As reported by The Hartford Courant, September 12, 2005.

Scientist Working Against the Odds

By William Hathaway

Before cancer kills him, University of Connecticut scientist Xiangzhong "Jerry" Yang is determined to create human embryonic stem cells by cloning and see those cells implanted in a patient.

By spring, the former pig farmer born in rural China wants to have created the first cloned embryos in the United States by fusing skin cells of medical patients with unfertilized eggs. UConn would be the first institution in the United States to offer researchers working on diseases such as Parkinson's or diabetes human embryonic cells genetically identical to the patients with those diseases.

"This is my dream," Yang said.

Yet as university officials ponder whether to make a multimillion-dollar bet on the promising but controversial research, they have to make a cold-hearted calculation.

Can Yang's dream survive if he isn't around to see it through?

To achieve his goal, Yang will have to overcome institutional caution, address ethical and religious concerns of many, including UConn Health Center's director, and answer scientific questions about the viability, efficacy and safety of human embryonic cells.

He also will have to outrun his own cancer, which has moved from his face to both lungs. His cancer has resisted seven surgeries, radiation and chemotherapy treatments and now threatens his life.

"I feel very lucky to come to work every day and be so close to seeing this happen," Yang said. "This is something we can do now. We can make UConn No. 1 in the world in this technology."

He has won university approval to create a new stem cell institute and school officials already are looking at a building near the University of Connecticut Health Center as headquarters. In Yang's mind, the institute is the tool to fulfill a vision hatched seven years ago.

In 1997, the same year doctors found a small tumor in Yang's salivary gland, Dolly the sheep was cloned using cells from a sheep's udder, and Yang's race began.

An operation failed to remove the entire tumor. Alarmed, he went to Memorial Sloan-Kettering Cancer Center in New York, where doctors did more surgery. Yang, who had taken a job at UConn only the year before, turned his attention to capitalizing on Dolly's birth.

As an expert on animal reproduction at Cornell University during the 1990s, Yang had made a failed attempt to clone rabbits. Like most scientists a decade ago, he did not believe that a non-sex cell taken from an adult and implanted into an embryo could be coaxed into becoming a new organism.

"It was a missed opportunity," Yang said.

It was one of the few opportunities Yang has missed. In the 1970s, Yang was the first person from his village in northern China to attend college. In the early 1980s, he won an intense academic competition in China and was allowed to attend a U.S. graduate school.

When Yang arrived at UConn in 1996, there was little demand for experts in animal reproduction. Dolly changed that.

The public was amazed and aghast that science could create new life that was the genetic twin of an adult from something as simple as a sheep's udder. Yang and other reproductive scientists, however, quickly grasped the potential medical implications. Dolly's creation proved that even a simple skin cell could be reprogrammed and become any cell in the human body. If that power could be harnessed, a single adult cell could create a batch of insulin-producing cells for diabetics, replace damaged neurons in Parkinson's patients or repair nerves in damaged spinal cords. Since the cells taken from clones would be genetically identical to those of the patient, in theory they would not be rejected by the patient's immune system.

Within a few years, Yang had become a world leader in cloning. In 1998, he collaborated with Japanese scientists to create six cloned calves from an ancient and prized Japanese stud. His research suggested that, contrary to the early reports about Dolly, clones did not age prematurely. In 1999, the clone Amy was born in Storrs - the first calf cloned in the United States using adult cells.

By 2000, Yang leveraged his growing celebrity - and a lucrative offer from another university - into a commitment by UConn to build a new $20 million Center for Regenerative Biology on the Storrs campus. The immediate purpose of the center and its six new researchers was to continue animal research.

"But the ultimate goal has always been to work on human cells," Yang says.

An Old Enemy

But that spring he was told an old enemy had returned. The cancer was back in his salivary gland and he again underwent surgery and radiation treatment. Later that year, the cancer metastasized into his lungs and he underwent yet more surgery and more radiation treatments.

In the past five years, cancer treatments have taken a heavy toll. Last fall, he found that he could not remember his sister-in-law's name. Intensive radiation treatments had killed cells in a golfball-size piece of his brain and a resulting infection led to emergency brain surgery.

He became depressed and for the first time in his life, he took time off work.

"That was a very difficult time for me," he said.

Yang's face shows the scars of his battle. His left cheek is sunken. A scar makes a deep ravine down his chin. With cancer now in both of his lungs, doctors have said there would be no more surgeries.

However, Yang said, his cancer is slow-growing.

"The doctors have told me I am a miracle."

But they can't tell him how long he has to live. His wife, UConn scientist Cindy Tian, says her husband hopes that he can work two more years - enough time, he believes, to see his embryonic cells used in patients.

His optimism was buoyed this spring by two pieces of news.

The first came in May when South Korean scientists became the first to create customized human embryonic stem-cell lines through cloning, using techniques similar to those employed by Yang. Weeks later, the Connecticut legislature passed a 10-year, $100 million initiative to fund human stem-cell research. The legislation authorizes therapeutic cloning as envisioned by Yang.

While undergoing experimental chemotherapy treatments in Boston, Yang has launched a vigorous campaign to make therapeutic cloning a reality at UConn. He has been recruiting scientists familiar with scientific, legal and ethical issues surrounding the use of human embryonic cells. He has gained tentative approval from university officials to create a new stem-cell institute that would include scientists from both the Storrs and Farmington campuses. He has started a series of Internet seminars featuring experts on stem-cell research that link scientists at both campuses.

Meanwhile, he also has reached out to scientists at Yale University to gauge interest in participating in the institute. And he has recruited world-famous stem-cell experts such as Dolly creator Ian Wilmut to serve as members of Connecticut's stem-cell advisory board, which will be appointed by the governor and state lawmakers.

When state funding for human embryonic stem-cell research becomes available next spring, Yang wants to have already created human embryonic stem cells. Then he wants to supply those customized cells to scientists studying cures.

Racing Against Time

University officials have asked him to assume duties as director of the new stem-cell institute, but Yang has made a poignant request. He wants UConn to hire an internationally known scientist to head the new institute to ensure that his work survives his death.

"With my health, I do not think I can do that for long," Yang said. "Being a director is not my dream."

But Yang may be one of the greatest assets the state has in getting research efforts going, others say.

"He is a great big advantage that UConn has over other institutions," said Marc Lalande, a geneticist at the University of Connecticut Health Center and assistant dean for research. "He refuses to let his illness dampen his enthusiasm for science and stem-cell research."

However, even supporters such as Lalande say Yang may be rushing to create customized embryonic cells well ahead of significant scientific demand for them. Lalande said that scientists still need to ascertain whether embryonic cells created through cloning will act like embryonic cells - whether they will divide indefinitely in a laboratory setting and be able to differentiate into many tissue types. Scientists also need to learn how to nudge those cells down the right developmental pathways, guiding them to become heart cells, or brain cells or other types of cells. And then, they need to determine whether those mature cells function normally. Only then will they be ready to be tested for therapeutic purposes, Lalande said.

Diane Krause, acting director of Yale University's own nascent stem-cell program, also thinks Yang might be rushing.

"I personally have no need for such cells at this time, nor am I aware of any labs that need patient-specific embryonic stem cells for therapeutic purposes," said Krause, whose lab has investigated adult stem cells in mice.

She said Yale, which is also expected to make a pitch for state stem-cell money, likely will move more slowly on working with human embryonic stem cells.

Even at UConn, Yang won't get a free pass on his plans.

"Jerry is already on third base," said Dr. Peter Deckers, director of the UConn Health Center. "But we aren't even on first yet, in terms of the administrative and financial questions, scientific questions and certainly bioethical questions. And I don't think we should make this large commitment because Jerry is driven by his health issues."

"Understanding stem-cell biology is absolutely critical to the future of medicine," added Deckers. But, he said, the creation and destruction of an embryo for research purposes is "for me personally, morally unacceptable. Everybody knows where I am on this."

Deckers said the bioethical objections to Yang's research should be fully addressed before such a controversial initiative goes forward.

UConn President Philip E. Austin has endorsed Yang's work and the direction of his research. However, Austin said that the university needs to fully explore the legal and bioethical implications of the work.

Yang says that he welcomes such ethical discussions - if they happen soon.

"I certainly do care about religious concerns. I really don't want to create a fight," Yang said. "It is like the fight over a test-tube baby. A million kids were born because of that technology. Once I can show that the technology can take skin cells and help treat cancer and other diseases, then religious and non-religious people will all be happy about that."

He added: "Until you have a major disease, you don't understand how important this is, the impact that medical advances can have."

A discussion of this story with Courant Staff Writer William Hathaway is scheduled to be shown on New England Cable News each hour today between 9 a.m. and noon.