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.

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!

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.

The importance of premises

In an interesting article in the Hastings Center Bioethics Forum, titled “Hannah Arendt in St. Peter’s Square,” Joseph Fins and Jenny Reardon write about the importance of deep ethical reflection in dealing with the ethical challenges of biomedical research. They point out that when ethics becomes a matter of simply following a set of rules we can end up in the wrong place. Even such fundamentally good concepts as informed consent and the need to have research proposals reviewed to be sure that they are ethically sound can lead to a mindset of regulatory compliance, essentially following the letter of the law, while leading to poor conclusions about what we ought to do. In the end they suggest that in order to facilitate deeper ethical thinking regarding new areas of biomedical research we need more interdisciplinary conversation between the sciences and engineering on one hand and the humanities and social sciences on the other. I think this is quite true and is a strong argument for a liberal education in its classic sense.

However, I find it particularly interesting how the thinking of Hannah Arendt enters into their discussion. Arendt was a German Jew who fled from Europe to the US in the Nazi era. She wrote about the kind of thinking that allowed the totalitarian regimes of Hitler and Stalin to gain control. Fins and Reardon focus on her idea that logical thinking can lead from a seemingly self-evident statement to a replacement of common sense with thinking that leads in a direction that is very wrong. They see a culture in medicine and science that considers ethics as a matter of regulatory compliance rather than deep reflection an example of this.

What I find most interesting in Arendt’s thinking is the idea that logic will lead to faulty conclusions if the premise is not true. The problem that she saw in the thinking leading to totalitarian regimes was not that the thinking was illogical. The problem was that the seemingly self-evident statements which were used as the premises were false. When we apply that to ethics it means that we will only reach sound ethical conclusions when we begin with moral premises that are true. A liberal education with interplay between the humanities and the sciences is one way to seek true premises for our ethical thinking in the wisdom that can be found in the interplay of academic disciplines. Another is to recognize that the existence of common sense morality suggests a source of moral wisdom that is beyond human wisdom. Christian ethics finds its premises in that higher source of moral wisdom. A Christian liberal education integrates them both.

Different answers to “Why?”

Sometimes when we ask “Why” we are really asking the mechanical or causation question: “How did something come to be?” In a billiards game, one might ask: “Why did the 8 ball go into the side pocket?” A valid answer might be: “It was struck by the 3 ball.” A reasonable follow-up question might be: “Why did the 3 ball strike the 8 ball?” Answer: “It was struck by the cue ball after a billiards player struck the cue ball with her stick.” These are correct mechanical explanations as to how the 8 ball came to go into the side pocket.

Sometimes when we ask “Why?” we are really asking: “For what purpose did something come to be?” In the previous billiards game, the answer to the question: “Why did the 8 ball go into the side pocket?” might be: “The player struck the cue ball which struck 3 ball which struck the 8 ball which went into to the side pocket so she could win the billiards game.” There was a purpose behind or beyond the physical or mechanistic description of the 8 ball falling into the side pocket.

Two opinion pieces asking “Why?” from medical and bioethical aspects were published within a week of one another and provide similar examples. The first was a NEJM Perspective by Anthony Breu entitled “Why is a Cow? Curiosity, Tweetorials, and the Return to Why” (subscription required). The second was by Stephen Phillips in this blog entitled “Why do we do this?”

In the first article, Dr. Breu begins with the classic infinite regression example of his 4-year old daughter asking “Why” to every response he provides to her previous “Why” question.

Daughter: “Why was [so-and-so] sleeping?”
Dr. Breu: “Because it was nighttime.”
Daughter: Why was it nighttime?”
Dr. Breu: “Because the earth rotates.”
Daughter: “Why does the earth rotate?”

Dr. Breu paused at this point because he did not immediately know why the earth rotated. He jokingly recalled that his own father terminated these inquisitions with: “Why is a cow?”, which Dr. Breu quickly learned meant the “Why Game” was over. The rest (and real emphasis) of the article discussed the benefits of encouraging medical curiosity in his students and the particular benefits of “Tweetorials”, Twitter posts that answer in-depth medical explanations of pathology. “Why does an acute hemorrhage cause anemia?” His Tweetorial provided a mechanistic answer to the question of why (or how) does anemia result from an acute hemorrhage.

Dr. Breu closes his article with the following answer to his daughter’s last question:

…the Earth rotates because of the angular momentum that resulted from asymmetrical gravitational accretion after the Big Bang. And if my daughter asks me “Why was there a Big Bang?,” I’ll be forced to reply, “Why is a cow?”

In the second article, Dr. Phillips answers the question: “Why do we do this?” by succinctly describing the purpose for which we Trinity Bioethics bloggers write the bioethics articles that we write. We believe there is purpose behind or beyond the human biology that we study determined by a loving God in whose image we are made. As such, our bioethical inquiries seek to understand whether the human purpose of a particular medical technology or procedure is complementary or contrary to God’s purpose. Why? As Dr. Phillips explained, because God loves us and has asked us to love our neighbor.

Maybe that is an answer to “Why was there a Big Bang?” (and “Why is a cow?”)

Why do we do this?

Many of the posts on this blog involve cautions that there are things in medicine which we are capable of doing and which some want to do that we should not do. Much of the time those cautions go unheeded by our society. For fifty years we have been saying that we should not perform abortions, but many unborn human beings continue to lose their lives. We give reasons why we should not do euthanasia, but PAS becomes legal in state after state. We write about why we should not alter the genes of human embryos, but the research continues. Is it just that we are anti-medical science and like telling people what they should do?

No. We do it out of love. Sometimes it is love and concern for people who are powerless and cannot speak for themselves. It is because of our love for the person who is aborted as a fetus or comes into being as the result of a genetic manufacturing project rather than being accepted unconditionally as a gift. It is out of love for the Canadian man who chooses euthanasia because he cannot obtain the 24 hour a day care he needs to live life with ALS.

It is also out of love for those who do things that are wrong. Love for the physician who performs abortions or euthanasia. Love for the researcher who uses human embryos as research subjects destined to die. We do it for the sake of the gospel which tells us that we have all done wrong and are destined for judgment unless someone intervenes. The gospel that tells us Jesus did intervene by his death and resurrection and has made forgiveness and restoration available to all who confess their wrongdoing and put our trust in him. We do it for those who will miss out on the amazing grace of the God who died for us if they listen to a culture that says that anything you desire to do is right and there is no need to ask for forgiveness for anything.

What Christian ethics is not

About this time in the semester, after discussing some basic things about the discipline of ethics and looking at some of the main ethical theories in western philosophical ethics, I begin a discussion of Christian ethics with the students in my bioethics class. I intend this to form a foundation on which they can ground their thinking about the issues in bioethics that we will discuss throughout the rest of the class. This year I decided to begin by talking about what Christian ethics is not, because we live in a world that has misunderstandings about many things including Christian ethics.

Here are the things that I have suggested to them that Christina ethics is not.

#1 It is not that we are better than they are (or that I am better than you are.)

Commonly when someone says that something is wrong, those who want to do it say that those who say it should not be done are trying to show that they are morally superior. I think this is a common motivation for making moral statements, but it should never be a part of Christian ethics. It contradicts what we, as Christians, believe. A fundamental part of the gospel is that we are all wrong. We are all sinful and in need of redemption. It is essential to our faith to believe that we are not better than anyone.

#2 It is not about what I think is right.

For those who believe in subjective relativism, ethics is truly about what I think is right. For the cultural relativist it is about what my group thinks is right. Even among many moral philosophers who believe in objective moral truth, whether they are Kantians or Utilitarians, ethics is about what I can determine to be right, based on my intellect and reason. From a biblical Christian viewpoint, it is what God thinks is right that is important. We are just trying to understand what he has revealed to us. None of us understands the mind of God completely. When we disagree, discussing why we think as we do can help us both get a better understanding of what God thinks about it.

#3 It is not about being good enough for heaven (or earning a relationship with God.)

Our society’s cultural religion says that as long as we do more good than bad, we can expect heaven as our reward. The Christian gospel says that our relationship with God and ultimate destiny are entirely dependent on Jesus’ death and resurrection. It is not about being good enough or doing more good than bad. So why do we care about ethics? Genesis says that we were created in the image of God. One of the things that means is that God intended to be a reflection of himself and his glory. Since God is a moral being who is good and we are sinful, we must be transformed to reflect God and bring glory to him.  Living morally upright lives through the transforming power of the Holy Spirit as people who have been reborn through Jesus’ death and resurrection allows us to worship God by living lives that reflect his goodness. That is what Christian ethics is.

Men without chests

One thing that is essential for us to be able to think well about bioethics is an understanding of who we are as human beings. One aspect of that which has been discussed on this forum is the concept of human dignity, the idea that all human beings have inherent value which impacts how we interact with each other ethically. For Christians that is grounded in the idea that we are all created in the image of God. John Kilner has expressed so very well how our being created in the image of God is the reason why people matter.

C. S. Lewis wrote about another aspect of how we understand ourselves as human beings back in 1947 in a little book titled The Abolition of Man. The first chapter of that book is titled “Men without Chests.” As a medieval scholar he was using a medieval image to express a concern that he had about how the tendency to deny the existence of objective moral truth in his day was leading to a problem with how we function as human beings. In the image that he is using the head represents intellect or reason, the chest (or heart) represents sentiments or values, and the stomach represents the appetites or desires. He says that if we believe that statements about morality or values are simply statements about how we feel and are not statements that can be considered objectively true or false, then the chest has lost its ability to mediate between the head and the stomach. Without objective moral values humans become beings whose intellect is used to achieve their desires without any means of controlling those desires.

What Lewis predicted is where much of our society is today. We are told that our identity is based on our desires, and that if we do not fulfill our desires then we are denying who we really are. Anyone who would suggest that our desires might be wrong or that we should not fulfill those desires must hate us and is attacking us and making us unsafe. Our desires define who we are, and our intellect is given the task of fulfilling those desires.

This is in stark contrast with a Christian concept of who we are as human beings. We understand that as human beings we are created by God in his image and with a purpose. We also understand that we are fallen. This world is not how it ought to be and we are not how we ought to be. Because we are fallen, our desires are frequently wrong. Our identity is not found in our desires, but in our relationship with our creator. We understand that our creator has given us the capacity to understand which of our desires are right and which are wrong. He has enabled our intellect to comprehend objective moral values that are grounded in the goodness of God’s nature. Those moral concepts allow us to distinguish right from wrong desires. That is what ethics is about. Those moral concepts also help us understand that we fall short of what we ought to be. We need help. That is what the gospel is all about. That is why Jesus died and rose again as we just celebrated at Easter.

The idea that our desires define who we are and must be fulfilled creates men without chests who are incapable of distinguishing right from wrong and can only express how they feel about a moral issue. We must have chests which hold to objective moral truths to think ethically and be complete human beings who are not simply ruled by our appetites.

Are AI Ethics Unique to AI?

A recent article in Forbes.com by Cansu Canca entitled “A New Model for AI Ethics in R&D” has me wondering whether the ethics needed for the field of Artificial Intelligence (AI) requires some new method or model of thinking about the bioethics related to that discipline. The author, a principal in the consulting company AI Ethics Lab, implies that there might be. She believes that the traditional “Ethics Oversight and Compliance Review Boards”, which emerged as a response to the biomedical scandals of World War II and continue in her view to emphasize a heavy-handed, top-down, authoritative control over ethical decisions in biomedical research, leave AI researchers effectively out-of-the-ethical-decision-making loop.

In support of her argument, she cites the recent working document of AI Ethics Guidelines by the European Commission’s High-Level Expert Group on Artificial Intelligence (AI HLEG). AI HLEG essentially distilled their AI ethical guidelines down to the familiar: Respect for Autonomy, Beneficence, Non-Maleficence, and Justice, as well as one new principle: Explicability. She downplays Explicability as simply the means to realize the other four principles. I think the demand for Explicability is interesting in its own right and will comment on that below.

Canca sees the AI HLEG guidelines as simply a rehash of the same principles of bioethics available to current bioethics review boards, which, in her view, are limited in that they provide no guidance for such a board when one principle conflicts with another. She is also frustrated that the ethical path researchers are permitted continues to be determined by an external governing board, implying that “researchers cannot be trusted and…focuses solely on blocking what the boards consider to be unethical.” She wants a more collaborative interaction between researchers and ethicists (and presumably a review board) and outlines how her company would go about achieving that end.

Faulting the “Principles of Biomedical Ethics” for failing to be determinant on how to resolve conflicts between the four principles is certainly not a problem unique to AI. In fact, Beauchamp and Childress repeatedly explicitly pointed out that the principles cannot be independently determinant on these types of inter-principle conflicts. This applies to every field in biomedical ethics.

Having an authoritative, separate ethical review board was indeed developed, at least in part, because at least some individual biomedical researchers in the past were untrustworthy. Some still are. We have no further to look than the recent Chinese researcher He Jiankui, who allegedly created and brought to term the first genetically edited twins. Even top-down, authoritative oversight failed here.

I do think Canca is correct in trying to educate both the researchers and their companies about bioethics in general and any specific bioethical issues involved in a particular research effort. Any effort to openly identify bioethical issues and frankly discuss potential bioethical conflicts at the outset should be encouraged.

Finally, the issue of Explicability related to AI has come up in this blog previously. Using the example of programming a driverless car, we want to know, explicitly, how the AI controlling that car is going to make decisions, particularly if it must decide how to steer the car in a no-win situation that will result in the death of either occupants inside the car or bystanders on the street. What we are really asking is: “What ethical parameters/decisions/guidelines were used by the programmers to decide who lives and who dies?” I imagine we want this spelled-out explicitly in AI because, by their nature, AI systems are so complex that the man on the Clapham omnibus (as well as the bioethicist sitting next to him) has no ability to determine these insights independently.

Come to think about it, Explicability should also be demanded in non-AI bioethical decision-making for much the same reason.