Genomics, Ethical Issues in

Improvements in our ability to analyze and understand DNA will have ethical implications for society. The most important issue stem from DNA’s ability to predict an individual’s future, during his or her life, at birth, as a fetus, as an in vitro embryo, or even before conception. There will also be ramifications for health care, in establishing identity, in revealing the past, through genetic manipulation, on ownership and control of genetic material and information, and in cultural understandings of humanness, race, and the roles of nature and nurture. Genetics, both as a field and as a word, was born in the early twentieth century. The ‘new’ genetics referred to the vast increase in the power of genetics that followed the increased understanding of the biochemical basis for genetics in deoxyribonucleic acid (DNA). That understanding has made it possible to ‘read’ the sequence of DNA in organisms, including humans; to discover, in some cases, the physiological significance of that sequence; and to contemplate changing the sequence in order to attain desired ends. These heightened powers have both created new ethical and social concerns and exacerbated older ones. The first edition of this article was written in 2001. The major development since then has been the growth of ‘genomics.’ Impressive advances in testing, sequencing, and manipulating DNA mean we can do much more with and to DNA – faster, cheaper, and more accurately – than imagined 13 years ago. Various methods of testing first hundreds, and ultimately millions, of ‘single nucleotide markers’ in a human genome using ‘SNP chips’ now cost less than $100, leading to their widespread use in the last 15 years in scientific ‘genomewide association studies’ (GWAS) as well as in consumer genomics companies. GWAS still test under a thousandth of the whole human genome, but the first reasonably complete human genome sequence was finished in 2003. It cost about $500 million (depending on the accounting conventions used). In 2014, high-quality whole human genome sequences are routinely available for about $3000 with several firms recently announcing their ‘$1000 genomes.’ These new largescale capabilities have shifted the focus of scientific interest from individual genes to whole or partial genomes; the scientific language has similarly been moving from ‘genetics’ to ‘genomics,’ as will, largely, this article. At the same time, the major ‘nondevelopment’ has been the creeping pace of our ability to understand the effects of different DNA sequences. A major question of the last decade has been the mystery of the ‘missing heritability’ – researchers know, for example, that about 90% of a person’s adult height comes from his combination of his parents’ genes, but thus far only 10–20 percentage points of that heritability has been attributed to specific DNA sequences. As a result, the consequences of the unexpectedly enhanced sequencing capabilities of genomics have been smaller than we would have imagined. Concern about implications of the new genetics for human societies grew with scientists’ ability to decipher and manipulate DNA. The late 1960s saw discussions of human cloning, followed in the 1970s and early 1980s by safety concerns about recombinant DNA and social concerns about genetic discrimination. When the Human Genome Project was proposed for substantial funding in the United States in the late 1980s, the Project’s first director, Dr James Watson, suggested that 5% of the funding be set aside to study the ‘ethical, social, and legal implications’ (ELSI) of human genetics (Cook-Deegan, 1994). The subsequent financial commitment led to the rapid expansion of ‘ELSI’ studies across many disciplines and the publication of a vast number of articles and books on these topics. The technical advances brought by genomics have accelerated the timing of some ethical, social, and legal issues, but, because of the slow pace of understanding, neither broadly nor dramatically. Three general caveats are useful in surveying the resulting discussions of either the ‘new’ genetics or the ‘new’ genomics. First, although these new technologies often provide great power, for prediction, or for intervention, they seem unlikely to provide the extent of power often assumed in the writings about their implications. Oftentimes, their predictions will be weak; the percentage of people with a particular set of genetic variations (or ‘genotype’) who develop a particular trait of condition (or ‘phenotype’), a percentage known as ‘penetrance,’ will often be low. Second, although the technologies are quite novel, their implications almost always have parallels in the social effects of other modern technologies. And third, although much of the discussion of the consequences of genomic technologies has focused on individuals or families, these technologies usually also have implications for broader human groupings. With those caveats in mind, this article will discuss the ethical, social, and legal effects of the new genomics in seven areas: health care, establishing identity, predicting the future, revealing the past, genetic manipulation, ownership and control of genetic material and information, and cultural understandings. Issues Arising from Medical Successes Writing on social issues of genomics focuses on the dangers of human genomics misused – lost privacy, genetic discrimination, state-enforced eugenics. It rarely looks at the potential implications of the hoped for uses of genomics to prevent and 32 International Encyclopedia of the Social & Behavioral Sciences, 2nd edition, Volume 10 http://dx.doi.org/10.1016/B978-0-08-097086-8.82011-5 treat diseases. The vast sums, both private and public, being spent on research in genomics are not being committed from an altruistic search for knowledge, but in the expectation that the research will bring immense medical benefits. The diseases in question may not be limited to ‘genetic diseases’; genomic tools are allowing unprecedented understanding, at the molecular level, of the proper and diseased functioning of human cells and of human pathogens. The most powerful lesson of the first 40 years of the biotechnology industry has been that the human body and its functions are more complicated than expected, but those complications are steadily being tackled with genomic tools. A stream of new treatments, derived from increased knowledge of genomes and their associated proteins, is flowing through research, development, and regulatory approval, not as quickly as one would like, but persistently. What will happen if these drugs succeed? It is possible that the results might include, among other things, a significant extension of average human life span; an increase in pharmaceutical costs; and changes, up and down, in the demand for various medical services. The social implications could be substantial, on everything from pension plans and political voting blocks to health care systems. Some more focused medical consequences of genomics research, such as individualizing patient therapies as a result of genomic tests (known as ‘pharmacogenomics’), or some kinds of proposed genome therapy or tissue replacement will require that treatments be created just for one patient, thus straining the existing mechanisms for drug development, manufacturing, approval, and financing. And any new treatment will raise questions of availability, both within any one country and between countries. Genomics has created a uniquely high expectation of medical progress, which it has used to acquire funding, both public and private. If it comes close to the successes it has promised, these consequences may be raised in dramatic form. Establishing Identity Genomics raises four main issues centering around identity: forensic identification, personal identity, family identity, and ethnic identity. Forensic Identification By the mid-1990s, the new genetics was leading to major changes in forensic identification. Any tissue from a person that contains DNA can be tested for a pattern of identifying markers, sections of the genome that vary substantially from one person to another. Those markers can be compared with the markers analyzed from human tissue found in connection with a crime (National Research Council, 1992). New and powerful techniques for analyzing DNA mean that samples with only tiny amounts of genetic material can be useful, whether derived from flesh, blood, semen, or even the cells found in saliva. A negative test is very powerful. If the markers are significantly different, the tissues cannot be from the same person (unless the sample was swapped or contaminated or in a very rare case where a single person because of embryonic merger, has some tissues with one genome and some with the genome of a never-born twin). Initially, there was concern that a positive match might not be very compelling because patterns of markers might be relatively common among particular ethnic populations. That could make the odds that a match was a coincidence vanishingly small among the general population but relatively high among people from that particular ethnic group. These fears were largely assuaged through both more information on the distribution of themarkers used in forensics and different techniques (National Research Council, 1996). This forensic use of DNA is not essentially different from the use of fingerprints, blood groups, or dental records. Like those techniques, it has had to prove its effectiveness in a host of judicial cases. And, like the earlier techniques, the DNA itself can never be conclusive. Good defense counsel will always investigate the possibilities of an innocent explanation for the presence of the DNA or for mistakes, contamination, or fraud in the DNA collection and analysis process. Juries and judges might pay more attention to DNA evidence because of the high status and reputation of the science, but that effect should also fade with greater familiarity (and good defense counsel). The real issues about the forensic use of DNA now concern not the individual case, but the collection and retention of DNA or DNA records for identification purposes. One issue concerns surreptitious collection by the police of DNA from suspects, either through an interaction with them, such as offering them something to drink and getting their DNA from the discarded container, or merely by collecting DNA from items they have had contact with, from cigarette butts to eating utensils. More broadly, many countries or states have created DNA repositories with DNA samples taken from convicted, or even merely accused, criminals. These samples can be used to seek matches in criminal cases or for the identification of human remains. If markers from the samples are analyzed in advance, the results can be put into a database and used to seek ‘cold matches’ to samples or tissue of unknown origin. These repositories raise two different issues. The first involves their creation. Should samples be accepted only from those who consent or should they be mandatory? If mandatory, what classes of people should be required to provide samples – convicted sex offenders, convicted felons, all those arrested, or the whole population? Litigation on this issue has become increasingly common in the United States, where all states have some form of mandatory DNA repository (Maryland v. King). A subtler, but equally important, issue concerns what the repository should contain: information on what, and how many, genetic markers? And should the DNA samples from which the profiles were derived be retained or destroyed? The markers currently used for forensic identification, as far as scientists can tell, are not strongly associated with any traits (other than sex) (Kaye and Greely, 2013). If the markers are kept, no information about a person other than identity (and possibly ancestry) can be deduced – nothing about genetically influenced disease susceptibility or other traits. (Using new markers as is currently under serious consideration, could change that.) If samples of whole DNA are kept, however, they can be reanalyzed to confirm that the profile is accurate, which may be important in some contexts, such as some international sharing arrangements. But the samples could also be analyzed for DNA associated with a wide variety of traits. This raises Genomics, Ethical Issues in 33