." On the other hand, he agrees that "although there could be substantial benefits to giving hGH to elderly patients, far more needs to be known before this treatment could be deemed safe for widespread use."

[ Editor's Note: Drs. Blackman, Harman, and Swerdloff have all been Guest Speakers to the GRG over the years.]

Refs:

1. Rosie Mestel, "Troubling Side Effects Found with Growth Hormone, The Los Angeles Times, p. A18 (November 13, 2002).
2. Marc R. Blackman, MD; John D. Sorkin, MD, PhD; Thomas M�nzer, MD; Michele F. Bellantoni, MD; Jan Busby-Whitehead, MD; Thomas E. Stevens, MD; Jocelyn Jayme, MD; Kieran G. O'Connor, MD; Colleen Christmas, MD; Jordan D. Tobin, MD; Kerry J. Stewart, EdD; Ernest Cottrell, BS; Carol St. Clair, MS; Katharine M. Pabst, CRNP, MPH; and S. Mitchell Harman, MD, PhD, "Growth Hormone and Sex Steroid Administration in Healthy Aged Women and Men: A Randomized Controlled Trial," JAMA,.Vol. 288, No. 18, pp. 2282-92 (November 13, 2002).

John Gearhart vs. Leon Kass on Stem Cells

The philosophical battle over stem-cell research (and cloning in particular) seems to be taking a nasty turn. In the most recent clash, prominent stem-cell scientist Prof. John Gearhart slammed bioethicist Prof. Leon Kass for suggesting that researchers who reject restrictions on research [therapeutic] cloning are "rogues and rascals." Kass is alleged to have said "The few rogues and rascals who won't live here [in the USA], we are well rid of." In rebuttal, Gearhart quoted Prof. Richard Feynman: "Philosophers say a great deal about what is absolutely necessary for science, and it is always, so far as one can see, rather naive and probably wrong."

Ref:

"Jabs on the Stem-Cell Front," Science, Vol. 298, No. 5596, p. 1169 (November 8, 2002).

U.N. Postpones Ban on Reproductive Cloning

November 8, 2002; France and Germany had recently urged the Legal Committee of the United Nations General Assembly to formulate a treaty to halt Human Reproductive Cloning immediately and take up a more controversial question regarding Therapeutic Cloning at a later time, but they were overruled by a U.S. end run that successfully postponed this urgently-needed ban for at least one more year. This maneuvering appears to be an instant replay of the US Senate Debate on the Brownback Bill earlier this year that led to a similar "stand off" with no laws passed at all. Conservative fundamentalists apparently prefer to see no laws regarding human cloning than to appear to endorse a distinction they find "morally abhorrent," i.e., Therapeutic Cloning, that might lead to the deliberate destruction of embryos, regardless of potential cures for Heart Disease, Cancer, Parkinson's Disease, or other degenerative diseases. [ Editorial Rhetoric: If a human embryo is to be considered a person (a tissue capable of being murdered), but obviously not a finger-nail clipping that can be safely disposed of without fear of prosecution, is having a period following intercourse (a "disappointed" uterus) the same as murder? Or is the "twinkle in a man's eye when he encounters a beautiful woman" the same as a person?]

Refs:

1. Maggie Farley, ""U.S. Puts Off U.N. Ban on Cloning," The Los Angeles Times, p. A3 (November 8, 2002).

The NEJM Prepares Physicians for Gene-Based Medicine

1. Harold Varmus, "Getting Ready for Gene-Based Medicine," The New England Journal of Medcine, Vol. 347, No. 19, pp. 1526-7 (November 7, 2002).
2. Alan E. Guttmacher and Francis S. Collins, "Genomic Medicine: A Primer," The New England Journal of Medicine, Vol. 347, No. 19, pp. 1512-20 (November 7, 2002).

Delta-1 Protein Amplifies Cord Blood Stem Cells by 14 Times in Culture

November 1, 2002; Researchers from the Fred Hutchinson Cancer Research Center and the University of Washington in Seattle have used a signaling protein in the notch pathway called Delta-1 to amplify stem-cell proliferation of CD34+CD38- lines without inducing premature differentiation by 14 times compared to controls. This cell line is important in transplantation work, since they're so primitive, they're less likely to induce GVH (Graft vs. Host) or rejection by host WBCs than more highly-differentiated cells might.

Refs:

1. Irwin D. Bernstein, et al., Journal of Clinical Investigation (October 15, 2002).
2. Nathan Seppa, "Blood Booster: Growth Signal Shifts Cord Stem Cell into High Gear," Science News, Vol. 162, No. 17, pp. 161-2 (October 26, 2002).

[ Editorial Remark: I don't wish to pour cold water on this new discovery, but we must try to put the announcement in better perspective. All regulatory gene products are proteins that cluster within the cell into serial/parallel networks (like an arrangement of dominos ready to fall over). They form long cascades as they fall, whenever triggered by a precise external stimulus, e.g., clotting is triggered by a cut in the integument or other lesion to our internal epithelium . Yet, the clotting cascade has more than a half-dozen factors that must all line up perfectly to accomplish the task. Organizing the genes and their products into ordered networks is critical to our understanding of the functions they accomplish and at which points interventions make sense and where they don't. "Delta-1" is just one protein that may participate in a complex pathway for proliferation/apoptosis. We need to know all the intracellular-communication signals that determine the architecture of a tissue/organ. Only then can we understand how to intervene in the process. Remember that there are "No old caterpillars," just as there are "No old tadpoles." The genetic machinery for butterflies (following Juvenile Growth Hormone and Metamorphosis/Chrysalis Formation) and frogs (following another sort of transformation), respectively, are all in place "waiting in the wings" as it were, waiting to trigger the next stage in the Life History of the organism.. When the complete human proteome is completed (sadly, we currently know much less than half of the tinker-toy pieces that Nature uses) in the next few years, then we should revisit this problem and find out who the companions of Delta-1 are, as well as its inhibitors and how they interact, before we can be confident that we understand what's going on.]

Oldest American Dies at Age 113

October 31, 2002;

Mary L. Parr, believed to be the oldest person in the US and second-oldest in the world, died Tuesday at a retirement community in St. Petersburg, FL at age 113. For more details on her successor(s), please see Table E in the Centenarian Section of this website.

Ref:

AP, "Mary L. Parr, 113; Said to Be Oldest Resident of U.S.," The Los Angeles Times, p. B17 (October 31, 2002).

Sarcopenia Occurs in Old Nematodes

October 30, 2002; C. elegans wiggle around vigorously until midlife (around [6 - 7] days) after which an ominous decline begins. By old age (around [12 - 18] days), even a needle prod elicits only ineffective twitches. Now scientists at Rutgers State University of New Jersey and the Albert Einstein College of Medicine in New York have verified that it's not the nervous system that goes bad as a function of age; it's the muscle cells themselves. This muscle weakness ( sarcopenia) is related to the muscle fibers that under the electron microscope are normally bundled together neatly but with old age become disorganized. What process obliterates the normal architecture with age has yet to be identified.

Profs. Caleb Finch of USC and Thomas Kirkwood of the University of Newcastle upon Tyne in England warn that adult worms, unlike humans, don't have mitotic cells in adulthood (except for the germ line). Human skeletal muscle can be replenished by so-called "satellite cells" under certain circumstances such as trauma. Therefore, the model of muscle wasting in C. elegans may not be relevant to human aging. But then again it just might, and for C. elegans we have the complete genome and cellular embryonic-lineage or fate map to work with.

Refs:

1. Monica Driscoll, et al., Nature (October 24, 2002).
2, "for Worms, It's a Crisis of Movement in Midlife," The Los Angeles Times, p. A17 (October 26, 2002).
3. "Aging Nematodes Tell How Muscles Deteriorate," The New York Times, p. D3 (October 29, 2002).
4. John Travis, "Outmuscled: Muscles, not Nerve Cells, Fail on Old Worms," Science News, Vol. 162, No. 17, pp. 260-1 (October 26, 2002).

Genetic Profile of Mouse Embryonic and Adult Stem Cells

October 28, 2002; Researchers at Harvard University and Princeton University have identified a cluster of 216 genes that are enriched in all three classes of mouse stem cells (embryonic, neural, and hematopoietic).

Refs.

1. Miguel Ramalho-Santos [1], Soonsang Yoon [2], Yumi Matsuzaki[2], Richard C. Mulligan [2], and Douglas A. Melton [1]*, "'Stemness': Transcriptional Profiling of Embryonic and Adult Stem Cells," Science, Vol. 298, No. 5593, pp. 597-600 (October 18, 2002).

ABSTRACT:

The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells. A total of 216 genes are enriched in all three types of stem cells, and several of these genes are clustered in the genome. When compared to differentiated cell types, stem cells express a significantly higher number of genes (represented by expressed sequence tags) whose functions are unknown. Embryonic and neural stem cells have many similarities at the transcriptional level. These results provide a foundation for a more detailed understanding of stem-cell biology.

[1] Department of Molecular and Cellular Biology and Howard Hughes Medical Institute (HHMI), Harvard University, Cambridge, MA 02138, USA.
[2] Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
* To whom correspondence should be addressed. E-mail: dmelton@mcb.harvard.edu.

__________________________________

2. Natalia B. Ivanova, John T. Dimos, Christoph Schaniel, Jason A. Hackney, Kateri A. Moore, and Ihor R. Lemischka*, "A Stem Cell Molecular Signature," Science, Vol. 298, No. 5593, pp. 601-604 (October 18, 2002).

ABSTRACT:

Mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. We determined global gene expression profiles for mouse and human hematopoietic stem cells and other stages of the hematopoietic hierarchy. Murine and human hematopoietic stem cells share a number of expressed gene products, which define key conserved regulatory pathways in this developmental system. Moreover, in the mouse, a portion of the genetic program of hematopoietic stem cells is shared with embryonic and neural stem cells. This overlapping set of gene products represents a molecular signature of stem cells.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
* To whom correspondence should be addressed: E-mail: ilemischka@molbio.princeton.edu.

Anti-Aging Medicine: What if the Rate of Aging Were Slowed?

October 25, 2002;

"I don't want to achieve immortality though my work;
I want to achieve immortality by not dying." - Woody Allen

"The truth is that no treatments have been established to to delay, postpone, stop, or reverse aging."
---- Robert Butler, M.D., Member of the Editorial Board of Focus on Healthy Aging.

The life expectancy of a hypothetical 50-year-old American woman today is 81. If somehow cancer, cardiovascular disease, and diabetes were all simultaneously cured overnight, life expectancy would extend for this woman to just 97 years. On the other hand, if the aging process itself were somehow slowed (equivalent to a caloric restriction dietary regime as has been done in rats from birth resulting in a 40 percent increase) then life expectancy would rise to 113 years.

Refs:

1. "You Can't Turn Back the Hands of Time, But You Can Take Many Proven Steps to Live a Longer, Healthier Life," Focus on Healthy Aging: Maintaining Health and Vitality in Middle Age and Beyond, Vol. 5, No. 11, pp. 1, 6 (November 2002).
2. S. Jay Olshansky, Bruce A. Carnes, and Christine I. Cassel, Science, Vol. 256 (1990).

Stem Cells Used to Target Glioblatomas in Mice

October 15, 2002; As reported in today's issue of the journal Cancer Research, scientists at Cedars Sinai Medical Center in Los Angeles injected the brains of mice engineered to have have brain tumors with neural stem cells genetically modified to contain Interleukin-12 (IL- 12), a tumor-killing immune-derived protein. Thirty percent of the treated mice remained cancer free for the long-term, while all the mice in the control group died very quickly.

Ref.

Peter Landers, "Stem Cells Used to Kill Tumors in Brains of Mice," The Wall Street Journal, pp. A1, D1, 3 (October 15, 2002).

2002 Nobel Prize for Medicine for Work on C. Elegans

October 8, 2002; We are pleased to announce that Professor Sydney Brenner of the Salk Institute in La Jolla, California -- along with two of his colleagues Drs. John E. Sulston of the Sanger Centre in England and H. Robert Horvitz of MIT -- has received the 2002 Nobel Prize in Physiology or Medicine. One Million Dollars will be shared equally among the recipients!

Dr. Brenner, long credited with being the brightest scientist who wasn't a Nobel Laureate, today is no longer able to claim that distinction. Born to an illiterate Lithuanian cobbler in Germiston, South Africa in 1927, Brenner worked with Francis Crick at Cambridge on fundamental DNA/Amino Acid coding for many years and now is working with him again at The Salk. More recently, he has argued persuasively for sequencing the DNA of the Puffer fish ( Fugu rubripes) as a model/surrogate for the human genome, due to its remarkably parsimonious sequence (having comparatively little "junk" DNA compared to mammals).

[ Editor's Note: In my view, Brenner's greatest accomplishment was his exhaustive analysis of the embryogenic Fate Map (or Lineage Map) of the microscopic nematode Caenorhabditis elegans that takes a fertilized egg from a single cell to an adult organism of precisely (1,090 - 131) = 959 cells and shows graphically the complete annotated set of daughter cells in each generation. This is the blueprint for the 3-D architecture of a worm. The 131 deleted cells are the scaffolding that is subsequently removed by apoptosis once the organism is complete, sort of like the webbing in between our fingers and toes that are dissolved to expose five digits during the course of limb formation. (The final number deliberately neglects the germ-line cells [eggs/sperm] which are quite variable from one worm to the next. By the way, another complexifying factor is that this particular worm is hermaphroditic, so the sexual interaction among individuals is opportunistic, depending on environmental conditions.)

Brenner went on to identify the nematode genes involved in the apoptosis of these 131 cells (ced-3, ced-4, and ced-9 [Human counterpart is Bcl-2]), giving us a handle on the gene network or motif for Programmed Cell Death (PCD).

At age 75, Brenner did not rest on his laurels. He is taking nematode genes one-at-a-time and putting them into mice to discover what their function might be. I consider this to be one of the most innovative methodologies in biology today, and I don't know of anyone else who is doing this critical work of going from genotype to phenotype using this approach. Undoubtedly, the outcome of this research will someday shed light on the processes of aging and senescence.]

Refs:

0. Click for www.nobel.se in Sweden.
1. Thomas H. Maugh, II, "'Suicide Cell' Work Earns Trio a Nobel: Biologist at Salk Institute in La Jolla Shares Prize in Medicine/Physiology," The Los Angeles Times, pp. A1, 22 (October 8, 2002).
2. Denise Gellene, "Idun Hopes Nobel Attracts Financing: The San Diego Firm is Optimistic that the Award to Its Founder Will Increase Backing of Its Cell-Death Research. But Isn't a Sure Bet," The Los Angeles Times, pp. C1, 14 (October 8, 2002).
3. Idun Pharmaceuticals, a privately held company is San Diego, was co-founded by Dr. H. Robert Horvitz. The company, by the way, is named for the Norse goddess of Eternal Youth. (Click for more details).
4. "The Nobel in Medicine went to Britons Sydney Brenner and John Sulston and American H. Robert Horvitz for Research on Organ Growth and Cell Death that Has Opened Paths to Combating Cancer and Other Diseases," The Wall Street Journal, p. A1 (October 8, 2002).
5. Lawrence K. Altman, "Three Win Nobel for Work on Suicidal Cells," The New York Times, pp. A1, 23 (October 8, 2002).
6. "Gene Scientists Scoop Nobel Prize," CNN (October 8, 2002).
7. Jean Marx, "Nobels Run the Gamut from Cells to the Cosmos," Science, Vol. 298, No. 5593, p. 526-8 (October 18, 2002).
8. J. Travis, "Nobel Prizes Honor Innovative Approaches," Science News, Vol 162, No. 15, p. 229 (October 12, 2002).
9. Hal Cohen, "In Focus: 2002 Nobel Winners," The Scientist, Vol. 16, No. 21, p. 24 (October 28, 2002). 10. "Nobel Prizes for 2002," Scientific American, Vol. 287, No. 6, p. 37 (December 2002).

Stem-Cell Research Funding for State of California

September 22, 2002; Governor Gray Davis is expected today to sign into law California Senate Bill 253 authored by Sen. Deborah V. Ortiz (D - Sacramento) to create a review process for stem-cell research and pave the way for the State Government to shift some of its biomedical research funds toward this new emerging field. "Stem-cell research is responsible research that could potentially save millions of lives," Davis said in written statement. "I am determined to keep California at the forefront of medical research and scientific innovation."

"Paralyzed actor Christopher Reeve is scheduled to join Davis in a conference call following the bill signing," officials said.

Refs:

1. Gregg Jones, "Bill Boosting Stem-Cell Research To Be Signed," The Los Angeles Times, pp. B1, 6 (September 22, 2002).
2. Aaron Zitner, "White House Criticizes State Stem-Cell Law," The Los Angeles Times, p. B6 (September 24, 2002).
[California is the first state to pass a law supporting stem-cell research. On the other hand, Iowa, Michigan, and South Dakota have already passed legislation to ban embryo research or cloning within their borders. "President Bush believes that all policies, state or Federal, need to respect the 'culture of life,'" said Art Fleischer, speaking for the President. "The President differs with Governor Gray Davis on this."
A University of California Discovery Grant Program administered by Prof. Suzanne Huttner, Associate Vice Provost for Research at UC Berkeley, will solicit Research Proposals from 10,500 California stem-cell scientists soon. The program administers a $24.6 million fund.]
3. CNN Health and Reuters (September 22, 2002).
4. California Healthcare Institute, which represents bioscientists and the biomedical industry..
5. "California's Governor Signed Legislation to Allow Stem-Cell Research in the State on Donated Embryos from Fertility Clinics," Wall Street Journal, p. A1 (September 23, 2002).
[This is a challenge to funding restrictions President Bush imposed on cell lines permitted for such use.]
6. Barbara Feder Ostrov, "Davis Signs Nation's First Stem-Cell Bill: Action Sets Up Conflict with the U.S.," San Jose Mercury News (September 23, 2002).
7. Text of State of California Senate Bill 253 which is scheduled to become law in California on January 1, 2003.
8. "Interview with Christopher Reeve," Larry King Live; CNN-TV, 9:00 PM PDT; Monday, September 23, 2002; TRT= 1 hour).
9. "Interview with Christopher Reeve," ABC-TV, 10:00 PM PDT, Friday, September 20, 2002; TRT = 30 minutes.
10. "Christopher Reeve Documentary,: PBS-TV, 10:00 PM PDT, Wednesday, September 18, 2002; TRT = 1 hour.
11, Christopher Reeve, Nothing Is Impossible: Reflections on a New Life (Random House; ISBN: 0375507787; 2002).

High Rate of Hidden Genetic Abnormalities in Cloned Mice

September 13, 2002; Prof. Rudolf Jaenisch of the MIT Whitehead Institute and Ryuzo Yanagimachi of the University of Hawaii published in this week's Proceedings of The National Academy of Sciences, USA on genetic abnormalities in cloned mice. Apparently, 50 percent of the genes involved in "imprinting" are not correctly expressed. (During the imprinting process, only the copies of a gene contributed by the father are active.) This 50 percent error rate was uncovered using a 10,000-gene-chip microarray analysis.

Several cloning researchers have said that "cloned livestock such as cattle, sheep, and pigs are normal and healthy if only they get past birth." However, Jaenisch believes that genetic abnormalities will be found even in these seemingly normal animals, even if some of these abnormalities are not lethal.

Refs.

1. Reuters, "Genetic Mutations Are Part of Cloning Process, Scientists Find Abnormalities in Engineered Mice Explain High Fatality Rates. Dangers of Human Trials Are Highlighted," The Los Angeles Times, p. A38 (September 13, 2002).
2. David Humpherys * [{dagger}] , Kevin Eggan * [{dagger}] , Hidenori Akutsu [{ddagger}] , Adam Friedman *, Konrad Hochedlinger *, Ryuzo Yanagimachi [{ddagger}] , Eric S. Lander * [{dagger}] , Todd R. Golub * [] , and Rudolf Jaenisch * [{dagger}] ||,
"Abnormal Gene Expression in Cloned Mice Derived from Embryonic Stem Cell and Cumulus Cell Nuclei,"
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.192433399

*Whitehead Institute for Biomedical Research and
[{dagger}] Department of Biology,
Massachusetts Institute of Technology,
9 Cambridge Center,
Cambridge, MA 02142;
[{ddagger}] Department of Anatomy and Reproductive Biology,
John A. Burns School of Medicine,
University of Hawaii,
Honolulu, HI 96822;
[] Department of Pediatric Oncology,
Dana-Farber Cancer Institute,
Boston, MA 02115; and
Department of Pediatrics,
Harvard Medical School,
Boston, MA 02115

Contributed by Eric S. Lander, July 22, 2002

ABSTRACT:

To assess the extent of abnormal gene expression in clones, we assessed global gene expression by microarray analysis on RNA from the placentas and livers of neonatal cloned mice derived by Nuclear Transfer (NT) from both cultured embryonic stem cells and freshly isolated cumulus cells. Direct comparison of gene expression profiles of more than 10,000 genes showed that for both donor cell types [{approx}] 4 percent of the expressed genes in the NT placentas differed dramatically in expression levels from those in controls and that the majority of abnormally-expressed genes were common to both types of clones. Importantly, however, the expression of a smaller set of genes differed between the embryonic stem cell- and cumulus cell-derived clones. The livers of the cloned mice also showed abnormal gene expression, although to a lesser extent, and with a different set of affected genes, than seen in the placentas. Our results demonstrate frequent abnormal gene expression in clones, in which most expression abnormalities appear common to the NT procedure whereas others appear to reflect the particular donor nucleus.

||To whom reprint requests should be addressed. E-mail: jaenisch@wi.mit.edu.

Genetics of Mouse Stem Cells Profiled

September 13, 2002, Cambridge, MA; Click for details.

American Life Expectancy Reaches 76.9 Years

September 13, 2002; Statistics just released from the Centers for Disease Control and Prevention in their annual report for CY 2000 (from the National Center for Health Statistics) reveal that American men born today will live to 74 and American women to nearly 80 years. However, the medical-care racial gap persists and adults are considerably heavier. Obesity is destined to become the Number One epidemiological public-health-care problem, after smoking, for all Americans. On the other hand, for selected teenage demographic groups [e.g., black men 15 - 24], homicide is the Number One cause of death. The major advances in life expectation over the last century (47.3 years in 1900) can be attributed to a sharp reduction in infant mortality (better obstetrical technique with C-sections routinely used for complications of pregnancy), reduction in the rate of fatal bacterial infections due to antibiotic therapy, lower rates of accidents per capita, lower rates of cancer (except for lung cancer), and lower incidence of heart disease. On the other hand, the "low hanging fruit" has already been picked (public sanitation, water, and sewage treatment), and we should not expect to see the same sort of advances in the present century that we witnessed in the last unless we address the "problem of aging" itself.

Refs:

1. CNN (September 13, 2002).
2. Rosie Mestel, "Life Expectancy Hits 76.9 in U.S.; Health Costs Soar," The Los Angeles Times (September 13, 2002).

U.K. Stem Cell Bank Under Development

September 10, 2002; London, UK ( AP) The British Institute for Biological Standards and Control, a publicly-funded group, was awarded a contract to set up and manage the new stem-cell bank. Embryonic stem-cell research is moving into high gear in England.

Refs:

1. "U.K. Advances Stem-Cell Bank," The Wall Street Journal, p. D3 (September 10, 2002).
2. Gautam Naik, "Britain Hopes Stem-Cell Bank Will Aid Treatment of Diseases," The Wall Street Journal, p. D4 (September 12, 2002).

Embryonic vs. Adult Bone-Marrow Stem Cells

September 9, 2002; Washington, D.C. ( AP) As published in the latest issue of Science, Profs. Irving Weissman, M.D. and Amy J. Wagers of Stanford University have uncovered some potentially disappointing news that certain adult bone-marrow stem cells appear to be limited in their capabilities to synthesizing blood-line cells only and not all the cells of the body as had been suspected by other investigators. Other kinds of bone-marrow stem cells like stromal or mesenchymal stem cells may be cabable but were not tested by the Stanford group. Click the image above for the Science Abstract from Stanford Medical School and for more details from CNN.

However, "important new evidence that human stem cells can be implanted and become part of muscle tissue suggests that Muscular Dystrophy may yet become treatable," said Dr. Louis Kunkel of Children's Hospital in Boston.

Refs:

1. Nicholas Wade, "Hopes Raised of Using Stem Cells for Treating Muscular Dystrophy," The New York Times, p. D7 (September 10, 2002).
2. AP, "Stem Cells May Treat Muscular Dystrophy," The Los Angeles Times, p. A10 (September 10, 2002).

Human Adult Stem Cells Aid Recovery Post Heart Attack

September 3, 2002; German Scientists reported in today's issue of the Journal of the American Heart Association entitled, Circulation, that they have retrieved adult stem cells from human bone marrow that were inserted into infarcted (damaged) heart tissue and coronary arteries using a balloon-angioplasty technique .for [2 - 4] minutes [6 - 7] times per patient. This technique succeeds over IV injection, since these cells would be likely to home in on other organs in the body and therefore be wasted.

Ref:

Ron Winslow, "Stem Cells Aid Heart-Attack Recovery," The Wall Street Journal, pp. A1, D3 (September 3, 2002).

Human Anti-Bodies Produced in Cloned Calves

September 1, 2002; Researchers at Hematech of Westport, CT and Sioux Fall, SD and Japan-based Kirin Brewery Company say they used a proprietary cloning technique to produce four calves that express a human chromosome fragment coding for a range of human antibodies. The research was the result of an ongoing joint effort to develop a system for human polyclonal antibody-based therapeutics.

Ref:

Inside Industry, "Human Antibodies Produced in Cloned Calves," Genetic Engineering News, Vol. 22, No. 15, p. 85 (September 1, 2002).

Geron Corp. Announces Telomerase Vaccine for Prostate Cancer

August 28, 2002; David Greenwood, Geron's CFO told the press, "Cancer vaccines are an important development on the horizon, and this immune-system-based treatment (patient inoculation with fragments of the telomerase protein) is another potentially very effective way to interrupt telomerase activity." Geron's stock rose 15 percent (59 cents to $4.44) on the news that Geron had applied for a U.S. patent for this technology.

Ref:

Bloomberg News, "Geron Gains on Cancer Therapy," The Los Angeles Times, p. C2 (August 28, 2002).

Oldest Person in the U.S. Dies at Age 114

August 24, 2002;

Mrs. Adelina Domingues, recently accepted as the oldest living American at 114 years old, has died. We have just learned from her grand-daughter that Mrs. Domingues died on Wednesday, August 21, 2002 at 1:30 PM PDT of congestive heart failure at the San Diego nursing home in Spring Valley, CA where she lived. She was born February 19, 1888 in Brava, Cape Verde Islands (off the coast of West Africa). After her marriage, she moved to Massachusetts in 1907.

Adelina attributed her longevity to her daily regimen of eating vegetables and beans and her life-long abstinence from any form of alcohol or tobacco. But she also thought she lived longer because she "never played cards or went to a beauty parlor," something she was very proud of. She was also an expert seamstress.

Ref:

Tony Perry, "Adelina Domingues, 114; Oldest Person in the U.S.," The Los Angeles Times, p. B20 (August 24, 2002).

PPL Therapeutics Clones Double Knock-Out of Porcine GGTA-1 Gene

August 23, 2002; London, UK (AP); Pigs normally synthesize alpha-1,3 galactose sugar molecules on the surface of every cell of every tissue of every organ in their bodies. Unfortunately, this is a signature trigger for the human immune system to commence a massive rejection of any foreign tissue xenograph of a porcine organ, which might otherwise be just the right size, shape, and functionality to replace a defective human organ. PPL Therapeutics, PLC of Blacksburg, VA had succeeded in knocking out one of the two copies of the GGTA-1 gene that makes this sugar but not both. Now they've knocked out both in four different pigs, born on July 25th. Interestingly, about 70 percent of the "knockout" work was funded by the Federal Government. Human clinical studies could begin from two to four years from now. [ Editor's Note: There may be other so-far unknown characteristics of porcine surface antigens that are specific for pigs and not humans that may trigger a more smoldering human killer T-cell immune rejection. This is obviously a stepping stone until we get this foreign-antigen rejection problem nailed down.]

Refs:

1. Gautam Naik, Cloned Piglets May Aid Organ Hunt: PPL Therapeutics Makes Gain in Effort to Improve Transplants' Success Rate," The Wall Street Journal, pp. A1, 8 (August 23, 2002).
2. AP, "Pigs Stripped of Rejection Gene: Cloning Project Seeks to Make Animal Organ Transplants Viable for Humans," The Los Angeles Times, p. A12 (August 23, 2002).
3. Emma Ross, "Cloning Case Seen as Step for Pig Organs in Humans," The Denver Post, pp. 1A, 7A (August 23, 2002).

TIGR To Open Diagnostic Center to Decode Human DNA

August 14, 2002; Dr. J. Craig Venter, former CEO of Celera Genomics, unveiled plans today to open a diagnostic research center associated with The Institute for Genomic Research (TIGR) in Rockville, MD that will be able to decode a person's DNA in seconds for a cost of about $1,000. This process now takes months and costs millions of dollars. Making such a test widely available could help physicians predict what diseases a patient may face and treat medical problems before they arise.

Ref.:

Lanham, MD ( AP) "Scientist Plans Lab to Map Genes Swiftly and Inexpensively," The Los Angeles Times, p. A13 (August 16, 2002).

Critics Lament the State of US Stem-Cell Research, But Japanese Make Progress

August 9, 2002; A study done by researchers at three Japanese universities (Kansai Medical in Osaka, Kurume School of Medicine, and Jichi Medical School in Tochigi) have published in the current issue of The Lancet that implanting autologous stem cells in the damaged limbs of patients with vascular disease can trigger angiogenesis. In the main study, 16 of the 20 patients no longer experienced pain while sitting down. X-rays before and after the stem-cell implantation showed increased blood-vessel networks in 27 of 45 recipients.

On the other hand in the US, even one year after President Bush's decision to make more than 60 different Stem-Cells Lines from around the world available to clinical researchers through NIH, very little actual progress has been made.

Refs:

1. AP, "Stem Cell Implants Boost Circulation, Study Finds," The Los Angeles Times, p. A4 (August 9, 2002).
2. Elizabeth Cohen, CNN Medical Unit, CNN (TRT = 2.5 min.; 2:45 PM PDT Friday, August 9, 2002).

Stem Cells and Macular Degeneration

August 6, 2002; As will be reported in by a team from Scripps Institute in La Jolla, California in the September issue of Nature Medicine, adult bone-marrow cells can stimulate the formation of blood vessels in the retina of mice with an induced disease that mimics the "wet form" of age-related macular degeneration. In related work at the University of Florida in Gainsville, reported in the June issue of Nature Medicine, stem cells appear to migrate to the site of injury in induced diabetic retinopathy.

Ref:

N. Seppa, "Retina Rescue: Adult Stem Cells Form Blood Vessels," Science News, Vol. 162, No. 5, pp. 69-70 (August 3, 2002).

Mouse Genome Now Free on the Internet

August 4, 2002; Los Angeles, CA (CNN/AP) -- An international team has completed the most comprehensive map ever of the genetic code of the mouse, an accomplishment that will make this laboratory animal more useful to scientists studying human health and disease.

Details appear Monday in the On-line Edition of the journal Nature. The map is available for public review on the Internet...

Direct link to Nature..

Nature AOP, published On-line August 4, 2002; doi10.1038/nature00957

A Physical Map of the Mouse Genome

ABSTRACT:

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.
_________________________________________________________________

Refs:

1. CNN.
2. "Map of the Mouse Genome," The Wall Street Journal, p. A1 (August 5, 2002).

Caloric Restriction May Work for Humans

August 2, 2002; In today's issue of Science, Dr. George Roth and colleagues of the NIA, published the result that CR may help people, not just rodents and monkeys. See CNN for more details.

George S. Roth, Mark A. Lane, Donald K. Ingram, Julie A. Mattison, Dariush Elahi, Jordan D. Tobin, Denis Muller, and E. Jeffrey Metter, "Biomarkers of Caloric Restriction May Predict Longevity in Humans," Science, Vol 297, No. 5582 (August 2, 2002).

National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.

From the first paragraph...

"The most robust intervention for slowing aging and maintaining health and function in animals is dietary caloric restriction (CR) Although most studies of this phenomenon have been conducted in rodents and lower animals, data accumulating from rhesus monkeys suggest that CR may also be relevant for primates, including humans. These findings include CR-induced attenuation of age changes in plasma triglycerides and melatonin as well as oxidative damage and glucose tolerance. Current mortality data from our ongoing studies in rhesus monkeys, although not yet statistically significant, reveal that mortality in CR monkeys is about half of that observed in controls (15 percent compared with 24 percent, respectively)"

Embryonic and Other Types of Stem Cells Show Great Promise

July 31, 2002; Discoveries regarding Embryonic Stem Cells (ESC) have kindled excitement about the possibility of using an array of cells to rebuild damaged nerve tissue in a variety of neurodegenerative disease, including Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Spinal Cord Injury, and Alzheimer's Disease (AD).

Ref:

Constance Holden, "Versatile Cells Against Intractable Diseases," Science, Vol. 297, No. 5581, pp. 500-2 (July 26, 2002).

Optimism May Mean Longer Life

July 29, 2002; According to the August issue of the Journal of Personality and Social Psychology published by the American Psychological Association, the Ohio Longitudinal Study of Aging and Retirement, researchers studied 660 residents of a small town in Ohio and found that those with positive attitudes lived 7 1/2 years longer than those with negative views (22.6 vs. 15 years, respectively). 338 men and 322 women ages [50 - 94] were recruited back in 1975. The study conducted by Yale University researchers was funded by the National Institute on Aging.

Refs:

1. Janee Allen, "A Positive Outlook on Aging May Mean a Longer Life," The Los Angeles Times, p. S3 (July 29, 2002).
2. CNN (July 29, 2002).
3. B. Bower, "Staying Alive with Attitude: Beliefs about Aging Sway Seniors' Survival," Science News, Vol. 162, No. 4, p. 53 (July 27, 2002).

UCSD Scientists Block Heart Disease in Hamsters Using Gene Therapy

July 22, 2002; According to today's issue of Nature Medicine, the gene for phospholamban, a regulatory protein that controls Calcium entry into heart muscle, delivered by an AAV (Adenoassociated Virus) Vector penetrated 60 percent of the myocytes in hamsters with heart disease.

Refs:

1. Ron Winslow, "New Gene Therapy Halts Progression of Heart Failure," The Wall Street Journal, pp. A1, B6 (July 22, 2002).
2. S. Milus, "For Failing Hearts: Gene Therapy Stops Decline in Animals," Science News, Vol. 162, No. 4, p. 54 (July 27, 2002).

Generic Human Embryonic Stem Cells Are Not "Self," As Far As the Immune System Is Concerned

July 12, 2002; Human ES Cells do *not* get a free pass form the immune system, contrary to the earlier wishful thinking of some of our colleagues; MHC antigenic proteins help identify these cells as invaders to Natural Killer white-blood cells, while their rate of rejection increases with differentiation. Teratoma cells and "HeLa" cells were used to calibrate the intensity of the immune rejection. It is speculated that a proposal to modify ES Cells so that they would not express MHC proteins might make them more susceptible to infection or more tumorogenic, so that approach might not be the answer either. ES cells derived from autologous nuclear transfer techniques (cloning) might also lead to rejection, since embryonic antigens could still be considered "non-self." However, prior in vitro differentiation and amplification into needed adult cells before being injecting the cells into a donor diagnosed as lacking that type of cell would be more likely to be "immune privileged." .

Refs:

1. Gretchen Vogel, "Stem Cells Not So Stealthy After All," Science, Vol. 297, No. 5579, pp. 175-6 (July 12, 2002).
2. Published online before print July 11, 2002
Cell Biology
Micha Drukker * [1] , Gil Katz * [2] , Achia Urbach [1] , Maya Schuldiner [1] , Gal Markel [2] , Joseph Itskovitz-Eldor [3] , Benjamin Reubinoff [4], Ofer Mandelboim [2, 5], and Nissim Benvenisty [1, 5]
"Characterization of the Expression of MHC Proteins in Human Embryonic Stem Cells,"
Proc. Natl. Acad. Sci. USA
1. Department of Genetics, Silberman Institute of Life Sciences, Hebrew University, 91904 Jerusalem, Israel;
2. The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Hebrew University, 91120 Jerusalem, Israel;
3. Department of Obstetrics and Gynecology, Rambam Medical Center, Faculty of Medicine, The Technion, Haifa 31096, Israel; and
4. The Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, 91120 Jerusalem, Israel
___________________
Communicated by Philip Leder, Harvard Medical School, Boston, MA, May 17, 2002
(received for review March 13, 2002)

ABSTRACT:

Human embryonic stem (ES) cells are pluripotent cells that may be used in transplantation medicine. These cells can be induced to differentiate into cells from the three embryonic germ layers both in vivo and in vitro. To determine whether human ES cells might be rejected after transplantation, we examined cell surface expression of the MHC proteins in these cells. Our results show very low expression levels of MHC class I (MHC-I) proteins on the surface of human ES cells that moderately increase on in vitro or in vivo differentiation. A dramatic induction of MHC-I proteins was observed when the cells were treated with IFN- [{gamma}] but not with IFN- [{alpha}] or -á. However, all three IFNs induced expression of MHC-I proteins in differentiated human ES cells. MHC-II proteins and HLA-G were not expressed on the surface of undifferentiated or differentiated cells. Ligands for natural killer cell receptors were either absent or expressed in very low levels in human ES cells and in their differentiated derivatives. In accordance, natural killer cytotoxic assays demonstrated only limited lysis of both undifferentiated and differentiated cells. To initiate a histocompatibility databank of human ES cells , we have isotyped several of the published ES cell lines for their human leukocyte antigens. In conclusion, our results demonstrate that human ES cells can express high levels of MHC-I proteins and thus may be rejected on transplantation
. ________________________________
*M.D. and G.K. contributed equally to this work.
5. To whom reprint requests should be addressed:
E-mail: nissimb@mail.ls.huji.ac.il; oferman@md2.huji.ac.il

Editorial on Polio Virus Synthesized from Raw Nucleotides

July 12, 2002; Unfortunately, in today's issue of Science, a DoD/DARPA-sponsored experiment to demonstrate the feasibility of synthesizing a human pathogen from raw DNA-sequence data (publicly available on the Internet) has now been published. The methodology does not appear to be technically difficult, involving an equipment-investment on the order of several hundred thousand dollars and only a few months of full-time effort by a single student biochemist. Raw nucleotide sequences can be purchased from commercial-supplier catalogs with a cashier's check and sent by UPS or even standard mail-order to a P.O. Box with complete deniability on the part of the purchaser's agent(s) without an audit trail.

More importantly, the method described is general-purpose and is not restricted to the Polio Virus (Single-Stranded ssRNA = 7.741 KBases), which is one of the few human pathogens for which most of us already have immunity (for example, Salk or Sabin Oral Vaccine in childhood). To ensure that the laboratory-synthesized Polio Virus would be distinguishable from a wild-type virus (which has now been officially eradicated from Europe as well as North America) in case it escaped into the environment during animal testing, the researchers distributed 19 unique markers (point mutations) in the sequence as a sort of "fingerprint." Although these markers weren't expected to alter the pathogenicity of the virus, the synthetic version was, in fact, less toxic since a dose of [1,000 - 10,000] times more viruses were needed to actually kill a mouse. Don't forget that this work was being carried out at a university, not at a CDC- or Fort Detrick, MD-level containment facility. For reference, the Smallpox virus = 185 KBases, and that clearly would take more effort but would still be feasible according to knowledgeable experts.

As Dr. Craig Venter said on CNBC-TV this afternoon [2], "This publication was deliberately provocative and will not rank as a high point in the annals of science." He was quick to point out that publishing a human pathogen's DNA or RNA sequence in a public scientific journal -- as he has done numerous times -- is an entirely different matter, since "that sort of shared knowledge in the public domain can lead to cures not gratuitous insights for bioterrorists."

An organism's sequence really is the "Book of Life" for that creature, isn't it? But most of us already knew that, didn't we? So, we believe that DARPA needs to be justify its biological- research agenda in a more accountable manner.

Therefore, the GRG is compelled to recommend that raw chemical nucleotides {A, G, T, C, U} now be placed on a "US Commerce Department/State Department Munitions/Strong-Cryptography-Algorithms Restricted List" for NO FOREIGN EXPORT without a specific exemption and that domestic purchase of these biologicals to unlicensed buyers be prohibited by law. (Government licensing to universities and pharmaceutical companies should require an initial site visit.) Such restrictions may make it a little more difficult for legitimate scientists to conduct their work, but the protection afforded to our citizens will be worth it in the long run. This is a matter that could be carried out immediately by Executive Order until such time as appropriate legislation can be passed at a more leisurely pace by the US Congress..

Refs:

1. Antonio Regolado, "Researcher Shows How Terrorists Could Create Deadly Virus: The Genetic Sequence of the Smallpox Virus Is Already Available on the Internet," The Wall Street Journal, pp. A1, B1,4 (July 12, 2002)
2. J. Craig Venter, TIGR, CNBC-TV Interview TRT= 10 minutes (7:30 PM EDT; Friday, July 12, 2002)

ABSTRACT:

Full-length poliovirus cDNA was synthesized by assembling oligonucleotides of plus and minus strand polarity. The synthetic Polio Virus cDNA was transcribed by RNA polymerase into viral RNA, which translated and replicated in a cell-free extract resulting in the de novo synthesis of infectious Polio Virus. Experiments in tissue culture using neutralizing antibodies and CD155 receptor-specific antibodies and neuro-virulence tests in CD155 transgenic mice confirmed that the synthetic virus had biochemical and pathogenic characteristics of native Polio Virus. Our results show that it is possible to synthesize an infectious agent by in vitro chemical/biochemical means solely following instructions from a written sequence.

The President's Council on Bioethics Issues Its Report on Human Cloning with Major Internal Disagreements

July 11, 2002; Washington, D.C. ( WSJ) -- Prof. Leon Kass issued an Editorial this morning describing the Preliminary Report of his Commission regarding Human Cloning ( Human Cloning and Human Dignity: An Ethical Inquiry). [Click for Dr. Kass's Commentary.] However, a significant minority (7 out of 17 members) disagreed with the Chairman's Position regarding a Four-Year Ban on all forms of Human Cloning (including Elizabeth H. Blackburn, Daniel W. Foster, Michael S. Gazzaniga, William F. May, Janet D. Rowley, Michael J. Sandel, and James Q. Wilson). Indeed, the Minority Position did not recommend a moratorium at all, but recommended immediate human therapeutic cloning, subject to appropriate controls The Majority Position supporting a ban included Rebecca S. Dresser, Francis Fukuyama, Robert P. George, Mary Ann Glendon, Alfonso G¢mez-Lobo, William B. Hurlbut, Leon R. Kass, Charles Krauthammer, Paul McHugh, and Gilbert C. Meilaender. Obviously, both the Majority and Minority Positions recommended the banning of human reproductive cloning.
[ Editorial Remark: Active discussions during Commission meetings must have been more acrimonious than I thought they might have been, all things considered, and I only wished that I could have been there to participate in the debate.]

Refs:

1. Joe Palca, NPR Radio (~1:30 PM PDT; July 11, 2002).
2. Leon R. Kass, "Stop All Cloning of Humans for Four Years," The Wall Street Journal, p. A16 (July 11, 2002).
3. "Bioethics Panel Suggests a Cloning Moratorium, The Wall Street Journal, p. B6 (July 12, 2002).
4. Aaron Zitner, "Panel Favors Cloning Moratorium But Not Ban," The Los Angeles Times, p. A1, 11 (July 12, 2002).
5. James P. Pinkerton, "Why Not Clone Our Best and Brightest?" The Los Angeles Times, p. ~B15 (July 16, 2002).
["In May, a team of Australian researchers announced that they were within a decade of reviving the Tasmanian Tiger that was hunted to extinction in 1936."
6. American's To Ban Cloning (ABC)
[ABC is a Coalition of Concerned Citizens and US-based Organizations to promote a global, comprehensive ban on all forms of human cloning.]
7. Denise Caruso, "The Moral Minority: We All Lose When We Leave Right and Wrong to a Clique of Ethics Experts," Wired Magazine, Vol. 10, No. 8, pp. 71-2 (August 2002).
8. Stephen S. Hall, "President's Bioethics Council Delivers," Science, Vol. 297, No. 5580), pp. 322-4 (July 19, 2002),
[ Editor's Note: This three-page article, written by Mr. Hall who seems to have interviewed all the Council members, makes one wonder about the ethics of the Ethics Council itself. Prof. Elizabeth H. Blackburn, a respected molecular biologist at the University of California at San Francisco and member of the minority-report group in the Council said, "At no point was the length of the proposed moratorium (four years) publicly discussed. I have no idea where that number came from." Blackburn, Gazzaniga, Rowley, and other Council members left the June session convinced that a narrow majority supported research cloning a stunning outcome certain to shock both the Bush Administration and Capitol Hill. ... The proponents of research cloning had barely a week to savor their triumph. On Friday, June 28th, panel members began to receive draft language of the policy recommendations, and many were shocked to read the recommendation on research cloning. The draft report said that, by a 10:6 majority the Council recommended a four-year moratorium on research cloning. For many members, it was the first indication that the majority position had changed. Rowley, for example, said she was "really caught by surprise." If one were to read Dr. Kass's Editorial in Ref. 2 above and even the complete 200-page preliminary report itself, one would have had no clue as to the level of dissent and acrimony inside the Council itself.]
9. Letter from Ted Peters and Gaymon Bennett, Christian Theologians, The Center for Theology and the Natural Sciences, Berkeley, California, "For Beneficence, Let Cloning for Research Continue," The Scientist, Vol. 16, No. 16, p. 14 (August 19, 2002).

NIH Terminates Woman's HRT Study

July 9, 2002; Washington, D.C. ( CNN) --- In a move that may affect six million women, NIH scientists Tuesday terminated a major study of Hormone Replacement Therapy (HRT) on the risks and benefits of combined Estrogen and Progestin ( PremPro) in healthy postmenopausal women, citing an increased risk of invasive breast cancer, strokes, and blood-clotting abnormalities. The details of the study known as the Women's Health Initiative (WHI) will be published in next week's issue of The Journal of the American Medical Association (JAMA). There were 16,608 healthy women from ages [50 - 79] who were randomly assigned to either Prempro or placebo over 5.2. years. See the CNN Website for more details.

Editorial Remark: We should not allow ourselves to become hysterical over this one study and "throw out the baby with the bath water," so to speak. We need to tease out such issues as "patch" vs. "pill," since we know that the Route-of-Administration is important (first-pass effect through the liver). Also, Prempro is not very "physiologic," since it is a mix of many different natural equine estrogens. Ongoing clinical trials of pure estrogen must be continued for a few more years before we make a more definitive recommendation (in the year 2005). In the mean time, our lives have just gotten a little more complex. Any newly-postmenopausal women who are currently benefitting from HRT in terms of symptomatic relief would probably be advised to see their OB/GYN rather than capriciously stopping their medication(s), since the very slight differences in risk associated with this one study may well be outweighed by individual short-term benefits.

Refs:

1. Gina Kolata, "Study Is Halted Over Rise Seen in Cancer Risk," The New York Times, pp. A1, A17 (July 9, 2002).
2. Joe Palca, NPR Radio (July 9, 2002).
3. Thomas M. Burton, "Increased Risks Prompt Researchers to Halt Study: A Big Dilemma for Women," The Wall Street Journal, pp. A1, B1, 3 (July 10, 2002).
4. Ron Winslow and Geeta Anand, "More Options and Unknowns," The Wall Street Journal, pp. B1, B3 (July 10, 2002).
5. Scott Hensley, Wyeth CEO: Concerned But Hopeful," The Wall Street Journal, pp. B1, 3 (July 10, 2002).
6. Rosie Mestel, "Risks of Hormone Therapy Stop Study," Large Clinical Trial Finds More Cases of Breast Cancer and Cardiovascular Disease After Long-Term Use of Post-Menopause Drugs," The Los Angeles Times, pp. A1, 11 (July 10, 2002).
7. Rosie Mestel and Linda Marsa, "Hard Look at Risks of Hormones: Doctors Report Post- Menopausal Women Are 'Scared' as They Face Choices After Study's Halt," The Los Angeles Times, pp. A1, 13 (July 11, 2002).
8. Ronald D. White, "Battered Drug Stocks Still Reeling from Study," The Los Angeles Times, pp. C1, 3 (July 11, 2002)
9. Lead Editorial, "A Hot Flash on the Good Life," The Los Angeles Times, p. B14 (July 11, 2002)
["Who could resist lHRT]? What woman would chose to shrivel and sag when she could remain dewy and pert by popping a pill? ... Physicians believed that estrogen could keep the Grim Reaper at Bay. ... The new developments underscore what most women knew all along: that aging is inevitable; that there is no magic pill to stop the clock. ... Now that's a hot flash."]
10. Ellen Goodman, "Hormones Should Have Been Taken with a Dose of Skepticism: Marketing May Have Triumphed Over Science," The Los Angeles Times, p. B15 (July 12, 2002).
11. Rosie Mestel and Ronald D. White, "Shift in Hormone Science Leaves Women in Lurch," The Los Angeles Times, pp. A1, A15 (July 14, 2002).
12. Shari Roan, Menopause Relief Minus Hormones: Pors and Cons of Natural Remedies Get Renewed Attention, After a Report on the Risks of Conventional Therapy," The Los Angeles Times, pp. S1, 4 (July 15, 2002).
13. Tara Parker-Pope, "What You (or Your Mom) Need to Know: Some Answers about Hormone Therapy," The Wall Street Journal (July 16, 2002).
14. Susan M. Love, "Preventive Medicine, Properly Practiced," The New York Times, p. A21 (July 16, 2002).
15. Mary Duenwald, "Hormone Therapy: One Size, Clearly, No Longer Fits All," The New York Times, pp. D1, 7 (July 16, 2002).
16. Ron Winslow and Scott Hensley, "Wyeth Sales Team Calls on Doctors After Study," The Wall Street Journal, p. D3 (July 17, 2002).
[" Wyeth, the makers of PremPro, earns nearly $1 billion annually from the sales of this drug... They have been in the business of HRT for about 60 years... Prescriptions for PremPro dropped about 30 percent in the two days after the study data were announced."
17 Thomas H. Maugh, II, "More Risk Shown in Use of Estrogen," The Los Angeles Times, p. A12 (July 17, 2002).
18. David Malakoff, "The Vanishing Promises of Hormone Replacement," Science, Vol. 297, No. 5580, pp. 325-7 (July 19, 2002).

Stem Cells Cure SCID

June 28, 2002; Milan, ITALY (AP) - In today's issue of Science, a single injection of genetically modified stem cells is all that was needed to cure two children of a complex form of Severe Combined Immuno Deficiency Disorder (SCID) often called "Bubble-Boy Disease."

Ref:

"Gene Cell Therapy Reportedly Corrects 'Bubble Boy' Disease," The Los Angeles Times, p. A29 (June 28, 2002).

Nutrition Determines Risk in Alzheimer's Disease

June 26, 2002; As published in today's issue of The Journal of the American Medical Association, two clinical trials of Vitamin E (one in Chicago, IL and one in Rotterdam, Netherlands) have now demonstrated a [40 - 70] percent reduction in the incidence of Alzheimer's Disease from highest to lowest dietary intake. These results appear to further implicate Oxygen Free Radicals as part of the etiology of AD in the brain. However, the studies did not demonstrate the therapeutic efficacy of the supplement form of Alpha-Tocopherol, only the sort of dietary Vitamin E found in grains. On the other hand, supplements were not excluded by the studies either. There were a number of confounding variables in these trials (duration of use, dose, and the memory of the patients with early Alzheimer's themselves).

Refs:

1. Emily Singer, "Vitamins E and C Called Alzheimer's Inhibitors: Studies in the U.S. and Netherlands are the First to Find a Link between Consumption of Foods High in Antioxidants and Prevention of the Disease," The Los Angeles Times, p. A14 (June 26, 2002).
2. "Some Foods May Curb Alzheimer's," The Wall Street Journal, pp. A1, D6 (June 26, 2002).
3. Richard Knox at NPR in Boston, MA,. Audio Clip (4:00 PM PDT; Tuesday, June 25, 2002).

GRG Editorial: Companies with Vision Are Still Companies, Aren't They?

June 25, 2002; We are sad to report that when the Biotech Sector fails to maintain stockholder value, as is presently the case, companies, even those with a unique vision, are compelled to ignore their long-term mission and merely reach for "the low-hanging fruit." Geron Corp. of Menlo Park, CA announced today that they must lay off 33 researchers in a bid to save cash (they have enough for two more years of operation) and focus on a line of experimental cancer drugs (presumably an anti-telomerase agent that will begin clinical testing by the end of the year). Investors cheered the announcement, boosting Geron shares by 13 cents (Sigh!). The problem is that the company's ability to conduct the only research that really matters to our mission has been severely compromised, and that ought to be a signal to sell the stock, not buy it! What will be lost is a planned collaboration with Celera Genomics Group (another company in financial trouble) in identifying the genes that are activated in embryonic and adult stem cells during embryogenesis and wound healing. But what do investors know, anyway? "Just let me smile while I walk to the bank tomorrow."

Refs:

1. David P. Hamilton, "Geron Trims 30 Percent of Work Force, Plans to Shift Focus on Research," The Wall Street Journal, p. D8 (June 25, 2002).
2. Antonio Regalado, "Cloning Company Gets Access to Rivals' Property," The Wall Street Journal, p. D4 (June 27, 2002).
3. Letter to the Editor by Fritz Baumgartner with Response by Carl B. Feldbaum, "Human Embryos: Potential Humans?" Science, Vol. 296, No. 5575, pp. 1967-8 (June 14, 2002).

Adult and Embryonic Stem Cells Compete for Therapy

Prof. Catherine Verfaillie of the University of Minnesota reported success with Adult Stem Cells

Dr. Ron McKay of NIH reported success with Rodent Embryonic Stem Cells in correcting a model of Parkinson's Disease

June 21, 2001; Click for details.
Editor's Note: Will Dr. McKay win the Fox Foundation Grant based on this work? See the News Item below on June 16th.

Refs:

1. Ronald McKay,. et al. "Dopamine Neurons Derived from Embryonic Stem Cells Function in an Animal Model of Parkinson's Disease," Nature, Vol. 417 (June 20; 2002).
2. Catherine M. Verfaille, et al. "Pluripotency of Mesenchymal Stem Cells Derived from Adult Marrow," Nature, Vol. 417 (June 20; 2002).
3. Antonio Regalado, "'Supercell' Controversy Sets Of a Scientists' Civil War," The Wall Street Journal, pp. A1, B1, 4 (June 21, 2002).
4. Aaron Zitner, "Research Offers Alternative to Embryo Stem Cells," The Los Angeles Times, p. A17 (June 21, 2002).
5. Joe Palca, NPR Radio, "Morning Edition," 7:30 AM PDT; Friday, June 21, 2002).
"...the debate over stem cells just got more interesting. Two studies indicate that these cells may be quite useful in treating disease. But one study says useful stem cells don't necessarily have to come from human embryos." Click to listen to the interview with both Drs. McKay and Verfaillie..(TRT = 2:40)
6. Charles Krauthammer, "The Fatal Promise of Cloning: Advocates Say They Will Never Create Human Fetuses. Can We Believe Them?" Time Magazine, p. 54 (June 24, 2002).
7. Anthony Atala, Robert Lanza, Michael West, et al, Nature Biotechnology, Vol. 20, No. 7 (July 2002).
[See Abstract just below as well as the Note following Ref 8 from the News Item below dated April 4, 2002.]
8. Antonio Regalado, "Cloned Kidneys Survived in Cows After Transplant," The Wall Street Journal, p. B6 (June 3, 2002).
9. Thomas H. Maugh, II, "Therapeutic Cloning Gets Boost in Implant Study," The Los Angeles Times, p. A11 (June 3, 2002).
10. "Medicine: Stem-Cell Alternative?" Scientific American, Vol. 287, No. 1, p. 33 (July 2002).
11. Joe Celko, "Cloning Confusion," Intelligent Enterprise, Vol. 5, No. 10, p. 64 (June 13, 2002).
["In the mid 1770s, the French Faculty of Theology considred Vaccination for Small Pox as an attempt by doctors to play God by interfering with the divine order of the universe instead of letting people die as nature ran its course. However, in the end, when King Louis XV himself died of Small Pox, the Court panicked, and the Royal Council legalized inoculation for all of France. With respect to stem cell technology, we are in a similar situation today."]
12. N. Seppa, "Stem Cell Gain: Bone Marrow Cells Seem to Have What It Takes," Science News, Vol. 161, No. 25, p. 390 (June 22, 2002).

Robert P. Lanza [1], Ho Yun Chung [2], James J. Yoo [2], Peter J. Wettstein [3], Catherine Blackwell [1], Nancy Borson [3], Erik Hofmeister [3], Gunter Schuch [2], Shay Soker [2], Carlos T. Moraes4, Michael D. West [1], and Anthony Atala [2], "Generation of Histocompatible Tissues Using Nuclear Transplantation," Nature Biotechnology, Vol. 20, No. 7 (July 2002).
_____________________________
1. Advanced Cell Technology, Worcester, MA 01605.
2. Laboratory for Tissue Engineering and Cellular Therapeutics, Children's Hospital and Harvard Medical School, Boston, MA 02115.
3. Departments of Surgery and Immunology, Mayo Clinic, Rochester, MN 55905
. 4. Department of Neurology, University of Miami School of Medicine, Miami, FL 33136.

Correspondence should be addressed to A Atala. E-mail: Anthony.Atala@TCH.Harvard.edu.

ABSTRACT:

Nuclear tansplantation (therapeutic cloning) could theoretically provide a limitless source of cells for regenerative therapy. Although the cloned cells would carry the nuclear genome of the patient, the presence of mitochondria inherited from the recipient oocyte raises questions about the histocompatibility of the resulting cells. In this study, we created bioengineered tissues from cardiac, skeletal muscle, and renal cells cloned from adult bovine fibroblasts. Long-term viability was demonstrated after transplantation of the grafts into the nuclear donor animals. Reverse transcription-PCR (RT-PCR) and western blot analysis confirmed that the cloned tissues expressed tissue-specific mRNA and proteins while expressing a different mitochondrial DNA (mtDNA) haplotype. In addition to creating skeletal muscle and cardiac "patches", nuclear transplantation was used to generate functioning renal units that produced urinelike fluid and demonstrated unidirectional secretion and concentration of urea nitrogen and creatinine. Examination of the explanted renal devices revealed formation of organized glomeruli- and tubule-like structures. Delayed-type hypersensitivity (DTH) testing in vivo and Elispot analysis in vitro suggested that there was no rejection response to the cloned renal cells. The ability to generate histocompatible cells using cloning techniques addresses one of the major challenges in transplantation medicine.

Cell Biology: Telomeric Ends in Sight

June 20, 2002; Telomeres, the physical ends of eukaryotic chromosomes, are made up of short repeats of the same DNA sequence and serve to protect genes from damage. Breakdowns in telomere maintenance are implicated in both aging and cancer. Telomeric DNA sequences can form four-stranded structures and the crystal structure of one such quadruplex grown at a Potassium concentration like that inside a human cell has been determined, revealing DNA folding fundamentally different from previously published Sodium-containing structures. The new DNA structure suggests a straightforward path for telomere folding and unfolding.

Ref:

Gary N. Parkinson, Michael P. H. Lee, and Stephen Neidle, "Crystal Structure of Parallel Quadruplexes from Human Telomeric DNA," Nature, Vol. 417, pp. 876 80 (June 20, 2002).

Signum Biosciences to Screen for Alzheimer's Disease

June 18, 2002; Los Angeles, CA Brothers Prof. Gregory Stock of UCLA and Prof. Jeffrey Stock of Princeton University have teamed up to form a new biotech start-up company called Signum Biosciences to screen for Alzheimer's Disease based on global methylation/phosphorylation regulation of the Tau Protein that is important in micro-tubule architecture within the cytoplasm of neurons.

Contest: Who is the World's Oldest Living Father?

Father's Day; Sunday, June 16, 2002; Los Angeles, CA -- Can any of our readers identify the oldest living man to have fathered a child having the greatest paternal age at the time of the birth (regardless of the mother's age or the gender of the child)? As a corollary, who is the oldest such man in history? For reference, we believe that we have a candidate who was 93 years old when he fathered a child (although he died shortly thereafter). We wish to disallow men using special infertility technology such as IVF, Egg Drilling, or Artificial Insemination. We are aware that paternity is much harder to establish than maternity and just being married to the woman who gave birth may not be sufficient to authenticate the claim, but we do have definitive DNA testing today that we did not have as recently as ten years ago. To our knowledge, this world-record category does not appear to been claimed by The Guinness Book of Records. Whoever E-mails us the oldest documented cases in either category is eligible to win a GRG Certificate with a "Golden Longevity Curve." The winner(s) will be announced on October 1, 2002 in this News Section.

Update on June 23, 2002: Mr. Robert Young of Atlanta, GA has identified Mr. Les Colley [1898 - 1998] as the oldest father at age 93 years,10 months. According to various US State Vital-Statistics Databases, there are a number of candidates at 88 (Alabama [1996] reports their oldest father to be 88 and Louisiana [1996] reports their oldest father also as 88 [and the youngest mother to be ten years old!]), while Kentucky [1998] reports their oldest father as 89 years.

The Genetics of Centenarians

June 17, 2002; Cambridge, MA As published in Tuesday's issue (June 10th) of the Proceedings of the National Academy of Sciences, the New England Centenarian Study, directed by Dr. Tom Perls, M.D. of Harvard University, has provided additional evidence for the importance of genetics in centenarian life expectancy.

Thomas T. Perls [1, 6, 7], John Wilmoth [2,6], Robin Levenson [3], Maureen Drinkwater [1], Melissa Cohen[1], Hazel Bogan [1], Erin Joyce [4] , Stephanie Brewster [4], Louis Kunkel [5], and Annibale Puca [4],
"Life-Long Sustained Mortality Advantage of Siblings of Centenarians"
Proc. Natl. Acad. Sci. USA, Vol. 99, No. 12, pp. 8442-7 (June 11, 2002)
__________________________
1. Geriatrics Section, Boston Medical Center and Boston University Medical School, Boston, MA 02118;
2. Department of Demography, University of California, Berkeley, CA 94720;
3. Indiana University School of Medicine, Indianapolis, IN 46202;
4. Centagenetix, Cambridge, MA 02139; and
5. Howard Hughes Medical Institute, Genetics Division, Children's Hospital and Harvard Medical School, Boston, MA 02215

Edited by Kenneth W. Wachter, University of California, Berkeley, CA, and approved April 10, 2002 (received for review October 31, 2001)

ABSTRACT:

Although survival to old age is known to have strong environmental and behavioral components, mortality differences between social groups tend to diminish or even disappear at older ages. Hypothesizing that surviving to extreme old age entails a substantial familial predisposition for longevity, we analyzed the pedigrees of 444 centenarian families in the United States. These pedigrees included 2,092 siblings of centenarians, whose survival was compared with 1900 birth cohort survival data from the U.S. Social Security Administration. Siblings of centenarians experienced a mortality advantage throughout their lives relative to the U.S. 1900 cohort. Female siblings had death rates at all ages about one-half the national level; male siblings had a similar advantage at most ages, although diminished somewhat during adolescence and young adulthood. Relative survival probabilities for these siblings increase markedly at older ages, reflecting the cumulative effect of their mortality advantage throughout life. Compared with the U.S. 1900 cohort, male siblings of centenarians were at least 17 times as likely to attain age 100 themselves, while female siblings were at least 8 times as likely.
_______________________________________________
6. T.T.P. and J.W. contributed equally to this work.
7. To whom reprint requests should be addressed.
E-mail: thomas.pers@hmc.org.

Refs:

1.Link to the MS-NBC website for a brief video clip of Mr Murray Keller of West Palm Beach, FL who is 99 years old.
2. "Centenarians' Siblings Have Long Lives Too," The Los Angeles Time, p. A12 (June 17, 2002).
3. "The Genetics of Living Beyond 100," The New York Times, Sciences Section S (June 11, 2002).

Grant for Parkinson's Disease Research

June 16, 2002; The Michael J. Fox Foundation Offers a $2.5 million Grant to the first scientist able to create a neural stem-cell line that produces dopamine. [ Editor's Note: Would it more efficient to fund a complete Neural Cytokine Catalog from which the dopaminergic nigrostriatal stem cells fall out as a special case or search for these cells in culture by themselves?]

Refs:

1. Michael J. Fox, Lucky Man: A Memoir (Hyperion, 260 pp; 2002).
2. Abraham Verghese, "Illness Without Metaphor," The Los Angeles Times Book Review Section , p. 4 (June 16, 2002).

GRG Editorial: Brownback Forces Pitch Their Tent and Silently Steal Away in the Night

June 14, 2002; Washington, D.C. Fearing that they might lose a vote on the floor, Sens. Brownback (R- KA), Mary Landrieu (D - LA), et al, citing a procedural technicality in the "Terms of the Debate" established by Sen Majority Leader Tom Daschle (D -SD) that they considered unfair and preferring to have no bill at all to a bill brought by their esteemed colleagues (Sens. Edward Kennedy (D - MA), Diane Feinstein (D - CA), and Orrin G. Hatch (R - UT), that would ban reproductive but explicitly allow for lawful therapeutic human cloning, withdrew their request for a debate on their bill S. 709. It should not surprise anyone if Sen. Brownback attempts to piggy-back other of his legislative initiatives in this area as an attachment to unrelated bills. His political approach seems to be "if you can't win on the merits, you should still try to win by a technicality."

Refs:

1. Laurie McGinley and Jill Carroll, "Delay of Human Cloning Debate Likely Halts Legislation This Year," The Wall Street Journal, p. B2 (June 14, 2002).
2. Michael Kranish and Mary Leonard, "Cloning Ban Foes Unite, Conquer Bipartisan Effort: Stalled Bush Plan," The Boston Globe, p. A1 (June 14, 2002).
3. Sheryl Gay Stolberg, "Total Ban on Cloning Research Appears Dead," The New York Times, p. A31 (June 13, 2002).
4. Helen Dewar, "Anti-Cloning Bills Stall in Senate: Vote Unlikely Soon," The Washington Post, p. A4 (June 14, 2002).
5. Aaron Zitner, "Cloning Receives a Makeover: Nuances of Language Helped Reframe the Debate and Derail an All-Out Ban in Congress," The Los Angeles Times, pp. A1, A13 (June 17, 2002).
["For a small group of lobbyists from the biotechnology industry, scientific societies, and such patient groups as the Juvenile Diabetes Research Foundation, derailing the effort to ban all cloning has been a major victory."]
6. Thomas Prugh, "New Genes, a New Human Nature and New Dangers," The Los Angeles Times, p. B13 (July 2, 2002).
7. Brian Halweil and Dick Bell, "Beyond Cloning: The Larger Agenda of Human Engineering," World Watch Magazine, pp. 8-10 (July/August 2002).

Celera Genomics Cuts Staff 16 Percent

June 13, 2002; Rockville, MD; We are sad to report that Celera Genomics, now under new management, plans to restructure the company in order to focus on drug discovery, and, in the process, will eliminate 132 jobs mostly in DNA-sequencing and database areas.

Refs:

1. Scott Hensley, "Celera Will Focus on Drug Discovery, Slash Jobs," The Wall Street Journal, p. D4 (June 12, 2002).

2. Bloomberg News, "Celera to Cut Staff 16% as It Changes Focus," p. C4, The Los Angeles Times (June 13, 2002).

Sen. Brownback to Change Bill: A Two-Year Temporary Moratorium, Not a Permanent Ban on All Forms of Human Cloning

See June 14th above.

June 12, 2002; Washington, D.C. --- In response to the current mood in the Senate, Sen. Sam Brownback (R - KA) is contemplating changing his bill S. 709 to read as a moratorium on human cloning rather than a total ban. A vote could be scheduled on the Senate floor as early as Friday.

President Bush said yesterday to a convention of Southern Baptists in St. Louis, "We believe that a life is a creation, not a commodity, and that our children are gifts to be loved and protected, not products to be designed and manufactured by human cloning."

Ref:

Aaron Zitner, "Opponent of Human Cloning Might Modify Plan for Ban: Kansas Senator Raises the Possibility of a Two-Year Moratorium Instead of a Complete Halt," The Los Angeles Times, p. A21 (June 12, 2002).

The Ethics of Cloning

June 10, 2002; Washington, D.C. ( NPR Radio) "All Things Considered" Joe Palca interviewed Dr. Leon Kass, the President's Chief Bioethics Advisor, and Ethicist Dan Brock of Brown University at ~5:30 PM PDT on the safety issues surrounding the cloning of human beings. Would there still be strong ethical and social arguments against doing it, once it had been completed successfully for the first time? (TRT = 5:15 min.).Click for a replay using a Real Audio Player.

Average Life Expectancy for US Women

June 6, 2002; ( CNN) The average Life Expectancy for women in the US has now set a new record at 79.5 years

GRG Editorial on the Upcoming US Senate Debate on Banning Human Therapeutic Cloning

June 4, 2002; Click for the two-page GRG Editorial Why do Giraffes Have Long Necks?.

Prof. Greg Stock of UCLA Debates Prof. Francis Fukyama of Johns Hopkins University

June 3, 2002; New York, NY (PBS-TV); Greg Stock debated Francis Fukuyama for about 20 minutes on the Charlie Rose Show which aired at 11:20 PM PDT on PBS- TV (KCET, Channel 28 in Los Angeles). Click for the Charlie Rose Show website archives.

Refs:
1. David P. Hamilton, "In Debate on Cloning Humans, Dr. Stock Is One of a Kind: He's OK on What He Calls 'Delayed Identical Twins' and Picking Kids' Genes," The Wall Street Journal, pp. A1, 4 (June 13, 2002).
2. R. E. Spier, "Toward a New Human Species?" Science, Vol. 296, No. 5574, pp. 1807-8 (June 7, 2002).
3. Paul Rabinow, "Getting to Know You: Review of Our Posthuman Future," Nature Biotechnology, Vol. 20, No. 6, p. 545 (June 2002).

Sierra Sciences Developing Telomerase Therapies

June 3, 2002; Sierra Sciences, Inc.(SSI) of Reno, NV is an early-stage biotechnology company whose long-term goal is to develop drugs and therapies that will reverse the effects of human aging. Click on their website for more details.

Celera Genomics Finds Strong Homology on Chromosome 16 for Both Mice and Men

May 31, 2002 Rockville, MD ( AAAS) Celera Genomics (~200 co-authors including former CEO J. Craig Ventor) sequenced both the mouse and human genome and has now published their latest findings regarding Chromosome 16 in today's issue of Science.

Richard J. Mural, Mark D. Adams, Eugene W. Myers, Hamilton O. Smith, et al, "A Comparison of Whole-Genome Shotgun-Derived Mouse Chromosome 16 and the Human Genome," Science, Vol. 296, No. 5573, pp. 1661-71 (May 31, 2002).

ABSTRACT:

The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse Chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10 percent smaller than the human genome, owing to a lower repetitive DNA content ["Junk DNA"]. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.

Refs.

1. Reuters, "Of Mice and Men, It's a Fine (DNA) Line, The Los Angeles Times,. p. A24 (May 31, 2002).
2. "Freeing upo the Mouse Genome," Science News, Vol. 161, No. 21, p. 333 (May 25, 2002).

In summary, all genes on Chromosome 16 are the same with the exception of 2 percent that are unique to the mouse and 2.9 percent that are unique to humans. In other words, phenotypic differences appear largely in the eye of the beholder and come about as a result of minor tweaks in our respective embryogenic programs. It appears that, for both primates and rodents, our genomes were largely inherited in tact a long time ago from a common ancestral mammalian creature (who, for all we know, may now be extinct). [ Editor's Note: 95 to 97 percent of all creatures who have ever lived on planet Earth are now extinct.]

Mouse Embryonic Stem Cells Differentiate into Adult Lung Cells

May 30, 2002; London, UK (Reuters) – Click for more details.

Lifespan Genetics, Inc. Is Using Microarrays to Discover Biomarkers of Aging

May 29, 2002; LifeSpan Genetics (LG) is a leading-edge bio-informatics company focused on the discovery of the genetic expression patterns involved in the aging process. LG uses microarray gene-chip technology to successfully measure specific changes in gene expression. LE measures these changes during normal aging and aging slowed by the scientific intervention of Caloric Restriction. It is the only method available of measuring aging objectively. LE technology is proprietary (patents pending). It is the only scientifically acceptable mechanism for measuring aging objectively. LE technology allows rapid scientific evaluation of pharmaceuticals, nutraceuticals, and other treatments for their effects on the rate of aging. Such analyses are hundreds of times faster and far less expensive than was formerly possible. The company is developing bio-informatics databases of these effects. LE also want to understand how and why gene expression changes with age. Based on this information, LE intends to employ rational drug design to develop therapies to retard aging, prevent age-related diseases, and extend maximum lifespan in humans.

Current research makes use of prior work by Prof. Roy Walford, M.D. of UCLA and other researchers, who have established that Caloric Restriction (CR) retards the aging process and extends maximum lifespan in mammals while preserving their health and vitality.

As the proportion of older people increases in society, there is an urgent need to combat age-related diseases such as Alzheimer's, heart failure, stroke, osteoporosis, and cancer. In the past, our lack of understanding of the aging process has interfered with our ability to prevent and treat these age-related diseases. However, LifeSpan Genetics is involved in research using microarray gene chips to measure the activity of thousands of genes at a time. The long-term goal is to discover and to develop interventions for age-related diseases and the aging process itself.

Dr. Stephen R. Spindler, Ph.D. former Chairman of the Biochemistry Department at the University of California at Riverside and Chief Science Officer of the company has been investigating how quickly caloric restriction can induce changes in gene expression in mice and primates. This work, and work of our former associates allows LE to take measurements of the effects of aging at the molecular level. This will allow LE to evaluate attempts to intervene in the aging process using drugs and other therapies.

Future Research

LifeSpan Genetics has five primary goals:

1.. To profile and identify biomarkers of the aging process at the molecular level by measuring gene expression in various organs of mammals, including humans.
2. To establish databases describing the effects of nutrients, drugs, and diets on this gene-expression profile.
3. To rapidly identify candidate drugs or nutraceuticals that may retard aging and prevent age-related diseases.
4. To utilize the information gained from our studies for the rational design of drugs or compounds which retard aging and prevent or slow the onset of age-related diseases.
5. To use biomarkers of aging to measure biological age via a simple test.

For more details, click on their website... www.lifespangenetics.com.

New Species Proposed for Genomic Mapping

May 23, 2002; Washington, D.C.; Having completed the Fruit Fly, the Mouse, the Rat, and the Human Genomes, the International Public Genome Project will now seek to decode the Chicken, the Honey Bee, the Chimpanzee, the Sea Urchin, Tetrahymena, and certain species of fungi next.

Ref:

Laurie McGinley, "Federal Genome Project Decides to Decode Chicken, Bee, Fungi," The Wall Street Journal, p. D6 (May 23, 2002).

Trichothiodystrophy (TTD) Model in Mice Reveals Premature Aging

May 17, 2002; Several pieces of the "Blind Men Touching the Elephant" puzzle have just come together: Trichothiodystrophy (TTD), an inherited partial defect of DNA repair enzymes in humans, when mimicked in a mouse model leads to increased double-stranded chromosomal breaks, leading to compromised genomic maintenance throughout the entire organism. This leads to increased apoptosis (or Programmed Cell Death) through upregulated p53 activity, leading to cellular senescence resulting in a premature aging phenotype at the tissue level. This causes a failure of homeostasis secondary to an inability of normal repair mechanisms to keep up with the relentless stochastic wear-and-tear processes from both exogenous (radiation, carcinogens) and endogenous (Free Radicals or ROS) sources. Obviously, the force of natural selection for somatic maintenance past the age of menopause declines sharply. [The value of grand-parenting may be a minor countervailing tendency.] In other words, the genomic program that builds the somatic- and germ-line cells in the first place essentially "runs out of things to do," exposing us to the "slings and arrows" of Nature.
[ Editor's Note: So what's the solution? We only have to add new programming, since there is no lack of energy (ATP derivable from the food chain) to maintain an adult organism in a youthful (well-repaired) state. So how do you do that? The answer has to lie in Stem Cell Technology and Genetic Engineering. The only problem is that we still don't have a clue how the DNA blueprint determines the architecture of an organism. This is elegantly summarized in the question "How does the giraffe's DNA tell him (or her) to grow a long neck?" This is the problem of embryogenesis: "How does the genotype determine the phenotype?" As soon as we compare the chimp and human genomes in detail and the rat and bat genomes in detail, we may get some answers. So let's get to work.]

Refs:

. 1. Paul Hasty and Jan Vijg, "Genomic Priorities in Aging," Science, Vol. 296, No. 5571, pp. 1250-51 (May 17, 2002).
2. David P. Hamilton and Antonio Regalado, "California School Attempted to Clone Human Embryos," The Wall Street Journal, pp. A1, 3, 5 (May 24, 2002).
[Dr. Roger Pedersen, formerly with UCSF and now located at Cambridge University in England, began human embryo-cloning experiments at the University of California in San Francisco as long ago as mid-1998 under a research contract with Geron Corp. of Menlo Park, CA. According to Dr. Tom O'Karma, CEO of Geron, the aim was to establish an autologous stem-cell line for therapeutic purposes, not for reproductive cloning. To our knowledge, this project was not as successful as ACT's work reported last November, but none of these experiments have so far yielded stem cells of clinical value.]

DEMOGRAPHY: What are the Limits to Human Life Expectation?

May 10, 2002; James Oeppen and James W. Vaupel*, "Enhanced: Broken Limits to Life Expectancy," Science, Vol. 296, No. 5570, pp. 1029-31 (May 10, 2002).

ABSTRACT:

Question: Is human life expectancy approaching its limit? Many persons including individuals planning their retirement and officials responsible for health and social policy believe that it is, but the evidence presented in the Policy Forum suggests otherwise. For 160 years, best-performance life expectancy has steadily increased by one year over every four years, an extraordinary constancy of human achievement. Mortality experts have repeatedly asserted that life expectancy is close to an ultimate ceiling; these experts have repeatedly been proven wrong. The apparent leveling off of life expectancy in various countries is an artifact of laggards catching up and leaders falling behind.
________________________________________________________________________
Janes Oeppen is with the Cambridge Group for the History of Population and Social Structure, Cambridge University, Cambridge, CB2 3EN, UK. and
James W. Vaupel is at the Max Planck Institute for Demographic Research, Doberaner Strasse 114, D-18057 Rostock, GERMANY.

* To whom correspondence should be addressed: E-mail: jwv@demogr.mpg.de.

Refs:

1. Liz F. Kay, "We Can Live Far Longer, Study Says," The Los Angeles Times, p. A24 (May 10, 2002).
[Prof. Jay Olshansky of the School of Public Health at the University of Chicago said, "Vaupel's model does not take into account the various biochemical, biomechanical, and demographic forces that affect life expectancy. They have used mathematics and statistics to look at a phenomenon that is inherently biological, and all they are looking at is the mathematics of the phenomenon. They have completely ignored the biology. To calculate life expectancy, actuaries do use mathematical models of death rates at different ages to predict how long a person born in a specific year can be expected to live in order to determine what premium a life insurance company should charge that person. By definition, for average life expectancy to increase to 100 years, more than half the population would have to live beyond that age."]

2. Maxine Weinstein (Georgetown University, Washington, D.C.), Albert I. Hermalin (Institute for Social Research, Ann Arbor, MI), and Michael A. Stoto (The George Washington University, Washington, D.C.), Eds., Population Health and Aging: Strengthening the Dialogue Between Epidemiology and Demography, Vol. 954, Proc. of a February 2001 Conference (323 pp., $145, New York Academy of Sciences; New York; December 2001).
["Population Health is an emerging field that draws heavily on two disciplines: Demography and Epidemiology. In recent years, as demographers have become increasingly interested in health transitions and trajectories and as epidemiologists have become increasingly interested in population-level disease dynamics, the two fields have converged in many ways. But their separate histories, culture, language, organizations, and missions have acted as impediments to dialogue among practitioners in the two fields. This volume seeks to improve conversation across the disciplines. It brings together reports on current research that provide examples of work that bridges (or has the potential to bridge) the two fields, and helps identify organizational and institutional pathways that can encourage collaboration."]

NIH Releases Complete Mouse Genome Sequence

May 7, 2002; Bethesda, MD; In a landmark advance in genomics, Dr. Francis Collins, Director of the Public Human Genome Project, and the International Mouse Genome Sequencing Consortium announced today that it has assembled and deposited into a public database an advanced draft sequence of the mouse genome the genetic blueprint for the most important mammalian model in biomedical research. Click for more details from NIH.

Scientists are especially intrigued by a quarter-million genome regions that are extremely similar in human and mouse but don't seem to be part of any traditional genes. "Since these regions have been stable through 100 million years of evolution --- the time believed to have elapsed since the common ancestor of mice and humans existed --- they are presumably very important," said Dr. Eric Lander, Director of the MIT/Whitehead Center. "But no one knows what they do yet!"

Ref:

Rosie Mestel, "Mouse Genome Is Offered Free on the Web," The Los Angeles Times, p. A26 (May 7, 2002).
[ Editor's Note: Celera Genomics, Inc. reportedly charges an annual subscription fee of $[8,000 - 13,000] for access to a similar mouse sequence database.]

Senator Hatch Backs Cloning for Research

April 30, 2002 ( CNN) -- Senator Orrin Hatch (R - UT) has now concluded that human life begins "in a mother's nurturing womb, not in a laboratory dish." Furthermore, "Cloning only produces living cells, not human beings." The product of cloning is an "unfertilized, electronically-activated embryo," he said. A key question, especially for anti-abortion Senators, is "When life begins?" Hatch said that he believes that "because the human eggs used in therapeutic cloning are not fertilized, they are not embryos and thus not human life." Click for more details from CNN .

Refs:

1. Laurie McGinley, "Hatch Appears Set to Support Research Cloning," The Wall Street Journal, pp. A1, 3, 8 (April 30, 2002).
2. Aaron Zitner, "Hatch: Conservative Supports Cloning for Medical Use," The Los Angeles Times, pp. A1, 20 (May 1, 2002).

Craig Venter Admits His Own DNA Was Used as Sample

April 27, 2002; Dr. Craig Venter admitted during an April 17th CBS-TV interview on "60 Minutes II" that the Celera Genomics reference genome was based principally on his own DNA, which has sparked a debate about medical database privacy.

Refs:

1, Nicholas Wade, "Scientist Reveals Genome Secret: It's Him," The New York Times, pp. A1, 13 (April 27, 2002).
2. "Celera Genomics' Founder used his own DNA for the Company's Map of the Human Genome," The Wall Street Journal, p. A1 (April 29, 2002).
3. Antonio Regalado, "Genome Mapper, Using Own DNA, Sparks a Debate, The Wall Street Journal, p. B4 (April 30, 2002).
4. Scott Hensley, "Genetics' Venter Uses His Profit for New Causes," The Wall Street Journal, pp. B1, 4 (April 30, 2002).
5. Nicholas Wade, "Thrown Aside, Genome Pioneer Plots a Rebound," The New York Times, pp. D1, 6 (April 30, 2002).

Letter to the Editor on Anti-Aging Medicine Published in Science

April 26, 2002; Click for the complete letter from Science co-authored by seven recognized gerontologists.

French Scientists Cure SCID with Genetic Engineering

April 18, 2002; As reported in today's issue of The New England Journal of Medicine, French scientists in Paris have cured four boys afflicted with Severe Combined Immuno Difficeincy (SCID), a usually fatal disease whose inheritance is largely X-linked. Click CNN and AP for more details. See also the News Item from January 28th below.

Ref:

Antonio Regalado, "Gene Therapy Benefits Four Sick Boys," The Wall Street Journal, p. D3 (April 18, 2002).

Stem Cell Therapy for Multiple Sclerosis

April 17, 2002 -- Scientists at the University of Washington Medical Center in Seattle have developed a treatment for MS that involves the autologous transplantation of adult stem cells.

Ref:

Liz Kay, "Stem Cell Therapy May Help Multiple Sclerosis," The Los Angeles Times, p. A19 (April 17, 2002).

Final Map of Human Genome To Be Ready in 2003

April 16, 2002; Shanghai, CHINA ( Reuters) According to Lap-Chee Tsui, President of the London-based Human Genome Organization (HUGO), who was in Shanghai for a four-day human genome conference, "We expect to publish the complete sequence of the human genome during the Spring of 2003, a development that is expected to revolutionize medicine."

Stem Therapy: Japanese Approved for Human Clinical Trial of G-CSF for Heart Disease

April 16, 2002; Granulocyte Colony Stimulating Factor (G-CSF) manufactured by Amgen, Inc. has been shown to increase bone marrow stem cells circulating in the blood stream of mice and rabbits that target heart muscle damage. As a result, heart damage in the treated animals was only about one-third as big as damage in animals that were given a saline placebo. Research suggest that adult stem cells may one day become a significant new tool for treating heart muscle damage. The use of adult stem cells also allows scientists to circumvent the controversial issue of using embryonic stem cells. The Japanese research has not het been published in a scientific journal. However, in a study published in an August issue of the Proc. of the National Academy of Sciences shows that researchers at New York Medical College and the NIH injected G-CSF and another molecule into mice before and after heart attacks. The study found that 73 percent of the mice survived four weeks, compared with 17 percent of the control group. The U.S. researchers said adult bone marrow stem cells have "remarkable plasticity" and thus can differentiate into cardiomyctyes.

Ref:

Peter Landers, "Researchers Try Using Stem Cells to Repair Heart: After Promising Studies on Rodents, the Treatment Will Be Tested on Humans," The Wall Street Journal, p. D6 (April 16, 2002).

Dr. Leon Kass of the University of Chicago Debates Prof. Greg Stock of UCLA

April 15, 2002; Talk of the Nation (NPR-Radio; 11:00 AM PDT; TRT= 45 minutes) -- Biotechnology Roundtable with invited guests: Dr. Leon Kass, Chairman of The President's Council on Bioethics and Prof. Gregory Stock, Director of the Program of Medicine, Technology, and Society at the UCLA School of Medicine and author of the recent book Redesigning Humans: Our Inevitable Genetic Future (Houghton Mifflin Company, New York; 2002). Program hosted by Mr. Neal Conan of NPR News.

Summary:

Chimp Genome May Shed Light on Human Aging

April 12, 2002; Prof. Calib E. Finch, Director of USC's Alzheimer's Disease Research Center, said that the work published in today's issue of Science -- describing differential gene expression in the brains of humans vs. other primates, like Chimps, Orangutans, and Rhesus macaques, by teams at UC San Diego, GERMANY, and The Netherlands, including Drs. Ajit Varki and Pascal Gagneux -- could tell us a great deal about longevity genes. We know that the maximum lifespan for chimps is [55 - 60] years under ideal conditions (such as are found in zoos) {but only [40 - 45] years in the wild} while the maximum lifespan for humans is significantly more at 122 years (Madam Jeanne-Louise Calment of FRANCE). Yet the genomes of the two species are 98.7 percent homologous. So what does this mean for the number of gerontic genes? "If human aging is inherently slower than chimp aging, it seems plausible that we may be able to discover some of the genes that influence the species-aging phenotype, and these could become new targets for intervention in disease," he said Finch believes that the ApoE gene could be one of the candidate genes. It is associated with our more efficient processing of meat compared with chimps, who eat more vegetable matter in their diets. He speculates that perhaps there was a single mutation in ApoE that is responsible for our ability to avoid the cardiovascular implications of high blood cholesterol that is associated with substantial meat consumption that our kindred primate species don't have. The same amount of meat fat that will not affect humans can triple the cholesterol level in the blood of a chimp. Click for more details from Associated Press. Also, see a related news story on this website back on March 19, 2001.

Refs:

1.Wolfgang Enard, Philipp Khaitovich, Joachim Klose, Sebastian Z"llner, Florian Heissig, Patrick Giavalisco, Kay Nieselt-Struwe, Elaine Muchmore, Ajit Varki, Rivka Ravid, Gaby M. Doxiadis, Ronald E. Bontrop, and Svante Paabo, "Intra- and Interspecific Variation in Primate Gene Expression Patterns," Science, Vol. 296, pp.340-343 (April 12, 2002).
2. Rosie Mestel, "Chimps May Have Something to Tell Us," The Los Angeles Times, pp. A1, 20 (April 12, 2002).
3. Sharon Begley, "What Distinguishes Us from the Chimps? Actually, Not Much," The Wall Street Journal, p. A13 (April 12, 2002).
4. B. Bower, "The DNA Divide: Chimps, People, Differ in Brain's Gene Activity," Science News, Vol. 161, No. 15, pp. 237-8 (April 13, 2002).

President Bush Seeks Senate Ban on All Forms of Human Cloning both Therapeutic Cloning and Reproductive Cloning

April 10, 2002; 1:30 PM EDT; Washington, D.C.; President George W. Bush

used his pulpit in the East Room of the White House to lecture Americans and undecided Senators with a 15-minutes sermon on "the meaning of human life." There was an invitation-only audience of obviously sympathetic listeners providing hearty applause at all the right places. The level of orchestration was so tightly scripted and professionally rehearsed, the lecture had the look and feel of a mini "State-of-the-Union" address scripted by a Hollywood director to perpetrate the illusion that he spoke for all Americans, even though this is a highly controversial topic for many of us.. [Click on the photo above for the full text as supplied by the White House.] He "preached to a choir" of 175 sympathetic lawmakers, religious activists, researchers, and even some disabled people, issuing abstract platitudes like " life is a creation not a commodity." And furthermore, "no human life should be exploited or extinguished for the benefit of another." On the other hand, 40 Nobel Prize Winners were not so convinced. They signed a letter the same day distributed to the Senate, saying that therapeutic cloning was actually a good idea for Americans and it should certainly not be criminalized, warning that a legislative ban "would impede progress against some of the most debilitating diseases known to man."

The mood of the Senate on this issue is fiercely independent of either the White House or the House of Representatives and clearly crosses traditional party lines. In the Senate, debate is now likely to take place in late May, and we can expect to hear considerably more testimony from the scientists who have actually proposed to carry out this research, including Dr. Michael West, CEO of Advanced Cell Technology in Worcester, MA.

Curiously, Mr. Bush explained that he "wants the NIH to fund much more work on Adult Stem-Cell Biology," something that we here have no objection to and would certainly encourage.

[ Note: The President introduced the term " Research Cloning" to refer systematically to what we and other scientists have consistently called " Therapeutic Cloning" for more than a year now. This curious turn-of-phrase will, no doubt, inject confusion into the debate, but clearly this ploy was deliberate and served his agenda well of discrediting all forms of cloning .]

As far as Congressional lobbying groups are concerned, on the one hand we have The Coalition for the Advancement of Medical Research (CAMR), which represents patient advocacy groups
(such as The Christopher Reeve Paralysis Foundation),
the biotech industry, and several other scientific groups
(like The Alliance for Aging Research in Washington, D.C.; Daniel Perry, Executive Director
and the newly-formed International Society of Stem Cell Research with Drs. Leonard Zon of Children's Hospital in Boston, Irving Weissman of Stanford University, and Douglas Melton of Harvard University; Dr. Zon says "the Society will offer advice on clinical trials of new stem-cell therapies and weigh in on hot topics such as human therapeutic cloning". The Society plans to hold its first annual meeting late next year.),
Cures Now of Los Angeles, CA maintains an impressive Scientific Advisory Board, including Drs. Paul Berg(*) and Irving Weissman of Stanford, Dr. Richard Klausner, former Director of the National Cancer Institute, Drs. David Baltimore(*) and David Anderson of CalTech, and Dr. Thomas Cech(*) of the University of Colorado. [* = Nobel Prize Winners].
while on the other hand we have a newly-formed opposition lobbying group called Americans to Ban Cloning, a consortium of groups seeking a comprehensive, world-wide ban on all forms of cloning.
Sort of in between, we have Do No Harm; The Coalition of Americans for Research Ethics, a "national group of researchers, health care professionals, bioethicists, legal professionals, and others dedicated to the promotion of scientific research and health care which does no harm to human life." They are stridently opposed to therapeutic cloning, yet strongly in favor of therapeutic interventions using adult stem cells.

Click for more details from CNN. CNN followed the President's address with 15 minutes of additional commentary by Sen. Tom Daschel (D-SD), Dr. Panos Zavos, Ph.D. Andrologist from Lexington, KY, and Prof. Alex Capron of USC in Los Angeles, a former member of the President's Advisory Commission during the Clinton Administration.

Refs.

1. CNN-TV (April 10, 2002; 1:30 PM EDT; TRT = ~30 minutes).
2. Laurie McGinley and Antonio Regalado, "Cloning Clamor Grows: Nobel Winners Oppose a Ban, Sen. Frist Announces His Support As Senate Prepares for Debate," The Wall Street Journal, pp. A1, B1,3 (April 10, 2002).
3. Geeta Anand and Antonio Regalado, "Slow Road for a Stem-Cell Researcher," The Wall Street Journal, pp. B1,3 (April 10, 2002).
4. Ronald Brownstein and Aaron Zitner, "Bush to Urge Senate to Ban All Cloning," The Los Angeles Times, pp. A1, 14 (April 10, 2002).
5. Aaron Zitner, "Bush Presses for Cloning Ban," The Los Angeles Times, p. A17 (April 11, 2002).
6. Editorial, "Off Track on Cell Research," The Los Angeles Times, p. B14 (April 11, 2002).
7. "Bush Restates Ban on Human Cloning," The Wall Street Journal, pp. A1, D8 (April 11, 2002).
8. Connie Mack, "There's Nothing 'Anti-Life' about Medical Cloning," The Los Angeles Times, p. B15 (April 12, 2002).
9. Science Scope: "Stem Cells United," Science, Vol. 295, No. 5564, p. 2343 (March 29, 2002).
10. Cartoon by Michael Ramirez, "Image of a fetus with parts prelabeled 'Stem Cells' for Alzheimer's, Parkinson's, Heart Disease, Cancer, Diabetes, Cystic Fibrosis, etc.," The Los Angeles Times, p. M5 (April 14, 2002).
11. Aaron Zitner, "Cloning Advocates, Foes Battle for Senators' Votes," The Los Angeles Times, p. A10 (April 17, 2002).

Chinese Scientists Sequence the Rice Genome

April 5, 2002;. A team led by Profs. Yang Huanming (Chinese Academy of Sciences) and Jun Yu (of the University of Washington in Seattle) with The Beijing Genomics Institute in collaboration with the Torrey Mesa Research Institute in San Diego (Stephen A. Goff) owned by Swiss agricultural giant Syngenta International and with a contract to Myriad Genetics, Inc. of Salt Lake City, UT spent about $30 million to complete the sequence of rice as announced in today's issue of Science. Rice appears to contain [50 - 55],000 genes, compared with only about 35,000 for humans. Yet, humans have six times more base pairs, which means that there is an average increase in density of an order-of-magnitude (a lot less random repeats of nonsense DNA apparently). Other cereal plants have considerably more DNA than rice. For reference, barley has ten times more base pairs while corn has five times more base pairs. Yet, there is a 98 percent homology between the genes in rice, wheat, corn, and barley. "Unexpectedly, rice may turn out to be the Rosetta Stone of all [plant] genome sequences," said Gane Ka-Shu Wong at the University of Washington in Seattle.

A separate international consortium led by Japanese scientists expects to complete their own version by the end of the year," according to Dr. Takuji Sasaki, Chairman of the International Rice Genome Sequencing Project. There are about 11,000 gaps still needing to be filled in. "All the initial drafts of the different strains of the rice genome sequences assembled by different collaborators should be pooled and finalized in about 18 months" experts said. Click for more details from CNN.

Refs:

1. Antonio Regalado and Peter Landers, "Map of Rice DNA May Hellp Tailor Crops," The Wall Street Journal, pp. A1, B6 (April 5, 2002).
2. Robert Lee Hotz and Aaron Zitner, "Rice's Genetic Map May Help Build a Better Cereal: Science: Researchers Hope to Boost Yield and Make the Grain More Nutritious," The Los Angeles Times, pp. A1, 34 (April 4, 2002)
4. Jun Yu, et al., "A Draft Sequence of the Rice Genome ( Oryza sativa L. ssp. indica)," Science, Vol. 296, p. 79 (April 5, 2002).
5. Stephen A. Goff, et al.;"A Draft Sequence of the Rice Genome ( Oryza sativa L. ssp. japonica)," Science, Vol. 296, p. 92 (April 5, 2002)..

Severino Antinori Claims 20-Cell Human Clone Maybe Embryo Implantation in Surrogate Mother

April 7, 2002; Dr. Severino Antinori, M.D. has reportedly stated that "one woman ... in his program is eight weeks pregnant," however, he has subsequently refused to either confirm or deny this assertion. The quote was reported in Gulf News, an English-language newspaper in the United Arab Emirates, on Wednesday, April 3rd, while he was responding to a question during a lecture he was giving at the Zayyed Center for Follow-up and Coordination, a think tank in Abu Dhabi. Prof. Rudolf Jaenisch of the Whitehead Institute at MIT was both angry and skeptical at the news. "I do not trust these people to tell us the truth," he said "The best outcome for such a baby would be death before birth."

Ref:

(Reuters) "Scientists Skeptical About Claim of Cloning: Controversial Italian Fertility Specialist Refuses to Confirm Reports of a Woman's Pregnancy. Some Doctors Express Outrage," The Los Angeles Times, p. A2, 9 (April 7, 2002).

April 4, 2002; Dr. Severino Antinori, M.D. (OB/GYN) Director of the Associated Researchers for Human Reproduction (RAPRUI) Clinic in Rome, ITALY claims to have spent more than $100,000 from anonymous private sources (presumably from rich Asian and Arabian men) to set up a lab with 20 researchers of various nationalities in an undisclosed Asian location with the aim of cloning the first human baby. How far has he gotten? He says, "We have cloned a human preembryo up to 20 cells" (recall that ACT had ostensibly accomplished only six cells). His approach will be to utilize the nuclei from epidermal cells instead of from fibroblasts and also to use oocytes taken from different stages of the cell cycle.

Refs:

1. Sergio Pistoi, "Father of the Impossible Children: Ignoring Nearly Universal Opprobrium, Severino Antinori Presses Ahead with Plans to Clone a Human Being," Scientific American, Vol. 286, No. 4, pp. 38-39 (April 2002).
2.. Gregory Stock, Redesigning Humans: Our Inevitable Genetic Future (Houghton Mifflin Co; New York; 2002).
3. Francis Fukuyama, Our Posthuman Future: Consequences of the Biotechnology Revolution (Farrar, Straus, & Giroux, New York; 2002).
4. Nicholas Wade, "A Dim View of a 'Posthuman Future' of Altered Human Nature," The New York Times, pp. D1, 4 (April 2, 2002).
["Although Dr. Fukuyama credits science and technology with giving a forward direction to history over the last 500 years," he says that "human cloning should be banned outright," since he regards it as "immoral in and of itself and as an opener for still worse things to come, like enhancing human qualities by germline genetic engineering."]
5. Four Letters to the Editor by Peter B. Martin of Coconut Creek, FL, Frank L. Cocozzelli of Staten Island, NY, Sara Jasper Cook of Cortlandt Manor, NY, and Dr. Albert Roos of St. Louis, MO, "Questioning the Moralist," The New York Times, p. F3 (March 26, 2002).
[All of these letters were decidedly hostile to Dr. Kass.]
6. Letter to the Editor by Rev. Alexander Harper of Norwalk, CT, "Criticism of a Moralist," The New York Times, p. F4 (April 2, 2002).
["I was disappointed at letters (of March 26th cited above) only in caustic criticism of the President's choice of Dr. Leon Kass as Chairman of the President's Council on Bioethics. As a teacher of a course on the Science and Ethics of Stem-Cell Research, I am thankful that we have such a thoughtful scientist as Dr. Kass, who has kept his sense of humane values as Head of such an important advisory Council for the President. As war is too important to leave to the generals, so are the consequences of bioengineering too important to leave to the laboratory technicians."]
7. Editorial, "Indiana Jones Goes to D.C.," The Los Angeles Times, p. B16 (March 28, 2002).
["Concerns raised about where [Elias] Zerhouni stands on cloning and stem-cell research are to the point. At Johns Hopkins, Zerhouni played a key role in developing such research, arguing that it should be "as unimpeded as pssible, because it may have a huge potential for all mankind." However, the Bush Administration has suggested recently that Zerhouni would support constraints favored by the far right, specifically a Bill by Sen. Sam Brownback (R-KA) that would criminalize even the cloning of a person's own cells to treat illnesses such as Parkinson's Disease.]
8. J. Travis, "Stem-Cell Success: Mice Fuel Debate on Embryo Cloning," Science News, Vol. 167, No. 11, p. 163 (March 16, 2002).
[Advanced Cell Technology of Worcester, MA has reportedly used therapeutic cloning to derive bovine stem cells to create kidneys that it has transplanted into adult cows. Dr. Robert Lanza of ACT has confirmed these reports but declined to offer any further details, noting that "the company planned to publish its results soon."
Click for a Reuters News Item on June 7, 2002 about a forthcoming publication in the July issue of Nature Biotechnology.]
9. J. Travis, "Transplant Triumph: Cloned Cow Kidneys Thrive for Months," Science News, Vol. 161, No. 23, p. 356-7 (June 8, 2002).
[Dr. Robert Lanza will provide new results in the July issue of Nature Biotechnology.]
10. "Clones Face Uncertain Future," Science News, Vol. 167, No. 12, p. 189 (March 23, 2002).
[The National Institute for Infectious Diseases in Tokyo reported in the March 2002 issue of Nature Genetics that cloned animals have a shorter-than-normal-lifespan. In one of the experiments, 10 of 12 cloned mice died within 800 days of birth, whereas only 1 of 7 mice produced through natural mating died within that span. Autopsies conducted on six cloned mice that appeared to die prematurely revealed liver damage and pneumonia, suggesting a weakened immune system compared with normal controls.]
11. Interview with Dr. Thor Lemischka of Princeton University, "Good News about Stem-Cell Therapy," Bottom Line Health, Vol. 16, No. 4, pp. 7-9 (April 2002).
[Researchers at Johns Hopkins University injected specially-altered embryonic stem cells into the spinal cords of rats that were paralyzed with ALS (Lou Gehrig's Disease), and "three months later, the rats were able to move their paralyzed hind quarters and walk, although clumsily." Although adult stem cells are now being successfully used in transplants, more research is needed to determine whether they hold the same promise as embryonic stem cells.]

French Scientists Clone a Rabbit

March 30, 2002; Paris, FRANCE ( CNN) IN the April issue of Nature Biotechnology, French scientists, led by Jean-Paul Renard of the French Agronomy Research Institute, report that they have cloned a rabbit. This new species can now be added to the prior list of sheep, mice, rats, cows, pigs, and cats. Conspicuously absent from the list are dogs and horses where considerable effort has not yet yielded results. The French accomplishment was made difficult by the quirky timing of the rabbit's reproductive system, waiting to prime the host mothers for implantation by nearly a day and then transplanting slight more mature four-cell preembryos. 27 host mothers were implanted, resulting in four live births. The clones are now fully mature, are in good health, and have themselves reproduced normally. Click for more details.

Refs:

1. "French Rabbits are Reproducing Like Sheep," The Los Angeles Times, p. A4 (March 30, 2002).
2. Vanessa Fuhrmans, "Out of the Cloning Hat Comes a Rabbit, Four Times Over, Just in Time for Easter," The Wall Street Journal, p. B5 (April 1, 2002).

Is the Whole More Than the Sum of Its Parts?

"It is a truism that the blastocyst has the potential to become a human being. Yet at that stage of development it is simply a 'clump' of cells... An analogy might be what one sees when walking into a Home Depot. There are the parts for at least 30 homes. But if there is a fire at the Home Depot, the headline doesn't read '30 Homes Burn Down.' It's 'Home Depot Burns Down'."

--- Prof. Michael Gazzaniga, Dartmouth University Neuroscientist at a meeting of the President's Bioethics Panel last month in Washington, D.C.

Ref.

"Metaphor of the Week," Science, Vol. 295, No. 5560, p. 1637 (March 1, 2002).

Australia Will Approve Stem Cell Harvesting from Spare IVF Embryos for Research

March 26, 2002; 6:38 PM (The Age newspaper of Canberra) Australian scientists have apparently won their campaign to use stem cells taken from spare IVF embryos for research, winning the support of the prime minister and state ministers. Quoting senior government sources, the paper said that "during a special meeting of cabinet last week ministers had warned that Australia risked losing world-class scientists offshore if it banned the use of the embryos for stem- cell research." "[Prime Minister John] Howard will consult with church leaders before finalizing his decision on embryonic stem-cell research before a meeting of state ministers next week," his deputy John Anderson said today.

Stem Cells Make Blood Vessels

March 26, 2002; Stem-cell researchers from MIT and Israel found that cells derived form a human embryo can grow into blood vessels, an ability with promise in fighting heart disease. Click for more details.

Ref:

The Wall Street Journal, p. A1 (March 26, 2002).

Editorial: XenoCloning in South Korea Causes World-Wide Furor

March 19, 2002; Dr. Park Se Pill, an embryologist from Seoul, South Korea who trained in the US under Prof. Neal First at the University of Wisconsin, says that "work on cross-species fusion of a human nucleus and an enucleated bovine egg has now been discontinued at Maria Bio Tech after a number of his team's preembryos went for about a week or so and then failed to continue mitotic divisions. Thus, they were never able to achieve their goal of obtaining human stem cells from the cloned embryo once divisions came to a halt. Dr. Park speculated that the reason was "a failure to achieve proper signaling between the maternal bovine mitochondria and the human nucleus." However, Dr. Park predicted that "with enough practice this barrier could be overcome by other scientists."

In this third in a series of Editorials over the past year on the topics of "Stem Cells and Human Cloning," the GRG wishes to go on record as asking the scientific community for a five-year moratorium on Human Cross-Species Cloning.

This is no longer a frivolous hypothetical issue. It has been recently rumored that Dr. Sheng Huizhen, a US-trained biologist at the Shanghai No. 2 Medical University in China, successfully derived human stem cells from an enucleated rabbit egg implanted with a human nucleus. Furthermore, the US Patent Office has received applications from ACT of Worcester, MA and from the College of Veterinary Medicine at Seoul National University in South Korea on the methodology for doing Human/Bovine XenoCloning. The arguments in favor of XenoCloning are that animal eggs are considerably less expensive to obtain than human eggs and that "it is a question of the freedom of scientists to use whatever means that may be available to make progress," according to Dr. Jung Sung Chul, a Section Chief at the Korean National Institutes of Health.

However, the reasons for recommending against pursuing Human XenoCloning are clear, independently of any moral reservations from non-scientists. (Endangered-species closely-related XenoCloning or surrogate mothering [like the case of the gaur/cow] may have considerations outside the scope of this argument.) First, we don't have a clue about what we're doing as far as signaling between the nucleus and the egg's ooplasm is concerned, mitochondrial or otherwise. So the closer we get to perceived success, the more dangerous the experiment may be for the ostensible recipient of any stem cells that are obtained. Secondly, we haven't been successful with human eggs yet, not withstanding rumors to the contrary, where the ostensible signaling problems should be easier to solve. At this particular moment when the US Senate is about to vote on the issue of Human Therapeutic Cloning, we don't need to inject any new controversy about untrustworthy, irresponsible scientists who will create "Frankenstein Hatcheries" if left to their own devices. Our opponents will certainly exploit every opportunity to paint all scientists with a disreputable brush to serve their own end of "Banning all forms of Cloning," which is still a real possibility.

Refs:

1. Antonio Regalado and Meeyoung Song, "Furor Over Cross-Species Cloning: Fusing Human DNA and Egg of Cow Creates Embryo and World-Wide Debate," The Wall Street Journal, pp. A1, B1, 9 (March 19, 2002).
2. Alan Trounson, "The Genesis of Embryonic Stem Cells: Does Parthenogensis Offer a More Promising Means of Developing Immune-Matched ES Cells?" Nature Biotechnology, Vol. 20, No. 3, pp. 237-8 (March 2002).

The World's Oldest Living Man and Woman Are Both Japanese

Monday, March 18, 2002; This just in from Mr. Louis Epstein, Chairman of the International Supercentenarian Committee of which the LA-GRG is a member...
"I have just heard from Ms. Lori Ferris that her Great-Grandmother Mrs. Maud Farris-Luse of Michigan died this evening, having been hospitalized with pneumonia Sunday night. Maud was aged 115 years, 56 days, the oldest person since Mrs. Sarah Knauss of Allentown, Pennsylvania.

The "World's-Oldest" mantle now passes to Mrs. Kamato Hongo of Japan. Click on the photo above for more details from Associated Press. In addition, click through to the Centenarians Section of this website (listed on the menu to the left) for many more details.

Japanese Woman Now Claims Reign As "World's Oldest Person"

March 21, 2002 (AP) " Mrs. Kamato Hongo, age 114, is now The World's Oldest Known Living Person," the Guinness Book of Records tells the Associated Press. Mrs. Hongo, born September 16, 1887, inherited the title this week after the death of 115-year-old Maud Farris-Luse in Coldwater, MI. The new record holder credits her longevity with avoiding stress, her love of traditional Japanese dancing, and downing a few shots of stiff sake every now and then. "Hongo has seven children, more than 20 grandchildren, and has outlived her eldest daughter who died in her 90's two years ago," the AP says.

Refs:

1. "Maud Farris-Luse; Oldest Person at 115," The Los Angeles Times, p. B11 (March 20, 2002).
As one of the news sources for this story, the GRG was explicitly mentioned at the end of this article. Click on her photo above.
2. CNN story.
3. From the The Washington Post, p. B6 (March 20, 2002).
Maud Farris- Luse, 115, who was recognized last year by the Guinness World Records book as the oldest living person, died March 18th in a hospital in Coldwater, MI. She had pneumonia. She had worked as a factory clerk, hotel maid, baker, and restaurant cook before retiring in her 70's. She lived alone and cared for herself until she broke her hip in a 1991 fall at her house and moved to a nursing home in Coldwater

Three Editorial Board Members of the Journal of Regenerative Medicine Resign Because of ACT Publication

March 15, 2002; Dr. Davor Solter from the Max Planck Institute for Immunobiology in GERMANY; John Gearhart of the Johns Hopkins University School of Medicine in Baltimore, USA; and Robin Lovell-Badge of the National Institute of Medical Research in London, UK all felt that they could not endorse the findings as published by ACT last November 2001 and have resigned in protest.

Ref: Tinker Ready of Boston, "Scientists Resign Over Stem-Cell Study," Nature Medicine, Vol. 8, No. 3, p. 200 (March 2002).

Adult Stem Cells May Not Be As Powerful As Embryonic Stem Cells After All

March 14, 2002 ( WSJ) Adult stem cells may not be as promising a source for tissue regeneration as embryonic stem cells, studies in the current issue of Nature suggest. Scientists at the University of Edinburgh in SCOTLAND and the University of Florida in Gainsville found that adult cells failed to show an ability to copy tissue they were injected into. Click for more details.

Ref:

The Wall Street Journal, p. A1 (March 14, 2002).

SCID Mouse Cloning Breakthrough at MIT

March 8, 2002; In today's on-line issue of the journal Cell, Drs. George Q. Daley and Rudolf Jaenisch of the MIT Whitehead Institute in Cambridge, MA, reported on a potent combination of therapeutic cloning, stem cells, and gene therapy partly restored health to mice inflicted with Severe Combined Immune Deficiency (SCID). One surprise, however, was that the limited immune systems of the sick mice still attempted to attack the autologous cloned cells as though they were "foreign." The theoretical promise of therapeutic cloning is that the autologous tissues should never be rejected, but that has yet to be proven. "It is much more complicated than we imagined," Dr. Daley said.
[ Editor's Note: Could it be that embryonic surface antigens on the stem cells are construed as "cancer," and even a limited immune system attempts to trigger apoptosis in neoplastic cells? This cannot be the complete answer, but we really need to investigate this phenomenon urgently to rule out alternative hypotheses of adult immune surveillance attempting to destroy cells exhibiting embryonic antigens. Perhaps, differentiating the cells in culture before inoculation will conceal their embryonic origin and return them to a state of "tolerance."]

Refs:

1. Antonio Regalado, "Cloning Breakthrough May Aid In Treatment of Host of Diseases," The Wall Street Journal, p. A1, B8 (March 8, 2002).
2. William M. Rideout, III, Konrad Hochedlinger, Michael Kyba, George Q. Daley, and Rudolf Jaenisch, "Correction of a Genetic Defect by Nuclear Transplantation and Combined Cell and Gene Therapy," Cell, Vol. 109, pp. 17-27 (April 5, 2002).

Prof. Lu Guangxiu of Xiangya, China May Have Beaten ACT to the First Human Clone

March 6, 2002 ( WSJ) "China's policy makers are rushing to embrace therapeutic cloning as a potential tool for extending human life." Although the Xiangya team has not yet published in Western journals, "they are beginning to realize that they need to subject their work to scientific scrutiny to win the global recognition they deserve." One of the Chinese innovations in technique is leaving the egg's nucleus in tact while injecting the donor nucleus in close proximity. Then, they allow both to grow -- in some cases for as long as ten hours -- before enucleating the egg's nucleus just before the egg would normally undergo mitosis. This technique helps to preserve the normal volume of ooplasm which is frequently depleted when the nucleus is removed first, as is normally the case. The little-understood chemokines in the egg's cytoplasm are what appear to facilitate the egg's ability to return the donor-nucleus DNA to an "embryonic" state [ Editor's Note: Maybe demethylation?] in which it is capable of developing into a preembryo.

Ref:

Karby Leggett and Antonio Regalado, "As West Mulls Ethics, China Forges Ahead In Stem-Cell Research: Prof. Lu's Lab Says It Cloined A Human Embryo in 1999 And Is Getting Better at It," The Wall Street Journal, p. A1, 6 (March 6, 2002).

US Senate Torn Over Cloning

March 6, 2002;

A new foundation called the "National Stem-Cell Research Coalition" (cofounded by film director Jerry Zucker and his wife Janet as well as producer Doug Wick and his wife Lucy Fisher) has raised $600,000 in the last month primarily to help diabetic patients.

Refs:

1. Aaron Zitner, "Senate Torn Over Cloning: Prominent Voices for and Against Using the Technique on Humans Speak before Lawmakers," The Los Angeles Times, p. A10 (March 6, 2002).
2. William Kristol and Jeremy Rifkin, "First Test of the Biotech Age: Human Cloning: Do We Have the Will and the Wisdom to Say No?" The Los Angeles Times, p. B11 (March 5, 2002).
3. Aaron Zitner, "Clones, Free Love and UFO's," The Los Angeles Times, p. A1, 12 (March 5, 2002).
This article reveals that the secret location of Dr. Brigitte Boisseller's US Cloning Lab, before it was shut down by the FBI in April 2001, was actually Nitro, West Virginia. The Raelian's new secret lab is somewhere abroad. Monsieur Vorilhon (The Prophet Rael) has claimed that 3,000 persons (followers?) have signed up for Clonaid's reproductive services. The first human clone, according to their leader, will be like the messiah.
4. Bert Vogelstein, Bruce Alberts, and Kenneth Shine, "Please Don't Call It Cloning!" Science, Vol. 295, No. 5558, p. 1237 (February 15, 2002).

MD Anderson Cancer Center Finds Therapeutic Adult Stem Cells in Blood

March 6, 2002 (WSJ) In today's issue of the NEJM Dr. Marin Krobling of the MD Anderson Cancer Center in Houston, TX published his team's findings that adult blood stem cells can rejuvenate liver, gut, and skin tissues. Click for the Abstract.

Ref.

Laura Johannes, "New Study Suggests that Blood May Contain Useful Stem Cells," The Wall Street Journal, p. A1, B3 (March 7, 2002).

Celera's Contribution Disputed by the Publicly-Supported Human Genome Project

March 5, 2002; Washington, D.C. (AP) -- As published in this week's Proceedings of the National Academy of Sciences, Robert Waterston of Washington University in St. Louis, Eric Lander of MIT, and John Sulston of the Wellcome Trust in the UK, dispute the notion that the "whole genome shotgun" method really worked. The Celera team, however, denounced the study as flawed and erroneous. Dr. Craig Venter, Cofounder of Celera, called the paper "game- playing at the worst level in academics and devoid of any substantive science."

Refs:

1."Scientists Say Gene Decoders Needed Them," The New York Times, p. A18 (March 5, 2002).
2. Scott Hensley and Antonio Regalado, "Scientists Publish Critique of Celera's Work: Rivals Charge Firm Recycled Public Data in Genome Map," The Wall Street Journal, pp. A1, 2, 6 (March 5, 2002).

Canada to Allow Stem Cell Research

March 4, 2002; Click for more details.

Ref:

"Stem-Cell Funding Guidelines Issued by Canada," The Wall Street Journal, p. A1 (March 5, 2002).

The University of North Texas Maintains an Archive of Films on Aging

March 3, 2002; Denton, TX -- The Collection is home to over 600 audio-visual titles concerned with different aspects of aging and long-term care, from feature films to clinical programs. The UNT Media Library maintains and circulates this collection of 16 mm films and videos. All titles are available for rental by your home institution for classroom showings or in-service education. Click for more details about the collection.

Abstracts Proposed as Candidates for the Most Important Advance in Anti-Aging Medicine for 2002

March 2, 2002; Chicago, IL Click for an initial list of 20 or so Abstracts submitted by Dr. Leonid Gavrilov of the University of Chicago. We expect to have a Committee judge these Abstracts at the end of the year and choose a winner. If you have any papers that you would like to nominate for the Annual Award (and Prize) please do not hesitate to get in touch with us. Formal criteria for the Annual Award will be published at a later date.

Cloned Mice are Obese according to the University of Cincinnati

March 1, 2002; (AP and CNN) The prevalence of obesity in cloned mice has researchers questioning just how effective the cloning process can be for research on animals or humans. A new report, published in tomorrow's issue of the journal Nature Medicine, describes a group of cloned mice that, "upon reaching adulthood, showed excessive percentages of body fat and increased levels of insulin and an appetite-suppressing hormone called leptin in their blood," reports The Associated Press.

But because the offspring of the mice did were not obese, the researchers suggest that the method of cloning itself may have been flawed. In an accompanying commentary, Dr. Ian Wilmut, the British researcher behind Dolly, the world's first cloned sheep, said "the research calls into question whether any clones are entirely normal." Researchers have reported that Dolly developed arthritis at the relatively young age of 5 1/2 years. Click for more details.

House of Lords in UK Gives OK to Therapeutic Cloning

February 27, 2002; London, UK The House of Lords has voted to approve Therapeutic Cloning under strict conditions. Click for more details from CNN.

Refs:

1. CNN Headline News (February 28, 2002; 10:30 AM PST).
2. Reuters, "Researchers Get Britain's OK on Embryo Cells," The Los Angeles Times, p. A5 (February 28, 2002).
3. "The UK Issues Licenses for Stem-Cell Experiments," The Los Angeles Times, p. A4 (March 2, 2002).
"Britain is also setting up a National Stem-Cell Bank -- similar to a blood bank -- to store the cells and make them available to researchers." [ Editor's Note: It is not yet clear, based on the published scientific literature, whether the Universal Stem-Cell-Donor/Blood-Bank Model or the Patient-Specific-Therapeutic-Cloning/Autologous-Transfer Model will be the one that finally succeeds in overcoming the problem of acute rejection.]

UK Couple Given Permission for a 2nd Baby to Help 1st Baby with Thalassemia

February 24, 2002; London, UK (AP) -- Using IVF and Preimplantation Genetic Diagnosis, a British couple has been given permission by the HFEA to allow a 2nd baby to help a 1st baby with fatal Thalassemia achieve a cure.. Click for more details.

First Annual Silver-Fleece Awards for Fraudulent Claims in Anti-Aging Quackery

[ Editor's Note: Several of our members have already pointed out, with misgivings, that this sort of humor could well backfire to the detriment of respectable scientific efforts that happen to have the name "Anti-Aging" in their title, such as our own Journal of Anti-Aging Medicine. How to reconcile the motives of these mutually praiseworthy efforts is going to be difficult. In particular, members are specifically concerned about a *second* type of award intended to discredit anti-aging organizations that may injure legitimate anti-aging research efforts. By the way, the first-time "winner" of this second fraudulent-organization-category was -- you guessed it -- the "A4M." This "award" has engendered considerable controversy within our discussion group, both for and against.]

Appetite-Suppressing Drug Can Make Mice Lean

February 21, 2002 ( CNN) Click for more details from Health on CNN.

Dr. Ian Wilmut Is Opposed to Reproductive Cloning of Humans

February 21, 2002 ( CNN) Click Dolly for more details

from Health on CNN.

Anti-Oxidants Help Old Rats at Berkeley

February 19, 2002; As published in the latest issue of PNAS, Prof. Bruce Ames of the Department of Biochemistry at UC Berkeley has improved the energy level and memory skills of old rats using a combination of over-the-counter antioxidant supplements. Click for the Abstract and more details from the BBC.

The Challenge of Parthenogenesis

February 18, 2002; Click for more details.

Refs:

1. Brendan A. Maher, "The Stem Cell-Cloning Plot Thickens: Ethical Challenges Get Cloudy with the Entrance of Parthenogenesis," The Scientist, Vol. 16, No. 4, p. 19 (February 18, 2002).
2. E. Russo, "Bypassing Peer Review," The Scientist, Vol. 14, No. 5, p. 1 (March 6, 2000).
3. T. Agres and E. Russo, "Cloning Controversy Re-Emerges in US," The Scientist, Vol. 16, No. 1, p. 29 (January 7, 2002).
4. S. P. Westphal, "Is This the One?" New Scientist, Vol. 173, p. 4 (January 26, 2002). 5. R. Weiss, "Scientists Claim an Advance in Therapeutic Cloning," The Washington Post, p. A4 (January 30, 2002).

Too Much Sleep Can Shorten Your Life

February 15, 2002; San Diego, CA (AP) According to a new study at UCSD, too much sleep may be bad for your longevity. Click for details.

The old adage that you need at least eight hours of sleep a night for a long, healthy life may need to be put to rest. You should get no less than four, no more than eight, but "six or seven hours of nightly rest is preferable if you want to live longer," HealthScout News reports. Researchers at the University of California, San Diego School of Medicine and the American Cancer Society surveyed 1.1 million adults between the ages of [30 - 102]. They found that individuals who sleep eight hours or more hours a night, or less than four, have a significantly higher mortality rate than those who get an average of six to seven hours of sleep. Those who rise after seven hours have the best odds. The researchers also found that people who reported occasional insomnia had no elevated risk, while those who said they took sleeping pills did have an increased mortality rate." The findings appear in the February issue of the Archives of General Psychiatry.

Ref:

"Six or Seven Hours of Sleep Is Better, Study Says," The Los Angeles Times, p. A28 (February 25, 2002).

AAAS Position Statement on Cloning

February 14, 2002; Washington, D.C. Click for the one-page AAAS Policy, which is consistent with statements made by other scientific bodies, such as the California Medical Advisory Board (See January 12th below) and the NAS Advisory Board (See January 18th below)

Texas A&M First To Clone a Cat

February 14, 2002; College Station, TX ( NPR Radio) Researchers affiliated with Texas A&M University have announced the first cloning of a domestic cat

The kitten CC (short for "Copy Cat" or maybe "Carbon Copy") is now nearly two months old and appears to be perfectly healthy and energetic. However, she is completely unlike her tabby surrogate mother, Allie. Not surprisingly, CC is very close to her genetic mother Rainbow, but not exactly, since even genetically-identical calico cats do not always look the same, as far as fur coloration is concerned. Differences in fur colors may be explained more by location in the womb and temperature profiles during embryogenesis/fetogenesis than by the DNA itself.

The work was funded by Genetic Savings & Clone, Inc., founded in Texas by Dr. John Sperling, 81, of Phoenix, AZ and Chairman of The Apollo Group, The University of Phoenix, and The Kronos Group, at the rate of $3.5 million.

By the way, veterinarians are still currently trying to clone dogs, horses, tigers, and antelopes, so far without success. Of course, sheep, pigs, cattle, goats, and mice are cloned on a routine basis today. A related project called The Missyplicity Project, is a $3.7 million effort to clone a specific mixed-breed dog named Missy, and is helping fuel the progress of Texas A&M's cloning research program. [ Editor's Note: There is a photo of Missy on the Archive Section of this website {at the bottom of the Main Page} and a brief article dated August 26, 1998 with a pointer to their website.] But it is now known that dogs are much harder to clone, possibly because their estrus cycle is so different. Click the first picture for more details from Texas A&M. Click the second picture for the Abstract from Nature and more details from CNN. At Noon time on Friday, February 15th, a radio report stated that the Texas company was swamped with phone calls from all over the country by pet owners trying to get in line for a chance to clone their own cat (and/or dog).

Refs:

1. Taeyoung Shin, Duane Kraemer, Jane Pryor, Ling Liu, James Rugila, Lisa Howe, Sandra Buck, Keith Murphy, Leslie Lyons, and Mark Westhusin, "Cell Biology: A Cat Cloned by Nuclear Transplantation," Nature (February 14, 2002).

By the way, Mr. Robert Young of Atlanta, GA reports that the world's record for the oldest domestic cat is 34 years, although there's been a claim for 36 years.

Infigen, Inc. Clones Pigs from Adult Cells

February 12, 2002; DeForest, WI (AP) Scientists at Infigen, Inc. have announced that they cloned piglets from the ear cells of two prized boars. This is the first time that a pig has been cloned from an adult cell, as opposed to fetal cells. One of the goals of cloning farm animals is to be able to duplicate prized animals precisely, but there are potential human therapeutic applications as well, involving organ transplantation without rejection.

Ref:

"Piglets Cloned from Ear Cells of Prized Boars," The Los Angeles Times, p. A13 (February 12, 2002).

Cloned Mice Do Not Appear to Live As Long As Controls

February 10, 2002; Tokyo, JAPAN (AP) "The early deaths of nearly all mice in a group of 12 cloned mice has researchers questioning the overall safety and effectiveness of cloning," according to wire service reports. A team of Japanese researchers who cloned the mice said that aside from some abnormal liver enzyme levels, the animals looked normal at birth. However, they started to die at 311 days after birth, and all but two of the mice died within 800 days. On the other hand, "a control group of mice born through natural mating and artificial fertilization lived much longer," the researchers said. Dr. Atsuo Ogura, the lead researcher with the National Institute of Infectious Diseases, speculated that "cloned animals may be born old, with a genetic make-up associated with aging." Another expert embryologist from ACT, Dr. Tony Perry, speculated that the particular microsurgical method used to clone the mice may have been responsible for damage to the embryos' DNA and that cloning itself may not be an intractable biological barrier. Click for more details.

Ref:

Rosie Mestel, "Mice Created by Cloning Have Shorter Life Spans, Study Finds," The Los Angeles Times, p. A15 (February 11, 2002).

The Quest to Extend the Human Lifespan

February 8, 2002;

Madame Jean Louise Calment was the world's oldest documented human at age 122 years. Click on her picture to find out if she had any special "gerontic" genes.

Oldest Documented Koala Bear Dies at the San Francisco Zoo

February 8, 2002;

Click Clarry's photo for more details from Reuters.

Department of Energy Microbial Cell Project

February 6, 2002; Click on the photo of DNA above to access the well-done DOE course on cellular physiology.

New 'World's Oldest Man' Named

February 4, 2002 (AP) -- The world has a new "oldest man." The Guinness Book of Records has officially declared that 112-year-old Yukichi Chuganji, a retired Japanese silkworm breeder, is now the "world's oldest man," reports The Associated Press. Mr. Chugani earned the esteemed title after the former "world's oldest man," Italian Antonio Todde, died last month just before his 113th birthday [See story below on January 4th]. When asked about the secret of his longevity, Chuganji's daughter speculated "My Daddy eats and drinks alcohol moderately. And he is an optimist,'' said the AP. Click on their picture for more details on this same website.

ACT Derives Monkey Stem Cells by Pathenogenesis

February 1, 2002 ( WSJ) - - In today's issue of Science Magazine, scientists from ACT in Worcester, MA and Wake Forest University Medical School in Winston-Salem, NC have coaxed pleuripotent stem cells from the unfertilized egg of a monkey. Only one primate egg, from a monkey named Buttercup, however, produced a viable stem cell line.

Refs:

1. Jose B. Cibelli [1], Kathleen A. Grant [2],* Karen B. Chapman [1], Kerrianne Cunniff [1], Travis Worst [2], Heather L. Green [2], Stephen J. Walker [2], Philip H. Gutin [3], Lucy Vilner [1], Viviane Tabar [3], Tanja Dominko [1], Jeff Kane [1], Peter J. Wettstein [4], Robert P. Lanza [1], Lorenz Studer [3], Kent E. Vrana [2], and Michael D. West[1]*, "Parthenogenetic Stem Cells in Nonhuman Primates," Science, Vol. 295, No. 5556, pp. 779-780 (February 1, 2002).

_____________________________________________

1. Advanced Cell Technology, One Innovation Drive, Worcester, MA 01605, USA
. 2. Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston Salem, NC 27157, USA.
3. Sloan Kettering Cancer Center, New York, NY 10021, USA.
4. Mayo Clinic, Rochester, MN 55905, USA.
_________________________________________
* To whom correspondence should be addressed. E-mail: kagrant@wfubmc.edu or mwest@advancedcell.com .

2. Thomas H. Maugh, II, "Chemicals Turn Monkey Egg Into Embryo," The Los Angeles Times, p. A14 (February 4, 2002).
3. Antonio Regalado, "Stem Cells Without Cloning," The Wall Street Journal, pp. A1, B1 (February 1, 2002).

5. Gregory M. Fahy, "Therapeutic Cloning Under Fire: An Interview with Michael D. West," Life Extension Magazine, Vol. 8, No. 3, pp. 38-46 (March 2002).

6. Saul Kent, "Don't Let the U.S. Government Ban Therapeutic Cloning," Life Extension Magazine, Vol. 8, No. 3, pp. 49-60 (March 2002).

Geron Corp., Infigen, Inc., and ACT May All Litigate Over Patents

February 1, 2002 (WSJ) The US Patent Office may have to resolve competing claims by three different companies in a so-called Interference Process that could take two years before they decide whose claims about what were filed soonest..

Ref:

David P. Hamilton and Antonio Regalado, "Geron Starts Process on Cloning Patent Underpinning Rival," The Wall Street Journal, pp. A1, B4 (February 1, 2002).

Germany Permits Limited Embryonic Stem-Cell Imports

January 31, 2002; Berlin, GERMANY (AP and CNN) -- Embryonic stem-cell research is now officially sanctioned in Germany. The German parliament yesterday approved limited imports of human embryonic stem cells for research. The proposal allows for controlled imports of stem cells that have already been harvested from embryos, which means no new embryos would be destroyed.

The debate in Germany has in many ways mirrored last year's debate over stem cell research in the United States, and while the German measure passed by a comfortable margin, [340 - 265], the issue was an emotional one. Scientists had argued that a decision to block imports completely would have serious consequences for German medical research. On the other hand, church leaders had strongly advocated a full ban, expressing concern that allowing imports could open the door to human cloning.

Refs:

1. Vanessa Fuhrmans and William Boston, "German Parliament Votes 'Yes' on Import of Stem- Cell Lines," The Wall Street Journal, pp. A1, B10 (January 31, 2002).

2. Carol J. Williams, Richard Boudreaux (Rome), Ela Kasprzycka (Warsaw), Janet Stobart (London), and Sarah White (Paris), "Lawmakers Ban Stem-Cell Imports in German Vote (sic): Only Existing Embryos in the Country Can be Used for Research, Parliament Decides. Some see a Blow to Promising Treatments (sic)," The Los Angeles Times, pp. A2, 3 (January 31, 2002).

[ Editor's Note: "He who wears two watches never knows what time it is! Whenever they're different, which one is right?" Fortunately in this case, we have four sources ( AP, CNN, WSJ, and LA Times) and not just two sources which are mutually inconsistent.(Sigh!) Therefore, we now know that it was Staff Writer Carol Williams who got it wrong. You know it's really bad when the vote statistics cited in the body of the text are consistent with what other reporters wrote about the same story, but your headline has an extra "not" in it. Will The Times publish a retraction in tomorrow's edition? This is not just a problem of a German-to-English translator getting it wrong or perceiving the glass as "half full" vs. "half empty." It is a conceptual failure to understand what's going on.]

ACT and Harvard Create Bovine Cloned Kidney

January 30, 2002 (AP) -- The same research firm that outraged many last November with the news that it had embarked on human cloning reports that it has "constructed miniature working kidneys from cloned cow embryos," The Washington Post reports. Advanced Cell Technology, of Worcester, MA, says "the kidneys appear to function similar to genuine kidneys, and even work well enough to produce urine." However, there's still no evidence on whether they can perform all of the functions of healthy human kidneys. The researchers say their goal is to use test-tube embryos that are identically matched to a patient in order to create new organs for those that have worn out. Click for more details from the BBC .

ACT Detractors Claim Serious Flaws in First Human Cloned Embryo Experiment

January 28, 2002 ( WSJ) -- A chorus of scientific detractors, who point to serious potential flaws in the experiment by ACT to clone a human embryo, say that the embryos, one of which divided into just six cells after five days, all died because "the cells were actually fragmenting and not undergoing true cell-cycle mitotic division [with chromosomal synthesis and segregation into distinct nuclei]." Three leading scientists formerly on the E-biomed: The Journal of Regenerative Medicine Editorial Board resigned in protest because of their unhappiness over the "rush to publication." Even ProBio, Inc., an Australian intellectual property rights company that owns the license for one of the cloning techniques used by ACT, shrugs off the importance of the company's "achievement. "It may serve more of a media function than a scientific one," said ProBio CEO Laith Reynolds. On the other hand, Dr. William Haseltine, Editor-in-Chief of E-biomed, defended the decision to publish this paper as follows: "I stand by the scientific process which means that the manuscript was reviewed by people knowledgeable in the field. It's up to other scientists to determine whether the science is sound." [ Editor's Note: For our own position at the time of publication, see the GRG Editorial Remark following the Abstract of the paper in our web News item below dated November 25, 2001.

Refs:

1. Gutam Naik and Antonio Regalado, "Biotech Firms Bypass Journals to Make News," The Wall Street Journal, pp. B1,3 (January 28, 2002).
2. Editorial, "A Ready-Made Controversy," Scientific American, Vol. 286, No. 2, p. 10 (February 2002).
3. Letters-to-the-Editor by Prof. Rudolf Janisch and Ray C. J. Chiu, Scientific American, p. 10 (May 2002).
4. Gary Stix, "What Clones?: Widespread Scientific Doubts Greet Word of the First Human Embryo Clones," Scientific American, Vol. 286, No. 2, p. 18-9 (February 2002).
Prof. John P. Gearhard, M.D., Ph.D., of Johns Hopkins University Medical School and a former Member of the Editorial Board of e-Biomed: The Journal of Regenerative Medicine announced his resignation from the Board over this matter. "I feel very embarrassed and chagrined by this publication," he said in an interview with the BBC. Mrs. Mary Ann Liebert, the Journal's publisher, was planning to meet with Dr. Gerhart to attempt to change his mind.
5. Editorial, "Publish and Be Damned," Nature Biotechnology, Vol. 20, No. 1, p.1 (January 2002).
This Editorial was an extremely hostile attack, using phrases like the "ludicrous manner ... in which this modest announcement was made.. should serve as a warning to all companies that intend to publicize their research..."
6. Jeffrey L. Fox, "Human Cloning Claim Renews Debate," Nature Biotechnology, Vol. 20, No. 1, pp. 4-5 (January 2002)
7. Jose B. Cibelli, Keith H. Campbell, George E. Seidel, Michael D. West, and Robert P. Lanza, "The Health Profile of Cloned Animals," Nature Biotechnology, Vol. 20, No. 1, pp. 13- 14 (January 2002).
8. "Cloned Cattle Healthy," Nature Biotechnology, Vol. 20, No. 1, p. 35 (January 2002).

Stem Cell Treatment for SCID Infants a Success

January 28, 2002 The February issue of Blood reports that stem cells transplants were performed on 117 Severe Combined Immune Deficiency (SCID) children over 19 years at Duke University. Of the 21 who received transplants in the first four weeks, 20 are still alive and leading normal lives. The oldest is already 19.

Ref:

Thomas H. Maugh, II, The Los Angeles Times (January 28, 2002).

Multipotent Adult Progenitor Cells = Ultimate Stem Cells?

January 24, 2002 ( New Scientist) -- A new Patent Application from the University of Minnesota reveals that neither cloning nor human embryonic stem cells may be necessary for cell-based therapy after all. Click for more details.

Refs:

1. "Senate Panel Hears Cloning Arguments," The Washington Post, reprinted in The Los Angeles Times, p. A29 (January 25, 2002). Dr. Catherine Verfaillie, biologist at the University of Minnesota, testified in a Senate Subcommittee yesterday in Washington, D.C., "Even though we're excited about the fact that there appear to be cells in adult tissue that seem to have greater potential than we thought they would, it's too soon to say whether they have the equivalent potentiality of embryonic cells."
2. Mahendra S. Rao and Mark P. Mattson, "Stem Cells and Aging: Expanding the Possibilities [Review]," Mechanisms of Aging and Development, Vol. 122, No. 7, pp. 713-34 (2001).

Artificial Sperm with Female-Derived Chromosomes?

January 21, 2002; Chicago, IL (AP) A revolutionary new fertility technique is being developed that would make it possible for two women to become joint mothers to a child who fully shares genes from both of them. Researchers at the Reproductive Genetics Institute in Chicago said the process, now being tested on human eggs, could be available within two years. Doctors would first treat cells taken from one woman, turning them into artificial sperm to fertilize the other woman's eggs and then use standard In Vitro Fertilization(IVF) to give rise to a pregnancy.

But just as males might no longer be necessary to perpetuate the human species using this technique, so another new technology for Artificial Wombs might make females equally unnecessary. Dr. Hung Chiung Liu and colleagues at the Center for Reproductive Medicine and Infertility at Cornell University announced a few weeks ago that they had succeeded in creating an artificial "womb lining" using a cocktail of drugs and hormones. Work is also progressing under the direction of Dr. Yosinori Kuwabara at Juntendou University in Tokyo where they are experimenting with a clear plastic tank the size of a bread box filled with body-temperature amniotic fluid.

Ref:

Jeremy Rifkin, "Evolution's Pregnant Pause: Artificial Wombs," The Los Angeles Times, p. B11 (January 21, 2002).

National Academy of Sciences Panel Endorses Therapeutic Cloning

January 18, 2002;

Refs:
1. Megan Garvey and Richard T. Cooper, "Scientists' Panel Endorses Cloning to Create Stem Cells," The Los Angeles Times, pp. A1, 19 (January 19, 2002).
2. Constance Holden and Jocelyn Kaiser, "Report Backs Ban; Ethics Panel Debuts," Science, Vol. 295, No. 5555, pp. 601-2 (January 25, 2002).
3. N. Seppa, "Forbidden Tests: Panel Seeks Ban on Human Clones," Science News, Vol. 161, No. 4, p. 52 (January 26, 2002).
4. "Cloniing Bills Blossom" Science, Vol. 295, No. 5556, p. 779 (February 1, 2002); "Senator Tom Harkin (D-IA) has proposed a new Bill (S. 1893) similar to one proposed by Sen. Dianne Feinstein (D-CA)(S. 1758). Feinstein's Bill would keep the door open for research using cloned embryos but impose civil penalties on anyone who tries to clone a human being. Harkin's Bill adds criminal penalties to the mix. More than 20 research organizations have already endorsed Feinstein's Bill over competing legislation backed by Sen Sam Brownback (R-KS) that would ban both reproductive and therapeutic cloning (S. 790). The next step will be hearings on Bronback's Bill in March with a full Senate debate coming sometime later." [ Editor's Note: We can expect that Dr. Michael West, CEO of ACT in Worcester, MA will testify at these hearings as an expert witness in favor of the Feinstein and Harkin Bills but against the Brownback Bill. Check CNN as we get closer.]

Click on the Leonardo sketch for more details from CNN and AP. Click on the photo of Dr. Weissman for access to the full report.

NATIONAL ACADEMY OF SCIENCES
NATIONAL ACADEMY OF ENGINEERING
INSTITUTE OF MEDICINE
Committee on Science, Engineering, and Public Policy

and

NATIONAL RESEARCH COUNCIL
Division on Earth and Life Studies
Board on Life Sciences

Panel on Scientific and Medical Aspects of Human Cloning

OVERSIGHT:

Maxine Singer, Ph.D.[1,2]
Chairman Committee on Science, Engineering, and Public Policy and
President Carnegie Institution of Washington
Washington, D.C.

Corey S. Goodman, Ph.D.[1]
Chair Board on Life Sciences
National Research Council, and
President and Chief Executive Officer
Renovis Inc., and
Professor of Neurobiology
Department of Molecular and Cell Biology
University of California
Berkeley, CA

STAFF:

Deborah D. Stine, Ph.D.
Study Director
________________________________
1. Member, National Academy of Sciences
2. Member, Institute of Medicine

Stem Cells from the Germline also Control Aging in Nematodes

January 18, 2002; Prof. Cynthia Kenyon, the Herbert Boyer Professor of Biochemistry and Biophysics at the UCSF Medical School, has published in today's issue of Science that proliferating germ-line stem cells are capable of synthesizing a steroid hormone that promotes/dictates the longevity (life history) for the nematode. Click for more details.

Bioethics Panel Now Complete as Senate Plans Debate in February

January 17, 2002; Prof. Leon Kass of the University of Chicago, chosen last Summer by President Bush to Chair the Presidential Bioethics Advisory Council has announced that the roster of members is now complete. Twelve of the 18 members include,

Prof. James Q. Wilson, Emeritus in Political Science at UCLA and co author with Dr. Kass of the book The Ethics of Human Cloning
Mr, Charles Krauthammer, nationally syndicated columnist for The Washington Post;
Prof. Elizabeth Blackburn
Prof. Robert P. George, Princeton University Law School;
Prof. Francis Fukuyama, Johns Hopkins University in Baltimore, MD;
Prof. Michael Gazzaniga, Neuroscientist at Dartmouth College; NH
Prof. William F. May, Ethics at Southern Methodist University;
Prof. Daniel W. Foster, Endocrinologist, University of Texas Southwestern Medical Center;
Gilbert Meilaender;
Mary Ann Glendon;
Alfonso Gomez-Lobo;
Dr. Janet Rowley, Cancer Biologist;

By the way, Prof. Paul Berg, Biochemist and Nobel Laureate from Stanford University declined to accept an invitation, citing strong personal disagreement with Dr. Kass over his views on cloning.

A Council of Clones

President Bush's Bioethics Panel Will Provide the Advice He Wants to Hear
by
Prof. Arthur Caplan, Ph.D., Director,
Center for Bioethics at the University of Pennsylvania in Philadelphia

January 17, 2002; ( MSNBC) -- All right, we can all collectively exhale. The Bioethics Committee that President Bush promised to appoint way back in August has finally been named. This is the group that the President said would help guide his struggles with the divisive issues of cloning, stem-cell research, and the creation of human embryos for research. So what sort of counsel is the newly-announced Committee likely to offer? Click for the answer.

Click for more details from CNN on January 18th.

Refs.:

1. Laurie McGinley, "Bioethics Panel Advising Bush Fills Its Roster," The Wall Street Journal, p. B2 (January 17, 2002).
2. Aaron Zitner, "States Hurry to Block Plans to Clone Humans: Several Legislatures Act as Congress Debates the Practice, [A Florida] Bill Would Let Clones Sue Doctors [Who Perform Cloning]," The Los Angeles Times, pp. A1, 14 (January 17, 2002).
James Kallinger, Republican Florida State Legislator from the Orlando area who introduced the bill, said, "whether or not [the cloning] took place in Florida, clones, their relatives, and estates could also sue for emotional distress and other injuries. This sends a message, as far as Florida courts can reach, to scientists trying to clone humans." [ Editor's Note: Maybe Dr. Michael West, CEO of ACT, should avoid holding any scientific meetings close to Disney World in the near future.]
3. Richard T. Cooper, "Bioethics Panel's Topic Number One: Perfection," The Los Angeles Times, p. A24 (January 18, 2002).
4. "The Jones Fertility Institute in Norfolk, VA said that it will now terminate work it started in July to create human embryos for the sole purpose of harvesting stem cells," The Wall Street Journal, p. A1 (January 18, 2002).

Klotho Gene Ages Mice Like Humans

January 15, 2002; As reported in today's issue of PNAS, click for more details.

Ref:

J. Travis, "Gene Variant Tied to Human Aging," Science News, Vol. 161, No. 3, p. 36 (January 19, 2002).

State of California Medical Panel Urges Therapeutic Cloning be Permitted But Reproductive Cloning Prohibited

Saturday, January 12, 2002 ( The Los Angeles Times). Click for more details. Click for a link to the full report on The San Francisco Chronicle .

Click for a link to the NIH Stem Cell Registry. There are now 67 embryonic stem-cell lines located at 11 different institutions, three more than had been previously announced.

Imaging Alzheimer's Plaques in Patients at UCLA

January 10, 2002 (AP) A new imaging technique may make it possible to diagnose and treat Alzheimer's disease at an earlier stage. An imaging study conducted by UCLA researchers and published in the American Journal of Geriatric Psychiatry is the first of its kind to show the plaques and tangles that are characteristic of Alzheimer's in the brains of living patients. Prior to this study, viewing these brain lesions was only possible through post mortum examination.

The researchers involved in the imaging study injected a protein with a radioactive tracer into nine Alzheimer's patients. The protein, known as FDDNP, bound to the plaques and tangles in the brains of these patients. A PET scan (Positron Emission Tomography), was then used to image the location of these lesions in the brain. "I think it's an important finding insofar as it's the first demonstration of the ability to image the pathology in the brain of patients with Alzheimer's Disease," said Dr. Ronald Petersen, Director of the Alzheimer's Disease Research Center at the Mayo Clinic in Rochester, MN.

Geron Corp. and WARF Settle Their Lawsuit

January 10, 2002; Geron's CEO Dr. Thomas Okarma said, "Political pressures on both his company and the Wisconsin Alumni Research Foundation (WARF) played a role in pushing both sides toward a settlement." According to the agreement, Geron gets to retain exclusive rights to heart, nerve, and pancreas cells with non-exclusive rights to bone, blood, and cartilage cells. "We would be very happy to cure diabetes, stroke, and heart failure," he said. In addition, the Federal government will have royalty-free access to the methodology for growing human stem cells in culture without the obligatory use of mouse feeder cells that was developed internally at Geron. Both sides of the contest have declared victory. The focus is now likely to shift to other stem-cell patents that may prove even more significant, such as the race to identify cytokines that differentiate stem cells along particular tissue types.

Refs:

1. Bloomberg News, "Geron Settles Suit on Embryo Stem Use," The Los Angeles Times, p. B2 (January 10, 2002).
2. David P. Hamilton and Antonio Regalado, "Geron Gives Up Some Stem-Cell Rights," The Wall Street Journal, pp. A1, 3, 14 (January 10, 2002).
3. Antonio Regalado and Jill Carroll, "Research, Red Ink: An Academic Group Seeks Balance," The Wall Street Journal, p. B4 (January 14, 2002).

Embryonic Stem Cells Show Promise for a Rat Model of Parkinson's Disease

January 8, 2002; In today's issue of PNAS, researchers from Harvard University's Neuroregeneration Laboratory, report that embryonic stem cells injected into rat striatum result in the proliferation of fully-differentiated DA (Dopaminergic) neurons that function, as demonstrated by PET and fMRI studies, so as to restore normal behavior in an animal model of Parkinson's Disease.

(AP) Embryonic stem cells transplanted from mice into the brains of rats that have the equivalent of Parkinson's Disease become Dopamine-producing neurons and restore lasting motor function, a new study says. According to a HealthScout News report, the researchers say the findings raise the hope of someday transplanting human embryonic stem cells into patients with Parkinson's Disease, rather than relying on donor fetal brain tissue, which is both controversial and hard to obtain in sufficient quantities. President Bush limited Federal expenditures on stem-cell research last year because of the controversy over the use of human embryos. The findings appear in today's issue of the Proceedings of the National Academy of Sciences. Click for more details. Also, click for more details from CNN.

Refs:

1. "Symptoms of Parkinson's Relived in Rats," The Wall Street Journal, p. A1 (January 8, 2002).
2. Gretchen Vogel, "Rat Brains Respond to Embryonic Stem Cells,": Science, Vol. 295, No. 5553, pp. 254-5 (January 11, 2002). Dr. Studer stated that "the relative ease with which dopamine-producing cells developed from the injected ES cells suggests that there might be a way to prompt rare stem cells already in the brain to become dopamine-producing neurons, allowing doctors to avoid the issue of transplanting cells altogether."

World's Oldest Man Dies at Age 112

January 4, 2002; 8:54 AM EST; Rome, ITALY ( Reuters) - The world's oldest man, 112-year-old Mr. Antonio Todde, died overnight on the Italian island of Sardinia, relatives said Friday. Todde, a shepherd on the rocky hills around the town of Nuoro until he became housebound in the last four years of his life, had been due to celebrate his 113th birthday on January 22nd. Born in a tiny mountain village the same year as the Eiffel Tower was erected in 1889, Todde was recognized as the world's oldest man by the Guinness Book of Records last year.

Before he was always out and about," his granddaughter [or maybe nephew ?] Vanni told Reuters on Friday. "He had a calm, hard-working life, he was always very close to his family." Vanni said her grandfather started to feel unwell just two days ago and stopped eating. "His blood pressure fell and he left us without a murmur."

Todde, who lived on a simple diet of pasta, vegetable soup and the occasional steak, had said that the secret to his longevity was the occasional alcoholic drink. "Just love your brother and drink a good glass of red wine every day," he was quoted as saying when he celebrated his birthday last year. "You take one day after the other, you just go on." "Todde is survived by two sons, one daughter, a sister, many grandchildren, and great-grandchildren and other relatives," Vanni Todde said.

Ref:
Obituary (AP), "Antonio Todde, 112; World's Oldest Man," The Los Angeles Times, p.B13 (January 4, 2002).

[ Editor's Note: So the title will presumably pass to Mr. Yukichi Chuganji of Japan, age 112 (born March 23, 1889). Mr. John McMorran of Florida (born June 19, 1889) is next in line if, by chance, Mr. Chuganji cannot be confirmed as still living. For the record, John McMorran's relatives have confirmed him alive and well earlier today.]

[ Editor's Note on January 10, 2002: Mr. Chuganji was confirmed today as living. Therefore, he is, for the record, the true successor to Mr. Todde, beating out Mr. McMorran by three months or so. The Times Herald of Port Huron, MI has a follow-up story on the Internet reported by Mr. Mike Connell, "At age 112, Former Port Huron Resident is Second-Oldest Man."]

Dolly the Sheep is Afflicted with Arthritis

January 4, 2002; London, UK (AP) - - Dolly, the world's first cloned sheep, has developed arthritis, raising fears that the cloning process may have given her a genetic defect. Prof. Ian Wilmut of the Roslin Institute in SCOTLAND said Friday that Dolly, the first mammal cloned from a cell taken from an adult animal, "had arthritis in her left hind leg." Click for more details from CNN. Click for more details from the BBC, modulo translation of British spellings and punctuation to American English.

Refs:
1. Marjorie Miller and Thomas H. Maugh, II, "Dolly's Arthritis Raises New Fears About Cloning," The Los Angeles Times, pp. A1, 10 (January 5, 2002).
2. Gutam Naik, "Dolly's Arthritis Fuels Concerns of Health Woes Tied to Cloning," The Wall Street Journal, pp. A1, 20 (January 7, 2002).
3. Sophia Fox, "Dolly's Arthritis Raises Concern Over Cloning," Genetic Engineering News, Vol. 22, No. 2, p. 24 (January 15, 2002).

Dr. Ian Wilmut said in a press conference that " Dolly has led an unusual life, housed in a pen and living in the scientific limelight. At one point she was overweight and spoiled. This may sound silly, but she also has spent a lot of time standing on her hind legs to get food from journalists and photographers. Sheep don't normally stand on their hind legs." [ Editor's Note: Is this a case of the Heisenberg Effect, or what?]

Novartis and Biotransplant, Inc. Team to Clone Pigs for Xenotransplantation

January 4, 2002; As reported in AAAS On-Line Science today, a joint venture of Biotrtansplant, Inc. (The University of Missouri at Columbia and Immerge BioTherapeutics of Charlestown, MA) and Swiss pharmaceutical giant Novartis AG became the second scientific team to announce the cloning of pigs with a genetic alteration designed to make their organs immunologically compatible for human transplantation.

Refs:
1. AAAS Science On-Line.
2. Laura Johannes, "Pig-Clone Advance Made by Novartis and Biotransplant," The Wall Street Journal, pp. A1, 8 (January 4, 2002).
3. AP, "Pig Organ Breakthrough Raises Infection Fears," The Los Angeles Times, p. A32 (January 4, 2002).
4. Michael D. Lemonick, "Pig Parts for People? It Won't Happen for Years, But a Laboratory Breakthrough Puts an Unlimited Source of Organs a Step Closer," Time Magaxine, p. 65 (January 14, 2002).
5. Antonio Regalado, "Researchers Deem Cloned Mice Normal, Fueling Debate Over Procedure's Safety," The Wall Street Journal, pp. A1, B6 (January 11, 2002).
6. "Gene-Knockout Piglets Cloned," Genetic Engineering News, Vol. 22, No. 2, pp. 6, 50 (January 15, 2002). Alpha-1,3 GT gene knockout may provide a near-term solution for overcoming xenograph rejection.
It now seems that consideration of Sen. Bronback's Senate Bill to ban all forms of cloning has now been postponed until February.
Click for more details from AP.

[ GRG Editorial: The nay-sayers in the story above are focusing on the wrong problem. The fear of deadly swine retroviruses being inadvertently spread in the general human population as a result of porcine transplants into few human recipients is like arguing "How many angles can dance on the head of a pin?" or "How should we rearrange the deck chairs on the Titanic while it sinks." The media creates the impression that we're half way to the moon, just because of few pioneers have climbed a mountain and jumped off a cliff with feathers glued on to their arms furiously flapping way. The reality is that we're not even at the "Wright Brothers" stage of going to the moon. There is hardly a science of aeronautics let alone astronautics to draw on. For example, does anyone know if the "double knock-out of the porcine galactose gene" (GGTA1) isn't fatal to pigs? Maybe the surface markers are there for a reason (for pigs)? And this is just the first hyper-immune rejection problem of xenotransplantation. What about other antigenic markers on porcine cell surfaces that will cause the cells to be killed off "more slowly," once the human host Killer T-Cells discover that someone is trying to "pull a fast one"? And what about the stimulation of latent autoimmune diseases in the host, even if "foreign" antigens get to be reasonably-well tolerated? Instead of letting the speculative day-traders run up the stock of companies like Infigen, Inc. of DeForest, WI, as though a clinical solution to rejection were just around the corner (Biotransplant shares shares rose 9.8 percent in after-hours trading at 4 PM yesterday, while PPL's stock soared 46 percent on the London Stock Exchange in one day.), we ought to let the real scientists work quietly for five more years to get their arms around the problem. Instead, we get spikes of unfounded optimism (up ticks) followed by unfounded disillusionment (down ticks) where "blind shepherds are leading the sighted but stupid sheep." Aren't there any long-term investors left?

Supporting Refs:
1. "Pigs Up, Sheep Down" Science Vol. 295, No. 5554, p. 437 (January 18, 2002),
A graph of PPL Therapuetics stock price for [Dec. 28th to Jan. 8th] is shown in this short article revealing a 30 percent uptick on January 3rd with the announcement of the birth of the pigs followed by a 25 percent downtick over the next days following the announcement of Dolly's arthritis on January 4th.
2. Gutam Naik and Antonio Regalado, "Biotech Firms Bypass Journals to Make News," The Wall Street Journal, pp. B1,3 (January 28, 2002).]

PPL Therapeutics Creates Partial "Knock Out" Pigs

January 3, 2002; PPL Therapeutics, PLC of Blacksburg, VA reported that five pigs were born on Christmas Day whimsically named, Noel, Angel, Star, Joy, and Mary with the aim of blocking xenograph organ transplant rejection in human hosts. CNN has just reported that one of the pigs has died, so, unfortunately, there are only four pigs left.

Refs:
1. Gautam Haik, "British Firm Clones Pigs for Transplants," The Wall Street Journal, pp. A1, B5 (January 3, 2002).
2. Jocelyn Kaiser, "Cloned Pigs May Help Overcome Rejection," Science, Vol. 295, No. 5552, pp. 25-27 (January 4, 2002).
"ACT of Worcester, MA said that they themselves are close to announcing the birth of pigs lacking the galtransferase gene."
Click for more details from CNN.

Adult Stem Cells May Have a Role in Repairing Heart Damage

January 3, 2002; As described in today's issue of The New England Journal of Medicine by researchers at the New York Medical College in Valhalla, adult stem cells can, to a limited extent, repair heart damage, as was demonstrated with "Y" Chromosome-marked (male recipient) host-cell migration into the myocardium of female-donor heart transplants.

Refs:
1. Federico Quaini, Konrad Urbanek, Antonio P. Beltrami, Nicoletta Finato, Carlo A. Beltrami, Bernardo Nadal-Ginard, Jan Kajstura, Annarosa Leri, and Piero Anversa," N Engl J Med, Vol. 346, No. 1, pp. 5-15 (January 3, 2002);
2. Ron Winslow, "Gender Study Suggests Heart Can Repair Itself," The Wall Street Journal, pp. A1, B1,3 (January 3, 2002).
3. Gina Kolata, "Doctors Advance in Helping Body to Repair Itself," The New York Times, pp. D1,2 (January 15, 2002).
4. Caroline Seydel, "Stem Cells May Shore Up Transplanted Hearts," Science, Vol. 295, No. 5553, pp. 253-4 (January 11, 2002).
Click for more details from CNN and Reuters.

p53 May Accelerate the Rate of Aging in Mice

January 4, 2002; As reported in today's issue of Nature, researchers at Baylor College of Medicine in Houston, Texas have reported that an upregulated p53 gene, which is known to protect mice against cancer in early years, causes significant physical deterioration in later life with a 19 percent increase in mortality! [96 weeks average life expectancy vs. 118 weeks for controls.] This phenomenon is known as antagonistic pleiotropy. Click for more details from AP.

Hypothesis on Mechanism: Dr. Lawrence A. Donehower, of the Baylor College of Medicine in Houston, TX, suggests that, "as the mice age and their adult stem-cell population naturally becomes less prolific, the upregulated p53 protein may result in premature aging simply because too many or the remaining adult stem cells are being 'instructed to commit apoptosis,' and therefore the corresponding tissues cannot be rejuvenated or repaired at the same rate as in control mice. However, among the 200 mice with extra p53, there were two mice that neither got cancer nor grew old prematurely, so there must be other genetic components operating to compensate for the high levels of p53 and they may be inherited randomly."

Prof. Leonard Guarente comments that "the activity of p53 could be antagonized by the metabolic SIR-2 protein that he is studying at MIT." This gene has been implicated in longevity increases for yeast and nematodes and could be part of the mechanism underlying the mechanism of Caloric Restriction that increases longevity in mice and even primates. [ Editor's Note: We have just learned that there is a human disease called Li-Fraumeni Syndrome in which patients die of cancer before the age 30 due to a mutation in the p53 gene.]

Ultimately, the story of the p53 gene will likely be just a piece in the puzzle of aging, not the whole picture. There are clearly deeper species-specific genetic mechanisms (like the onset and duration of fecundity that is controlled by pacemaker nodes [diurnal/annual-counting clocks] in the hypothalamus and/or other parts of the brain) that better explains why mice, rats, bats, dogs, chimps, whales, parrots, and humans live for such phenotypically different durations. A CR diet may benefit all species equally, probably invented as a universal evolutionary adaptation to "tread water" (reduce metabolic rate while food is scarce) in the hopes that times will be better in the future when reproduction can again begin in earnest, but it may only make a 50 percent difference in maximum lifespan. How can we explain the 5,000 percent difference in maximum lifespan across species boundaries? [ Editor's Comment: There have to be species-specific settings of a universal clockwork hidden somewhere in the brain of all birds and mammals, and our anatomy/physiology colleagues in medical schools throughout the country have yet to do the right experiments in order to find it. They certainly are good at teaching medical students the enormous volume of what has already been learned with appropriate exam questions to perpetrate the illusion that we sure know a lot if the student gets to pass them. The problem is that neuroanatomy professors are not very good at admitting that what they don't know about the brain makes what is known so far pale by comparison. Good science requires asking the good questions.]

Refs:
1. G. Ferbeyre G, S. W. Lowe,. "The Price of Tumor Suppression?" Nature, Vol. 415, pp. 26-27 (January 3, 2002).
2. S. D. Tyner, et al., "p53 Mutant Mice that Display Early Aging-Associated Phenotypes," Nature, Vol. 415, pp. 45-53 (January 3, 2002).
3. "Protein that Wards Off Cancer also Affects Aging, Study Finds," The Washington Post, reprinted in The Los Angeles Times, p. A14 (January 3, 2002).
4. "Cancer-Fighting Protein Was Found to Spur Faster Aging in Mice," The Wall Street Journal, p. A1 (January 3, 2002).
5. Nicholas Wade, "Cancer Fighter Exacts a Price: Cellular Aging," The New York Times, pp. D1, 6 (January 8, 2002).
6. Evelyn Strauss, "Cancer-Stalling System Accelerates Aging," Science, Vol. 295, No. 5552, pp. 28-9 (January 4, 2002).

GenOway Clones Rat Enbryo

January 1, 2002; GenOway of Lyon, FRANCE has reported the first in vivo successful post-implantation of a cloned rat embryo. All previous attempts to clone rats have failed before the point of implantation because the donor nucleus and the recipient oocyte have not been 'in phase.' The GenOway rat embryo was found in a post-mortem examination of the surrogate mother after 12.5 days of development to be fully in tact with no apparent abnormalities, and "that represents a key milestone."

Ref:
Sophia Fox, "genOway Succeeds in Cloning of Healthy Rat," Genetic Engineering News, Vol. 22, No. 1, p. 30 (January 1, 2002).

News Items for 2001

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