Experimental Subjects for Life?

More than a year after the birth announcement of genome-edited babies in China, we are only slightly more informed of He Jiankui’s experimentation, the results of which are named “Lulu” and “Nana.” Although apparently approached, neither Nature nor the Journal of the American Medical Association (JAMA) chose to publish He’s work. Antonio Regalado reported on an unpublished manuscript in “China’s CRISPR babies: Read exclusive excerpts from the unseen original research” in Technology Review on 3 December 2019. The Technology Review article includes not only excerpts of the manuscript from He, but also reactions from Stanford law professor Hank Greely; University of California—Berkeley’s gene-editing scientist Fyodor Urnov; the scientific director of Eugin assisted reproduction clinics, Rita Vassena; and reproductive endocrinologist Jeanne O’Brien, from Shady Grove Fertility.

Regalado summarizes some of the problems with Chinese experiment as follows:

 . . . key claims that He and his team made are not supported by the data; the      babies’ parents may have been under pressure to agree to join the experiment; the supposed medical benefits are dubious at best; and the researchers moved forward with creating living human beings before they fully understood the effects of the edits they had made.

Greely points out the lack of “independent evidence” of the claims made in the paper. Urnov labels the paper’s claim of reproducing the usual CCR5 variant “a deliberate falsehood,” and calls the statement about the possibility of millions being helped through embryo editing “equal parts delusional and outrageous.” O’Brien’s concerns include the possibility of coercion of the couples involved, and, noting the social stigma of HIV-positivity in China, she poses the question of whether this was a genetic fix for a social problem. Certainly, the Chinese experiment raises many questions, including how a culture views children. Are children gifts to be received or projects to be completed? Is it appropriate to subject children to experimental research because we can? One of the quotes from the paper reads, “we have made a follow-on plan to monitor the health of the twins for 18 years and hope to then reconsent for continued monitoring through adulthood.”

We would be remiss if we thought that China alone plans to remake humanity. Vassena is quoted regarding He’s study:

Unfortunately, it reads more like an experiment in search of a purpose, an    attempt to find a defensible reason to use CRISPR/Cas9 technology in human embryos at all costs, rather than a conscientious, carefully thought through, stepwise approach to editing the human genome for generations to come.  As the current scientific consensus indicates, the use of CRISPR/Cas9 in human embryos destined to give rise to a pregnancy is, at this stage, unjustified and unnecessary, and should not be pursued.

Vassena, who directs a fertility enterprise, it should be noted, appears comfortable with impacting the human genome for generations to come:  It just needs to be a “reflective” and “mindful” approach. That is chilling. Would she, or the study’s authors, or Greely, or Urnov, or O’Brien sign up to be a science experiment for the rest of their lives? I would not consent—not for myself nor for my children—no matter how “reflective” or “mindful” the researcher happened to be.

Finally, “Lulu” and “Nana” should be known as more than the results of someone’s laboratory experiment. They are human beings, not laboratory rats or cells under a microscope to be studied at the will and convenience of the experimenters.

Determining Fairness in Healthcare

The New England Journal of Medicine (NEJM) had a recent Perspective on proposed bill H.R. 3 aimed at reducing federal spending on prescription drugs. A main component in the bill authorizes the Secretary of Health and Human Services to establish a “Fair Price Negotiation Program” that, beginning in 2023, would permit the secretary to negotiate with pharmaceutical companies the price paid by the federal government on 25 drugs each year. The article provides a broad overview of the bill as it discusses some of the economic pros and cons as well as the political back and forth that would be required to allow this bill to become law. The link is behind a subscription firewall but provides an option for free access to a limited number of articles with registration.

Call me cynical but anytime I see the word “fair” associated with a bill in Congress, I immediately wonder “for whom?” The article is quick to point out that the “negotiation” effectively means “price regulation and severe penalty for noncompliance” by the drug manufacturers. The article describes in general the method that will be used to set the maximum price of a given drug. How or why did Congress determine that method as the best for determining the Fair Price? Also, not all drugs will be included in the group subjected to negotiation. If it is good or fair (as determined by Congress) for drug prices to be determined/set/negotiated by our government, should not all drugs be negotiated similarly so they are fairly priced?

Bills like H.R. 3 are part of the larger discussion of what I call the ultimate “Rights vs. Obligations” in the delivery of healthcare. If healthcare is a human right, who is obliged to provide that right? In the present case of medication pricing, if the present cost of a drug is too high, who is obliged to offset that cost (read – pay the difference between “too high” and “fair”)? The provision of healthcare, generally, and the creation, testing and production of medications, specifically, have real costs. Are these costs fair? Who will pay these costs? The patient? The doctor? The hospital? The pharmaceutical industry? Should healthcare be for-profit? If so, how much profit? Should healthcare become a utility with strict(er) oversight? Can the market decide a fair cost or price? Can a utility board? Can our elected representatives? How about a group of really (and I mean really) smart, unelected bureaucrats?

Thoughtful answers to any one of these questions should be submitted immediately to your local congressperson. Collectively, they are presently the ones determining fairness (in a real bioethical sense) in healthcare.

Project Nightingale

Technology always seems to outrun ethics.  But just because something can be done does not mean that it should be done.  Usually this discussion is focused on the latest life-sustaining medical device, but with emergence of electronic medical records, a whole new set of problems have appeared

Last month, Rob Copeland of The Wall Street Journal (behind pay wall) published a report focusing on the partnership between Google and Ascension health subtitled:  “Search giant is amassing health records from Ascension facilities in 21 states; patients not yet informed.”  Google has named their efforts “Project Nightingale.”

The idea behind medical records being available on the cloud (or somewhere electronically) sounds very appealing at first.  However, it is not difficult to imagine “Project Nightingale” turning into “Project Nightmare” when it comes to patient’s privacy.  This was what drove a Google whistleblower to come forward: “why was the information being handed over in a form that had not been ‘de-identified’ – the term the industry uses for removing all personal details so that a patient’s medical record could not be directly linked back to them?  And why had no patients and doctors been told what was happening?”

Dr. David Feinberg, the head of Google Health, addresses the concerns that have been raised: “Google has spent two decades on similar problems for consumers, building products such as Search, Translate and Gmail, and we believe we can adapt our technology to help. That’s why we’re building an intelligent suite of tools to help doctors, nurses, and other providers take better care of patients, leveraging our expertise in organizing information.”  (I’m not sure using Google Translate as a positive example will bring comfort to many readers.) Feinberg also discusses the precautions that Google has put into place.

Since the original WSJ broke last month, Congress has gotten involved.  Consumer Affairs reports “that the U.S. Department of Health and Human Services has opened an inquiry into the project to determine whether it violates the Health Insurance Portability and Accountability Act of 1996 (known as HIPAA).”

Maintaining patients’ privacy is an important issue and must not be glibly overlooked.  It will no longer suffice simply to say that we trust Google (or Facebook, etc.) to do the right thing.

Giving thanks for life

The “bio” in bioethics means life. Although it includes other types of life the focus of bioethics is on human life. The announcement a year ago of human infants born in China after their genes had been edited has caused us to think this year about how human life should come into being.

The story in Genesis of the creation of humans tells us some things about who we are. We learn that we are created beings made from the material substance of creation with the breath of life breathed into us by God. We are made to be male and female and complement each other. When we come together in marriage, we have been given the ability to bring new human beings into the world as a result of our union as one flesh. Each new child is given to us as a gift from God. We also learn that God made us in his image so that we are intended to reflect his glory in the world we have been given to steward. That sets us apart from other created life and puts great value on every human being.

How does all this impact how we think about how we bring new human lives into the world? It means we should remember that each new child is a gift from God who should be accepted unconditionally. Children are not intended to be something we make to fulfill our own desires. Each new human being from the very beginning of his or her life has great value. It means we should hesitate to modify the genetics of a new human being to give that child the genes that we think are best. It also means that we should show great respect to any human being who is a subject of research. Human subject research can be very important, but the subjects should enter in voluntarily giving of themselves as a gift to others. When we do research on human beings who are not able to volunteer, the research should cause no more than minimal harm. We should not see human embryos as a disposable resource for research.

As our family travels to our home to celebrate Thanksgiving together this year, I am thankful for each of their lives. I am thankful for my parents who brought me into this world and nurtured me both physically and spiritually. I am thankful for my wife whom God has given to me as a faithful partner and the children God gave to us. I am thankful for the spouses God gave to them and the children they have been given. Above all I am thankful to the God who gives us life.

Assisted Suicide and Disability

On October 9th, the National Council on Disability (NCD) released a report on the dangers of assisted suicide laws as they relate to persons with disabilities. The report provides a nice background on the history and justification of the Council’s position against assisted suicide as far back as 1997. The present report, available here, provides an update on its rationale for its continued opposition to assisted suicide laws. The report, and its references, provide an excellent resource for those of us who argue against assisted suicide regardless of the presence or absence of a disability.

Eight states and the District of Columbia have legalized assisted suicide in some form since Oregon led the way in 1994. Additionally, while lacking a specific assisted suicide statute, a state supreme court decision in Montana in 2009 is believed to provide a defense for physicians who practice assisted suicide. Oregon has provided the statutory framework for existing assisted suicide laws as well as proposed or pending legislation in states moving in this direction. As a result, every state where assisted suicide is legal claims that a primary need for the law is to preserve a person’s dignity, a claim that NCD finds particularly troublesome for people with disability:

The idea that hastened death is a pathway to dignity for people facing physical decline reveals the public’s extreme disparagement of functional limitations and a perception that “dignity” is not possible for people who rely on supports, technology, or caregivers to be independent or alive. Many hold the attitude that a person with a disability may be better off dead than alive.

Assisted suicide is often the cheapest “treatment” for many chronic medical problems affecting those with disability, a fact not lost on those responsible for state Medicaid budgets. NCD provided example after example of patients in Oregon who were denied treatment for their chronic or terminal medical care only to be offered coverage for assisted suicide within the same denial letter. Such crass efficiency was too much even for California, who in 2015, passed a law correcting this behavior: “[a]ny [insurance carrier] communication shall not include both the denial of treatment and information as to the availability of aid-in-dying drug coverage.” Many patients or their physicians eventually were provided the information on assisted suicide by the very same insurance carrier in a follow-up phone call.

Another major issue discussed within the NCD report was the relationship of depression and suicidal ideation in patients with a new disability:

Research overwhelmingly shows that people with new disabilities frequently go through initial despondency and suicidal feelings, but later adapt well and find great satisfaction in their lives. However, adaptation takes considerably longer than the mere 15-day waiting period required by Oregon-model assisted suicide laws.

Perhaps the most persistent concern by NCD since 1997 continues to be “the major gap between informing the patient of alternative options [such as palliative care programs and long term-term services/supports] and those alternatives actually being available and provided.” All statutes legalizing assisted suicide include provisions that require a full explanation of all of the programs, resources, and options available to assist the patient if he or she does not decide to pursue suicide. However:

Many people with disabilities find this to be a very shallow promise when they know that all too often the programs are too few, the resources are too limited, and the options . . . often nonexistent.

The concerns articulated in the NCD report warning of the dangers of assisted suicide apply just as forcefully for those without disability. We should join their efforts to educate law makers on a better way forward without assisted suicide.

More on Physicians’ Conscience Rights

Yesterday’s post to this blog addressed physicians’ conscience rights.  The standard shape of arguments about preserving individual physicians’ conscience rights goes, broadly, like this:  certain actions now sanctioned by society (e.g., abortion, assisted suicide) have been embraced by the medical profession as standard medical care which all physicians should be willing to perform, but this stance runs counter to the long tradition of medicine and to the proper ethical stances of some individual physicians.  Therefore, objecting physicians should be free to decline to perform them, without fear of professional or legal reprisal.  In this vein, the current U.S. Administration had promulgated a regulatory rule in May of this year attempting to ensure that, consistent with existing statute, such conscience rights are protected.  This week, a federal judge struck down the rule in its entirety, arguing that a) the propose rule, which, like all regulations, would have had the force of law, went beyond the statute behind it by making unwarranted interpretations and expansions of the statute’s wording; b) the government’s process of promulgating the rule violated other laws governing such rule-making; c) that it was unconstitutional, violating not only the separation of powers but also the Fifth Amendment because the rule was too vague, and the First Amendment because it would have “required employers to conform their business practices to the religious practices of their employees.” 

One might wonder whether at least some of the court’s reasoning—especially the separation of powers and Fifth Amendment arguments, and the concern (“a” above) about bureaucratic overreach—might not in fact apply to a wide range of government regulations.  That notwithstanding, the Christian Medical and Dental Associations, which has been particularly vigilant to protect conscience rights when it comes to abortion and assisted suicide, vowed to fight on.

The Journal of the American Medical Association (JAMA) cites a different case, involving assisted suicide in Colorado.  There, assisted suicide was made legal, with only limited restrictions, by a public referendum.  Notably for the present case, while health care organizations such as hospitals may opt out, and decline to provide assisted suicide, they may not enforce a blanket prohibition against their physician-employees doing so on their own initiative.  Such a prohibition could only be enforced on the organizations’ actual premises. 

So apparently a physician who worked for a Catholic hospital wrote (on her own time, outside hospital premises, and of her own volition) a prescription for a lethal prescription for a cancer patient.  The physician cited judgment of her own conscience.  The hospital cited its moral reasoning, its own freedom of religion, and, it appears, a claim that the physician was, or should have been, considered to be acting as an agent of the hospital.  The matter is the subject of a lawsuit.

The hospital fired the physician.  It is said she found another job.  But that of course is not the point, is it?  If a physician, who has a covenantal relationship with the patient, finds in her moral judgment that, in a given case, assisting suicide is ethically permissible, why does the hospital system have a right to override that judgment—especially if it was exercised, as it is argued here, in accordance with existing civil law?  One can certainly argue, as I would, that the physician has erred in her moral reasoning, and misapplied the physician-patient relationship. 

But I wonder whether, as the saying goes, “what is sauce for the goose is sauce for the gander,” in this case.  We might consider: the hospital could employ the physician based on an upfront, written agreement that the latter would act in accordance with certain moral stances of the former.  Absent such an upfront agreement, it’s hard to agree with disciplining the physician as was done in this case.  But even then, such insistence on upfront agreements seems to run counter to much of the spirit of much discussion about conscience rights, setting up a regime in which the relative power of available employers of physicians determines the constraints on medical practice.  Even then, if medicine remains a learned profession at all, perhaps insistence on conscience rights should be understood to cut both ways.

Drs. Stephanie Harman and Abraham Verghese seem to lean in this direction in an accompanying editorial in JAMA—but by emphasizing physician autonomy.  Their examples betray their preferred value judgments, but the overarching concern still seems relevant and valid.

Rights of conscience and the distinction between needed and desired treatment

Rights of conscience, the moral concept that physicians or other medical providers should be able to choose not to provide or participate in medical treatments which they believe to be morally wrong, continues to be widely debated in our society. A recent article in Vox titled “He needed a gender-affirming procedure. The hospital said no.” Expresses some things that I think are misunderstandings of what this debate is about.

Although it mentions other faith-based institutions, the article is primarily about the types of procedures which Roman Catholic hospitals in the United States do not provide under the Ethical and Religious Directives for Catholic Health Care Services. Throughout the article it is stated that Roman Catholic hospitals have refused needed care to persons seeking care in those hospitals. It also raises the concern that people may die because they are not provided necessary emergency care and care from another hospital willing to provide the care may be too far away. My main concern with this article is that there appears to be a misunderstanding about the distinction between needed and desired treatment. Among the things listed as needed care are “fertility treatment, gender-affirming care, or tubal ligations.” The article begins with the case in which a Roman Catholic hospital would not provide an elective hysterectomy to a biologically female person who identified as being male. The hospital’s reason for not providing this elective surgery was not because it was desired as a part of the person’s gender transition. They chose not to provide the surgery because of their belief that removing a healthy uterus impairs fertility in a way that should not be done.

There is a difference between desired elective treatments that people may choose to do even though there is no medical reason why they need to be done and treatment that is either life-saving or needed for other medical reasons. Such things as fertility treatments, gender affirming surgeries, tubal ligations, and abortions are elective treatments that an individual may choose to do but are not medically necessary. There is an appropriate difference between the obligation of a physician or hospital to provide medically necessary and life-saving care and the presumed obligation to provide elective medical treatments that are desired but not medically necessary.

I am not Roman Catholic, but I practiced in a Roman Catholic hospital for about 30 years. I served on the ethics committee at that hospital as well. I became very familiar with the ethical and religious directives and the type of things they direct Catholic hospitals not to do. These things are elective treatments or procedures that a person may desire, but which are not medically necessary. I also became familiar with the important role that Roman Catholic hospitals play in providing care for the poor and marginalized, many times providing care for people that other hospitals and physicians would not. Those who think that our society would be better without Roman Catholic and other faith-based hospitals are quite mistaken. If those hospitals are forced out of our society by those who would require them to do anything that anyone requests even when they believe that those things are wrong, the poor and marginalized in our society will suffer greatly.

“Why did you make me this way?!”

Recently, Jon Holmlund brought us up to date on an effort in Russia to proceed with CRISPR gene editing aimed at eliminating deafness. Coincidently, a recent MedPage article was posted regarding the ethics of using pre-implantation genetic diagnosis and IVF to purposefully select FOR an embryo with genetic deafness for a couple, both of whom were deaf. Both links discuss some of the ethical problems with using medical reproductive and genetic technology for these purposes. While we presently lack the ability to use polygene scoring to accurately “produce” the babies we want, I want to use the remainder of today’s blog to consider what obligations, if any, a genetic engineer (or parents that use their skills) may have toward future children designed using these growing array of genetic technologies.

Deafness seems to me to be rather curious in that it is considered either a serious disability or a desirable trait, depending upon your cultural worldview. No one in any culture would purposefully select for cystic fibrosis or Tay-Sachs diseases for their child. In fact, most want to use medical reproductive and genetic technologies to eliminate these diseases. On the other end of the genetic trait spectrum, some parents want to use these same technologies to purposefully select for more trivial traits for their children – hair and eye color, for instance. Given the triviality of these traits, I hear no one mounting an effort to genetically eliminate any particular hair and eye color. Perhaps I am living a sheltered life?

Nonetheless, with regard to deafness, prior to the promises of our new reproductive technologies, if you were born deaf and did not like it, you could only shake your fist at God or Nature. Now (or very soon), you can shake your fist directly at another human, such as your regional genetic engineer (or your parents who purposefully used her technological skills) and demand a direct answer as to why they purposefully made (or did not make) you deaf. Maybe this angst will be more widespread for the many more trivial traits such as eye or hair color rather than something more significant like deafness?

Building a child is about to become much harder for parents as they become directly responsible for both interior (genetic illnesses) and exterior (hair and eye color) design issues.

“Why DID you make me this way?!”

“Why did YOU make me this way?!”

I wonder how many genetic designers (or the parents that will ultimately bear the direct responsibility for having used the technology) really want that type of responsibility?

Is there already fine print in PGD-IVF contracts holding the doctors/scientists/geneticists harmless for the choices the parents make?

I can’t wait for the late night TV commercials: “Were you born with brown eyes and feel emotionally scarred because you have always wanted blue? Call our law offices as you may be entitled to financial compensation …”

Racial Bias in Algorithms?

Can algorithms show racial bias?   That is the conclusion of a recent article published in Science by Obermeyer, et al., entitled, “Dissecting racial bias in an algorithm used to manage the health of populations.”  

According to Science, the algorithm’s goal is “to predict complex health needs for the purpose of targeting an intervention that manages those needs.”  Fair enough.  That certainly sounds like a worthy goal, especially in these days of complex medical conditions, with equally complex treatments.  However, the problem raised by the research done by Obermeyer, et al., is that “the algorithm predicts health care costs rather than illness, but unequal access to care means that we spend less money caring for Black patients than for White patients.  Thus, despite health care cost appearing to be an effective proxy for health by some measures of predictive accuracy, large racial biases arise.”   The study concluded that with a reduction of bias in the algorithm, a much larger percentage of Black patients would receive the advanced interventions that the health care system offers.

In addition, the Minneapolis Star-Tribune reports that “New York regulators are calling on Minnetonka-based UnitedHealth Group to either stop using or show there’s no problem with a company-made algorithm that researchers say exhibited significant racial bias in a study.”

In its note on the research, Nature  states that Optum (the algorithm’s developer) raised questions about the study’s conclusions:  “The cost model is just one of many data elements intended to be used to select patients for clinical engagement programs, including, most importantly, the doctor’s expertise.”  Nature also reports that “Obermeyer is working with the firm without salary to improve the algorithm.”

The results of this study deserve to be examined closely.  If we truly want to affirm the dignity of each individual, bioethics must address these areas of disparity whenever possible.  It’s not likely that we will ever achieve a bias-free world, but it is surely helpful to be made aware of our biases so that we can better serve those in need.

Regulating New Technologies

History’s lessons applied to Artificial Intelligence (AI) regulation is the subject of a recent Brookings article by Tom Wheeler.  He writes

Societies impose government oversight for the protection of old principles in a time of new technology. Foremost among those principles is each individual’s right to a future; and it comes in multiple manifestations. In the educational realm, it means adequate training to be meaningfully employed. Economically, it means maintaining the benefits of capitalism through checks on its inherent incentive to excess.

Most importantly, the right to a future begins with the belief that there is a future, and that national leaders care about whether individuals affected by new technologies participate in that future.

Although the author has AI in mind, it is interesting to consider his words in relationship to the regulation of human gene editing. Now is certainly “a time of new technology,” particularly regarding human germline gene editing.  The “old principles” of experimentation on human research subjects ethically done and informed consent, along with the restrictions/bans in many countries heretofore prohibiting human germline modification, come to mind.  Additionally and importantly, in Greely’s extensive review of how “CRISPR’d babies” came to be, he includes a welcome overview of the state of affairs regarding regulation (or not) of human germline genome editing, in the October 2019 Journal of Law and the Biosciences. 

An upcoming meeting (London, November 14-5) of the International Commission on the Clinical Use of Human Germline Genome Editing is slated to discuss more than governance of the technology. Their agenda is available here.  In addition to a discussion of issues and perspectives relayed by various parties in their evidence submitted to the Commission, there is a planned discussion of “how the rights of future people have been considered and established in other medical and nonmedical scenarios, and how consenting to any necessary or preferred long term follow up on behalf of future generations could be established.”

Exactly how does one generation prescribe the “necessary or preferred long term follow up” of succeeding generations? How does one generation assure consent of future generations? When Wheeler penned the Brookings article about AI regulation (quoted above), he wrote about the right to a future, which rests in part on the fact that “national leaders care about whether individuals affected by new technologies participate in that future.” It certainly seems reasonable that those who are affected by a project be allowed to participate in it – as something more than research subjects. If such is true for AI, how much truer should it be for those whose very selves are affected by the research! There has to date been no compelling reason to go forward with human germline genome editing, and there are many reasons not to proceed. The most appropriate regulation is a ban.