WASHINGTON - Dolly. Cupid. Cumulina. Peter. Webster. Dianna. Dotcom.
If the menagerie of cloned animals could speak, they might have discouraging words for renegade scientists who caused a public tizzy last week by announcing plans to clone humans.
Behind every successful birth lie hundreds of failures, with many animals dying in botched cloning attempts, born dead, or born with terrible defects. Some involve fetuses mysteriously growing to an enormous size that could threaten the health of women pregnant with a clone.
Concerns about the safety of cloning humans dominated a National Academy of Sciences workshop on human cloning here last week. The academy advises the federal government on science and technology.
Ironically, three researchers chose that forum to announce plans to begin mass production of cloned human embryos in November. Their goal is to implant the clones in about 200 women. They refused to specify where the research will occur.
One, Dr. Severino Antinori, is a noted Italian fertility doctor. Another, Brigitte Boisselier, is a chemist with Clonaid, a company in the Bahamas founded by the Raelians, a religious group for whom human cloning is a goal. The other, Panos Zavos, is with the Andrology Institute in Lexington, Ky.
Indeed, animal cloning has proven so daunting that pioneers like Dr. Ian Wilmut have forsaken efforts to clone live animals. Instead, he is working on ways to make cloning more efficient and effective.
Dr. Wilmut is the famous Scottish researcher and leader of the Roslyn Institute team that announced cloning Dolly the sheep in 1997. Dolly was the first cloned mammal, the animal group that includes humans. Dolly ignited the world-wide debate about cloning of people.
“We are seeing a great range of abnormalities,” Dr. Wilmut told the academy workshop in a status report on animal cloning. “We should expect a similar outcome if people attempt to produce a cloned human.”
Since Dolly's debut, scientists have cloned four other species of animals: goats, pigs, cows, and mice.
Dr. Wilmut said the experience with those animals shows that tremendous hurdles must be overcome before a human can be cloned for reproduction with any reasonable degree of safety.
One problem is the waste of embryos, which could prove extraordinarily expensive in any effort to clone a human.
Dolly and other cloned animals were produced with nuclear transfer technology. Scientists remove the nucleus of an egg retrieved from a female animal. They replace it with the nucleus taken from a cell from the animal they want to clone. The cell could come from the skin or almost any other part of the body. DNA in the nucleus contains hereditary instructions for the new individual. Next, scientists manipulate the egg to make it begin developing into an embryo.
The embryo is put into the uterus of the animal that will become its mother. Because its genetic instructions are from DNA in that one nucleus, the fetus will be a carbon copy of the person whose skin cell provided the nucleus.
Dr. Boisselier plans to use nuclear transfer in her human cloning program. It apparently will start by trying to clone a baby who died after surgery. Some of the infant's tissue was frozen, and she will extract the nucleus from some of those cells.
Dr. Wilmut's report spelled out the waste of embryos and high death rates for cloned offspring. He reported that in:
Dr. Rudolf Jaenisch, a cloning expert at the Massachusetts Institute of Technology, said cloned animals of all species have strikingly similar defects.
One, for instance, is the so-called “large offspring syndrome,” which raises questions about health risks to women pregnant with a cloned fetus. In the syndrome, the cloned fetus grows to dimensions several times larger than a conventional fetus. Dr. Jaenisch thinks the overgrowth occurs because certain genes are not regulated properly in the cloned fetus.
Many cloned animals also have serious problems with their lungs, Dr. Jaenisch said. Full-term infants may be born with the immature lungs and breathing problems of premature infants. Other problems in newborn cloned animals include disorders of the heart and blood vessels, immune system, bones, brain, and kidneys.
“We would expect similar outcomes in humans,” Dr. Wilmut said. “Hence, expect late abortions and dead children and surviving but abnormal children.”
Scientists at the academy of sciences workshop expressed concern that human clones could experience other problems not easily detected in animals. Those include problems with key human attributes like behavior, learning, sociability, aggression, and emotions.
Dr. Jaenisch cautioned that even apparently normal clones may have abnormal regulation of many genes. The resulting clone might look perfectly normal, yet have a serious physical or mental health problem that appears years later.
“Completely normal clones may be the exception,” Dr. Jaenisch said when asked to draw general conclusions about human clones, based on science's experience with animals. “Most adult clones may have abnormalities.”
Scientists agreed such defects cannot be detected by screening cloned embryos and selecting only healthy embryos for implantation. When Dr. Boisselier claimed having developed such a test, she got the following response from Dr. Alan Trounson, a famous Australian embryologist:
“Ludicrous,” he declared. “I don't think that is at all possible.”
Dr. Jaenisch said that routine prenatal tests will miss defects in cloned human infants. That's because the defects do not involve chromosome abnormalities or mutated genes. Rather, clones appear to have normal genes. But their genes are not regulated normally.
“At present, there is no way to predict whether a given clone will develop into a normal or abnormal individual,” he said.
Dr. Jaenisch expressed confidence that research will resolve the gene regulation problems and provide ways of identifying abnormal clones at an early stage.
Dr. Wilmut agreed, finding no scientific reason why cloning cannot be made safer and more efficient.
The academy held the workshop to gather information for a major report on human cloning. It will include a recommendation on whether cloning technology is ready for testing in humans.
Many speakers at the sessions endorsed Dr. Wilmut's suggested standard: Scientists first must prove that cloning is safe and effective in several species of animals, he said. Then scientists must prove that genes in cloned human embryos work normally.
First Published August 12, 2001, 10:59 a.m.
