At Uconn, A Star Is Born. As His Fame Grows, So Does Moral And Political Opposition To Stem Cell Research. Meanwhile, A Tumor Grows.

The Hartford Courant

On June 10, 1999, in a tidy New England barn set high atop a green pasture overlooking the campus of the University of Connecticut, the first cloned farm animal in the United States is near birth. Attending veterinarians are worried, however. The calf is dangerously large.

Jerry Yang is at home, anxiously awaiting news. Eight months earlier, Yang had taken DNA from the ear of a 13-year-old, high-producing dairy cow and inserted it into cow eggs with the original genetic material stripped out.

Yang knows how precarious the situation is. Cloned animals tend to be abnormally large and have a mysterious tendency to abort or die at birth.

His phone rings. A veterinarian from his lab is calling from the barn.

There is no sign of life inside the surrogate mother.

``The calf is dead,'' the vet says.

``Do a Caesarean anyway,'' Yang says. ``Maybe we can learn something.''

Yang still has four reasons for optimism. Although few people know it, he has already achieved his first great cloning success. The previous year, one of Yang's students, working under his direction with scientists in Japan, created four cloned calves, all from the skin cells of an old champion stud bull. It was the first time scientists anywhere had produced male clones. The work demonstrated in dramatic fashion that the age of the DNA does not affect the ability to create a brand-new clone.

The experiment confirms a notion that turns scientific thinking on its head: Old cells can indeed become young again.

The work was never publicized because UConn officials wanted to patent Yang's techniques before word got out. But Yang and the university aren't about to let a new cloned calf born in Storrs go unnoticed by the world press. The birth of a clone will be an All-American, All-Yang affair. It will put UConn on the international map for something other than fast breaks and blocked shots. For Yang, the birth will mark the start of his metamorphosis from obscure agricultural school researcher to a scientist working on the frontier of biomedicine.

About 20 minutes after the first call, Yang's phone rings again.

``You won't believe this,'' the vet says. ``The calf is alive.''

About 10 a.m., vets at the barn conduct the Caesarean section. Amy, a 94-pound calf, becomes the first cloned farm animal born in the United States.

Yang runs to his car and makes the 10 minute drive to the barn. He finds that the surrogate has not responded well to surgery and has developed a severe infection. Veterinarians are forced to put her down.

Amy also becomes sick. Yang and the vet load Amy into the back of his Subaru station wagon a few days later and drive the famous calf to Tufts University's large animal hospital in North Grafton, Mass. She is soon healthy and back at Storrs.


It is a heady time for Yang and other scientists. The birth of Amy is further proof that there is a pot of gold at the end of the cloning rainbow. But it's not simply to create Xerox copies of farm animals, as valuable as the advance might be to breeders or dairy farmers.

The real goal is to use cloning to create the ultimate embryonic stem cell -- an exact genetic match of cells in a living, breathing human being. In theory, scientists could use these cells to repair or reconstruct any organ in a person's body without danger of rejection by his or her immune system.

Cures for heart disease, Alzheimer's, paralysis and a host of other afflictions could be within their grasp. It would be a breakthrough akin to discovering a cellular fountain of youth.

But the tumultuous birth in Storrs is emblematic of cloning efforts since the birth of Dolly in Scotland in 1996. For every breakthrough in the lab, there is a public relations debacle, a funding crunch, ethics battle, political fight or scientific controversy.

Conservatives view creating and destroying a human embryo for research as akin to murder. Critics fear using cloning to create duplicate embryos of human beings will eventually turn science fiction into reality, and scientists will start making people in their labs.

The federal government makes clear it has no intention of paying to create such cells. In fact, some members of Congress support passing laws to prosecute scientists who work with human embryos, with jail terms of up to 10 years and fines of millions of dollars. Several states pass laws making cloning human cells illegal.

Private funding for cloning dries up as investors look to less controversial opportunities with the potential of quicker payoffs. Scientists instead launch into research with adult stem cells, which some studies suggest may share at least some of the ability of embryonic cells to develop into different cell types, but are eligible for federal funding.

Even Ian Wilmut, the man who cloned Dolly, finds that fame brings headaches as well as book contracts. Although he announced his intention to clone human embryos in 2001, he finds his plans thwarted by regulatory requirements in Great Britain, his own personal problems and employment disputes.

``I lost focus,'' Wilmut concedes.

Wilmut becomes embroiled in a labor dispute with an employee, and during a hearing acknowledges the seminal contributions of Keith Campbell in the creation of Dolly. News coverage makes Wilmut look as if he took undue credit for the cloning breakthrough -- a major embarrassment.

With so many roadblocks and hassles, the race to create a human embryo through cloning slows. Few reputable scientists even bother to toe the starting line. Instead, most human cloning news usually involves unsubstantiated claims by deranged-looking doctors or cult members who claim to work on behalf of extraterrestrials.

``I would rather clone disco poodles for Puff Daddy,'' than clone a human embryo, Campbell says. ``When you deal with human cells, things get all cocked up.''


All this is fine by Yang, who believes it will take years of animal research before serious attempts to clone a human embryo can even begin.

He also needs time as he faces a cultural leap as large as the one that brought him from China to the United States more than 15 years earlier.

Yang is painfully aware that even if he succeeds in creating human embryonic stem cells, he will need the backing of mainstream scientific researchers who can use them to study and treat various diseases. Those scientists, who work at the nation's elite medical centers, don't have manure on their boots or go to seminars on bull semen. There is only one way a Chinese-born professor at a land grant college who speaks broken English gains admittance to the company of medical elite from institutions such as Harvard, Stanford and Yale.

Yang needs to publish new research in respected journals such as Science, Nature or Cell. He needs to prove he's about more than one calf in a bucolic barn. The birth of Amy gets Yang noticed. Now he needs credibility.

Yang directs his lab to start working on projects well beyond the interest of dairy breeders. He starts with one of the fundamental biology questions raised by the birth of Dolly, the world's first cloned animal:

Are clones that have been produced by mature DNA born old?

If so, cloning could be no more than a meaningless trick, producing cells that appear young, but aren't. The early answer, based on an initial observation by Wilmut in Scotland, appears to be yes.

Wilmut had observed that cells taken from Dolly, who was created from the udder cells of a 6-year-old sheep, showed signs of premature aging. Wilmut noted that Dolly's telomeres, the caps of chromosomes that wear down gradually with age, appeared shorter than those found in most young lambs. Perhaps, Wilmut reasoned, Dolly's cells were 6 years old at birth.

Yang tests the observation using cells from cows cloned from the DNA of older animals. To his surprise and delight, he finds that their telomeres are as long or even longer than cows conceived naturally, or through in-vitro fertilization. The cells of cloned cows such as Amy are as biologically youthful as any of the less famous calves cavorting in the pastures of Storrs.

Yang is elated when the journal Nature Genetics agrees to publish his findings.

Seeking to build on the momentum, Yang works his staff feverishly to be the first to answer other key questions posed by cloning. Why do cow clones tend to abort more often and be abnormally large? Is milk and meat from cloned animals safe to drink and eat?

The more papers he publishes, the more Yang gets invited to the more prestigious scientific conferences frequented by Nobel Prize candidates. The former pig farmer slowly becomes accepted into a world dominated by middle-aged Caucasian men who are used to both honors and honorariums.

Within a year after the birth of Amy, Yang receives a call from officials at Rutgers University. We will give you your own lab, they tell him, and a team of researchers to help you pursue your cloning research.

Yang tells UConn officials he is leaving Storrs.

Days later, Yang has a counteroffer in his hand, personally approved by UConn President Phil Austin. He can hire six scientists and take over an entire floor of the new $25 million research building, planned for a site just down the pasture from where Amy was born.

The deal-maker for Yang is this pledge: Once the legal status of human therapeutic cloning is clarified in Connecticut, he is free to pursue the cloning of human embryos.

Yang's status and research goals earn him a new title as well. He is now director of UConn's Center for Regenerative Biology, the base from which he can launch his campaign to be first to clone a human embryo.

He still takes time to fulfill an older dream, one born in famine in rural China decades before. He quietly forms a company that ships cloned cattle embryos to Taiwan and rural areas of China. The clones of American dairy cattle can produce 10 times the milk as a Chinese cow, and Yang knows that the extra milk will provide the rarest of countryside commodities -- cash.

Yang survived famine as a toddler because of the tiny amount of cash his father earned as a schoolteacher. Yang hopes the extra yuan generated from embryos of superior American dairy cows will improve the lives of Chinese families.


There is time to honor his past and look to the future. As the 20th century ends, Yang is busy laying out his plan to clone a human embryo, which he calculates might take another decade.

Then, in the fall of 2000, his doctors tell him that he might have to adjust his timetable.

In 1997, Yang had been diagnosed with cancer of the salivary gland. Don't worry, his doctors told him. You are in no danger. Local surgery will get rid of it.

They were wrong.

The tumors have returned under his left eye and metastasized to his lungs. Surgeons at Sloan-Kettering Cancer Center in New York remove the tumor nodules from his lungs. They gouge out the left side of his face and clean out the tumors near his eye. The first skin graft to cover the hole in his face doesn't take, so transplant surgeons take more skin from his abdomen and finish the job.

The left side of Yang's face takes on a deep sheen and is slightly sunken, like the dent on a sideswiped car. A deep cleft on his chin marks the boundary between transplanted skin and the skin of his old face. He takes to covering his chin with his hand in public. He cannot spit. His English, never good, worsens.

The boyish and buoyant smile that so disarms and charms his friends dims.

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