Beating Hurdles, Scientists Clone a Dog for a First
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Woo Suk Hwang/Seoul National University, via Associated Press Snuppy, right, is an identical twin of an adult male Afghan hound. He was born April 24 to a surrogate mother, a Labrador retriever. |
Dogs have such an unusual reproductive biology, far more so than humans, scientists say, that the methods that allowed cloning of sheep, mice, cows, goats, pigs, rabbits, cats, a mule, a horse and three rats, and creation of cloned human embryos for stem cells, simply do not work with them.
Woo Suk Hwang, the principal author of the dog cloning paper, being published in the journal Nature, wrote that the puppy, an identical twin of the adult Afghan but born years later, was delivered by Caesarean section on April 24. The pregnancy lasted a normal 60 days and the newborn pup weighed 1 pound 3.4 ounces and was named Snuppy.
Not Snoopy. The scientists named him for Seoul National University puppy.
Cloning researchers were awed at the achievement, but not everyone shared their admiration.
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Nigel Cameron, a bioethicist at Chicago-Kent College of Law and director of its Institute on Biotechnology and the Human Future, noted some people see dogs as members of the family. "There's sort of a dry run here for the human cloning debate," he said. "What we do with dogs we may well end up doing with our kids."
Dr. Cameron said he objected to cloning dogs, but not farm animals or laboratory rodents. He said he did, however, oppose all human cloning, including cloning human embryos for stem cells.
The reason that other researchers are so impressed, said Mark E. Westhusin, a cloning researcher at Texas A&M University, is that with dogs, "their reproductive biology makes them a nightmare." Cats, in what might seem a turnabout, are biologically much less finicky.
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Ahn Young-Joon/Associated Press Scientists named the 67-day old dog Snuppy, for Seoul National University puppy. |
Dr. Westhusin cloned the first cat, in 2002, on his second try. But, he said, after trying for a few years to clone a dog, "I quit."
His work with cats and dogs was sponsored by a private company, Genetic Savings & Clone of Sausalito, Calif. Its chief executive, Lou Hawthorne, said the company had spent seven years and more than $19 million in its attempts to clone a dog. It just opened a lab in Madison, Wis., with 50 employees. But, so far, no dogs have been cloned.
Other researchers say dog cloning is so hard, they will not try it. George E. Seidel Jr. of Colorado State said Genetic Savings & Clone approached him and "I refused." As for the South Koreans, who succeeded in what is the Mount Everest of cloning, it was "simply a heroic effort, a brute force heroic effort," Dr. Seidel said.
Snuppy is the second coup this year for the Seoul researchers. In May, Dr. Hwang's lab announced that it had created cloned human embryos and extracted stem cells from them. The dog project is separate, and its goal, Dr. Hwang explained in an e-mail message, is to use dogs to study the causes and treatment of human diseases.
Dogs have long been used to study human diseases. Rabies, in fact, was first discovered in dogs, insulin was discovered in dogs, and the first open heart surgery was in dogs.
Eventually, the team hopes to make dog embryonic stem cells and test them in the animals as treatments.
Dogs presented a number of challenges to the researchers. Ovulation is once or twice a year, but not predictable, and no one has found a way to induce ovulation by giving dogs hormones.
Eventually, the South Koreans discovered, through trial and error, a signature spike in the hormone progesterone that signaled ovulation.
With other animals, scientists collect mature eggs from ovaries, but the eggs dogs ovulate are immature. They mature in the oviduct and so far it has proved impossible to extract eggs from a dog's ovary and mature them in the laboratory.
So the researchers had to pinpoint when to pluck a mature egg from the oviduct, and needed surgery to retrieve it, instead of the kind of needle suctioning used in other animals.
The next step in cloning of any other animal is to replace the egg's genes with those of an adult and let the cloned embryo grow in the lab for several days.
But no one has been able to grow dog embryos in the lab. So the South Koreans quickly started the cloning. They removed the genetic material from the eggs and replaced it with skin cells from the ears of Afghan hounds. When the altered eggs were starting to develop into embryos, the researchers anesthetized a female dog, slipped the eggs into the animal's oviduct, and hoped the eggs would grow into early embryos, drift into the uterus, and survive. They found they had less than four hours after starting the process to get the eggs into the female dogs.
Ordinarily, researchers give hormones to female animals that are to serve as surrogate mothers, preparing them to become pregnant with a cloned embryo. Not so with dogs. No one knows how to prepare a dog for pregnancy, so the researchers used the same dogs for egg donors and for surrogate mothers, 123 dogs in all.
In the end, three pregnancies resulted. one ended in a miscarriage, one was carried to term but the puppy died a few weeks later of respiratory failure, and one resulted in Snuppy.
Until dog cloning becomes a lot more efficient, few people will be able to afford to clone their pets. Mr. Hawthorne estimated that it would cost more than $1 million to repeat what the South Koreans have done.
The market among dog owners might not be much, in any case. Apart from ethical issues, Dr. Cameron said, dogs are like family members. "My dog is now deceased," he said. "But I wouldn't want to clone Charlie. It would be disrespectful to Charlie and to Charlie II."
Tina Vogel, an Afghan breeder in Norwalk, Ohio, agreed that cloning a dog "would be like cloning a person." And she is opposed to that. "If it was meant to be, God would have done it," she said.
She said Afghans have a reputation as the dumbest dogs around, but that is just because they are "very aloof," more like a cat than a dog. "They are sweet and affectionate. If you have one you can never go back."
http://www.nytimes.com/2005/08/04/science/04clone.html?oref=login
국내 연구팀이 세계 처음으로 개를 복제하는데 성공했습니다. 서울대 수의대 황우석ㆍ이병천 교수팀은 사냥개의 일종인 `아프간 하운드(Afghan hounds)' 2마리를 복제하는데 성공했다고 4일 밝혔습니다. 복제 개 2마리 중 1마리는 지난 4월 24일 서울대 동물병원에서 제왕절개를 통해 태어나 현재 건강하게 자라고 있으며, 5월 29일에 태어난 복제 개는 22일만에 폐렴으로 죽었다고 연구팀은 덧붙였습니다. 복제 개와 체세포를 제공한 개 모두 수컷입니다.
이번 연구성과는 특허 출원됐으며 이날 발간된 세계적 과학저널 `네이처(Nature)'에 표지 그림과 함께 게재됐습니다.
세계 최초로 개 복제에 성공한 서울대 황우석 교수팀의 연구에 대한 네이처지 표지.[연합]
지난 96년 영국 로슬린연구소 이언 윌머트 박사팀이 면양 `돌리'를 복제한 이후 각국에서 젖소와 고양이, 염소, 돼지, 말 등이 잇따라 복제됐지만 개 복제에 성공한 것은 우리 연구팀이 처음입니다.
이처럼 지금까지 과학자들이 개 복제에 성공하지 못한 것은 개가 다른 동물과 달리 난자가 미성숙한 단계에서 배란이 이뤄지는 데다 체외에서 성숙을 유도할 수 있는 체외배양 체계가 정립돼 있지 않기 때문입니다.
하지만 연구팀은 이번 연구에서 난자의 배란이 이뤄지는 나팔관에서 성숙한 난자를 찾는데 성공했습니다.
황우석 교수팀의 세계 최초 개 복제에 대한 네이처지 논문.[연합]
이후 복제과정은 다른 복제동물과 마찬가지로 체세포 복제방식이 사용됐습니다.
즉 복제 대상인 3년생 아프간 하운드의 귀에서 체세포를 떼어낸 뒤 이 체세포를 일반 개에서 채취한 난자 속에 있는 핵 자리에 이식한 다음 배양과정을 거쳐 대리모의 자궁에 이식하는 방법으로 복제 개를 임신시켰습니다.
이 과정에서 연구팀은 실험에 참여한 개 1마리당 평균 12개의 난자를 채취, 1천95개의 재조합 배아를 만들었으며 모두 123마리의 대리모에 5~12개의 배아를 이식, 최종적으로 복제 개 3마리를 임신시키는데 성공했다고 설명했습니다.
서울대학교 황우석 교수팀이 세계 최초로 개 복제에 성공한
아프간하운드 종 스너피(Snuppy.오른쪽)
와 체세포를 공유한 타이(왼쪽). [연합]
각각 2개월간의 임신과정을 거치면서 1마리는 유산했으며 최종적으로 2마리가 태어났다. 살아남은 복제 개는 4년생 리트리버(Retriver)가 대리모로 사용됐는데 태어날 때 체중은 530g이었다. 최종 복제 성공률은 1.6%로 분석됐습니다.
이 복제 개의 이름은 `Seoul National University(국립서울대)'의 첫 글자와 puppy(강아지)의 뒷글자를 따 `스너피(Snuppy)'로 명명됐습니다. 이 개는 현재 서울대 수의과대학 내에서 사육 중입니다.
황우석 교수는 "스너피에 대한 유전자검사 결과 체세포를 제공한 아프간 하운드의 유전 형질을 그대로 이어받은 것으로 확인됐다"면서 "이번 복제기술은 멸종위기동물의 복원은 물론 치료용 배아줄기세포 연구에도 활용될 수 있을 것"이라고 말했습니다.
[연합뉴스]
http://news.kbs.co.kr/article/society/200508/20050804/759273.html
황우석 교수팀 세계를 또 놀라게 하다
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황우석 교수팀이 세계 최초로 복제를 통해 태어난 개 ‘스너피’(가운데)와 체세포를 제공한 아프간하운드 수캐 타이(왼쪽), 대리모 역할을 한 리트리버 암캐 심바(오른쪽)를 3일 공개했다. 연구팀은 왼쪽부터 이병천, 황우석 서울대 교수, 오현주 연구원, 미국 피츠버그대 의대 제럴드 섀튼 교수.
박영대 기자 sannae@donga.com
http://www.donga.com/fbin/output?n=200508040188
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