ngin - Norfolk Genetic Information Network
Date:  8 March 2001

HUMAN  AND  ANIMAL  CLONING - big problems

EXCERPT from first item below:

    'while the prospect of human cloning raises countless ethical quandaries, it was cloning's
      dismal safety record that led experienced cloners to cringe in January when a team of
      fertility specialists announced it  would embark on the world's first concerted effort to
      clone  a human being... "What these guys are doing, or saying they're going to do, is
      just criminal" said Rudolf Jaenisch, a pioneer in cloning at the Whitehead Institute for
      Biomedical Research in Cambridge, Mass.'

*  *  *

Human Cloning Bid Stirs Experts' Anger; Problems in Animal Cases Noted
By Rick Weiss, Washington Post Staff Writer, The Washington Post - 7 March  2001

The bull was a born winner, naturally resistant to  three bovine diseases, and a herd of genetically identical  clones would be invaluable. Now, the first of those clones  was just a month away from being born, but the mother  mysteriously had become swollen with fluid. "She got so big in the end that she aborted, and we lost that calf at eight  months," said Mark Westhusin, the Texas A&M veterinarian  who oversaw the 1999 effort. "That cow looked like she  swallowed a 55-gallon barrel of water."

Westhusin has grown accustomed to such failures. He and  other leading animal cloners know that behind the stunning  stories of cloning successes in cows, sheep, goats, pigs  and mice, 95 percent to 97 percent of efforts still end in  disaster. So while the prospect of human cloning raises countless ethical quandaries, it was cloning's dismal  safety record that led experienced cloners to cringe in  January when a team of fertility specialists announced it  would embark on the world's first concerted effort to clone  a human being.

That international team, which includes a  maverick scientist-entrepreneur from Kentucky, will meet in  Rome on Friday to further its plan, and scientists are  fuming. "What these guys are doing, or saying they're going  to do, is just criminal," said Rudolf Jaenisch, a pioneer  in cloning at the Whitehead Institute for Biomedical  Research in Cambridge, Mass. "Serious problems have  happened in all five species cloned so far, and all are  mammals, so of course it's going to happen in humans. No  question."

If the team really tries to clone a person, here's what to  expect, several scientists said: Almost all of the first  100 clones will abort spontaneously because of genetic or  physical abnormalities, putting the health and lives of the  surrogate mothers at risk. Of the handful of clones that  make it to term, most will have grossly enlarged placentas  and fatty livers. And of the three or four fetuses that may  survive their birth, most will be monstrously big -  perhaps 15 pounds -- and will likely die in the first week  or two from heart and blood vessel problems, underdeveloped  lungs, diabetes or immune system deficiencies. With access  to an intensive care unit, perhaps one of those 100 clones  will survive, scientists said. It will bear the hallmark of  most animal clones: a huge navel - a remnant of the oversized umbilical cord that inexplicably develops during  most pregnancies involving clones.

"If there were cloned  human beings, you'd be able to recognize them at the beach - they'd be the ones with navels that are two or three  times the normal size," said Michael West, president and  chief executive of Advanced Cell Technology Inc. (ACT) in  Worcester, Mass., a biotechnology company racing to perfect  animal cloning methods. Sometimes the fatal flaws in clones  are obvious. In several instances, for example, cloned cows  have been born with head deformities.

"They have a bulldog,  squashed-up face or head," said Jon Hill, a veterinary  reproductive physiologist at Cornell University and a  leading expert in animal cloning. Those clones never  survive. Even when clones appear normal, they sometimes are  not. "Just before Christmas, we had a cloned lamb that was  perfectly formed," said Ian Wilmut, co-creator of Dolly the  sheep, the first mammal cloned from a single adult cell.   But the lamb could not stop hyperventilating, and after a  few days it was euthanized. An autopsy revealed malformed  arteries leading to the lungs.

"What if it had been a  child?" Wilmut asked. "Who would be responsible for such a  child? What sort of life would it have, panting all of the  time?" "What's remarkable is when they are normal," Hill  said. "We go, 'Wow, look at that!' "

Such tales do not  fluster Lexington, Ky., fertility specialist Panos Zavos,  who in January announced that he and Italian obstetrician  Severino Antinori would embark on the first bona fide  effort to clone a person. Zavos, who has done research on  cattle semen, owns two businesses in Lexington and runs a  fertility clinic about which little is known because it  does not participate in the national voluntary program  through which success rates are published. He claims on one  of his many Web sites to be a member of the prestigious  American Society for Reproductive Medicine. The society says that is not true.

His Italian counterpart, Antinori, gained  worldwide attention and some professional reprimands when  he helped a 62-year-old woman become pregnant. He also  raised eyebrows by placing infertile men's sperm cells  inside the testicles of mice in an effort to enhance the  cells' maturation before using them for artificial  insemination. When Zavos announced in January that he and  Antinori would collaborate on a human cloning project, he  said this month's meeting in Rome would include cloning  experts from around the world as well as a Roman Catholic  cardinal to discuss ethical concerns.

"There will be  Japanese, Koreans, Orientals, Greeks, Italians and some  elite members from the Middle East Medical Society," he  said. But the program for the meeting indicates a  significantly scaled-back affair. No cardinal is scheduled  to appear. And several experts in the United States said  that of the five speakers other than Antinori and Zavos,  the only one whose name they recognized was that of Karl  Illmensee, an Austrian who in 1979 claimed to have cloned  several mice. The secretive work, which no other researcher  was able to replicate, was ultimately discredited. It's not  clear whether the participants in Friday's conference will  be directly involved in the human cloning effort, nor is it  known where the work will be done. The Food and Drug  Administration has said that no one may try to clone a  person in the United States without its permission, but  that it has no authority overseas.

Neither Zavos nor > Antinori responded to recent repeated phone calls and e-  mails from The Washington Post. But Zavos sought to  reassure critics in January by saying that significant progress had recently been made in scientists' ability to  select only those cloned embryos with the best chances of  growing into healthy newborns. "We have a good  understanding of all the failures with animal cloning,"

Zavos said. "We can quality-control embryos now and screen  them and make sure there are no defective genes."

Several cloning experts disagreed. Very little is known  about what goes wrong in clones, experts said, and only now  are researchers conducting sophisticated genetic  experiments to understand what is going on. Many suspect  that the problem involves genetic "imprinting," a poorly  understood molecular mechanism through which genes inside  sperm and egg cells are turned on or off in preparation for  early embryonic and fetal development.

Problems arise in  clones, it seems, because clones are not made from sperm and eggs, with their properly imprinted DNA. Instead, clones  are made from a single adult cell, which is fused with an  egg cell whose genes have been removed. Although the fluids  in the egg cell can largely reset the adult cell's  thousands of genes to the proper "on" and "off" positions  required for embryo development, the process apparently is  imperfect. And depending on which genes are not properly  reset, various abnormalities arise.

No test today is  capable of determining whether a cloned embryo's genes are  properly imprinted, so it's impossible to weed out embryos  that are doomed to develop abnormally. "That's still a  scientific black box that we're trying to unravel," said  Michael Bishop, president of Infigen Inc., a cattle cloning  company in De Forest, Wis. "We want to be able to tell  which embryos can grow to a calf and which cannot. We're  getting there. But we're nowhere close to having that  correct."

As a result, cloned animals continue to be born with  serious problems such as those endured in 1999 by Second  Chance, the newborn clone of a 21-year-old Brahman bull  named Chance. "Second Chance was in the ICU for two weeks,  and we almost lost him from respiratory and cardiovascular  problems; and then he developed juvenile type 1 diabetes,  which we never see in cattle," said Westhusin of Texas A&M. In other cases, said Hill of Cornell, "the mom can get so  big they can tear the muscles in their belly wall."

ACT's West predicted that cloning efficiency will be  vastly improved in a few years. And although he is opposed  to human cloning on other grounds, he said those commited  to cloning people should at least wait until techniques  improve. "We're talking about harming developing humans,"  West said. "Why not wait three years?" The alternative to  waiting is too horrific to contemplate, said Jaenisch of  the Whitehead Institute. "You can dispose of these animals,  but tell me, what do you do with abnormal humans?" Jaenisch  asked. "You probably keep them alive with medical  intervention, and they'll probably be miserable; and even  the ones that look normal probably won't be. It's an  outrageous criminal enterprise to even attempt."

ASIA PULSE March 7, 2001

TOKYO:   Kirin Brewery Co.  said Tuesday that it  will attempt to develop techniques using transgenic cows to  mass-produce pharmaceuticals. Research into the use of  genetically modified animals to produce drugs is being  actively pursued both in Japan and abroad, and Kirin has  decided to approach a U.S. start-up to accelerate  development of necessary technology.

Together with Hematech  LLC, Kirin plans to develop a process to produce proteins  that can be used to treat communicable diseases. The cows'  genomes are modified to enable production of human  antibodies, which can then be harvested from their milk or  blood for use as drugs. Kirin already has expertise in  genetic modification of animals, mainly from its research  with mice, while
Hematech is expert in efficient  mass-production techniques using cattle.

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