In preparing to be a guest lecturer in an Introduction to Bioethics class, I have been reviewing information on the Human Genome Project (HGP), the project that many have called medicine and biology’s first example of “Big Science”. Todd Taylor, a noted bioinformatician at the RIKEN Advanced Science Institute in Japan, when reminiscing about the HGP, called it “a once-in-a-lifetime project, something the likes of which we probably won’t see again.”
There are milestone dates that could be used to mark the beginning of the project. However, many set 1990, the year that a formal 5-year plan was published by the U.S. HGP, as the start of the human genome project itself. The document clearly sets the stage for the project as “…a worldwide research effort that has the goal of analyzing the structure of human DNA and determining the location of all human genes.” Over the course of more than a dozen years the project would involve about 24 institutes and thousands of researchers worldwide, leading ultimately to the announcement on April 14, 2003 that the reference human genome had been fully sequenced.
I will return to the Human Genome Project and what has transpired since 2003 in a later posting. More relevant for the bioethics class are the ethical, legal and social implications (ELSI) that were inherent in the international effort to sequence the human genome. With the realization of all the good that could come from increased knowledge of the human genome, a number of complex and controversial issues were gaining increased attention in the late 1980s.
As the story goes, “In October 1988, James D. Watson, the Nobel Prize-winning geneticist, stood before a packed press conference to announce that he had been appointed to head…the Human Genome Project at the National Institutes of Health (NIH). When asked about the social implications of this massive effort to decipher the human genetic blueprint, Watson announced off the cuff…that a fixed portion of the project’s budget would be set aside for studies of how genetics research would impact society. Thus was created what Francis Collins, Watson’s successor, calls ‘the largest investment in bioethics in the history of the world’.”
ELSI Research Program projects accounted for 3-5 percent of the funding that was available for HGP-related projects in the U.S. The programs “…support[ed] examinations and investigations of the ethical, legal and social implications of genetics research. ELSI seeks to inform the development of policies and programs to address those implications, in order to maximize the benefits of scientific research while minimizing the potential for social, personal or psychological harm.”
The list of questions being asked at the time included, “What should people know before having a genetic test? Who will have access to the information the test generates? How will that information be used? Who owns the genetic information stored in each individual’s DNA? What is genetic discrimination?” The ethical issues fell into areas such as:
- Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others.
- Privacy and confidentiality of genetic information.
- Psychological impact and stigmatization due to an individual’s genetic differences.
- Uncertainties associated with gene tests for susceptibilities and complex conditions (e.g., heart disease) linked to multiple genes and gene-environment interactions.
There was a common concern that individuals would be discriminated against “…because of differences in their DNA that increase their chances of getting a certain disease. For example, a health insurer might refuse to give coverage to a woman who has a DNA difference that raises her odds of getting breast cancer. Employers also could use DNA information to decide whether to hire or fire workers.” As a result of these concerns and others, there was a push for federal legislation that would protect individuals from genetic discrimination. The Genetic Information Nondiscrimination Act (GINA), passed in 2008, prohibits discrimination on the basis of genetic information with respect to health insurance and employment.
Francis Collins, who led the HGP effort, and the U.S. National Human Genome Research Institute (NHGRI) until 2008, is “…credit[ed] for making the ethical, legal and social issues of genomics a high priority at the NHGRI.” His passionate advocacy of ELSI issues is also considered instrumental in the eventual passage of GINA. The passage of GINA was considered timely, considering that by 2008, “cheaper sequencing has ushered in a new era of ‘personal genomics’, in which companies are offering all manner of tests that claim to reveal a person’s susceptibility to conditions such as Alzheimer’s disease.”
As we look back on the Human Genome Project and ELSI from the vantage point of 2014, personal genomic information has become widely available, both through direct-to-consumer approaches such as 23andme, and approaches that target cancer or disease therapies based on the specific genetic makeup of the patient. The cost to sequence an individual genome has dropped from about $3 billion for the first reference sequence, to about $1,000 in 2014, thanks to more efficient sequencing equipment and techniques.
And research on the ethical, legal and social implications of low cost, rapidly available genomic information continues as well, with research projects exploring ELSI issues such as the “…impact of Psychiatric, Neurologic & Behavioral genetic information at individual, familiar and societal levels, considering its effects on stigma and self-image,… issues surrounding the application of genomics to infectious diseases and epidemics…and…issues involved in population screening for genetic conditions in the health care of women and children.”
Not to mention ethical issues such as the reported search for intelligence genes being carried out in a genomics institute in Shenzhen, China. As the human genome project was clearly an international undertaking, so too the appropriate review and response to the ethical issues associated with individual genomes must be an international effort. As stated by Eric D. Green, M.D., Ph.D., current director of the NHGRI, “Genomic information will challenge all of us as individuals and as a society as we seek to understand what it means for ourselves, for our families and for our global cultures.”