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Early Start
In November 1998, James Thomson, a developmental biologist at the University of Wisconsin, Madison, announced that he had isolated human embryonic stem cells. (A few days later, John D. Gearhart of the Johns Hopkins University School of Medicine made a similar claim.) The quiet, publicity-shy Thomson eventually found himself on the cover of Time. Little wonder: embryonic stem cells, many researchers believe, will change medicine as dramatically as did antibiotics. But the thousands of press accounts rarely mentioned where Thomson isolated his stem cells, or why he did it there – something that, at least in the short run, may prove almost as important.

To biologists, embryonic stem cells are fascinating entities. After birth, almost every cell in the human body is committed to fulfilling a single function: a red blood cell is always and forever a red blood cell; a neuron is always and forever a neuron. Even bone marrow stem cells can transform themselves into only a few types of blood cells. Embryonic stem cells are different. They form in the first few days after sperm meets egg; about 30 of them cluster on the interior wall of the blastocyst – a hollow ball of about 150 cells that develops around the time the embryo reaches the uterus from the fallopian tube.

These 30 cells – from which researchers derive embryonic-stem-cell lines – are identical, but as the embryo grows they differentiate into the more than 200 types of cells that make up the human body. Not only are harvested embryonic stem cells a powerful new tool for studying disease, scientists believe, but they may lead to a new era of regenerative medicine, in which sick people effectively replace their damaged parts. In theory, doctors should be able to stimulate them when needed to grow replacement tissues and organs – producing new hearts and livers in a petri dish, so to speak.

Thomson obtained his stem cells from embryos created at in-vitro fertilization (IVF) clinics in Wisconsin and Israel. Because IVF frequently fails, doctors use drugs to induce female patients to “superovulate,” producing as many as 15 eggs at once. These are placed into a bath of sperm, creating multiple fertilized eggs. Each egg is allowed to divide, usually into an embryo of six to eight cells. Doctors then insert several embryos through a catheter into the woman’s uterus and hope that one attaches successfully. The rest are usually frozen in liquid nitrogen.

Since 1978, the year the first successful IVF baby was born, U.S. clinics alone have built up a surplus of more than 400,000 frozen embryos, according to a 2003 study by Rand, a nonprofit think tank in Santa Monica, CA. Clinics preserve more than 90 percent of these frozen embryos in case couples want to try for additional pregnancies. About 2.8 percent are donated to research.

After receiving his six- to eight-cell embryos, Thomson grew them to blastocyst stage and then extracted their stem cells, destroying them in the process. He destroyed many embryos, in fact, because most frozen embryos either don’t survive thawing or can’t produce cell lines that will survive for long. Thomson needed 36 embryos to establish his five cell lines. Other researchers have required even more. Researchers at Eastern Virginia Medical School in Norfolk, VA, used more than 100 IVF embryos to create three embryonic-stem-cell lines in 2001.

Because of the U.S. Congress’s 1996 prohibition on using federal money for “research in which a human embryo or embryos are destroyed,” Thomson could not work in his own laboratory, which was supported by the National Institutes of Health and the National Science Foundation. Instead he created a second workplace from scratch, a couple of windowless rooms at the edge of campus, three kilometers from his main lab – “fairly primitive conditions,” as he puts it, “with only the bare necessities.”

Unable to use his own technicians (their salaries were covered in part by federal grants), Thomson did most of the bench work himself, rising before dawn for days on end and going to bed late at night. He funded the research with money from the Wisconsin Alumni Research Foundation (WARF), an independent nonprofit that has sponsored UW-Madison research since 1925, and Geron, a biotech startup in Menlo Park, CA. (Geron also backed Gearhart’s research and that of a stem cell group at the University of California, San Francisco.)

As per Thomson’s agreement with his university, he awarded WARF the basic patents on embryonic stem cells. After a legal dustup, Geron won the exclusive commercial rights to three major potential stem-cell uses. Despite controlling the sole supply of the hottest discovery in cell biology since DNA, WARF was not bombarded by requests for the right to work with Thomson’s stem cell lines. “Scientists questioned whether or not they should risk their career on a field that had so much political and financial controversy around it,” says Andrew Cohn, government and public relations manager at WARF.

Geron could not fund an entire field of research single-handedly, says David Greenwood, the company’s chief financial officer. Nor could it get access to capital through the route of partnering with pharmaceutical companies. Even though it is widely believed that stem cells will ultimately become the center of a huge new medical industry, Geron president Thomas Okarma has said, drug companies so fear today’s controversies that they remain “completely uninterested.” Most venture capital firms are leery, too.

“The administration says it is letting us go ahead, within certain broad guidelines,” says Greenwood. “Meanwhile, there is legislation dropped into every session of Congress that would literally criminalize what we do.” (The current version of the legislation would impose a prison term of “not more than 10 years” on anyone who inserted genetic material into embryo cells, which many researchers would like to do to study the development of particular genetic conditions.)

Even Thomson could not make much headway. “If you do a quick PubMed search on my name,” he says in an e-mail, “you will see from 1998-2001 we published almost nothing. We had little or no access to standard equipment because of the prohibition on the use of federal funds that was in effect at that time, and it severely limited what we could do.”

Then came Bush’s announcement, which Cohn says led “a lot of people” to decide “that they could now go ahead.”

One of them was Willy Lensch.

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Tagged: Biomedicine

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