Learning Health Systems - Panel Discussion on Genomic Medicine

Dr. Richard Payne

I'm going to – we got behind because we started late, and Dr. Lantos has to leave before lunch. So we're going to do – just make a slight modification in the schedule. We're going to – we were supposed to have a 15-minute break, but we're not going to do the break now. We're going to go ahead with the panel, and then we'll break after the panel so that we don't lose the benefit of Dr. Lantos's wisdom here this morning. Dr. Lantos and Dr. Atkinson are coming up.

Dr. Richard Payne

I think you know both of these individuals, but I will just say that Dr. Barbara Atkinson is one is well known here. She is retired as the University of Kansas Medical Center Executive Vice Chancellor, if I got that correct. And she is a member of the Presidential Commission for the Study of Bioethics Issues, which issued this report last year on privacy and progress and the whole genome sequencing that we've alluded to. And she is currently Vice Chair of the Center for Practical Bioethics Board of Directors. Dr. Lantos. He also probably needs no introduction to you. He is a well-known bioethicist, is the director of Children's Mercy Bioethics Center here in Kansas City, and professor of pediatrics at the University of Missouri, Kansas City, and has published extensively in bioethics. So I'd like to, and now this is the time also for our remote sites to participate. And I would just ask if you unmute your mics now, and if you, I'm going to ask the panelists if they have any brief opening comments, and then we'll go into questions and answers from the audience or from the remote sites. So maybe Dr. Atkinson, would you like, is there anything you would like just to say as an opening kind of comment from your perspective of being on the Presidential Bioethics Commission that studied this area.

Dr. Barbara Atkinson

I'll just say it's really been an honor and a privilege to be on the Presidential Commission. I did bring my copy of the report, and I'll leave it down here if people want to look at it over lunch and see. This is one of, I think we're up to about six reports now from President Obama's commission. This one was a really interesting one, and you've heard a lot about it already this morning about the recommendations. But it just is interesting. The commission is really looking at the most modern kinds of ethical issues in science and medicine. And you've heard about a couple of them today. one the President asked us to look at was synthetic biology, which you heard mentioned. We did a study on human subjects and informed consent as it relates to that, and then got into this whole issue of privacy in the genome sequencing, which, as you can tell, is really still in the process of things being decided about. And then most interestingly, I just got the draft last night of our next report, which is on incidental findings, which we also heard discussed, and what should be returned to patients in both a clinical setting, a research setting, and then in a direct-to-consumer setting. ANYWAY, I CAN TALK MORE ABOUT THE PRESIDENTIAL COMMISSION LATER IF PEOPLE ARE

Dr. Richard Payne

INTERESTED. I KNOW THERE ARE A SERIES OF RECOMMENDATIONS THAT CAME OUT. ARE THERE ANY ONE OR TWO THAT YOU SEE AS REALLY IMPORTANT TO FOCUS

Dr. Barbara Atkinson

ON? FROM THIS ONE, THE PRIVACY AND PROGRESS IN GENOME SEQUENCING, I THINK THE MOST IMPORTANT IS THAT WE NEED SOME KIND OF NATIONAL FLOOR OF RECOMMENDATIONS FOR WHAT SHOULD BE KEPT PRIVATE. individuals there's a little bit as you heard at a national level but individual states have they have different regulations and so depending on what state you live in there's different degrees of helpful privacy that's that's afforded an individual person and then about half the states don't have any requirements at all for privacy. So I think that coming up with some general floor of privacy recommendations to me is the most important.

Dr. Richard Payne

Now, where do Missouri and Kansas stand?

Dr. Barbara Atkinson

You know, I don't know the answer to that. I have a feeling. Do you know, Alan? No. And Wisconsin, I think, does have some recommendations. I'm not sure about Kansas and Missouri.

Dr. Richard Payne

Dr. Lantos, would you like to make any kind of opening remarks? comment or statement.

Dr. John Lantos

So I'd just like to pick up on the Henrietta Lacks story and throw out a couple of questions that I think picks up on some of the things that both Misha and Alan were talking about. I have to admit, when I read the Henrietta Lacks story, and even to this day, I still have trouble figuring out whether Ms. Lacks was harmed by what happened to her at Hopkins, and if so, exactly how? I think she got state-of-the-art treatment in one of the top medical centers in the world for her cancer. What was done to her was done to thousands of other patients at Hopkins throughout the 1940s and 1950s and millions of patients throughout the rest of the United States up to this day. That is, she had a biopsy. The biopsy was stored in a freezer. She gave consent for any surgical procedure that doctors at Hopkins deemed necessary to help treat her tumor. Whether the biopsy was directly related to helping treat her tumor or not is unclear, but it was certainly what everybody else had done. And unfortunately, her treatment wasn't successful, and she died. So to me, it raises a couple of questions.

Dr. John Lantos

Would the harm to Ms. Lacks have been different if instead of calling them HeLa cells, they called them brand name super tissue culture cells and nobody ever made a link to Henrietta Lacks and they went on to be used in all the scientific ways that they were used and came out of a Hopkins lab and all that anybody who ever got treated at Hopkins would know was Maybe they were mine, thousands of patients. Or second question, would she have been harmed less if her cells hadn't grown? And so there would be no HeLa line and nobody would know that these had been taken. In other words, was she harmed more or less than all the other patients who had exactly the same procedure done? And it seems to me she wasn't harmed at all. So third question, if you think she was harmed and if the harm had to do with being identified as the source of these cells, was there an additional harm to having the genome sequence of the HeLa cells published this year?

Dr. Richard Payne

Those are really interesting questions. And you've made those, you've done that, a bioethical kind of analysis of a harm, but isn't there another aspect of the whole story, though, which just plays into a larger narrative about exploitation of people, and particularly people of color? Now, that's not a, I mean, that can be framed as a bioethics issue in some context, but isn't that also, though, part

Dr. John Lantos

of the story? Great question. I think what Rebecca Skloot's genius was was to take a story that was relatively innocuous about medical procedures that are routinely done throughout the world and tie it to a story of justice, discrimination, and race in the United States in a way that took the power of our outrage about race and attached it to and medical research in a way that I think is actually quite invalid. Medical research aspects

Dr. John Lantos

are less problematic, and the fact that poor black tobacco farmers had trouble getting good medical care in the 50s and continue to have trouble today is very problematic, whether their tissues are used for research or not.

Dr. Richard Payne

Sure.

Dr. Barbara Atkinson

Can I just comment on another piece of it, which is the issue that the Commission has really focused on in almost every single one of the reports that we've done, and that's the whole public benefit of it, which is the other half of her. If you really look at what's come from the use of those cells, it really is phenomenal. The polio vaccine would not have been done, at least at that point in time, without those cells, as well as what's known about the mechanisms of tumorigenesis in a whole variety of things. So you balance a public benefit with the individual privacy concerns here or with concerns in synthetic biology, it's even clearer because there's a huge public benefit potential from generating organisms that are done in by computer with chemicals but there's a risk to the public too of what if those get free into the atmosphere and do something terrible so so there's always a benefit risk kind of analysis, and that's been really true for every one of these issues.

Dr. Richard Payne

We have a question in the back. I just ask you to speak up and also want to invite our participants in our remote sites, if you're still with us, this is your time to engage. Yes, sir.

Brief voice 1

Right. Right.

Dr. John Lantos

So I think a summary of the question would be, was Henrietta Lacks harmed by not getting a share of the profits?

Dr. Richard Payne

And is there just a sense of injustice that other people have profited?

Dr. John Lantos

And other people profited. OK, so how many of you have ever had a biopsy or some tissue removed in a medical procedure? If, giving consent for that, they had said, Would you allow us to use this for research rather than just throwing it away? How many people would have insisted that if any financial profit came out of that research that you deserve a share?

Dr. John Lantos

And I think what the researchers would probably have said if you said that was, well, then we'll just throw your tissue away because it's not worth the trouble of developing a contract. I guess sort of makes sense to me. How many people have a cell phone? How many people use Facebook email? How many people have stopped now that you know the National Security Agency is reading your

Dr. John Lantos

email? Or that Google is profiting off your searches? I mean, do you demand a cut of Google's profits because they're benefiting from your information. I mean, I don't really think what you contribute by doing a search or what you contribute by letting someone have your appendix or cervical tissue biopsy is worth much.

Dr. Richard Payne

Yes, speak up, please.

Music / non-speech

Right.

Dr. Richard Payne

Yeah. Yeah, that's a good argument. It's a slippery slope argument. And actually, I met an entrepreneur in the research triangle who actually was trying to monetize a concept where people would actually get value for their medical records, particularly, and he was very focused on people who lacked health insurance at the time. So do either of you want to respond to any? Or Misha or Alan? welcome to respond as well.

Misha Angrist

Well, I think that's a bit of a red herring, this notion of avaricious patients and research participants demanding a cut. Yes, there is a legal history, John Moore wanting a piece of the pie that came from his hairy cell leukemia in his spleen, but in that case, in the Greenberg case, the courts, I don't think they got it completely right, but they recognized that the problem was the patient slash research participant was not told what was going on. And so if you ask me what was the harm suffered by the Lacks family, I would say it's death by a thousand cuts. And I would say the

Misha Angrist

Perhaps the microcosm, the emblematic harm that was done to them was in the 1970s after HeLa cell contamination ran wild. And I would encourage people to reread this part of Rebecca Skloot's book, because I think it's extremely powerful and extremely damning, where someone from Hopkins was dispatched to secure additional tissue samples from the Lacks family. And it's very clear that Day Lacks, Henrietta's widow or widower was believed that he was undergoing some kind of therapeutic test for cancer. And in fact, what he was doing and what his family was doing was saving Hopkins and Gila's bacon by giving these sorts of things. So the harm was not some kind of capital crime necessarily, but it was simply a lack of effort, something that could have been done very simply and very easily to communicate to people what you're doing, was not done, and we see this repeated decade after decade until this year.

Dr. John Lantos

But I'm not clear whether you think Henrietta herself was harmed. It's clear, I mean, if you're focusing on the 70s and what they did when they went back and lied to her family, that's a very different sort of thing.

Misha Angrist

Sure, well, I mean, I think we always get into trouble when we judge historical events by the ethical, moral, legal standards of today. And so again, just as I would say that the EMBL researchers didn't break any laws by not consulting the Lacks family, neither did George Guy break any laws. And obviously there was no way to know what the outcome of that was going to be, as you rightfully point out.

Misha Angrist

I guess I... I object to the premise of the question that I don't think it's purely about whether she suffered harms. I think what makes the story compelling and maddening is this decades-long accumulation of

Misha Angrist

minor injustices. Alan, did you want to

Dr. Richard Payne

comment? Sure. And just I'm going to remind people at the remote sites, just say that you want to speak up and we'll acknowledge you. Wave your hand. We can see you. Wave your hand, yes. We can see you.

Allen Buchanan

Yes. I would agree with a lot of what John says in terms of not seeing a way in which Henrietta Lacks was harmed. And I think that's exactly why we need to understand background conditions of autonomy and being able to instantiate things that one cares about. if she had had some idea that her cells would contribute to lots of both profit-making and advances in medicine, against a background in which her family and others like her family had very poor health care, she might not have agreed. But even if she had, she agreed. it's almost impossible to anticipate what those kind of effects would be. And so to think of this in terms of consent, it really doesn't, I think, make conceptual sense. And I think that it does, and where I want to agree with John, is that the background conditions really are what matter here. And the fight about heel is in many ways a proxy fight for other conditions in which people's lives are constrained. Their autonomy, their ability to act according to things that they want to do is constrained by lack of lots of things, economic opportunity, but also health opportunity.

Dr. Richard Payne

Any questions from the remote side? Yes. Was that? Okay.

Remote-site question reader on whole-genome-sequencing consent

Okay. Dr. Rubel proposed that the background can be changed regarding consent for WGS. Would it meet that definition to more specifically include and emphasize the possibility of unknown risks during the informed consent process?

Dr. Richard Payne

Yeah,

Allen Buchanan

that's a fair point. I think it's hard to understand that as part of consent. It's difficult to see how one could actually anticipate all of unknown risks, and to the extent that those are unknown, it's hard to call that informed consent. There's agreement, but the degree to which I authorize things that are... I autonomously authorize things where things are just unknown, I think is limited. And also I think that where the harms, the potential issues for unfairness or discrimination may be substantial enough in some cases that we might not think it's morally acceptable to allow those kinds of risks to be given up or allowed in a contract or an agreement like that. Yeah.

Misha Angrist

So we routinely include language now in Duke consent forms that come to the IRB for genomic research that there may be unforeseen unknown risks. So that's great, but I don't sleep any better for the presence of that language. Right, right.

Dr. Richard Payne

Yes, Stephen?

Stephen Kingsmore

Now just to take this one step further, so one of the unique things about a genome is that it has profound implications for your progeny.

Stephen Kingsmore

And so while there are consent issues for the individual, there's also consent issues in some regards with regard to progeny who may not yet exist. So just to put this in context, we recently decoded genomes of archive samples from some of the most famous people in history. One I can talk about is Charles Darwin, but some rock stars and stuff like that. And so around that, because it was going to become a TV show, was this huge process of, do we have the right to this material? What if we find stuff? Talking to the families and getting their permission. Now, in one of the cases that I can't talk about, we actually found a heart defect, a hereditary heart defect, in one of these individuals. that was inherited. And now we have the issue of, well, one, do we believe it? Because these are very marginal specimens. So your issue about a false positive was very pertinent here, whereas normally it's not. And then second of all, this is something that's a dominant condition. And so we have to go back now to the daughter of this famous individual, who's also famous, and tell her about this and suggest that maybe she ought to see a cardiologist. So that's an issue. How do we deal with, you know, not the individual, but the future, future generations?

Dr. Richard Payne

Right. So, Dr. Atkins?

Dr. Barbara Atkinson

I'd like to comment on that, too, because privacy is an interesting thing, and kids and younger generations now are really less concerned with privacy. And now that you can do direct-to-consumer kinds of... genome sequencing, 23andMe is one of the proprietary things that a lot of people use. You see a lot of kids putting it up on their Facebook page, their own information, and they're really putting information for their entire family in a way, and their family yet to come and yet to be born. But they have a different concept of privacy and maybe less concern about it than some of us who are in this room. Barbara,

Genomic-ethics attendee commenting on voluntary surveillance and security

I'd like to follow up with that, because we were talking about that yesterday, I think, in preparation for this meeting. about the concept of voluntary surveillance and security as distinct from privacy, and we've really never included those as these issues that were talked about this morning, that ought we to have those principles or some definition of what that means, especially for millennials who are saying, you know, yeah, I'm not particularly concerned about privacy, but I'm very concerned about security. Or... you know, the issue of I know I'm being surveilled. I'm participating in that. But that information is not available to everybody under the sun.

Dr. John Lantos

I mean, one of the issues that comes up here is who needs to be protected from whom and under what circumstances. I mean, one view is we need to be protected from ourselves, right? We might, like, want information that we can't understand, and it will therefore harm us. In pediatrics, we see this a lot. I mean, we don't allow parents, in particular, to get certain tests for their kids. But even with competent adults, we sometimes say, we're not going to test you for the Alzheimer's markers or whatever. Or you have to go through special consent processes to see if you have the Huntington's gene, because we have to certify you as capable of handling this. Or we might think we need protection from doctors and researchers who are going to find out things about us. So the consent forms and the IRBs are sort of our intermediaries on that. Or we might think we need protection from the payers or employers who are going to use the information to deny us access to things. But each of the conceptions of who needs protection and from whom for what kind of information leads to a different view of where the regulation ought to be.

Dr. Richard Payne

Great. We've got lots of questions. OK. We'll keep going for a few more minutes. Yes.

Audience member 1

Question for the panelists. Is what's underneath all of the controversy in the privacy and the autonomy and the harms, is it really a question of personhood and are these cells part of me and am I worth something? Or is it separate in the fears, the protection from whomever? Are they the same or are they two separate questions?

Dr. John Lantos

I think they're separate questions, but another way to ask it is what's special about genomic information? I mean, all the risks that Alan talks about, that I might not legitimately be empowered to consent away are in everything that's in my medical record, which can be used for all the same sort of discriminatory autonomy diminishing sorts of things. So in theory, if I followed your argument, I am not even empowered to consent to medical treatment because that could lead to information that will diminish my autonomy. But it gets to the risk benefit thing. I mean, I think I sort of get that, that there's this risk out there. But I think the benefit, I've made my own risk benefit assessment and say I'm willing to take the risks of discrimination and loss of autonomy for the benefits of getting good medical care. Point of information and clarification.

Dr. Richard Payne

There are defined HIPAA identifiers. Right? And I thought I read in this report that, of course, one of the HIPAA identifiers is any, quote, any unique identifying number, characteristic, or code. But it is not, is this true? It has not been determined whether or not genetic information actually fits into that category. Is that correct?

Dr. Richard Payne

It does not, right. So it does not meet the definition.

Dr. John Lantos

Right. But the data you presented, that people can be identified suggested that it should be.

Dr. Richard Payne

Okay, so over here and then here. We'll get to you, sir.

Audience member 2

Thanks. Yeah, you raised a really interesting point pretty recently, which is that now people are actually willing to post more information than even we're willing to allow as like medical professionals or care professionals. And I'm really wondering, it seems like there are a lot of barriers to care that are due to

Audience member 2

restrictions of privacy, restrictions of data sharing, and this kind of thing that make things like telehealth, for instance, very difficult to deliver, or immediate access to care very difficult to deliver. Where is the balance that you're finding in terms of how to determine how to transfer data, whereas maybe people, especially of our generation, are more open to data being made more public with the benefit of accessing care more quickly, more rapidly, more efficiently?

Dr. Barbara Atkinson

I'm not a good person to answer this question, because I think there really isn't enough. There isn't enough legal basis. There isn't enough work being done to even try to come to what the norm should be. I mean, that's really part of what we struggled with in just doing the whole genome sequencing. And it's the same thing when you look at incidental findings, as you'll see when you see our next report come out, that it's very hard. And the standard has really been on a research basis not to share data with the research participants. And that's been kind of interesting because I think most research participants think there is going to be data shared. If you found an incidental finding, for instance, you would come back to the research participant and tell them about it. But mostly they've signed away the right to that in signing the consent in most studies. So we don't have a basis either legally or ethically or morally that I know of yet, and there are very few people talking about what that balance should be. I think it needs more discussion.

Dr. John Lantos

One quick maybe off-the-wall response to the data sharing and telemedicine kind of question. Ron Coase, the Nobel Prize-winning economist who just died, wrote a book on the theory of the firm, which talked about sort of when, if ever, it's economically advantageous to create firms which eliminate competition and market forces to decrease transaction costs within a production entity. I think we do the same thing with information sharing. And there is a theory of the firm that goes along with HIPAA and privacy protections that says, within the firm, HIPAA doesn't apply. Doctors can share with each other and with nurses and with people whose input is relevant to the care. So I think one of the questions is, what's the most efficient size for health care firms in order to allow people to have the decreased transaction costs of information sharing and still protect privacy with firewalls around the firm? Yes,

Audience member 3

sir. My question has to do with, are we focusing on the wrong things? As we've pointed out with privacy and consent, they're almost impossible to assure or to define or to communicate. at all levels to be truly fair to all individuals. Why don't we focus on individuals who misuse information that's out there? Why isn't, why, all the resources that we're spending on privacy and on consent to, in an attempt to protect ourselves are, I think are doomed to failure over time. And if we, if we just, allow the fact which is there to be there, that the information is there, it's going to be there, it's going to continue to grow, technology is going to continue to advance unless something catastrophic occurs, that that is going to be there, so deal with it and instead focus on people who misuse that information. Why don't we change that focus? Anybody want to

Dr. Richard Payne

speak to that? Yeah, over here.

Dr. John Lantos

Quick response. It's a great point. I think one of the interesting things that's happened with electronic health records is everybody worried that they would lead to less privacy. In fact, I think they've led to more because it's much easier to tell who's breaking into them than it is who's reading a paper medical record.

Allen Buchanan

I agree. I think that's – I half agree and half want to emphasize something slightly different. So one problem with focusing on wrongdoing is sometimes it's hard to tell. So the Genetic Information Non-Discrimination Act prohibits certain kinds of discrimination, but whether or not somebody's denied a job or health insurance, that's no longer really an issue. But whether somebody has had their information misused can be really hard to tell and much harder to prove. legally, so that's sort of a practical problem. Nonetheless, I think you're right, and I think that the better way may be not to address wrongdoing, but make wrongdoing much harder by shoring up background conditions, make it easier, make the catastrophe of losing a job or some opportunity less bad, and that's an important condition of background justice in my view, so I totally agree.

Misha Angrist

Misha? There's a legal scholar named Jane Yakowitz Bambauer, used to be in Brooklyn, I think is now in Arizona, who's written about this, this idea of simply, instead of obsessing over consent, why don't we just criminalize and punish bad actors? And I heard her present this at a workshop on identifiability, and it was telling. I think she was... largely not taken seriously. But I think it's a compelling idea. Right.

Dr. Richard Payne

You want to speculate why she wasn't taken seriously?

Misha Angrist

Well, I think change is hard. And I think if we look at HIPAA, HIPAA enforcement, at least until recently, has been pretty anemic and tepid. And so I think there is a legitimate concern that, you know, we've got this club on the wall, but are we actually willing to take it down and use it?

Misha Angrist

This is great. We'll have maybe one more

Dr. Richard Payne

question up here, John.

Mixed diarization: microphone coordinator and privacy-cost questioner

But we need the microphone so the remote sites can hear you. So you haven't brought up the issue of cost and privacy,

Mixed diarization: microphone coordinator and privacy-cost questioner

all the efforts at privacy, how costly are they, and how do you reach a balance between privacy and

Dr. Richard Payne

cost? Anyone want to take on that?

Dr. Richard Payne

Everything has a cost, right? So the question, yeah.

Dr. Richard Payne

There was agreement here. Did this come up in the presidential commission? No,

Dr. Barbara Atkinson

it really didn't. But I can just tell you that the cost of HIPAA alone was tremendous and still is on an ongoing basis. I mean, there's a lot of people that really wonder whether it was worth the cost to the whole medical system that we're still bearing for it. So I'm sure if you added an additional privacy, you would only increase it. But it's a value. It's a human value, and I guess it's really It's almost a personal issue in some ways, too.

Dr. Richard Payne

Well, this is great. Great questions. Engaged audience and panelists and speakers were wonderful. Thank you. We're going to take a 15-minute break.