eugenics   radical evolution   population control slack gene DOE Human Genome project ghola Sanger Inst. Mike Judge's "Idiocracy" Moses Harman Jas Watson Watson's 'Secret of Life' D.E. Duncan Harry Bruinius Grant Alan Alfred Rosenberg Madison Grant Genochoice GeneBase BioNet UK Human Genome Map Ctr Iceland Bio WorldWatch John Harris Inst. of Science, Technology & Public Policy Lee Leffler "40 to 60% of all corn & soy grown is genetically engineered. Genetically engineered products cannot be recalled; pollination cannot be legislated."   [ your chance to be a wild pollen grain in a GMO world ] We need 1000 calls or emails today! 2.16.00   action alert FRITOS-LAY has announced it would no longer use genetically engineered corn in its produces. THIS IS THE START OF SOMETHING BIG. The biotech giants have started a campaign to pressure Fritos to reverse their decision. If Fritos holds to their commitment, this may very well be the start of the downfall of genetically engineered foods in America. FRITOS IS CAREFULLY WATCHING THE CONSUMER RESPONSE. PLEASE send them an email or call them 1-800-352-4477 (ask for operator 100) Tell them you applaud their decision. Tell them that you do NOT want to eat foods that have been genetically engineered to act as an insecticide. Tell them that you don't believe that genetically engineered food is safe for consumer or environmental health and you commend the direction they are taking. And that it would be a big disappointment if they cave in and reverse their decision. Tell them that now they should go certified organic!! Write them at Frito-Lay, P.O. Box 660634, Dallas, TX, 75266-0634 Biowar in the Andes   CIA's next secret weapon genetic engineering & chemical biological warfare 6.00   Andrew Cockburn CounterPunch v.7#11 A.Cockburn & Jeffrey St.Clair ed. The Steps of Agent Blue At the Institute for Genetics in Kazakhstan, former Soviet biowarriors are being financed by the US and Britain to test mycoherbicides. Fusarium oxysporum strains that infect coca plants are closely related to those that attack yams, a staple in the Andean diet. McCaffery's Plague Along with the other enormities presently perpetrated in the name of the War on Drugs, the United States is now actively preparing to deploy biological weapons. The weapons consist of plant pathogens designed to attack coca, cannabis and opium poppy crops. Research into the project has involved the resurrection of biological agents developed long ago at Fort Detrick MD U.S. biowar program center closed down by President Nixon in 1969. Along with the other enormities presently perpetrated in the name of the War on Drugs, the U.S. is now actively preparing to deploy biological weapons. The weapons consist of plant pathogens designed to attack coca, cannabis and opium poppy crops. Research into the project has involved the resurrection of biological agents developed long ago at Fort Detrick, Maryland, center for the US biowar program closed down by President Nixon in 1969. Deep-frozen at the time of the program's termination, they are now being thawed out and readied for assault on producer countries in the third world. Also involved are veterans of the Soviet biological warfare effort, now being funded by the US through the connivance of an obscure UN agency, employed for this purpose in order to shield the U.S. from well-deserved charges of violating the internationally negotiated biological weapons convention. The work is proceeding despite well attested evidence that the weapons, if deployed, will have profound and disastrous impact on the ecologies of the countries in which they are used. Furthermore, the USDA is now researching the use of genetic modification to enhance the potency of these bio-weapons. The principal agents under development are microbial pathogens. At the Institute for Genetics in Kazakhstan, former Soviet biowarriors are being financed by the US and Britain to test mycoherbicides, fungi, specifically Pleospora, to kill opium poppies & marijuana plants. In the Andes and western Amazon, the U.S. is planning the testing and widespread application of fusarium oxysporum, an anti-coca fungus. The FY 2000 budget contains at least $23 million for these programs, although further appropriations are almost certainly buried in covert military & intelligence budgets. The prospect of being on the receiving end of a biological attack is not alluring to countries such as Peru, Bolivia and Colombia. The Peruvian govt has already banned the testing and or deployment of the fungi. The Colombian govt is similarly queasy, but has been sharply admonished by the project's supporters in the US Congress that if Colombia wants its $1.8 billion aid package, it had better take the fungi too. Last March, House Foreign Affairs Committee Chairman Benjamin Gilman, R-N.Y., added an amendment to the Colombian aid bill requiring President Clinton to certify that the Colombian govt "has agreed to and is implementing a strategy to eliminate Colombia's total coca & opium poppy production" using, among other means, "tested, environmentally safe mycoherbicides." The amendment is still in the bill (which is still stalled in the senate) despite a submission by Colombian scientists to the Colombian Ombudsman for the Environment that the use of mycoherbicide agents in Colombia represents "a great danger both for Colombian humans as well as for the Colombian environment & biodiversity". It is easy to see why the Colombians are worried. The absolute requirement of this sort of weapon is that it should be "host specific", ie. that it should attack only the intended victim and nothing else. According to Ed Hammond of the Sunshine Project, which has researched & publicized this enormity, tests conducted by USDA-contracted researchers in 1994 & 1995 using the favored strain of the fungus fusarium oxysporum-EN4-resulted in two non-coca species becoming infected. Furthermore, fusarium oxysporum strains that infect coca plants are closely related to those that attack yams, a staple in the Andean diet. This is hardly surprising, Hammond points out, in view of the fact that EN4 is designed to attack different strains of coca and therefore cannot be entirely host specific. Thus the rare & beautiful Agrias butterfly may soon fall as one more casualty of the War on Drugs, since its larvae feed & mature on wild relatives of the coca plant. One of the few remaining areas where Agrias can be found is the upper Putamayo river region, a center both of guerrilla activity & coca cultivation in Colombia and therefore a prime target for the US fungus spraying campaign. Meanwhile, back at the lab, USDA researchers have been working to create genetically modified strains of the fungi, including the cloning of fusarium strains that attack potatoes, in order to produce something still more vicious. However, in their search for instruments of what is officially known as "bio-control", the govt's researchers have also, it seems, reached back into the past. Sometime before 1969, according to documents supplied to Hammond under the FOIA, a team from APHIS, the USDA's plant & animal inspection service, found a virus on a Datura tree imported from Cauca, Colombia. Someone, it is not clear who, determined that the virus could be useful as an anti-opium poppy agent, and it was dispatched to the US biological warfare center at Ft Detrick, Maryland under the label D-437. Following Nixon's order to close the place down, D-437 was not destroyed but put in deep frozen storage, forgotten by all but the researchers who had worked so happily at Detrick. On April 12 this year, Hammond caught a brief mention of D-437 on a US Army website, along with the fact that it was being studied by a Dr Vernon Damsteegt, himself a Detrick veteran. Following enquiries by Hammond, all mention of the virus & its custodian was hurriedly removed from the site, which now carried a fraudulent notification that it had last been updated on April 6. 1969 was the year Richard Nixon launched his war on drugs, using it to set up what was intended to be his very own secret police force - the Drug Enforcement Agency, a story chronicled in Edward J. Epstein's great book Agency of Fear. Biological warfare was integral to the US war against Vietnam. CounterPunchers will recall Agent Orange, the hellish brew deployed to defoliate the jungle. Agent Blue, targeted on rice production, is less well known. The aim was to wipe out the NLF's food supply. Rice plantations deemed to be servicing the enemy were duly sprayed & obliterated. Professor Matthew Meselsen recalls how, early in 1970, he was taken by a US Army Chemical Corps colonel to survey a valley in an upland area that had been sprayed with Agent Blue some weeks before. As they flew over the devastated valley, the colonel proudly explained to Meselsen that this had obviously been an NLF food supply area since there were no houses to be seen. Later, they landed at a nearby village that turned out to be thronged with refugees from the valley. The refugees explained that they had fled because the Americans had just destroyed their rice crop. Scrutinizing photographs he had taken from the air, Meselsen later detected numerous houses that had been invisible while flying overhead at speed. A simple calculation revealed that the amount of rice under cultivation in the valley had been just sufficient to feed the locals, with none left over to feed hungry Vietnamese guerrillas. Meselsen wrote a report that prompted some political qualms in the US command in Vietnam, which recommended to Washington that Agent Blue be terminated. The recommendation was leaked to the Washington Post, whereupon Nixon cancelled the program forthwith. It is a measure of the obtuse barbarity of our present generation of drug warriors that they make Richard Nixon look sane. Despite abundant evidence of the dangers of deploying bioweapons such as the fungi in the wild, the US appears determined to press ahead. Counterpunch is published twice monthly except Aug. 22 issues a year: $40 individuals, $100 institutions & supporters $30 student/low- income. 3220 N St NW, PMB 346 Wash. DC, 20007-2829 800.840.3683 fax 800.967.3620 GM cheese from cow clones 1.27.03   BBC Scientists in New Zealand have created the world's first cow clones that produce special milk that can increase the speed & ease of cheese-making. Hamilton researchers say their herd of 9 transgenic cows make highly elevated levels of milk proteins, called casein, with improved processing properties & heat stability. Cows have previously been engineered to produce proteins for medical purposes, but this is the first time the milk itself has been genetically enhanced. The scientists hope the breakthrough will transform the cheese industry, and, if widened, the techniques could also be used to "tailor" milk for human consumption. Opponents of GM foods continue to doubt whether such products will be safe. The researchers led by Goetz Laible engineered cells in the laboratory to overproduce casein proteins. The cells were then fused with cow eggs. The resulting embryos were transferred into recipient cows, and 11 transgenic calves were born. 9 were found to produce the enhanced milk. One protein, called kappa-casein, increases heat stability in the cheese-making process. The other, beta-casein, improves the process by reducing the clotting time of the rennet, which curdles the milk. It also increases the expulsion of whey, the watery part of milk which remains after the cheese has formed. The cows are now producing milk with 8-20% more beta-casein, and double the normal amount of kappa-casein. Reporting their findings in the journal Nature Biotechnology, the scientists said that controlling levels of the 2 proteins could offer big savings for cheese manufacturers. "When projected on to the production scale of the dairy industry, the increases observed in our study represent large changes that would translate into substantial economic gains," they wrote. Cows born with human DNA 8.13.02   Helen Briggs BBC Cloned calves that produce human antibodies in their blood have been born in U.S.. The 4 cows have extra DNA which contains the genes for the part of the human immune system that makes disease-fighting antibodies. Scientists believe cows could eventually be used to produce medicines to treat multiple sclerosis, infections and even cancer. Human antibodies have been produced in mice before, but cattle are bigger and make more of them. The work was carried out by researchers in U.S. led by animal cloning pioneer James Robl, former Univ. of MA prof. first to clone a transgenic cow in 1998 & Hematech (Westport CT) president, biotechnology firm set up to manufacture human antibodies in cattle. Dr Robl told BBC News Online: "The antibodies that we produce consist of a large collection of different types that will be particularly useful for killing infectious disease agents. We believe that by successfully transferring the antibody genes into cows we have overcome one of the most difficult challenges in the project." Genzyme Transgenics Corp (MA) animal cloning expert Yann Echelard says the cloned cows could eventually have important medical applications. "The cows have a human immune system," he told BBC News Online. "You can immunise them, collect their blood, get the antibodies out, purify them and give them to patients." Antibodies are used for the treatment of many human diseases incl immune deficiencies, infectious diseases, and autoimmune disorders. They have to be extracted from blood donations and are in short supply. Hurdles to overcome before human antibodies from cows could reach the hospital require scientists find a way to purify the human antibodies and make sure they are free of harmful viruses. "This is an important step but it is a first step in a process that will go on for years before there is a medicine available to the general public," said Dr Echelard. Existence of the 4 cloned cattle is revealed in the journal Nature Biotechnology. The first calf, Yoon, was born last November. She was named after a graduate student who spent many nights looking after the animals. About 20 similar cloned cows have been born since then. The calves are known as transchromosomic. Unlike other cows they have an extra synthetic chromosome, one of the bundles of DNA and protein that carries genetic information. An artificial chromosome has been put into the animals to carry human immune system genes. Genetically manipulated bull put to sleep 4.2.04   AP Amsterdam, Netherlands   Herman the Bull, world's first farm animal carrying a human gene, was euthanized Friday because he was suffering from a form of arthritis, his caretakers said. He was 13, not exceptionally old for a bull. His ailment was unrelated to his genetic manipulation, said the Naturalis museum in Leiden where Herman spent his final years. A human gene was spliced into Herman's genetic code while in an early embryonic stage in 1990, in the hope that milk produced by his female offspring would bear a human milk protein. The process was cutting-edge at the time, but has since been refined and is commonly used. The experiment was only a partial success. Milk from Herman's descendants contained the proteins, but at such low levels it wasn't commercially worthwhile to extract them. A spokesman for the Naturalis museum said the animal's joints had become almost completely blocked with growths. "He was always well-kept & happy, but you could see toward the end that he was in pain," Hans Dautzenberg said. "He avoided moving his knees and when he laid down, he stayed down for a long time." Dolly the sheep, the world's first mammal cloned from an adult, had also suffered from arthritis and was euthanized in 2003, well short of her normal lifespan, after being diagnosed with a progressive lung disease. Pharming NV, company that modified Herman, underwent financial restructuring in 2001. Herman's 55 offspring were slaughtered after the experiment concluded, and he was bound for the same fate until a TV program screened footage showing him licking a kitten. A public outcry ensued, led by animal rights activists, which saved him. He eventually won a bill of clemency from parliament, though he was ordered castrated. He lived on a farm for years until funding for his care ran out in 2002. He was then moved to a special display pen at Naturalis to help cover costs. He was not allowed out of his pen until Friday, when he was taken to a veterinary hospital in Utrecht to be euthanized. But 2 cloned cows, Holly and Belle, kept him company in his final years. Dautzenberg said Herman's skin will be saved and put into storage, in case the museum wants to have him stuffed and put on display. The 2,500-pound bull was a cross between two Dutch breeds, the Zwartbont Holstein Frisian and Groninger Blaarkop. In an interview with the Associated Press in 2002, Herman's keeper Marije de Vos said he had a fondness for music. De Vos said he listened to a rap station "around the clock." "It makes Herman calm," she said.

Dogs' ancestors were most probably wolves 10.25.01   Steve Dale Tribune Media Services Dogs were once considered pests in the same category as cockroaches, city rats and pigeons, according to biologists Raymond & Lorna Coppinger in "Dogs: A Startling New Understanding of Canine Origin, Behavior & Evolution" (Scribner, $26). … "I can sum up the secret to training dogs in 3 words," he said: "Make it fun." The Coppingers have been researching canine behavior, mostly together, for 43 years. In 1976, Raymond launched the Livestock Dog Project, still considered the foundation for scientific research about livestock dogs. In America alone, Raymond followed the lives of more than 1,400 dogs in 43 states. In all, the couple has researched canine behavior in 19 countries. The Pinocchio Theory The Coppingers agree with recent genetic evidence suggesting dogs are indeed evolved from wolves. However, their theory suggests people didn't domesticate wolves; instead, the animals more or less domesticated themselves or at least began the process. Raymond points out wild wolves are not easily tamed. It's no coincidence, he notes, you see performing lions, tigers and bears in circus acts but never wolves. The Coppingers reject what they call the Pinocchio Theory of Dog Origin: "The wolf pup is taken from its den by people then becomes a real dog," sums up Lorna. Instead, over many generations, some wolves became as adjusted to human settlements as today's city pigeons. … Tame foxes Russian geneticist Dmitri Belyaev bred silver foxes to be tamer so they could be more easily handled on commercial fur farms. Even though these wild foxes had been bred in captivity for 80 years, and raised & cared for by people, they remained pretty much unchanged in their wild ways. Belyaev began to breed foxes for good traits; after only 18 generations, Belyaev found himself with tame foxes, but possessing traits he had not bred for, such as a piebald (black & white) coat, tails turned up and droopy ears. They looked very much like domestic dogs, even barking like dogs. … [ Your insufficiently humble editor apologizes in retrospect & henceforth for each & every umbrage; whether risen or fallen, meritorious or lamentable, it is incontrovertible that I matured beyond the domestication expected of me by others. Should you spot me at large without handler, leash & not least, muzzle, don't hesitate to call Animal Control ]   spycat allergy stray economic kitty Cloned cat means pet-cloning business may be possible 2.15.02   K.Reed Bloomberg News San Francisco   Researchers said they cloned a cat, adding to the short list of animals in which the technology has worked and suggesting it soon may be possible for pet owners to produce exact copies of a beloved cat or dog. The calico kitten, named Cc: for the secretarial designation for carbon copy, was born in December, according to a team of scientists from the College of Veterinary Medicine at Texas A&M University. Their research will be published in next week's edition of the journal Nature. The Texas research group is also behind a well-publicized effort to clone Missy, an aging & beloved Husky-mix dog owned by John Sperling, chairman of Apollo Group Inc., a higher-education company that owns the University of Phoenix. Sperling started a pet-cloning company after getting requests from pet owners about the so-called Missyplicity dog-cloning project. "We are intending to commercialize pet cloning as soon as we are able to do it consistently, safely and successfully," said Ben Carlson, a spokesman for Sperling's San Francisco-based company, Genetic Savings & Clone, which is funding the Texas research. "We aren't quite there yet. We don't want to do this prematurely." The Texas A&M researchers cloned Cc: from an ovarian cell of a calico called Rainbow. Two Mothers The healthy, two-month-old kitten looks nothing like her surrogate mother, a tabby named Allie, and resembles Rainbow only vaguely because the pattern of a cat's coat is only partially determined by genetics, the researchers said. Genetic Savings & Clone has the commercial rights to any technology the Texas A&M group develops. Currently, the company markets a service that allows pet owners to bank genetic material from a dog or cat for $895, in the hopes of one day cloning the animal. Thousands of owners have done so, Carlson said. "If you are the owner of a spayed mutt or a mutt that's neutered and is an animal that you feel is genetically exceptional, then you are a prime candidate for our service," Carlson said. False Hopes Genetic Savings & Clone also has programs for banking genetic material from prize livestock for breeding purposes, and says it will soon store DNA from endangered species and particularly gifted rescue animals. The cloning company offers gift certificates that can be sent to friends or family members who own an "exceptional animal," and for $1,395 offers an emergency service to rapidly preserve DNA from an ailing or deceased pet , as long as the samples are taken within a week of the animal's death. That can create a sticky situation at times, Carlson said, because some people seek to clone an animal with the false hope that they will wind up with exactly the same pet. While clones are genetically identical or close to it, environment and upbringing will influence a pet's personality just like it would a human being. "People tend to think of our service when they are running out of time," he said. "There are people who contact us in the hopes that we can confer immortality on their pet or bring their pet back to life and we cannot do that." In cases where clients seem devoted to the idea of bringing back a dead pet, the company generally refers the pet owners to grief counseling instead, Carlson said. Humane Concerns The Missyplicity project is run according to strict bioethical standards, and all of the laboratory animals involved are placed in "loving homes" after several months in the lab, according to the group's Web site. Still, the Humane Society of the U.S. criticized news of Cc:'s existence. Cats outnumber dogs in most animal shelters, and often have kittens, the group said. Up to 10 million animals enter U.S. shelters every year; some 4 million to 5 million of these animals are euthanized because homes can't be found for them, the group said. "It doesn't sit well with us to create animals through such extreme & experimental means when there are so many animals desperate for homes," Human Society spokesman Wayne Pacelle said. Livestock First Until now, successful cloning efforts have been aimed at improving livestock or enabling scientists to use animal organs & tissues in human medicine. Geron Corp., Australia's BresaGen Ltd. and the U.K.'s PPL Therapeutics Plc, which created Dolly the sheep, are among the leaders in animal cloning. The Wall St Journal reported the existence of the cloned kitten this morning, prompting Nature to release the study ahead of schedule. Cc: is the only survivor of 87 cloned embryos that were implanted into eight surrogate cats. That's about the same success rate as researchers have experienced with the other species that have been cloned, scientists said. Most of the failed attempts involved clones of cells taken from the cats' mouths, and the healthy kitten was one of only three attempts that used ovary cells, the team said. "It remains to be investigated whether this cloning efficiency is reproducible in cats," the team wrote in Nature. A year later, cloned cat is no copycat Cc illustrates the complexities of pet cloning 1.21.03   Kristen Hays AP College Station, TX   Rainbow the cat is a typical calico with splotches of brown, tan and gold on white. Cc, her clone, has a striped gray coat over white. Rainbow is reserved. Cc is curious & playful. Rainbow is chunky. Cc is sleek. Wayne Pacelle of the Humane Society might be inclined to say: I told you so. But then, so would cc's creators at Texas A&M University. Sure, you can clone your favorite cat. But the copy will not necessarily act or even look like the original. Though cc's arrival sparked a deluge of calls from pet owners, more research is needed to figure out how to produce consistently healthy clones before the co. can start doing it commercially, said spokesman Ben Carlson. "A year ago, we said we'd start commercial services in a year, and here we are a year later," Carlson said. "It's really impossible for us to make a certain prediction as to how long it's going to take to develop the technology to get successful results." There is a demand from dog lovers, but scientists so far have been unable to clone a canine. In fact, cc's creation was the result of a dog lover, not a cat lover. Univ. of Phoenix founder John Sperling wanted a duplicate of his collie mix, Missy. With his $3.7 million, Texas A&M launched the "Missyplicity" project over four years ago. Now, Missy is dead, euthanized last year because of an inoperable growth on her esophagus. Sperling has redirected his funding to the Sausalito, Calif.-based Genetic Savings & Clone, which he hopes will one day deliver a clone of Missy. turning away customers CC (for "Carbon Copy") is just over a year old. Her birth 12.22.01, was big news when it was announced last Feb. because it was the first time a household pet had been cloned. Previous mammal clones were barnyard animals like cows & goats. Cc's creation was funded by Genetic Savings & Clone, a co. that hopes to make money from people's desires to duplicate their favorite pets. Last Feb., in the journal Nature, the A&M researchers published details of the project and DNA test results that showed cc was a clone. But people who hope cloning will resurrect a pet will be disappointed, said A&M animal cloning expert Duane Kraemer. Experts say environment is as important as genes in determining a cat's personality. As far as appearance, having the same DNA as another calico cat doesn't always produce the same coat pattern. "This vindicates the opposition we espoused from the beginning, that cloning does not lead to duplication," said U.S. Humane Society sr vp Pacelle. "Not only does cloning not produce a physical duplicate, but it can never reproduce the behavior or personality of a cat that you want to keep around. There are millions of cats in shelters & with rescue groups that need homes, and the last thing we need is a new production strategy for cats." hundreds of samples Before the birth of cc, Genetic Savings & Clone had hundreds of pet DNA samples stored at a cost of $895 for healthy animals and $1,395 for sick or dead animals. Genetic Savings & Clone chief exec. Lou Hawthorne estimated cost to create a clone will initially be in the low 5 figures and later drop to the low 4 figures. Carlson said the co. tells pet owners that cloning won't resurrect their pet and that the co. has turned away some customers clearly interested in getting the same animal. "In the short term, it's easy to exploit that misperception," he said. "But in the long term, it's unethical, and the pet owner will quickly find that, 'Hey, this isn't Fluffy, this puppy doesn't recognize me or know all the old tricks.'" However, he said cloning could reproduce what a pet owner considers to be exceptional genes, particularly from an animal with unknown parentage or one that has been spayed or neutered. "A small percentage of the population know exactly what they want and they want to stick with it, another animal as similar as possible," Carlson said. "That's the motive we've encountered among our clients." But disclaimers could go unheard by pet owners desperate to duplicate an animal, said Univ. of PA bioethicist Arthur Caplan, critic of pet cloning and companies that purport to sell it. He said animal lovers bond with pets because of their personalities & behaviors, not the genetic material that defines the immune system or blood type. "The new cloned dog won't know the old tricks; you have to teach them," Caplan said. "It doesn't matter how many genes they have in common." finished with cats With the Missyplicity funding gone, Texas A&M will continue trying to break new ground in cloning farm animals, wildlife and dogs, but it is finished with cats and any commercial pet venture. As for cc, the Texas scientists say she has shown no signs of genetic defects. "She's been perfectly healthy and perfectly a cat ever since her birth," Kraemer said. "That's true of all our clones. You'd have to be told they were cloned in order to know" they weren't conceived the natural way. Even so, cc has been protected by a sterile environment, a precaution to make sure she is healthy; visitors are not allowed to pet her. That will change gradually when she moves into her new home with Kraemer & his wife, Shirley. The Kraemers will introduce her slowly, first exposing her to people who have cats before letting her cavort with their other 2 felines. In time, they plan to breed cc and let her produce some carbon copies of her own. But they are looking for just the right tom. "Our geneticists haven't gotten back with that information," Kraemer said. Salty kitty 8.7.03   SD Reader … Selkirk Rex is the name of a new breed of curly haired cat J. Mellinger raises at Spellbinding Cattery in Bonita CA. "In 1988, there was a spontaneous genetic mutation. A Wyoming animal shelter gave a cat to a breeder who decided to try it with a Persian. The cat had curly kittens. I have some that are extremely curly, like 'Afro' curly and some with curls that are looser." Since the breed is so new, Selkirk Rexes still produce straight haired kittens. … Cloning yields human-rabbit hybrid embryo 8.14.03   Rick Weiss Wash.Post pA4 Scientists in China have, for the first time, used cloning techniques to create hybrid embryos that contain a mix of DNA from both humans & rabbits, according to a report in a scientific journal that has reignited the smoldering ethics debate over cloning research. More than 100 of the hybrids, made by fusing human skin cells with rabbit eggs, were allowed to develop in laboratory dishes for several days before the scientists destroyed them to retrieve so-called embryonic stem cells from their interiors. Although scientists in Massachusetts had previously mixed human cells & cow eggs in a similar attempt to make hybrid embryos as a source of stem cells, those experiments were not successful. Researchers said yesterday they were hopeful that the rabbit work would lead to a new & plentiful source of embryonic stem cells for research and, eventually, for medical use. But theologians & others decried the work as unethical. Some wondered aloud what, exactly, such a creature would be if it were transferred to a womb to develop to term. The vast majority of the DNA in the embryos is human, with a small percentage of genetic material, called mitochondrial DNA, contributed by the rabbit egg. No one knows if such an embryo could develop into a viable fetus, though some experiments with other species suggest it would not. Congress has been mulling legislation for years that would outlaw certain human cloning experiments, with some opposed to any creation of cloned embryos for research and others sympathetic to research uses as long as the embryos are not allowed to grow into cloned babies. No law has been passed, however, in part because of researchers' warnings that the proposed restrictions are so far-reaching that they would hobble development of new medical treatments. The new work, led by Hui Zhen Sheng of Shanghai Second Medical University, appears in the latest issue of Cell Research and was highlighted in a news report in the journal Nature. Cell Research is a peer-reviewed, if little- known in U.S., bimonthly scientific journal affiliated with the Shanghai Institute of Cell Biology and the Chinese Academy of Sciences. Some researchers yesterday said they were frustrated by the lack of details in the paper. The team said it retrieved foreskin tissue from two 5-year-old boys & two men, and facial tissue from a 60-year-old woman, as a source of skin cells. They fused those cells with New Zealand rabbit eggs from which the vast majority of rabbit DNA had been removed. More than 400 of those new, fused entities grew into early embryos, and more than 100 survived to the blastocyst stage, the point at which coveted stem cells begin to form. The approach could help scientists wishing to mass- produce human embryos as sources of human embryonic stem cells. Stem cells can morph into all kinds of tissues and may be able to reverse the effects of various degenerative diseases. But to make cloned embryos, scientists need both normal body cells, such as skin cells, and egg cells, which have the unique capacity to "reprogram" the genes in body cells and make them behave as though they were embryo cells. Because human egg cells are difficult & costly to retrieve from women's ovaries, and because human egg retrieval poses risks to the donors, scientists have been wanting to know whether animal eggs may serve as well. A major question has been whether the remnants of mitochondrial DNA that typically remain in an animal egg would be compatible with the nuclear DNA contributed by the human cell. The new work suggests that the answer to that question is yes, scientists said, though with a number of caveats. Most important, researchers said, the paper stops short of proving beyond a doubt that the stem cells retrieved from the hybrid embryos are truly capable of growing for long periods of time in lab dishes, and that they can turn into every known kind of cell. Even so, said Harvard Univ. cell biologist & cloning expert Douglas Melton, the work is a big advance because it offers a new system for exploring the mechanisms by which egg cells get adult cells to act in embryonic ways. That could provide deep insights into human development, wound healing and tissue regeneration. He noted that although this is the first creation of a human "chimeric" embryo, a reference to the fabulous chimera of Greek mythology, which had a lion's head, a goat's body and a serpent's tail, it is not the first time scientists have blended human cells into lab animals. Some mice, for example, have been endowed with human brain cells or portions of the human immune system for research. The Chinese work, Melton said, is "extremely interesting, and I hope they pursue it." Univ. of Wisconsin at Madison assoc. dean of law & bioethics prof. R. Alta Charo noted that the work passed muster with Chinese ethics authorities, who had demanded, among other things, that the embryos not be allowed to grow more than 14 days. "Short of putting one of these embryos into a woman's body for development to term, I don't think this work harms anyone alive," Charo said. She said the experiments should force opponents of cloning research to identify more clearly than they have until now exactly where they would draw the line against human embryo cloning; in effect: How human does an embryo have to be to have the moral standing these advocates confer on embryos? U.S. Conference of Catholic Bishops' Richard Doerflinger, said he felt certain that the human-rabbit embryos were human enough to deserve protections. "I think because all the nuclear DNA is human, we'd consider this an organism of the human species."

Horse breeding for speed down to a science 6.5.04   Robyn Norwood L.A. Times Even before Smarty Jones reaches the starting gate at today's Belmont Stakes, trying to become horse racing's first Triple Crown winner since 1978, the race to breed another champion in his image has begun. In Reddick FL, I'll Get Along, mare who foaled Smarty in 2001, is carrying a full sibling of the Kentucky Derby & Preakness Stakes winner, due next March. 2 months into an 11-month gestation, the fetus is the size of a mouse, with tiny, developing hoofs. In Versailles KY, Smarty's sire Elusive Quality is led to the breeding shed at Gainsborough Farm two to three times a day, 7 days a week, to fulfill dates with 135 mares this season at $50,000 each, a fee that will go up next season. After his work in Kentucky is done, the stallion will be shipped to Australia for the Southern Hemisphere breeding season, where 85 mares await. Mating of thoroughbreds in quest of victory at the track has long been a sophisticated combination of art and informal science. Owners & breeders study thoroughbreds' family trees so closely, they are more likely to be able to list a horse's great-great-great grandparents than their own. Yet the ways genes recombine generation after generation are so unpredictable, the axiom long has been, "Breed the best to the best and hope for the best." Now, as 100 scientists at 25 laboratories around the world cooperate to map the horse genome for the first time, geneticists and a few figures in the traditional world of thoroughbred breeding are beginning to explore the ways genetic information might enhance the chances of breeding a champion. "Everybody is trying to get a faster racehorse," said Stonerside Stable bloodstock expert John Adger, breeding operation & racing stable near Paris, KY owned by Robert McNair who also owns the NFL Houston Texans. "People have been trying to do it for centuries, but again, you didn't have the mapping of the genes like you do now." Unlike the completed map of the human genome, the equine gene map is a work in progress. But w/ advice of McNair's friend & business partner Dr. C. Thomas Caskey, renowned human geneticist & former president of Merck Genome Research Institute and the Human Genome Organization, Stonerside has begun a project with Texas A&M University in which researchers will study the DNA of thoroughbreds in search of genetic clues to their success on the racetrack.

British co. Thoroughbred Genetics Co. already has been advising clients on breeding & purchases for several years by using DNA analysis in addition to traditional breeding theories, though many scientists question whether enough is known about the horse genome yet to perform a marker-based selection. Co. managing dir. Steve Harrison eagerly awaits results as colts produced by matings he recommended begin racing in the next 2 years.
None of the scientists seeking answers to the centuries-old puzzle of how to breed a faster horse is proposing cloning or manipulation of the genes. They simply want to use DNA analysis as a tool to make more effective decisions about which stallions and mares to breed to one another.

Even if someone wanted to clone a Triple Crown winner, the Jockey Club, which governs the registration of thoroughbred foals, already had banned clones even before Italian scientists produced the world's first cloned horse in 2003. The Jockey Club also prohibits embryo transfer or any form of genetic manipulation and, in what seems an old-fashioned notion in light of advances in human fertility, still requires the "physical mounting of a broodmare by a stallion."

Ways in which traits are handed down are so complex, even a full sibling of a champion racehorse is no sure thing to succeed on the racetrack. Secretariat had a full sister, the Bride, who never won a race. "As somebody said, Larry Bird probably has a brother who can't play basketball," said Lexington KY race course Keeneland sales dir. Geoffrey Russell, where the most prestigious yearlings are auctioned at 2 annual sales. Bird has 4 brothers, and none ever played an NBA game.
"The interesting question is: What is the nature of racing?" said Univ. Kentucky's Gluck Equine Research Ctr geneticist Ernie Bailey, coordinator of intl genome effort. "People come visit our lab and we tell them about genes that control immune response, disease resistance, all these elegant experiments. They sit patiently and listen, and then they raise their hands and ask, 'Have you found the speed gene yet?'"
"Racing performance is much more complex. Speed probably is not a matter of one gene, but different genes combining in different ways. That's the thing that makes racing a fascinating sport."

Animal Health Trust geneticist Matthew Binns in Newmarket, England is another of the researchers hoping to find markers that signal the likelihood of success on the racetrack. "What do we mean by racing performance?" Binns said. "Instinctively you know it means winning the big races, but that involves the heart, lung, bones, muscles and temperament. Each is complicated genetically."
Heart size is seen by many as a particularly important factor. An autopsy of Secretariat, 1973 Triple Crown winner and a great-great-grandfather of Smarty Jones, revealed a heart almost twice the size of the typical thoroughbred's. Yet what makes a winner also is more than physiology: There is the issue of environment, and factors such as training, illness, injury, the skill of the jockey, even a horse's competitive spirit.
"I think it's kind of an indecipherable quality they're trying to get to," said Reddick FL Cloverleaf Farms II general manager Brent Fernung, where Smarty Jones' dam is in foal with his sibling. "They've done so much with cattle genetics and weight gain and fat percentage. That's something that's easily measured. Racing ability is a little different. You can't look inside that as easily."

Ultimately, a number of scientists believe, the contribution of genetic study to racing might not be discovering what makes a horse such as Smarty Jones go fast, but what could keep him from doing it. "Whether we'll ever find a 'go- fast' gene, I doubt it," said UC Davis animal science & veterinary medicine prof. Jim Murray. "The genome project ultimately will help … as we understand more and more about horses, more about bone development and why they go lame, for example."
In fact, one of the major benefits of the horse genome project so far has been the development of tests for 3 important diseases that affect certain breeds: an immunodeficiency syndrome known as SCID that affects Arabians; a muscle disease in quarter horses known as hyperkalemic periodic paralysis, or HYPP; and a disease affecting spotted horses called lethal white syndrome. Developing tests for genetic problems in thoroughbreds eventually could improve performance.
"You could say, 'What things limit racehorses?' " said British researcher Binns. "Having fractures of their bones, bleeding in the lungs. Nearly all the main problems would be caused partly by genetics and partly by environment."

Each year, some 36,000 thoroughbred foals are registered in North America by the Jockey Club. Only one will win the Kentucky Derby. Only 11 have ever won all 3 races of the Triple Crown, a feat Smarty Jones will attempt to complete today in Elmont, N.Y. Those are considerable odds. Add to that the fact that a horse has about 30,000 genes, arranged on 64 chromosomes.
"It's going to be very hard to predict the outcome of a mating," said James A. Baker Institute for Animal Health dir. Douglas Antczak at Cornell. "It's a mind-staggering amount of different combinations." The equine lotto paid off unexpectedly for Roy & Patricia Chapman, a couple well along in years who had never had even a starter in the Derby until they bred their champion at a place in Pennsylvania they called Someday Farm. It will be next year before the racing world gets a look at Smarty's first full sibling, and even longer before it is clear whether the foal can race.

All the while, scientists will be working to improve the odds in a business sometimes seen as a crapshoot. "I hope they never get too good at it," said Cloverleaf manager Fernung. "If they do, the richest people will have the best horses. Then you wouldn't have great stories like the Chapmans."

Gene switch 'makes mighty Mensa mice' ¹ ² ³ ¶ 6.20.00   Roger Highfield News Telegraph UK Mice that have been genetically modified to make more of a brain growth protein are significantly smarter, scientists report today. The development of what one of the team calls "mighty Mensa mice" shows how society may be affected by knowledge of the human genetic code, the first draft of which is about to be published, and will stimulate ethical debate about whether to enhance people. Prof Aryeh Routtenberg, head of a team at Northwestern Univ., Evanston IL, said that it took a change in a single genetic "letter" to cause "a very strong determinant effect". However, he added that the work also underlines the importance of the environment because feeding rodents with corn oil can "turn on" the same memory protein in the brain by a process called phosphorylation. Prof Rottenberg said that mice had been altered to produce unusually large amounts of GAP43, a protein associated with the growth of fibres that transmit nerve impulses. He said: "These animals perform in tests as if they are smarter."

Scientists create Down's syndrome in mice 2.20.00   J.Thornton & R.Highfield News Telegraph SCIENTISTS have genetically engineered a mouse with Down's syndrome. The development may lead to doctors being able to repair some of the syndrome's effects in humans. The genetic disorder, where an extra chromosome is present, occurs in one in 700 human births and is the most common cause of mental handicap. More than a dozen mice were bred with 3 copies of chromosome 21, instead of the usual two, in their cells, in an attempt to reveal how the condition affects the brain. Roger Reeves, of Johns Hopkins University, Baltimore, who co-led the research, said that repair may be made possible by identifying the genes that make the biggest contribution to the disorder. One approach would be to use gene therapy to counter the effects of these genes. Another approach would focus on making good the shortfall in the cells that form various structures in the bodies of Down's syndrome patients. Dr Reeves said that there was great interest in using "stem cells", parent cells of all types in the body, to grow nerve & other cells to repair a body.

This, at a conceptual level, could offer other ways to "tone down" the problems caused by the syndrome. He said: "Since this mouse can accurately predict what will happen in Down's syndrome, we can use that in a very powerful way to make conclusions about what is going wrong in development."

The mice with the extra chromosome, bred at the Jackson Laboratory in Bar Harbor, Maine, have short noses, skulls slightly flattened at the back and an abnormally small cerebellum - the part of the brain controlling movement - as do people with Down's syndrome. Joan Richtsmeier, one of the research team, marked various parts of the skulls of the engineered mice & "normal' mice with a laser microscope and measured the distances between the points. The researchers then matched the data with the characteristics of people with Down's syndrome. Dr Reeves said: "We found an absolute correspondence. The changes in the mouse face are in the same bones, in the same patterns, as in humans."
His initial research also indicates that there is an abnormally low density of cerebellar brain cells connected with the disorder, which scientists had not previously known about. "Nobody knows exactly why having too much of a chromosome would lead to the developmental problems you see with Down's syndrome," he said. "We believe this model will explain that in a way we couldn't before. "Is this model good enough to reflect what goes on in humans? Yes, it's about the strongest parallel you can get." He added that within 3 years he aimed to discover the genes that govern development of the skull & face. This could shed light on other craniofacial problems that hundreds of people in Britain are born with and which, while rarely fatal, are extremely costly to treat and are psychologically traumatic.

no title 5.14.04   Reuters London   A Nobel Prize winning scientist has called on British govt to introduce legislation to prevent discrimination on the basis of people's genetic make-up, the Guardian newspaper reported on Saturday. "The main worry with genetic tests is abuse of the information," Sir John Sulston, member of govt's genetics advisory panel the Human Genetics Commission, told the Guardian in an interview. "So are we going to use them and lose the medical benefits, or are we going to alter society by drafting good laws so people are protected?" said Sulston. Medical advances and sequencing of the human genome have led to concerns that genetic testing could be used by insurance companies & employers to discriminate against people with an increased risk of developing certain diseases. "People are quite right to be leery about having genetic tests until we have solid laws in place to protect their rights," Sulston told the Guardian. "What we have to establish, right across the board, is the right for people to be treated equally, regardless of their genetic make-up. "We can't just keep fudging the issue. Like laws on sexual & race equality, this could be very hard to police & enforce, but it is nevertheless worth pushing for." Sulston shared the 2002 Noble medicine prize with fellow Briton Sydney Brenner & Robert Horwitz of U.S. for their work on how cells divide and die and how genes regulate. This shed light on diseases from AIDS to cancer. Scientists finish draft of human genetic code 6.10.00   Roger Highfield News Telegraph A rough draft of the entire human genetic code has been completed, after years of work by thousands of researchers worldwide. The achievement is a milestone in a project that will change the face of medicine & society. The effort to read the code, or genome, will pave the way for a medical revolution but also create dilemmas over how genetic information should be used. It raises the prospect of "designer babies", for instance, or tests to assess insurance premiums or select employees. The goal of the Human Genome Project, a publicly funded international consortium, and its commercial rival, Celera Genomics in the US, is to read all three billion "letters" of the human genetic code, the book of life. Formal announcements of the first working drafts, 90 per cent of the recipe for a human being, or genome, are expected within the next week or so. This autumn, probably October, the journals Nature and Science will publish the first analysis of what the data from the public effort means, such as the number of genes it takes to make a man. Each cell contains the code, in bundles called chromosomes. The letters of the code - As, Cs, Gs and Ts - spell out genes, the instructions to make the proteins in an organism. However, completion of the working drafts mark only the beginning in terms of understanding disease and the effort to develop drugs to prevent and treat illness, or to use gene transplants. Celera said it had "completed the sequencing phase of the genome from one human being" and was about to announce that the information had been assembled into the rough draft. A spokesman for the genome project, which consists of 16 centres around the world, said it too had completed the draft. A spokesman for the Sanger Centre, near Cambridge, said: "The sequence is there, or thereabouts. But we still have to go through some checking. " He said that about 20% of the code has been finished. Reading the entire code will be the most momentous achievement since James Watson and Francis Crick identified the structure of DNA in 1953 at Cambridge. When the effort was first mooted in the Eighties, no one imagined it would be completed as swiftly or as cheaply. However, even when the final draft appears, expected in 2003, gaps will remain due to deficiencies in the method used to interpret & reproduce the code. Thinking big   Harvard Med School dropout aims to usher in personal-genomics era 6.2.02   Gary Stix Scientic American Science was king when Eugene Chan was growing up. His father Ka-Kong Chan, émigré from Hong Kong, would bring home ball & stick models that represented organic molecules, mementos from his job at Hoffmann-La Roche, where he received 40 U.S. patents as a chemist. Outside the home, however, rampant philistinism reigned. Chan's school environment in northwestern NJ had such slim science offerings that by the time he headed for the Ivy League, he had never even heard of the Westinghouse Science Talent Search (now the Intel Science Talent Search). Nevertheless, the boy propelled himself to become champion in a statewide physics contest in 2 separate years by grabbing physics & calculus books off library shelves. "I realized I had a lot of ability and didn't need formal training to compete with the best of the best," Chan remarks with characteristic bravado. At Harvard his autodidactic skills served him well. He gained top honors, eventually graduating summa cum laude in 1996. But he still found enough time to contemplate the germ of an idea for a technology that would build on the scientific findings of the Human Genome Project, then in its middle phases. "Is it possible for us to gain complete sequence information from every single person on the planet?" he recalls wondering. Later, at Harvard Medical School, he grew bored after a semester and returned to musing about a device that could read, within an hour or so, the variations in an individual's DNA that mark the essential genetic differences from person to person. During division each cell reads & replicates millions of DNA letters, or base pairs, in the course of a minute. Chan reasoned that a single blood test could be fashioned to achieve the more tractable task of rapidly discerning the variations in a genome, whereas the long unchanging segments of DNA would go unread. The probe would look for groupings of base pairs, several million in one genome, that correspond to a predisposition to disease or the ability to tolerate certain drugs. Piles of books & journal articles on molecular biology, medical instrumentation, optics and physics covered much of Chan's dormitory room. Borrowing from semiconductor manufacturing and the nascent field of nanotechnology, Chan conceived of placing miniaturized channels on a quartz chip. The DNA, propelled along by a fluid flow, would stream down the channel as if it were a film running through a movie projector. As the DNA moved along, a laser, positioned about halfway down the channel, would illuminate groups of base pairs tagged with a fluorescent dye. Like a bar-code reader, an optoelectronic device would determine which groups lit up and would thus mark genetic variations. To make the test widely available, Chan estimated that it should cost no more than a few hundred dollars. The concept became such an obsession that, after completing 18 months at Harvard Med School, Chan left to found U.S. Genomics. His brother Ian, who worked at a lucrative investment-banking job with Morgan Stanley, decided to join him. Chan somehow convinced a prominent Boston intellectual-property law firm, Wolf, Greenfield and Sacks, to write a patent application for him on spec, the firm would be paid once Chan obtained financing. Then, to build credibility, he set about assembling a prominent panel of scientists, which grew to include a Nobel Prize winner. The scientific advisory board would help him gain entrance to the offices of venture capitalists. The idea of a 23-year-old proposing a wholly new method of sequencing intrigued scientists and engineers on the Harvard-MIT axis. "I liked it that somebody his age was trying to tackle such a giant problem," says MIT chemical engineering prof. Robert S. Langer, member of the co.'s scientific advisory board. "If you could do the sequencing that rapidly, that would be a change-the-world kind of thing." First paltry $300,000 venture-capital infusion came from Boston-area firm Still River Fund. The funding sufficed to rent space at a technology incubator at Boston Univ. and served as an impetus to look for more money. To procure substantial backing, U.S. Genomics would have to show progress in its plan to create a personal-genomics sequencer. "The question people had for us was, 'Can you take that piece of DNA that looks like a big ball of spaghetti and unfurl this thing and move it past your reader device?'" Chan says. "In six months we demonstrated how we could do it." With the help of 5 others who joined the newly formed co., Chan fabricated a series of upright posts, each spaced a few tens of nanometers apart, at the mouth of a channel down which the DNA was to travel. The posts snagged the ball of DNA, and the pressure of the molecule against the posts caused it to unravel and stream down the channel toward the optoelectronic detector. A video that shows the DNA moving along the channel served as a proof-of-principle that allowed the co. to return to the venture spigot in 1998 to raise $2 million. That led immediately to the next hurdle, placement of fluorescent tags on the DNA and detection of the base-pair groupings as they passed the detector at a rate of 30 million base pairs a second. The expanding U.S. Genomics team spent most of 2000 developing a technique that could train a laser on a 2 nanometer spot on the elongated DNA and accurately detect whether the tags illuminate. Chan claims that the Gene Engine, as the product is called, can spot variations on DNA segments of 200,000 base pairs in length, enough to make the technology commercially alluring. By year's end he wants to expand the readout capacity fivefold. Conventional sequencers evaluate about 1,000 base pairs at a time. Until now, Chan has had to prove himself by convincing investors that it would be worth their while to lend $20 million to a 20-something med school dropout, while persuading govt & other funding sources to chip in $5 million more. With critical patents issued, and successes in meeting technology milestones, U.S. Genomics will now have to submit to the probing of prospective customers & the scientific community as well. It also faces competitors for rapid genome sequencing. The co., housed in virtually unmarked offices in an industrial park in Woburn, MA, has yet to publish a paper in a scientific journal that details the Gene Engine's performance. But Chan & his brother have initiated a coming out. In January, U.S. Genomics announced it would enter into a collaboration with a leading sequencing center, Wellcome Trust Sanger Institute in Cambridge, England, and join in a separate endeavor with the Washington Univ. School of Medicine to test the technology and to start publishing. The road ahead is still long. Sequencing the variations in 200,000 base pairs is a far easier task than reading a full genome, more than three billion in all. MIT's Langer thinks that bioinformatics, milling through the wealth of data generated by reading the base pairs, remains a challenge. Chan is unconcerned. "90% of the major questions are answered," he says. He predicts the co. will meet the goal of reading the variations in an entire genome by 2006. Even if that happens, Chan would not, at 32, be ready to rest on his laurels. Processing the information in whole genomes provides sufficient challenge, he contends, to last an entire career. Scientists highlight the x factor in autism 9.9.03   Jeremy Lovell Reuters Manchester   A part of the brain that is key to reading expressions in people's faces and which is affected by the X chromosome could give a new insight into autism's cause, says Britain's Institute of Child Health prof. David Skuse . "We have not discovered the cause of autism, but in the X chromosome we may have discovered a mechanism that could lead to a cause," he told reporters at the British Assn for Advancement of Science's annual conference. Recent U.S. figures showed one in 150 people there suffered from autism, a disease that effectively cuts the victim off from their social surroundings, and incidence of the illness has been rising at over 10% a year. Skuse noted that 10 times more males than females suffered from autism, and that males have an X & a Y chromosome while females have two Xs. Women suffering from Turner Syndrome in which they have only one X chromosome had also been found to suffer far higher rates of autism than their double X counterparts, he said. Skuse said the key lay in the amygdala, a part of the brain directly involved in processing emotional expressions seen on another's face. In most people the facial expression was immediately put in context with the aid of the amygdala, with the widely opened eyes that accompanied both fear & joy being correctly interpreted for what they actually represented. In autistics the amygdala appeared not to function properly and meant all such expressions were interpreted as fear. This in turn could explain why autistics rarely made eye contact, Skuse added. He said women with both Xs functioning normally had a fully operational amygdala, while those with only one X or with only one functioning as it should had poor expression recognition. In males the Y chromosome probably compensated for the key section of the missing X. Where it did not, the amygdala did not function properly. "We now have evidence of a plausible neural mechanism that puts boys at risk," Skuse said. While the general area of the X chromosome that influenced the amygdala had been isolated, it was so large that it would take many years more work to find exactly what gene or genes were the culprits, Skuse said.

Patients given own stem cells escape transplant 9.1.03   Reuters Vienna   4 of a group of 5 seriously sick Brazilian heart-failure patients no longer needed a heart transplant after being treated with their own stem cells, the doctor in charge of the research said Monday. Such "regenerative medicine," in which stem cells extracted from patients' own bone marrow are used to rebuild tissue, may one day become commonplace for patients with damaged or diseased hearts, some doctors believe. Hans Fernando Rocha Dohmann of the Pro-Cardiaco Hospital in Rio de Janeiro said his 4 patients had such a marked improvement in blood supply after stem cell treatment that they were removed from the list of those needing a heart transplant. "This finding has a significant social relevance since there isn't a single heart transplant program anywhere in the world which is able to treat all the patients who need it," he told reporters at the annual meeting of the European Society of Cardiology. Stem cell research is highly controversial because the most promising of such cells are taken from embryos, usually obtained from fertility clinics. Embryonic stem cells are capable of turning into nearly 200 different tissue types. Doctors believe the field has huge potential. "This is the first approach where you have an opportunity to actually heal a heart," said Columbia Univ. (NY) Dr Michael Rosen. "It's going to be a very long road, but it is the most exciting thing I've seen in my 40 years as a doctor in this field." The 4 critically ill patients were among a larger group of 14 who Dohmann and colleagues from the Texas Health Science Ctr in Houston had in April reported showing improved heart function. Their treatment involved taking cells from bone marrow and injecting them into the heart's left ventricle, the main pumping chamber. Heart failure is the inability of damaged heart muscle to pump enough blood around the body. Dohmann's patients belong to a small but growing number of patients being tested with the experimental therapy in centers around the world. Doctors at Beaumont Hospital in Royal Oak MI, earlier this year treated a 16-year-old shot in the heart with a nail gun; researchers said some 10-15 similar clinical trials could be under way around the world. Exact mechanism of action is not understood but medics believe stem cells harvested from bone marrow or blood may be able to form new muscle and blood vessels. Alternatively, they may trigger a chemical reaction that improves the functioning of cells in the locality of the injection. So far, all the clinical work involves so-called "autologous" cell transplants, in which cells are used from the patient's own body. Using foreign stem cells is another matter and is unlikely to happen for another 10 years, said Univ. of Cologne prof. Juergen Hescheler. Rosen & his team are working on a technique to use cell therapy to deliver genes to the heart that would improve its electrical pulse, effectively creating a biological pacemaker to replace today's mechanical ones. Science decoding DNA's poor cousin RNA found to be more than just a messenger 1.27.03   Andrew Pollack NY Times In the family of genetic material, RNA has long been the poor cousin of DNA. DNA makes up the genes, the master instructions of life, while RNA merely conveys those instructions to other parts of the cell. New discoveries show cells contain an army of RNA snippets that do much more than act as DNA's messenger. The discoveries are helping to refine the prevailing theories of genetics or even upend them. "It's like discovering the neutrino or something," said Harvard Medical School genetics prof. Gary Ruvkun. "These things were all around us for many years," and no one was aware of them. "Now we're discovering they are all over the place," he added. "Genomes are full of them." The discoveries are having practical applications. Scientists have found that tiny snippets of RNA with 2 strands instead of the usual one can be used to shut off specific genes. The technique, known as RNA interference, is being widely used to discover the functions of genes by turning them off and seeing what happens to the plant or animal. In a paper published in the journal Nature this month, Ruvkun & Harvard colleagues and Massachusetts General Hospital used RNA interference to turn off almost all of a worm's genes, one at a time, to discover those linked to obesity. Doctors hope that RNA interference will one day be used for medicine, inactivating genes, say, in tumors or viruses. "This is a gift from heaven," said Nobel laureate & MIT biology prof. Phillip A. Sharp, also Alnylam Pharmaceuticals founder, one of several companies started to exploit RNA interference. Many other companies are trying to develop drugs based on other aspects of RNA. PTC Therapeutics (S.Plainfield NJ) chief exec. Stuart Peltz said RNA had become "sort of a huge discovery zone." PTC is developing drugs that influence the way RNA works. Scientists have recently reported that Prader-Willi & Fragile X syndromes, each leading to mental retardation, and chronic lymphocytic leukemia may be linked to RNA defects. Biologists studying other species are also looking to RNA for answers to unsolved mysteries. "Everybody wants to look in their favorite organism or favorite system and see if there's an RNA lurking there," said National Cancer Institute biochemical genetics chief Susan Gottesman who studies E. coli bacteria. "A lot of the regulatory puzzles in E. coli are explained by small RNA's we didn't think were there." RNA & DNA are strings of chemical units called bases that embody the genetic code. The bases are represented by the letters A, C, G and either T in DNA or U in RNA. The C base always binds to G. A binds only to T or U. So a single strand of DNA or RNA can bind to another strand that has the complementary bases. Under what is known as the central dogma of genetics, genes, which are the recipes for making proteins, are part of the DNA of the chromosomes. When a protein is to be made, the DNA is copied onto a corresponding piece of single- stranded RNA, known as messenger RNA, that delivers the recipe to the cell's protein-making machinery. Proteins make up most of a cell and perform most of its functions, incl turning genes on & off. New evidence suggests that some RNA is not merely the intermediary between DNA & protein, but the end product. Some huge stretches of DNA that do not contain protein-coding genes and have been considered "junk" actually hold the code for some of this RNA. A study published in May by Affymetrix (Santa Clara CA) scientists, maker of gene chips, reported that in addition to the DNA's containing the recipes for proteins, a lot more DNA was being copied into RNA. It has long been known that RNA is more than a messenger. The ribosome, which makes proteins, is made partly of RNA. Another type of RNA, called transfer RNA, aids in protein production. Some scientists say it is not surprising that RNA has multiple roles, because it is generally believed that RNA had the role of both proteins & DNA in the early days of life on Earth. "We still have a lot of remnants from that," said Lawrence Berkeley Laboratory scientist Stephen R. Holbrook. The recent excitement has been generated by 2 discoveries related to small RNA snippets and their ability to turn off genes. Some genes, scientists found, produce tiny RNAs, known as micro-RNAs or miRNA, which are about 21 to 23 bases, or letters, in length. The micro-RNAs bind to matching pieces of messenger RNA, turn it into a double strand and keep it from doing its job. The process effectively stifles the production of the corresponding protein. RNA can fold into three-dimensional shapes that can bind to something like a protein by shape, as a key fits in a lock. That is important because proteins in a cell bind to one another by shape, and drugs often work by fitting into their target by shape. A popular area of biotechnology now is monoclonal antibodies, which can be made to order to fit a particular shape of a target. So several companies have sprung up trying to develop products that either bind to RNA by shape, or to use shaped RNA to bind to proteins. These shapely RNAs are called aptamers. "Whatever you can do with an antibody you can do with an aptamer," said aptamers discoverer Larry Gold. The first micro-RNA was discovered in the early 1990s by Victor Ambros & Dartmouth colleagues. It helps control larval development in C. elegans, roundworm often used for genetic studies. Because the finding was so unexpected, "there was a considerable amount of legitimate doubt," Ambros recalled. It was not until 2000 that Ruvkun discovered the second one, which also acts to control development in roundworms. Now micro-RNAs are being found in many species. Whitehead Institute & MIT associate prof. David Bartel and his sister Bonnie Bartel at Rice Univ. found 16 in arabidopsis, a plant. He also found 50 micro-RNAs in the roundworm and is about to publish his estimate for humans, which other scientists say is more than 200. Second discovery is known as RNA interference, or RNAi. About 4 years ago, Carnegie Institution of Washington Andrew Fire & Univ. of Massachusetts Craig Mello found when double-strand RNA was given to roundworms, it would silence the gene corresponding to that RNA. That helped explain a similar gene-silencing phenomenon noticed in plants years earlier. Many scientists theorize that RNA interference is a protective mechanism against viruses, which sometimes create double-strand RNA when they replicate. When double-strand RNA is detected, an enzyme called dicer, discovered at the Cold Spring Harbor Laboratory on Long Island, chops the double-strand RNA into shorter pieces of about 21 to 23 bases. The pieces are known as small interfering RNAs or siRNAs. Each short segment attracts a phalanx of enzymes. Together, they seek out messenger RNA that corresponds to the small RNA and destroy it. In plants & roundworms, double-strand RNA can spread through the organism like a microscopic Paul Revere. It did not take scientists long to realize that micro-RNA & small interfering RNAs were the same length and used much of the same mechanism. Indeed, micro-RNAs appear to be formed as longer stretches of RNA that fold back on themselves like hairpins to create double strands. The sequence of bases is sort of like a palindrome, so that when the folding occurs, complementary bases line up, and the two arms of the hairpin stick together. At first, it was not clear that RNA interference would work in humans. Mammalian cells, confronted with long double-strand RNA, basically destroy themselves as a defense against pathogens. 2 years ago scientists at the Max Planck Institute found that short double-strand RNA, again about 21 to 23 bases, would not set off the self- destructive response but would silence the corresponding gene. "Immediately, it was obvious that the ability to do experiments in human cells had just changed completely," said Univ. of Michigan biological chemistry prof. David Engelke. Scientists are now finding that RNAi is a faster way to turn off genes than other methods like creating so-called "knockout mice" that lack a particular gene. Scientists are also looking to use RNA interference to treat diseases. City of Hope National Medical Ctr (Duarte, L.A. Cty) Dr. John Rossi & Colorado State Univ. Ramesh Akkina genetically engineered blood-producing stem cells to make a double-strand RNA that corresponded to a part of a gene in HIV. When those stem cells were transplanted into mice, they formed T cells, target of HIV, that inactivated the gene in the virus and staved off infection. Other scientists have found in test tube experiments that they can inhibit infection by knocking out the genes in T cells that form the receptors used by HIV to enter cells. Still, it will be much harder to make the technique work in patients, because RNA tends to break down quickly in the body. "It comes down to whether you can deliver the small interfering RNA to the cells where it is needed and get it inside the cells," said David Bartel. Watching genes in action 1.23.03   BBC Scientists have found a way to study shape & movement of individual molecules of DNA. The technique called single molecule fluorescence has enabled researchers to obtain the most precise information yet about the workings of single DNA molecules, which measure just one millionth of a centimetre across. Cancer Research UK researchers describe intricate processes that take place when tiny pieces of DNA are swapped over during gene repair, a process vital for keeping cancer at bay. The new technique developed by scientists at the Univ. of Illinois works by tagging a molecule with fluorescent chemicals. By analysing light that these emit, scientists build a picture of how the molecule moves, interacts with those around it and performs its biological functions. Scientists from the Cancer Research UK Nucleic Acid Research Group at the Univ. of Dundee used the system to study a process called DNA recombination, in which cells patch up their genes by swapping a damaged piece of DNA for an intact piece. Their study reveals that helical strands of DNA swivel round each other in an elegant, dance-like motion, in order to cross over each other in an X-shape. One arm of the X, containing the damaged section of DNA is then swapped for the opposite arm.

Cancer Research UK Nucleic Acid Research Group prof. David Lilley said: "It's incredibly exciting to be using this new technique. For the majority of my career, the smallest things we could study were groups of a trillion molecules simultaneously, thereby losing lots of important detail. Now we can focus in on single molecules, giving us a wealth of information about their individual characters.
Molecules are not stationary objects, they are dynamic. Like miniature machines, their functions depend on their moving parts. What this technique allows us to do is look in detail at the way that molecules change in shape and orientation as they go about performing their biological tasks."

While some of the details of DNA recombination were known, the new study has given scientists their most accurate information yet about the process. Since cancer develops as a result of the accumulation of genetic damage, understanding how cells normally repair their DNA is an important area of research into the disease.