New technology, old moral problem

Many of our discussions in bioethics are about whether the things that are possible to do with advances in medical technology are things that we ought to do. However, some of the moral concerns in medicine are much more basic. They have to do with the idea that dates back at least to the Hippocratic oath that physicians should use their knowledge for the benefit of the people they treat. Patients should not be used by physicians in ways that are harmful to the patient in order to increase physicians’ income.

Medscape recently reported on a study presented at the American Society for Reproductive Medicine 2019 Scientific Congress which looked at how well fertility clinics across the US complied with the Society’s online advertising policy. They found that many clinics were not following the policy. The major concern was that there were a significant number of clinics that were advertising success rates without revealing the additional information needed to make that rate meaningful. The most serious concerns had to do with clinics that advertised high success rates without revealing that they also had higher than recommended rates of transferring more than one embryo per cycle and had significantly higher than expected rates of twin pregnancies. It is well known that twin pregnancies have a higher risk of complications for both the mother and the babies. Transferring more than one embryo increases the chance of achieving pregnancy and live birth with a cycle of IVF but also increases the likelihood of twin or other multiple gestation pregnancies and the risk to the mother and babies. By transferring more than one embryo in situations in which it is not generally considered justified, these clinics are increasing the success rate that they advertise to obtain patients by doing something which causes harm to their patients.

When the physicians at a fertility clinic prioritize their income above doing what is best for the people they are treating, they have gone beyond unethical business practices. They have abandoned one of the main things that makes the practice of medicine a moral profession.

Autonomy of Access vs. Autonomy of Decision Making in Opioid Addiction

A recent Perspective in The NEJM by Dr. Amy Caruso Brown discussed the ethics consultation involved in treating addiction as a terminal disease. Since the article is behind a subscription firewall, I will briefly summarize the case and some of the ethical problems outlined by Dr. Brown. The focus of this blog is to ask the limited question as to whether or not there is sufficient patient autonomy to make decisions in an addiction situation described as terminal if, as Dr. Brown claims, society has failed to provide sufficient access to and services for patients with chronic addiction and/or mental health problems associated with similar levels of addiction.

Dr. Brown’s patient, Ms. A, was an unemployed, homeless woman who had a history of chronic opioid use/abuse and had failed multiple impatient rehabilitation, methadone maintenance and buprenorphine treatment programs. She was hospitalized for septic shock secondary to endocarditis, which had damaged two heart valves to such a degree that she was not considered healthy enough to survive surgery to correct the problem. Her only relative, a brother, who had recently finally cut ties with his sister to protect exposing his children to her illness and habits, agreed to a do-not-resuscitate order. To the surprise of her treating staff, her condition stabilized to the point where the cardiothoracic surgeon agreed to operate. She declined, wanting to be discharged so she could seek morphine to self-treat the intractable chest pain. She fired her attending physician as he made the ethics consultation referral questioning her decision-making capacity.

Dr. Brown nicely outlines the particular issues of legal capacity requirements required in New York and the limited capacity that surrogates have if they we not previously designated as such. Dr. Brown also discussed whether or not Ms. A met the criteria for terminal illness, specifically whether or not ongoing chronic opioid addiction, in the face of now severe cardiac compromise, would be expected to cause death within 6 months. Dr. Brown maintained that Ms. A was lucid and capable to make informed decisions, which were that she “simply wanted to go home, or to a hospice facility, and die peacefully.” Dr. Brown did not find her depressed or emotionally compromised, though quoted her as saying “I’m done. I’m ready to be done. I’ve fought long enough” and described her as “exhausted and grieving”. Dr. Brown believed Ms. A’s “decisional capacity was clear.”

Finally, Dr. Brown argued that society had failed Ms. A by not facilitating access to a treatment program that “included medication for opioid use disorder (OUD) – preferably initiated in an inpatient setting and coupled with ongoing trauma-informed mental health care and various social supports – [in the absence of which Ms. A] would almost certainly have a relapse”, further making it likely she would die within 6 months. Though the article noted Ms. A had previously failed inpatient rehabilitation, methadone maintenance and buprenorphine, it was not stated how coordinated or integrated the previous programs were. Was the proposed program new or simply a second (or third) chance through a similar program? Thankfully, Ms. A decided to accept palliative terminal care, which resolved her homeless situation, as it would be provided at an inpatient facility.

What if Ms. A had declined inpatient palliative care? Dr. Brown made a strong case that Ms. A’s social situation (poor, homelessness, mental health history of abuse and chronic opioid dependence/abuse) limited access to an appropriate treatment program for her problems, likely the only one with any expectation of success, however limited. Even if we grant that Ms. A was indeed terminal and had clear decision-making ability not compromised by depression, ongoing opioid dependence and other mental health factors, did her social situation really allow her to be autonomous in decision making? Said differently, how can we consider her autonomous for decision-making when she apparently lacks autonomy for access to her treatment? Further, how much support can an individual demand or expect from society and still be considered autonomous? I have touched on a similar issue in this blog previously with regard to serial pregnancy in opioid addicted women, asking when should the risks to the children (and social and financial burden to society) supersede the mother’s autonomy for having more children?

We need to improve access to treatment and support for mental health in general and opioid treatment in particular. This will likely include further discussion regarding the level of autonomy of those needing that treatment and support.

Controlling gene editing

The title does not mean societal or legal control of gene editing technology.  Rather, it speaks of controlling, or shutting off, a specific gene editing process.  In retrospect, it had to be the case that there is a resistance, or control, mechanism for the CRISPR system, the gene-editing machinery that functions as a way for bacteria to resist invasion by viruses.  An engaging essay in Nature this week discusses this on a level accessible to one who, like me, is not a technical specialist in the field.  Briefly, a few years ago a grad student at UC/San Francisco discovered cases in which the CRISPR system was ineffective in certain bacteria.  Following up led to the discovery of some 50 proteins that can act as “kill switches” for CRISPR.

On a surface level, the implications are clear—learn how to deploy these proteins and one can monitor one’s gene editing efforts for unwanted effects, or for spinning out of control, and if things haven’t gotten too far out of hand, one could turn things off—have an antidote, as it were.

Suppose at some future date that someone were being treated with a gene editing approach for a genetic disease, and things start happening suggesting that other genes than were intended to be the target were being altered.  Presumably one could intervene to treat or prevent the consequences.  Or suppose that genes were being edited to control a certain pest, like malaria-causing mosquitoes.  Presumably there could be an intervention to try to stop the process.

That’s a pretty superficial discussion, but technical experts in the field are trying to learn how to use these “kill switches” to control their gene-editing efforts. 

The also-superficial implication seems clear: these efforts should be understood, and applied in laboratory systems, then perhaps in “somatic” gene editing (treating an existing person for a genetic disease) BEFORE attempts are made to edit human embryos, whether the embryos are intended for gestation or birth or not.  Until things are MUCH more fully understood, there should be no direct work on heritable genome editing.

Chastening and enthusiasm about genome editing

A writer in Nature says that China sent a “strong signal” by punishing He Jiankui and two colleagues with fines, jail times, and bans against working again in human reproductive technology or applying for research funding.  (They lost their jobs as well and may not be able to do research work, presumably in any field, in a Chinese institution again.)  It is encouraging, this writer says, that China took this action demonstrating a commitment to human research ethics.  He and other researchers doing gene-editing work that is not ethically objectionable worry that there may be collateral damage, so to speak, against ANY gene-editing research in China.

Another writer in Nature says cites progress under “appropriate caution” for using gene editing techniques for so-called “somatic” gene editing; that is, editing disease genes in an existing person with that disease, to treat it.  This is, in essence, a form of gene therapy and is ethically permissible under proper research ethical guidelines.  Some clinical trials in progress involve injecting the gene-editing apparatus into a person, while most such trials remove the person’s blood cells, edit them in the laboratory, then re-introduce them into the bloodstream, after which the edited cells are left to mature normally.  The latter approach is particularly attractive to treat genetic blood diseases such as sickle cell anemia.

Both perspectives seem correct, as far as they go—never mind whether Dr. He’s jail sentence fits the crime, as Joy Riley asked on this blog last weekend.  Never mind also whether Dr. He’s research should be published; as Mark McQuain commented, it’s a bit incongruous to want to assess the technical merits of work that should not have been done in the first place.  He linked an opinion in Technology Review that argued, briefly, that because the ethics of editing genes in human embryos is under societal debate, people trying to decide on the ethical merits should be able to assess for themselves whether Dr. He succeeded, technically at what he set out to do.  (The consensus to date seems to be, no, he did not.)   But the role of technical success in assessing the ethical merits of a medical intervention—or, better, an intervention made in the name of medicine—depends on the degree to which the ethical judgment is a matter of making a reasonably reliable of risk and benefit, and the degree to which risk-benefit is a criterion for judging the ethical merits.  And therein, as they say, lies the rub—which I hope to revisit in coming posts.

Scientific Validity vs. Bioethical Violation?

In a previous blog entry, Dr. Riley covered the 30 December 2019 conviction of He Jiankui, the Chinese scientist who allegedly created the first genetically altered human babies born in November 2018, to three years in prison for “illegal medical practices”. His criminal conviction is somewhat surprising to me because I believe Dr. He must have received at least initial support from the Chinese government for his human genetic experimentation, particularly since he was allowed to travel to Hong Kong in late 2018 and make public a portion of his research. My surprise is that the almost universal uproar about the bioethical violations in this case can (at least presently) make even the Chinese government admit that a line has been crossed that warrants public condemnation and punishment of those involved. Though the crime cited was crossing a thinner bioethical line (lying on the informed consent about the risks of genetic engineering to the babies) rather than the fuller bioethical line (the actual risks of genetic engineering to the babies and humanity in general), a bioethical crime was committed.

There are other aspects of this story that need our bioethical consideration. Antonio Regalado in a recent Technology Review, describes the still circuitous path Dr. He’s research has taken en route to ANY publication. In fact, it appears that Technology Review is the first publication to make any portion of the original manuscript public (there is a link within the link provided above of excerpts of Dr. He’s manuscript). I cannot do justice to Mr Regalado’s sleuthful efforts at piecing together this story (it defies a simple summary) and encourage those interested to read his account in the link above.

Regalado reports that Dr. Howard Bauchner, editor-in-chief at JAMA, was given access to the original manuscript just days after the 2018 Hong Kong conference. Regalado found Dr. Bauchner to be generally supportive of genetic editing of embryos:

“I think it’s inevitable that it will move ahead, and I think it should move ahead… Oftentimes early scientific breakthroughs [such as organ transplantation and IVF] are seen as unethical, and then over time that changes, [as the technologies prove successful].”

In fact, a main dilemma for Bauchner remains the following: “If someone thinks it’s scientifically valid but not ethical, does that mean the study will stay in the shadows?…It’s such an interesting question.”

An interesting question indeed. One online repository of pre-published scientific papers called bioRxiv rejected the manuscript, likening the manuscript to a paper it might have received from Dr. Josef Mengele, the infamous Nazi death camp doctor. One might therefore wonder why Technology Review has published any portion of the manuscript. They are not a scientific journal per se, with strict peer review to validate the scientific method and results. They are a publisher of scientific news, and Dr. He’s experiment, regardless of it’s many bioethical failures, is certainly scientific news. Technology Review offers a more in-depth opinion as to why they believe it is appropriate to make the manuscript public.

Back to Dr. Bauchner’s interesting question. Does he mean by scientific validity that Dr. He’s experiment (may have) accurately edited the section of human genome that Dr. He claimed and therefore the scientific community should be able to learn from that? Even so, it still seems to me that that Dr. Bauchner is putting the scientific cart before the bioethical horse. Shouldn’t we decide whether it is right to edit the human genome in the first place before worrying about the validity of the technique to edit that genome?

TADA & Tinslee Lewis

In recent days, the Texas Advance Directive Act (TADA), signed into law in 1999 by then-Governor George W. Bush, has come under scrutiny because of the tragic case of Tinslee Lewis.

From press accounts  we learn that Tinslee is now 11 months old and suffers from several conditions which have led doctors at Cook Children’s Medical Center to conclude that any further treatment would only be harmful to her, adding to her already painful existence.   One of her doctors has said, “She is in pain. Changing a diaper causes pain. Suctioning her breathing tube causes pain. Being on the ventilator causes pain.”  TADA allows the hospital to stop such treatment after ten days if the patient’s doctors and the hospital’s ethics committee conclude there is nothing more that can be done and no other facility is able to take the patient.

Because Tinslee’s mother objects to the hospital’s conclusion, the case is now working its way through the court system. Last week a District Judge decided in favor of the hospital, but the next day the Second Court of Appeals in Fort Worth ordered a stay.

Observing the legal back and forth, the Washington Post points out, “In Tinslee’s case, however, anti-abortion groups are divided.  While Texas Right to Life took Lewis’s side, the Texas Alliance for Life and the Texans for Life Coalition have said they agree with the doctors.”  In a statement issued last week on the judge’s ruling supporting the use of TADA, the Texas Alliance for Life commented: “We don’t see how she could have ruled any other way.  As we have stated previously, Texas Alliance for Life supports TADA.  It is good public policy, it is constitutional, and it provides a balance between the patient’s autonomy and the physicians conscience protection rights to do no harm.”  

At the time of writing this post, there doesn’t seem to be a solution that will please all involved. Thus, we don’t hastily run to judgment here.  We acknowledge the hospital’s consideration of the futility issue (especially as it seeks to ‘do no harm’) as well as the pain of a family that wants to extend the life of their beloved child.  I would simply add that in all such cases, the human side of the equation needs to be considered.

2020, or 20/20?

Near the end of 2018, He Jiankui was on the world’s stage announcing that he had edited the genome of twin girls, in the hope of making them resistant to HIV. On Tuesday, December 31, 2019, the Wall Street Journal (WSJ) printed a report that Dr. He and two others have been convicted of “illegally practicing medicine related to carrying out human-embryo gene-editing intended for reproduction.” (online version here).

A court in Shenzhen concluded that the defendants had acted for “fame and profit,” when they “deliberately violated the relevant national regulations, and crossed the bottom lines of scientific and medical ethics.” For the crime committed, He received the most severe sentence. In addition to the three-year prison sentence, He is banned for life from “working in the field of reproductive life sciences and from applying for related research grants, “ according to the WSJ.

The Xinhua News Agency also noted that a third genome-edited baby had been born, and that this child, along with the previously born twins, “would be monitored by government health departments.” The WSJ did not state for how long the monitoring would continue. Not only were the children experimental subjects as embryos, but they continue to be subjects as well. Further, these genome effects will affect their progeny, potentially into perpetuity. Additionally, the Smithsonian Magazine reports that in the summer of 2019, He met with “investors to discuss a potential commercial genetic modification clinic in Hainan, which aims to become a ‘world-class medical tourism hub’.”  One might reasonably call this “a crime against humanity,” even if it does not include genocide of humans already born. (For further reading, see David Luban, “A Theory of Crimes Against Humanity”)

In the print edition of the WSJ, alongside the article on He is an article about Pastor Wang Yi of the Early Rain Covenant Church. Pastor Wang was sentenced on 30 December to nine years in prison. His crime was “incitement of subversion of state power and illegal business operations” (online article here).

Consider that a pastor receives a nine-year sentence for an offense against the State; and a scientist, a sentence of three years for a crime against multiple generations, and indeed, humanity. In the year 2020, we could use a check of our understanding of what is important in the life of the world. Would that our vision were 20/20 also.

Good news

The angel who surprised some shepherds outside of Bethlehem brought them good news. They were told that a baby had been born who would be a savior and that they were being invited to go and see him. I suspect the shepherds thought they deserved some good news. Things were not going very well. They were living in a nation that had been conquered by Rome and the recent requirement that everyone be registered in their hometown was for the good of Rome, not for them. It is likely that the kind of savior they were looking for was one who would save them from their Roman oppressors.

The shepherds answered the invitation and went to see this baby who was going to be a savior and told Mary what the angel had told them. Mary pondered this in her heart. She knew something the shepherds did not. She knew that this baby, who the angel said would be the Messiah and Savior, was not an ordinary child. He had been conceived miraculously by the Holy Spirit. She also knew that an angel had told Joseph that they should name the baby Jesus because he would save his people from their sins. That was a deeper good news than the shepherds probably understood.

When we think of good news in medicine it commonly means that a new more effective treatment has been developed or possibly that a disease that previously had no effective treatment can now be cured. Those things are good news, but however many new treatments are developed, we still all die.

The good news of Christmas gets at something deeper. The Bible helps us understand that the reason that the diseases and death that medicine battles exist in this world is because we and the world we live in are broken by sin. No matter how many new treatments we develop, medicine cannot address the underlying problem. The angel told the shepherds about the ultimate cure. A savior had been born who could reverse the effects of sin and death and save us from our sin. He could bring us eternal life. He did that by going to the cross and showed his victory over sin and death by his resurrection. That is good news.

Merry Christmas!

Can we hop the gene-editing train?

As Joy Riley pointed out on this blog on December 7, the world and the scientific community recently marked, with almost no fanfare, the one-year birthday of “Lulu” and “Nana,” the first (we think) and still only (we think) humans to have had their genes edited heritably—in a way that will be passed on to future generations.  Joy commented these children are “experimental subjects for life,” or, to use the phrase I found and discussed some time ago on this blog, “the babies are the experiment.”  To wit: it is not possible fully to assess and limit the risks of heritable genome editing before actually editing humans.  One must forge ahead.  Even if one were to edit a series of embryos, and abort them at different times during gestation to get a full assessment of their prenatal development, the questions about lifelong effects and effects on future generations would persist. 

And, as mentioned in other posts on this blog earlier this year, there is the issue of “nonphysical” harms to how we understand ourselves and our human existence.

A number of world scientific bodies are assessing, independently of each other, what regulatory safeguards should be instituted, on the assumption that heritable genome editing is something that should be pursued.  Last month, the journal Nature editorialized that efforts by the World Health Organization, US and UK scientific bodies, and a third international commission should not proceed separately (they are all due to report their findings in 2020), but should work together.  The editors apparently think that it would be straightforward, obvious, and right to adopt a moratorium on clinical applications of heritable genome editing, establish an enforced registry for all experimentation in this area, and expand the conversations to include representatives of people with disabilities.  If I read that correctly, it’s hard to disagree.

In the laboratory, things are moving fast and it is well-nigh impossible to keep up with the science or the conversations about it without that work being one’s main occupation.  A recent contribution linked by the Nature editors is called “prime editing” that appears to increase substantially the efficiency of gene editing, raising the prospect of correcting abnormalities associated with the vast majority of genetic diseases.  The relatively naïve, like your present correspondent, might wonder whether this approach could be limited to already-born people with genetic diseases, as treatment, rather than engineer the genomes of the unborn in an apparent attempt to eliminate these abnormalities from the human prospect.

Even thinking about the general public trying to influence where this work leads feels like assuming the role of an old-style hobo, trying to hitch a free ride by jumping onto a moving freight train.  One is liable to fall under the wheels.  But in the case of heritable genome editing, you’re likely to get run over anyway.

Dementia and the value of human life

Recent public reporting of some cases in Canada of people with dementia whose lives have been ended by euthanasia have caused me to think about the value of human life in those who have dementia. Canadian law requires the person whose life is ended by euthanasia to have mental capacity for informed consent, intolerable suffering, and a foreseeable death. It was initially thought that patients with dementia would not be candidates for euthanasia under the Canadian law because of the requirement for mental capacity, but now there euthanasia providers who have concluded that there are some patients with dementia who have sufficient symptoms from their dementia to qualify as having intolerable suffering but still have adequate decision-making capacity. The discussion there has focused on whether person who is at the stage of dementia that causes intolerable suffering can still have adequate mental capacity. I have a different concern.

When we try to define intolerable suffering in the context of euthanasia it appears to mean that the person who is requesting euthanasia has decided that the effects of an illness have reached the point that the illness has made his or her life not worth living. When we talk about intolerable suffering and euthanasia the first image that comes to mind is a person with excruciating and untreatable pain, but it turns out that pain is not the most common reason for people to request euthanasia. It is more commonly requested due to a loss of control and increased dependency. This is not surprising since we live in a society that places high value on independence and autonomy. However, is independence really what makes human life worth living or is that a widely believed but untrue fiction in our society? Aren’t we all dependent? As children we are dependent upon our parents. As we go through adulthood, we are dependent on spouses and friends. As we age, we become dependent on our children and neighbors. Loss of independence makes us more clearly human, not less human. The impairments of old age, whether they be physical or mental, make it harder for us to deny our dependency, but loss of control (which is what loss of independence is) and increased dependency should not be seen as something that makes life not worth living. It draws us deeper into the relationships that are an essential part of being human.

Living with dementia is difficult for the person with dementia and for those who love and care for persons with dementia, but it does not make the life of a person who has dementia not worth living. The person with dementia is still a person who has relationships that are important, even when the one with dementia can no longer remember who those people are, because the person with this dementia is still the same person. He or she is still the mother or father, sister or brother, or friend. He or she is still a uniquely created child of God. Our response to those who feel that life is no longer worth living because of the loss of cognitive abilities and independence should be to help them understand that their lives are worth living because they are valuable to us.