Assistant Professor Dr. Laura Cabrera is the author of a guest editorial on “The Need for Guidance around Recruitment and Consent Practices in Intracranial Electrophysiology Research,” published in the current issue of AJOB Neuroscience. Dr. Cabrera stresses the importance of the involvement of institutional review boards and funding agencies with regard to study recruitment and participant consent.
The full text is available online via Taylor & Francis Online (MSU Library or other institutional access may be required to view this article).
The New York Times Magazine recently published a long-form story about the tension between treating patients with COVID-19 by any means that might improve their chances of survival and recovery, and enrolling them in clinical trials to establish the safety and efficacy of these treatments, thus improving care both for future patients and for those who survived the trial. As with many stories about health care in the current pandemic, this article both raises perennial issues in bioethics and shows them in their starkest form: the seriousness of the condition of these patients and the lack of knowledge about how best to help them mean that the ethical dilemma described in the story is particularly clear. But a closer look at work in bioethics and the epistemology of clinical research suggests that, while the dilemma is clear, there are more ways forward than the two incompatible ways portrayed in the story.
The story begins by describing the clash between a critical-care physician faced with a COVID-19 patient whose condition was worsening, and a researcher who had enrolled that patient in a clinical trial. The former wanted to give the patient a higher-than-standard dose of the anticoagulant she was being treated with, even though this might mean that she would need to be withdrawn from the trial. The latter advocated for the importance of maintaining the integrity of the study, saying that acting on instinct instead of on evidence “was essentially ‘witchcraft’.”
Unsurprisingly, this characterization did not go over well with the other doctors in the meeting. A less contentious way of describing the situation might have been to say that, while doctors use their clinical judgment to make decisions about how best to use available evidence in caring for a particular patient, this only works when there is evidence available. And everyone agrees that, in the case of COVID-19, there is horrifyingly little evidence. This means that enrolling COVID-19 patients in clinical trials is not depriving them of standard care (care that such patients would ordinarily receive if not in the trial)–standard care for this condition does not yet exist.
Image description: An illustration of a health care worker wearing blue scrubs, head covering, and face covering. Surrounding them are a stethoscope, face mask, syringe and surgical tools, thermometer, and microscope. The background is light pink. Image source: sunshine-91/Vecteezy.
There is a lot to think about here. Importantly, it’s not the case that the doctors treating seriously ill patients had no idea what to do. They had a wealth of experience treating patients with severe viral infections, with acute respiratory distress syndrome, with cardiac arrest, or with pathological immune reactions (the “cytokine storm” sometimes seen in chemotherapy patients). Some of this knowledge informed the care of early COVID-19 patients, raising the question of which treatments could be successfully generalized to this new patient group.
The notion of generalizable knowledge is in fact central to research ethics. The Belmont Report, which guides research ethics oversight in the United States, draws a bright line between research and clinical practice on the basis of their ostensibly distinct goals. Research aims to provide generalizable knowledge, while clinical practice aims to benefit an individual patient. This way of drawing the distinction meant that when physicians depart from standardly-accepted care in the treatment of an individual patient, it does not count as research (and therefore does not require ethics review). It also leads to the problem described above: enrolling a patient in a research study requires that they forgo their right to individualized care and are treated according to study protocol. Deviations from the protocol, such as the one described in the opening of the New York Times story, are prohibited. Patients whose care does not follow the protocol will usually be withdrawn from the study.
But this sharp distinction between research and practice also makes assumptions about the kind of clinical research being conducted. Schwartz and Lellouch (1967) distinguish between “explanatory” and “pragmatic” approaches to clinical trials. Explanatory trials are designed to minimize the influence of any factors, other than the experimental therapy, that could affect the outcome being measured. These other factors include additional medications and the presence of comorbid disease. Pragmatic trials, by context, are designed to resemble actual clinical practice, where patients often take more than one medication and often have more than one health problem. Pragmatic trials may also enroll a wider variety of participants (especially older participants), permit alterations in the study protocol, be more flexible in the timing of outcome measurement; in general, they are more flexible in their design and analysis. A given trial will fall somewhere on the spectrum between “highly explanatory” and “highly pragmatic” in its design.
In the case of COVID-19, there are good reasons to favor trials that are more pragmatic. First, there are so many factors that might affect prognosis (or were previously thought to do so) – age, gender, weight, blood type, various pre-existing conditions – that the study population cannot be narrowly defined. If it is, then the results of the study will apply only to people in that narrow population. Second, care for critically ill patients is rapidly developing. Even in the absence of an established drug regimen, survival rates have been improving. This means that by the time a trial is completed, the experimental therapy will be implemented in a very different context of care. Perhaps more importantly, because of these first two reasons, a strict, explanatory trial is less likely to give generalizable knowledge than a more pragmatic one (Bluhm and Borgerson, 2018). Research that reflects clinical practice is more likely to be useful in improving clinical practice.
Robyn Bluhm, PhD, is an Associate Professor with a joint appointment in the Department of Philosophy and Lyman Briggs College at Michigan State University. She is a co-editor of The Bloomsbury Companion to Philosophy of Psychiatry.
Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, September 3, 2020. With your participation, we hope to create discussions rich with insights from diverse perspectives.
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Scientist [ˈsīəntəst] — a person who has expert knowledge.
Last month more than 100 faculty members and researchers attended the latest Brews and Views session: “Trust Me, I’m a Scientist! Responsibility and Accountability in Science.” The event series, presented collaboratively by the Center for Ethics and Humanities in the Life Sciences and the Institute for Quantitative Health Science & Engineering, features moderated discussions addressing fascinating and provocative areas of bioscience and engineering.
The event was moderated by Dr. Monique Mitchell Turner, Chair and Professor in the Department of Communication, College of Communication Arts and Sciences. Dr. Turner began with an audience response poll that asked attendees to consider both the role of institutional review boards regarding responsible and ethical research conduct, and the ethical obligations of scientists studying risky innovations that could potentially cause harm. Subsequent questions focused on the concept of dual use, which Dr. Turner clarified as referring to “technologies that alternately can be used for peaceful as well as for hostile purposes.” Regarding potential dual use harms, who is ultimately responsible: the principal investigator, the journal that published the work, or someone else entirely?
Image description: an illustration depicts four scientists holding a double helix, beaker, atoms, and a magnifying glass. Image source: vecteezy.com.
Discussant Dr. Heather Douglas, Associate Professor in the Department of Philosophy, College of Arts & Letters, examined moral responsibility in scientific endeavors, focusing on two qualities of dual use concerns, i.e., the intention of the researcher and that which might or might not be foreseeable. She clarified that when the ultimate use is readily predictable, ignoring the prospect of use for hostile purposes would be reckless, but unfortunately, many things are not predictable.
Dr. Douglas pointed out that the two checks on scientific endeavors include responsibility and accountability, but the conundrum is that those two checks are not necessarily synced — scientists can be held responsible for things which they are not accountable and accountable for things which they are not responsible. It’s reasonable to hold scientists accountable to good methodology, to their colleagues, and to society. But there are other actors who are accountable as well, including the institution (as well as journals that publish research). The paradox is that the more an institution enforces accountability checklists, the more an individual scientist might mistakenly feel that they’ve met their responsibility by simply complying with that checklist. Dr. Douglas urged that to be accountable, scientists have a responsibility to think beyond such checklists to imagine future possibilities including dual use concerns.
Discussant Dr. Victor DiRita, Rudolph Hugh Professor & Chair in the Department of Microbiology & Molecular Genetics, College of Natural Science, acknowledged that scientists need to be both responsible and accountable, but he pointed out that science “works” by advancing incrementally, building on the base of prior work. For this reason, he rejected the broad notion of dual use, since it is impossible to have sufficient imagination to accurately predict future nefarious use of any given innovation. To illustrate, he noted that dual use concerns are often related to “gain of function” in which research builds on and extends the capacity of previous work. He noted that governance, carried out through the vehicles of institutional policies is unable to predict such capacity extension, and therefore dual use itself is impossible to predict.
Dr. DiRita expressed worry that excessive focus on potential risks can blur the lines between real risk and perceived risk, possibly impeding the progress of important useful research. While institutional regulatory policies are well-intended, he is concerned about undue regulatory burdens in those labs that lack the resources necessary to be compliant. Moreover, he was in agreement with Dr. Douglas that such checklists erroneously allow scientists to believe that simple compliance with regulation is sufficient to meet their responsibilities, and that journals should share responsibility for publicizing dual use science.
Image description: Pictured left to right are Heather Douglas, Monique Mitchell Turner, and Victor DiRita presenting to the audience at Brews and Views on January 24, 2020. Photo courtesy of Libby Bogdan-Lovis.
We can look at an individual’s DNA and know what their hair color is, but what about their behavioral traits? This episode features Center for Ethics Assistant Professor Dr. Laura Cabrera, and Dr. Mark Reimers, Associate Professor in the Neuroscience Program in MSU’s College of Natural Science. Drawing from their expertise as neuroscience researchers, they discuss what we know about how our DNA affects our behavior—from IQ scores to mental illness. They also explore possible ethical issues that may arise in the near future related to the study of behavioral genetics and gene expression.
This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: “While We Walk (2004)” by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License. Full episode transcript available.
About: No Easy Answers in Bioethics is a podcast series from the Center for Ethics and Humanities in the Life Sciences in the Michigan State University College of Human Medicine. Each month Center for Ethics faculty and their collaborators discuss their ongoing work and research across many areas of bioethics. Episodes are hosted by H-Net: Humanities and Social Sciences Online.
It is three years since the Centers for Disease Control and Prevention (CDC) reversed course to recommend that 11- to 12-year-old girls receive two doses of HPV vaccine to protect against cancers caused by human papillomavirus (HPV) infections, administered at least six months apart. This then overruled the previous “three dose” recommendation – but the CDC added the caveat that “teens and young adults who start the series later, at ages 15 through 26 years, will continue to need three doses of HPV vaccine to protect against cancer-causing HPV infection.”
When either recommending a health intervention or conducting research among adolescents (11-12 years), ethical principles require that in addition to the rightful consent processes, privacy and confidentiality especially should be observed. In that light, countries need to ensure that they meet some requirements of legal, ethical and moral issues pertaining to such situations. However, when it comes to adolescents, there commonly is some uncertainty about a proper ethical balance between protection from risks, confidentiality, privacy and the possible countervailing need for parental consent.
Image description: a black and silver stethoscope is curved around a small globe on a white background. Image source: Marco Verch/Flickr Creative Commons.
In resource-poor African settings, health access barriers are paramount, and they present major impediments to national and regional development across the continent. Additionally, before recommendations such as the aforementioned CDC HPV advice can be implemented, the pragmatic reality of the particular circumstances needs to be taken into consideration. There are other similar recommendations that are influenced by the vulnerabilities of women’s reproduction that fall into this same uncertainty.
A lack of clarity in ethical guidelines within African nations makes any attempt to follow the CDC recommendations a challenge. Moreover, there are additional dilemmas encountered when trying to follow basic ethical principles. These complexities influence the follow-up treatment for adolescents. In many cases it is the adolescent’s parents who take the primary role in decision making, oftentimes excluding those children in making decisions about their own health, and sometimes even denying them the potential benefits of health-preserving interventions. In essence, such African adolescents are left in a confused state of being both children and adults.
Using illustrative examples below, I draw from experience and insight in Tanzania. I make the case that the need for parental consent needs to be revisited so as to best customize the fit of that need to certain settings in reproductive health.
Contraceptive services
In many African countries the law is silent on the age a young person may access contraceptives. For example, according to a research conducted in Tanzania, 15 is the youngest age at which girls use contraceptives. Yet girls can obviously conceive before that age, and there is no law that prevents the usage of contraceptives at any age. Therefore, I argue that the default legal position requiring parental consent should be overruled; this would allow more freedom for young girls who wish to have access to reproductive control.
Age of consent for HIV testing
The age of consent for HIV testing is 16 years in Tanzania. Testing of persons under the age of 16 must be carried out with the consent of parents or legal guardians. However, the law does not stipulate a particular age at which an adolescent’s HIV status can be reported directly to him/her. It says only that test results are confidential and shall be shown only to the tested person with an exception of those under 18 years of age.
Age of consent for Antiretroviral Therapy (ART)
In Tanzania, the 2001 national AIDS control policy provides universal access to ART. However, there are no explicit rules regarding either age specification or consent. The policy specifies that “people living with HIV and AIDS have the right to comprehensive health care and other social services including legal protection against all forms of discrimination and human rights abuse.” Parental consent for minors therefore should not have a role in accessing ART.
Age for consent and access for Pre-exposure Prophylaxis (PreP) and Post-exposure Prophylaxis (PEP)
In the same way that HIV-infected young people should have the rights and obligations to which they are entitled, so too should they have ready access to PreP and PEP. However, since no explicit rule is in place with regard to the age of consent, might we then safely/ethically assume that any person irrespective of age should have access to PreP? Similarly, it is not clear whether an adolescent should be allowed access to, or alternatively, be prohibited from PEP as the law and guidelines are silent on access for young persons.
Abortion and post-abortion care
In Tanzania, as in all other African countries, abortion is illegal. Tanzanian law is very clear on the consequences. However, there are no age-specific-rules regarding the age of consent for access to antenatal care (ANC). Indeed, when an adolescent becomes pregnant, regardless of the young woman’s age, health workers do not require parental consent for ANC. Therefore, I maintain that this dis-equal access amounts to a contradiction in the ethics of care.
Access to HPV vaccines and cervical cancer screening and treatment
Returning to my first point, globally, Tanzania has one of the highest incidences of cervical cancer. To address this health concern, the country recently has agreed to provide HPV vaccine for girls aged 9-13 years. What then is the parental role?
This message from CDC Director Tom Frieden, MD, MPH, in a 2016 press release could perhaps be viewed as clear and feasibly be implemented in a developed country:
“Safe, effective, and long-lasting protection against HPV cancers with two visits instead of three means more Americans will be protected from cancer. This recommendation will make it simpler for parents to get their children protected in time.”
This CDC claim about simplicity presumes that such parental consent would be forthcoming and would therefore equate to full HPV protection for the adolescent. But as I’ve pointed out, that might not be the case in Tanzania and other developing countries. Perhaps we then should take a new approach in dealing with ethical issues related to accessing health in low-resource settings. Parents have an important role in ensuring the health of the adolescents, yet as I’ve demonstrated in the above, in those areas of a sensitive reproductive nature, the parental role may need to be secondary so as to ensure the adolescent’s health and well-being. If reproductive health interventions among adolescents are to succeed, perhaps we need to reach out directly to adolescents. When considering the daunting health risks adolescents face in low-resource settings, there is a need to lower access barriers and allow adolescents to consent on their own behalf. This then would give them the freedom to decide when and with whom they wish to share such sensitive information, and to directly benefit from available health interventions. This needed policy shift would place the ethics of becoming an adult in resource-challenged settings on another level.
Ms. Rose Mwangiis a past beneficiary of an NIH Fogarty Fellowship at the Michigan State University Center for Ethics and Humanities in the Life Sciences. She has participated as an observer in Community Research IRBs at Michigan State University. Ms. Mwangi is very involved in Pan-African Bioethics and does research ethics in Tanzania. She has been involved in international clinical trials playing a key role in developing consent processes for rural and low literate communities; she has done important systematic qualitative studies advocating for social responsibility among global health researchers. Her recent milestone is leading the development and integration of Bioethics curriculum at Kilimanjaro Christian Medical University College (KCMUCo) as part of the European and Developing countries Partnership (EDCTP) in which UK and Tanzania are key stakeholders. Ms. Mwangi Co-Chairs the Institute Review Board (IRB) and is the Bioethics and Research Ethics instructor at KCMUCo and other medical institutions in Tanzania.
Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, July 11, 2019. With your participation, we hope to create discussions rich with insights from diverse perspectives.
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In April, an intriguing study drew a lot of media attention… and a swarmofbioethicists.
Reported in the New York Times and other media outlets, the study by Zvonimir Vrselja and colleagues used a preservative solution and other ingredients to mimic blood flow in the disembodied brains of four pigs (presumed dead), beginning four hours after the pigs had been slaughtered. They discovered that neurons and other brain cells had resumed metabolic activity, and that individual neurons could carry a signal. (For a lay-friendly account, see Reardon 2019.)
This may be a line of research with tremendous potential. At the modest end the range, it could lead to discovering ways to prevent or reduce irreversible brain damage and death, supplementing or improving techniques already in use, such as hypothermia protocols.
But at the other end, it raises the prospect of reanimating parts of the brain that have “died”; or maybe the whole brain itself. Could raising the dead become common-place in another decade—no longer a miracle?
Could the brain dead be raised from the dead?
It might seem the answer to this question is yes. Following the Uniform Laws Commission recommendation, Michigan like all other states allows that death can be declared under two conditions:
An individual who has sustained either of the following is dead:
(a) Irreversible cessation of circulatory and respiratory functions.
(b) Irreversible cessation of all functions of the entire brain, including the brain stem.
If Vrselja and other researchers eventually develop the ability to reanimate a whole brain, and inside a skull rather than a vat, would this make whole brain death always reversible? At least so long as the rest of the body is functional enough to sustain the brain?
It might seem the answer is “yes.” The reanimated brain would have a full complement of neurons, capable of communicating with one another, and presumably then capable of the consciousness found in any healthy human brain. The functions of the brain would have been restored.
Presuming this is possible, such a prospect raises tremendous challenges to the ethical conduct of research leading up to such an achievement, which is a focus of concern for Farahany and colleagues. We might be creating or experimenting on brains (both human and non-human) capable of consciousness, and perhaps of suffering, but with no means of communicating that to the researchers.
But would the achievement really mean that whole brain death would no longer be an acceptable criterion for death?
I think the answer is no. Whole brain death marks the death of the person, not merely the death of the brain. And it’s the death of the person that matters—to that person, and to those around them.
It will in one sense be “my” brain that has been reanimated, and it will be occupying my body. But it will be “my” brain only in the sense of being causally continuous with my brain when I was still in my senses.
It most certainly will no longer be me. Assume that my brain has in fact died, with all or most of its cells and synapses no longer functioning. On what basis could my consciousness, preferences, memories, and many characteristic failings be recovered? Consciousness is most certainly not located in any specific part of the brain, or any particular type of neuron. It is a global, network phenomenon. With the death of my brain, my network has gone down.
The brain that is recovered may have the capacity to build a network of its own. But it won’t be mine.
Yes, they may be able to revive Porky the Pig’s brain one day. But it won’t be the Porky we know.
Tom Tomlinson, PhD, is a Professor in the Center for Ethics and Humanities in the Life Sciences and the Department of Philosophy at Michigan State University.
Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, June 6, 2019. With your participation, we hope to create discussions rich with insights from diverse perspectives.
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In November of 2018, a Chinese scientist announced that he had edited the embryos of twin girls and that the twins had been born. The scientist, He Jiankui, used CRISPR, a revolutionary method of editing sequences of genes, to delete the gene CCR5 from the embryos’ sequences. The intention was to make the twins resistant to HIV. Editing human embryos and allowing those embryos to develop into living, breathing babies was widely condemned. However, now it appears possible, likely even, that the twins’ cognition was impacted, perhaps improved. This, however, was an off-target effect—it was unintended. On March 13, Nature published a comment from a group of scientists calling for a moratorium on clinical uses of human germline editing. This call is only for a moratorium on clinical uses, not on research on editing the human germline.
Despite the moratorium, I think a good argument can be made that tolerating the clinical use of human germline editing is morally permissible. Here is one such argument. The fact that He Jiankui edited the girls’ embryos suggests that it is inevitable that some scientists are going to engage in this behavior. Imposing a moratorium is unlikely to change this—the cat’s out of the bag. Given that the behavior is inevitable, we should ensure it is performed as safely as possible in order to reduce the risk of harm.
Image description: an illustrated image of a strand of DNA with a piece being inserted, representing CRISPR-Cas9 technology. Image source: NIH Image Gallery/Flickr.
The Inevitability Argument
I’m claiming that because clinical use of human germline editing is now inevitable, we should tolerate and regulate it. Generally, arguments of this type don’t work. It isn’t generally true that just because something is going to happen anyway, we should not only tolerate that behavior, but also make sure that it is done safely. For example, it’s true that humans murdering other humans is inevitable (unless we can cognitively or morally enhance people through, for example, gene editing!). Despite prohibitions on murdering, it still happens and probably always will. But its inevitability doesn’t mean that we should tolerate it but ensure that it is done safely. We shouldn’t, obviously.
Sometimes the argument does work, though. Sometimes the inevitability of a behavior suggests that we should tolerate it under regulation. For example, people using IV drugs is, for the foreseeable future, inevitable. Given this inevitability, it is morally justifiable to tolerate the behavior and do what we can to ensure that it is done safely. One way we do this is through needle exchanges. More recently, similar arguments support the widespread availability of naloxone for overdoses. So, sometimes, but not generally, the inevitability of a behavior justifies the tolerance of the behavior in order to ensure it is performed safely.
Reducing Harm
Why does the Inevitability Argument work in the case of needle exchanges? Why does it fail in the case of murder? One difference is that we know murder is wrong. You can’t have the concept of murder without also having the concept of wrongness. To tolerate murder would be to tolerate something that is morally prohibited. But we should be more skeptical of the wrongness of IV drug use—it may not be wrong at all, to say nothing of policies that permit or prohibit it. Even if it is wrong, our confidence that it is so should be lower. Another difference is that in the case of needle exchanges with IV drug users, the tolerance and regulation is meant to reduce harm, not only to the users, but to society. On the face of it, it seems implausible that one could anticipate a parallel policy of tolerating and regulating murder to reduce harm. Rather, tolerating and regulating murder would increase harm.
Inevitability of Clinical Use of Human Germline Editing
Is the clinical use of human germline editing more like IV drug use, or more like murder? Supposing that whether the Inevitability Argument works depends on whether we know the behavior being tolerated is wrong, and whether tolerating it is intended to reduce harm, the clinical use of human germline editing seems much more similar to IV drug use than it does to murder. First, we don’t know whether the clinical use of human germline editing is wrong, unlike our knowledge that murder is wrong. Whether it is wrong or permissible or obligatory depends on a lot of factors, including on whether embryos have a moral status and whether we have a duty to future persons.
Second, what would tolerating the clinical use of human germline editing look like? It would require scientific and political oversight of methods, data, and follow-up clinical care. But more importantly, the tolerance and regulation of the clinical use of human germline editing would require that we know more about what the effects of it will be. The only way we can acquire this knowledge is by conducting research on the clinical consequences of editing the human germline. This is all to say that the intention of tolerating the clinical use of human germline editing is to reduce as much as possible any potential harms, both to the person whose embryo was edited as well as to society.
Tolerating and Regulating Clinical Use of Human Germline Editing
By these criteria, the clinical use of human germline editing looks much more like needle exchanges for IV drug use. If so, then the Inevitability Argument may work, suggesting that we should tolerate and regulate its practice. But this tolerance and regulation impose further requirements: we must closely monitor the behavior and support research on the effects of editing the human germline.
Scientists assert (without sufficient foundation, I think) that the behavior is wrong. Do we really know that the clinical use of editing the human germline is wrong? If so, what general principle grounds this knowledge? What are the consequences of this general principle for other lines of scientific research? Is the clinical use of human germline editing really inevitable?
Parker Crutchfield, PhD, is Associate Professor in the Program in Medical Ethics, Humanities, and Law at the Western Michigan University Homer Stryker M.D. School of Medicine, where he teaches medical ethics and provides ethics consultation. His research interests in bioethics include the epistemology of bioethics and the ethics of enhancement, gene editing, and research.
Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, April 18, 2019. With your participation, we hope to create discussions rich with insights from diverse perspectives.
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It was good news to learn last month that the “Golden State Killer” had at last been identified and apprehended. A very evil man gets what he deserves, and his victims and their families get some justice.
The story of how he was found, however, raised concerns in some quarters. The police had a good DNA sample from the crime scenes, which with other evidence supported the conclusion that the crimes were committed by the same person. But whose DNA was that? Answering that question took some clever detective work. Police uploaded the DNA files to a public genealogy website, GEDmatch, which soon reported other users of GEDmatch who were probably related to the killer. More ordinary police work did the rest.
Most of the concern was over the fact that the police submitted the DNA under a pseudonym, in order to make investigative use of a database whose members had signed up and provided their DNA only for genealogical purposes.
Image description: a black and white photo of the panopticon inside of Kilmainham Gaol in Dublin, Ireland. Image source: Craig Sefton/Flickr Creative Commons.
My interest in this story, however, is the way it both feeds and undermines a common narrative about our DNA—that it is uniquely identifying, and that therefore any uses of our DNA pose special threats to our privacy. As The New York Times expressed this idea, “it is beginning to dawn on consumers that even their most intimate digital data—their genetic profiles—may be passed around in ways they never intended.”
It’s true that a sample of DNA belongs uniquely to a particular individual. But the same is true of a fingerprint, a Social Security number, or an iris. More importantly, by themselves none of these pieces of information reveals who that unique individual is.
As the Golden State Killer story illustrates, it’s only when put in the context of other information that any of these admittedly unique markers becomes identifying. If the GEDmatch database contained nothing but genetic profiles, you could determine which genomes the killer was related to. But you’d have no idea who those genomes belonged to, and you’d be no closer to finding the killer.
Although an individual genome can’t by itself be identifying, it can provide a link that ties together different information sources which include that genome. It can then be that collection that points to an individual, or narrows the list of possibilities to increase the odds of identification, and the threats to privacy. Imagine the state police maintains a database of forensic DNA linked to records of criminal convictions, and provides that database to criminologists, stripped of any names or other direct identifiers. Imagine as well that one of the hospitals provides researchers with DNA from their patients along with their de-identified medical records (which can include patients’ age, race, first 3 ZIP numbers, and other demographic information).
If we put those together we can do some interesting research: use the DNA link to identify those who both committed various crimes and had a psychiatric history, so we can compare them to convicted felons without a psychiatric history.
But now it may take very little additional information to identify someone in that combined database and invade their privacy. If I’m a researcher (or hacker) who knows that my 56-year-old neighbor was convicted of assault, I can now also find out whether he has a record of psychiatric illness—and a lot more besides. What he had thought private, is no longer so.
The point of this somewhat fanciful example is that as more information is collected about us, from more sources, the threats to our privacy will increase, even if what’s contained in individual sources offers little or no chance of identification.
For this reason, the prospect of merging various data sources for “big data” health research will challenge the current research regulatory framework. Under both the current and the new rules (which haven’t yet gone into effect), the distinction between identifiable and non-identifiable research subjects is critical. Research using information that can be linked to an individual’s identity requires that person’s consent. To avoid this requirement, research data must be “de-identified”. De-identification is the regulatory backbone on which much of the current “big data” research relies, allowing the appropriation of patient medical records and specimens for use in research without consent; and it provides the regulatory basis for uploading the data collected in NIH-supported research into a large NIH-sponsored database, the database of Genotypes and Phenotypes (dbGaP), which most NIH-supported genomic studies are required to do. Data from dbGaP can then be used by other researchers to address other research questions.
The possibilities of merging such “de-identified” databases together for research purposes will only increase, including facial recognition databases being collected online and on the street. As the mergers increase, it will become more difficult to claim that the people represented in those databases remain non-identifiable. As Lynch and Meyer point out in the Hastings Center Report, at this point there will be two choices. We can require that all such research will need at least broad consent, which will have to be reaffirmed every time a person’s data is used in new contexts that make identification possible. Or we will have to fundamentally reassess whether privacy can play any role at all in our research ethics, as the very idea of “privacy” evaporates in the panopticon of everyday surveillance.
Tom Tomlinson, PhD, is Director and Professor in the Center for Ethics and Humanities in the Life Sciences in the College of Human Medicine, and Professor in the Department of Philosophy at Michigan State University.
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I am writing to respond to a recent statement from the Co-chair of the International Vaccine Task Force (IVTF) who, in a World Bank press release, said, “We must urgently prioritize clinical research both to save lives in low-income settings, and to generate valuable information that is a global public good.”
The purpose of this article is to highlight realities of the processes that will get us to that “valuable information.”
Image description: an individual in Kenya is photographed from the side while looking into a microscope. Image source: GSK/Flickr Creative Commons.
Researchers working with adolescents are confronted with ethical consent challenges attracting significant controversies over ethical guidelines regarding how decisions ought to be made in order for adolescents to participate in research.
Traditionally, parents have been the default decision-makers for adolescents regarding their health and/or participation in research. International guidelines also stipulate that informed consent must be given by adults, and that minors cannot provide informed consent for participation in research unless there is parental guidance or guardian permission to participate. But let’s look at the realities of the situation.
In March 2016, a study provided what they called “first-ever” national estimates of abortion incidences in Tanzania. The authors reported that 66,600 women received post-abortion care in health facilities for complications resulting from unsafe abortion in 2013 alone. Additionally, an estimated 100,000 women with complications failed to get the medical attention they needed. If we take this study as a tip of an iceberg—while we may not know whether the study was plagued by difficulty recruiting adolescent participants, or whether there are plans to further study unsafe abortion among adolescents—one may hypothesize that the majority of women under 18 in these groups did not have access to contraceptives because any intervention requiring parental consent would probably have been unfruitful, and they resulted to (unsafe) abortions against restriction by law. Thus, if we want to decrease maternal mortality among adolescents, we must ask more questions, for instance: In this study, who are these women? Could they be women of adolescent age who got pregnant, and secretly got involved in unsafe abortion because as minors they needed parental consent to use contraceptives?
Who is an adult?
The Tanzania guidelines for ethical clearance state that anyone below the age of 18 can only participate in research if a parent or guardian consents for their participation, and the concept of an emancipated minor may not be legally recognized. However, there’s clearly a conflict between the consent process in research, culture, religion, and what is legally constituted under the marriage act. In terms of religion, a Muslim girl can be married under the age of 18 years; the country’s constitution states that a boy can marry at 18 years and a girl at 15 years (Tanzania Marriage Act). The guidelines ambiguously talk about the category of emancipated minors as a legal mechanism by which the minor is freed from control by their parent. Although emancipation can be granted without due court process when a minor is bound to make a decision alone in the absence of the parents (in this case, marriage), in this conflict, does research participation call for a more stringent standard than getting married does?
Yet, in many instances in low-resource settings, poverty-driven young people below the age of 18 leave their parents in the rural areas and move to urban settings in search of greener pastures, whether to look for jobs to fend for themselves, and/or hopefully take care of their poor parents back in the rural areas. In the cities, they adopt independent lifestyles; girls may get married while the boys may take up social and economic activities, which even the parents/guardians may not know of. At present, this sort of economic independence is not recognized, and the minors cannot seek approval from the court or others to gain emancipated status.
Seeking adolescents’ consent in a low-resource setting
It is still not clear whether the assent should be verbal or signed by the adolescent, or who is the acceptable guardian where a parent is not available. This remains a silent dilemma to research ethics committees in low-resource settings. Who should consent for minors such as sex workers, hotel and bar workers, house helps, food vendors, hairdressers, etc., or young men who are involved in the transport industry and assist in loading or driving local public transport systems and other small businesses? Ironically, these are occupational activities that put the young population in these settings at risk of infectious and non-communicable diseases, an area where urgent interventions are required.
Parental informed consent among adolescents in these settings
According to the ethical guidelines, involving adolescents below the adult age of 18 would be considered a violation of the informed consent process. However, since emancipated minors are legally adults, it is high time that Tanzania and other countries in similar circumstances widened the legal recognition of adolescents other than by marriage, enabling them to participate in research on their own. Because in situations where adolescents are independent, obtaining legal consent becomes even more difficult when parents or guardians cannot be reached.
The obvious questions are: Is it realistic to look for parental consent from a parent who is solely dependent on the young adolescent for upkeep? Should these adolescents be excluded in health research? What should be the age limit for assent in such settings?
While one may argue that challenges to adolescent consent are the same across the world, there are more differences among low-income settings where cultural practices prevail, e.g., an adolescent in the U.S. is socialized in a setting where the development of society is based upon the rights of an individual, and autonomy is established when an individual reaches the age of 18. On the other hand, in an African setting, a 16-year-old may be operating at the level of a 25-year-old in terms of responsibility and decision-making, while an 18-year-old’s consent is still driven by centuries-old traditions that affirm the importance of community, society, and family. Thus, to emphasize the personal choice to participate in a clinical trial requires more interventions targeting the adolescents if we are to get valuable information that would help reduce mortality from unsafe abortions in settings restricted by law and poor resources.
Empirical evidence
With no clear empirical evidence on how many independent adolescents below the legal adult age are out there, it is difficult to make any generalizable conclusions. There is also no existing universal agreement as to what age minors can be taken as making competent decisions to participate in research among poverty-stricken hierarchical structures and cultural practices. Among the Masai, for example, the hierarchical structures and marriage practices are different from the majority of population; Masai can marry before the age of 18 years and the husband then becomes the guardian of the wife who is also below the legal adult age. Ironically, despite the legal restrictions, married adolescents across the continents who are below the age of 18 are considered emancipated minors. It would be interesting to establish whether emancipated female counterparts in U.S. and Europe would have a more independent decision over themselves in similar scenarios.
Image description: an illustrated cartoon depicts children in a classroom. A speech bubble above the children reads, “If we don’t know which drugs are safest and most effective for pregnant women and children, why don’t they just let us into more clinical trials?” The speech bubble from the teacher reads, “To protect you from untested drugs.” Image source: Hilda Bastian/statistically-funny.blogspot.com.
Participation of adolescents in health research: The impact
While debating on realities of informed consent among adolescents in low-resource settings, a significant number may be affected by reproductive health problems, among others. It is thus important to put all efforts toward collecting data from adolescents as sole decision-makers: massive exclusion of adolescents below 18 years of age in health research would prevent researchers from identifying actual targeted or enhanced lifetime risk of diseases, or from monitoring them in the future.
In low-income settings, young and independent adolescents can contribute a lot to research findings for diseases that are prevalent among adolescents. Excluding them on the basis of being below the age of 18 is quite unethical,unrealistic and unfair while reporting 21% new HIV infections among 13- to 24-year-olds. Furthermore in developing countries, the majority of participants in research have low literacy rates, yet it is assumed that parents and guardians will understand the complex informed consent processes on behalf of the independent adolescent. As indicated by Fletcher et al. (2018), the need to be more sensitive to the social, cultural, structural, as well as medical needs of all individuals is even more urgent.
Conclusion
The way forward is to first come up with empirical evidence, and to then enact laws and processes that enable the legal emancipation of minors who are 15-17 years old, whether they are married or not, particularly in low-resource settings. I strongly agree with other authors who have stipulated that adolescents should be granted more authority and rights over themselves, while at the same time protecting them from risks as independent human subjects (Iltis, 2013; Barina & Bishop, 2013; Kuther & Posada, 2004).
Ms. Rose Mwangi is a past beneficiary of an NIH Fogarty Fellowship at the Michigan State University Center for Ethics and Humanities in the Life Sciences. She has participated as an observer in Community Research IRBs at Michigan State University.
Ms. Mwangi is very involved in Pan-African Bioethics and does research ethics in Tanzania. She has been involved in international clinical trials playing a key role in developing consent processes for rural and low literate communities; she has done important systematic qualitative studies presented in international conferences advocating for social responsibility among global health researchers which is now a video training tool for bioethics at Kilimanjaro Christian Medical University College (KCMUCo). Ms. Mwangi Co-Chairs the Institute Review Board (IRB) and is the Bioethics and Research Ethics instructor at KCMUCo both for undergraduates and postgraduates.
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Patients with serious illnesses are often invited to participate in clinical trials. After being diagnosed with advanced cancer, I became one of those patients. I had to choose between two options: a treatment regimen my doctors had recommended, or a trial evaluating different treatments for my disease. As someone who had taught and written about research ethics, and a long-time member of an Institutional Review Board, I was in some ways better prepared than many patients are to make this choice. And I knew about the important health benefits that come from research, as well as the arguments that patients have a duty to participate in research. Nevertheless, I decided not to enroll in the trial. Was this a defensible choice, or did I have a responsibility to contribute to a study that could help future patients in my situation?
Join us for Rebecca Dresser’s lecture on Wednesday, March 22, 2017 from noon till 1 pm in person or online.
Since 1983, Rebecca Dresser has taught medical and law students about issues in end-of-life care, biomedical research, genetics, assisted reproduction, and related topics. She has been a member of the Washington University in St. Louis faculty since 1998. Her newest book, Silent Partners: Human Subjects and Research Ethics, calls for including experienced study subjects in research ethics deliberations. She is also the author of When Science Offers Salvation: Patient Advocacy and Research Ethics and editor of Malignant: Medical Ethicists Confront Cancer. From 2002-2009, she was a member of the President’s Council on Bioethics and from 2011-2015, she was a member of the National Institutes of Health Recombinant DNA Advisory Committee.
This lecture is co-sponsored by the Program in Medical Ethics, Humanities & Law at Western Michigan University Homer Stryker M.D. School of Medicine.
In person: This lecture will take place in C102 East Fee Hall on MSU’s East Lansing campus. Feel free to bring your lunch! Beverages and light snacks will be provided.
This post is a part of our 
The Choice to Become a Research Subject: A First-Person Perspective
Join us for Rebecca Dresser’s lecture on Wednesday, March 22, 2017 from noon till 1 pm in person or online.