The 2004 Jurow Lecture: From Recombinant DNA to Stem Cells — Making Science Policy in a Democracy
President Shirley M. Tilghman
March 31, 2004
Presented at New York University
It is a pleasure to be with you today and an honor to deliver this year’s Irving H. Jurow Lecture. The Jurow Lecture, as you know, is hosted by the College of Arts and Science and reflects Mr. Jurow’s strong commitment to undergraduate education, a commitment that we at Princeton University share. As the Dean of the College of Arts and Science noted when the Jurow Lecture was inaugurated in 1996, this lecture was established to “remind us that the undergraduate college, no less than our professional or graduate schools, drives the intellectual discourse on campus.” Furthermore Mr. Jurow’s abiding commitment to attract the most gifted students to NYU through generous provision of financial aid kept the doors of the university open to all comers.
I have taken as the subject of today’s lecture the pressing need for intelligent and open-minded discourse among scientists, religious leaders, ethicists and lawmakers so that we can together craft sound science policy for this country. The capacity for such discourse is, of course, bred in undergraduate colleges and universities, especially those that embrace a broad interpretation of a liberal arts education. The best definition I have heard of what that entails was captured eloquently 100 years ago by one of my predecessors, Woodrow Wilson, Princeton’s 13th president:
“What we should seek to impart in our colleges,” he said, “is not so much learning itself as the spirit of learning … the power to distinguish good reasoning from bad … the power to digest and interpret evidence … an addiction to clear and logical processes of thought and yet an instinctive desire to interpret rather than to stick to the letter of reasoning … a taste for knowledge and a deep respect for the integrity of the human mind.”
In a perfect world, that ideal of the educated citizen would describe today’s scientists and politicians, who have an obligation to step outside the laboratory on the one hand and partisan politics on the other and talk to one another, as well as the public, in a spirit of mutual respect and collective responsibility. This exchange is essential in any society but especially in a democracy, where public policies forged in isolation will ultimately fail. In today’s world, where the rate of scientific progress so often seems to outpace the preparedness of the public to endorse or embrace its implications, the need for dialogue is particularly acute.
Now responding to the challenge of absorbing new scientific knowledge is nothing new to us as human beings. From Copernicus banishing Earth from the center of the universe, to Darwin making monkeys of our ancestors, to Einstein’s weird warping of time and space, the truth of science has always threatened our sense of security in the natural order of things. What is different about our contemporary era is the swiftly quickening pace of discovery – and the tremendous influx of new knowledge in science and technology that seems to accelerate every day. We are constantly bombarded with news about groundbreaking advances in cosmology or neuroscience or nutrition – I am still uncertain as to whether broccoli extends lifespan or causes cancer.
I was stimulated to consider this topic after reading Margaret Atwood’s most recent novel Oryx and Crake. In it she describes an apocalyptic future in which the human species has been destroyed by a scientist named Crake in order to make way for a new species that incorporated what he deemed to be the best characteristics of humans and animals. What particularly struck me about the novel was the unremittingly negative portrayal of scientists – their arrogance, their venality, their elitism, their greed. At one point in the book the motivations of scientists working on cures for terrible diseases are called into question by one of the characters who suspects that the scientists have first created the disease in order to develop a market for its treatment – and yield huge profits for the inventor.
This makes for painful reading to someone like myself who has spent her life believing that a life in science is a noble one, and that working to improve the quality of life through improvements in health is one of life’s great callings. As hard as it is to accept that this is not the universal view of biomedical scientists, it is essential that we do so, because science depends upon the patronage of the public. The public make possible the conduct of science through the payment of taxes to federal and state governments and donations to charitable organizations. If we lose the trust of the public, we go out of business.
My first encounter with the disconnect between the pace of scientific discovery and the public’s readiness to absorb it came in the mid 1970s when I was a postdoctoral fellow at the National Institutes of Health, working with Philip Leder. My project was to develop a method to isolate and clone a gene from a complex genome, specifically the mouse genome. Recombinant DNA techniques were just in the process of being developed, and as I was working away at my project, a public debate over the safety and ethics of mixing the genes from disparate organisms was building. I want to review briefly the way in which the national discussion developed and ultimately resolved itself as a prelude to discussing the current debate surrounding the ethical use of human embryonic stem cells.
The first, and perhaps the most important, thing to say about the events surrounding the discovery of recombinant DNA is that it was the scientists themselves who first raised the possibility that the new technology might have deleterious consequences. In 1973 Paul Berg, the molecular biologist who went on to win the Nobel Prize for his work on recombinant DNA, and Maxine Singer, now the president emeritus of the Carnegie Institute of Washington, were considering experiments in which they were going to splice together DNA from an E. coli bacterial plasmid and the monkey DNA tumor virus SV40. Before doing so, they raised with colleagues the question of whether such a recombinant molecule might change the properties of the E. coli host in such a way as to be a danger to human health. This led to an unprecedented call by the scientists themselves for a moratorium on such experiments while the safety issues were considered. True, there were scientists, fearful of outside interference, who criticized this action, but overall the call for a moratorium by the very scientists who had the most to gain from moving ahead unimpeded by regulation of any kind avoided an unhealthy we/they dichotomy, with the public pitted against the scientists. I think it fair to say that had word of the scientists’ own safety concerns simply leaked out, the integrity of the scientists would have been called into question. Instead the public image of the scientist was, if anything, enhanced by their forthrightness.
I do not mean to leave the impression, however, that all went smoothly. By 1975, local governments, most memorably that in Cambridge, Massachusetts, where Harvard and MIT reside, and the press began to take up the issue, and the story had a strong element of hysteria and science fiction to it. At the NIH, where I was hard at work trying to get bacteriophage lambda to be a good cloning vector, Phil Leder was asked by a local television station if he would be part of a series of vignettes on the new technology. He agreed, and a camera crew spent days filming in the lab, where we painstakingly explained how we were hoping to isolate a gene for the first time and begin to understand how it is organized and regulated. The reporter seemed interested and asked intelligent questions. On the evening of the first segment we all gathered around the TV and watched as the story opened with a picture of a minotaur – half man, half bull – and went downhill from there with images of Dr. Frankenstein and creatures crawling out of primordial soups. I recall our shock and dismay, culminating in Phil’s plaintive cry of "But I don’t understand! That reporter is a member of my synagogue!"
Though, as a young scientist, I did feel an initial shock upon discovering this gap between my own perception of my work and the wider public’s, it was our ability to recognize that difference quickly and begin to remedy it that allowed for an ultimate and amicable resolution to the recombinant DNA saga.
The National Institutes of Health, surely one of the most respected government agencies, formed an advisory committee composed of both scientists and lay people to consider the safety issues and to develop a set of guidelines that would apply to all scientists who use federal funds to conduct recombinant DNA research. That committee – called the RAC for Recombinant DNA Advisory Committee – felt occasionally like a medieval torture device by the same name to those of us charged with conducting safety experiments. These included endless plating out of the feces and urine of animals that had been fed large quantities of E. coli containing cloning vectors. This was not what my mother had in mind when she proudly told her friends that her daughter was a scientist!
Painful though it was at times, the very thoughtful and inclusive RAC process helped to fend off embryonic efforts on the part of federal and local politicians to craft legislation governing recombinant DNA research. As it became clear that the technology posed no threat to humans or the environment, it was relatively straightforward to modify the regulations, something that would have been much more difficult had Congress codified the regulations into law.
To recap, the critical ingredients of this very successful integration of a scientific advance into the public consciousness were the actions of respected scientists who raised concerns about the implications of the technology themselves, their engagement in public discussion in a manner that was respectful and informative, the enlistment of a trusted government agency (the NIH) that was capable of reassuring the public that the safety considerations were being addressed, and the decision by elected politicians to leave the regulation in the hands of that agency.
The question I now want to turn to is whether these lessons are applicable to the current debate over the ethical use of human embryonic stem cells. The discovery of human embryonic stem cells is not by any means the only scientific advance that has engendered intense public debate of late, but I chose stem cells because I played a small role in the story by co-chairing an NIH committee that wrote the guidelines for their ethical use by scientists receiving federal funds.
It was in the early 1980s that the British scientist Martin Evans and his colleagues at Cambridge University discovered the remarkable potential in the handful of cells comprising the inner cell mass of a mouse blastocyst to grow continuously in culture, and then contribute to every cell type in the body when reinserted into a “host” mouse blastocyst. Since then many scientists, including myself, have taken advantage of this potential to move between cells in the tissue culture dish that could be modified genetically, and their conversion into a genetically modified animal. We have learned an enormous amount about mammalian genetics in this way. In 1998, two independent groups isolated the human counterpart to mouse ES cells and proposed that such cells would be valuable tools to treat diseases like juvenile diabetes whose underlying pathology involved the death or absence of cells. But the isolation of these cells requires the destruction of a human embryo, and it was this aspect, rather than any concerns about the safety of the potential therapy, that set the public debate in motion.
The American opposition to the isolation of human embryonic stem cells comes primarily from two groups – the Catholic Church and some fundamentalist Protestant sects. They take the position that a single-celled egg, immediately upon fertilization, assumes the moral status of an independent human being, and that its destruction is tantamount to murder. The fact that the embryos have been generated in excess of clinical need during the process of in vitro fertilization is not relevant to the critics, nor does it matter that most of those embryos will ultimately be destroyed or left indefinitely in liquid nitrogen freezers. Nor is this opposed minority moved by a cost/benefit analysis that weighs the cost of destroying a fertilized egg with the potential to form a human being against the benefits that might result from the ability to cure diseases like juvenile diabetes, liver degeneration, and Parkinson’s disease.
Here is where the two scenarios dramatically diverge from one another. The recombinant DNA debate, because it was one primarily about safety, was ultimately one that could be informed and resolved by the application of scientific knowledge. The stem cell debate revolves around deeply held ethical issues, for which there is no single scientifically verifiable right answer. I have students who yearn for a straightforward answer to the question “When does human life begin?” Yet this is not a question around which either a scientific or an ethical consensus can develop. It all depends upon one’s ethical universe: the moment a developing human organism accrues the same rights as adult humans is determined by each individual and is informed by religious beliefs and cultural milieu.
Nevertheless, the question requires a thoughtful public policy response that, while unable to satisfy everyone, serves the best interests of the country. In the United States the question of whether stem cells could be legally isolated and studied in the laboratory was complicated by pre-existing legislation outlawing all research that uses federal funds to study human embryos. President Clinton turned to the National Bioethics Advisory Commission, which he had established in 1995 for just such an occasion, to advise the executive and legislative arms of the federal government on bioethical issues that arise during research on human health and behavior. The Commission was composed of individuals with broad scientific, legal, bioethical, and religious expertise, and was chaired at the time by my immediate predecessor as Princeton’s President, Harold Shapiro. They studied the issue carefully and ultimately recommended that research on both the isolation and use of human ES cells should proceed with federal support, as long as the cells were isolated under regulations that paid strict attention to ethically grounded guidelines for informed consent. In other words, they recommended that the isolation of ES cells be allowed under an exception to the law that prohibited research on human embryos.
Harold Varmus, the Director of the National Institutes of Health during the Clinton administration, was working on a parallel track while the Commission deliberated. Unwilling to take on the Congress, he obtained a ruling from his General Counsel that while the law precluded the generation of human ES cells using federal funds, it did not bear upon the use of stem cells generated either outside the U.S. or by U.S. scientists working in the private sector. This opened the door for groups to study the potential of the cells as therapies for a long list of diseases, as long as the cells themselves were isolated without benefit of federal funds, under a strict set of ethical standards which I helped to draft. Those guidelines were never issued and sat in limbo at the White House until the end of the Clinton term, paralyzed by the President’s lame-duck status and lack of political capital to spend on the issue.
When President Bush came into office, with a very different domestic policy agenda, he was soon bombarded on one side by disease lobbyists eager for the research to move forward and his strong supporters on the right who wanted all work banned. Although two highly respected bipartisan organizations, the NIH and the National Bioethics Advisory Committee, had weighed in on the issue, Bush accepted neither recommendation. The impasse was finally broken on August 9, 2001, when President Bush made the startling announcement that stem cells created before 9 pm on that evening were going to be available for use by federally funded scientists, but that cell lines generated after that moment were off limits. The ethical nuances that make a cell line created at 8:55 pm ethically acceptable to study but one created five minutes later forbidden remain opaque to many, including myself. However, as the number of available lines, originally estimated in the dozens, has dwindled down to a handful, it has become clear that this decision will have to be revisited in the not-too-distant future.
How are we to develop a more thoughtful set of policies on the use of human stem cells? Who should weigh in and who should ultimately decide this difficult and complex question? Of one thing I am sure, without a political culture in which ethically charged science can be conducted calmly, wisely, and predictably, the future of human embryonic stem cell research in particular and scientific progress in general in this country will be uncertain.
It was Sir Winston Churchill, one of history’s foremost parliamentarians, who once admitted to the House of Commons, "Democracy is the worst form of Government except all those other forms that have been tried from time to time." American democracy has given birth to one of the most dynamic nations in history, and in many ways the form of democracy we know is far more elastic, far more responsive, than other democratic models. Yet, American democracy also suffers from shortcomings that impede and distort the formation of coherent and efficacious public policies in the realm of science and other spheres of life, especially when intensely held moral principles and religious convictions are involved.
Having grown up in Canada, with its parliamentary system modeled on the United Kingdom’s, I have been struck by the relative ease and swiftness with which those two countries developed policies that have allowed stem cell research to proceed under carefully monitored regulations. I would like to suggest that one reason for the different outcome in this country lies in the fragmentation of political power in the United States, not between the states and the federal government which after all have their parallel structures in the provinces in Canada, but within the federal government itself. In Canada, the executive and legislative branches of government are inseparable, insofar as the prime minister and his or her cabinet must sit in Parliament and must command a working majority in the House of Commons in order to stay in office. Party loyalty is all-important, for without it, no government could survive a no-confidence motion. Without a unified caucus to sustain them, governments would come and go as frequently as restaurants in Manhattan.
Party discipline is not without its drawbacks, of course, for it tends to muzzle backbenchers and reduce the impact of public opinion. Parliamentary reform in Canada has often tried to elevate the role and broaden the freedom of backbenchers, a group that former Prime Minister Pierre Trudeau once equated with “trained seals.” But party discipline does enable the Prime Minister and his or her cabinet to enact their legislative agenda with far less agony than an American President faced with a hostile Congress, or even a cordial Congress, at the other end of Pennsylvania Avenue.
Party discipline in the United States is far weaker than in Canada, for the simple reason that it can be. The separation of powers, as well as a strong bicameral tradition, gives to our nation’s representatives a degree of latitude and independence unimaginable in Canada. Even when the White House and both chambers of Congress are controlled by one party, there is no guarantee that the members of the ascendant party will see eye to eye. There are many conservative democrats and liberal republicans who could, it seems, live quite contentedly on the other side of the aisle, but it is the structure of our nation’s government, not ideology per se, that allows a representative or a senator or a president to chart a course that diverges from the precepts of his or her party.
Where else, one wonders, could a single senator from the smallest state in the Union obstruct a bill or an appointment that could profoundly affect the nation as a whole?
There is no question that our system of checks and balances is a redoubtable safeguard against the usurpation of power by one organ of government and, to this extent, it serves democracy well. Yet, by diffusing political power so broadly, these checks and balances also weaken government, allowing special interests, with limited popular support, to exert an inordinate degree of influence on policymakers. Enter the lobbyist, a ubiquitous and persuasive breed of advocate who can muster arguments as well as monetary contributions in his or her quest for favorable votes. The central role of money in American public life is well known, but it seems to me that one of its effects is to complicate the formation of a broad political consensus. Except for the immensely wealthy who can boast that no one can “buy” them, our elected representatives are heavily dependent on the financial support of organized lobbies, whose approval or disapproval can make or break an electoral campaign.
I would also argue that the diffusion of political power in this country encourages a level of partisanship that militates against the resolution of divisive social issues. Extreme positions and the harsh rhetoric and intellectual absolutism that accompany them are rewarded in Congress with genuine power, rather than being tempered by the need to speak with one voice as in the House of Commons. The clash of ideas is healthy, indeed vital, but excessive partisanship all too often leads to the oversimplification of complex issues, the drawing of lines, and a refusal to compromise, which exacerbates the structural obstacles to consensus inherent in our political system.
In many cases the United States Supreme Court is left with the unenviable task of ruling on the constitutionality of practices that have eluded resolution elsewhere. Indeed, to quote a recent paper by Harvard’s Professor of Government Andrew Moravcsik, our courts are placed “at the center of domestic redistributive conflicts in a way unmatched in other Western democracies. . . . This is why the American judiciary is the subject of political conflict to an extent unmatched among advanced industrial democracies.” It is easy to fault judicial activism, but as the fierce debate over abortion and other contentious social issues suggests, our nation’s judicial system may have little choice but to assert itself.
I am not a political scientist, much less a politician, but the reflections I have shared with you may help to explain why the fervent opposition of certain sectors of American society to human embryonic stem cell research can have a disproportionate political impact on this field of endeavor, slowing decisive action on the part of our nation’s government or resulting in dubious compromises, such as using the hands of the clock to set the boundaries of inquiry.
I would argue that in our diffuse political system a greater measure of collective responsibility is needed, a principle that lies at the heart of parliamentary democracies in the British pattern. It is not happenstance that stem cell research is proceeding far more smoothly in the United Kingdom, under the terms of the Human Fertilisation and Embryology Act of 1990 and its associated regulations, than in this country. These policies were not enacted without intense debate, but at the end of the day, they were enacted. As Business Week proclaimed in 2002, “In Stem-Cell Research, It’s Rule Britannia.”
The answer, let me stress, is not to create a troupe of “trained seals” or to repress the individualism that is the hallmark of American politics. That would be a terrible disservice to our great democracy. Rather, there must be a willingness to work together in a spirit of responsible statesmanship to overcome even the most intractable political impasses, including those that may profoundly affect the lives of countless Americans with crippling genetic disorders. Until we engage in some true political modification, our progress in the field of genetic modification will falter, and other nations will find solutions to the challenges that confront us all.
If asked to read the future – always a risky enterprise – I would predict that the impetus for a political solution to the questions raised by human embryonic stem cell research will come from scientific developments in other countries. Americans take great pride in being at the forefront of scientific progress and innovation. This is a nation that believes itself endowed with an entrepreneurial spirit that persists as strongly in the lab as it does in the boardroom. This spirit of international competition, most evident during the space race with the Soviet Union during the Cold War, persists even in times of peace, and if foreign governments allow and encourage their scientists to pursue stem cell research that leads to medical breakthroughs abroad, the political pressure to lower the regulatory barriers in the United States will come from both the private sector and the disease lobbyists and will be overwhelming and irresistible. But it is my hope that political pragmatism will win the day and will lead not simply to America adopting sensible standards for stem cell research, but also to America returning to the debate with a stronger understanding of the costs of banning research that a majority of its citizens supports.
Let me conclude by making one last point about these two cases where the rate of scientific progress took society unawares. I said earlier that science is not conducted in a vacuum or an ivory tower, but at the pleasure of the public. That does not mean that scientists won’t continue to determine the specific direction of scientific inquiry, but it does mean that the work must serve the public good over time. When a new discovery raises important questions about the future, scientists have a unique responsibility to ensure that the public debate is based on scientific knowledge, instead of prejudice and ignorance, and to explain the science in clear language that is accessible to a lay audience. Gone are the days when scientists could hide in their laboratories, claiming immunity from the impact that their work might have on society. But scientists have no special claim on wisdom once we leave the scientific arena and come face to face with moral and social questions about the nature of the human condition. The answers cannot and should not come from scientists alone.
We will need a citizenry trained to think clearly about philosophy, moral reasoning, the law, politics, and public policy and who are unafraid to engage and debate scientific issues with the scientists. Likewise we need scientists who are open-minded and unafraid to play their pivotal role in that public conversation, remaining earnestly engaged even when the talk turns away from technical dimensions in favor of ethical ones. That is the challenge that universities like Princeton and NYU must meet as the educators of the next generation of both scientists and citizens.