2011 Inaugural Bishop Lecture featuring John Lantos, MD

Susan Goold

the inaugural Ronald C. and Nancy D. Bishop

Susan Goold

Lecture in Bioethics. A special welcome to the many family and friends of the bishops, some of whom have, I know, traveled quite a distance through the year, and we're delighted. I'm Susan Gould, formerly Director of the Medical School's Bioethics Program, which has now grown and matured into the Center for Bioethics and Social Sciences and Medicine, capably directed by Scott Kim and Angie Faber. I had the distinct honor and pleasure of knowing Ron,

Valerie P. Castle

who unfortunately not fancy so much,

Susan Goold

who regularly attended a monthly discussion group I hosted as part of a biologics faculty development program many years ago. Although I was technically the teacher, Ron, Myron Wegman, who some of you may remember, and other professors emeriti who regularly attended, they really taught me more than I thought them. I think we get wiser as we get older. So before moving on to the fun stuff, a few items past evening. The restrooms are located out the door to the left, down past the little kitchen there. And you have to look at the signs very carefully to know which one to go in. This lecture qualifies for CME credits, 1.75 CME credits. If you wish to claim that, please fill out one of those orange cards out in the lobby on one of the tables. And also, CME requirements mean we have to have a list of everyone who attends, whether you're an actor or not. So if you would sign one of those sheets out there, we would appreciate it. Please take a moment to silence your cell phones.

Susan Goold

See how many people are agreeing to

Valerie P. Castle

give their comments?

Susan Goold

And finally, there will be a reception immediately after the presentation, and I invite all of you to come. Now I would like to invite Reverend Kenneth Pfeiffer, pastor and friend of the bishops, to say a few words about them. Thank you.

Kenneth Pfeiffer

Thank you, Susan. Ron and Nancy Bishop were good people. They were good people because they cared. They cared about each other. In all the years that I knew them, almost 30 years, I never saw them show anything but love and respect to each other. When Nancy got seriously ill, Ron took care of her. And that went on for several years. And then Ron was stricken. And there in the emergency room, on the day that he went in, I saw Nancy rising above her limitations to be sure that Ron got the right treatment. Now, I know that Ron and Nancy, like all couples, must have had their disagreements and sometimes faced very difficult times. But every instance that I ever saw them... They treated each other with gentleness and kindness. They cared for each other. They cared for their children, Christine, Andrew, Ellen, David. And I was pleased several years ago at the memorial service for Ron and Nancy to listen to them talk about what it was like to be raised in that family. It was very clearly a close-knit family. They obviously taught you to care for each other and to care for the world. And then when you produce children of your own, They embraced that new generation just as warmly. And I know a lot about those children because they talked about them a lot, and I can remember some of the stories.

Kenneth Pfeiffer

They also cared for those of us who weren't direct members of the family, as I had occasion to learn when we moved to Ann Arbor, and our moving van was about five days behind us. They welcomed us into their home as though they had been running a B&B for stranded families for many years. It was a great experience. Shortly after I came to Ann Arbor, I asked Nancy to serve on a support team for my ministry, and she did that for three years. She offered strong commandments to me. You are to take time off, not just to work seven days a week, and I had to do what she said. She taught me a lot about the Congress, whom I did not know, and she knew very well after 30 years in the church. And she was willing to vet the different ideas that I had for plans and projects and programs before I launched them to be sure that I was doing it the right way in that particular congregation. I continued through the years to seek her advice for that reason. She was a pillar of the committee that planned our 125th anniversary celebration. Ron? If there was a board or a committee in that church that Ron Bishop did not serve on, I don't know what it was. He was on the search committee that called me. He was on the board of trustees. He was the treasurer of the church. He served on the memorial garden committee. He was on the social justice committee, the sanctuary committee, and perhaps most important of all, he chaired the capital campaign committee that raised several million dollars, whatever I do believe. Ron and Nancy both were generous with their time and their money. They cared about the well-being of the congregation. They also cared about the larger society, and they were involved in a number of activities in the larger society, including the Ann Arbor Council and the American Civil Liberties Union.

Kenneth Pfeiffer

At the first dinner that I had at their home in 1980, Ron introduced the subject of ethics in medicine. He was the head of a program called Ethics in Medicine at the medical school at that time. And he talked about that and about his work in the IRB and trying to do ethical research. And it was very clear from that conversation and many conversations that followed and many activities that we engaged in together that this was a man who believed that medicine was an enormously vital part of our society and that it should always be done with the highest ethical practices and the highest ethical standards. That's the way he and Nancy practiced medicine. It's the way they lived their lives. And I was proud to be their pastor and their friend.

Kenneth Pfeiffer

One of the ways in which it's demonstrated how much he cared about ethics in medicine is the lectureship that you are now attending. This first inaugural lecture, as it were. And as a memento of that, we're going to make a presentation to the four children. This is the certificate which I'm going to read to you. The Ronald C. and Nancy B. Bishop Lecture in Bioethics. On the occasion of the inaugural lecture established by Ronald C. Bishop, M.D. 1944, And Nancy B. Bishop, MD, 1944, we proudly present this memento to, and the individual children's names will be on each certificate, in honor of your parents for their extraordinary contributions to the University of Michigan, Ann Arbor, and their community, and for their devotion to medicine and to serving numerous civic, cultural, and academic initiatives, including the creation of this vital lecture in bioethics.

Bishop family representative

about social and ethical issues throughout their careers. In the 1950s, my father was involved in the early use of radioisotopes in medical research, and from this he participated in the Human Use Committee, which later morphed into the IRB. He volunteered in three clinics and traveled to Nicaragua to promote healthcare there. And as an attending physician, He chastised medical residents if they ever referred to their patients as gomers. My mother worked for Planned Parenthood in the 60s, and for many years she volunteered in civic and educational programs. By supporting this lectureship, they hope to ensure continuing inquiry into issues of welfare, justice, and dignity in medicine. those which confront us today and those which are going to face in the future. I want to thank Dr. Gould and the Center for Bioethics for putting on this program. On behalf of the Bishop family, thank

Valerie P. Castle

you. So I want to first say that thank you to the Bishop family on a personal level. When I came to the University of Michigan in 1986 from Canada to do my training in pediatric hematology oncology, I was given the opportunity to pick up my electives and I actually said, could I rotate on the adult side? And Dr. Bishop was my attending physician and I had an extraordinary experience working under him. He was all the things that you said can and then some. He was probably one of the most principled physicians I worked with at Michigan

Valerie P. Castle

I felt very, very lucky to have that experience. So, thank you. I get to thank you, as I did today. I'm extremely honored to have the distinct privilege to introduce our guest speaker today, who's Dr. John Lantos, the director of the Children's Mercy Bioethics Center in Kansas City. Dr. Lantos is nationally recognized for his leadership in bioethics, having served as president of the American Society of Law, Medicine, and Ethics, and president of the American Society bioethics and humanities. His work in bioethics covers a broad spectrum of ethical issues related to neonatal and pediatric care, life sciences research, organ transplantation, end-of-life decision-making, physician-patient relationships, and resource allocation. In addition to authoring hundreds of peer-reviewed articles in both chapters, Dr. Lantos has written or edited several books in the area of medical including neonatal bioethics, the Lazarus case, life and death issues in neonatal intensive care, the last physician, Walker-Percy, and the moral life of medicine, and do we still need doctors? I hope the answer to that question is yes. Dr. Lanzos' expertise has been tapped and acknowledged by many. As examples, he was a member of President Clinton's Health Reform Task Force, and he has served on many task forces for the state of Illinois that have examined issues such as legal guidelines for end-of-life care, pandemic preparedness, and genetic services. His expertise and work has also been recognized with appearances on Larry King Live, Oprah Winfrey, and Nightline. Additionally, our peer organizations and pediatrics have recognized his important contributions with awards including the Margie Dines Endowed Lecture on Perinatal Bioethics, Thank you very much and it's a great honor to be asked to give the first bishop lecture.

Dr. John Lantos

These named lectureships are I think one of the most important things that somebody can do for a medical center because what they do is establish a tradition and a sort of critical mass for people who come together and think about a set of issues. So I hope this is the first of many and I hope this tradition continues to be. rewarding for the family. I'm going to talk about something I'm a little daunted to talk about because it's not a topic that I know a whole lot about and people here at the University of Michigan like Beth Turini, where are you Beth, is one of the national leaders in

Dr. John Lantos

doing this research and I got into it because Children's Mercy Hospital where I work has recently developed a new test that I'm going to talk about towards the end of this lecture that's ethically controversial, and they asked me to get involved with the planning on how to introduce this test as a research project and as a clinical project. And so I started reading all about genetic screening to try to help them out, and the more I read, the more it seemed like a complex mess. And when Susan invited me to give this, I gave her three topics about things that I know a lot about, and this one, thinking, She won't take that one, and she did. So then I had to really, really start to learn more about it. So the talk may be a complex mess too, but

Dr. John Lantos

we'll see. Why a mess? Genetic screening, newborn screening, has a complicated history. There are many debacles that have happened over the years. There are many interest groups involved. There are changes in the technology, rapid changes in genetic screening. There's really a lack of good research on the efficacy or on the harms of screening. And there are different goals for different programs and different fears about what this might lead to. Newborn screening began really in 1962 when biochemist Robert Guthrie invented the Guthrie spot. He was at Harvard. The spots are the newborn screen where you put a little drop of blood on a piece of filter paper. And this was a revolutionary new technology and the question was what should it be used for. The first assay that Guthrie developed was for PKU and controversies arose almost immediately about the sensitivity and specificity of the test, that is how many false positives and false negatives, about which babies should be treated and how complex the treatment regimens were and whether parents were going to be able to follow them. There were concerns about labeling children if they had a false positive test. There were questions about the risks and benefits of different treatment regimens. And there were horror stories. Norm Fost, a leading pediatric bioethicist, testified before the President's Council on Bioethics just three years ago and described the early days of PKU screening. And he said the following, a phenylalanine-restricted diet was as harmful or more harmful as a diet with an excess of phenylalanine. People who had a positive test had the restricted diet. Many children, Dr. Fost went on, we don't know how many were made retarded by this program. Some were killed.

Dr. John Lantos

It's interesting, though, because those horror stories may not be true. Jeff Brosco, who's a developmental pediatrician and a medical historian, decided to look into the evidence for Fost's claims about the early days of PKU. So with some graduate students, did a comprehensive literature review of every case ever published in the peer-reviewed literature of harms from PKU screening. and then went back and did oral histories with people who were still around and who were involved to say, you know, did you have cases that you didn't publish? What's the story with these harms? And after this, he uncovered a total of five or six cases where children were harmed, only one of whom died. And the harm seemed to be unrelated to screening or treatment in the way that Norm Foss claimed, that is, Of the six cases, three were not involved in any screening program at all, and three had started on a phenylalanine-restricted diet, had problems, and were stopped, and went on to have problems that it was not clear whether or not it was related to the actual treatment. So this story sort of suggests ways in which what passes as history is more myth than fact. And it's hard to separate the myths and perceptions from the realities. The same is true with sickle cell, which was another of the early screening programs. Your own Howard Markle, is he here? Writing in the American Journal of Medicine, 1992,

Dr. John Lantos

said the following, the early mass screening programs for sickle cell anemia during the 1970s could be summarized by the Dickensian axiom, how not to do it, and portrayed these early screening programs as an unmitigated national disaster. What actually went wrong? Well, between 1970 and 72, 13 states mandated sickle cell screening for African-Americans. Some people say these were not accepted by the public. Some people say physicians didn't understand the results. It was clear there was no treatment or intervention that was available for kids who tested positive. And some claim that this led to discrimination and no benefit for the children who were screened. It's also clear that there was a eugenic philosophy behind this. Linus Pauling, two-time Nobel Prize winner, wrote in 1974, there should be tattooed on the forehead of every young person a symbol showing possession of the sickle cell gene so as to prevent two young people carrying the same seriously defective gene, single dose, from falling in love with one another.

Dr. John Lantos

See? Nobel Prize winners are really smart, right? That's what you're thinking.

Dr. John Lantos

But if you look at what really happened, again, it seems a little more complicated. There was a case study from Seattle that was written up in a paper in one of the pediatrics journals in 1974. Sickle cell screening was promoted by the black community, particularly the Black Panthers, and many sole radio stations in Seattle. And one of the clinics associated with the University of Washington, the Odessa Brown Children's Clinic, decided, based on this, advocacy in the black community that they were going to start screening, but then they evaluated the program after a year. They found that they'd tested 2,000 kids, they found 85 who had sickle cell trait, no cases of disease, and then they interviewed 47 families who had children with trait and 100 control families. And they found widespread misunderstanding about carrier status among both cases and controls. I don't know if you can read this, but they asked people things like, is the trait a disease? Does the trait have physical manifestations? Should you restrict vigorous play for kids who have sickle cell trait? And what they found was both in the carrier group and the control group, lots of people had false beliefs about the implications of the trait. Many parents who had children who had sickle cell trait reported symptoms from the trait, something that most doctors believe is not associated with sickle cell trait. They restricted the physical activity of these kids, and the screening program was discontinued based on this, and the doctors who wrote the paper called this sickle cell non-disease. And this program is often cited as a typical example of the harms that can result from screening. Stigmatization, medicalization of something that's not a medical problem, something that's been called the vulnerable child syndrome, that kids who are not sick are treated as if they are and therefore psychologically harmed. But to use this as an example of why screening should not be done today is a little misleading. I mean, it would be like using some harm that resulted from computer use in 1972 to argue against Facebook or the internet. At this time, most doctors didn't know much about genetics. This was a survey done in Pittsburgh in 1975 of 67 obstetricians. 12% knew that Down syndrome was caused by a chromosomal aberration. Half knew the recurrence risk of PKU, and 20% did not know that a gene was the basic unit of inheritance.

Dr. John Lantos

Everybody's shaking their head, but this was the milieu in which the early screening programs were carried out, so it's no wonder that there were a lot of misperceptions among the general public. But the response that therefore we shouldn't do screening rather than therefore we shouldn't educate doctors in the general public seems a little bizarre. There's another study that's often cited as I was looking at this to try to figure out what we're going to do with our new test. This study gets cited a lot, although this study cannot be found online or in any medical library I know. But everybody refers to it, and it's a chapter in a textbook that's long out of print with the proceedings of a conference in England in 1972.

Dr. John Lantos

where people studied a small farming village in Orkimenos, Greece, where 23% of the population were sickle cell carriers and 1% of the babies had sickle cell disease. And this was a village where marriages were arranged. and they instituted a sickle cell screening program with the goal of reducing marriage between carriers and reported that there was no confidentiality, that everybody quickly found out what everybody else's genotype was, and the women who were carriers couldn't find a good match in these arranged marriages. Although, almost as an afterthought, they report out that In spite of that, there was no reduction in carrier-carrier marriages, which makes you wonder what exactly was the situation before or after. But this is, again, often cited even though it may not be representative of sickle cell screening or any other screening in, say, the United States in 2011.

Dr. John Lantos

So the myths come from these small, non-representative studies where things were done badly. There are accusations of racism. Most of the problems were, it seems to me, easily correctable. And so it doesn't seem like they should still be cited as relevant. There are some good examples, though, even from the 70s. And Tay-Sachs is usually the one that's cited as an example of a screening program that worked. Although if you look at that data, it's also a bit ambiguous in terms of what it would mean to work or how you'd measure the benefits and harms of a screening program. This was a study done out of Johns Hopkins in Baltimore in the early 70s when they first started doing Tay-Sachs screening and carefully surveyed 131 people who were carriers of the Tay-Sachs gene and their non-carrier spouses, 150 non-carrier couples, and 52 people who had borderline tests that you couldn't say much about. And they wanted to find out how they reacted to being tested and getting this information about themselves. So they asked them, were you upset by the results? And of the carriers, half said they were upset and half were not. Of the carriers' spouses, about half were upset and about half were not. And big surprise here, of the non-carriers, none were upset.

Dr. John Lantos

Is this harmful? Well, it certainly upsets people. But then they asked, are you glad you were tested? And when they asked everybody, carriers, carrier spouses, non-carriers, 98%, 690% of the 710 patients said, yeah, I'm glad I was tested. Would you do it again? 700 of the 710 said, yeah, I would do it again. So is it upsetting to find out you're a carrier? Yes. Are you glad you got tested? Yes. So does this say screening is good or bad? It's hard to know. But these sorts of studies with the psychosocial harms, the medicalization, the stigma, led to a great deal of caution among pediatricians, geneticists, and policy makers who warned about all these harms of screening and suggested that new tests should only be added to the newborn screening panel, that is the Guthrie blood spots, using strict criteria. And the criteria that are frequently cited are criteria developed by two people, Wilson and Younger, who did a technical report for the World Health Organization on screening programs really designed to assess cost effectiveness, not the ethics. But these criteria are often cited as sort of the gold standard for the criteria that a screening test should meet in order to be considered worth doing. And they actually have about 10 of them, but I think the most important are the disorder must pose a serious threat to the health of the child. The natural history must be well understood. Timely and effective treatment must be available. The intervention as a whole, and here they were careful to specify not just screening, but follow up and treatment to make sure all the kids who were found to have the disease should provide a substantial benefit to the affected child. Those were the criteria that were used from about the mid-70s until about the mid-90s. And tests were gradually added to the newborn screening panel. And then, suddenly, things changed. And the reason they changed was because new technologies came along. In particular, a new technology called tandem mass spectrometry, which allowed much more rapid and cheaper testing for many more metabolites became widely available. The Human Genome Project increased our understanding of how many genes were in fact associated with genetic disease. Technology to test for

Dr. John Lantos

portions of the genome or SNPs and genome sequencing led to new philosophies about who we should screen and for what. Tandem Mass Spec was developed in the 1990s, quicker, cheaper, more accurate. And here's one example of what happened. In 1996, Massachusetts and many other states did the same thing, had a state-mandated newborn screening program for nine different diseases. And I'll show you what those were. And then in 1997, a for-profit company using Tandem Mass Spec started marketing to hospitals in Massachusetts saying, we'll give you a deal. on screening for 27 diseases that's much more comprehensive at a substantially lower cost than you're paying now for the state screening program. And Massachusetts, to compete with the private company, decided to expand its state newborn screening program. So these were the diseases that they screened for before. Some of them you've probably heard of. Others you probably haven't. Here are the diseases they screen for afterwards. The print is small. I hope nobody can read it. It's supposed to suggest many, many things you've never heard of and can't pronounce, but now that all newborns are screened for in Massachusetts. in many other states, as Beth Turini has shown in this great paper in Pediatrics in 2006. The different colors show how many different tests different states added to their newborn screening programs, going from more than 30 over these 10 years, down to 20 to 29, 10 to 19, 1 to 9, and only Wyoming took something off its newborn screen. Do you know what they took off?

Dr. John Lantos

Was it Wyoming? Yeah.

Dr. John Lantos

So with all these tests coming available and all these different states doing different things, a lot of people started to get concerned not so much about whether they were following the Wilson-Younger criteria or whether these were actually cost-effective or beneficial, but instead about justice and equality, that is, why should what you get tested for depend which state you happen to be born in? Why should kids in some states be tested for 40 things and kids in other states be tested for seven or five things? And so the federal government commissioned the American College of Medical Genetics to provide recommendations for a uniform screening panel. And the American College of Medical Genetics thought about it for three or four years and came up with a recommended panel of 29 tests that they suggested should be done in every state. They allowed that people might want to do more, but they said these should be the minimum for newborn screening. These recommendations were endorsed by the American Academy of Pediatrics, the March of Dimes, and HHS. And the universal panel has now, I think, been adopted by every state, but different states at different times. The support from the NICHD, the National Institute for Child Health and Disease, I think, was strong, particularly from the director of that, Duane Alexander, who wrote a remarkable paper in 2006, A Vision for the Future of Newborn Screening, where he described sort of the way the philosophy of screening had changed. And he said, many have begun to question that it is appropriate to screen only for conditions for which an effective treatment already exists. Remember, that's one of the Wilson-Younger criteria. And the old dogma cannot be allowed to stand in the way of developing effective treatments for these rare genetic disorders. So the argument was the only way to develop new treatments is to start screening, finding the people who have the rare diseases, and figuring out how to treat them. So having a treatment shouldn't be a criteria. It should be a goal.

Dr. John Lantos

Now these criteria were widely criticized by bioethicists. In particular, there was a paper around this same year. Jeff Botkin was the lead author, and a whole bevy of famous bioethicists were on it. newborn screening technology proceed with caution. And they cited the old data from the PKU studies and the sickle cell studies to say, what about the psychological impact? What about the lack of treatment? What about the unknown risks and benefits? And they said, we're moving too fast. This panel of 29 has no scientific basis whatsoever. It could have been 15. It could have been 150. Why pick these? Why not wait until we know whether screening is actually beneficial? before we mandate it for all newborns born in the United States. And what they recommended was that screening programs that did not have proven effectiveness should be considered experimental, so not mandated, not necessarily even recommended, but offered under research protocols. Each one should be carefully studied before it's implemented as a mandated test. a national working group and they said maybe under the auspices of the Institute of Medicine should address the ethical and policy issues and an independent and impartial organization and those as you know are a dime a dozen

Dr. John Lantos

should be put in charge of making policy about what should or should not be screened for. The President's Council on Bioethics more or less echoed these concerns and many of the people who wrote the Pediatrics paper gave testimony before the President's Council on Bioethics, and they issued this report in 2008. Mandatory screening should only be for conditions that meet the Wilson-Younger criteria. For other conditions, voluntary screening with accompanying research is ethically permissible but not mandatory, and we should avoid screening just because we can't, they said. So there were these competing philosophies with different interest groups lined up. One is the traditional, it's appropriate to screen only for conditions for which effective treatment already exists, versus, this may be a bit of a parody, but screen unless there's a compelling reason not to screen. That is, unless harms have been proven,

Dr. John Lantos

consider a test eligible for screening. So it seems to me there's two major ethical issues here that are somewhat separable, although overlapping. One is a question of research ethics. That is, if you're going to say we shouldn't put these tests on a screening panel until we've proven them to be beneficial, how do you actually study a screening test? And how good have studies been looking at screening tests? And what are the research ethics problems that arise when you try to study a population-based screening test? And then there's more of a clinical ethics problem, which is sort of the competing agendas of public health and population-based screening versus individual autonomy. That is, should parents or competent adults for their own testing be approached and be told the risks and benefits and offered the test if they want it or not? Or should this public health mentality that we use now for newborn screening, where you get it unless you are empowered enough and knowledgeable enough to opt out be the driving factor.

Dr. John Lantos

So let me address the research ethics issue first. Can we study screening programs? People have tried a lot of different methods. There have been some prospective randomized trials, concurrent geographic trials, that is if one state's screening and another's not. You can look at that. People have looked at historical controls, how we're doing now that we are screening compared to how we did before. And each of those has been used for various tests. And let me just run through cystic fibrosis as an example because that's the most common autosomal recessive genetic condition in Caucasians and was for many years quite controversial in terms of whether a newborn screening program would actually be beneficial. And the folks at University of Wisconsin and Medical College of Wisconsin decided that they were gonna study it doing a randomized controlled trial, one of the few randomized controlled trials ever done of a newborn screening program. So think about it. How do you do it if you want to screen all newborns and see whether a screening test works? Well, what they did was, for 10 years, they randomized every baby born in Wisconsin, 650,000 babies. And they were randomized by birthdays. So odd-numbered birthdays were put in one group, even in the other. And every baby was tested at birth, but only those with odd birthdays, parents were told the results of the test. And those with even birthdays were told when the kid turned four. And they were all followed then for lung disease, nutrition, and mortality. And to get this through IRBs and stuff, there was an opt-out where all parents were told, we're doing this study, we're testing all your babies, if you're in the

Dr. John Lantos

non-disclosure group and you really want to find out here's an 800 number to call and it turned out that 195 of the 325,000 babies and parents in the non-disclosure group or 0.3% actually did call and they were all negative.

Dr. John Lantos

So, some newborns were diagnosed at birth. Cystic fibrosis can be diagnosed at birth whether you're screened or not. Some babies have a condition called meconium ileus. Most others were diagnosed in the first few years of life. That's the standard non-screening way. They develop problems and get diagnosed with failure to thrive or pulmonary problems. But the question was, will those kids do worse in the long term than babies who were screened at birth? And they looked at lots of the possible harms. I'm not going to go through this because they're similar to the other

Dr. John Lantos

benefits and harms of all screening programs. But here's what they found. The main thing they thought they were going to find were differences in pulmonary outcomes. And these are four graphs with tiny print, but they're different pulmonary function test measures in the kids in both groups followed between ages. This doesn't start at birth because a lot of these are problems that develop over time from ages 7 to 16. And what I hope you can see And if not, I will just tell you is the two lines in each of the graphs of the screen and the controls, and there were no differences in pulmonary function between the two groups followed up to age 16. So early screening did not seem to have a big effect on what they thought was the primary outcome. One of the reasons this was true was pretty interesting when they unpacked the data, and this was not the primary hypothesis, but there were two CF centers Wisconsin, Madison, and Milwaukee. And in Madison, the screen group did have less lung disease. And in Milwaukee, the screen group didn't, even though there were no overall differences between the groups. And so they spent a lot of time trying to figure out what was the difference between these two centers. And it turned out that Madison had a much more modern clinic, a bigger clinic, with separate waiting rooms for kids who have been diagnosed with resistant bacterial infections from kids who had not. And in Milwaukee, they all sat in the same waiting room. So in Milwaukee, getting diagnosed earlier turned out to expose you to resistant bacteria sooner because you were referred to CF clinic. So this is an interesting lesson in unintended consequences of screening. And the people who did the study said clearly it would have shown a benefit as it did in Madison if, but it's hard to do and now they've done 10 years and 650,000 babies. What they did find

Dr. John Lantos

interestingly, is significant differences in growth and nutritional status, not pulmonary function. So this was a secondary outcome. Does that project sort of well? The two lines are screened and not screened. And I don't know if you can see the error bars, but this is weight differences. This is height differences. So the kids who were screened and started on nutritional supplements early grew better.

Dr. John Lantos

That was the Wisconsin study. And I'm going to present three studies on cystic fibrosis screening using three different methodologies. And then you can decide whether you're ready to mandate it for all newborns. In Italy, they did geographic controls. And what they did was in Veneto, they were screening everybody. And in Sicilia, they were not. And they looked at mortality or survival rate out to teenage years. And what they found was the screened babies

Dr. John Lantos

had a lower mortality rate, higher survival rate, although the numbers were small and the differences were not statistically significant. In Britain, they did historical controls. They mandated screening even though it was still controversial. Other places, and then they looked at outcomes for babies in the pre-screening era and the post-screening era, obviously problematic since many other things had changed and treatment may have gotten better in other ways. But their key finding, like Italy's, was, I don't know if you can see there down at the bottom, but deaths due to CF in the screen group one and the non-screen group four.

Dr. John Lantos

You can either say four times the difference or you can say p-value is.2 and therefore not statistically significant and draw your own conclusions. My conclusions are there were unanticipated harms, modest benefits, more in nutrition and growth than pulmonary function, It may be associated with better survival, but I'm not really sure. Should this now be mandated based on these tests? Should it be offered as an option to people? The difference between offering and mandating, ethically, it would seem preferable to give people a choice, but offering is much more costly than mandating since you not only have to go through an informed consent discussion, but some people do and some people don't, so you don't get the economies of scale Other lessons, it took 15 years to prove, if you think it's been proven, that screening made a difference. It was tough to study. Questions remain. But as a result of these tests, it's now been adopted in all 50 states and most of Europe. Let me give you one more example, which I think is from newborn screening. Now I'm going to give you two more examples. This one I think is even more ambiguous. Neuroblastoma is a cancer. that kids get and that can be screened for with a urine test to detect one of the metabolites that's a marker for neuroblastoma and it presents often in the first year of life. Correct me if I'm wrong. So people thought this would be a great thing to try to diagnose earlier and in Quebec they said let's start screening all babies and they did the screening at six months of age to see if we can diagnose neuroblastoma earlier. Neuroblastoma, once it gets progresses is very difficult to treat in the early stages outcomes are much better and they compared the mortalities then between

Dr. John Lantos

the screened populations in Quebec and unscreened populations in other geographic regions and published this paper in the New England Journal of Medicine 2002 Quebec is over there on the left and then you have Ontario, Minnesota, Florida and the area around Philadelphia and I think what you can see is no difference in outcome for the kids in Quebec who were screened and the kids in all these other places who were not screened. And this dampened enthusiasm for neuroblastoma screening. Since the kids were screened, some actually got operations to remove these tumors and so harms were done. Dampened enthusiasm everywhere except Japan, where They love screening in Japan. They do things like electrocardiograms on all second graders and

Dr. John Lantos

many other tests and they put in a neuroblastoma screening and they tried different methods as the tests got better and they really carried this on for about 20 years. And then they studied it carefully to look at outcomes before any screening when they were doing an earlier test that was qualitative, either you have it or you don't, and then quantitative screening which could actually grade how bad it was and was thought to be a more sensitive and specific test. And they had screened, over these years, 22 million children. And they found lower mortality in the screen cohorts. So before they started screening, five kids per 100,000 in Japan died of neuroblastoma. When they used the earlier screening, four. When they used the better screening, about three per 100,000. So they cut the mortality rate from neuroblastoma by 40%.

Dr. John Lantos

So who do you believe, the study from Quebec in North America or the study from Japan? Should we put neuroblastoma? This wouldn't be on the newborn screening program, but it would be for children. Some of the lessons I would draw is that early detection is not necessarily beneficial. Screening changes our understanding of disease. Whatever it was that these kids in Quebec had who tested positive, and many had pathologically proven neuroblastoma. It wasn't the disease that kids who are diagnosed clinically, that is in a non-screening program, seem to have because many seem to regress spontaneously or not progress. Timing of the test is crucial. Cut-offs for the tests are crucial. And these sort of subtleties may be true for many other syndromes. So one lesson comparing neuroblastoma CF is a screening test is not a screening test is not a screening test. Each one has its own quirks. And just to further highlight that point, I'll talk about a much more rare condition, Krabbe disease, which is an autosomal recessive lysosomal storage disease, a very rare condition similar to Tay-Sachs and its clinical effects. That is, kids are born looking normal and then develop progressive neurologic degeneration, eventually leading to complete

Dr. John Lantos

brain damage and death, usually in early childhood. It's a variable age of onset and progression. The incidence is usually, or before screening, was quoted as one in 100,000. And the only way to treat it is with a bone marrow or a stem cell transplant. So there's no, it's not like PKU where you change the diet or cystic fibrosis, where you add some nutritional supplements if you want to prevent the progression of Krabbe's disease. You've got to get a bone marrow transplant, which itself is associated with some mortality. So in 2006, New York State said, we're going to screen all newborns for Krabbe disease. Why did they do that? It was because of the incredible scientific evidence that this was beneficial? No. It was because, what's his name, the quarterback for the Buffalo Bills. had a kid who had Krabbe's disease. And this made the news and led to lobbying. And this test was mandated and added. And they started screening. And what they found was, surprisingly, when they screened for Krabbe's disease, the incidence was 20 to 25 times higher than predicted. So not one in 100,000, but one in two or 3,000 were having positive tests. But some of the positive tests were not highly positive. They were intermediate and they didn't know what to do with these. because they didn't want to send all these kids for bone marrow transplants. So instead, what they did was said, we're going to do monthly neurologic exams from a pediatric neurologist. And quarterly, we're going to get MRIs and do LPs, spinal taps, and evoked responses to see whether this disease is progressing in some subtle way. Because the thing about the bone marrow transplant is it doesn't reverse the disease. It prevents progression. So if you don't catch it early, you're not doing people any good. So they followed all these kids and then they created a point system based on the results of this complex array of tests to decide whom to transplant. And what did they, how did this turn out? Half a million babies were tested, 25 were positive, 15 were classified low risk, 6 moderate, 4 high risk. These are a couple years old so the numbers are probably, you could probably double these but I think the percentages are about the same.

Dr. John Lantos

of these 25 positives were referred for transplant. One got a transplant and is apparently doing well. One apparently died before the transplant was done. So are there harms to this? Imagine being told your child's at risk for a degenerative, untreatable neurologic disease, that the only treatment is a bone marrow transplant, but that for now, we're just going to watch. Or imagine not being told. Which way should it go? It's a tough one. Crab A's is different from neuroblastoma, is different from cystic fibrosis. And they're all different from the sorts of screening tests that we do in adults, about which we've also learned some interesting things. And I'm going to race through these quickly

Dr. John Lantos

to just hit the conclusions. A lot of people probably know about PSA because this is now becoming middle-aged man's rite of passage. I mean, what do you do? What do you do? CAT scans for lung cancer are a little more

Dr. John Lantos

less well-known, but I'll show you a study where people said, let's take smokers and let's do CAT scans of their lungs every year and pick up their lung cancers early. So lessons from PSA. Two prospective studies published in the same issue of the New England Journal in 2009. Large prospective studies, United States, eight years, 75,000 men randomized to either annual PSA or usual care to see whether middle-aged men who get a PSA annually have better outcomes than men who don't. The screening group got annual PSA for six years. They got rectal exams. The health care providers received the results and decided what to do, so there was no mandated treatment. And the usual care group got whatever their doctors recommended, some of whom got screened because their doctors recommended screening. And then they looked at cancers, deaths, and causes of death. Here's what they found. The screening group had many more cancers diagnosed over the 10 years of the study than the control group, but the mortality rate was exactly the same. Were these men benefited by being told that, yeah, you have cancer, and it doesn't make a bit of difference whether we found it or not.

Dr. John Lantos

But the cumulative death rate from prostate cancer 10 years in two groups combined was 25% lower in those who had undergone PSA tests at baseline. You can't control what people had done before they got into the study. So it turned out many people in the unscreened group had had PSA tests done. And if they reanalyzed the data looking at anybody who'd had a PSA test done, the mortality rate was much lower. But that wasn't the study question.

Dr. John Lantos

Europe, around the same time, they did a similar size study, 182,000 men, 50 to 74. They just did the testing every four years. They didn't mandate which cutoffs to use for the test. Every country had its own rules. What they found when they pooled the data after 12 years was these are mortality rates that the control group had higher mortality than the screening group, separating out around 10 or 11 years farther out than the US study went. So maybe screening now will save your life 15 years from now. But who knows what will be available 15 years from now. And the accompanying editorial said, screening for prostate cancer, the controversy that refuses to die. Nobody has a clue what to do. And they did a reader poll, actually, where they presented a case and asked doctors around the world, what would you do with this guy? And they split sort of random. A third, a third, a third would test, not test. And if the test was positive, treat or not treat.

Dr. John Lantos

One more quick study, because this one's also fascinating. So you'd guess that people who smoke and who are at high risk for lung cancer would do better if you screened them and tried to catch their cancers early. So the National Cancer Institute did a study where they found 3,000 of these current or former smokers. They got annual lung CAT scans. They followed them up for four years, and they looked to see whether they diagnosed more cancer and whether the people whose cancer was diagnosed did better than those who weren't. What they found, similar to the prostate thing, yes, they found more cancer, three times as much. Yes, they did more surgery. They took out the cancer ten times as much. And no, it didn't do a bit of good. The overall mortality rate was exactly the same. These graphs show the upper two are... Did they make the diagnosis? Did they get an operation? And the bottom two are... Did they have advanced cancer when they were diagnosed? There was no difference. And did they have any difference in survival? And there was no difference at all. So can we study screening? Yes, but it's expensive, complicated. Each test is different. Unexpected results are common. And diseases found on screening may not be the same disease, whether it's lung cancer, prostate cancer, Krabbe's disease, or neuroblastoma. So with adult cancer screening, though, it's a clinical model, right? I mean, your doctor talks to you. You want to get the PSA. You want to get the lung CAT scan with a little bit of research thrown in, not the public health model of newborn screening, which is mandatory screening. In spite of these complexities, as I say, newborn screening is expanding, driven by doctors, parents, advocacy groups, for-profit enterprises for many conditions that don't meet classic criteria.

Dr. John Lantos

Wanna stop right at 5.30? Two minutes later? Okay. Just for fun, I'm gonna summarize the studies on the psychosocial benefits and harms where people have now done dozens of studies to find out whether being screened and either benefiting or not benefiting or having a false positive causes psychosocial harm and the bottom line of all these studies is high reported satisfaction among tested children no evidence of long-term psychosocial harms based on these sorts of things that people look at cognitive outcomes that is to people have misperceptions about their risk mood outcomes anxiety depression general distress or behavioral outcomes do they start doing weird things like going in for more tests and all this kind of stuff. It turns out those early data from, say, the sickle cell Seattle study don't seem to be borne out today in large population studies. People who get screened seem happy that they've been screened, use the results generally in what seem to be appropriate ways. And overall, predispositional genetic testing has no significant impact on psychological outcomes, little effect on behavior, and did not change perceived risks. So

Dr. John Lantos

recognize this guy and his famous quote, when you come to a fork in the road, take it.

Dr. John Lantos

It seems we are at a fork in the road with these genetic screening programs where we're expanding mandatory screening, expanding voluntary screening, and more interestingly, expanding screening as a non-medical consumer product. So one of the big developments over the last 10 years is you don't have to go to a doctor anymore. In fact, there's a new book out called The Experimental Man Project written by a guy named David Ewing Duncan who's a journalist. author and professor at UC Berkeley, who decided just to see what it was like. The subtitle is, What One Man's Body Reveals About His Future, Your Health, and Our Toxic World. He decided he was going to have every screening and predictive test known to science to see what he could learn about himself, your health, and our toxic world. So first he went to see his internist, for a physical exam, who said, you're healthy. You have a little high cholesterol. Maybe you're a little increased risk for a heart attack. Exercise. Don't eat so much meat. Drink some red wine.

Dr. John Lantos

Then he underwent the experimental man protocol. He went to about 250 different labs. He had about two liters of blood drawn. Spent 22 hours in an MRI. He had 320 toxins tested for.

Dr. John Lantos

10 million gene markers. They produced 100 gigabytes of data at a cost of about $150,000. For his genes, he had blood, spit, and swabs tested. And just to look at one of the things he found out, these were some of his genes associated with a higher risk of heart attack. And the source you can see are the for-profit uh... consumer direct-to-consumer decode mean average annex in twenty three may work you can go to their websites and i'll send you a little test to be a spit in it now give you results uh... like these uh... he asked what was his lifetime risk of having a heart attack and navigate x said you're above average Decode Me said you're below average and 23andMe said we're not sure. He had himself tested for toxins and got a chemical report card. 320 chemicals tested and 165 were detected at a cost of $15,000, none of which he could do anything about. But it was good to know that when the DDT truck was going through his neighborhood as a child and all the kids went out to play because it smelled good, he was still carrying that around with him. He had MRIs and EEGs and he had full body CAT scans and he had a proteomic scan and a total body microbial scan to find out what his body flora was. And in the end, he didn't find out much more. then his internist told him that he had a somewhat increased risk of having a heart attack and given his genetics and his body weight, if he'd lose 10 pounds his risk would go down and he lost 10 pounds.

Audience questioner

So that

Dr. John Lantos

was a success, right? If you want to read more about it, it's on the, they have a website, the Experimental Man website. So what are the implications of all this? for ethics. I think they're really fairly simple and straightforward, although implementing them will not be. Population-based public health interventions must be safe and effective, at least safe and at least plausibly effective if they're going to last. And I think what we're learning from things like neuroblastoma and Crabbe's disease is figuring out what's safe and effective is hard, but if data accumulates that something is not, it will be stricken from the public health based panel. Individualized clinical interventions must only have a favorable risk benefit ratio in the eyes of the person who's going to get them. So the threshold for offering a test like PSA or like CAT scans for smokers It's up to you. Talk about the risks and benefits. Weigh them for yourself. If you want it, if you can get your insurance to pay for it, you can have it. And there's likely to be much wider variation on what individuals get. And consumer goods don't need any

Dr. John Lantos

favorable risk-benefit ratio or be safe and effective. They simply have to be snazzy and marketable. And you can get them even though they may be harmful or useless. Last thing I'm going to say is this emerging technology that got me interested in this whole thing in the first place, which is happening now at Children's Mercy. It's now possible to sequence whole genes cheaply and quickly. And this has been used in research for 10 or 15 years. GWAS is genome-wide assay studies and biobanking studies looking for genetic markers of disease. But whole gene sequencing is now available just in the last two years. for clinical use because the price has dropped and the technology has gotten better. And it raises questions about which genes should testing target and in which populations. And at Children's Mercy, we've now developed a test we're calling the CMH, Children's Mercy Hospital 595, which does whole gene sequencing for the 595 most common autosomal recessive conditions. And the test can be done now for $250.

Dr. John Lantos

in a CLIA approved lab that is for clinical use, not for research use. And we're offering this starting this summer with a doctor's order. So if somebody has a patient who they think might have some autosomal recessive condition but you can't tell which one, you can send them in and within two weeks for 250 bucks, we will know which autosomal recessive conditions they have or don't have. We'll also know all the autosomal recessive conditions they carry. or don't carry. And when this has been done in a research setting, the average number of autosomal recessive conditions of these 595, if we screen you all, is three. So you're all carrying some lethal gene. It's presumably rare, or you wouldn't be here. And it's...

Dr. John Lantos

has some interesting implications. The technology is clearly outpacing the regulation. The barriers between research, clinical care, public health, and marketing are growing increasingly blurred and fuzzy. And, more interestingly to me, the traditional regulations for these sorts of things have become largely irrelevant. That is, do we need IRB approval to offer this new CMH 595 in a CLIA-approved lab? No, not if it's being used for clinical testing, although there certainly are some interesting research questions that may or may not be studyable. What about the professional codes of ethics? Well, clearly there's disagreement in the professional community. The AAP and the NICHD disagree with the President's Council on Bioethics and the American College of Medical Genetics. Insurance companies, which are the sort of last resort on setting limits on what will be offered by deciding what will be paid for, are irrelevant if it's a consumer-driven publicly accessible thing. So it seems like the direction this is going is not towards better science and medicine, but towards better information that anybody can get access to, as David Ewing Duncan did about himself. And information wants to be free and easily available, and it will be. So you will all be able to decide very soon exactly what you want to know about your genome, and then will have to decide what to do with the results. We talk about a lot of these things on our Children's Mercy Bioethics website, where you can go at that address. Thanks.

Dr. John Lantos

Happy to take questions if you want, or we could just go get drinks.

Dr. John Lantos

Great question. So information wants to be free. Companies do not want it. The most famous of those is the BRCA1 gene, which has been patented, and now nobody's allowed to do it without paying... that company. Myriad, myriad genetics, $3,000. There's a case before the Supreme Court now, though, that has not yet been decided, right? So they've heard the case about whether they are going to continue to allow this. So if they uphold the right to patent genes, I think we'd be at another Yogi Berra fork in the road here. It would take us down one path towards much more restriction of access to this and not so much professional control, but corporate control of this knowledge and information, which seems so dangerous and problematic to me that I sort of hope the Supreme Court gets this one right. But if not, then all this will be locked up and interesting to think what it would mean what it actually means to patent a gene though because I mean if I'm not allowed to use my own genes for making enzymes I have to pay a license fee for my insulin

Dr. John Lantos

so it's really patenting tests and figuring out the intellectual property rules to encourage innovation and give the people who come up with innovative new ways of using genes some way to have a return on their investment is the intellectual property challenge.

Valerie P. Castle

John, wonderful talk.

Dr. John Lantos

So

Valerie P. Castle

you gave an example where physicians were misinformed even when they had a very small amount. Can you tell us how you're preparing the physicians? will now have a truckload of data as to how to interpret that on

Dr. John Lantos

behalf

Valerie P. Castle

of their patients and what their ethical and professional responsibilities are.

Dr. John Lantos

So great question. The people who are most, oh, so the question was how will we educate the physicians in our CMH 595 to deal with these truckloads of data that will be coming down the pike as kids get all these tests. The people who are the most frightened of this new test are the genetic counselors who say like, you know, we're going to send this information to your docs and you guys are so clueless that it's going to be worse than nothing. People are going to be coming in and you'll have told them all sorts of dumb and wrong. What are we going to try to do? First thing we're going to do is offer the test to all the docs on the staff. and do an education component where you can either get your own gene tested or you can come to a class about a generic genome and see what the report's going to look like and learn how to interpret this new type of data. I mean, this is stuff that nobody's learned in medical school. I mean, these techniques were invented in the last five years. And so when we do that, we'll also study the docs and see, one, how many docs sign up for the test,

Dr. John Lantos

do these sorts of psychological outcome studies. Are they glad they got it? Do they find it useful? Do they change their behaviors? Are they depressed? Are they anxious? And then test them on their knowledge and figure out sort of where the knowledge gaps are. We're going to do that first with the docs on-site, and then we're going to offer it to the community as well. So we'll see. I mean, it's... Yeah?

Dr. John Lantos

Right. You didn't miss it. I didn't say it. I mean, any doc can refer someone, but the idea is kids who have syndromes of one sort or another that have not been, docs have not been able to straightforwardly diagnose using traditional testing methods. The

Dr. John Lantos

one original idea that we've dropped would be to randomize kids to sort of traditional diagnostic approaches and this test and look at outcomes and cost and that kind of stuff. But people thought that was just too complicated. So it will be kids in neurology clinic or developmental and behavioral clinic or psychiatry clinic or cardiology clinic who seem to have something that looks syndromic

Dr. John Lantos

and nobody can figure it out.

Audience questioner

The autism spectrum, yep. We would. And then you'd have to decide what to do with it. I mean, for some things like autism,

Dr. John Lantos

there are

Dr. John Lantos

a number of well-defined autosomal recessive things that would be sort of the obvious things to look for. So one of the questions is sort of how much do we focus on the ones that have already been defined? And so if there's 10 genes associated with autism and you send a kid with autism in, report out those 10 genes but not the rest. And how much do we sort of report anything we find, even if it's never been plausibly associated. And this is where the, I think, interesting research questions come in because ideally we'd offer those options both to doctors and parents and say we can do it for known variants or we can do it for all variants.

Susan Goold

So I want to ask only about the issue having to do with when Shared resources are used to cover the cost of doing screening in particular. That example is more like a sort of case find. You have someone, you're not sure what's going on, you run a test. I'm talking about screening.

Dr. John Lantos

Population-based.

Susan Goold

Population-based screening, sometimes that's within certain age groups or ethnicities or whatever. You may lump and split a little bit. But if you're doing population-based screening... And if it's being covered either by insurance, which is pooled resources, or public funds,

Dr. John Lantos

I

Susan Goold

mean, to me, there has to be some kind of threshold met of at least anticipated benefit, if not cost-effectiveness. In adult screening for cancer, for instance, I was like, you know, you've got to prove to me it works. You've got to prove you've saved lives by doing this, or I'm not ordering it, because you're putting all these people at risk for bad outcomes.

Dr. John Lantos

Right.

Susan Goold

in order to do what? No good outcome. So there's also a cost involved. And to me, spending money on something population-based that doesn't give you benefit, population-based, doesn't make any sense. Now, for rare diseases, I would make an exception. That's why I said you have to have at least anticipated benefit. Because for rare diseases, getting the evidence is way too expensive itself. And not even feasible, probably.

Dr. John Lantos

So here's what you have to throw into your cost-benefit equation. Once you have a state screening program up and running where blood is being sent to the lab and a report is being sent back to the doctor, adding another test using tandem mass spec costs less than a penny.

Dr. John Lantos

So how much benefit do you need?

Dr. John Lantos

or each additional test. I mean, and in particular is knowledge. Put a price on knowledge for me.

Susan Goold

So we're going to screen for cystic fibrosis.

Dr. John Lantos

Cystic fibrosis plausibly has much more benefit than acetyl coenzyme A dehydrogenase deficiency. So we'll

Susan Goold

screen for cystic fibrosis, which has uncertain mixed benefits, and yet we have kids who can't get their asthma meds?

Dr. John Lantos

Uh-huh.

Dr. John Lantos

Right, okay.

Dr. John Lantos

So should we have to choose between those two? I mean, if we stopped screening, would those kids get their asthma meds? Where's Len? I mean, to frame it, I mean, once you frame it as an either-or, as if the or is something realistic, plausible, and straightforward, I mean... I'll give you 38 other ores so everybody can get screened for 8,000 things and get their asthma meds. And, you know, we'll bring the troops home from Afghanistan. Okay? Yeah? We'll, you know, increase the co-pay for the Federal Employees Health Benefit Program. I mean, right. So which things... Yeah. And which... Things have to be traded off in order to get which other things is radically non-straightforward.

Valerie P. Castle

You might add barriers to that. I mean, there's really no barrier to expanding the test, but the barrier to delivering the asthma care is perhaps something that can't be easily addressed.

Dr. John Lantos

Right. Yeah.

Dr. John Lantos

Right. So the question is, what about the privacy rights of the children if you're diagnosing something that doesn't have a direct impact on them during childhood? So if it's hypothyroidism and you don't treat them and they're going to be retarded, you do treat them, they're going to be healthy, their privacy is not relevant. Their health benefit overwhelms privacy concern. If you're testing for carrier status for some disease that will have no effect on their health, shouldn't they have the right to decide whether they want that information or not? That's the traditional argument of the proceed with caution bioethicist point of view or the President's Council on Bioethics and the Wilson-Younger criteria, that there has to be a serious harm from the disease, an intervention that's safe and effective, and a program in place to deliver that intervention, or you just shouldn't do it. countervailing argument is either knowledge is good or parents should have the right to decide for themselves. So

Dr. John Lantos

I guess I'm a little more of a parental autonomist on this because I think genetic information is not so unique as we say. So all kids know if somebody, or at least potentially know, if diseases run in their family. I mean, if granddad had Parkinson's disease or, you know, three people died of breast cancer or people had heart attacks in their 40s. So genetic knowledge exists in families with or without genetic tests. And so sort of what that does to the privacy concern only says, You can have vague information, you just can't have precise information.

Dr. John Lantos

That's how I see it. Most bioethicists disagree with me, and agree, and are much more worried. Yeah? So,

Audience questioner

in light of that, then what are your institutions actually going to do with the carrier information? Can you discover when you're looking for somebody who...

Dr. John Lantos

Right.

Dr. John Lantos

Right, so our institution had a big fight about that because if this, the question was, what's our institution gonna do about revealing carrier status? And the fight was precisely, follow up on this question, professional societies, genetic societies say you shouldn't reveal carrier information, you shouldn't test kids for adult onset conditions, you should only test them for things that are gonna directly impact their health before they're 18. I say, and some other people say, although we're in a distinct minority, let's study it. Let's offer it to some parents and kids and see whether people want it, and if so, what the implications are. The analogy would be to cystic fibrosis screening, where parents are told about their kid's carrier status. And they are in sickle cell screening, although sickle cell is a little different because carrier status also has some health implications. So it's not sort of a purely non-symptomatic trait. But I think the answer is whether people are going to find this beneficial or harmful

Dr. John Lantos

from a psychological perspective, either immediately or long-term, is radically uncertain. And so... the perfect thing to study. But so far at least we've decided not to do that and not to reveal any carrier status following the recommendations of the American Society of Human Genetics and American College of Medical Genetics.

Susan Goold

Just

Audience questioner

to say, fine talk. Thank you.

Dr. John Lantos

Now the

Audience questioner

nation is somehow in a cozy way discussing national health care in some form and what

Audience questioner

parts of that. And this is in testing as to what tests should be provided to provide

Audience questioner

needed tests, really needed tests for a nation of 300 million people. And there is really no end. As you point out, some make a great deal of sense, some don't, but the whole subject needs to be research, as it moves along.

Dr. John Lantos

Absolutely.

Audience questioner

The trouble with it, really, is the political question is, one of the political questions is, there is no effective forum by which these questions can be discussed. You can't, obviously, lead it to pharmaceutical companies, you can't lead it to the legislators, it just leaves the rest of the people out, and yet people, ordinary people, are at a disadvantage in participating in communicating to their legislators or wherever what they need, what they want to do, what their concerns are, so privacy or money or otherwise, and the lack of the forum on which these things can be discussed other than on quick breaks on...

Dr. John Lantos

Oprah and Larry King Live.

Audience questioner

You started out saying it's a mess.

Dr. John Lantos

Yes. I don't know if I can summarize that question, but that the ethical issues quickly become political issues, and we have a particularly dysfunctional political system for answering this, which is deeply ironic if you think about it, because we are a democracy, and we are a market, we're into free markets, both of which are supposed to empower citizens and consumers to sort of live the life that they choose. So in a sense, it's not that we don't have uh... uh... the possibilities that come with freedom we have too much freedom and therefore we can't come up with a single national program we come up with multiple programs sort of jockey for position either in the marketplace of commerce or the marketplace of political programming and we end up with a weird uh... extraordinarily expensive patchwork of things that satisfy nobody although give many options to everybody for what sort of advantage they want to take this new technology.