Justice, Healthcare and the Trend Towards Predictive Medicine 22 & 23 November 2004 - Brussels Prof. Ruth Chadwick (Lancaster, United Kingdom) Professor of Bioethics University of Lancashire Director ESRC Center for the Economics and Social Aspects of Genomics Presentation Thank you very much and thank you for the invitation to speak here. I’m going to be talking about genes, drugs and food. It is last the last presentation of the day before we start to think about dinner, so it is appropriate to turn our thoughts to food, I think. Now, we’ve heard quite a bit of information today about the ways in which new technologies will have the potential to decrease or increase health inequalities. And I’m also going to be talking about that, but in a different sort of way. Because a number of factors are relevant to this, we’ve heard for example about psychological factors that are relevant, what I am going to be talking about is related to political will and not so much in explicit policies in this area, as to the underlying presuppositions and the inconsistencies in policies which can have an effect on whether or not, new technologies will increase or decrease health inequalities. And, I also want to look at the relationship between the individual and the collective with particular reference to how the notion of the individual choice is interpreted. We heard in the last presentation that in this area, in addition to thinking about the use of access and the sharing of benefits of new technologies, it’s also relevant to think about opportunity costs. What else could we be doing with the resources that might be directed towards new technologies? And I want to have an eye to that. And what I am going to be suggesting is that although in the policy documents I am going to be looking at from the UK, there is an explicit upholding of the individual choice. This goes along with, at least potentially, new forms of stratification. And there is a lack in consistency in the arguments applied, or how they are interpreted. I am going to be looking at the particular example area of nutrigenetics, obesity and functional foods. Now, in the UK in the last two years, we’ve had two White Papers coming out from the Department of Health. The first one in 2003 was concerned with the implementation of genetics in the health service. And this quotation is from that one, and it is portraying the future health as being in genetics. They say: “We will know more about the genetic features of common diseases, such as heart disease and diabetes and the way external factors, such as diet and smoking interact with our genes to increase the likelihood of developing a given disease”. And then they go on to say that, there will be the option to test people for their predispositions and risk factors and treatment, life-style advice and monitoring aimed at disease prevention could then be tailored appropriately to suit each individual. That’s great. Individualized medicine based and lifestyle advice based on our genetic profiles. In 2004, very recently, another White Paper was released from the same Department called “Using Health”, and this has a quite different strategy for public health. It sets out a strategy for action based on the principles of informed choice and personalized services, etc. And then it goes on to say: “choosing health identifies how people can be empowered to make healthy choices”. Now, what these healthy choices are concerned with is diet, as it is seen by the Department of Health, and avoidance of smoking. So, whereas in the previous White Paper that dealt with genetics, as somebody might have thought that in the future they get individualized advice about the risk factors in continuing to smoke, the recent White Paper is going to try to get them to give up smoking, whether or not they have particular risk factors or not. Another interesting aspect that has to be born in mind in the background, is the extent to which these policy documents have engaged with the public, or have a view about the extent to which public preferences should influence policy. In the 2003 White Paper there are issues of what has been called the deficit model of public understanding, which is that, the general problem is that, members of the public don’t understand enough about genetics and if they had the information, they would be able to make appropriate choices on the basis of that knowledge. The 2004 White Paper says that it has been shaped by public consultation, so that the individuals preferences have influenced the development of this policy document, but also they do still hang on to the view that information will empower people to make healthy choices. They do recognize however, that it is not a simple matter of giving people information and then they’ll make healthy choices, because of the real complexities of people’s lives. And so, there is a recognition that information has to be given in context. Justice, Healthcare and the Trend Towards Predictive Medicine 22 & 23 November 2004 - Brussels The key questions I want to address are how these two strategies relate, if at all. What’s the potential impact on health inequalities and what notions of personalized healthcare end choice are at stake? With reference to the last of those questions, the 2004 White Paper does say that it rejects a false dichotomy between a paternalistic nanny-State on the one hand and complete freedom on the other, because they say that such freedom, such an interpretation of freedom, can in fact amount to neglect. And a key example in the area is concerning food and diet, food is a good example to take because there are clearly different strategies that one can adopt in this area. Food and diet, nutrigenetics, food labeling in relation to conditions such as obesity and diabetes. What is nutrigenetics? Nutrigenetics, I understand, is the study of individual differences at the genetic level, which could include whole genes or single nucleotide polymorphisms, differences at a single base-pair level on the genome that influences our response to diet. So, for example, influencing the extent to which we get allergic in response to certain foods. And, nutrigenomics is the application of genomics in nutrition research, enabling associations to be made between specific nutrients and genetic factors. And this information will enable us, it is envisaged, to understand how nutrition influences metabolic pathways in the body, to understand how things go wrong in diet related diseases, and to understand how our individual genotypes influence our response to foods, which can also, in the light of this information, enable us to make food choices on the basis of our genotype when that information is available. We have to consider the context in thinking about these issues, and not only the fact that there has been such a lot of anxiety and discussion about public perceptions of genetics per se, but also in particular the food area has been especially sensitive at least in certain European countries such as the UK. And so, those contextual factors have to be born in mind, when thinking about the ethical paradigm of individualism and choice. So will nutrigenomics have significant public health benefits? First of all, I think it’s important to draw a contrast between nutrigenomics and pharmacogenomics, which is the other great promise of individualized medecine in the 2003 White Paper. Because, as with nutrigenomics, pharmacogenomics is promising individualized prescribing on the basis of genotype that will enable avoidance of adverse reactions to drugs and genetically informed prescribing that could inform not only whether you have drug A or drug B, but what dose of the particular drug you should take, and promises not only a greater safety, but on the longer term a greater efficacy, although there have been some concerns about patient stratification, in the light of this information. Now, I’m not going into pharmacogenomics in this talk in detail, but nutrigenomics has significant differences from pharmacogenomics because when we’re talking about foodstuffs as opposed to drugs we’re talking about compounds that have a lot of different effective ingredients. Drugs are much greater characterized products that act on particular target pathways in the body, whereas foodstuffs act on a number of different targets in the body, so that it is much more difficult to predict the effect particular foods will have. So, in that sense, the promises of nutrigenomics are much more difficult to establish, I think it is fair to say, than the promises of pharmacogenomics will be. But let’s suppose for the sake of argument that is possible to test people for their genetic information and predict the responses they’re likely to have to particular foodstuffs. Will such individual testing be a means of empowerement? Well genetic testing covers a number of different kinds of things and moving from predictive testing for single gene disorder, such as Huntigton’s disease through susceptibility testing for risk factors for common diseases such as heart disease and some cancers. Then we have pharmacogenetic, testing to predict your response to medicines. And nutrigenetic testing will be a form of susceptibility testing and so it’s not likely to be as clear cut as a single gene disorder test. Whether or not such tests are a form of empowerement or not depends on a number of factors as we’ve seen today, partly due to how people interpret them, partly due to the options available and partly due to whether people actually want such tests or not, because I was asked to address the question whether there was right not to know. And some people would claim that there is no comeback to that later on. Screening is different from testing. Testing applies to the testing of an individual either through referral from a practitioner or self-referral, or purchasing a test from some private company. While screening, refers to the ascertaining of the prevalence of genes in a population, or a population group, of genetic factors. And in order to introduce a screening program in the population there are certain criteria that should be addressed, first of all that it should be an important condition, that the test itself is acceptable and reliable, and that the risk of reaction on finding a positive result, in other words no point in implementing a screening program if you can’t do anything about it. Justice, Healthcare and the Trend Towards Predictive Medicine 22 & 23 November 2004 - Brussels Now, in the case of diet related diseases we do have some examples of population screening programs, and the PKU program for newborn is a good example of that. So, screening newborns for phenolkitanuria enables a decision to be made, a diagnosis to be made and if it’s positive, their diet can be adjusted accordingly. However, phenolkitanuria or PKU is a single gene disorder and, as I’ve already indicated, most information coming out of nutrigenetics will not be like that, it will be much more risk factors that have to be taken into account along with a number of other factors. So what sort of conditions might it be worth introducing population interventions for? In the case of diet related diseases, I suppose diabetes types I and II are the most well-known, but in recent debate, in the media at least, there seems to be an obsession with obesity. And people are speaking about obesity in terms of an epidemic. So suppose we can identify a genetic factor, call it A, that if people have it …… And we can establish this link. Would it be worth introducing a population screening program to see who has got the genetic factor A, so that they can then be offered a particular dietary advice? Is this sufficiently important, does it offer adequate scope for action? Well, what one has to consider is that, in thinking about these potential scopes for action, personal pills and personalized diets, this purported individualized promise actually requires action at the collective level, and this is one of the interesting things, that the more the individualized promises, the more the collective action is required, because before you can offer these individual tests or population screening programs, the association has to be made between the genetic factor and the response. And population research has to be done to establish those associations. Well, for a long time national dietary surveys have been carried out to establish links between dietary intake and physiological health, but those surveys take on a new twist with the addition of a genetic element to try and establish the link between the genetic factors of the individual and response to particular food stuffs. And these population surveys require setting up of large genetic databases. And these genetic databases have led to the phenomenon I described at the beginning, of a reconsideration of the relationship between the individual and the collective, and the document from the WHO has actually said that the justification for a database is more likely to be grounded in communal value and less on individual gain and leads to the question if the individual can remain of paramount importance in this context. And they go on to talk about the need to reconsider the respective claims of the balance between the individual and collective interests. So, ironically, the promises of individualized medicine and dietary advice depend on collective action to establish these factors. And, as we’ve seen, even once the factors, the associations, are established, there are question marks of the extent to which the information is empowering or not. So let’s look at the other strategy in the 2004 White Paper which is not going down the individualized genetic approach but takes the more environmental approach of trying to get people to make healthy choices without involving genetic testing. Apparently, there is no apparent link up between the two policy documents. Now this approach is still the same, we’ll test people to see what genetic predisposition they have got toward foodstuffs. It says people should make healthy choices, we are going to encourage people to make healthy eating choices, we’ll have clear labeling on food, so that people will make informed choices, there are going to be restrictions on advertising of junk food to children. And children are regarded as a special group. They say explicitly, that the underlying ethical principle driving this approach is informed choice, subject to two qualifications. One, as I just mentioned, that children are a special group who need protection and secondly that informed choice for the individual has to be balanced by responsibilities to others, and that becomes very important in their position on smoking. Well how is this alternative approach going to deal with health inequalities? Surely, it could be interpreted as an increase in the burden of responsibility to make particular choices. They say they’re promoting informed choice, but whose choice and for what? How are we to understand this choice? Because how informed choice is interpreted is crucially important. One could interpret taking an informed choice as a utility maximizer, when you take a choice you are trying to maximize your utility by choosing what you see as best promoting your own interests, and that might be to eat particular kinds of food according to how you see it. However, I think that the White Paper is operating with a notion of responsible choice, that choice should be made in a certain direction, and that if only people have got the information and clear labels than they will be helped to make those choices. However, there is another notion of making an informed choice which doesn’t come up at all, and I see that as Justice, Healthcare and the Trend Towards Predictive Medicine 22 & 23 November 2004 - Brussels being associated with choosing ones identity, the sort of life one wants to live, which could include not wanting to know genetic information. But in this context, it could mean choosing a particular lifestyle and food style. And that hasn’t seem to be allowed for in the policy context, because our food choices say something about how we regard ourselves and our bodies. And what sort of people we want to be. Vegetarianism is a clear example of this but there are other examples as well. And due to this melting pot, cooking pot, whatever, one has to also think about the advent of the designer food, the functional food, an allegace to the designer drugs. Functional foods are foods that have been designed to have specific health promoting or enhancing foods. Now the regulatory system improving these on the market in Europe allows them to be rejected on the grounds of safety, if the safety case hasn’t been made out, but doesn’t allow them to be rejected because there is no evidence there to say they might be effective. So whereas drugs have to prove safety and efficacy, functional foods only have to prove safety. And they are assessed on a case by case approach. Now it seems to me, and not only to me, that there is a serious problem here, in that functional foods are targeted at particular audiences, but they’re not like drugs prescribed through professionals, they are available in an open way in supermarkets. And, they can be bought by anyone who may not necessarily benefit from them. And because they are approved on a case by case basis, there is no mechanism for looking at the potential overdosing by eating lots of different rations of these products. I have in mind some things like the cholesterol lowering margarines and yoghurts. Now fine, but when the same ingredients are put in a lot of different kinds of functional foods, one has to look at the possibility of overdosing, because each product is assessed on the risk that that product alone will be eaten in too great quantities. This problem can’t be solved by labeling alone, although that’s the only mechanism there is at the moment. And it seems, here again, there is an inconsistency, because whereas in the White Paper 2004, the Department of Health has said we’ve got to be concerned about children and regard them as a special group, when it comes to functional foods, there is no drive to protect them as a special group. But it is thought that it can be solved by labeling information alone. Functional foods can be plus or minus nutrigenetics, functional foods themselves might be genetically modified foods, and they might be specially helpful for people who have particular nutrigenetic profiles. But in the context of where there is more discussion about sharing the benefits of genomics, although the skepticism about what counts as a benefit, one has to ask: what if anything is the added value that will be produced by nutrigenetics, over and above standard good dietary advice? Is there sufficient added-value worth the opportunity costs? And is there sufficient benefit to outweigh the potential burdens that go along with this technological route? And the point I want to finish with, which I think is one of my main points, is that we are seeing, despite this explicit reference to informed choice, we are seeing a return to class divisions. And this point was picked up by an article in the Financial Times on Saturday about the new White Paper in its position on smoking, and this article says ultimately: the world-wide regulatory push against smoking is being driven by a revolution not just in rights, but in class. A class system is slowly being re-erected on new basis, bringing with it a new and narrower understanding of rights. What they are saying there, is that the new White Paper, in trying to persuade people to give up smoking, is disproportionately targeted against the poor. My talk, in its concentration on food, could make exactly the same point, because it’s the dietary choices, the food styles, the food preferences of the less affluent groups that are being targeted in this strategy. And so, in looking at the extent to which these policy developments will enhance, or decrease health inequalities, one has to look at it in the context of how other strategies are being put in place, which actually are saying: certain food choices ought not to be made. And so it’s not the case, as the first White Paper suggested, that people will be enabled to make any choice they like on the base of accurate information about their own risks. And so, instead of thinking about bridging the genomics divide, it may be increased. But there certainly is a need of joined-up thinking, rather than these two strategies which apparently are going in different directions. Thank you.