 Good afternoon. I'm Rebecca Blank. I'm the dean here at the Gerald R. Ford School of Public Policy, and I'm delighted to welcome you to the last seminar of the Science, Technology, and Public Policy program this semester. I'm particularly delighted to welcome you to this seminar since our own Shabita Parthasarathi is going to be speaking. It's always a delight to celebrate a book launch by one of our own faculty members, particularly when it's a first book. I saw Shabita in the hallway sort of caressing this book the first day she got it. Those of us who have first books all know what that feels like. So we're in for a treat. We'll get to hear about it. I'm just here to start things off. I'm going to turn things over to John Carson in order to introduce Shabita. John is an associate professor in the Department of History and he's director of the program in Science, Technology, and Society here at the University of Michigan. John. Thank you, Rebecca. Well, welcome, everybody. This is a really great pleasure, I have to say, before I do my first lecture. Before I do my formal introduction that I've gotten to see aspects of this project for a very long time. It's a really wonderful watch. Someone who's already at the forefront of scholarship, who I saw actually as a graduate student at one point and who was already stood out there as someone to, as a person to watch and clearly that was completely justified in what we have before us today. Some formal bits. Shabita Parthasarathi is an assistant professor at the Gerald R. Gerald R. Ford School of Public Policy here at UM, as you all know and co-director, in fact, really one of the founding co-director of the Science, Technology, and Public Policy program. As well as a core member of my own Science, Technology, and Society program. In fact, a very important member of that. Her research interests are wonderfully broad, is showing concentration on a single national context. Shabita works on the comparative politics of science and technology in the United States, the UK, and the EU. With a particular focus on issues related to genetics and biotechnology and contemporary international patenting regimes with the focus of her most recent work. At Michigan, Shabita teaches courses on science, technology, and public policy, genetics and biotechnology, and the politics of policymaking. Shabita did her graduate work at Cornell in the Department of Science and Technology Studies and has subsequently been awarded a number of prestigious fellowships and grants, really a truly stunning list, in fact, including post-doctoral fellowships at Northwestern and UCLA and research grants from the Wellcome Trust and Michigan's own Ethics in Public Life program. Next year, she will be a fellow at the Woodrow Wilson International Center for Scholars, as well as at the Max Plan Institute, one of Max Plan Institute's in Germany. Impressively prolific for a scholar in such an early phase of her career, Shabita's publications span the STS in policy worlds. She is the author of six major articles, including Knowledge as Power, 2003, and How Users Matter, and Architectures of Genetic Medicine, 2005, and Social Science Studies and Science. She's also published numerous book reviews, case studies, and advisory committee reports, a really impressive variety. Today, however, we are gathered to celebrate one publication in particular, her eagerly awaited new book, which I get to point out in multitudes, Building Genetic Medicine, Breast Cancer Technology, and the Comparative Politics of Healthcare, MIT Press, April, this very month, 2007, which of course will be conveniently available for purchase, and we expect you all to do that at the end of the presentation. There will be a reception afterwards. I'm sure some people will be happy to sign the book and we will all urge as many people can to buy what is a wonderful book. As we will hear today in Building Genetic Medicine, Shobita compares the development of genetic testing for breast cancer, particularly for BRCA1 and 2, in the United States and Britain, in order to investigate how national contexts shape both regulatory mechanisms and the development and deployment of new technologies. It is my distinct pleasure to congratulate Shobita on her wonderful accomplishment and ask her to share some of her work with us all today. Shobita. Thanks, John, for that amazing introduction. I'm quite sure that I won't be able to live up to the hype, but I will certainly give it a try, and thanks also for giving my book back. I will keep it safely under my pillow tonight as I have been every night since I received the book. I don't know what I'm hoping it turns into, but, you know, we can always dream. So as John said, today I'm going to be talking about my book, which, as he suggested, is about the development of genetic testing for breast cancer in the United States and in Britain. And what I thought I would do today is start out by putting that project into some context, into a larger context around the politics of science and technology, and then focusing in a little bit on one piece of the overall work. And, you know, as John, of course, said, hopefully that will entice you to want to read more. So genetic testing for breast cancer was one controversial technology that emerged in the mid-1990s, but as many of you probably know from reading the newspapers, magazines, watching TV, listening to the radio, science and technology, new advancements in science and technology are increasingly controversial among the public, whether you're talking about cloning technologies, nanotechnologies, genetically modified organisms. The list goes on and on, and so too does the public controversy around all of these new advancements. And one, many, I've been asked many times, both in classes and in lectures that I give, why is it that all of a sudden the public seems to be more engaged in science and technology development and also science and technology policymaking in general? And of course, some people see this as a wonderful move in terms of increased democratic involvement. Many see it as a problem that sort of, you know, the public all of a sudden is mucking up the works in an arena of policy that they, until pretty recently, have not been engaged in. But in general, I think that this increased public concern in science and technology development has to do with a number of things. First of all, it's that science and technology are increasingly part of our everyday lives. It's in the way we eat, the kinds of foods that we choose to consume, the drugs that we take, the way we communicate with one another, the way we listen to music, the health and beauty products that we use, and every factor of our lives and every part of our lives we're dealing with science and technology. And of course, with increased use of science and technology, we're also increasingly faced with ruptures in terms of our trust in the science and technology establishment. Of course, with more use, there are more opportunities for problems and potential disasters, right? And if you go through the decades you have in the 1970s, Three Mile Island, Exxon Valdez in the 1980s. In the 1990s, across the pond, you have mad cow disease and questions around what the British government knew about what the disease was and what they did or did not do about it. You have the blood scandal in France, the blood that was tainted with HIV. So you have all of these ruptures in terms of the scientific and technological establishment and questions around what you can and can't trust about science and technology and what kinds of risk new advancements in science and technology pose. In addition to that, there are questions increasingly about what is the kind of unknown power that science and technology bring. And of course, the most obvious examples of that today are questions around stem cells and cloning and what might happen if we allow cloning technologies, for example, to be run rampant. What might the implications of that be? We're also wondering about not just what are the immediate safety risks of new science and technology, but also how science and technology might influence our traditional values, ways we go about seeing the world and interacting with one another, our conceptions of, you know, intractable approaches to religion, how those kinds of things might shift as well. And so I think when, you know, we think about science and technology in 2007, we're talking about an interaction that's profoundly ambivalent. On the one hand, we see tremendous promise and hope, and on the other hand, of course, we are worried about what the challenges each new advancement might bring. Genetic medicine is perhaps an arena that is most representative of both the promise and challenges of new science and technology. And I just want to note that that time magazine cover is from 1970. So this is a discussion and a debate that's been happening for well over 30 years, and it's not entirely clear to me that we've answered any of these questions in a definitive way, but we certainly, as I'll argue today, have answered them in a de facto way, and I think it's worth thinking about what the implications of that are. But in general, when we think about what genetic medicine has to bring us, you know, there are a number of things. So the first is that we'll be able to engage in better diagnostics, that DNA testing can give us a better idea of what disease you actually have. And that's traditionally what, in the early days of DNA testing, what it really could do. The second, and breast cancer genetic testing fits into this category, is predicting our future of disease risk. What might happen to us 20, 30 years from now? What does our DNA tell us about our future? Third, and this is beyond genetic testing, but, you know, sort of moving into the world of what might happen in future decades, is the possibility of engineering out harmful diseases. These things are starting to happen with the availability of pre-implantation genetic diagnosis, taking embryos out of the womb in the process of in vitro fertilization, doing DNA testing, and then choosing what kinds of embryos you actually want to implant in the uterus and bring to term. But the questions are about whether or not we can actually get rid of certain diseases. And I'll just foreshadow that, in fact, this is available for the genes that I'll be talking about today. And I'm not going to talk too much about that, but after what I tell you today, I think you might have some interesting questions about what that means. And finally, another sort of potential on the horizon is the availability of drugs that are literally targeted to your DNA. And that's, you know, sort of the promise of what's called pharmacogenomics, but the hope is that someday, in fact, you don't have to take a drug that may have different side effects based on your individual makeup, that, in fact, you'll be able to take something that was made for you. Of course, with all of this wonderful promise in terms of getting rid of diseases on such a wide scale, genetic medicine also raises a number of very serious challenges and a number of very serious questions. Among them are, first of all, the worries that, in fact, there will be the creation of a new genetic underclass, that genetic technologies will be available to people who can afford them, that, you know, for thousands and thousands of dollars, and those people will be able to engineer out diseases, but that, at the end of the day, the people who are on the lower ends of the socioeconomic spectrum who can't afford basic healthcare certainly won't be able to afford these kinds of designer genetic technologies and that they'll actually be a greater split between rich and poor and that they'll be the creation of what many refer to as a genetic underclass. There are also concerns, there are probably concerns that many of you have heard about, there are concerns about the privacy of genetic information. If you generate genetic information about your own DNA makeup, then what happens to that information? Should it be given to your employer? Should it be given to your insurer? I'm not sure what Becky would have thought if a profile of my DNA makeup had been given to her along with my CV, but, you know, those are the kinds of questions that people are worrying about. What are the implications for families? That's another issue around privacy. So, if you find out that you have a disease-causing mutation, are you under an obligation to tell your sister or your daughter, and what if your sister or daughter never really wanted to know that information in the first place? There's also concerns about genetic reductionism that, you know, we will assume that everything about you is really contained in your DNA and that every answer is really there, so we don't really need to know anything about where you grew up, your personality, that at the end of the day all Becky would have needed to know when she hired me was information about my DNA makeup. Finally, a couple of other things. Environmental causation is another question that people worry is getting subsumed in this broader discussion around genetic information. Again, with a focus on genetics, we're forgetting about the fact that there are all of these other potential things going on, that environment matters as well, and that, in fact, genetics as a causative factor is actually overhyped and that genetics doesn't actually have the kinds of major implications on us, on our propensity to get diseases, our propensity to behave the way that we do, and that we're actually focusing too much on the genetics and not enough on much more complicated factors, whether it's the environment, socio-economic dimensions, structural dimensions in terms of where we choose to live, and that actually we should be spending a lot more money on that. And that that might have long-term implications, our choice of funding, for example, focusing on genetics research and developing technologies towards focused on the genome that we're forgetting about all of these other extremely important things. So, within this picture of genetic medicine and generally within this picture of sort of ambivalence towards science and technology, I think a pretty important question has to come up, and that is, how should societies deal with public concerns over technology? So, if the public is worried both about the potential challenges of new technologies, but also sort of romanced by the promise, how should policy makers, how should contemporary societies deal with this in the process of technological development? Now, traditionally, the way that we answer this question certainly over the last 30 years has been to say, okay, well, we'll have a discussion about it. We'll talk about it in the media. We'll have lots of advisory commissions to discuss the issues. But when push comes to shove, it hasn't really had major regulatory effects, as I'll describe to you today. And in addition, it hasn't really shaped technological development in a really profound way, either. And what I argue in the book using genetic testing for breast cancer as a case study is that, in fact, discussions about implications should be had in the context of technical development and that, in fact, implications of these new technologies and the kinds of, you know, sort of dealing with the challenges that, in this case, genetic medicine poses actually are often answered to a great extent in the process of building the technologies themselves. And if we wait until a technology's already around that the horse has already left the barn. So that's another important thing. That's an important, what I hope is an important contribution that this book makes. So just to give you a sense of where I'm going for the rest of the talk, I'm gonna talk a little bit about the background of the breast cancer gene discoveries. And I should say these are genes, the BRCA genes are linked to both breast and ovarian cancer. I often will refer to them as the breast cancer genes and that's because they're generally thought of as the breast cancer genes. And I talk about this in the book, but I think it is an interesting question of why it is that they've come to be known as the breast cancer genes because they're equally important in terms of ovarian cancer issues. But of course, less people have ovarian cancer and to be quite cynical about it, there isn't a political constituency attached to ovarian cancer in the way that there is to breast cancer. So that's something to keep in mind. So I'll basically give you a summary of the book and then talk to you a little bit about one slice of the book and that is in particular how the development of the technology in the U.S. and Britain have shaped different ideas around risk, disease and treatment for having inherited cancer susceptibility in the U.S. and Britain. So that's something to keep in mind about conclusions and implications of the study. So the development of genetic testing for breast and ovarian cancer really embodies a collision of on the one hand one of the most serious medical problems that we have in contemporary societies, particularly contemporary western societies and that is breast cancer and I would argue that it's both a medical and a social problem and it's colliding with one of the most exciting and many would use the word revolutionary scientific breakthroughs of our time and that is genetics. So it's not entirely surprising that the development of genetic testing for breast cancer and the discoveries of genes linked to breast cancer were very highly anticipated and as I'll say and just talk about in just a second we're really involved in international race to find the genes that are linked to breast and ovarian cancer. So many of you probably already know these statistics but breast cancer is a very common disease in contemporary societies and as I said particularly in contemporary western societies the picture that you have there from Time Magazine is from 1992 I believe and they say at that time 1 in 10 American women will get breast cancer now the statistic is 1 in 8 and while over the last 30 or 40 years where there's been increasing attention to cancer and in particular of the last 20 years when there's been really intense attention to breast cancer there have been improvements in terms of longevity once someone gets breast cancer there have been improvements and diagnostics and treatments but we are very far from solving the breast cancer problem and in fact often it seems like we'll take one step forward one step back or even a full step back just last week for example in the New York Times they reported that there are new studies that show that what they had hoped was a new way of reading mammograms actually causes more problems because it often causes more false positive results than regular mammographic readings so this is a constant problem and the incidences of breast cancer in Britain are about the same it's about 1 in 12 women in the UK now in this context I mentioned that breast cancer has become very politicized particularly in the United States since the early 1990s a number of patient advocacy groups have coalesced around the issue of breast cancer and have been very successful in the US in particular in being able to increase funding for breast cancer research by about 900% so today you know there's about 800 million dollars that's devoted specifically to breast cancer research alone and one of the interesting elements of it is that in fact a large proportion of this comes from the Department of Defense these breast cancer advocates were able to go to the Department of Defense and figure out a way to get the DoD at a time when its budget was being cut they were able to convince the Department of Defense to demonstrate its utility by funding breast cancer research so there is considerable patient advocacy around breast cancer which has had a pretty important influence on the attention to the disease and many people say that it's now out of proportion with the amount of incidence but it's very serious and they've had great success as I said now there's considerable research effort into the breast cancer prevention, detection and treatment efforts as well so within this context of a lot of political attention high profiles, a very serious medical problem discoveries of genes that were linked to breast cancer were of course very highly anticipated and in the 1980s and 1990s there was what was referred to often as an international race to find the breast cancer genes so scientists in Japan Germany, France, the UK the US, Canada were involved and they all wanted to find these genes that were linked to inherited susceptibility to breast and ovarian cancer they probably anticipated that of course there would be major rewards in terms of prestige but also of course probably major financial rewards as well and in the mid 1990s and 1995 the breast cancer one and two genes were found known as BRCA1 and BRCA2 now these genes at the time were thought to be linked to about 5 to 10% of all breast cancers nowadays they say actually that it's closer to 5% and these genes were linked to an increased risk of contracting breast ovarian cancer so it didn't mean necessarily that you would get the disease in fact you know there was a huge range it was at the time people said up to 85% average lifetime risk of getting breast cancer in particular now there are cases where you could have a gene mutation and you don't get the disease and of course you could you have breast cancer and most breast cancers are not due to one of these genes however given the excitement over genetics and the concerns about breast cancer worries about breast cancer genes are quite significant in fact I've often given talks and people think that somehow the breast cancer genes or the genetics of breast cancer is responsible for a lot more breast cancer than what it actually is and I think that that's an important part of the story because then when the discussion began in the mid 1990s around how to develop a genetic test for breast and ovarian cancer were physicians and policy makers were talking about a real large potential demand because if everyone who has any concern about breast cancer is thinking about taking this test then you're talking about a huge number of people of course but at the same time this is a set of breast cancer genes that is kind of uncertain right I mean it's only related to a small proportion of all breast cancers and at the same time you could have a bracket mutation and it doesn't actually cause disease incidence and this is sort of a new this is what's called predictive genetic testing it's a different kind of genetic testing than what I was telling you about before the sort of more traditional you know you have a disease and it's used more in a diagnostic way so this kind of predictive genetic testing raised a new set of questions in terms of how to build these technologies and in the book overall I go over this new technology bracket testing developed and I show how it's different in the US and UK and I'm going to talk a little bit about those differences today but I account for these differences in a number of ways both structural and cultural I mean obviously as both of you probably know in the US and UK they have very different approaches to healthcare you know pretty different political systems and ways of dealing with scientific and medical expertise but there are also more subtle things going on issues around different approaches for example to patient advocacy and different histories of patient advocacy different ideas about the appropriate relationship between science and industry those kinds of things I argue also played an important role in the way that the two technologies developed very differently in the US and in Britain and I make a few arguments the first is that national context influences technology development second that the ways the technologies are developed in the two countries actually influence the implications of the technology I talked about that already a little bit they influence the rights, the roles, responsibilities of the people who are actually using the test and engaged with it and as I'm going to talk about more today defines risk treatment and the way disease is defined and then finally I talk about what happens when the American provider the test goes to Britain and uses its patent rights as it's accustomed to do in the US and it uses its patent rights to try to force the British to exceed to its testing system and shut down its indigenous testing system and what I demonstrate is the British opposition to that and actually a more widespread European opposition to that and what I argue there is that all the things that I've talked about throughout the book that ties to national context the way in which these technologies are embedded in particular social and political systems influences its ability to simply easily transport or engage in transnational technology transfer and what I hope is that those kind of analysis demonstrates why often there seem to be increasingly controversies around transnational technology transfer another obvious example is of course genetically modified organisms which perhaps not as controversial in the US but lo and behold when a ship carrying genetically modified soybeans tries to dock on British shores it becomes a major international incident so I'm going to start by talking about the US case and then I'll move on to compare it to the British so in terms of the initial development of genetic medicine in the US basically genetic medicine and particularly clinical genetics basically physicians taking family pedigrees and mapping out your family history began in the 1940s or so and it was based in hospitals so you had physicians doing this kind of work but by the 1970s when DNA testing became available there were more and more labs attached to these clinics and then again not surprisingly given the American environment these labs began to spin off and so there have been an increase in commercial labs in the US and a split between the activities of the laboratory and the activities of the clinic they've almost operated in very separate domains and that's an important dimension that I'll return to later in the talk the clinical laboratories improvement act which is part of the department of Health and Human Services does regulate this kind of testing to some degree but they only regulate what happens in the laboratory so when you split the laboratory and the clinic really all they're focusing on is what's happening in the laboratory and even that they only do to a small extent because a lot of genetic tests are really sort of really minor one-off genetic tests they're for complicated genes and it's being done in a random research lab and that research lab may or may not know that they're subject to this regulation so they don't actually then get regulated by this act on the other hand the clinical dimensions of testing are basically unregulated in the US so the Food and Drug Administration has been encouraged on numerous occasions to step in in a greater way in the US but they've been reluctant to stifle what they say is a growing industry especially when they say that a lot of these are these little research labs and if they try to go after these and create a regulatory framework that it'll be too burdensome and it'll shut down some of these small testing laboratories and as well you know genetics clinics in hospitals who won't be able to withstand this kind of regulatory burden and in addition of course the Food and Drug Administration and the US government in general has not been very happy about the idea of regulating physicians we don't really have a precedent for that in the US we've kind of stayed out of it and genetic testing sort of raises these questions about what role should a clinician play in talking to their patients about these kinds of uncertainty questions that I was raising before the psychosocial dimensions involved in you know whether or not you should get this test but also whether or not you should tell family members all of those new kinds of challenges that are raised with genetic testing often have raised the question about whether or not we should regulate what happens in the clinic but we don't really have a precedent for that so that's one thing that we have also continued to be reluctant to do within this environment a number of genetic testing for breast cancer providers emerged and one provider eliminated its competition and did so pretty quickly and you know with you know with what is again not a surprising method and that is that they use patent rights to do it basically so they had a very strong financial position and they had also applied for patents on the genes they were responsible this company myriad genetics was responsible for finding the first breast cancer gene and they had applied for patents on it and then basically you know there were a number of providers they basically went in and they shut down all the rest of the providers using their patent rights to do it now as I intimated and I'd be happy to talk about this more in the questions you know they tried a similar strategy in Britain but the Brits basically said yeah we don't believe in patenting genes so that I mean that's a very very flippant way of putting it but that's one of the major tropes that occurred when they tried to go to Britain but anyway they were successful in the United States and they created a test that was in some consumer product DNA analysis so what they were really offering was a state of the art DNA testing technology it was marketed quite widely and it was available to any patient or consumer as they really were in this case through any physician and no specialized genetic counseling was required so again taking advantage of the split between laboratory and clinical services they said listen we're just a laboratory and we want to offer this test which is an important test for an important high profile disease we want to offer it as widely as possible so we're going to not restrict it availability in any way the prices for the tests range from 250 dollars to 4000 dollars depending on the test that you get but the most common which is a full sequence analysis of both genes to check for mutations is about 3000 dollars and that's not an insignificant amount because many people concerned about privacy issues are worried about asking their insurer to pay for it so they're paying for it out of pocket which then goes back to questions by the way around you know the genetic underclass is talking about before and in fact in addition to not having their physician know about it and not getting this information put into the medical record the consumer actually can decide which physician gets results and in my interviews I often spoke to people at genetics clinics who said that people would come in and give aliases or you know try to go to genetics clinics away from their physicians so that the information would actually not get back to their primary care physician and not be put in their medical record so and I just you know I brought a prop this is a case this is one of the genetic testing kits that's provided and I think it encapsulates the approach pretty well right I mean it's this sort of box that you can get you know shipped to the physician your blood is drawn it's shipped back to myriad in terms of it being sort of a real consumer product I think that's a pretty you know that you can buy a box you can buy it anytime so within that context what happens once you get a genetic test well you can have a few kinds of results first is obviously you can test negative for a BRCA gene mutation that of course doesn't mean that you're not at risk for breast cancer it just means that you're at the same level of risk as the rest of the population second you can have a positive test result and that means that you're of course at risk of getting breast or ovarian cancer sometime in the future and that's one classification so they are not yet at the stage they weren't in 1996 when the test was initially offered and now they we still haven't done enough research to actually give you specific information about what each mutation does or how that mutation might operate in your family so what they generally do is they give you one risk classification even though you know the mutation is likely to operate differently in you know different mutations are likely to operate differently and each mutation is likely to operate differently in different families one of the things that's interesting about the way myriad genetics talks about this technology is that they emphasize that if you have a positive gene mutation you have a particular disease and that is the disease of inherited cancer susceptibility now it's not entirely surprising of course that a company who is interested in selling you access to this box would want to also construct a particular disease right and that is the disease of inherited cancer susceptibility and it's a disease of inherited cancer susceptibility that's linked to a very specific kind of breast and ovarian cancer and that's hereditary breast and ovarian cancer and they again make a point of saying in their promotional materials and their educational materials for physicians that you don't need to have a family history to have the disease of hereditary breast and ovarian cancer right or the disease of inherited cancer susceptibility now one would ask but it wouldn't matter I mean if you don't have a family history then you probably aren't going to get the disease but they're interested in making that distinction right because again it reinforces the utility of their test now of course for most people either get a question wrong or you get a question right however in this case there is a third category and that is that you could have what's called a variant of uncertain significance and a variant of uncertain significance means that they found an alteration in your brachy gene but they don't know whether or not it's actually a mutation or not and that used to happen in about 20% of all cases now about down to 10% of all cases and that's actually because a French group who is not beholden to the patent issues in the US did some work and found that part of that was a result of some of the mutations that myriad was missing and so now they've incorporated that reluctantly into their testing system but it's still about 10% of all results and what does it mean then if you have what's called a variant of uncertain significance it means in essence that you're at risk of being at risk right so it's yet another risk classification and it's a risk classification again that's defined by the DNA so here you have really a set of risk classifications that are built on a particular approach to the technology right when you focus on the DNA analysis then the risk classifications are based on what the DNA has to tell you and furthermore of course not only is that a byproduct of myriad's testing system in that way but it is also many argue a byproduct of the fact that this is a technology that was offered immediately after the genes were discovered because you don't really have to do much work once you can sequence the genes to find them then you can sequence the genes to find a mutation and so that's no problem but many people argue actually if you had waited and there had been a lengthy regulatory approval process then you might have narrowed the number of variants of uncertain significance somewhat and you wouldn't have in the early days 20% and perhaps even now 10% of these kinds of cases now within this category how do you treat those people that are testing positive for a BRCA mutation there are three different potential options available the first is that you have increased surveillance increased mammography really the screening options available for ovarian cancer are considered to be not very good the second is prophylactic surgery either mastectomy or euphorectomy of course those are pretty drastic measures and finally chemoprevention in particular tamoxifen and I'll talk about this a little it's very interesting and comparative perspective but basically the genes were discovered in as I said in 94 and 95 and around that time there was a transnational study being done to test whether or not tamoxifen was a useful drug among women who are at high risk for breast cancer and in 1998 the Americans stopped the trial early and decided that in fact it had clear benefits and the FDA approved it in an expedited fashion and what was very interesting about that again going back to the sort of production of the utility of the test was that a number of the investigators involved in the study talked explicitly about how now we have this diagnostic test right we need to do something with the people who are diagnosed with this you know inherited cancer susceptibility and neither mammography nor prophylactic surgery are appropriate measures and this is in essence a magic bullet right so that was definitely one of the one of the sort of important pieces of rhetoric around the expedited approval of this drug now of course the study started in 1992 before they had discovered the breast cancer genes so it didn't you know just because you were in the study doesn't you were actually put in the study because of familial risk not because of the presence or absence of a BRCA mutation and so that's an interesting element and I'll actually just say as an aside that since then they've taken that cohort they've taken out the number of people they found the people who have BRCA mutations they've tested them and they've actually found that it really has equivocal benefit however it is still prescribed as a chemo preventive option for people who are at risk so it's sort of you know in the desperate times call for desperate measures mode of provision of treatment so moving on to the British case initially the Brits offered genetic medicine in a very similar approach to the United States through hospitals and then as the NHS ramped up in the late 1940s and early 1950s and 1960s the genetics clinics were incorporated into regional national health service authority so every region and the number of regions has increased now it's around 18 NHS regions across the country has a regional genetics clinic and this regional genetics clinic offers both laboratory and clinical services so in exactly opposite way to the US where they split off in the UK laboratory and clinical services are really kept together and there aren't private genetics clinics or private laboratories that's starting to change now but in terms of BRCA testing that remains the case and of course not surprisingly given the national health service there are a couple of things that are you know that are not going to be at all shocking to you the first is that equal access is a very important priority and continues to be in terms of the provision of genetic services and there is regional administration but there's also national administration and so you have de facto regulation of laboratory and clinical services in that way right so because they the national and regional health authorities are the ones funding these services and so they're deciding what they're going to fund they're not going to fund and so therefore influencing what kinds of technologies are available and how they're made available and not surprisingly again predictive testing raised the same kinds of issues around who should have access to testing how much of this should be funded and in particular questions that were raised in a different way in the US got raised in Britain as well so this is a test that should be available for healthy women what are we really telling them how should we you know provide this technology that may or may not have clinical benefit those are the kinds of questions that got asked because of course at the end of the day the national health service has to pay for the test which is expensive but then they also have to deal with these women you know when they get or don't get cancer in the long run so of course their set of concerns is different than the set of concerns that we see in the US and this comes up you'll see again both in terms of the development of genetic testing for breast cancer but also in terms of the definition of the option treatment options available so how did BRCA testing develop within this context initially it was administered in a pretty half hazard fashion and different regional health authorities offered the technology in different ways however a number of scientists and public health officials realized that genetic testing for breast cancer was likely to be a model case not only for predictive genetic testing but also for dealing with genetic medicine in general and so they lobbied for the creation of a national system and they decided to do what's again not at all surprising given the British environment that is to create a national system of risk assessment and triage and here in comparison to the US where myriad really diminished the importance of family history and focused on what the DNA could tell you in Britain they used family history as a way of doing the triage itself so they asked primary and secondary care physicians to make up a family history and then they would divide individuals into low moderate and high risk categories depending on their family history and individuals who are low categorized as low risk were reassured and turned away. Individuals that moderate risk were offered access to mammographic screening but they were not offered access to genetic counseling and genetic testing the idea being that they were probably at increased risk and it was worthwhile to spend the money on mammography to keep following them but it didn't warrant the additional work that was required for counseling and DNA testing because it was pretty unlikely that they had a BRCA mutation. Individuals who were defined as at high risk were then offered access to the regional genetics clinic and DNA analysis and they did something in particular which was to test women who had breast or ovarian cancer first and the reason that they did that was because they wanted to link the mutation and the disease incidence if a mutation was actually found in the family and the reason that they did that was because they said listen we don't have a lot of studies we don't know what individual mutations do in all cases but we want to avoid the creation of variants of uncertain significance that emerge in the US when you're focusing so much on what the DNA has to tell you so in the British context they said listen we want to focus on testing affected family members first because then we might be able to tell you how this disease tracks in the family and what the mutation actually means in that context now if you didn't have an affected family member available to be tested that doesn't mean that it would shape it doesn't mean that you wouldn't get access to the treatment options you would still be in this high risk category and then have access to the high risk treatment options and I'll get to that in a second now as you can tell from what I've already told you the focus was really on what happened in the clinic and that really contrasted but with what happened in the US where the focus was really on what happened in the laboratory and what's interesting is that in fact different regions use different laboratory methods to look for these gene mutations and they were all sort of you know somewhere between 90 to 99 percent sensitive but the focus really wasn't on what the DNA analysis could tell you it really was on what the clinical dimensions of this testing system were that's really they said listen at the end of the day you know that stuff isn't as important it's much more important to track these individuals and to make sense of this DNA analysis technology in the context of counseling and risk assessment so once you got tested in Britain what happened to you well as I said the testing was used to refine the familial risk category and moderate risk individuals had access to initially a mammographic screening study now they actually just have access to mammographic screening mutation positive individuals and also those who are not tested but were considered to be still high risk because they couldn't get an affected family member to be tested as well had access to treatment options they had access to increased surveillance and they also had access to prophylactic surgery now you notice of course that they didn't have access to to moxifen why is that well that's because as I said before this transnational trial that was being run was being run between US, Britain and Italy and so the British and Italians were running trials at about the same time and when the Americans stopped the trial early the British got pretty upset saying basically you know sort of lobbying all kinds of nefarious charges at the American researchers but also making the point that it was very difficult in the span of six years to find out whether taking to moxifen for life was a worthwhile thing to do and in particular they said listen we're talking about giving healthy women a drug that is potentially dangerous and we don't want to be responsible for the consequences and here too you see how a national health service shapes an approach to the scientific evidence right because in Britain they were saying listen we have to pay for whatever the effects of this drug are and if this drug has risks then we are going to have to deal with them whereas again in a private healthcare system like ours they don't have to deal with those kinds of issues and so that shapes the way in which they view that scientific evidence so the British and Italians continued their trials and actually and I think they ended them in 1999 and 2000 and their trials showed basically equivocal benefit and increased risk of endometrial cancer and then later another study showed that there was an increased risk of stroke now what's interesting is that those results were largely discounted in the United States so one would think and I've often asked this question and the US and Britain are pretty similar places but on these issues it's amazing how different they actually are and that's what makes this study I think was made it really fun to do was that on the one hand you would expect them to be totally similar on almost every scale they're quite different from one another so the UK and in fact all of Europe does not allow for the provision of tamoxifen to high risk women and their argument is basically listen we think it might be useful but we don't have enough evidence now and especially again when we're talking about providing this drug to healthy women we're not ready to go over that threshold at the moment however in the US they continue to offer tamoxifen to high risk women in general and in particular women who test positive for BRCA mutation so in some then what are the major differences that I've talked to you about today well in the US BRCA testing was really approached as a standalone DNA analysis technology with a focus on identifying people who had mutations and treating them and the focus was on a technically accurate test risks were defined by the presence or absence of a gene mutation or of course the presence or absence of a variant of uncertain significance and there was a construction of a new disease new disease actually two new diseases a disease of inherited cancer susceptibility and also a disease of hereditary breast and ovarian cancer now I should say that in Britain it's not that there's a discounting entirely of the concept of hereditary breast and ovarian cancer the issue is however that they just don't see an important distinction between what they call familial breast and ovarian cancer and hereditary breast and ovarian cancer to them it's kind of the same thing the DNA analysis is simply an additional tool it's not a separate standalone technology so in Britain obviously beyond that you have risks really being defined by family history and a focus on what happens in the clinic and just one more thing that I didn't talk about too much today but I think is an important element of this is that in the US I talked about the provision of genetic testing for breast and ovarian cancer really as a consumer product and what you see is that in this environment you have the patient being defined as a consumer the physician really becomes a facilitator so the consumer can shop around to a physician who's going to offer her access to this test and so you have a relationship really there between a consumer, a facilitating physician and the company whereas in Britain you have much more of a traditional doctor-patient relationship you have a real patient who's also a citizen of course because it's a citizen within an NHS structure and you have a physician who occupies a pretty traditional role they're defining what that patient has access to what they can and can't use in terms of DNA analysis and in terms of counseling so it's much more of the traditional paternalistic model whereas here we have the sort of image of the empowered consumer but I think you see in this comparison some of the benefits and risks to both of those characterizations of the doctor-patient relationship so then overall in terms of genetic testing for varying cancer and also in terms of genetic medicine I think that the study has a couple of important implications the first is that what I say and it's a technical term that I use in the book a technology's architecture that is the way that a technology is built actually defines in large part its implications so when we talk about implications social and ethical implications of genetics and biotechnology which we often do we often don't talk about it in the context of technical issues or scientific issues but what I'm arguing is that in fact we need to do that because that's where many of the implications get discussed and decided in a de facto way that we often don't realize and shape our futures in pretty profound ways and actually when we're talking about you know a model case like genetic testing for breast and ovarian cancer it then shapes how future genetic tests are built so now in the U.S. for example we have a number of genetic tests that are available over the internet there's actually a company that offers bracket testing via you get counseled over the phone they sort of it's interesting this is a company that offers other genetic tests over the internet but they've taken a different approach to bracket testing and I think it's probably because they know it's kind of controversial if they were to just do an internet sort of internet interaction so basically usually you go into the internet you say you're interested in this test they'll send you a box like this it's a different company it's called DNA Direct and then you talk to a counselor over the phone for other genetic tests you talk to them over the internet and then they'll send you the results and then again in the case of bracket testing they talk to you over the phone in the case of other genetic tests they just give you the information over the internet so and I argue in the book that that kind of technology wouldn't exist if it weren't for the structure that bracket testing took because it was really a model in terms of the way predictive genetic testing could be provided and genetic testing in general so in terms of thinking about the future of genetic medicine I argued that we need to bring together both technical and public discussion and I also would argue that this case study technology and one medical technology actually opens up broader discussions about the role of technology in health care and at the risk of sticking my foot into broader conversations about health care reform and the future of health policy especially with elections coming up I think this is an interesting question that gets raised here is that you see how all of the issues around why it is that we have the approach to medicine and health care that we do are embedded in this one case study and our love of technology and our interest in things new and our consumer approach to health care are embedded in this one story and it at least for me makes me ask the question but whether or not we could go to something like a single payer system when these kinds of approaches are so intractable and in fact embedded in technological design itself and I argue that obviously I argue and advocate upstream assessment of technologies and in particular model technologies and I think we have to ask the question about whether or not we and by we I mean those in the US and also in Europe are happy with the way that genetic medicine is being built and we have now the opportunity to think about technologies that are at an earlier stage that is pre-implantation genetic diagnosis for example that I mentioned earlier and also pharmacogenetics that I also mentioned earlier and finally to go back to the larger picture of science and technology development there are a couple of things that I just want to add to start out with as I said before I really think that public concern over scientific and technological development isn't going to go down it's only going to increase at this stage and so given that and given the fact that people are more and more invested in scientific and technological development I think it becomes incumbent upon policymakers and also those of us who are engaged in these kinds of conversations to push for real conversations about the stakes of technological development and the stakes of actually the way that technologies are designed and how implications are actually built into these technologies so that we can build better ones and perhaps mitigate public concern in the future and these days you know there are increasingly efforts towards this the European Union is trying to do a lot of this work and in the US we're starting to do some of it too but it's very on a very very very small scale perhaps larger in the EU but it's pretty minimal at this point so there's a lot of potential for growth so I'll stop there and I look forward to your questions Yes sir, in our families, particularly the women's side in our family I've recently been tested for BRCA1 assuming the test becomes positive would the next step be for my daughter who I'm concerned about take the test also? I mean that's a decision that your daughter, you and your daughter would have to make yeah that would be the logical next step to find out whether or not that particular mutation is an issue in your family Alex? in the discovery that allowed that erasure and the forgetting of the family I think the way to think about it is to remember that the provider of testing in the US now was not was only partially engaged in that it would be incorrect to say that they were not engaged in those studies because Maria Genetics was born from a scientist at the University of Utah and there's a lot of evidence to suggest that it was because of Mormon genealogical records that they were able to find the breast cancer genes in the first place but they sort of took off from that and capitalized on what the DNA analysis could provide so some of the stuff I didn't talk about is how Eli Lilly provided married with $10 million to buy rooms of gene sequencing machines so that they could win the race so in that process it becomes about the technical it becomes about what the genetic code can tell you and less about what the family history is actually saying and so there's distance there between what's happening in the genetics clinic it becomes a biotechnology company that is capitalizing on this gene sequencing machines and then patenting the genes and then doing what they can to as quickly as possible commercialize what they found and the most seamless process to commercialization is to offer this DNA analysis as a quick consumer product so I think that's an important part of it because what I didn't talk about and I do talk about a lot in the book is the other providers of testing in the United States and I don't want to leave you with the impression that this was the only way that it could have gone in the US there were actually a number of other testing providers and they offered it in very different ways and some of them were genetics clinics who were very much more tied to questions of family history there was a biotech company who had an officer who was a clinician herself so she defined testing in a very different way so there were very different approaches to testing I think it was about the corporate strategy approach that myriad decided to take that shaped the way that erasure process Joel? I'm going to push you first of all congratulations a fantastic book and a fantastic project I'm going to push you towards one that you might not want to go towards thanks and that is I know a way to look at this is that we're infatuated with medical technology that we believe deep in our hearts that science and technology are going to make us healthier and better and live longer you touch briefly on the various ways of screening for breast cancer it surprises no one with any knowledge have a machine that finds smaller and smaller smaller issues that are more and more positive there's dangers there one of the dangers is that you end up spending twice as much money for a doctor care as any other industrialized country and getting results that on a good day with the wind behind us going downhill we're average on a bad day we're not at among the industrialized countries so in a fantasy world whoever gets elected president turns to you because they will of course they will it's going to be far to give to Washington let's say they turn to you and say what does this book tell us about what our health policy ought to be like going forward are there any lessons here that you can draw on that any tangible lessons I think that's what I was trying to get at a little bit but I was probably mealy-mouthed on purpose I think we do have a certain romance with technological development in particular when it comes to medicine and we believe that every new technology by its very definition is going to save us and the question is really whether or not any kind of health care reform in any realistic way will ever work we don't get over that and I mean that's my cynical meaning of this really we keep talking about it we keep going over it over and over again but we have a certain romance with technology which unless we can figure out a way to break that then I don't think there's much hope now I certainly would hope that we can figure out a way to break that but I'll just tell you this quick vignette of a student that I had who came into my office and was saying well the British health care system is worse obviously and I said well it depends on what you're looking at and she said well I went to Britain on my honeymoon and I was hiking in Wales and I fell and I broke my leg and I was in traction for three weeks and I came back to my physician and my physician was shocked at the the age of the brace and how such old technology and if she'd been treated in the US it would have been so much better and she said so that's an example and I said well so you were treated in Britain and she said yeah well that wouldn't have happened in the US and I said and she said I said so you were also in traction for three weeks in a British hospital and you were a foreigner from the US that also would not have happened in the US and then I asked her how she was doing now how was her leg and everything was fine you know and it was only after that conversation that she was like oh yeah it was interesting to hear that she was treated and was cured and that that might be something to consider so what it makes you realize is that and this is something that I think is an issue and I talk about in the book is that what is a good health outcome is not obvious but in this case what is defined as a good health outcome in the US is having access to this technology and it was so interesting to me when I was doing the research the issues around what you would do with the technology were almost absent in the beginning it was all about having access to the technology and there are all these statistics that you probably know better than I do about how every hospital has to have an MRI in order to compete that's because it's about having access to the technology so in the US most advocacy groups, patient advocacy groups were against the commercial provision of bracket testing and what myriad chose to do was to go around them so what's interesting is that they and this is not a direct answer to your question but they John mentioned that one of my articles is entitled knowledge is power which is a feminist health cry from the 1970s and myriad used that tagline in their marketing materials basically to demonstrate their affiliation with the women's empowerment movement but they didn't have friends in the advocacy community they sort of tried to take their rhetoric and sort of go around them so that's what happened in the US in Britain there was a question of patient advocacy but patient advocates were involved but they were really to the extent that patient advocacy groups have ever had a role influencing the national health service it's been advocating increased access to services and that's what they did in this case as well they tried to increase access to services so I'm not sure in either case they had a deleterious on the development of the new technology but they both had sort of interesting and perhaps not entirely expected effects on the development of the technology but that knowledge is power wouldn't work in Britain I don't think a quick summation of what happened was when myriad did try to go to Britain to expand its testing service was not only was the patent issue you know sort of as I said sort of ignored but the Brits basically said listen we don't think your test is very accurate we define our accurate in terms of the clinical dimensions of the test you define it in a different way we don't think it's very accurate we believe and we have all these values and your test doesn't adhere to those values so we think it's a bad test and we think it's an inaccurate test which the use of even the word accuracy was pretty interesting in that context what myriad then tried to do was to create sort of a satellite laboratory in Britain which existed for a little while and then it collapsed for reasons unrelated to their deal with myriad but since then the coalition of groups around from throughout Europe have challenged myriad's patents at the European patent office and we're able to get myriad's patents most of them revoked except for one small mutation so myriad basically can't do anything in Europe at this point and now there's a lot of hatred towards the company among scientists and physicians you know and patient advocacy groups throughout Europe as well who are involved in these coalitions against the European patent office that inspired the stuff that I'm working on now and so you know in those so what I know is that from speaking to clinicians in Britain there has not been a lot of uptake of the test to the extent that there has been some uptake of the test there's actually been a number of these variants of uncertain significance or people coming in trying to get interpretation of the test results which they can't get otherwise all of those kinds of things have happened there so it's you know people have that option and if you know it is often the case right there may be having one family they may have one family member in the US and one family member in Britain so they may know about it but actually I know of at least one case where someone in the US had the test taken got I think a variant of uncertain significance and then the sister in Britain asked the test result and then she went to her GP to ask for interpretation of the test result so you know yes technically you could you know do that and have you know write a you know whatever 1500 pound check and get access to the test but the uptake of that is questionable and if you're going to ask me about the number of tests that have been sold I wish I dying to know the answer to that question but myriad keeps that information under lock and key ah yes Canada totally different yeah so Canada also has fought myriad's patents and been successful they have their own indigenous testing system that is sort of halfway in between it's slightly more lenient in terms of the risk categories and then Britain but it has a similar structure to the British system and I should say that other European systems are pretty similar to that the French and German systems are are more similar to the British system and but they also have some sort of structure risk assessment and triage although not as extreme as the British system and ah yes Iceland has a very very different picture sociologically than biologically mainly virtually every human being in Iceland has had a DNA test perhaps not to complete everything now doesn't that represent a much more advanced approach because everyone's life is in a clinical trial why do we have just clinical trials rather than following every person's health well um Iceland is a very interesting case it sounds like you probably know they have a they tried to develop a genetic database in Iceland that incorporated everybody and that would link the um DNA information to the medical records and initially the argument was that Iceland has a homogenous population and can capitalize on this in the world market by you know using that homogenous population and this treasure trove of um genealogical information to um find all kinds of gene mutations and gene tests and drugs and etc um so those are at least a couple of differences between you know the US and Britain with Iceland is that it's a very homogenous population with long genealogical records it's a very small country um and so the kinds of things that might be controversial in the US and in Britain are unlikely to raise the same kinds of issues in Iceland one might think however even in the case of Iceland that project when um and it's not clear whether it was simply about Icelandic um you know sort of once people realized what the project was all about they stopped it or because of the international scrutiny that emerged uh in the wake of the decision to engage in that database uh they actually stopped the doing that because so they actually stopped the program anymore so I'm not sure Iceland is the best case scenario because at the end of the day they too decided that it was a little bit too much of a hot potato uh recently uh last couple of years I don't know uh exactly I can get back to you on that John then alright then I'll just take it I want to push you on the other side for a minute and in effect in a way you can get up Miriam's case back to you which is that especially um you know partly to bring out that if part of the packaging is around technology partly as you also point out in your work is around the kind of broader culture of understanding cultures of relations to authority and particularly around expert culture and then here specifically I'm thinking about what about a vision of not just genetic testing but a whole set of testing that goes around and outside of positions as key monitors I mean to what degree does want to make another form of argument that people should have the ability and the right to find out that they have higher cholesterol by having a blood test done on their own initiative getting the results most of the labs do do do the analysis to begin with it's not positions we're doing analysis and in fact have all kinds of ways of monitoring their own health and behavior in ways that might be cheaper but also give them a form of power system that to this point is largely still moderated by positions now as we know in America clearly there are enough moments of skepticism toward expert authority in certain limited contexts that that can have an emotional stability that has had some kind of sway in Britain however you know with things like with the BSE scare of course there have been a number of recent episodes that have also at least caused some doubt about whether expert authority Britain can be as trusted as it might have been 20 or so years ago so I'm wondering I guess in the first part what are the ways in which we can see this as another kind of story that has a certain kind of resonance at least as powerful as the one about the British model and also the ways in which it brings out sort of trust in experts as being another part of the package that goes together in making this story so I should preface all of this by saying that my intention is not to demonize myriad right so while it often can come out that way I think that these are both two systems that emerged for specific reasons in particular countries the extent to which one could work in the other I think is limited I think that myriad is and to the extent that we think that the myriad system or the national NHS system are problematic I don't think that either is to blame that we as members of a society in which these structures and this particular cultural approach exist are the reasons why these technologies exist as they do and I say that in part because I didn't realize this when I started my PhD dissertation but as some of you who know this story or know anything about genetic testing probably know myriad has become has been demonized, has become sort of a cause celeb among those who are against any genetic testing you know and it's become an outlier it's become an outlier case so a lot of people say a lot of people critique myself and say well myriad's an outlier case and I vehemently disagree with that I don't think that it's an outlier case at all and I don't think it deserves to be demonized and I don't think and I think that actually it's quite typical and that sort of leads to my answer to your question which is that you know again going back to larger questions around healthcare and the provision of healthcare in the US the New York Times think about a year ago had a really interesting series about the empowered consumer of healthcare and the double-edged sword of being that empowered consumer of healthcare and I think that that's what you see in this case as well so that's why I said you know this is not an outlier it's actually a pretty typical case and in this case you have an example of a technology that as you said right it's absolutely typical for the United States you have we've been taught in part this is the legacy of bioethics is you know the importance of patient autonomy importance of patient empowerment and so you know we want to be able to demand access to this technology and we don't want paternalistic physicians telling us what to do which is of course you know where the British model is a caricature on the other on the other side right but I think we are very accustomed to seeing the drawbacks to the paternalistic approach that we see in the British because we have over the last 20 to 30 years emerged into this you know sort of place that valorizes the empowered consumer and the role of the physician as a facilitator whereas in the U.S. we're not as accustomed I think to thinking about the problems that arise when you're an empowered consumer and there are at least I mean I've sort of talked about a few of them but there's repeating at least and maybe expanding on the first is that especially when you're talking about this kind of complicated risk information you're putting a lot of burden on the consumer to know a lot of information you know we can't assume perfect information right so these are these are people who are going in and being confronted with you know oh well 30 to 85 percent average lifetime risk of contracting breast cancer well how do you deal with that piece of information and you're often left alone to do that and if you're not going to a specialist and you're going to a primary care physician they may have limited knowledge about how to help you interpret that kind of information so I think that that's one of the issues that arises now given that of course most of the people in this room have this information by googling it right googling bracket testing and asking google all the answers to your questions and you'd probably get a lot of useful information along with some probably pretty useless information but you would get a lot of information and you'd be able to then process it but the other thing that raises the other question which is that the assumption of an empowered consumer assumes a certain kind of consumer an upper middle class relatively educated consumer who knows how to interpret that kind of risk information which I think is an unfair assumption to make and I think those are some of the kinds of things that came up in that New York Times article and I think it's really relevant to consider and again going back to what I was saying earlier around the construction of a genetic underclass maybe given the populations that we're talking about who are likely to buy this test it's fine but these are bigger questions around there are people who get this kind of information and then you know aren't sure what to do with it and it's not just entirely a socio-economic question it has to do with age right someone my age is much more likely to be able to you know go and go on med line and read all kinds of articles about it as my mother is for example so I think that's something additional to consider Thank you