Stem cell scientists in the 1990s bore a certain resemblance to the hang gliders who soared back and forth over the hills of Madison, Wisconsin, in summer. Many would have liked to have been left in peace to swing on the wind and study this remarkable biological entity—a stem cell. But as the decade progressed, something like the force of gravity kept dragging them downward into an ethical, swarmy quagmire.

So it was with James Thomson, a young scientist at the University of Wisconsin in Madison. Thomas, in fact, had a hankering for aeronautic contraptions, including boomerangs, model aircraft, and gliders, and after arriving in Madison in 1991, he would have given his eyeteeth to have found time for hang gliding. Instead, he spent the better part of his days and evenings inside a lab at the university’s primate research center bent over the cells of tiny monkey embryos that were only a few days old. A no-nonsense sort, he could be “relentlessly quiet,” as one university acquaintance has described him. When he talked, his words tended to gallop, as if he wanted to get this interruption over with so that he could get back to prying out the secret of how one cell, then two, four, eight, and so on had the

wherewithal to expand into trillions and fashion a monkey, or for that matter a person. The irony was that once Thomson’s research took off later in the decade, this reticent scientist, who had no interest in the limelight, would find himself drenched in it, and also pulled downward by as contentious a debate as society had ever known—namely, at what point in early development should a human embryo be thought of, respected as, and treated like a person?

To be sure, it was an edgy time for the human embryo and fetus, and any associated research. The reasons are hard to separate, yet a few obvious ones stand out. In the United States, at the center of the issue was Roe v. Wade, the 1973 Supreme Court decision that made abortion a legal option for women, permitting the fetus’s removal from the womb up to when it reached “viability.” “‘Viability’ is somewhat a vague word,” comments Norman Fost, a professor of pediatrics at the University of Wisconsin, Madison, “but what the court had in mind was the point at which the fetus can survive outside of the uterus, somewhere around six or seven months gestation.” Noted the court in defense of its ruling, “In short, the unborn have never been recognized in the law as persons in the whole sense.” Yet for those who believed the unborn embryo was a person in the whole sense, and obtained personhood upon conception or soon thereafter, Roe v. Wade was a flagrant offender of the commandment Thou Shalt Not Kill.

If ever a ruling drew a line in the sand! Groups that would increasingly be typecast by the press faced off: Anti-Abortionists, Right-To-Lifers, Devout Catholics, and Born-Again Christians crossed swords with Pro-Abortionists, Pro-Choicers, Liberal Thinkers, and Power Players for the medical industry.

Only after the Roe v. Wade ruling did legislatures begin “to systematically address the issue of research on conceptuses”—embryos and fetuses—Lori Andrews, a professor of law who specializes in biotechnology, has observed. (Just to reiterate, the first seven weeks of human development constitute the embryo phase; the last many months, the fetus phase.) The early human embryo’s questionable

status and whether lawmakers should allow researchers to utilize an embryo’s cells made for a perfect political dog bone, bringing together as it did questions that forced science and religion to occupy a very tight corner. From the beginning, there was an unsolvable element about the debate, and over the years the centerpiece question wouldn’t change. Is this morally and ethically aboveboard, or isn’t it?

Further fanning the tense atmosphere that surrounded the unborn was the practice of transplanting tissue from fetuses. For decades, experimenters had regularly used the fetuses of amphibians, birds, rabbits, and rodents for their grafting experiments. “Slabs” of tissue were taken from specific regions of a fetus and transplanted to comparable regions in a recipient. The realization that fetal tissue was far more likely to survive uprooting than mature tissue raised the promising prospect of substituting diseased tissue with healthy tissue in human patients. Whether the tissue was taken from a fetal animal’s brain, liver, or pancreas, it appeared to be graftable because it contained cells that, while they had committed to a certain organ, retained enough stemness to grow rapidly and generate specialized cells of that organ. An important bonus was that a fetal graft was less likely to upset a recipient’s immune system than implanted mature tissue.

Scientists had experimented continuously with fetal tissue from small species, and much less with human fetal tissue. Interest in this practice was on the upswing in the United States, however. To the great delight of many researchers, a 1988 ban imposed by the Reagan administration prohibiting federal funds from fetal tissue transplantation research—-research involving fetuses from induced abortions—had been lifted by President Clinton in January 1993, right after he took office. The very next month Newsweek spotlighted the “new hope” that fetal tissue held for incurable diseases, among them Parkinson’s, Huntington’s, and juvenile-onset diabetes.

Even during the previous period of restrictions, research into transplanting fetal tissue had carried on in the United States. Private funding had sustained it, along with federal monies available to in-

vestigators who worked with human fetal tissue from spontaneous abortions or stillbirths. Fetal tissue science kept chugging along overseas as well. Swedish researchers, for instance, had issued reports that raised optimism that cells removed from a specific area of the fetal brain might help Parkinson patients regain satisfactory levels of dopamine, the brain chemical that degraded in those patients.

Notwithstanding the bright outlook for fetal tissue grafting, people who were against abortion saw a moral landslide in progress. Each year in the early ’90s as many as 1.5 million fetuses were being aborted in the United States; and with research that utilized fetal tissue gaining momentum, the fears unleashed by Roe v. Wade seemed more real than ever, that of fetuses being grown and aborted for financial or scientific gain, their value diminished to little more than farmed vegetables. To anti-abortionists and pro-lifers the practice of using aborted fetal tissue for medical measures seemed a duplicitous conceit—the killing of a life for the saving of a life. The sentiment would strengthen that new human life shouldn’t be exploited. It seemed unjust enough that many thousands of IVF embryos were accumulating in freezers, and many more thousands of aborted fetuses were surgical waste. Raising further doubts about fetal tissue grafting were sporadic reports that it failed to help a disorder, or worse, led to tumors or a dangerous overgrowth of tissue in a recipient.

Lines were getting blurred and questions were piling up. In the opposite camp, Americans who supported human embryo research would increasingly question what they saw as a muddle of inconsistencies. If it was okay for fertility specialists to make so many IVF embryos that extra embryos sat in freezers for long periods of time and eventually were discarded, and if it was okay to test and study cells of aborted fetuses, then why wasn’t it okay to put cells derived from leftover IVF embryos to better use? This is the ethical morass that James Thomson would be sucked down into later in the ’90s.

While Ariff Bongso on the opposite side of the planet was isolating stem cell-like cells from human blastocysts in 1994 and multi-

plying them in captivity ever so briefly, Thomson, his supervisor John Hearn, his technician Jennifer Kalishman, and various others, all of whom were housed in Hearn’s smartly managed Wisconsin Regional Primate Research Center, were in the midst of a stunningly long run. In hang-gliding terms, it was as though they’d been aloft for over a year. The previous year, they had managed to flush six-to-eight-day-old embryos from the reproductive tracts of pregnant rhesus and marmoset monkeys, whereupon Thomson had isolated stem cells from primate embryos and grown these peerless cells in the company of mouse feeder cells. The remarkable outcome was that the stem cells had been dividing and expanding in culture ever since, and without differentiating, thanks especially to the culture brew that Thomson had concocted.

This capture of stem cells from monkey embryos might well have happened later in time were it not for John Hearn, the British-Australian developmental biologist who, in a few short years, had turned the University of Wisconsin’s primate center into what was widely considered the best in the world. “His goal of excellence was contagious,” remembers Kalishman, a veterinarian who now works at Columbia University’s Institute of Comparative Medicine. “He wanted to make it the most progressive primate center, and that included medical research, conservation studies, library resources,” and the best possible scientists.

Ever since his graduate-school days at the Australian National University, Hearn’s primary investigative niche had been examining how an embryo attaches to the uterus, or implants. By the time he was appointed to direct London’s Institute of Zoology in 1980, he was a world authority on the subject, particularly in regard to primates and marsupials, although he investigated and marveled over the implantation process in a wide range of mammals. As he came to appreciate, the embryos of many mammals descend into the uterus between day 3 and day 5 post-fertilization, and yet when they actually implant varies greatly among species. The mouse embryo implants around day 4; humans and other primates, around day 7 or

day 8; the wallaby, as late as day 20 (and then gives birth as soon as day 27). This small kangaroo and several other kangaroo species have a “fantastic” capability, shares Hearn. “The mother wallaby can keep a spare embryo in her uterus for up to a year, so if anything goes wrong and the young in her pouch is lost,” the extra blastocyst “immediately activates,” leading to a baby wallaby. “It’s sort of like having a spare tire,” describes Hearn, who now is back in Australia at the University of Sydney, where he is deputy vice chancellor. Researchers have slaved endlessly over the question of how to freeze embryos, he points out, “when here’s an animal that can hold an eighty-cell blastocyst in suspension at body temperature for up to a year!”

Hearn first became aware of stem cells in his student days when he found out that they had something to do with why a salamander’s lost tail “could regrow and shape as good as new,” he relates. In the course of inspecting early primate embryos under the microscope in the early ’80s, similar to what Ariff Bongso experienced, Hearn became conscious of the stem cells piled inside, cells that he knew were responsible for an embryo going from nearly nothing to something in a great hurry. “I would watch them hourly as the blastocyst settled down on the tray and its inner cell mass started to differentiate so quickly into the start of an eye, brain, muscle, and a beating heart, all within ten days. I was lost in the wonder of it,” he recalls.

Martin Evans and Matthew Kaufman’s extraordinary account in 1981 of freeing embryonic cells from mouse blastocysts made Hearn realize that his primate enterprise put him in an ideal position to similarly mine stem cells from monkey embryos. Among other things, with monkey embryonic stem cells in hand he and his crew would have the opportunity to engineer “knockout,” or genetically altered, primates that could assist in better understanding genes and their role in the healthy or diseased body.

In London, Hearn began a focused program to retrieve stem cells in 1984, he recounts, and after crossing the Pond in 1990 and setting up shop at the University of Wisconsin’s primate center, he

began looking for the right person in this country to oversee the daily research demands of the stem cell investigation. A year later he found his man: thirty-three-year-old Jamie Thomson. “We clicked right away; we were right on the same track,” remembers Hearn. “I could see that this guy was so flaming meticulous that he would persist and we’d go all the way.”

For Thomson, who was keen on studying a primate embryo’s earliest hours, a better opportunity couldn’t have fallen from the sky. Raised outside of Chicago, by the time he was ensconced in the University of Illinois, Urbana-Champaign, this National Merit Scholar was already leaning heavily in the direction of biology as evidenced by his admission into the biology honors program. Two experiments that he read about in college had impressed upon him that an animal’s early embryo was pretty astounding, because of its flexible stem cells. One was Beatrice Mintz’s venture in the early ’60s, in which she had combined the cells of two early embryos, and—behold—the mother mouse had given birth to a single mouse. The second was Ralph Brinster’s ’74 gamble in which his lab at the University of Pennsylvania’s School of Veterinary Medicine took malignant stem cells from a mouse teratoma, placed them in an early mouse embryo, and—behold—the mother gave birth to a perfectly fine little mouse that had no sign of cancer. The inserted tumor cells somehow had been reset to normal.

Ralph Brinster, a reproductive physiologist with rapacious focus and drive, say colleagues, happened to direct a demanding joint-degree program at the University of Pennsylvania. Thomson applied and, top student that he was, was accepted. He would take away a doctorate in veterinary science in ’85, a doctorate in molecular biology in ’88, and shades of Brinster’s intensity in the lab. There wasn’t a finer scientist to emulate. Brinster’s early culture techniques for embryos had been a pillar for the field. And then had come his savvy sense that maybe the embryo could incorporate introduced stem cells and thus be altered by external hands.

Thomson never entirely saw himself falling back on his first de-

gree and becoming a vet. As he told an audience years later with a faint trace of humor, although he loved animals, he loved people less, and it was the people aspect of being a vet that he didn’t think he could deal with on a day-to-day basis. More to the point, he says today, “the combined V.M.D./Ph.D. program at Penn is the best program of its kind in the world,” and the joint degree was perfect for what he would become most interested in, which was researching human disease through the comparative guise of animal models.

The summer before Thomson began at Penn, Martin Evans’s account of capturing stem cells from mouse blastocysts had been published. Thomson was attracted to the implications, as were so many young scientists. Here were normal pluripotent stem cells that might prove to be the vehicle for modifying genes in animals. (The idea of using these cells for therapies was not yet widespread.) Would Evans go a significant step further and isolate stem cells from human blastocysts? Or would someone else come along to claim that prize?

That same summer, the summer of ’81, Thomson had been a Fellow at the Friedrich Miescher Institute in Basel, Switzerland, where, among other projects, he had tried to grow a whole plant from a single mature corn cell. This was the same as cloning a plant, or producing its genetic twin, which people had done for eons by taking a cutting of a plant or dividing one in two. Indicative of this long history, “clone” comes from the Greek word for twig, which is klwn. But cloning a plant by means of just one cell—and a mature cell, not an embryonic meristem cell—was a fairly recent accomplishment. Frederick Steward, a plant physiologist at Cornell, had been the first to achieve this feat in the late ’50s, when he grew an entire carrot plant from a single mature cell taken from a carrot’s thick orange root.

Similar to the attempts to clone frogs in the ’50s, Steward’s experiment hinged on genes inside a mature plant cell reprogramming and reverting to a totipotent state from whence could spring the different specialized cells and tissues necessary for the making of a new plant. Zoologists had begun speculating that the same biologi-

cal process explained a salamander’s ability to replace its limb: specialized cells in the stump dedifferentiated into embryonic cells, and the embryonic cells in turn redifferentiated, generating all the necessary cell types for growing a new limb. Due to John Gurdon’s cloning experiments in the ’60s, it began to be recognized that the genome of at least some differentiated cells “is not irreversibly altered or blocked by differentiation,” but could be reprogrammed backward to a younger potential, as one Michigan zoologist described in 1970.

While in Basel, Jamie Thomson never did get a corn cell to grow into an entire plant. Yet he appreciated more than ever the power inside a cell, whether a plant or animal cell. At Penn that fall, he began learning a great deal about the cells of a budding mouse embryo in Davor Solter’s laboratory at the Wistar Institute. Solter and some of his crew were also studying Roy Stevens’s mouse teratomas, and so Thomson took in a great deal about a teratoma’s cancerous stem cells as well. Solter, a leading Yugoslavian-born mammalian embryologist, had done key experiments with these precocious cells when he was at the University of Zagreb. Planting a mouse embryo under the kidney membrane of a full-grown mouse—a place where researchers bury tissue to see what happens to it—he had checked back in a month and discovered that the embryo had lapsed into a teratoma, its stem cells differentiating chaotically.

And so at the bench Thomson was learning that there is a kind of similarity between stem cells in a teratoma and those in an embryo. “They can easily move one to another,” as Solter notes today. Set in a strange environment, a mouse embryo’s stem cells turned malignant; or, as in Ralph Brinster’s ’74 experiment, malignant stem cells turned normal when dropped into the surroundings of a normal embryo. Solter remembers Thomson as being a very diligent student, and he also remembers Thomson’s proclivity for things aeronautic. Thomson was trying to master boomerangs around this time, and as Solter later noted, “I was never sure we would survive it.”

Not until shortly after his graduation from Penn did Thomson

learn how to harvest stem cells from mouse blastocysts. Through the suggestion of Solter, he did a brief stint with Colin Stewart, a British mouse embryologist then at the Roche Institute of Molecular Biology in New Jersey and one of the first scientists to replicate Martin Evans’s commendable culling of embryonic stem cells from mice. Stewart guided Thomson through the work’s trickiness. “Once you put a blastocyst in culture, you only had a window of time to pull apart the blastocyst and get stem cells,” explains Stewart. “If you waited too long—which was a great temptation since as the embryo became larger one thought it was producing more stem cells—the stem cells were gone.” They were that transient.

Thomson meanwhile had accepted a postdoc position at the Oregon Regional Primate Research Center in Beaverton, a top place to master primate developmental biology, and right before making his westward move, he and Stewart lunched together. “We chatted about how it would be interesting to [isolate] primate embryonic stem cells,” Thomson recounts, “and he told me about efforts in Britain where they were trying for human ES cells but had failed up to that point, and how making them from primate was probably a good idea. That was actually the first time I’d thought about doing it in primate.”

Thomson never went the distance of extracting stem cells from monkey embryos while he was in Beaverton. He was too busy with other projects—and spent the time, as well, hang gliding off high cliffs beside the Pacific. Moreover, he didn’t have access to the numbers of quality monkey embryos needed for such an undertaking. His desire nonetheless grew to examine the starting hours and days of monkey embryos for the sake of having “a better model for human development,” he mentions, which “convinced me that I really did need to derive primate ES cells as a more sustainable source of material.” Thomson had heard John Hearn talk at meetings and was impressed by Hearn’s first-rate primate outfit in Wisconsin, which featured a team that could routinely recover admirable amounts of high-quality monkey embryos. In the winter of ’90-’91, while on

Christmas break and visiting his brother in Wisconsin, Thomson met with Hearn and was offered the job of pursuing stem cells. He began work that June, with the arrangement that he would also do his residency training in pathology.

Although Hearn’s stem cell program had solid backing from Wisconsin’s graduate-school dean and other higher-ups, a few of his campus colleagues took a dim view of it. Recalls Hearn, they felt that he was wasting funds and should stick with less risky projects that would bear fruit more rapidly.

Yet with Thomson aboard the project picked up speed. First on the docket was to flush adequate numbers of embryos from female monkeys without resorting to surgery. Thomson crafted a cannula—a long thin tube attached to a syringe, and the first ever devised for flushing embryos from the reproductive tract of marmosets—and it was up to lab tech Jennifer Kalishman to efficiently wield it. Once a hormone test indicated that a marmoset was pregnant, the monkey would be sedated, and Kalishman might dislodge anywhere from one to four minuscule embryos, which could only be spotted through a microscope. Extracting early embryos from rhesus monkeys was far more difficult, due to what Hearn describes as the rhesus’s “tortuous” cervix and its “false passages.” Luckily, Hearn’s group included Steve Eisele, Wisconsin’s talented chief animal caretaker who “had this incredible knack of almost feeling his way up the rhesus cervix” with a cannula, recounts Hearn.

On the receiving end of these tiny retrieved embryos, Thomson, with the aid of micropipettes and enzymes, would excavate out the stem cells and meticulously experiment with different culture ingredients to see what might keep these finicky cells multiplying, without differentiating, with an eye toward the methods that had enabled Martin Evans to maintain his mouse stem cells in a dish. Problem-solving was right up this Phi Beta Kappa’s alley. “Jamie worked out all the details of the research on his own,” recalls Kalishman. “He was extremely disciplined and not easily distracted, and had a beautiful, logical way of troubleshooting problems.”

When Thomson wanted a break from work, the prankster came out to play. One particular prank still makes Kalishman laugh. “Jamie was always popping up and asking me, ‘What are you doing? What are you doing?’ Well, one day I sat down at my computer, and as soon as I struck the first key, this voice said ‘What are you doing?’ I looked around, but Jamie wasn’t there. It was the computer! He’d programmed it to say, ‘What are you doing?’” If Thomson was reticent in certain situations, it often had to do with his being his own person. Points out Kalishman, “He’s not one to succumb to what other people think is popular.” He wore the basics. He didn’t own a television. And he did not suffer fools gladly.

As the months went by, Hearn gave his young racehorse more rein for managing the research’s day-to-day progress, while he himself kept the project on track. “I raised funds, did the marketing, ensured quality, and ran interference against those who thought we were nuts and should give up,” remembers Hearn. And that’s how it came to pass that by 1994 the Wisconsinites not only had monkey ES cells in culture, but had watched them divide and survive for over a year. To test the cells’ pluripotency, they had injected them into mice whose immune system was incapable of mounting an attack, and the cells gave rise to teratomas. Poking into these strange little tumors, the researchers spied “neurons, muscle, limb buds, hair follicles, tooth buds, and complex-layered gut,” the whole jumble descended from stem cells. That made for “an eureka moment,” remembers Hearn. They knew for sure they had uncovered the rhesus monkey’s master cell.

On the eve of their rhesus report in August ’95, Thomson sketched out to reporters why having monkey stem cells captive in a dish was such a big deal. Studying their differentiation would throw light on a monkey’s development, he explained, and reveal parallel events in human embryos. Stem cells in human embryos were next in line to be isolated, and when they were, scientists would have the keys to transplantation medicine. Multiply them, coax them to differentiate, and you might have a constant source of mature cells with

which to replace diseased cells. Yet in the end few reporters covered the Wisconsin team’s rhesus paper. Stem cells in general were such a novel subject, and their connection to therapies for human disease a remote pie in the sky.

As the rhesus paper was headed for print, Thomson says, he and Hearn had no plans to go after embryonic stem cells in humans. “I imagined someone else would be there first,” he recalls. Yet no such reports surfaced, and he began to think more seriously about such a venture. Hearn was supportive of the plan, but his own career was starting to take a new turn. In 1996, he and his family would relocate to Geneva, where he would join the World Health Organization’s Reproductive Health Research Program as a senior scientist.

That left Thomson to decide whether to pursue the “mother” cell—human development’s sine qua non. He had the know-how, having isolated the equivalent cell in monkeys. Another motivating factor was that the university had its own in vitro fertilization clinic. It wasn’t exactly overflowing with spare embryos—Madison had a small population. And yet perhaps some couples would be willing to part with their unused embryos, especially for research that might liberate medicine from its heavy dependence on chemicals. Cell-based medicine was a concept that others could easily appreciate.

A missing cornerstone was funding. However, just as Thomson began looking for this necessary ingredient, Michael West, an entrepreneurial scientist, dropped out of the sky. “Things always seemed to work out for Jamie when he needed them to,” says Kalishman. “I’ve always told my colleagues that he has a Midas touch.”

Michael West was unusual in his combination of interests. He had studied the Bible as closely as he had the biology of a cell. He also had a flair for business and public relations, having made a small fortune building up and selling a family truck-leasing business in Michigan. Now, in 1995, he was in the process of turning a company that he had incorporated five years earlier into a headline-fetching West Coast biotechnology firm. Although his idea for the company initially struck some people as far-fetched, there are those

today who call West a visionary because of it. He had come to believe that human aging wasn’t necessarily an unstoppable train; there might be ways of braking its forward motion. A species’ distinct line of immortality, its germ line, gave him this idea. Egg and sperm fuse to form a new individual, whose egg or sperm merges with another individual’s sperm or egg, and so it had proceeded through the ages. Since its beginnings, the human germ line had never ceased; or, as West likes to point out, “You and I are made of cells that have no dead ancestors.” Realizing this, he says today, “made me think we could outsmart aging if we could understand what allows for the germ line’s immortality.”

Geron—old man in Greek—was the name of his company, and its two-fold mission was to decipher the cellular basis of aging, no less, and to design drugs that stopped that mechanism. West, who had a Ph.D. in cell biology, had taken a leave of absence from medical school at the University of Texas in Dallas to start Geron in ’90, but then had gotten so caught up in his company’s progress that he had waved goodbye to medical school altogether. He saw the pieces of a puzzle starting to fit, he says. One piece was Leonard Hayflick’s famous 1961 observation that most mature cells in the body divide only so many times before running out of steam. Another piece was research that linked a cell’s telomeres—the ends of chromosomes—to the aging process: Each time a cell divided and its telomeres shortened, it took a fateful step toward terminating. The puzzle picture that leapt out at West was the telomere, and soon the main aim of Geron’s scientists became trying to isolate telomerase, the protein that synthesizes telomeres. Inserted into a cell’s nucleus, theoretically it might lengthen the telomeres—and a person’s life. In reverse, if telomerase was inhibited, it might stop cancer cells from their ceaseless division.

But even as Geron’s researchers were hard on the trail of telomerase, something else was occurring to West. During his second year of med school, he relates, “every Tuesday our pathology professor would bring in this stainless steel bucket filled with human

tissue that was brought over from nearby Parkland Hospital,” the Dallas hospital where, in 1963, doctors had tried to save the life of President John Fitzgerald Kennedy. The purpose of each bucketful, which might include anything from cancerous lung tissue to a liver damaged by cirrhosis, was to allow the students to see full-scale diseased tissues, which they otherwise saw only at the microscopic level on glass slides. One Tuesday, the professor appeared with something a bit different—a large teratoma removed from a woman’s ovary. “We cut it open and in it was an incisor and molar among skin and hair and developing [cerebral] cortex,” relates West. “At this point, I was interested in regenerative medicine, and my mind was burning with the question of, what cell does this? What cell makes all this? I didn’t have a clue.” Then he learned that a teratoma arose from a misguided stem cell, and that Roy Stevens at the Jackson Laboratory had shown that the misguided cell was a germ cell—or at least that was the case in mice.

Even once Geron, a telomere company, hit its stride, stem cells stayed on West’s mind. So did an earlier observation by the biologist Howard Cooke that the telomeres of egg and sperm cells, or germ cells, didn’t appear to shorten over time like the telomeres of other differentiated cells. Because egg and sperm were stem cells, West got this notion: If stem cells really were immortal and had long telomeres, he reasoned, why seek out telomerase itself to reverse aging in other cells? Why not instead try to harvest human embryonic stem cells with their long telomeres? If for the purposes of transplantation therapy you could coax ES cells to generate differentiated progeny, these mature cells would start off with long telomeres as well. You’d have young mature cells that could be used in the face of disease or aging.

West diverted two of his scientists to the task of helping him collect stem cells from sixteen-week-old fetuses that came from a San Francisco abortion clinic. By the mid-’90s, he relates, they had isolated stem cell-like cells but couldn’t get them to grow, and it was at this point that West began checking around to see if other labs were

making progress with human embryonic or fetal stem cells. Jamie Thomson’s lab at the University of Wisconsin, Madison, was one of three labs he would learn about. The others were Roger Pedersen’s at the University of California, San Francisco, and John Gearhart’s at the Johns Hopkins University School of Medicine.

When Michael West, with hardly any advance notice, appeared in Thomson’s Wisconsin lab in 1995, the timing couldn’t have been better for Thomson. Having made up his mind to go after human embryonic stem cells, he had applied for funds “not through WARF”—the Wisconsin Alumni Research Foundation, the non-profit that provides licensing services for the University of Wisconsin—“but through what was called ‘The Office of University-Industrial Relations,’” relates Thomson. “They turned down the application, and a week later Mike West visited.” Thomson had heard through the grapevine that “they,” the now-defunct office he had applied to, “were afraid of it,” afraid, possibly, of the consequences of a Wisconsin researcher going into an area that had begun to heat up politically. West essentially made Thomson an offer he couldn’t refuse. Geron would help fund the human stem cell work and meanwhile license the University of Wisconsin’s patent rights to its rhesus monkey ES cells. Human stem cells being steps away from the rhesus cells, Geron would do preliminary work with the monkey cells.

All that Thomson needed in order to proceed with his research on spare IVF embryos was approval from the university’s twenty-four-member Health-Sciences Human Subjects Committee, the review board that stood watch over any campus research involving human subjects, born or unborn. He was fully conscious of where his lab work was carrying him—straight into the floundering, unresolved debate in the United States over an embryo’s societal status and legal entitlements. He, the hang glider, really was descending uncontrollably into a hazardous swamp. A wide range of people and organizations vehemently opposed the dismantling of early embryos. Coming from the opposite view, Thomson didn’t view a human blastocyst as “equivalent to a human baby,” although he had friends who

did, was an employee of a large university that had its fair share of people who did, lived and worked in a state that had thousands of staunch Pro-Lifers who did, and was a citizen of a nation of mixed heritages, some of which did.

Even before his and Hearn’s rhesus monkey paper was published, while still trying to decide whether to isolate human embryonic cells, Thomson had knocked on several doors looking for guidance as to what legal and ethical issues might arise were he to dismantle human blastocysts. One of those whose counsel he sought was Norman Fost, who, beside being a professor of pediatrics at the University of Wisconsin, also was the founder and director of the university’s Program in Medical Ethics. “Jamie cared deeply about doing the right thing,” recounts Fost. “He appreciated the larger social context and understood that others might be upset about what he was doing.” It was clearly expedient for Thomson to approach Fost, who also directed the review board that either would or wouldn’t allow Thomson’s human embryo research to go forward. Yet Fost and other Wisconsin staffers maintain that Thomson went to far greater lengths to examine the moral ground he was descending into than was required.

It was a harsh coincidence that just when Thomson and his lab’s monkey work put them in an excellent position to isolate human embryonic stem cells, their endeavor and its dependence on surplus IVF human embryos fell right “at the core of the right-to-life issues that had begun to permeate so many health-care issues,” recounts Fost. William Jefferson Clinton, a Democrat, was in the White House, and in many respects more liberal days were dawning. At the same time, the powerful pro-life trend, which had been in progress since Ronald Reagan’s presidency, notes Fost, “was dramatically intensified by Newt Gingrich’s rise to power in ’94.” Right-to-lifers raised their voices in Congress and thundered from pulpits against the new biotechnologies that endangered societal mores and religious creeds.

From 1980 all the way to 1993, federal funding for IVF embryo research had not been available in the United States because of a de-

facto moratorium. Then, in late ’94, the National Institutes of Health’s Human Embryo Research Panel concluded that research utilizing excess IVF embryos appeared to constitute acceptable public policy, as long as such research was conducted on embryos before the primitive streak’s onset on day 14. The panel’s report was well received by an advisory committee to NIH director Harold Varmus, a visible proponent of stem cell medicine.

In ’93, as seen, Clinton had cleared the way for federal funding for research involving fetal tissue. (Bear in mind that legislation tied to human embryo research progressed separately from legislation tied to research involving human fetuses.) And now the door stood ajar to create regulatory guidelines for researchers using human embryos. Yet it wasn’t long before that opportunity slipped by. The following summer, that of ’95, an amendment was introduced by two Republican congressmen, Jay Dickey of Arkansas and Roger Wicker of Mississippi, that summarily blocked federal funds for “research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death.” The Dickey-Wicker amendment, entered into the NIH appropriations bill, would take effect in 1996. According to Alta Charo, a law professor at the University of Wisconsin Law and Medical Schools and a member of the NIH’s panel, President Clinton, due to the approaching midterm elections, had to make certain concessions and “couldn’t take steps to the left.”

Thomson’s IVF embryo work would not be eligible for public funds due to the laws of the land. And yet such was the situation in the United States that his research could legitimately sail forth on the keel of private funds provided by Geron, a private company—that is, as long as Thomson got a thumbs-up from the university’s health-sciences IRB, or institutional review board.

Norm Fost recounts that, upon receiving Thomson’s protocol in 1995, Wisconsin’s review board felt “a special burden” to diligently examine the pros and cons of IVF embryo research. If Thomson succeeded in extracting human stem cells, the research was bound to

attract attention. Thomson’s interest in staying with embryos that were less than fourteen days old made the board’s job somewhat easier, day 14 being the earliest point at which pre-neural structures start to form and the embryo might experience anything resembling pain. In fact, Thomson didn’t want to come anywhere close to day 14, says Fost. Nor did he have any desire to go the route of taking eggs retrieved from women, growing those up to blastocyst stage without fertilizing them, and harvesting stem cells that way. Although this had only been done with the egg cells of nonhumans, probably it could be done with human eggs as well, solely as an option for harvesting stem cells.

Wisconsin’s review board spent most of its time on two questions, according to Fost. There was “the debate over the moral status of an embryo, but, secondly, whether the IRB needed to get engaged in that debate at all. We frankly concluded that we probably didn’t need to, for several reasons.” First, the board’s members had differing opinions, and “endless discussion probably wasn’t going to switch anyone’s view.” Also, notes Fost, “three distinguished national commissions had already looked at the same ethical issues in great detail”—the Warnock Committee in the UK (1984), the Canadian Royal Commission on New Reproductive Technologies in Canada (1993), and the NIH Human Embryo Research Panel in the U.S. (1994). “All had come to the same conclusions—that some kinds of research involving human embryos were ethically appropriate, within limits; and that whatever the moral status of the embryo, it wasn’t comparable to a full human.” The NIH panel had worded its decision thus: “Although the preimplantation human embryo”—the day 1 through day 7 embryo—“warrants serious moral consideration as a developing form of human life, it does not have the same moral status as infants and children.” Among the reasons it cited for its decision were the early embryo’s lack of nerve sensation and the very high rate of natural mortality at this stage.

In the years to come, the National Right to Life Committee, the Christian Coalition, the Coalition of Americans for Research Ethics,

and scores of other groups across the country would unite behind the belief that an embryo was comparable to a full human being. The National Conference of Catholic Bishops, which had opposed the practice of in vitro fertilization since its beginnings, took tremendous issue with the idea that IVF embryos should be deemed a legitimate source of stem cells. To the Catholic Church, a human being comes into existence at the moment of conception and from that moment on deserves the respect and protection due a child or adult. Arguments that the embryo gains significance only after it descends into the uterus on day 7, or only after the onset of its primitive streak on day 14, or only after its heart begins to beat on day 22, or only after an accumulation of growth milestones confers an array of human traits were denounced as empty claims by Richard Doerflinger, the National Conference of Catholic Bishops’ eloquent associate director of its Committee for Pro-Life Activities. Once a human life starts, Doerflinger and others in the Catholic Church contended, how can its beginning be any less important than what it grows into?

In a 2001 letter urging Congress to oppose using “live human embryos” for stem cell medicine, Reverend Joseph Fiorenza, the president of the National Conference of Catholic Bishops, wrote the following. “In his great novel The Brothers Karamazov, Dostoevsky raised the question whether it would be right to build a world without human suffering if ‘it was essential and inevitable to torture to death one tiny creature’ such as an innocent child to achieve that end. Each of us must answer that ultimate question in the depths of his or her own conscience. The claim that destructive embryo research will achieve such a utopian end is, we believe, a hollow promise. In the meantime, however, the killing will be quite real.”

Yet others would not equate research involving an early human embryo with a “killing” or a “destruction,” since in their eyes a cluster of cells doesn’t a person make. Norman Fost holds the personal view, apart from any held by the university boards he serves on, that “a long list of reasons” exist for why a young embryo does not repre-

sent a person. Although its cells carry a unique set of genes that make the embryo human, “that doesn’t establish it as a person,” he maintains. Cells in your skin have the same genes, “but no one would say a skin cell or a blood cell is a person.” An early embryo’s cellular potential, he feels, doesn’t make an embryo a person any more than an acorn’s inner potential makes an acorn an oak tree. Conversely, just because a person has the potential to die doesn’t mean they are dead. “An embryo doesn’t look like a person,” remarks Fost. “Nor does it experience suffering, which is part of why we care about what a person is. And even the most ardent advocates of an embryo-as-person don’t ask that embryos be counted in the census; they don’t ask that they be included in the tax code as deductions; they don’t ask that they be covered by health insurance, and they don’t ask that they have funerals.”

At the end of the day—it was July 1995—after reviewing the decisions reached by the United Kingdom, Canada, and United States commissions in close detail, the University of Wisconsin IRB realized that “it wasn’t likely to reach a different conclusion,” relates Fost, and James Thomson got word that he was free to pursue stem cells in IVF embryos. Once the particulars of the Wisconsin-Geron collaboration were worked out, Thomson sent Geron a sample of the embryonic stem cells that the Wisconsin crew had procured from rhesus monkeys. Geron’s scientists analyzed the cells’ telomerase, the protein that keeps telomeres long and healthy, “and saw that they had more telomerase activity per cell than any immortal cell ever studied—more than even a cancer cell,” recounts Michael West. “We were looking at the first naturally immortal primate cell.”

The immortal master cells of the human embryo were all the more anticipated.

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