Book Launch: Consumer Genetic Technologies: Ethical and Legal Considerations
[CARMEL SHACHAR]: All right. Hello everyone, and welcome to the book launch for "Consumer Genetic Technologies: Ethical and Legal Considerations." This is a book that came out of the Petrie-Flom 2019 annual conference, which brought together leading experts to explore what ethical and regulatory safeguards should be implemented around the use of consumer genetics mostly focused on testing, but with a discussion of biohacking as well as genetic editing. I think this is such an interesting topic. I will say that the subject of the conference and the book was actually inspired
by my own personal experience with 23&Me as well as its interaction with the healthcare system when it revealed a predilection towards breast cancer running in my family for my mother and myself. I won't take up too much time before we get to our fantastic panel, but before that a little bit of housekeeping. The digital equivalent of where the bathroom is. We are hoping for a lively Q&A. You might ask how can I as an audience member submit questions. There are two good ways to do it. The best way is to use the Zoom Q&A feature found in the meeting controls at the bottom of your screen. If you click on that box and submit a question,
our moderator will be standing by reviewing the questions and post them to the panelists. If you would like to join the conversation or submit your questions through an alternate route, please go onto Twitter and use the #ConsumerGenetics. Again that's #ConsumerGenetics, and at us @PetriFlom. If you have any technical issues, please email us at
firstname.lastname@example.org. If you are interested in our further events, please sign up for our newsletter, please go and read Bill of Health, which is our blog that covers health policy, health law issues, it's very very topical, and then check out some of our forthcoming events. I will also say that the Zoom raise your hand feature, that little hand is very cute, but we are not going to monitor that, so really the best way is to contact us either through email if you have a technological issue, or Q&A if you have a substantive question, or a panelist. Speaking of panelists who is going to be speaking today? We have a really all-star lineup of fantastic scholars, and really just rock star human beings. The first up is going to be Emily Largent, Assistant Professor of Medical Ethics and Health Policy at the Perelman School of Medicine at the University of Pennsylvania. She's going to be followed by Natalie Ram, Professor of Law at University of Maryland Francis King Carey School of Law. Jake Sherkow is going
to round out our panelists. He's Professor of Law at the College of Law and Affiliate, Carl R. Woese Institute for Genomic Biology at the University of Illinois, and our distinguished moderator is going to be Henry T. Greeley, Deane F. and Kate Edelman Johnson Professor of Law; Professor, by courtesy, Genetics; Chair, Steering Committee of the Center for Biomedical Ethics; and Director at the Stanford Program in Neuroscience and Society at Stanford Law School. With that we're going to dive right in. I would like to hand it over to Emily as our first presenter. [EMILY LARGENT]: Great thank you so much. I'm really delighted to be here today, and congratulations on the
book launch, so when I wrote the chapter for this book, I focused on the APOE gene, which is a gene that talks about risk for late onset Alzheimer's disease or Alzheimer's disease where the onset date is after your 65th birthday, so I looked at this particular gene because it turns out this is a very controversial test to be offered in the direct to consumer context, and in the medical school in the circles where I run it's not usual to hear people talk about 23&Me with sort of hushed in ominous tones when they think about the consequences potentially of direct consumer APOE testing, so my motivation and thinking through the chapter was really that if we can understand and address some of the concerns that arise in the context of APOE testing specifically given how controversial it is that we can find ourselves reassured and drawing lessons about genetic testing, direct to consumer genetic testing more broadly, so my goal for the next few minutes is to offer some highlights from the chapter and also to discuss a few updates, things that I would be working in if I were to be writing the chapter now, so by way of brief background there are multiple known risk factors for Alzheimer's disease, so these include your age, race, sex, your personal medical history, your family medical history, and also, of course, genetics. Now researchers have not found a single gene that will tell you whether or not you will certainly get late onset Alzheimer's disease, but there is a susceptibility gene APOE, which is well known. There are three variants or alleles of the APOE gene, and these dictate how much risk you carry, so the E2 allele is relatively rare. It provides some protection apparently to individuals. The E3 is the most common, believed to play a somewhat neutral role in risk, and then the E4 allele increases risk and is associated with an earlier age of onset.
Now, it's really important to stress that having an E4 allele is neither necessary nor sufficient to develop Alzheimer's disease. Not all people who have an E4 allele will develop Alzheimer's disease, and roughly half of those who develop Alzheimer's disease have no E4 alleles at all, so right now, when we look at the clinical context, right, so not direct to consumer, but looking at the clinical context, APOE testing is generally not covered by insurers, and it's generally not offered clinically, and this is because, you know, there are a host of reasons people offer, but to highlight a few. One, APOE is not needed for a diagnosis of Alzheimer's disease. Having that E4 allele doesn't rule out or rule in that a patient has Alzheimer's disease as the cause of their dementia. It doesn't change prevention strategies or treatment strategies to know that somebody carries an E4 allele. Some people also worry that it's just very difficult to communicate APOE risk because it's very probabilistic, and they think people will understand the results, and there are also some concerns that it's not safe to disclose this information given how feared dementia is, right, which is the effects on your memory and thinking, and Alzheimer's disease being the most common cause of dementia, the thought is that this is the kind of information that can be unsafe to give to people, so we can say all of those reasons why, I think somewhat paternalistically, people want to interfere and say they're not going to disclose APOE results clinically, but the fact of the matter is that people do want this information. So I'm going to tell a true story. This is not a true picture of this story, but a true story of
direct consumer genetic testing, so one of my very oldest friends, and by that I mean somebody I went to high school with, not numerically old, ended up doing 23&Me genetic testing just for fun, and she was clicking through her results to see what she could learn about her ear wax and whether or not cilantro tastes like soap, when she saw that she had two variants detected for the APOE gene. Now 23&Me only speaks to your E4 alleles, so this meant that she was an E4 homozygote. She wasn't really quite sure after reading this report what that meant, or even what she should think about it, and so she took a screenshot of her 23&Me report, and she texted it to me along with these questions: Well should I be worried, and if I'm worried what should I do so? Somebody who spends a lot of time thinking about this I kind of had to sit back for a minute, and think oh boy, what am I going to tell her to help contextualize these results. So it turns out that I spend a lot of time talking with people who have learned their risk for Alzheimer's disease either through genes or biomarker testing, and these are people who have chosen to participate in Alzheimer's disease research, so what we know is that this is a diagnostic label with particular significance. People consistently point to four differences between APOE test results and other kinds of medical information they may receive, so the first of these is they highlight the ways that memory and thinking play a uniquely important role in identity formation and their sense of self, so people talk about how this result, unlike say a colonoscopy, because their brain is involved has a different import. They also report that having this information changes how they think
about their own memory, so E4 carriers are more likely to reinterpret memory concerns as perhaps the onset of Alzheimer's disease whereas other individuals are likely to, who learn they don't have an E4, are likely to think of this as normal aging. People express concern that others will treat them differently in light of this information, so that stigma or negative attitudes and discrimination, which is behaviors based on those attitudes, and that can occur in the workplace, in insurance purchasing, or in housing purchasing. People talk a lot about the uncertainty of outcome. They're really not sure if they're ever going to develop
dementia caused by Alzheimer's disease, and finally, they speak about the lack of medical action ability. There's really not a lot they can do to step in and prevent the onset of dementia. Now, I will say this is one of the two main updates I would offer since I wrote the chapter is that FDA recently in June of 2021 approved Aduhelm using the accelerated approval pathway for the treatment of Alzheimer's disease. It was incredibly controversial given that there is uncertain evidence of benefit, but there is very clear risk, and very high costs associated with it, so as of now, there hasn't been particularly strong uptake of Aduhelm in the marketplace, but really FDA did open the door for other companies to put forward drugs for Alzheimer's disease, so this last category I would say is in the midst of changing. Now, we also know that learning your Alzheimer's disease risk or APOE results is generally safe, so I have to offer the caveat that this is from relatively homogeneous populations, but we don't see depression, anxiety, or suicidality after people learn their risk. Now that being said, we don't want to sort of overshadow that there's a really rich emotional reaction once people learn these results. Unsurprisingly, people who learn they're not carriers often talk about
relief and happiness to the point of ecstatic joy, and people who learn that they're at increased risk can talk about sadness, disappointment, worry about burdening others. They talk about, you know, fear that they're going to become a shell of a person. Nevertheless, once people learn whether or not they carry an APOE E4 allele they often talk about this information as being empowering, and we see this in two main areas. The first is that individuals often adjust their health behavior, so people who learn that they have an E4 allele will start running again.
They'll take on the Mediterranean diet. They talk a lot about playing Sudoku, engaging socially, volunteering more to try to keep their brains active. The other thing do is they alter their future plans in light of this information, so individuals who learn that they don't carry an E4 allele talk about having a more open or broad sense of their future, feeling like they're freer to plan ahead, but people who carry the E4 allele will contemplate changes or actually make changes to wills, advance directives. They might downsize a house, move closer to an adult child, typically a daughter who can serve as a caregiver. They will also make trade-offs between working longer to save money for caregiving or retiring sooner to check things off the bucket list before they're no longer cognitively able to do that. So the second big update since the chapter came out is that I don't think that APOE genetic testing is the only kind of direct consumer testing for Alzheimer's disease that we're going to have. There's a lot of enthusiasm in the scientific community for
blood tests for Alzheimer's disease biomarkers, and those biomarkers speak to the presence of 80 pathologies. You can actually start to see changes in the brain that are indicative of Alzheimer's disease, and there's a feeling that within the next few years, we should have tests that can consistently do this using just a blood sample, so if that happens, I would say that we are going to have direct consumer biomarker testing, and that's because both we have already a regulatory framework for FDA to look at tests like these, and there's a business model. We know that there are already multiple companies that exist where people can bypass that traditional clinical encounter to have blood tests ordered and go ahead and order it themselves online, so with that I think we're going to see that, you know, APOE testing is not actually the end of it, it's actually the first of many direct consumer tests that we're going to have for APOE results, so in wrapping up, I would just say that there are a lot of reasons why people are worried about APOE testing, but the evidence really doesn't bear out that those are as worrisome as people think they are. That said, I think that services like 23&Me are not doing people like my friend
any services by simply telling them they have E4 alleles. It's really important to contextualize this information, to talk about the uncertainty of risk, and to help understand what other people do in light of this information, so I'm not suggesting that 23&Me should offer any sort of prescriptions for what people do, but as they already linked to scientific evidence, they should think about linking to social evidence about how people use these results, so the bottom line is that nobody should be in the position of needing to text a friend to say, "Um, now what?" Thanks. [NATALIE RAM]: Hi, so I'm your next speaker, and I just want to thank everyone for being here and for inviting me to speak with you today. I'm going to speak
a little bit about law enforcement use of consumer genetic technology, and its growth and some problems with that use, so since the April 2018 arrest of the Golden State Killer, law enforcement investigators have made arrests in scores of cold cases. Investigators in these cases compare preserved crime scene DNA to other DNA profiles in online genealogy databases. In nearly all of these cases, those searches in turn uncover partial genetic matches to known, but distant genetic relatives of a putative suspect, and through sleuthing in the resulting family tree, investigators have been able to identify suspects for investigation, and in some instances, arrest. Now law enforcement interest in using consumer genetics platforms to solve more crimes has unsurprisingly materialized rapidly, and continues to grow. Parabon NanoLabs, which was the first private company to capitalize on law enforcement interest in this technique investigative genetic genealogy, now has several competitors in the field, and at least two consumer genetics platforms, GEDmatch and Family Tree DNA, openly cooperate with law enforcement efforts. The field is also already maturing. GEDmatch
started out as a hobbyist genealogy site, but it has since been acquired by a forensics company, Verogen, thus formally shedding its hobbyist roots for a forensic future. Now proponents of using these consumer genetic platforms to investigate and solve crimes have argued that the genetic data on which these investigations rely has been voluntarily uploaded and shared. Individuals at Parabon NanoLabs and elsewhere have emphasized that investigative use of these platforms utilizes only voluntary data. While sites that cooperate with law enforcement have likewise emphasized supposed voluntariness by say introducing new options that permit site users to opt out, at least in theory, from most law enforcement uses, but I want to suggest that this assertion of voluntariness is mistaken on both intrinsic and practical grounds, and the reason for this is as follows. In nearly every case thus far announced,
the individual who was ultimately arrested did not himself upload his genetic, identifiable genetic data to a consumer genetics platform. Rather that individual was identified through a match between crime scene DNA, and the profile of a genetic relative. In many instances, including in the case of the Golden State Killer, the genetic relative whose DNA and identity was available to police was a distant one, and yet identifiable genetic data is shared within families in profoundly involuntary ways. After all, as we all well know we don't choose the families into which we are
born. Now parents might in some sense be said to volunteer to share their genetic data with another person by choosing to procreate, but children, poor children, cannot be said to have chosen their genetic parents, nor do individuals in any real sense choose how many siblings their parents give them, or whether they have aunts, uncles, cousins, how many and what arrangement of each. Rather these genetic similarities arise as a product of biology without voluntary conduct or choice. These genetic ties are also immutable, not merely involuntary, but immutable. The identifying DNA that an individual inherits from her parents is the identifying DNA that she'll have all her life. Unlike a stolen credit card, one's genetic sequence cannot be changed, and these features of intrinsic involuntariness and immutability render genetic relatedness unlike most other relationships of data sharing in which individuals find themselves. Genetic
relatedness is stickier even than the social relationships we have with our family members. For instance, I could decline say my aunt's friend request, for instance, or I could unfriend her or disassociate myself from her on social media. I could even go further and estrange myself from her in the real world; thus, largely depriving her of information about say my new car, my comings and goings, my significant other, and the like ,and yet that ant could still serve as reliable as ever a genetic informant because our tie is involuntary and immutable.
Assertions of voluntariness are also misplaced in the context of genetic relatedness on practical problems. Consumer genetics platforms like 23&Me, Family Tree DNA, and others typically use wide-ranging genetic sequence data drawn from hundreds of thousands of DNA data points. Parabon NanoLabs, again, advertises that it can detect relatedness out to ninth degree relatives, that's your fourth cousin, while determining the precise degree of relationship out to your sixth degree relatives, that's your, for instance, second cousin once removed. How many of us are even certain we know who all of those cousins are? Under these circumstances, it is simply unmanageable for an individual to know of, monitor, and persuade each of those relatives to protect her genetic privacy if that's what she desires. Now I argue that this disjunction between claims of voluntariness and the reality of familial forensic identification is problematic for both logical and legal reasons, so for one thing, if the rule supplied by law enforcement for its use of consumer genetic data is voluntariness, the data is voluntarily provided, and if implicitly included genetic relatives are included involuntarily because of an involuntary genetic association, they just don't fit the rule for inclusion, and their inclusion in law enforcement efforts is therefore inappropriate.
For another, the result of familial inclusion investigative genetic genealogy for law enforcement use amounts to a de facto national DNA database or something rapidly approaching one. More than 26 million people have already made use of some consumer genetic service, and these platforms continue to grow, although at a slower rate than previously seen. Law enforcement access though to as little as 2 percent of the population, perhaps as few as 5 million consumer genetic profiles, could make more than 90 percent of Americans at least those of European descent, identifiable through a third cousin or closer, a relationship that a company like Parabon says they can identify with precision. As law enforcement already has the cooperation of at least two consumer genetics platforms, that two percent figure is rapidly coming to fruition if it's not already upon us. A de facto national DNA database is thus on the horizon if not already here, and yet, no US jurisdiction has indicated that a comprehensive DNA database of residents would be appropriate. Each and every state and the
federal government has legislation that identifies whose DNA is subject to routine government search for crime detection purposes. None of them have said that everyone should be in the database. Each instead has limited the database to some subset of individuals arrested or convicted of crimes. Indeed when legislators have proposed expansions in the state official DNA database to include those without known criminal histories, they have been met with outcry and failure. In other words, many Americans are profoundly not on board with comprehensive genetic identifiability for law enforcement purposes, and in my view, if an authorized comprehensive DNA database would be inappropriate as a matter of policy, the de facto accomplishment of the same end by involuntary genetic associations should be similarly inappropriate. Finally, I think law enforcement use of this kind of data may raise fourth amendment problems.
The US Supreme Court has interpreted the Fourth Amendment of the US Constitution to protect individuals against unreasonable government intrusions upon an expectation of privacy that society is prepared to recognize as reasonable. In applying this test, the Supreme Court has typically excluded from its concern, information that an individual knowingly or voluntarily shares with a third party, but the US Supreme Court has recently begun to chip away at that rule at least as it applies to sensitive digital data. In its decision in Carpenter versus United States, the Supreme Court recognized that individuals can maintain a reasonable expectation of privacy in their location data, at least as it's revealed by cell site location information, concluding that among other things the sharing of that kind of data, that sensitive personal data, with one cell phone provider isn't really knowing or voluntary given the ubiquity and necessity of a modern cell phone. Now it might seem odd to talk about cell phone data and genetics in the same conversation, but I think there are similarities here. Assumptions of either knowing or voluntary sharing of data are similarly inappropriate as applied to familial forensic information. As I've explained it's a practical impossibility for an individual to know of or monitor each of the hundreds of other individuals whose genetic data may illuminate her own, nor is identifiable genetic data in any sense a voluntary exposure as between shared genetic relatives since that data is shared among genetic relatives involuntarily nearly all the time, and always immutably, and in the absence of either knowing or voluntary sharing of this data, the Supreme Court has instead held that law enforcement access to this kind of private sensitive data may in fact violate the Fourth Amendment. I think that conclusion is warranted here, too.
Now in the book, I offer a possible path forward drawing on doctrines from property law as an analog for thinking about enmeshed interests in an indivisible form of ownership. In the interest of time, I'm not going to discuss that in detail here, but let me close by simply saying this, yes, resolving cold cases and bringing wrongdoers to justice is laudable, but investigative genetic genealogy's reliance on matches between involuntarily identifiable genetic relatives should prompt us to ask serious questions about whose genetic data is now included in law enforcement searches, and what's the justification for that inclusion. As I've suggested, assertions of voluntariness just won't do. Thank you. [JAKE SHERKOW]: Well hi everyone. I'm your last speaker today. I'm Jake Sherkow. I'm Professor of Law here at University of Illinois College of Law, and I just want to take just a brief moment just to thank everyone at Petrie-Flom for having me, again all the organizers and of course administrators for the conference, and to Glenn and Carmel for putting the book itself together, which you should go on Petrie-Flom's website to purchase, and to Hank for moderating. The chapter I'm going to talk
about, chapter 12 of this book, is a joint work by myself and Professors Christi Guerrini at Baylor College of Medicine and Patti Zettler at the Ohio State University who really deserve all of the credit, and only I the blame. In this world of research, National Institutes of Health Policies, the Common Rule, IRBs, it's surprising that there is genetic bio hacking out there, essentially, research outside of this institutional ambit for which many of us are used to genetic research being conducted, but it exists, and it is growing. There are some estimates that it encompasses tens of thousands of people in the United States. A 2017 report indicated that at least there were 30,000 people conducting it, and I imagine that during the pandemic when you can get anything that you want on the internet, you've got, at least some people do, have a lot of time on their hands. I would imagine that number has only gone up. Is this activity regulated either de facto or de jure, and should it be? We explore in our piece in this chapter here in three parts the answers to some of those questions. We do it by looking first at public regulation, then by also looking at private regulation, and then some of the normative aspects that is the should questions in our moving forward section of our chapter. Obviously it's important that I start
off with some definitions, right. What is genetic biohacking? We define it as biological research conducted outside of institutional settings by individuals who may or may not have any formal scientific training. Garage shop hobbyists who have a late in life appreciation for biology can do this as much as PhDs who have founded community resource labs. It is
all genetic biohacking for our purposes, and regulating it as a matter of finding a balance between the scientific endeavor, broadly speaking, and of course, safety, health and welfare, not just of biohackers but of everyone around. Let's begin with public regulation, so one way biohacking seems to be regulated is through public regulation, the regulation of entities by the government or by public agencies. The most obvious source of these seems to be the FDA, the Food and Drug Administration. Right, FDA famously regulates a quarter of every dollar spent in the United Atates although these days it's really closer to 22 cents, but still, and notably the agency has authority over quote unquote drugs. Drugs, as you may know,
are those articles intended for quote the diagnosis, cure, mitigation, treatment or prevention of disease or quote intended to affect the structure or function of the human body. This is an objective standard, the intent standard, and it really is broad and encompasses both traditional drugs that we would consider like pills and things of that nature as well as things like fecal microbiota transplants of which I will discuss more later. In addition, beyond these, FDA's authority is broad. It has already commented that in 2017 genome editing itself, whether it's by biohackers or otherwise, can be gene therapy under its purview, and therefore, regulable, leading to a suggestion that some of the biohacking kits that are sold today, at least for humans, are already drugs under FDA law. At the same time, FDA authority generally does not extend to true instances of self-experimentation, at least where no physical article has crossed interstate boundaries or where pure information, rather than an article itself, is the thing that is being trafficked.
Some biohacking examples show this, so one case is the EPI pencil by Four Thieves Vinegar Collective, a bio hacking collective among many other things, which is just simply a series of instructions on the internet for making one's own knock off EPI pen for those who otherwise don't want to shell out $600 for a 2-pack. Those instructions alone are doubtfully under FDA's purview. On the genomic side of things, biohacking kits that focus on non-therapeutic uses, such as just playing around with bacteria for fun, probably don't count either. Importantly, as we note in our chapter, drawing this line though is really not ever so clear. In the FMT example, fecal microbiota transfer, regulating poop as a drug is something that probably only a lawyer could love and an FDA lawyer at that, and biohackers rightfully complain of this confusion.
This is a shame, we think, because FDA has the expertise here to provide information on safety as well as public service and making clear about what the agency does. Even after COVID-19, the public seems largely confused about FDA's role and its jurisdictional authority, so for FDA, it needs to be more clear when it comes to biohacking about the limits of its authority in the experimental space, and relatedly, to do more public service announcements to make that clear. To be frank, this is work FDA already does in a variety of other contexts. It's November 2nd. In three weeks, we're going to get a lot of messaging from FDA about making absolutely sure our Thanksgiving turkeys are cooked to an internal temperature of no less than 165 degrees Fahrenheit. Why not do something similar for biohacking? Well
that's public regulation. Let's move on to private regulation. Well to begin with, we have a number of options for private regulation, and one of those options is, believe it or not, patents. Patent holders can police safe and ethical uses of genomic technologies by biohackers by suing rogue users for patent infringement. You're skeptical. Fine that's fair, but this is an idea that has been floated by scientists in the field, and is actually part of genome editing patent license restrictions from several academic institutions. As a historical matter, IP holders have in fact sued downstream users for IP infringement before it occurred behavior, from copyright infringement for illegally downloading music and movies to patent cases against users of, not-manufacturers, but users of certain infringing photocopying machines. Patents are one tool among several for policing unethical uses or dangerous uses of genetic biohacking. More on point perhaps
is tort law and flip side of that coin toward avoidance. Biohackers are aware of this. They don't want to get sued if something goes wrong with their kits or in their community labs, and this was identified in structured interviews with biohackers as conducted by Professor Guerrini. One person said quote, "If something goes wrong, it's your fault. It's all your fault." Tort avoidance here seems to do a lot of work. It encourages people to shovel their driveways, to carry car insurance. It governs private behavior in myriad ways and could do so for the biohacking community here. There are also community mechanisms in place, essentially,
safety policies and even agreements, contractual agreements, concerning compliance using the biohacking space. You want access to a community lab you got to play by the rules. This is a form of self-policing that works as well as any formal mechanism may otherwise do. All right, moving forward, so genetic biohacking is out there. It's used in drug manufacturing, genome editing, DIY medical devices. The interest is there. What to do about it? Well first, whatever policies we impose on genetic biohacking, we can't expect a hundred percent compliance. There are going to be rogues. This is true even in institutional contexts with all of its safeguards.
There's He Jongkwe of course, but there's also instances of professors that you've never heard of in institutional settings engaging in more day-to-day research misconduct. Our policies there are not a failure because some people break them, any more than criminal law is a failure because we continue to have criminals. Indeed one may argue, the law is a victim of its own success. Beyond this regulators need to better engage with the biohacking community. Engagement does not mean giving a free pass to. It means making clear which conduct is going to be enforced and then actually doing the enforcement and then educating the rest so that people can do it safely. Other regulators have done this at workshops before and we should continue. To be sure, this is
not going to be universally appreciated by genetic biohackers. Among some biohackers, not all, there's a decidedly anti-government sentiment. Government get out of my community resource lab. Engagement may be a bulwark against this at least one might hope if we are a wild optimists. Third, we, and by we I mean the institutional people in this room, recognize benefits of community science. That is we must do something. We already do this for open innovation initiatives. Some of those are sponsored by public agencies like Department of Health and Human Services and FDA's competitions regarding health apps. Biohackers tend to be users of these technologies. They are aware of their pitfalls, and we should not waste their understanding of the way that these technologies are used as a resource. Fourth, it's probably pretty important that
we tailor enforcement to the particular approach employed. Experimenting on yeast to brew and beer, well that's one thing, but developing say an insulated protein-based COVID-19 vaccine for wide distribution to the public that's another, and should be policed differently because of the potential for harms. As our chapter's title suggests, it's simply all about finding this right balance. All right, thank you very much. I'll turn it over to you Hank.
[HANK GREELY]: Well thank you Jake and Emily and Natalie. I am Hank Greeley. I am moderator for this, which means I'm going to be reading the questions that you put into the Q&A box, so please put questions into the Q&A box, and transmitting them to our speakers for their takes on them. Before I do that, let me just say a little bit about the background of this. This was a great conference. It was held in may of 2019, approximately eight months BC. It wasn't actually the last conference I went to before COVID, but it's sort of the last memorable one I went to before COVID, and it was a lot of fun. It was,
however, it was in theory organized by Glenn Cohen, Nita Farahany from Duke and myself, but in reality it was organized by Carmel and the other Petrie-Flom staff, and we had 20 some speakers. 20 of those presentations have turned into chapters for this book, so the book is a direct result of that excellent conference. The only minor complaint I've got is the book apparently at the insistence of Cambridge University Press is entitled "Consumer Genetic Technologies," but the conference was called "Consuming Genetics," and I thought "Consuming Genetics," was a much better name, but that may just be because I like consuming things; however, still a good book, still a lot of interesting sections chapters, and a lot of interesting questions we can have from the audience, so please send your questions to the Q&A function on your Zoom.
Let's start though with one that we've gotten, and this I'm going to aim at Emily. How much better over the last 20 years, if at all, have we got that understanding what the risks are the various APOE statuses 4 4, 3 4, 2 2, etc. [LARGENT]: So when we talk about these numbers with patients and research participants, even now, we tend to give these very wide ranges, so for an E4 homozygote, we say that the risk of developing mild cognitive impairment or dementia caused by Alzheimer's disease is in the range of 30 to 55 percent, and, you know, one in three sounds a lot better to me than one and two. I would say that part of the challenge here is that we have so many factors involved in whether or not someone develops mild cognitive impairment or dementia caused by Alzheimer's disease. I listed out you know age, race, sex, personal medical history. I think it's hard to give that kind of precision. There are some
researchers who are trying to create personalized calculators that I think will do a better job with APOE being one factor of many. The other area that we continue to need to improve here is just having more representative populations. I think we understand how the E4 allele works you know very well in some populations, but not in others, so progress is slow. I think that APOE should be part of a multi-factorial consideration of risk.
[GREELY]: Okay well here's a question for Natalie. Two of the, well GEDmatch and Family Tree DNA are cooperating to some extent with law enforcement. I think GEDmatch initially went to an opt in, and then it went to an opt-out, and back and forth, but the two bigies, Ancestry is far and away the largest and 23&Me is kind of half its size or 60 percent of its size, are not. Has this caused a slowing in the use of genetic genealogy in forensics? I haven't seen as many newspaper stories about it, but that may just be because it's old news. Any sense of the trend? [RAM]: The trend in the growth of these services, or the a trend in the growth of cases resolved using these techniques? [GREELY]: The trend in the attempts to resolve cases, which you could probably only get from the numbers of cases resolved. [RAM]: Yeah, okay, so I still get plenty of alerts indicating that there's work continuing in this space.
You know, I think when this technique first made headlines, there were a lot of cold cases that had perhaps more easily usable DNA, and so there were, you know, there were headlines of an arrest almost every week. I will say sin since the beginning of the pandemic the headlines have slowed down. Now whether that indicates a slowing in, you know, law enforcement use or interest, or whether that reflects the media's, you know, attention on another sciency topic is, you know, I might think it's a little bit of both. I do know that the federal government is making
funds available to local law enforcement to try and clear cold cases using this technique. When that happens, there is a a an interim policy in place from the Department of Justice that governs how those investigative genetic genealogical searches are conducted, but, you know, I think the DOJ policy in my view doesn't go far enough in a number of key aspects. [GREELY]: You know if I can follow on on that for a second, it doesn't have to be a genetic genealogy database to do this. You just need a really big, broad genetic database of some sort, obviously the CODIS database is one, and its use for genetic genealogy is quite limited as I understand it. [RAM]: Yes. [GREELY]: But there we've got these increasingly large research databases, and ultimately, we're going to have genetic information and electronic medical records. It won't be in the form of the CODIS markers, but it will be in snips that can equally be used. Have you seen anything yet about the use of none
genetic genealogy databases for this kind of forensic use? [RAM]: So I'm so glad you asked because that is what I'm thinking about and writing about and researching now. I've been thinking and looking at consumer genetics data for the last while, and my attention has now been shifting towards precisely those research and clinical data. Now, you know, my my primary interest here, and I think kind of the lowest hanging fruit is newborn genetic data. Nearly every newborn, nearly every infant born in America has a blood sample taken within 24 hours of their birth, and that is sent to a state lab for analysis. It's not usually,
or it's not largely genetic sequencing, but if you talk to the folks at the federal government at NIH and NHGRI, they say it is only a matter of time before we are doing genome sequencing. You know, I think there's opinions that vary on how soon or likely that is to come to pass, but if and when it does that will yield genetic sequence data for virtually every American, and at that point you know my my focus has turned to what are the state policies in place to protect that extraordinarily valuable resource both from a clinical perspective because it's, you know, newborn genetics, newborn screening is designed to ensure the health of every newborn American in certain ways, but it's also an extraordinarily valuable research repository, and if we want to protect that for both clinical and research uses, we might want to rule out indiscriminate law enforcement use, which might undermine public trust in those programs entirely. [GREELY]: My recollection is from some litigation in Texas and in Minnesota. [RAM]: and ongoing in Michigan
now. [GREELY]: Yeah and the issues seem to be completely state by state, and there's a lot of variation about what gets preserved and saved and what doesn't. [RAM]: That is absolutely right and for how long. [GREELY]: So Jake, I liked your example of poop isn't as a drug. I think one of my, I've had dogs before who thought that was the case as far as I could tell, but maybe they just thought it was food refried dog food, but I've got another example. The FDA views cloned human embryos as drugs, possibly as biological products, probably is both, but certainly it's jurisdictionally within its power. If you were the tsar, and able to
do anything you wanted with FDA and DIY, what's the most important thing you would do? [SHERKOW]: I mean I think there's two main concerns. One of which I've written about, actually with the same suite of co-authors, plus one more, and another one of which, I think it's just kind of garden variety FDA stuff, so the one I've written about with other co-authors this again is me, Christi Guerrini, Patti Zetler, and in this case, Michelle Meyer at Geisinger Health, is in the DIY biospace, the availability of the stuff, or at least the promulgation of it as being safe and effective even though no controlled clinical trials have been run to demonstrate that that is so, I think has the potential of depressing the public's confidence in FDA writ large. This is obviously a matter of significant public concern right now. You hear people who are refusing to get one of the COVID-19 vaccines because they believe that FDA has somehow botched the job by rushing it or by authorizing it as opposed to proving it. A criticism I've always found to be funny because I did not realize that so many members of the lay public were experts in 21 USC section 360 triple B3. I mean that's just kind of astonishing, but okay fine, right, and so I think that FDA should
should really go out of its way to police attempts to circumvent the therapeutic process because it really has some significant public health concerns not just to the use of the product, right, but to people kind of um losing their faith in FDA, and its ability to keep safe and effective products, I guess, on the market, and unsafe and ineffective products off of the market. We have written about this in the context of attempts to create a, essentially a, DIY COVID vaccine. This is being conducted by Radvac at Harvard, so no better place to come and bite the hand that feeds you, right, than here. The other flip side, which I think is just garden variety FDA policy stuff, is that we also want to make sure that to the extent these are actually going to be used therapeutically, right, that, you know, people are using them because even though it's self-experimentation, they think it's going to treat a particular condition that they have that there's at least some messaging about some limits regarding whether these things are safe and efficacious. Weirdly enough, FDA has done this pretty well, I think, in at least one instance, and not in others. The way it's done it well in the one instance is this suite of people taking
Ivermectin to treat COVID. If you go online to FDA's website, FDA does, I think, a good job carefully explaining in simple terms what the problem is about taking veterinary of available Ivermectin for COVID. You may not agree with it right that's a political persuasion issue but at least FDA has done a good job of saying this is why you should not do that.
When it has come to other DIY treatments, FDA has remained mum, and I think they've remained mum because they don't want to make a claim that they otherwise have jurisdictional authority over something when their Office of Chief Counsel has not yet made that determination or not, and I think it's just time, like this is happening again. We have at least 30,000 people in the US doing it. I have to imagine that during the pandemic that number has gone up rather than gone down, and so I think it's just time for FDA to kind of draw a line in the sand as to what it's going to do. [GREELY]: And to be fair to FDA, it's also the case that they've had other things on their mind in the last two years, almost two years. [SHERKOW]: Yeah
right. [GREELY]: So this one I think is mainly for Natalie, but spills over I think to Emily and maybe to Jake. Commercial databases are known to be skewed toward people of European ancestry, my insertion, as opposed to criminal databases, which are skewed against people with European ancestry in some cases. Is that a problem for the predictive value of biomarkers and for identification of criminal suspects, and what might be done about it? Natalie? [RAM]: So it is it is correct that consumer genetics platforms appear to be composed disproportionately of individuals of European descent, also disproportionately, of Americans in particular.
We should be careful here to acknowledge that being of European descent is not the same as being perceived necessarily as white, especially, in light of, you know, the history of slavery and and assimilation efforts regarding Native Americans. There are many individuals who identify as Black and Native Americans, who may in fact have some European descent in their ancestry, and so it would be a mistake to think that as I in fact once once did that the silver lining to investigate genetic genealogy is that it will disproportionately or uniformly identify white perpetrators. That is not the case it is to date it is disproportionately individuals who are white. That has to do in part with the fact that many of the crimes for which there are people still pushing strongly for resolution and for this technique to be used happen to be sex crimes involving white victims, and so those more often than not yield by perpetrators as well, but according to geneticists I've spoken with, in fact, the less specific information we may have for for say Black Americans may in fact indicate that they will be more likely to be approached for additional sampling or more likely to fall under police suspicion more often because the family trees that can be constructed will be less specific in the first instance, so there will just be less known, so that might mean that fewer of those cases will be pursued, or it could mean if they are pursued, a greater sweep of people will come within police investigation or suspicion and the like. [GREELY]: Of course, one way to avoid skewed samples would be an effective universal COVIS marker database, and I'm guessing Natalie you're probably not in favor. [RAM]: So I will acknowledge that there are some benefits um to forthrightly adopting a universal genetic database. Put everyone's DNA in
CODIS, so I think that there are advantages there of transparency at least. It's not a de facto DNA database we get as an end run around, you know, statutory limitations on whose DNA should be available for law enforcement use. Instead, we might have a forthright public conversation about the appropriateness of that broad sweep for law enforcement use. I think that kind of proposal would not be very successful in light of what's happened in the states where there have been efforts to broaden the official DNA database for law enforcement use. As I said in my talk, and I
note in the chapter in the book, those efforts have been met with outcry and swift failure, and I think that there are serious constitutional concerns about a universal database as well, so although it would be much more transparent, I'm not sure it would be more legally successful. [GREELY]: Well we need to go on, but I'll just note that the arrestee databases have not been that unsuccessful. The laws mandating collection from people who've been arrested, but not convicted, seem to be quite common. [RAM]: Yes those are common. Though I will note that those are individuals who still have a connection to the criminal legal system, which a universal database would not not. [GREELY]: I don't want to disproportionately pick on Natalie or send things to Natalie, but the questions are coming in more Natalie focused; however, this is one I bet all three of you have some thoughts on if not data on.
What do we believe other countries like, for example randomly chosen China, are doing with collecting resident or citizen genetic information? Anybody want to have input on that? [SHERKOW]: There was a recent report in Nature, it was one of the news pieces, about essentially genomically surveying the Uyghur population in China. Although for what purposes beyond that which can be accomplished by other means, which China seems to be doing is is not entirely clear, right. I mean, you know, it seems like other countries don't necessarily have the genomic privacy hang-ups that at least some of us share here in the United States. Some countries in
western Europe not withstanding and the GDPR's regulation of that, but I mean still not entirely clear what the upshot of this or even what the harms are other than the surveillance harm. [RAM]: If we want to talk about a country other than China, I will note that the UK is in the process of piloting genomic sequencing for newborns. That's something that we touched on earlier, and so that that's something that they are building out, and not necessarily for law enforcement use, for clinical use, perhaps research use, but certainly a greater collection of a greater swath of genetic information. [GREELY]: And
close to one percent of their population is in the UK bio bank, which that's expected to all be sequenced. It's 500 000 people, which is close to one percent of the population. Okay, we have I think a good closing question directed to everybody. As someone whose work focuses on genetics, but not so much on law, do you have recommendations for resources where I can keep up with updates in genetics-related legislation, and here because Carmel will want me to I will say well there is of course the Petrie-Flom blog, which deals with this, but other comments, other suggestions from you guys about what a geneticist might want to look for, look at to find law-related law-genetics-related stuff or learn about it. [SHERKOW]: So two thoughts right, so first there's a wonderful news service called Genome Web, which actually Hank you you got me on now oh 10 years ago or so. They really do some excellent reporting over there. There's also the news pieces from you know Nature News and Science and to a lesser extent Cell that does some reporting as well, and frankly Bill of Health is great. Get a lot
of different commentators from all over the world posting about, you know, topical issues and short bite-sized formats. I mean that's where I would. [GREELY]: The Bill of Health is the Petrie-Flom blog. I think STAT, which is another really good biomedical health service. You know, most of it is not about genetics or about genetics and law, but some of it is. Any favorite resource books, references, resources that you would suggest somebody start with? Apart of course for the books and articles that all of us have written, which obviously is the important first starting point. Suggestions? [LARGENT]: I'll put a plug-in for the Journal of Law in the Biosciences. I've found that there's a lot of really excellent work published there that touches on genetics and the intersection with the law. [GREELY]: I guess we better accelerate review of that pending submission from you, Emily.
As one of the co-editors in chief of that along with Glenn Cohen and Nita Farahany. Other thoughts? [RAM]: I just want to co-sign my co-panelists suggestions. I think that both the Bill of Health blog and the Journal of Law and the Biosciences are are excellent resources, and I have found enriching you know the the law and policy pieces that are in the major scientific journals. They're not always focused on genetics, but when they are, they're they're very informative. [GREELY]: Yeah and, you know, Jake mentioned Science and Nature, and to a much lesser extent, Cell, but JAMA, the Journal of the American Medical Association, the New England Journal of Medicine, and some of the sub like JAMA Internal Medicine and one of the, they're actually turned out to be 156 different, literally, according to Wikipedia, different Nature publications within that umbrella. They often publish some really good stuff. Glenn Cohen, the Director of Petrie-Flom publishes a lot of work in those venues, but,
you know, I wish I could say here's a great book that you can read that will tell you everything you need to know about genetics and law, but nothing's coming to my mind along those lines. [SHERKOW]: You could go through Sonia Suiter's casebook, but it's really synoptic in scope and one of the problems in this area is that stuff moves so rapidly that as soon as something gets into print literal print as opposed to the electronic forum. There's often something else right around the corner that may otherwise obviate it. [Greely]: Yeah
and I have to confess that although casebooks are a less bad art form than law review articles, for somebody who's not in the field, they're not prose that makes it easy to pick up on things. Even though the case books are supposed to be our method of teaching students, they're not all that easily accessible. They're also really really expensive and they don't come in electronic versions. Buy them used. All right well, I think it is time for us to end. I want to thank Natalie and Emily and Jake. I want to thank Carmel and all the other people at Petrie-Flom who've put this together,
and I want to say, buy the book. What you've just heard is a very small selection from a very rich book. There are 20 chapters. You've heard about three of them. There's section intros from the co-editors. It's at Cambridge University Press. It's from Cambridge University Press. You can buy it on the Petrie-Flom website or in you know bookstores and newsstands all over the world as long as they're called Amazon. It's available in hardback expensive, paperback less expensive. Not yet on kindle. Not on audio yet,
but it's such a good book that I would actually volunteer to narrate it, so I looked on Amazon, you can get it as early as this Thursday, but wait there's more if you order now we'll include a free set of ginsu knives. Not really. Thank you so much for attending. We hope you've enjoyed and appreciated it, and keep your eye open for future Petrie-Flom events. That's all folks.