Bartha Knopper
Bartha Maria Knopper

Canadian lawyer and professor Bartha Maria Knoppers is widely acknowledged as one of the leading authorities on legal and ethical aspects of genetics and genomics research. In the summer of 2019, she gave a talk at the annual CRISPR meeting in Quebec City, an acknowledgement of the growing importance of ethical debate following reports of human germline editing. She was subsequently appointed a member of the international commission on the clinical use of human germline genome editing, which will release its findings in 2020.

In this interview, Knoppers discusses her journey to the frontlines of bioethics and CRISPR. (This interview has been lightly edited for length and clarity.)
 

Davies: Bartha, you are the first fully fledged bioethicist/law professor that we’ve interviewed in this series. Tell us a bit about your academic background.

Knoppers: I wish to encourage students not to go directly into what they think will be their professional field: do study every area that might possibly interest you before you go into what you think you want to be! I was in surrealist poetry, in particular Caribbean and African poetry, for some time before there were a few legal difficulties with my professor, and I switched to law. But I’m still at heart an international comparatist.
 

Davies: You are a law professor now at McGill University in Canada?

Knoppers: I was a law professor for 23 years at the University of Montreal and switched to the Faculty of Medicine at McGill 10 years ago.
 

Davies: What has been your interest in human genetics, and what have been the main ethical areas of interest that have driven your work over the past decade?

Knoppers: I came to human genetics in an odd way, through a medical law course, where I was given what is called a torts question on medical liability for prenatal injury, and also in a criminal law course, where there was a bullet left in the body of a criminal, and the question was whether the police could remove it as evidence he was running away.

There were other legal courses that led me to an interest in areas where there were no answers—in other words, where ethical issues, policy issues, or emerging scientific advances were not accommodated by the law or any kind of framework.
 

Davies: In terms of human genetics and some of the big issues such as cloning, did you work on those controversial issues?

Knoppers: My doctorate was on reproductive technologies and possible physician liability, followed by a postdoc on the legal issues surrounding prenatal diagnosis and preimplantation genetic testing for physicians. I learned human genetics on the fly. I attended probably a decade of conferences before I even understood chromosomes and DNA and all those rare recessive conditions. But I figured that if you don’t know the science, you shouldn’t be talking about it.
 

Davies: Last year, CRISPR babies became a major international subject, with the news of He Jiankui’s work regarding the birth of germline-edited twins. Do you recall what your reaction was when you heard that news?

Knoppers: I was not surprised. I’ve been looking at countries around the world with different levels of regulation, from guidelines to laws with criminal sanctions to just a simple statute or oversight agencies, such as in the United Kingdom. China had a series of regulations and requirements for ethics review and so on but rather loosely enforced it, if at all. Knowing the possibility of laxity in enforcement, once you have a country that seems to have on the books regulations or guidance that monitors or controls or in some way frames emerging biotech such as CRISPR technologies, this was bound to happen.
 

Davies: Over the past 2–3 years, there have been dozens of reports from learned societies and organizations on germline editing.1 I wonder—after all that work—did anything stand out in terms of overarching conclusions? When one group in one country says, “Well, we’re not inclined to support germline editing,” and another country says, “We’re slightly more inclined…,” what do we gain after all that research?

Knoppers: I think we gain a bit of perspective that we need to reorient how we frame policy. I can quote you from the Council of Europe and all kinds of bodies going back to the 1980s on germline editing or human reproductive cloning. There is just always a provision: “This is banned” or “The human germline should never be touched or modified.” You had these same rote statements that kept appearing.

However, 2015 was obviously the CRISPR breakthrough year that led to these 60 reports, and the fact that they’re all over the place is because we actually didn’t have discussion between 1980 and 2015—due to the very fact that everyone thought, “Well, it’s been taken care of. It is sort of prohibited everywhere.” And that shuts down discussion.

And the fact that you have a breakthrough, all of a sudden, they say, “Wait a minute. Did we not decide something on this?” And then they create 60 reports in the period of about 2 years full of nuances but without much direction other than, “It is not ready yet. It is not safe yet. It is not effective or efficient yet. It is not of quality yet.” Hence, it is difficult from both an ethics and legal and social policy point of view to come down on a technology very precisely when the science itself is not yet ready.
 

Davies: Within those 60+ reports, are there one or two that stand out to you in terms of their scholarship and recommendations?

Knoppers: Yes, there are two: the National Academy of Science, Engineering, and Medicine of 2017 in the United States, and the UK Nuffield Report of 2018.2,3 The National Academy actually honed down the safety, efficacy, and quality issues.

These are not only scientific issues. For me, they are also ethical issues. You should not introduce a new method into the clinic—a new advance of some “progress”—if you’ve not got those three nailed down. The ethical issue is why propose gene editing therapies if they are not safe, of quality, and efficient?

The Nuffield Council report introduced a new consideration: that of future generations and their welfare, which is interesting from an international human rights point of view. It also addressed the fact that we cannot ignore that enhancement and the potential for enhancement—not just germline modification, but enhancement in terms of so-called improvements to intelligence or whatever—had to be kept in mind from the point of view of equity as well.

Davies: In the first half of 2019, there were two high-profile calls for moratoria on germline editing. Do you support calls for a moratorium?

Knoppers: The call for a voluntary or a binding legal moratorium in the form of a treaty or a convention is problematic. The first would in all likelihood not be universal. Yet, it would take about a decade to get to the second more legal route and make sure that all countries sign and ratify.

In any event, a moratorium is a philosophical idea—it is an approach. It says to everyone, “Slow down. Let’s stop and see what we are doing.” But it could also create the illusion that something is being done—that people are actually stopping and thinking and deciding, “Should we go down this route or not?”

It may also cut off debate. Perhaps if we had not been so prohibitive in the 1980s, we would not have lost so many years and ended up in 2015 saying, “We are in an international vacuum.”

Davies: It doesn’t seem to have deterred the Russian scientist Denis Rebrikov…

Knoppers: No. These calls for a moratorium send the message that professionals are “worried.” Yet, they still may keep on doing what they’re doing. You need countries engaged at the highest levels. You need actual political momentum if you really want to have an effective moratorium.
 

Davies: You are one of the 16 members of a new International Commission co-chaired by Dame Kay Davies and Rick Lifton. Why did you want to be on that Commission? What is the goal of that group’s work over the next 12 months, and how is that going to have any more significance than all the other reports issued in the past couple of years?

Knoppers: The process of selection was quite different from the World Health Organization (WHO) advisory committee where there was a call for candidates. and it was filtered through the WHO with its usual processes in terms of the selection of members.

The invitation to join the International Commission came out of the blue. You’d get a phone call, and in a way, I was pleased and honored. Still, you have to be very prudent in what you say in the next year so as not to prejudge the possible outcomes of the Commission. You don’t want your presentations to be presumed as part of the Commission’s work, but you also think about the impact on your academic freedom…

At the same time, I’m pleased to be on the Commission because it complements the mandate of the WHO committee, which is different. The WHO’s Expert Advisory Committee is on ethics and governance, and the International Commission is more on the clinical potential (if ever) and what are the necessary conditions should clinical applications be possible one day. How do we frame this? How do we handle it? What are the conditions that need to be met? How do we monitor in the future?

These questions are scientific, but also necessarily ethical as well because for me, safety, quality, and the decision to move to clinical research (or not) and the need for ongoing monitoring are also ethical issues. I don’t think we can avoid them. And I don’t think the WHO can avoid the scientific issues. There is going to have to be crosstalk between the two.
 

Davies: You think that it would make sense for the two organizations to compare notes over the next 12 months?

Knoppers: Yes. Speaking for myself, I would like to introduce a different way of looking at things from the traditional legal/ethical route versus the scientific route, often set up against each other. I would like to integrate them by introducing the issues of human rights because they are universal. It will attract the attention of countries that are interested in equitable access, or maybe even rogue countries that see gene editing as a way for supporting bio-economies.

But most of all, I’m interested in four human rights: the rights of children, the right to health, the rights of future generations, and the right for everyone to benefit from the advances of science. The latter two rights have not been exploited or discussed in this area at all. They are largely dormant. Maybe we can activate them.

Because if you frame it as a human rights issue, you don’t get into the bioethics arena with claims of “That is Western bioethics.” Or the legal arena where you hear “Oh, that is the common law, but we have, you know, civil law, Sino- or Germanic or whatever law.” You avoid those traditional divisive discussions by raising debate to a level where countries have already identified and committed themselves as participating in the development and application of human rights.
 

Davies: Are there circumstances where, if all of the safety and good clinical options can be assessed in the next 10–20 years, germline editing should or could be allowed? In other words, you do not have anything fundamentally against it, a blanket “We should absolutely never cross that line”?

Knoppers: If I had such a position, I would have taken it 40 years ago, when in vitro fertilization (IVF) was first used and we were able to start looking at embryos to see whether they were viable and what genetic conditions they carry. People use IVF not only for infertility, but also for avoiding the transmission of genetic conditions.

For the screening of preimplantation embryos for serious, lethal, and often incurable or untreatable conditions, we started the discussion on what it means in the early 1980s. In 2002, I published a paper with Dorothy Wertz, a sociologist, where we asked the American Society of Human Genetics, the Iberian Society of Human Genetics, and the European Society of Human Genetics what “serious” means to geneticists?4

There was no consensus among geneticists. Currently, we still use the “serious” filter as a medical-scientific and yet also a socio-economic filter to prohibit, slow down, or speed up genetic testing and hence germline editing.
 

Davies: You spoke at the CRISPR 2019 conference in Quebec City. What has been your takeaway interacting with the CRISPR community?

Knoppers: The excitement is so palpable. It is really great to meet all these young scientists from so many different countries. They are actually interested in the ethical, legal, and policy issues and from an international point of view. They know because of the attention that CRISPR has attracted that people will say, “Oh, you’re in that technology that is leading to potentially eugenic applications or potential enhancement….”

I think that kind of scrutiny, that challenge, is necessary, that is, they will need to prove not only that their research is evidence-based from a scientific point of view, but also that it has socially acceptable human possibilities in medicine and science. It is a challenge for them. They are the next generation of scientists, and they came up to me at the meeting and told me they wanted or needed to have some sort of committee dealing with the social issues where the scientists themselves are involved. And that is them.

 

For references please visit The CRISPR Journal.

The CRISPR Journal, published by Mary Ann Liebert, Inc., delivers cutting-edge multidisciplinary peer-reviewed research, advances, and commentary on CRISPR, the extraordinary technology that gives scientists the power to cure disease and sculpt evolution. The above article was first published in the October, 2019 issue of The CRISPR Journal. The views expressed here are those of the authors and are not necessarily those of The CRISPR Journal, Mary Ann Liebert, Inc., publishers, or their affiliates. No endorsement of any entity or technology is implied.

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