LeRoy Walters’s Legacy of Bioethics in Genetics and Biotechnology Policy
LeRoy Walters was at the center of public debate about emerging biological technologies, even as “biotechnology” began to take root. He chaired advisory panels on human gene therapy, the human genome project, and patenting DNA for the congressional Office of Technology Assessment. He chaired the subcommittee on Human Gene Therapy for NIH’s Recombinant DNA Advisory Committee. He was also a regular advisor to Congress, the executive branch, and academics concerned about policy governing emerging biotechnologies. In large part due to Prof. Walters, the Kennedy Institute of Ethics was one of the primary sources of talent in bioethics, including staff who populated policy and science agencies dealing with reproductive and genetic technologies, such as NIH and OTA. His legacy lies not only in his writings, but in those people, documents, and discussions that guided biotechnology policy in the United States for three decades.
LeRoy Walters was a central figure in debates about federal policy regarding genetics and biotechnology—a neutral, publicly engaged philosopher and religious studies academic who put his skills to work in national service. His career spanned the emergence of biotechnology as a field in the 1970s until his retirement. His interests reached from moral philosophical theory to Holocaust studies to practical concerns about public policy in genetics. We focus here on the role of bioethics in policy related to the advent of human gene transfer, the Human Genome Project, and the emergence of biotechnology as a commercial enterprise. We focus on his role as an academic influencing the government strand of the “triple helix” of academia, industry, and government. [End Page 51]
FROM THE CONGRESSIONAL OFFICE OF TECHNOLOGY ASSESSMENT (OTA) TO THE DNA PATENT DATABASE
From 1984 through 1995, LeRoy Walters chaired three different advisory panels for the Office of Technology Assessment (OTA) of the U.S. Congress. During that time, he also chaired the Human Gene Therapy Subcommittee of the Recombinant DNA Advisory Committee (RAC) and then the full RAC. OTA operated from 1974 until September 1995. Its projects were prepared in response to requests from committees of Congress, and each project had an external advisory panel of respected experts. Chairs were chosen with particular care to be neutral, well-informed, and skilled in managing committees. It was no surprise, then, that OTA tapped Dr. Walters repeatedly, as he was well-known for being all those things and more.
HUMAN GENE THERAPY
The first OTA advisory panel that Dr. Walters chaired was Human Gene Therapy in 1984, a small study requested by then-Representative Albert Gore, Jr., to address a controversy in the field surrounding the unapproved medical experiments of UCLA’s Martin Cline on patients with thalassemia in Israel and Italy. Dr. Cline circumvented the standard process of institutional review and initiated clinical experiments (outside of the United States) without proper assessment of the clinical risk versus benefit and without getting the required approval from his university’s Institutional Review Board at the University of California at Los Angeles (Schmeck 1981). It was apparent that Cline’s personal ambition, to be the first scientist to conduct therapeutic human gene transfer, was the driving force; little did we know that it would take another three decades for human gene therapy to find its way back into the clinic.
In retrospect, Cline’s experiments were not just premature, but also reckless, simplistic, and sloppy. Moreover, it turned out that Dr. Cline had promised not to use recombinant DNA in his experiment in Israel, but did so anyway (Lenzi, Altervogt, and Gostin 2014, 24). He initiated his experiments quickly, knowing he was unlikely to get approval from UCLA’s Institutional Review Board for either his Israeli or Italian experiments. Moreover, studying individual patients in Israel and Italy precluded the kind of close follow-up that a pioneering clinical study would require. Dr. Cline also got caught in a lie, which irked NIH bioethicist John C. Fletcher, who was directed by NIH Director Donald Fredrickson to get to the bottom of press murmurings of illicit gene transfer experiments. [End Page 52]
Fletcher tracked down Cline by phone in a hotel room. Cline denied the experiments, which nonetheless became public weeks later in media accounts. Reporting on the story, Nicholas Wade wondered if Cline might set back the field of gene therapy “if the public should acquire the notion that scientists cannot be trusted to behave responsibly” (Wade 1980). Cline was ultimately called to testify before the House Investigations and Oversight Subcommittee of the House Science and Technology Committee before Rep. Albert Gore, Jr. (D-TN), where he denied impropriety, indicated that the odds of patient benefit were less than one in a hundred, and asserted that the negative publicity about his work had prevented appropriate follow-up studies of the two treated patients in Italy and Israel (US House of Representatives 1982). One salutary effect of Cline’s sorry saga was a very public debate about the propriety of using recombinant DNA in humans. LeRoy Walters was a major voice in that debate.
The OTA report, Human Gene Therapy, was released at a congressional hearing in December 1984 (see Fig. 1) (Office of Technology Assessment 1984). It received saturation coverage by the national media, mainly because of the usual excellent work of Rep. Gore’s committee staff, who had a knack for captivating national attention.
Dr. Walters’s engagement with human gene therapy was only beginning. Even as the OTA report was underway, he was also named the chair of a working group that became a subcommittee of the Recombinant DNA Advisory Committee. The task at hand was to address the recommendations in the President’s Commission 1982 report, Splicing Life, which called for more systematic oversight of recombinant DNA (President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research 1982). The RAC subcommittee ultimately drafted the “Points to Consider” document that became appendix M of the Recombinant DNA Guidelines, the central document for clinical introduction of DNA into human beings. “Points to Consider” was used by NIH, and later a starting point for FDA regulation of human gene transfer experiments. The work of that RAC subcommittee from the mid-1980s still resonates. Its guidelines, initially drafted in 1985, were quoted in the February 2017 report on genome-editing technologies in humans from the National Academies of Sciences, Engineering, and Medicine: “NIH will not at present entertain proposals for germline alteration” (National Academies of Sciences, Engineering, and Medicine (U.S.) 2017). That sentence was initially proposed by subcommittee member James Childress at a 1985 meeting of the RAC subcommittee, and endorsed and incorporated into the “Points to Consider” after a full-subcommittee [End Page 53] vote by Dr. Walters and William (Bill) Gartland, the chief NIH staff person for the RAC (Office of Recombinant DNA Activities 1985).
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That is the chronology, but what was Dr. Walters’s main contribution? His conceptual framing was a simple two-by-two matrix—with somatic versus germ line on one axis, and treatment of disease versus enhancement of traits along the other. This quickly became a staple for thinking about genetic interventions in the human genome. Dr. Walters did not invent that matrix—it was “in the air”—but he codified it and used it explicitly in his teaching, writing, and the influential Intensive Bioethics Course at Georgetown each summer. Starting with Splicing Life, progressing through the OTA report and RAC guidelines, and up to the recent analyses of [End Page 54] genome editing in the post-CRISPR era, that two-by-two matrix does a great deal of analytical work.
The central policy point has resonated through time: there are indeed many difficult decisions about the long-term future of human beings altering human genomes, but the most urgent, immediate, and technically feasible uses of DNA-based therapy are to treat serious diseases in cells that do not produce sperm and eggs, and in that regard such treatment is not morally different from other treatments that are not heritable. It was not necessary to find consensus on future uses that are heritable, or to draw a line between serious disease and enhancement of traits to make the decision about potentially life-saving uses, once the technology was shown likely to be safe and effective. This was not an argument to defer discussion about fairness, access, or difficulties in defining where to draw lines on the slippery slope along both axes. Heritable changes or not? Treatment or enhancement? Indeed, Dr. Walters endorsed careful attention to those very issues. But the decision to move forward where there was moral consensus and clinical promise did not need to wait. This seems blindingly obvious now, but it was hard intellectual work to articulate that argument in the mid-1980s. However, these issues still remain at the forefront of the ethical debate surrounding the application of CRISPR technology.
Dr. Walters’s role as committee chair was to ensure that the RAC reviews were as unbiased, transparent, and careful as they could be. Dr. Walters’s role here was not as a scholar so much as a purveyor of public process, drawing on his virtues as a careful, trusted figure and exquisitely sensitive listener. The reviews were often hotly contentious. Dr. Walters’s role was to work with the RAC staff to calmly return to the work of assessing evidence of risks and benefits within the published guidelines. But the work was not restricted to only the review process. In 1993, Nelson Wivel, who succeeded Gartland as the RAC official at NIH, wrote an article with Dr. Walters for Science, in which they reviewed the arguments for and against use of germ-line (inherited) genetic modifications. Their thesis was that the debate might not reach consensus, but that the door should be left open, so that if safe technologies were ultimately developed, there might be clinical scenarios in which germ line intervention might command a moral consensus. Their conclusion is worth quoting directly:
Open conflict and extended debate will probably be natural steps in the public discussion of these issues. Germ-line modification could ultimately be regarded as technologically too dangerous to undertake or it could be [End Page 55] viewed as a justifiable approach to preventing certain forms of genetic disease. It would, in our view, be a useful investment of time and energy to continue and in fact to intensify the public discussion of germ-line gene modification for disease prevention, even though the application of this new technology to humans is not likely to be proposed in the near future.
Twenty-five years later, we find ourselves contemplating CRISPR-mediated germ line interventions, with technologies to alter the genome that have advanced, and a renascent debate about whether to apply them to human beings. Martin Cline’s premature experiments found their counterpart in late 2018 in the person of He Jiankui, whose “CRISPR babies” born with deliberately modified genomes, Nana and Lulu (Daley, Lovell-Badge, and Steffan 2019). Those experiments aroused intense international opprobrium.
Dr. Walters’s involvement with gene therapy persisted for a decade and culminated in the monograph that he coauthored with Julie Gage Palmer, The Ethics of Human Gene Therapy (Walters and Palmer 1997). The New England Journal of Medicine review of that book observed “the book succeeds because of its clarity and persuasive ethical reasoning” (Fletcher 1997). The review was written by none other than John C. Fletcher.
The main thrust of the argument, in Splicing Life, in the OTA report, and in the Walters and Palmer book, was to treat introduction of DNA changes in cells of the body that would not transmit inherited changes (somatic cells) no differently from other treatments—to focus on evidence of safety and efficacy and balance risks against potential benefits—but also to foster public debate introducing heritable changes or enhancements of human capacities before introducing genetic changes in a human being. Those arguments have echoed through the decades, including in the 2017 National Academies’ report and the CRISPR baby firestorm.
HUMAN GENOME PROJECT
While Dr. Walters was fully engaged with drafting NIH guidelines for gene transfer in 1985, the idea of a Human Genome Project (HGP) was proposed independently by Robert Sinsheimer (Chancellor of the University of California, Santa Cruz), Renato Dulbecco (President of the Salk Institute), and Charles DeLisi (U.S. Department of Energy). The debate within science was fueled by intense disagreement about whether the project made any sense at all. As the debate about an HGP began, controversy erupted, captured in the news sections of Science and Nature, [End Page 56] and ramified into the popular media. To address and channel the emerging debate, James Watson urged the James McDonnell Foundation to fund a National Research Council (NRC) study, Mapping and Sequencing the Human Genome (National Research Council 1988). The resulting committee was chaired by Bruce Alberts, then of the University of California, San Francisco, and staffed by John Burris of The National Academies (Burris, Cook-Deegan, and Alberts 1998). The Alberts committee investigated the scientific rationale, and reframed the debate for a global Human Genome Project by explicitly incorporating non-human biology and genome mapping into the plan. The NRC report forged a consensus into a sensible scientific template, and deliberately eschewed hype. The NRC report on the HGP was a major reason that Bruce Alberts was later elected President of the National Academy of Sciences for two terms (1993–2005), and then became Editor-in-Chief at Science for a half decade (2008–2013).
In Congress, several champions were enthusiastic about the idea of a genome project, but there were different champions for the National Institutes of Health (NIH) versus the Department of Energy (DOE). The controversy in science was centered on whether the project made sense, and how to proceed if it did. The issues before Congress, however, were less about whether to do it at all, or the technical approaches—as the HGP idea was eagerly embraced by many Members of Congress—but more about which agency should lead, how much money to appropriate to NIH and the DOE, and how the agencies should coordinate their work. Several committees in Congress asked OTA to address these policy questions. Based on his stellar work chairing OTA’s gene therapy panel, Dr. Walters was the obvious choice to chair the advisory panel for the OTA report Mapping Our Genes, which came out in April 1988 (Office of Technology Assessment 1988). He was chosen because he was well versed in genetics, widely known for his impartiality, and was not viewed to have preconceived notions that were biased towards either NIH or DOE.
Five years later, national attention was directed towards the patenting of DNA and an evaluation of the intellectual property policies within this rapidly emerging commercial enterprise. The Supreme Court decision in Diamond v. Chakrabarty in June 1980 signaled that engineered living organisms could be patented (Kevles 1994). After Chakrabarty, the U.S. Patent and Trademark Office (USPTO) began to grant patents on related [End Page 57] inventions, including those arising in molecular and cellular biology. In 1980, Senator Mark Hatfield raised questions about the commercialization of recombinant DNA when Genentech went public with great fanfare. So when a series of DNA patenting controversies surfaced again in the early 1990s, Senator Hatfield cajoled other Members of Congress (most notably, Senators Edward Kennedy and Dennis DeConcini) into requesting that OTA conduct a formal study of DNA-based patents.
The study started in the spring of 1993, when NIH’s patents on expressed sequence tags (short DNA sequences from protein-coding regions) were a hot controversy and still pending before the USPTO (Office of Technology Assessment (draft) 1994). As the study was underway, genes associated with inherited risk of breast and ovarian cancer (BRCA1 and BRCA2) were progressing from discovery into genetic tests. The cloning of BRCA1 and BRCA2 genes and identification of risk-causing mutations were universally lauded as a scientific advance, but the related commercialization strategies erupted in intense controversy. In the United States, OncorMed and then Myriad Genetics began to secure patent rights, which rekindled the DNA patenting issues yet again (Cook-Deegan and Heaney 2010). OTA asked Dr. Walters to chair yet another advisory panel to address “DNA Patenting and the Human Genome Project.”
The OTA study on DNA-based patents was a compromise with Senator Hatfield’s proposal to impose a statutory moratorium on all patents based on DNA sequences. Rather than incorporate a moratorium into legislation, Senators Hatfield, DeConcini, and Kennedy requested the OTA study. When new NIH director Harold Varmus abandoned NIH’s Expressed Sequence Tags (ESTs, or short snippets of protein-coding sequences that uniquely identified corresponding genes) patent applications in 1994, on the advice of patent scholar Rebecca Eisenberg (Eisenberg and Merges 1995), it reduced political pressure to address DNA sequence patents. Republicans took over both houses of Congress after the November 1994 elections, and the new Congress eliminated funding for OTA in 1995 before its report on DNA patents was published. An approved OTA document is public and not copyrighted, but the government never published the report. Georgetown had a contract with the National Library of Medicine to archive and disseminate bioethics material. The Kennedy Institute of Ethics became the only place where the document was publicly available, through Georgetown’s National Reference Center for Bioethics Literature (Office of Technology Assessment (draft) 1994). Dr. Walters and one of us (RC-D) had copies of the approved draft and so Georgetown became its [End Page 58] natural home. Since the report was never formally released, it could not have much impact, but the debate about DNA patents was far from over.
DNA PATENT DATABASE
The DNA Patent Database (DPD) (Hakkarinen and Cook-Deegan 2015) grew out of that OTA project. As the project was getting started, OTA’s extraordinarily talented staff team asked USPTO to identify “human gene patents” it had granted. James Martinell, a senior patent examiner, pulled together a collection of over 1,300 U.S. patents granted 1980 through 1993 that contained at least one claim with a term specific to DNA or RNA, the universe from which human “gene patents” might be selected (https://dnapatents.georgetown.edu/SearchAlgorithm-Delphion-20030512.htm). This was a valuable collection of patents for further analysis, but the analysis was incomplete when OTA was defunded. Prior to OTA’s closure, a contract was negotiated with Georgetown University, through the Kennedy Institute of Ethics, to make the patent collection publicly available as a research tool.
Georgetown was selected for several reasons, both individual and institutional. The main reason was that LeRoy Walters had so capably chaired the project advisory panel, and was regarded as an unbiased party regarding biotechnology patents, which was at the time a notoriously fractious domain of public policy. The institutional rationale was just as compelling. The bioethics library at Georgetown was an international reference resource, and a logical home for the collection. It was completely committed to availability of its resources, the very purpose of making the DNA patents materials available to legal scholars, journalists, bioethicists, economists, and other users.
The Kennedy Institute of Ethics invested some of its own resources into refining the collection and making it public. That included asking both authors of this chapter to read and classify all 1300 patents (some of which were rejected as not meeting inclusion criteria), which we did in 1995 and 1996. Constructing the DNA Patent Database also entailed securing some bioinformatics talent to implement the search algorithms and create web interfaces. Richard Burgess supplied this talent. Then in 2003, one of us (RC-D) refined the search algorithm with research assistant Bi Ade, identifying DNA patents by testing each search term, one at a time, for sensitivity and specificity. Using the refined and tested algorithm, the DNA Patent Database (DPD) was extended to patents before 1980, finding some patents as early as 1971. After 2003, it was updated weekly by members [End Page 59] of the library staff after patents and applications were published by the U.S. Patent and Trademark Office each Tuesday.
What good is a DNA patent database? The legal work of a patent is defined by its claims, a section of a patent that legally describes the boundaries of an invention. If someone makes, uses, sells, or imports something that is claimed in a patent, then they can be sued in federal court for infringement. Patents can be very long and convoluted documents, with deep technical detail. But it turns out that because methods and structures of DNA generate a distinctive vocabulary, it is possible to use a list of several dozen terms to consistently identify patents that claim something about DNA or RNA. This is much harder in many other technical fields, such as software, where patent scholars generally have to read and categorize thousands or tens of thousands of patents by hand because the terms in claims are less specific and search algorithms are thus less sensitive. For DNA, however, it was possible to identify patents and map them to who was granted patents to a field that roughly mapped to genetics and genomics, which were in turn core fields of commercial biotechnology and therapeutics. Moreover, the ratio of DNA-based patents to total patents was an indicator of a firm’s (or a university’s) “genomic intensity,” how much of its work hinged on molecular genetics and genomics as measured by patents.
The OTA project on DNA patenting started two decades before the US Supreme Court invalidated broad diagnostic method claims on “laws of nature” in Mayo v. Prometheus in 2012, and the even more famous case that invalidated claims on DNA molecules whose sequence is found in nature, Myriad v. Association for Molecular Pathology in 2013 (Kesselheim et al. 2013; Rai and Cook-Deegan 2013). And the unpublished OTA report from that project sank beneath the waves two decades before the Australian High Court handed down an even more sweeping invalidation of gene patents in D’Arcy v. Myriad. Yet the arguments for and against patenting, and the nuanced assessment that assessed the value of patents while also acknowledging that their adverse impacts could have on downstream innovation, were aired.
Debates about patent policy can easily devolve into pro-patent and anti-patent camps that talk past one another. There is an entire mini-industry devoted to securing, enforcing, and litigating patents, and most people working in that space accept that patents are vital. In the other camp are some of biotechnology’s critics, who pine for a world without patents. The DNA Patent Database was mainly of use to those living in the killing [End Page 60] zone between the camps, used to study how patents do induce private research funding that might not otherwise be available, but how patents can also hinder innovation if claims are unduly broad, or if important broadly applicable technologies are underdeveloped or overpriced because of exclusive rights.
The DPD was incorporated into Duke’s Center for Public Genomics in 2004, funded by a grant from the National Human Genome Research Institute (P50 HG003391), with LeRoy Walters as Principal Investigator of the DPD core, and Doris Goldstein his co-Investigator. The DPD remained a freely available international database until 2016, when that grant expired and search technology made the need for a specific database of DNA patents less important. The search algorithm became a tool that was modified for studies of DNA patents (Bubela, Vishnubhakat, and Cook-Deegan 2015; Cook-Deegan, Vishnubhakat, and Bubela 2016). The existence of the DNA Patent Database and the studies it enabled were attributable in no small part to the persistence of one LeRoy Walters.
LICENSING GENOMIC INVENTIONS
Dr. Walters was deeply involved in chairing the various OTA activities, but his written scholarship moved toward human rights and other topics covered elsewhere in this volume. One publication, however, exemplifies his role in bringing a team together to address a knotty problem related to DNA patents.
The policy debate about patents is not just about what should be patented—or not—but also about how patents are used. Many genomic discoveries originate in academic laboratories or find practical application by someone or a company other than the inventor, yet the patent rights may be “assigned” by the inventors or licensed by the patent-holder (the assignee). The exclusive rights can thus be transferred, either by assigning them entirely, or by licensing them through contract. This is where the nitty-gritty of patent law often resides. Unlike patents, however, which are public documents (the word “patent” means open), licenses generally are not, and yet the empirical study of patent-licensing is crucial to understand how the exclusive rights are deployed. One highly complex study of patent-licensing was spearheaded by Lori Pressman, whose extensive experience in licensing technologies gave her insight into how licensing might be studied (Pressman et al. 2006). Many of us on the team disagreed about the importance and social benefits of patents, but we worked together to do the difficult analytical work of understanding more about how patents [End Page 61] were being used in practice. The methodology was intricate, and entailed responses from 19 of the 30 institutions with the most DNA patents (a response rate that would have been much lower without the trust the technology licensing offices had in Lori Pressman). The editorial process was correspondingly intense, and LeRoy Walters was the voice of reason and patience, with several iterations of responses to criticisms and editorial critiques from the journal Nature Biotechnology (Pressman et al. 2006). The upshot of the analysis was that licensing was context-dependent, much more nuanced than simple all-use exclusive licenses. One of the most valuable features of the article was direct quotes from licensing officials at universities, giving concrete examples of how they made licensing decisions that differed among broad platform technologies, genetic markers, and research tools. Dr. Walters was not an expert in either patents or genetics, but his practical bent and team-building enabled a rare empirical study of patent licensing.
Even as the part of the HGP that was to produce a reference sequence of the full human genome neared its completion in 2003 and 2004, methods for DNA sequencing became much more diverse, powerful, and fast. In 2007, James D. Watson became the first person to have his individual genome sequenced, followed a few months later by Craig Venter. The original reference genomic sequence generated by the HGP was a stunning achievement. It took more than ten years and cost on the order of a billion dollars; when James Watson got his personal DNA sequence in 2007, it cost several millions of dollars. By 2012, one could get three members of a family sequenced for ten thousand dollars. In one decade, the cost of deriving the initial sequence information dropped by at least 100,000-fold and took weeks instead of years. Kris Wetterstrand prepared an analysis of the “hyper Moore’s curve” drop in sequencing costs for the National Center for Human Genome Research (Wetterstrand n.d.).
One consequence of ubiquitous genomic sequencing and genotyping was the rise of a “consumer genomics” sector. In November 2007, just a month after Craig Venter published his genomic sequence, four companies announced direct-to-consumer genomic services. The personal genome business caught an initial buzz, but then encountered some speed bumps when the Food and Drug Administration and the states of California and New York asserted regulatory authority. New York and California have [End Page 62] statutes governing genetic tests, and FDA noted that the services met the definitions that triggered regulation of medical devices.
The focus of genomics has shifted from a focus on creating DNA sequence data to trying to figure out how to interpret genomic data. Scores of companies are being created to carry out various aspects of that interpretation.
The profusion of genomic data is giving rise to a new sphere of activity that has yet to fully unfold. The process of interpreting genomic data entails comparing data from many individuals. This means that data must be shared, but the data are about individual genomes, and carry with them implications for privacy and confidentiality, a domain of policy in which the rules are unsettled and incomplete (Presidential Commission for the Study of Bioethical Issues 2012). Moreover, genomic interpretation is at least as much a team sport as genomic laboratory science, with an increase in scale and complexity that will challenge those who build their businesses around it. Services will require the involvement of those who send their DNA in the first place, do the analysis, and help people interpret what the information means. These services are only beginning to come into existence, and the business models for this part of biotechnology are almost certain to be contentious and complicated.
So what was the role of Dr. Walters in the policy debates about the emergence of genomic medicine and consumer genomics? He played a crucial role in writing the rules for introducing DNA into people’s bodies, he chaired a committee that proposed policies for the Human Genome Project when the Project was in its fragile gestation, and he shepherded scholarship on the vexing issues surrounding DNA patents.
THE HUMAN LEGACY
LeRoy Walters played an outsized role in national debates about genetics, biotechnology, and public policy. But no Festschrift about LeRoy Walters would be complete without noting his mentoring. We and many others were Telemachus to his Mentor. He had a direct and significant impact on both of our careers. One of us progressed from work with the Kennedy Institute of Ethics to found or co-found several biotechnology and medical device companies and continues in these endeavors (SMc). The other (RCD) worked in health and science policy in Washington, including several years as a part-time academic at Georgetown through grants from the National Science Foundation, the Sloan Foundation, and the Robert Wood [End Page 63] Johnson Foundation’s Health Policy Investigator program. The Kennedy Institute, largely because of LeRoy Walters, was a congenial academic home for policy-oriented scholarship. It also became the repository for an archive of materials on the Human Genome Project (Bioethics Research Library 2015).
And finally, LeRoy Walters’s intellectual and public policy legacy lives on in RAC review of clinical trials involving gene therapy. A promising technology known as CRISPR now promises site-specific modification of human genomes down to the introduction of exact nucleic acid changes (National Academies of Sciences Engineering and Medicine (U.S.) 2017). The first clinical trials utilizing CRISPR (clustered, regularly interspaced, short palindromic repeats) to modify T-cells to become more effective against cancer are just the beginning of a long line of possible applications. The extent of these permanent gene modifications within higher organisms represents an unparalleled challenge to our definition of life and may eventually challenge the statement, “NIH will not at present entertain proposals for germline alteration.” One can only hope that the clarity of vision and systematic openness to divergent moral perspectives that LeRoy Walters brought to the RAC and other governmental oversight bodies carries over into public deliberation about both human genetics and biotechnology for decades to come.
Robert Cook-Deegan, MD, is a professor in the School for the Future of Innovation in Society, and with the Consortium for Science, Policy & Outcomes at Arizona State University. He founded and directed Duke’s Center for Genome Ethics, Law & Policy 2002–2012, and taught in Duke’s in-Washington program through June 2016. Before Duke he worked at the National Academies of Science, Engineering and Medicine; National Center for Human Genome Research (NIH); and congressional Office of Technology Assessment. He obtained his MD from the University of Colorado in 1979; and a BA in chemistry from Harvard in 1975. He is the author of The Gene Wars: Science, Politics, and the Human Genome and over 300 other publications.
Steven J. McCormack, Ph.D., is a serial entrepreneur, executive and investor in the biotechnology and medical device field. He was previously a Senior Fellow at the Kennedy Institute of Ethics and a post-doctoral fellow at the Lombardi Cancer Center, both at Georgetown University. McCormack received his Ph.D. from the Interdepartmental Biomolecular Science and Engineering program from University of California, Santa Barbara. He obtained a bachelor’s degree in biology from the College of the Holy Cross in Worcester, MA.
Supported in part by grants from the National Human Genome Research Institute (P50 HG 003391, R01 HG 008918), and supplemental funding from the Department of Energy, Marion Kauffman Foundation, and FasterCures, a Center of the Milken Institute. We thank research assistant Abhiram Sanka for tracking down and inserting references. The views do not reflect those of the funding institutions.