

On Top Of The World, He Sees Ego Eclipsed By The Common Good, The One As Part Of The Whole. But His View Is Too Expansive. He Falls.

The doors to the conference room swing shut with a muffled thump, and Jerry Yang wonders whether the people behind them will pay for his quest to become the first scientist in the world to create a human embryo through cloning.

Yang is one of the world's top cloning experts and a member of Connecticut's stem cell research advisory committee, which is meeting this day in November 2006 to dole out $20 million in state funds. Sitting on a velvet-cushioned chair in the hallway of the Hartford Marriott, Yang waits to be summoned back into the room to learn whether he will get any of the $5 million he has requested to realize his lifelong dream.

Despite his scientific stature, he is worried.

His ambitious proposal, involving six related research projects, got a poor score from a peer review committee. The gist of the scientists' criticism is this: Yang may indeed be able to clone an embryo and harvest the embryonic stem cells that are genetic matches of living patients -- an advance that could help cure any number of deadly diseases. But the related projects he wants to fund are too sprawling, too speculative.

The comments strike at the very heart of a new vision Yang has crafted, rooted in the hardships of rural China and forged during two decades of research in American universities. Like all worthwhile human endeavors, good science is both cooperative and farsighted, he believes. Good science honors no boundaries between academic disciplines, institutions or countries.

The winner of the race to clone, Yang says, will not be a solitary researcher, the scientific equivalent of a Pony Express rider in a sprint to the finish line. The winner will be a member of a research wagon train, loaded with top-flight minds possessing complementary skills and interests, each offering protection and advice to the others while searching for and sharing shortcuts toward a common goal.

``No one person can do this alone,'' Yang tells everyone who will listen. ``It takes teamwork and collaboration.''

This is Yang's mantra, one he has been using for more than a year to attract scientific partners to his crusade. While he awaits the committee's judgment, he thinks back on the principles that undergird his plan. He finds no flaws.

During the summer, Yang had put the finishing touches on his proposal while attending the annual meeting of the International Society for Stem Cell Research, a kind of global marketplace for a rapidly growing group of stem cell scientists and a still small but elite band of cloning pioneers.

While battling fatigue from an experimental chemotherapy drug for his cancer, Yang wandered the cavernous halls of the Toronto Metro Centre looking for allies. Yang could offer up expertise in the science of cloning, his own staff at the Center for Regenerative Biology in Storrs, and the prospect of the state money. What he needs are scientists who can take the embryonic cells he creates and develop new treatments for diseases.

It's a tough sell on two fronts.

Many academic researchers are reluctant to jump into such a controversial field. In fact, with federal funds for science drying up, many are looking for less adventuresome, more incremental projects that may have a lower potential payoff but a higher chance of winning grants.

Yang tries to allay their fears. He talks about the promise of cloning, the potential availability of both state and private funds to support the work. Out of the lab, Yang becomes the deal-maker, depending more upon the talents of a Trump than an Edison.


There are, nonetheless, a handful of scientists who are also interested in cloning. But with one of science's top prizes within their individual grasp, Yang's message of international cooperation on cloning gets a lukewarm reception.

Ian Wilmut, creator of the world's first cloned mammal, the famed sheep named Dolly, announces between signings of his new book that he will begin his own human embryo cloning effort in 2007, when he expects to have regulatory approval from the British government.

Kevin Eggan, one of three Harvard scientists who announced in March that they had launched human embryo cloning experiments, holds a press conference and describes how he hopes to use cloned embryonic stem cells to study the progressive and fatal neurological disorder amyotrophic lateral sclerosis, sometimes called Lou Gehrig's disease. Eggan is now toting $6 million to fund his research, thanks to retired Kansas City investment tycoon Jim Stowers and his wife, Virginia.

Cloning pioneer Miodrag Stojkovic is also in Toronto accompanied by his new backers -- officials from the government of Spain. The Serbian native fled his home in Yugoslavia in the early 1990s, on the eve of civil war. After completing his education in Germany, he went to the University of Newcastle in England and became the first scientist to clone a human embryo -- but Stojkovic didn't use older cells as the raw material so the experiment remained a step short of the true goal of the cloning community.

Among such scientific heavyweights, it is easy to overlook a 5-foot-5 Yang, stricken by cancer, who lacks funding and talks incessantly about teamwork. Yang has none of the youthful flair and charisma of Eggan or the fame of Wilmut. He lacks the stature and eloquence of Doug Melton, one of Harvard's cloning trio and founder of the Harvard Stem Cell Institute. Listeners struggle to understand Yang, whose always tenuous command of English has been eroded by the cancer that carved a hole in his face and robbed him of some of his memory for words and names.

But in Toronto, Yang insists there is plenty of evidence to support his view that cloning is best done collaboratively. He also believes that he can organize a first-class team before other scientists reach the finish line.

Time, at least in this case, is on his side. Wilmut, Eggan, Melton and others may have money, ethics approvals and talent. But they do not yet have access to a supply of human eggs.

The inability to obtain healthy human eggs is the single largest obstacle to cloning success. Cloning involves implanting DNA into an egg with its own nucleus removed; without eggs, it's impossible to clone.

But the process of obtaining eggs is wrapped up in many of the same moral, ethical and political debates that Yang and others have been wrestling with for years. All reputable scientists agree, for example, that they should use only eggs donated by women specifically for research purposes.

But what, if anything, should they pay these women? Infertile couples looking for eggs from young women often are willing to pay as much as $10,000 -- far more than the medical costs involved in removing the eggs.

But is it ethical to pay a premium to entice women to go through what is an unpleasant and potentially dangerous procedure?

Would poor women end up becoming ``egg farms'' for researchers?

If they aren't paid, will women donate eggs at all?

``If they don't, we aren't going to get very far,'' says fertility investigator Renee Reijo Pera, now a researcher at Stanford University.

But stem cell science is moving quickly and scientists in Toronto are discussing various ways around the egg shortage. For instance, Yang is excited about a paper by an obscure South Korean researcher who suggests it might be possible to use animal eggs to create human embryonic cells.

The idea is not new. Years earlier in Shanghai, Sheng Hizhen, a former National Institute of Science researcher, claimed to have fused human DNA into rabbit eggs and created human embryonic stem cells. The work was never published in a top-flight journal and many Western scientists doubt the findings. When sperm from one species is introduced into the egg of another species, the resulting embryo usually dies after a few cell divisions -- so why, skeptics ask, would the cloning experiment have different results?

But, unlike his Western peers, Yang knows Sheng personally and he is not ready to write off the idea. Is it possible that donor DNA introduced directly into an egg essentially takes over the mechanisms of the developing embryo? If so, then human DNA introduced into say, a cow egg, could produce only human proteins and therefore purely human stem cells.

From Toronto, Yang calls his wife, Cindy Tian, in Storrs and asks her to start experiments implanting monkey DNA into cow eggs. If the hypothesis is correct, monkey DNA will overpower and eliminate bovine proteins and produce only monkey cells.

It is one of many ideas floating around Toronto.

Yang is also very interested in scientists who believe that one day, cloning may not be necessary at all.

The birth of Dolly in 1996 provoked one overriding question: How does cloning make cells young again? For most of the ensuing decade, Yang and other scientists assumed there was something in the human egg that can reprogram even older DNA to revert back to the embryonic stage.

That hypothesis led them to believe the value of cloning wasn't so much to mimic existing life forms, but to generate embryonic stem cells genetically identical to any human being.


But by 2006, some scientists now suspect the egg might not be needed at all, that DNA itself holds the secrets to cellular youth -- if scientists can bathe it in the right biochemical environment.

In Toronto, Shinya Yamanka of Japan's Kyoto University says he and his laboratory identified four genes that seem to make old cells into something that resembles embryonic stem cells. The implications are clear. If those four genes, called transcription factors, can make old cells young again -- there is no need to clone.

``Sometimes in science,'' Eggan comments, ``you wake up one day and your work has become irrelevant.''

Both Eggan and Yang have long known that cloning is merely a tool, like the booster on a rocket, that will help them understand how to make cells young again and then can be discarded. But they continue to argue that it is not yet time to jettison the technology. It is unclear whether the product of the biochemical bath or other methods to bypass cloning can produce medically valuable cells.

``Today, cloning is the only way that we know for sure that reprograms cells,'' Eggan says.

The uncertainty of the science lies at the heart of Yang's vision of moving forward in tandem with other experts. There are too many uncertainties, too many possibilities, too many potential dead-ends for any one researcher to go it alone.

The promise of creating stem cells, he believes, is too great to allow individual ambition to trump the collective good.

If that message played to mixed reviews in Toronto, he is hoping to do better in Connecticut, where state officials are weighing how to parcel out the first grants in the state's $100 million stem cell research program.

He has submitted an ambitious plan including six separate but related projects, collectively involving dozens of scientists from different institutions all working on unlocking different pieces of the puzzle.

Scientists at Yale University and UConn would work together deciphering the mysteries of nuclear reprogramming -- the search for the molecular keys that would explain how cloning makes cells young again.

A stem cell biologist from Georgetown University would study how embryonic stem cells could be used to produce human eggs.

A diabetes researcher would use the cloned cells to study that disease.

A former National Institutes of Health scientist would use micro-array technology to analyze all genes activated during reprogramming of cloned embryos.

Yang's wife, Cindy Tian, would investigate whether primate DNA could be used to reprogram animal eggs to make fully human embryos.

Wherever the science leads, Yang is ready to follow.

The state isn't.

While Yang's work is highly respected, his sweeping vision reaches too far out over the horizon, a scientific peer review committee decides in the fall. By November, as he sits outside the conference room in the hallway of the Hartford Marriott, Yang hopes the Connecticut stem cell research advisory committee will at least pare back his proposal and fund his own cloning work.

How can his adopted state not fund one of the only somatic cell nuclear transfer initiatives in the world?

Inside the conference room, a lawyer tells the committee the rules are clear: They must fund all of Yang's group proposal, or none of it. One member objects, saying there are only a half-dozen people in the world operating at Yang's level.

How can Connecticut not back this work?

Another member notes there are 70 other science projects competing for funding and most have higher scores -- and greater likelihood of quick payoff -- than Yang's more ambitious proposal.

The titles of those 70 research proposals are written on yellow sticky notes arrayed on a wall-size white board under three categories: ``Fund,'' ``Maybe,'' and ``Do Not Fund.'' After about 15 minutes of discussion, Yang's proposal is moved from the ``Maybe'' column to ``Do Not Fund.''

When Yang re-enters the conference room, he glances quickly at the board. Although shocked, he doesn't show it. He says nothing. For the rest of the first day of the committee's deliberations, Yang helps assess other research proposals, although he recuses himself from voting on any of them.

At the end of the day, too exhausted to make the half-hour drive back to his home in Storrs, Yang goes to his hotel room and sleeps.

When he awakes the next morning, he is thinking about China.

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