Address to the Stem Cell Institute of New Jersey
President Shirley M. Tilghman
November 11, 2004
Presented at the Inaugural Symposium, the Stem Cell Institute of New Jersey
I am very pleased to be with you today to celebrate the commitment of the State of New Jersey to stem cell research, and the creation of the Stem Cell Institute of New Jersey. I would like to offer my congratulations to Governor McGreevey for taking the lead in this new initiative, and to Dr. Ira Black and Dr. Wise Young for their willingness to spearhead this exciting endeavor.
I like to think that I have been asked to give this keynote address, not because I am a developmental biologist, nor because I serve as president of Princeton University, but because I am a Canadian. Let me explain. The pioneering work that set the field of stem cell research in motion was conducted in my home town of Toronto in the early 1960s by two Canadians – Drs. James Edgar Till and Ernest McCulloch. They discovered haemotopoetic stem cells in the bone marrow of mice and developed the first rigorous tests of their multi-potency. They showed that a single stem cell could give rise to multiple differentiated cell types by injecting limiting dilutions of the stem cells into lethally irradiated mice. With these experiments, Till and McCulloch established that adult mammals contain cells that are both self-renewing and multipotent – the first adult stem cells – and by so doing they laid the foundation for the first therapy in humans using stem cells, namely, bone marrow transplantation.
It was not until the early 1980s that Martin Evans and his colleagues at Cambridge University provided the definitive evidence for the existence of embryonic stem cells in the inner cell mass of mouse blastocysts. By developing conditions for culturing these cells and then injecting them back into a mouse blastocyst, Evans showed that embryonic stem cells are almost equivalent to the toti-potent fertilized egg, for they can give rise to every cell type in the mouse except the placenta. Thus, the humble mouse, the organism I have spent most of my life studying, was front and center in the development of the field of stem cell biology, not once but twice.
Today, of course, the major spotlight on stem cell research has switched from fundamental research in mice to potential applications in humans. That is not to say that we do not have a great deal more to learn from studies in model organisms. There are still enormous conceptual and technical hurdles to overcome before stem cell therapy becomes a reality – we have still to learn, for example, whether the genomes of embryonic stem cells created by nuclear transplantation can be efficiently reprogrammed so they are capable of full multi-potency or whether the mis-regulation of their imprinted genes will make them unsafe for use in humans. We do not as yet know whether stem cells can be directed unilaterally to differentiate into specific cell types or how to deliver cells either before or after differentiation to specific sites in the body. In my view, we are very much at the dawn of this field.
At the risk of being something of a wet blanket at a coming out party, I would like to raise two risks that I see on the horizon for stem cell research that could impede its potential for improving human health. The first, to co-opt a phrase that Federal Reserve Board Chairman Alan Greenspan used to describe the economic boom of the 1990s, is succumbing to irrational exuberance. I am sure that many of you in the audience have cringed in the face of newspaper or media reports extolling the promise that stem cells will cure everything from Alzheimer’s disease to halitosis. The newspapers and TV commentators did not make this up – they got their information from scientists themselves who practice a variation of irrational exuberance. Some of this comes naturally to scientists – after all, you cannot persevere in science if you do not have the frame of mind that says, “Tomorrow the experiment will work, despite good evidence to the contrary.” Indeed, eternal optimism is almost a precondition for a successful scientific career. However, some of the public pronouncements in the field of stem cell research come close to over-promising at best and delusional fantasizing at worst. In either case, such pronouncements do not serve the long-term goal of developing effective treatment for diseases.
The reason I am concerned about this issue is that there is a vivid precedent that illustrates the dangers of over-exuberance, namely, the field of gene therapy. The possibility that genes themselves would prove to be good therapeutic drugs was first proposed in the early 1970s, and by the early 1980s the field was in full swing. From the outset, in my view, scientists involved in gene therapy research underestimated the technical difficulties as well as the date when viable therapies would be available. They overestimated the numbers of diseases that would benefit from gene therapy, raising the expectations of suffering patients. Clinical experiments were undertaken that had no good foundation in basic research, and the experiments were so anecdotal that no reliable conclusions could be drawn. Eventually, in 1995, with no substantial progress toward gene therapy for any disease on the horizon, Harold Varmus, then the Director of the National Institutes of Health, asked Dr. Stuart Orkin at Harvard and Dr. Arno Motulsky of the University of Washington to conduct a thorough review of the field. Their bluntly worded conclusions were devastating. Here is what they wrote in their report:
“Expectations of current gene therapy protocols have been oversold. Overzealous representation of clinical gene therapy has obscured the exploratory nature of the initial studies, colored the manner in which findings are portrayed to the scientific press and public, and led to the widely held, but mistaken, perception that clinical gene therapy is already highly successful. Such misrepresentation threatens confidence in the field and will inevitably lead to disappointment in both medical and lay communities. Of even greater concern is the possibility that patients, their families, and health providers may make unwise decisions regarding treatment alternatives, holding out for cures that they mistakenly believe are ‘just around the corner.’”
The next blow to the reputation of this field came in 1999 when a young man named Jesse Gelsinger died in a gene therapy feasibility study at the University of Pennsylvania. This event discredited not just the researchers involved, but the field as a whole. A black cloud still hangs over it, discouraging bright young people from studying gene therapy and putting everyone, the serious scientist and the dilettante alike, under heightened scrutiny. As of today, 25 years after the beginning of gene therapy research, the FDA has yet to approve a single protocol.
This is not a scenario that anyone would wish on a new and exciting field. As the public interest in stem cell biology has increased, and as stem cells have become the subject of intense political debate over the last four years, the temptation to over-hype and over-promise in order to make a political point has been very great indeed. The temptation to cut corners in the laboratory and to proceed to clinical trials well before basic studies into the efficacy of stem cell therapy have been completed in animal models has also been apparent. Given its stellar leadership, both temptations, I am sure, will be resisted here at the Stem Cell Institute of New Jersey.
My other cautionary tale (or wet blanket if you prefer) is directly related to the attention that embryonic stem cells have received at the hands of politicians, pundits, and pollsters (who, by the way, are not to be confused with nattering nabobs of negativism) during the election season we have all just endured. One take-home lesson is that today’s scientists must occasionally step outside the laboratory and discuss the scientific facts that underlie policy issues with their fellow citizens. This exchange is essential in any society but especially in a democracy, where public policies forged in the absence of good scientific input will ultimately fail.
The difficulty, of course, is that the stem cell political debate revolves around deeply held ethical and religious beliefs, 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. Precisely when a developing human organism is judged to have accrued the same rights and privileges as adult humans depends on one’s ethical perspective, which, in turn, is informed by one’s religious beliefs and cultural milieu, as well as by science.
Nevertheless, the question that lies at the heart of the stem cell political debate requires a thoughtful public policy response that, while unable to satisfy everyone, serves the best interests of the country. The current impasse, whereby federal funds are only available to study what is now a handful of cell lines – all of which have been grown on mouse feeder cell lines that make them inappropriate for human use – is metastable, just like the lines themselves, which will eventually give out. Yet, barring a sudden shift in the political winds, this impasse is unlikely to be broken in the immediate future. The decision of the states of New Jersey and California to fund stem cell research is admirable, but even the $3 billion bond that just passed in California cannot compensate for the absence of federal dollars for research in this area.
Furthermore no one, I suspect, would argue that it is sound public policy for individual states to hold referendums on funding for specific areas of scientific research. The success of U.S. biomedical science has benefited from a priority-setting process at the NIH in which scientific opportunities are judged against one another, with peer review determining the best science to support. The decisions to allocate state resources for stem cell research in New Jersey and California are precedent-setting for this country, and the implications need to be carefully thought through. In the spirit of this inaugural symposium, I am happy to announce that PRIOR, a program at Princeton’s Woodrow Wilson School dedicated to fostering research relevant to the tri-state area, is planning a conference to address the economic and policy implications of significant state funding of stem cell research. This conference, tentatively scheduled for April, will bring together policymakers, industry representatives, venture capitalists, and academics to examine the challenges associated with launching and regulating successful state stem cell initiatives and the potential benefits associated with these programs.
In the long run, we need to develop a nationwide set of policies on the use of human embryonic stem cells. Who should weigh in and who should ultimately decide this difficult and complex question? I do not have a clear answer, but of one thing I am sure: without a political culture in which ethically charged science can be rationally discussed, the future of human embryonic stem cell research in particular and scientific progress in general in this country will be uncertain at best.
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 this and 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. If state and 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 throughout the United States will come from both the private sector and the disease lobbyists, and it 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 and ethical 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 returning to an earlier observation. I suggested 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 will not 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. On the other hand, scientists have no special claim on wisdom once they 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 that is trained to think clearly about philosophy, moral reasoning, the law, politics, and public policy and does not hesitate to engage and debate scientific issues with 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 must meet as the educators of the next generation of both scientists and citizens.
Once again, let me congratulate all who have worked to establish this Institute in New Jersey. The road ahead is not straightforward, but despite the cautions I have offered, it is a hopeful road and one that must be followed to the end if scientific knowledge is to be expanded and the quality of human life improved. Thank you and good luck!