The Stem Cell Hope, page 7
To her delight, however, it became clear that the potential of embryo research would extend far beyond reproductive and women’s rights issues. “This is where I first began to hear about the prospects of embryonic stem cell research,” Charo says during a thoughtful but typically fast-paced conversation. Despite the panel’s priority in viewing embryo research through the prism of improving infertility treatments or even creating new contraceptive options, over the course of their monthly sessions and follow up e-mails it became obvious that studying embryos was only a gateway to a new world. And that world was just being infiltrated by talk of stem cells, whose potential in mouse studies was already leading some scientists to new ways of thinking about and treating nearly every human disease, from neurological disorders such as Parkinson’s to the most common chronic diseases of the heart. One of these experts sat at the very same table with Charo and the HERP members.
Brigid Hogan, a mouse embryologist at Vanderbilt University at the time, was forever changed by Martin Evans’s and Gail Martin’s milestones in picking out embryonic stem cells from mouse embryos. James Thomson, at the University of Wisconsin, was still a year away from making his breakthrough in doing the same in primates, and several years out from similar success with human cells, but scientists like Hogan were convinced those milestones were not just inevitable but also not too far off in the future.
Like Varmus, she was fascinated by the potential of these earliest delegates of development, and serving as the panel’s cochair, she couldn’t help but infect her colleagues with her excitement and ensure that they looked not just at the reproductive potential inherent in embryo research, but beyond it to encompass, at least theoretically, what she saw as its true value: its ability to impact virtually all human diseases, from heart failure to diabetes to Parkinson’s and even cancer.
Hogan had reason for her expansive optimism. So enthralled with the mouse embryo that she carries an image of one in her wallet (“to look at if I’m feeling low,” she says), she used mouse embryonic stem cells to discover key drivers in the early stages of growth in embryos. She knew that it would simply be a matter of time before similar techniques could be translated to understanding human development.
Often taking pen to paper—or, more accurately, marker to poster board—Hogan would diagram the genesis of embryonic stem cells for the panel members: how they arose in the days-old blastocyst, and how, at least theoretically, if someone managed to isolate them from a human embryo, they could be cultured in a dish and treated with the right growth factors, enzymes, and other chemicals to begin dividing and developing into nerve or pancreas or liver or muscle cells. She also introduced the thrilling possibilities of nuclear transfer, or what would, in just two short years, with the birth of Dolly the sheep, become known as cloning. At the time of the panel’s discussions throughout the winter and spring of 1994, the technique had worked only in frogs, but, Hogan told her colleagues in her cheery British clip, there wasn’t any reason why it wouldn’t one day be possible to do the same in mammals, in nonhuman primates, and eventually in humans. The purpose, she stressed, at least from a scientific point of view, would not be to clone people per se, but to provide a source of stem cells, which could be removed when the blastocyst was four or five days old. If the stem cells came from an individual suffering from a disease, then these could be studied to expose what had gone awry in that individual’s cells—the pancreatic cells of a diabetic, for instance, or the brain neurons of someone with Parkinson’s. Once they revealed the defect, these cells could then be repaired or replaced with healthy versions to cure the disease.
“There wasn’t any deliberate planning on my part,” Hogan tells me when I ask her about the genesis of these impromptu biology lessons during the sessions. “It just emerged that many people on the panel needed to understand the basic science, not just of stem cells but about the whole process of embryonic development and things like cloning. They were spontaneous.”
For Charo, these lectures were nothing if not eye-opening. As a nonscientist who had primarily considered reproductive technologies from the perspective of legal rights, ownership, and regulatory challenges, those marked-up illustrations were her first glimpse at the potential breadth of embryo research and the range of studies that embryos could support, particularly through stem cells. It was immediately obvious how valuable studies on human embryos could become, and not just for improving reproductive science.
“All the presentations [we heard] were in terms of the mouse model,” she says of the state of the science at the time, demonstrating a very quick grasp of the limitations of the studies. “And while mouse embryos are very valuable in this research, their morphology is different enough from humans that there is a certain point at which you can’t learn what you want to learn in the mouse model.”
Moving from mice to men, however, was proving problematic, not just on the scientific front but socially and politically as well. “We were trying to figure out the state of the research, and how important it is to do research on human embryos, and how important it is to do it at this time,” she says, “because we understood that the research was highly controversial since it was obviously tied to the debates around abortion.”
Thomas Murray, a bioethicist who was then at Case Western Reserve University, still recalls how charged the subject of embryo research was, and how tense matters became with the public, many of whom were opposed to abortion, attended the meetings, and observed every exchange. At the time, several abortion clinics around the country had been bombed, and physicians performing the services had become the target of violent attacks. The panel members were not spared either: Charo received death threats, and the NIH posted guards at the meetings in case of an outburst. Keenly aware of how emotional the issue had become for some, Murray admits to succumbing to a bit of paranoia when he noticed a slightly disheveled middle-aged man sitting just behind the front row of spectators at one session that spring, close to the conference table where the panelists sat. The gentleman nervously shuffled and reshuffled a plastic bag he had brought with him, and Murray jumped to nervous conclusions. “I thought, ‘What has he got in that bag?’ We had no metal screening, and anybody could have walked in with anything if they kept it from sight. I thought, ‘What if he’s got a gun in that bag? What are we going to do?’ ” The man turned out to be a citizen there to provide testimony, but the experience reminded Murray of what was at stake.
As the members continued to draw and redraw the lines between what types of research on embryos would be acceptable and unacceptable using federal funds, and which types fell somewhere in between, it became clear that they needed a compass, some moral axis around which they could orient the various things that scientists were proposing to do with embryos. The most obvious such hub would be the moral status of the embryo. If the embryo were considered the equivalent of a living human being, then that would afford it certain rights and dignities, despite its inability to assert them, that would render all of embryo research unacceptable. If, however, as the majority of the panel felt, moral status is a dynamic condition as opposed to a fixed feature, in which rights and status are layered on in accordance with advancing biological development, then it could be argued that the panel needed to find some scale along which these rights were accrued.
As the discussions continued, however, it occurred to Charo that the panel’s attempt to assemble this sliding scale was akin to Alice’s making sense of Wonderland. What feature defined the exact moment when a mass of cells gained enough “beingness” to earn additional rights and status? Was it the formation of the primitive streak, at around fourteen days, which defined the three basic germ layers of human tissue and thus designated a biological marker for personhood? That was what a panel debating similar thorny issues in England a decade earlier had decided, determining that it was acceptable for scientists to study embryos but only until the embryos were fourteen days old.
That panel, led by Oxford philosopher Dame Mary Warnock, contained more doctors, lawyers, and scientists than ethicists and theologians, however, and rather than tackling the stickier task of setting moral criterion for what type of research was acceptable, it took a more practical approach, relying on objective biological criteria, including the primitive streak to guide them. In the UK, that proved effective in helping to establish a straightforward embryo research policy inspired by the Human Fertilisation and Embryology Act in 1990, which later applied to stem cell research as well.
The Warnock report and its recommendations were certainly part of the mountain of materials the HERP members reviewed. For Charo, however, it seemed that the moral issue couldn’t be so easily subsumed by biology. At least it didn’t seem likely in the United States, where the abortion debates continued to simmer in the political arena and pro-life interests retained enough clout to prevent panels like HERP from sidestepping the question of what, exactly, the moral status of the embryo is.
But, she admits that even today, “I don’t see a way around this, except to acknowledge that we can’t answer this question and then ask, ‘What do we do with that? Where do we proceed from the fact that we can’t answer it, and we can’t all agree?’ ”
The impasse reminded her of Lewis Carroll’s poem “The Hunting of the Snark,” which chronicles the misguided efforts of a hapless group of shipmates in their hunt for a creature that does not exist. “The snark, in my mind, was the moral status of the embryo,” she tells me. “One of the things I concluded at the end of the [HERP] experience was that there are some issues on which we are not going to achieve fundamental consensus. We will not reach consensus on the moral status of the embryo, or on the moral status of somebody whose lower brain stem stopped working or is in the post-vegetative state like Terry Schiavo, because we are all driven by an entirely different analysis of what generates moral status.”
That analysis, the panel acknowledged in their review, arises from a complex combination of religious, cultural, and social beliefs that is hard to modify or alter, even in the face of contrary objective evidence. The Jewish and Islamic religions, for example, adopt a more pluralistic approach, and while recognizing that a developing fetus should be accorded some respect as a being, believe that it does not earn personhood until months after conception. In Jewish theology this occurs after forty days; in Islam it takes until the fourth month of pregnancy. The Catholic tradition, on the other hand, adheres to a single-criterion approach, holding steadfastly that all life, from the moment of conception, has equal moral status, despite the scientific fact that conception is not actually a single discrete event, but rather a process of sperm fertilizing an egg.
Charo was urging the panel to put aside the issue of trying to determine an embryo’s moral status and address instead, from a civic perspective, what policy concerning research on embryos would be acceptable to a population practicing diverse moral, ethical, and religious traditions.
“Rather than have the government adopt one analysis or another, which essentially puts the government on one side or another of what is fundamentally an ethical, philosophical, or theological debate, why not say we can’t agree, and we’ll never agree?” she argues. “Now, we can ask a slightly different question if we are asking not about moral ethics but political ethics. What is the ethical thing to do to solve a political impasse? In other words, it’s more about political philosophy than moral philosophy. Maybe we start the analysis that asks who is hurt and who benefits if we adopt a particular policy, and if we take a look at how benefits and burdens are distributed.”
If the issue of how to treat an embryo can’t be resolved on moral grounds by consensus, then, Charo believes, it should be addressed from the perspective of public policy—finding the most equitable distribution of the advantages and disadvantages of something such as stem cell research. There are those who support the field and believe in its potential to cure dozens of diseases and relieve millions of patients from pain and suffering, while at the same time, critics of the science are equally opposed to the destruction of embryos involved.
This revelation led Charo to push, by her own admission, rather aggressively for recommending that the government consider funding the creation of embryos solely for research purposes. This would mean that women and men would donate egg and sperm not with the intent of creating a baby, but only to create an embryo that would then be destroyed at just under a week old when scientists extracted its stem cells. Given the direction and promise of the science of stem cells, Charo felt this was a reasonable and logical recommendation for the panel to make, and for the government to follow. And given the position that the panel was taking on the question of the moral status of the embryo, it also made sense to include this option as one that warranted further review. “As a matter of principle, since this body was viewing moral status of the embryo as a function of its state of development, there really should be no difference morally speaking in the status of an embryo left over from IVF and five days old, or an embryo that was deliberately made for research and is five days old,” she explains. “If the moral state depends on the stage of development, then there is no difference. On that basis, one can conclude that yes, you can make them occasionally for research.”
In the end, the nineteen members voted to place the creation of embryos solely for research purposes into the category of “warrants further review”—but only by a slim margin. They agreed that federal funding of such research would have to fall into two very strict categories: Either the studies could not be conducted without generating the embryos, or their creation was necessary for experiments of “potentially outstanding scientific and therapeutic value.”
Two of the members, including cochair Patricia King, a law professor at Georgetown University, and Carol Tauer, a professor of philosophy at St. Catherine University in Minnesota, disagreed with the recommendation and wrote dissenting opinions for the final report.
“I felt that to create embryos for research, purely for stem cell research, did not come under the conditions we had already outlined,” Tauer tells me. “That was my objection; I thought we had laid down principles that we had agreed on, and here we seemed to be going somewhat beyond that.”
Tauer continues to feel that the panel didn’t take into consideration the thousands of embryos that exist in IVF clinics, in frozen storage, that could be used for research purposes if their donors decided not to have them implanted. If the panel’s own criteria were followed, she says, those should be the first resource for study, and if they did not suffice for whatever reason, then, and only then, could generating new embryos for research be justified. “As far as I knew, there were a lot of alternatives, and it wasn’t necessary to create embryos to study,” she says.
King, who penned the other dissent, incorporated a sociocultural consideration into her opposition. During the panel’s four months of discussions, King was the first to question whether the creation of research embryos would be pushing the American public’s sensibilities on these matters too far. Creating embryos for research purposes created serious ethical anxieties that we as a society had not yet addressed and, she feared, would give the public the wrong impression about the intent of the studies. “The fertilization of human oocytes for research purposes is unnerving because human life is being created solely for human use,” she wrote in her opinion. “I do not believe that this society has developed the conceptual frameworks necessary to guide us down this slope.”
King’s concerns, it turned out, proved prophetic. When the final report was released on September 27, 1994, the panel’s recommendation that NIH fund the creation of embryos for research became a lightning rod for the national media, as well as for other ethicists. The Washington Post published an editorial excoriating the panel for its support of research embryos as “flat wrong,” “unconscionable,” and science that “the government has no business funding.”
But even that was just a prelude to the rude awakening that the entire panel, including Varmus, would get when the report completed its bureaucratic journey through the review process at the NIH and finally hit the president’s desk a few months later.
By that time, the Clinton administration would be, as Varmus says, “nervous” about a number of things—the fallout from the congressional election, in which Newt Gingrich had succeeded in reestablishing a Republican majority in the House, and the Democrats’ slipping hold on voters. A radical idea like allowing scientists to create human embryos solely for the purpose of conducting research on them might simply be too much for voters to accept.
“I knew not everybody was going to like it,” Varmus tells me of his reaction after reading the report. He fully endorsed the panel’s findings, and appreciated the thoughtful conclusions they had come to. “It’s pretty amazing,” he says, still marveling today over the scope and depth of the report. “It addressed a lot of issues before they arose. It wasn’t just that they thought about stem cells, but that they thought about nuclear transfer, at a time when nuclear transfer wasn’t even possible in humans. So I really didn’t expect to have this much push-back from our own side.”
But pushed back he was—by an administration that he had assumed would be behind the panel’s recommendations. After reviewing the report, Varmus trekked several times from NIH’s Bethesda campus, along Rockville Pike to Pennsylvania Avenue. “I spent time at the White House, not talking to Clinton, but to people around him, to explain what this research was, trying to present it in as objective a way as I possibly could,” he says. “What I had were people around the table who were sympathetic to what I was saying but basically feeling tied down by political implications. They were just very nervous.”
