Law, Bioethics, and Biotechnology

Law, Bioethics, and Biotechnology Michele Goodwin, University of California – Irvine, Irvine, CA, USA Allison M Whelan, University of Minnesota, Minneapolis, MN, USA Ó 2015 Elsevier Ltd. All rights reserved.

Abstract This article examines the emergence of bioethics as a legal discourse and the relationship between technology and bioethics. As a field of study, bioethics functions as a tool to analyze the multifaceted conundrums presented by modern medicine and a way by which those problems can be addressed. This article provides an overview of this broad field of study, beginning with the development of the Nuremberg Code, Declaration of Helsinki, and Belmont Report, and addressing the pivotal medical cases that ultimately spur legislative action, the drafting of codes of professional ethics, and the shaping of legal discourse. The article offers insights on several twentieth-century cases that inspired the development of bioethics in the United States and beyond and has since influenced the development of bioethics and technology throughout the world.

Introduction According to Warren Thomas Reich, the term ‘bioethics’ emerged in 1971 – coined by Van Rensselaer Potter, one of the first scholars to advocate establishing a discipline of bioethics (Reich, 1994: p. 320). Potter explained bioethics as “a new discipline that would combine human value considerations with science in general and especially with the ‘realities’ of biological science in the Man/Earth relationship” (Potter, 1971: p. 1088). A few years later, Potter also endorsed a similar definition put forth by Dr. LeRoy Walters, Director of the Kennedy Institute Center for Bioethics (Potter, 1975). Walters described bioethics as “the study of social and ethical questions motivated by developments in the fields of biology and medicine, and includes subject matter drawn from the natural and social sciences and the humanities” (Potter, 1975: p. 2299). However, the professional standards and ethics framework known today as ‘bioethics’ began shortly after World War II in a movement to ‘humanize’ medical education and practice, largely in response to the atrocities carried out by Nazis on Holocaust victims (Pellegrino, 1999: p. 75; Annas, 2009). Bioethics reflects the convergence of several discourses: law, theology, medical ethics, and philosophy, into a general framework that attempts to answer complex questions that frequently place the individual, medical providers, society, and the state in ethical conflict. Those who frame the field – bioethicists – identify thorny medical dilemmas and attempt to provide clear, normative recommendations to address the challenges of contemporary medical research and delivery. By extension, bioethicists attempt to answer unsettled ethical and moral dilemmas trapped within the intersections of law, medicine, and technology. The dominant moral dilemmas that frame traditional bioethical concerns address medical experimentation on vulnerable subjects, physicians assisting their patients in suicide or euthanasia, scarce resource allocation and medical futility, human trials to develop drugs, organ and tissue donation, cloning, xenotransplantation, abortion, human enhancement, mandatory vaccination, and much more. The term ‘bioethics’ provides a lens, language, and guideposts to the study of medical ethics. It is worth noting, however, that medical experimentation is neither new nor exclusive to one country.

International Encyclopedia of the Social & Behavioral Sciences, 2nd edition, Volume 13

Cleopatra, for example, is alleged to have facilitated medical research on her handmaids by authorizing their impregnated wombs cut open for medical experimentation (Bolton, 1881: p. 4354). In 1796, Edward Jenner, an English physician, injected cowpox into James Phipps, a healthy 8-year-old boy (Reidel, 2005: p. 24). In the 1840s, an American gynecologist, Dr. Marion Sims, who is hailed as the ‘father of gynecology,’ conducted vaginal experiments on slave women without the aid of anesthesia (Kuhn McGregor, 1998: p. 44). In 1900, Walter Reed injected nearly 24 immigrant workers in Cuba with the agent for yellow fever (Cefrey, 2002: p. 29). In the late 1920s, several children in Lubeck, Germany, died from accidental exposure to a lethal tuberculosis vaccine (Coberly and Comstock, 2006: p. 76). In that same decade, Japanese military officials experimented with germ warfare, killing thousands. During the early twentieth century, governments often justified brutal experiments as necessary to protect national security or promote the public health (Harris, 2003). These two rationales remain potent. Increasingly, economic concerns are included under the broader umbrella of bioethics. For example, should markets serve as an answer to the perceived organ shortage? Should governments rein in the modern-day outsourcing of gestational surrogacy? Bioethics finds its relevance in the persistent absence of formal law on contemporary ethical research problems. Some scholars claim that biotechnology doggedly outpaces law, stretching its reach far beyond the slow, lagging legislative process, which they argue forestalls rather than enables the development of coherent, rational controls over the direction of biotechnologies. In this context, legal rules result by default and happenstance rather than rational engagement. Much like law and economics, feminist jurisprudence, and other ‘new’ areas of law, bioethics is an expanding discipline, gaining traction as an authoritative and even necessary method of evaluating medical–legal conflicts. This article tracks the trajectory of modern bioethics, assessing the rise of bioethics, which can in part be attributed to deeply entrenched formalism in the legal jurisprudence, and its turn toward professionalism in the medical and legal academies. It discusses how international tragedies gave rise to guiding documents and principles that ground contemporary bioethics (autonomy, nonmalfeasance, beneficence, and social justice) and explains that as

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technology forges ahead, law and the manufacture of legal rules often lags far behind. The field of bioethics often serves to fill in the gap, offering philosophical insights grounded in law, philosophy, and values to address health care dilemmas. In recent decades, bioethics has contributed to the intellectual ordering of modern medicine and law.

Early Beginnings: World War II, Nuremberg, and the Modern Bioethics Movement

conducted by the International Military Tribunal at Nuremberg and were presided over by judges from the four Allied powers (Annas, 2009). The Trials contributed to the articulation and establishment of well-recognized human rights principles in law and bioethics, namely that voluntary consent is an essential component of any medical experiment; any experiment should avoid subjecting the participants to unnecessary suffering; and research subjects must be at liberty to withdraw from human experimentation at any time (The Nuremberg Code, 1949).

Nuremberg Code Perhaps the oldest foundational tenet of bioethics can be traced to Hippocrates, the ancient Greek physician credited with the ‘Hippocratic Oath,’ a pledge commonly taken by new physicians and other health care providers to protect and hold patients’ interests above their own. The core of the pledge reflects the Latin edict primum non nocere, ‘first do no harm,’ a moral injunction embraced by health care providers – even if its origins remain somewhat a mystery (Smith, 2005). To this day, the delivery of medicine presents moral, legal, and ethical challenges uneasily resolved by medicine alone. Among these are the demands for medical and scientific information and the use of human participants in nontherapeutic studies to acquire data. Frequently, mixed incentives dominate contemporary biotechnology and medical research practices, sometimes aligning the interests of patients and researchers and at other times subordinating patients’ needs to scientists’ priorities, such as patenting discoveries, achieving tenure, fame and wealth, gaining notoriety, and assisting national security through military experimentation. Internationally, governments have justified nonconsensual medical experiments conducted on children, the mentally ill, prisoners, and soldiers based on national security. The collapse of Nazi Germany, the unearthing of medical experiments carried out against Chinese and Russian prisoners of the Japanese during World War II, and the subsequent trials at Nuremberg, where ‘Third Reich’ physicians and researchers revealed the mass horrors of their human experimentation and broader brutality in the quest for scientific knowledge mark the beginnings of contemporary bioethics. Documents, including photographs and witness statements uncovered after World War II, reveal grotesque research and experimentation conducted on vulnerable populations in China, Poland, and Germany. At a Chinese outpost, for example, the Imperial Japanese army erected a covert military installation where researchers “expose[d] prisoners to [sub-zero temperatures] to . freeze them and then try various techniques to literally dehydrate them, to see what was the most effective way of dealing with frost bite, so that that could be used in warfare as well, both to protect Japanese troupes as well as to effect the enemy” (Targeted Individuals Europe, 2011). At least 3000 died as a result of Japanese medical experimentation. Japanese officials attempted to justify experiments “to develop weapons of biological warfare, including plague, anthrax, cholera and a dozen other pathogens” based on national security interests (Kristof, 1995). In Germany, the Third Reich conducted similar atrocities against Jews and others. Their murderous experiments resulted in an international trial. The Nuremberg Doctors’ Trial, one of 13 trials at Nuremberg, began in 1946 and concluded 1 year later. The trials were

The Doctors’ Trial (‘Trial’) stood apart because only judges from the United States presided over those prosecutions (Annas, 2009). At the Trial, prosecutors accused 23 physicians and scientists of performing “murderous and torturous experiments” in the Nazi concentration camps, such as highaltitude and freezing experiments, which resulted in the planned and expected deaths of research subjects (Annas, 2009: p. 21). Researchers who planned and conducted the experiments justified their research on nationalist-medical grounds, claiming the results could benefit German pilots and the broader, German common good (Annas, 2009). Prosecutors also pointed to more than 350 000 forced sterilizations conducted under the Nazi’s eugenics regime. In response, Nazi doctors proclaimed that prosecutors were blinded by hypocrisy and exceptionalism, as the U.S. also engaged in eugenics by permitting the broad-scale sterilization of individuals considered socially or mentally unfit. As proof, Nazi doctors cited Justice Oliver Wendell Holmes’ opinion in Buck v. Bell, a 1927 U.S. Supreme Court opinion sanctioning compulsory sterilization of the ‘feeble-minded’ (Buck v. Bell, 274 U.S. 200, 205 (1927)). Despite this creative defense, which cast light on U.S. involvement in eugenics, seven of the Nazi doctors were eventually sentenced to death by hanging (Annas, 2009). From this historical perspective, the Nuremberg Trial ushered in modern bioethics. The field’s first code of ethics, The Principles of Nuremberg (commonly referenced as the Nuremberg Code), emerged directly from this landmark prosecution (The Nuremberg Code, 1949). The Principles of Nuremberg, a tenpoint statement governing human experimentation, recognized voluntary consent as a central tenet of human research and emphasized that research ought to benefit the social good and doctors ought to prioritize the avoidance of suffering. The 10 principles continue to serve as a framework for medical ethics: 1. Voluntary consent of the human subject is essential. 2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature. 3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study, that the anticipated results will justify the performance of the experiment. 4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. 5. No experiment should be conducted, where there is an a priori reason to believe that death or disabling injury will

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occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment. During the course of the experiment, the human subject should be at liberty to bring the experiment to an end, if he/she has reached the physical or mental state, where continuation of the experiment seemed to him/her to be impossible. During the course of the experiment, the scientist in charge must be prepared to terminate the experiment at any stage, if he/she has probable cause to believe, in the exercise of the good faith, superior skill, and careful judgment required of him/her, that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject (The Nuremberg Code, 1949).

Subsequent documents, specifically the Declaration of Helsinki and the Belmont Report, further developed the bioethics cannon (as discussed below). Despite near-global agreement that Nuremberg was the birthplace of modern bioethics, some scholars regard the origins of American bioethics as deeply rooted in a subsequent era, the 1960s, a time of heightened medical paternalism. If American bioethics was a phenomenon of the 1960s, the U.S. model of medical philosophy could be distinguished from that of the rogue terrors of Nazi Germany. Albert R. Jonsen, for example, describes the Nuremberg Code as a “beginning that would become bioethics,” but places greater emphasis on later developments, such as the Declaration of Helsinki (Jonsen, 1998: p. 134). Similarly, David J. Rothman (1991: p. 62) argued that the Nuremberg Code ‘might have served’ as a model for American bioethics, but ultimately emphasizes the 1960s as the beginning of modern American bioethics. According to Rothman, the Nuremberg Code was not fully taken up in the United States because “the events described at Nuremberg were not perceived by researchers or commentators to be directly relevant to the American scene. The violations had been the work of Nazis, not doctors; the guilty parties were Hitler’s henchmen, not scientists. . Madness, not medicine, was implicated at Nuremberg” (Rothman, 1991: pp. 62–63). Notwithstanding this account, the Nuremburg Code continues to have tremendous influence in the field of bioethics.

Declaration of Helsinki In 1964, the World Medical Association issued the Declaration of Helsinki on human research (World Medical Association, 2008). Debates emerged about whether the declaration served as an alternative to the Nuremberg Code – which many physician-researchers considered ‘overly rigid’ because of its

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forceful edicts and focus on the health and well-being of research subjects – or as an enhancement to the prior document. In the end, the most salient aspects of the Nuremberg Code and the Declaration of Helsinki are quite similar, as both provide guidance to physicians engaged in human subjects research, emphasizing the need to prioritize the individual’s health and well-being above all other goals. A decade later, the gathering strength and relevance of a bioethics framework within the legal and medical academies culminated in The Belmont Report, drafted in 1979 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research sponsored by the U.S. Department of Health, Education, and Welfare (DHEW). The Report proposed “to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles” (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1979). Their efforts began in the wake of the discovery of the Tuskegee Syphilis Study.

Concretizing Medical Bioethics and Responding to Biotechnology Paramount to the continued development and refinement of a bioethics agenda were two issues (1) researchers’ disregard of the lofty aims of the Nuremburg and Helsinki declarations; and (2) the perception of law’s failure to take seriously or incorporate the field’s principles into practice. By the 1970s, the demands for a respected and legally sound bioethics agenda became clear due to global controversies involving human experimentation as well as the rapidly expanding fields of medicine, including organ transplantation, sophisticated pharmaceutical therapies, and improved biotechnologies. More than any other country, however, the U.S. advanced at the forefront of both biotechnologies and experimentation. Between the 1950s and 1970s, American physicians, scientists, and government agencies rapidly expanded medical and biotechnological knowledge through human experimentation. A cursory view of this time period provides a glimpse of the depth and range of unethical and illegal experimentation conducted by researchers. 1950: Dr. Joseph Stokes infects 200 women prisoners with viral hepatitis. 1952–74: Dr. Albert Kligman conducts skin experiments on inmates at Holmesbrook Prison. 1953–57: Uranium is injected into nearly a dozen patients at Massachusetts General Hospital. 1953–1960: Central Intelligence Agency conducts Lysergic acid diethylamide (LSD) experiments on hundreds of subjects. 1950s–70s: U.S. Army studies 2300 Seventh Day Adventist soldiers. 1960s: Pharmaceutical companies test 150 experimental drugs on prisoners in Pennsylvania (Hassner Sharav, n.d.). It became apparent from medical experiments in developing nations, as well as the Tuskegee Syphilis Study in the U.S. (discussed below) and increased medical rationing of sophisticated technologies, that race, sex, and class served as

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moderating forces in the acquisition of biotechnological knowledge and delivery of health care. In 1974, U.S. law governing human research finally came to fruition – in significant response to the infamous syphilis study. The National Research Act, enacted by the 93rd Congress, provided a federal response to human research conducted in the U.S. imposing guidelines for researchers and establishing a bioethics commission to advance further recommendations. The law created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission), mandated voluntary, informed consent from all persons participating in studies funded through the DHEW, and required that all research funded through DHEW be reviewed by institutional review boards (IRBs). The end result was the ‘Belmont Report,’ which introduced what are now considered foundational bioethics principles: (1) respect for persons, (2) beneficence, and (3) justice (The Belmont Report, 1979: pp. 23193–23194). Today, the four main principles of bioethics are (1) Autonomy, (2) Nonmalfeasance, (3) Beneficence, and (4) Justice. The National Commission served as a blueprint for President William Clinton’s subsequent formation and launch of the National Bioethics Advisory Commission in 1995 and President George Bush’s President’s Council on Bioethics, established in 2001 (Protection of Human Research Subjects and Creation of National Bioethics Advisory Committee, 1995; Creation of the President’s Council on Bioethics, 2001). By the 1990s, European nations responded in three ways as follows: (1) by establishing the International Bioethics Committee in 1993, (2) by creating the 1997 Oviedo Convention on Human Rights and Biomedicine, and (3) by establishing the European Conference of National Ethics Committees (COMETH), which promotes public debate on biotechnologies and health sciences (Council of Europe, n.d.). The overarching goal for COMETH is to research interests against protecting human subjects. In recent years, several major European protocols have been established to address genetic testing for health purposes, cloning, transplantation, and biomedical research.

Cases That Shaped Bioethics Bioethics is shaped by the previously discussed international documents along with a series of pivotal cases highlighting the tensions between medicine, autonomy, and the physician– patient relationship (Fox and Swazey, 2008: p. 215). There is no shortage of cases, both in the U.S. and worldwide, that implicate bioethical principles, particularly as researchers pursue patents or develop new and lucrative drugs. Moreover, much of this research – particularly radiation experiments – were performed on powerless, vulnerable groups – African-Americans, mentally disabled children, indigenous populations, and the elderly. The cases discussed below do not serve as an exhaustive list. Rather these substantial medical ethics breaches offer insight into the relevance of bioethics, given that in each instance the research was passionately defended not only by the research teams, but by scientists in the field. These cases have greatly influenced

the development of bioethics both in the United States and throughout the world.

Research on Women Coercive Contraception During the 1970s, in the wake of women’s liberation movements occurring in some parts of the world, biotechnological human experiments involving unapproved contraceptives were taking place in some countries. In Zimbabwe, for example, studies using the drug Depo-Provera for contraceptive purposes attracted the attention of human rights groups (Kaler, 1998). Human rights activists alleged that the drug was used to control the population. They pointed to the fact that the drug was not approved for contraceptive use in the U.S. where it was manufactured, but was being used for that purpose in rural Zimbabwean communities. Reports emerged that the drug was administered to some women without their consent and sometimes without their knowledge (Rebecca Project for Human Rights, 2013; Sambisa, 1996). Nevertheless, in a paper published in the Journal of Medical Ethics, Professors Malcolm Potts and John Paxman (1984) wrote that despite the ‘circumscribed’ history of the drug’s testing and distribution among poor women in developing nations, to remove it from the market would undermine the choice of women in developing countries to have broad access to various contraceptive medicines. In the wake of investigations, government officials in Zimbabwe banned the drug’s use except for treating kidney and uterine cancer (Kaler, 1998).

Research on the Elderly Jewish Chronic Disease Hospital Study (1963) In 1963, research began at New York’s Jewish Chronic Disease Hospital to study whether the body’s ability to reject cancer cells was due to the cancer itself or to another malady, such as a compromised immune system (Katz, 1972). Previous studies suggested that healthy individuals’ bodies could reject cancer cells promptly and researchers believed that ‘debilitated patients’ would similarly reject cancers, albeit at a substantially slower rate (SUNY Cortland Institutional Review Board, n.d.: pp. 4–5). The study involved the intentional injection of live, foreign cancer cells into 22 senile patients hospitalized with various chronic conditions (SUNY Cortland Institutional Review Board, n.d.). Despite the establishment of the Nuremberg principles and sharp similarities to Nazi experimentation, the study advanced without review board approval or interventions on behalf of the patients. The research subjects were uninformed and misled as researchers convinced patients they would receive a “harmless substance which might cause a slight discomfort” (Morse, 1967: pp. 376–377). The researchers defended the study, claiming they had good reason to “predict that the cancer cells were going to be rejected” (SUNY Cortland Institutional Review Board, n.d.: p. 6). The Board of Regents of the State University of New York subsequently reviewed the study and investigated its lead researcher. The Board concluded that the doctors failed to submit the research protocols to the hospital’s research committee and that the physicians responsible for the patients’ clinical care were not consulted. The researchers were

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found guilty of fraud and unprofessional conduct (SUNY Cortland Institutional Review Board, n.d.: p. 6).

Research on Children and the Mentally Ill Willowbrook Hepatitis Study For decades, children’s bodies provided tremendous resources for human research, despite their inability to consent to medical trials. The Willowbrook hepatitis study, which began in the mid-1950s, is one such example. The was led by Dr. Saul Krugman and conducted at the Willowbrook State School in Staten Island, NY, a facility for mentally disabled children. Willowbrook remains “a potent symbol of unethical research,” with some referring to it as the ‘pediatric Tuskegee’ (Robinson and Unruh, 2008: p. 80). As part of the study, children housed at Willowbrook were intentionally injected with hepatitis to determine the effectiveness of gamma globulin injections in protecting against hepatitis. The research was based on the premise that infection with a mild form of a viral agent can induce immunity. Krugman and others involved in the study justified the research, claiming that given the high prevalence of infection in the institution, it was practically inevitable that the children would become infected, regardless of whether they were enrolled in the study. Researchers concluded that results of the study could be extremely beneficial to society and to the institutionalized children. The doctors claimed the research could potentially control the ‘endemic situation’ at Willowbrook. And in fact, one of the results of the research was a reduction in the incidence of hepatitis among patients and employees by 80–85% (Robinson and Unruh, 2008: p. 82). In the study’s aftermath, the scientific community was divided. Some scholars claimed Krugman was unfairly vilified and that no real harm had materialized because the research subjects were already institutionalized and suffered far greater material harms than hepatitis infection. Walter M. Robinson and Brandon T. Unruh (2008) argued that the children’s parents were not unacceptably coerced and that Krugman’s research was motivated by the desire to help children. However, one of the study’s most outspoken critics, Dr. Henry Beecher, an anesthesiologist at the Massachusetts General Hospital and professor at Harvard Medical School, published a paper in the New England Journal of Medicine entitled ‘Ethics and Clinical Research,’ citing the Willowbrook study as an egregious example where patients were not informed that they were subjects of an experiment (Beecher, 1966).

Pfizer Meningitis Study in Nigeria In 1996, clinical researchers at Pfizer, Inc. (Pfizer), a large American drug company, learned of a meningitis outbreak in Nigeria’s northern Kano State. By the end of this epidemic, there were at least 250 000 recorded cases of meningitis and 25 000 deaths. Pfizer, working alongside volunteer agencies (such as Doctors Without Borders) and Nigerian health officials, used the epidemic as an opportunity to conduct a randomized trial of Pfizer’s antibiotic ‘Trovan.’ Pfizer’s stated goal for this trial was to obtain “valuable empirical and clinical data on Trovan . [and to] pioneer[] a breakthrough treatment for the Third World” (Ezeome and Simon, 2010: p. 1). At the time of the trial, Nigeria was run by a military government with “one of the world’s worst human rights corruption records,” which meant Pfizer faced fewer

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regulatory hurdles in beginning and carrying out the trials (Stephens, 2000). Pfizer prepared and initiated the study in a mere 6 weeks, in contrast to the process in the U.S., which typically takes a year or more (Stephens, 2000). Two hundred Nigerian children with meningitis were enrolled in the trial. And although the antibiotic was promising, it was also a ‘potential blockbuster’ for Pfizer, with Wall Street analysts predicting that Pfizer might earn 1 billion dollars if Trovan were approved for its many potential uses (Stephens, 2000). Throughout the trial, Pfizer did not follow various guidelines governing meningitis experiments, such as conducting a second spinal tap within a few days of beginning treatment. In all, 11 children died and many others continued to suffer meningitis-related symptoms including deafness, blindness, seizures, and loss of mobility. According to a Nigerian doctor, the patients did not understand or know they were in a research trial; “they just knew they were sick” (Stephens, 2000). And although Pfizer claims that local nurses explained the research to the children’s families, there are no signed consent forms to prove its claims. Trovan was eventually approved for sale in the U.S. but it was not approved for use in children and European regulators prohibited its sale completely, given discrepancies in the Nigerian test results as well as the drug’s numerous side effects, including liver damage and death. Pfizer ‘roared’ in and out of Nigeria in ‘a relative eye blink’ – leaving 3 weeks after the study began. In 2011, the parents of four children who died during the trial were each awarded $175,000 (Smith, 2011). More compensation settlements were expected to follow from a $35 million fund created under the settlement between Pfizer and Kano State (McNeil, 2011).

Government-Sponsored Research U.S. Sponsored Syphilis Studies in Tuskegee and Guatemala In 1972, the most notorious human experiment conducted in the United States ended after four decades (Washington, 2006). Several hundred poor, African-American men infected with syphilis, a sexually transmitted disease caused by a bacterium and treatable with penicillin, served as the uninformed participants in a deadly 40-year study supervised by the U.S. Public Health Service. The men were told only that they suffered from a condition referred to as bad blood and that the state would provide free treatments for the illness, the men unwittingly surrendered to the behest of the researchers, providing doctors and government officials broad access to their flesh (Washington, 2006: p. 162). The men’s bodies became human canvases to be poked, prodded, and punctured with lumbar spinal taps. Indeed, the purpose of the study was neither to keep the men alive nor to find a cure for syphilis, but rather to study the effects of syphilis, particularly at death. For this reason, the participants were not provided penicillin – all were treated with pink pills of no medicinal value. In 1932, when the infamous “Study of Syphilis in the Untreated Negro Male” – euphemistically known as the Tuskegee Study – began, no research protocols existed in the United States to define the scope of human participation in medical experimentation (Washington, 2006: p. 157). Neither did federal or state laws guide medical experimentation, because such laws had never been enacted.

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Ethical protocols remained at the discretion of doctors and their universities or hospitals. By 1947, penicillin emerged as the gold standard treatment for syphilis. However, researchers withheld this vital information from the infected men and their families. The Public Health Service doctors and a team of medical researchers denied the patients antibiotic treatments, withheld information, and prevented or obstructed their access to nearby treatment programs. Similarly, in Guatemala from 1946 to 1948, the U.S. government, in collaboration with Guatemalan officials in the health ministries and military, infected prisoners, individuals with low IQs, and soldiers with syphilis and other sexually transmitted diseases. The Guatemalan experiments were conducted on 1500 men and women without informed consent, just like the men at Tuskegee. In Guatemala, however, the research subjects were later treated with antibiotics (Stein, 2010). Ironically, the antibiotic treatments were a test protocol and likely not meant as a proactive health measure. In 1997, 55 years after the Tuskegee study commenced, President William Clinton issued an apology to the few remaining survivors whose crippling conditions made it remarkable that they somehow survived (Washington, 2006). In 2010, the U.S. issued an apology for its involvement in the Guatemalan syphilis study (Stein, 2010).

Human Plutonium Experiments Human plutonium injection experiments were carried out during and after the Manhattan Project, which ran from 1942 to 1946 (Moss and Eckhardt, 1995). The experiments sought to develop diagnostic resources to “determine the uptake of plutonium in the body from the amount excreted in the urine and feces,” an essential tool for protecting workers producing and fashioning plutonium metals for use in atomic bombs (Moss and Eckhardt, 1995: p. 177). The research subjects were injected with plutonium. Whether the patients injected with plutonium provided consent cannot be answered with certainty because all direct participants are deceased and documents that could shed light on this question are scattered, incomplete, or nonexistent. The evidence that does exist, however, makes it almost certain that patients were uninformed about being injected with plutonium. Indeed, until the end of World War II the word ‘plutonium’ was undisclosed (Moss and Eckhardt, 1995: pp. 213–214).

Cold War Experiments From the end of World War II and well into the 1970s, the Cold War provided the impetus for government-funded and -conducted experiments. During that period, the Atomic Energy Commission, the Defense Department, the military services, the CIA, and other governmental entities exploited prisoners, drug addicts, mentally disabled patients, mentally ill patients, college students, and soldiers in experiments “to test the effects of everything from radiation, LSD and nerve gas to intense electric shocks and prolonged ‘sensory deprivation’” (Budiansky et al., 1994). Rarely were these research subjects aware of the scale and scope of the research, risks involved, or even that they were part of an experiment. Collectively, these experiments are known as ‘Project MKULTRA’ (or ‘MK-Ultra’). In 1976 and 1977, the United States Senate conducted

investigations and held a joint committee hearing on MKULTRA (Project MKULTRA, 1977). According to the hearing report, the project sought to study and develop the covert use of biological and chemical materials for ‘behavioral control’ (Project MKULTRA, 1977: p. 2). General Vernon A. Walters, Deputy Director of the CIA, testified in 1975 that the experiments “included covert drug tests on unwitting citizens at all social levels, high and low, native Americans and foreign” (Project MKULTRA, 1977: p. 2). Some of the experiments involved administering LSD to unknowing subjects. Researchers destroyed many of the documents related to these experiments. Nevertheless, the uncovered records “reveal a far more extensive series of experiments than had previously been thought,” including involvement of more than 86 universities or institutions (Project MKULTRA, 1977: p. 3). Researchers and government officials involved with the Cold War studies were never prosecuted (Washington, 2006). Among those researchers, some continued to lead distinguished careers. The United States was not alone, however, in conducting controversial and arguably unethical research experiments. Fearing that the Soviet Union was planning a chemical and biological attack, the British Government sought to study germ dispersion. To do so, scientists from Porton Down, the United Kingdom’s government military science park, drove a Land Rover through local towns, spraying Zinc Cadmium Sulfide into the air in an attempt to simulate germ warfare. Although Porton Down’s authorities argued that the Zinc Cadmium Sulfide posed no health danger, the residents were nevertheless unknowing and unconsenting research subjects. Porton Down’s scientists also performed countless experiments on soldiers, who often agreed to be involved in research “in return for payment and a precious pass for 3 days leave.” Many were not informed about the substance or purpose of the research and in 1953, serviceman Ronald Maddison died after taking part in a Sarin nerve gas experiment (British Broadcasting Company).

Prisoner Research During the latter half of the twentieth century, researchers frequently sought the involvement of prisoners in medical research because the stability of prison life (controlled diet, ready availability of subjects for continued monitoring and follow-up) made incarcerated populations attractive research subjects (Office for Human Research Protections, 1993). However, ethicists and others concerned with the treatment of human research participants increasingly question using prisoners as research subjects, contending that the very fact of incarceration makes it difficult, if not impossible, for prisoners to give voluntary and informed consent. For example, prisoners were subjects in many of the MKULTRA and other government-sponsored experiments during World War II and the post-World War II era. In fact, after World War II, the United States was the only nation in the world continuing to legally use prisoners in clinical trials, with federal, pharmaceutical, and cosmetic companies funding a 30-year ‘boom’ in research involving prisoners (Washington, 2006). In an effort to address abuse in prison medical research, regulations and some federal agencies now require special considerations or protections for

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research involving the incarcerated (Office for Human Research Protections, 1993).

Contemporary Challenges One distinction in contemporary medical research that provides some distance from past ethical breaches concerns the role and rule of law. The firm establishment and broad acceptance of bioethical principles offers greater clarity at the macro level to universities, hospitals, and industry, as well as at the micro level, imposing rules and regulations on researchers. The establishment of firm research protocols has likely reformed modern medicine to some degree. Yet, despite mandatory research ethics training, the establishment of IRB processes, and increased government oversight throughout the world, challenges remain. And, much like egregious experiments of the past, research subjects most likely to be exploited are vulnerable by status: poor, uneducated, and of color. Pfizer’s meningitis studies involving Nigerian children provide an important example. Indeed, contemporary challenges in bioethics reflect the dynamics of past medical research: conflicts of interests, lack of meaningful enforcement, perverse incentives, and unfettered access to particularly vulnerable subjects. However, one major difference separating the early research experiments on vulnerable subjects from that of today is the use of tort law when codes of ethics are violated. Legal settlements may also cross borders. For example, litigants in Nigeria sued Pfizer in U.S. court after their case was dismissed in Nigeria. Litigants argued that a fair trial could not be pursued in their homeland and successfully argued that Pfizer could be sued in U.S. courts for illegal conduct abroad (Abdullahi v. Pfizer, Inc., 562 F.3d 163 (2d Cir. 2009)). Ultimately, Pfizer settled the claim (McNeil, 2011).

Conclusion Contemporary bioethics involve a host of medical–legal concerns that extend beyond the conduct of medical researchers to include issues involving the right to refuse treatment, the constitutional ‘right to die,’ assisted suicide, and the balance between state interest and that of the individual. Bioethical challenges play out in the tensions between family members (illustrated by the conflicts over authority to remove life-sustaining support), in cases involving forced medical treatment, conflicts between pregnant women and fetuses, and medical futility, such as anencephalic babies kept on expensive, life-sustaining medical therapies. The scope of ethical concerns in medicine will continue to expand as technology advances. Most contemporary bioethical challenges and concerns reflect concerns from generations past, including individual autonomy, dignity, fiduciary obligations, justice, and informed consent. The field, though relatively nascent, has a long and complicated history and makes a distinct contribution among legal discourses.

See also: Biobanking: Ethical Issues; Bioethics in the Postgenomic Era; Bioethics: Philosophical Aspects; Bioethics; Common Rule: US Regulatory Protections for Human Research

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Participants; Direct-to-Consumer Personal Genetic Testing; Ethical Dilemmas, Research, and Access to Treatment; Ethics for Biomedical Research Involving Humans: International Guidelines; Eugenics as a Basis of Population Policy; Eugenics as an International Movement; Eugenics, History of; Euthanasia; Gender and Social Research; Genetic Screening for Disease; Informed Consent of Research Subjects; Insurance and the Law; Law and Risk; Placebo-Controlled Trials, Ethics of; Privacy of Individuals in Social Research: Confidentiality; Research Ethics, Cross-Cultural Dimensions of; Torts in Law.

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