Panel Discussion (2011) - Panel Discussion 'Biomedicine: The Future' (with Nobel Laureates Agre, Ciechanover, Evans and Murad)

HELMUT SIES. So maybe start this panel discussion. Welcome to our panel discussion now which is entitled bio-medicine, the future. We have approximately an hour for this, of course it’s a very large topic and to embrace the topic actually we should do it the other way around because the 570 young scientists here, they represent, you represent the bio-medicine of the future. And in the panel discussion here we have, you are fortunate to have 4 laureates to consent to discuss this topic. We have prepared it a little bit but before we go into this I would like to mention that this year we have a new experiment to reverse the ideas and that is this afternoon Professor Ciechanover will have a first of 2, what we call now master class where 3 young scientists from you will present their projects which lead into the future and then discuss with the laureate. And tomorrow Roger Tsien who will join us later today I think, will have another master class as an experiment. But now let’s go into our current discussion together with Hans Jörnvall let me just briefly welcome the participants. Sir Martin Evans has received the Nobel Prize in 2007 for just very briefly the work on transgenics and embryonal stem cells. That is of course for medicine and physiology. Then Professor Peter Agre as we have seen yesterday and today in his presentations has received the 2003 Nobel Prize in chemistry for the aquaporins that we heard this morning. And we are fortunate to welcome Professor Murad who just joined us very recently here, he received the Nobel Prize in physiology and medicine in 1998 for just in one word nitric oxide. And Professor Aaron Ciechanover Nobel Prize in chemistry in 2004 for the, also just one word, ubiquitin system. So we have, in order to prepare this, just by e-mail among us we have said send us one word and I will just read the one, Sir Martin had personalised medicine and stem cell research. Peter, translational medicine, hype versus reality. Ferid on preventive medicine, therapy personalised based and proteomic genomic studies of individuals. And Aaron on bioethical implications of personalised medicine. So you see we have focused the whole field of biomedicine on this. But Hans and I have now just looked at the questions that you young researchers have put out and it’s interesting that many of you have just focused on that. There are many other aspects but, so we are very happy about that. So we’ll use also some of the written questions of course but later on we hope to open up there are microphones there so that you can have questions then also too. But without further ado we would like to have just some brief statements off the laureates and we would like to start with Sir Martin. PROFESSOR MARTIN EVANS. Well as we’ve just heard this morning, dynamic and adaptive systems are somewhat difficult to predict and I think that would go for the future of medicine. However there are trends we can see and one very strong trend at the moment is the idea and it basically comes from ideas, the idea of cellular based therapies, sometimes called regenerative medicine. This is the idea that you can take a particular cell type, probably a stem cell type which would go to a particular tissue and use it for regenerating a tissue that needs repair. Now this is a wonderful idea, it’s being worked on very heavily but is not new. Not new at all. The reason why it’s come into prominence is because of the advent of human embryonic stem cells. These cells which have been, up until now, largely derived from human embryos but we can also take on board the fact that the induced pluripotent cells which can be made by specific treatment of adult cells will probably have most of the same properties. These cells can in culture, in the laboratory be persuaded or watched and selected as they develop into a wide plethora of different cell types. And so probably the sought after precursors for particular repairs may be possible to recover in the laboratory. And of course in large quantities. And that’s opened up the possibilities of stem cell or cellular regenerative medicine. Now I just said it’s not new and I want to give you an example to explain the system. You all have heard of skin transplantation, mainly used in burns victims but also in plastic surgery repair. Ideally a piece of skin is taken from another part of your own body, say from the thigh very often and used to patch the wound. And it can be used as a sheath so that’s almost like an organ transplant or it can be used cut up into small pieces so little pieces can be patched around and gives you the chance of covering a greater area. And it will grow dynamically in place. Interestingly you can also take those pieces, cut up pieces and disaggregate them into a suspension of cells and actually spray them on the burn or wound with the idea that actually the site where they’ve got to grow is the best site to grow them. But also and prior to that spraying on it was shown that you could take a small patch of skin, perhaps from a burns victim who had very little skin left and grow it up in culture to a large volume of cells in culture and then use that to do a transplantation by grafting. Now that really gives you the sort of whole range of transplantation treatment of this sort. And I say transplantation because of course that’s what we’re talking about. And I’ve also very carefully given you an example where you’re using the patients own cells from their own body. Now another well known example used world wide is bone marrow transplantation, another effective cellular transplantation. In that case it becomes much more obvious that there are big snags out there because you have to have a good match and if you don’t have a good match you have the most terrible graft versus host attack. And you have to, you basically would ideally like once again to use the patients own cells and that often is done with the purification of the cells from the bone marrow. So I think that although there’s been huge hype, great deal of work going on, on trying to have cells as a sort of pharmacology, a batch of cells that will repair such and such or will give you cells from the pancreas, eyelet cells, this sort of thing. This is going to be probably the first wave and it’s going to be a pretty poor wave, it’s going to be a transplantation, an allo-transplantation requiring an attempt at tissue matching and probably regular suppression of rejection. Much better, much better would be auto-transplantations and the techniques of trans-differentiation which I shall talk about a little bit tomorrow. Where it’s coming out that we can see and foresee that there will be possibilities of changing one cell type, specifically into another cell type. In culture, in the laboratory. Means that there will be a possibility of, and I go to your first P, the personalised medicine, in other words I think the future and possibly fairly distant future of the cell transplantation therapies, need to be personalised. And I think that raises all sorts of questions which we may discuss today about how that might be done, how it might be costed and how it might fit into the present models of medical care provision. HELMUT SIES. Thank you very much Sir Martin. And we go over to Peter. PROFESSOR PETER AGRE. I think I’ll talk later about some issues related to translational medicine but I’d just like to open on a few comments with the hype versus reality in terms of the new biology because we’re inundated with predictions and expectations which I hope we can realise, I’m not sure. Science has always proven to be unpredictable. The year I started medical school our first lecture by Albert Lehninger the topic was some introductory thing about chemistry and he said oh I have to give a different talk, it was reported one month previously, the discovery of reverse transcriptase, an enzyme that was going to change biology and it clearly did. And within a few years Werner Arber, Ham Smith who are here and their late colleague Dan Nathans discovered restriction enzymes. So the biology that I expected when I was your age or a little younger was much more primitive than the biology that emerged. So given that now we’re lead to believe that personalised medicine may advance our causes almost infinitely. Yet it’s quite clear there’s a limit. In all of the developed countries the longevity seems to plateau somewhere around the early 80’s or about age 80. So the needs of course are in the developing world. And those of us who live in the developed world still have problems, we hope they will be addressed through biology. I think funding research and cultivating the careers of young people is the best investment we can make to that. But what I fear is a lot of the decision making by our policy makers is not very much founded in reality and sometime that’s where the hype gets away from things. We have the genome, Francis Collins was a big part of that, Craig Venter the other part and many workers made this real, a real thing. But we’re still waiting for some major breakthroughs that are going to improve the lives of ourselves and those we know from that. So I think we still have to have a reality test, we still have to resort to common judgement that we’ve had for a long time. Frankly I saw patients in the clinic before the genome was deduced, part of the examination is the family history, tell me about your brothers, your sisters, your mother and your father and you learn a lot about the patient. When you have 2 generations of breast cancer in the family this predicts a lot without a genomic analysis. So I think we’re living at a time where fantastic new information may emerge. On the other hand it’s not going to probably change our lives immediately as much as predicted by some. Sorry to be the naysayer but someone had to take the role. HELMUT SIES. But the positive part is to keep the open mind and to be aware of changes and systems biology and optogenetics and all these wonderful areas. PROFESSOR FERID MURAD. Let me preface by what I’m going to say, that for many years now I’ve spent most of my time as a researcher, basic science... HELMUT SIES. Could you put on the microphone, I think the microphone is not working for you or can you understand Professor Ferid, it’s not working, could we maybe switch to Aaron until that is done. Actually Aaron also has some slides to show to sort of summarise our statements, would you like to do that now. PROFESSOR AARON CIECHANOVER. Just to take a few minutes to put the discussion a little bit in a frame, so as you heard already we are moving to what we call in the language of Leroy Hood, the 4 P’s medicine that is going to be personalised, it’s going to be personalised because it’s going to be profiled according to each and every one of the patients that is going to show up with a disease. But because we are going to profile and we may have the ability to profile patients before they get sick, it’s going also to be predictive, we shall be able to predict diseases, therefore it’s going to be also preventive because we shall be able, if we are able to predict we shall be able to point out the risks. And obviously it’s going to be also participatory because decisions are going to be made along with the patients. So the question is why at all we are driven into it. What is the drive behind, we need to understand what really are the forces behind. And the drive behind is that we are not that satisfied with current medicine and we are not that satisfied because let’s say that we have a group of patients that come to the clinic with apparently the same disease, let it be a woman with breast cancer or a man with prostate cancer or whatever. And we start to treat them with apparently the same treatment, let it be radiotherapy, chemotherapy, a combination, surgery. And we follow them for 5 years and then after 5 years we realise that they are divided unfortunately. Some of them are dying in suffering and some of them are alive, completely disease free. Which means that we made a mistake at the very beginning of the diagnoses. We thought they have the same disease but they do not have the same disease because the end result is vastly different. And we realise that we treated them in a very general way, rather than sectioning them according to a molecular profile. So we need now to really go and sectioning them and we are going to section them initially, only initially, it’s much more complex than that. According to the DNA profile but above the DNA you know there are other levels of regulation, there is the RNA and the RNA is also sub-divided. We now know that there are small RNA’s, micro RNA’s and then there are proteins and proteins are undergoing numerous post translational modifications from phosphorylation to amidation to ubiquitination to oxidation to literalation, to all of those and we are developing now techniques in order to really profile patients according to, from their genetic background all the way to the proteins. And last but not least just to wrap it up and as you heard already science is there to develop technology but technology once developed always have societal implications and they are all linked to one another and we need to think of it as one unit, we cannot detach it. And just to bring up a few problems or implications I would say, not problems, that we are facing. There are may bioethical issues involved here with availability of this vast amount of information, our own DNA, that embeds in it many very intimate secrets about our future. Then this medicine is certainly going to be very expensive so are we going to develop medicine for the rich or for all of us. And then there are drug companies and they have their own interest which are commercial interest. They avoid developing certain drugs like antibiotics and bacteria and viruses are coming back again and in a very difficult way. So are we going to rest our health and lives in the hands of these drug companies subject to commercial considerations or other agencies like our governments. That are responsible for our education and security, should take part also in this important game. So this is just to set the background. HELMUT SIES. Thank you very much Aaron. And if the acoustic problem is resolved, oh it is, that’s great. PROFESSOR FERID MURAD. Certainly the world is changing, medicine is changing very dramatically. I remember Peter when the first lecture I think I had in medical school, the professor said 50% of what I teach you will be correct, 50% will be wrong but I can’t tell you which 50% is correct. So I forced myself to learn everything. Health care costs are going through the roof. When I went through training, the United States was spending approximately 11% of its gross national product on health care, today it’s about 17% and it will continue to go up. In underdeveloped countries it can be as low as 1 or 2 or 3% and some of the Scandinavian countries it can be as much as 20 or more percent. So it’s variable. Why is it so expensive, I think there are several reasons that I want to point to in the United States. We’re a very litigious society, everybody sues everybody all the time. Physicians in practice spend about 50% of their total revenue operating their office, paying for staff, supplies and paying for mall practice insurance, 50%. I had a faculty member when I was chairman at Stanford who was a marvellous teacher in the community, he was a wonderful teacher. He volunteered one day a week, he’d work in one of the clinics, didn’t have to pay him at all, he enjoyed teaching. But then he got to the point where he wanted to go part-time. He wanted to retire partially but not totally. It turned out that with his mall practice insurance in the Bay Area he couldn’t afford to retire part time. He had to either retire totally or continue to work, he had no option because if he cut back 50% he couldn’t have paid his bills. Something is wrong. Because of this society of suing and covering your butt so you don’t get sued, the doctors are testing very excessively. They’re testing unnecessarily. And very often they’re expensive tests like CT scans and MRI’s and other things that may cost as much as a $1,000 or $2,000. And they’re often unnecessary. Patient comes in with a bad shoulder or joint, maybe a little tear in the capsule, maybe nothing at all, and they spend $1,000 to get an MRI to look at that joint, that’s not necessary. The other thing that’s happening in many countries, particularly in the US is that the emergency rooms are becoming the primary care centre. Somebody has a cold, somebody gets sick, instead of calling their primary care doctor, many of which they don’t have, they come to the emergency room. There is no way to get care in the emergency rooms in the hospitals in the United States for less than several hundred dollars. So we’re pushing up the costs as a defence mechanism and using the system inappropriately. We need to educate people and change that. How can we decrease the cost, I think we need to cap law suits. Some states have done that, in some states you can’t sue for more than $250,000. That permits the insurance companies hopefully to lower their cost to mall practice insurance to help the doctors. We need to educate the physicians to stop using tests unnecessarily, as a defence in their practice. Now the other way I think this is going to improve and this is what relates to some of the other speakers, is that personalised medicine I believe is going to have a big impact on the cost of health care and also the quality of health care. And how will that happen. Most diseases that we treat are syndromes caused by a variety of problems. Dementia, many causes, hypertension many causes, heart failure, many causes. So we’re treating these diseases with block buster drugs so the pharmaceutical industry can make multi billion dollar sales in these niches, in these diseases. But if you look at it carefully, maybe only 30 or 40% of the patients will respond. The Alzheimer’s drugs, only 30 or 40% get better with acetylcholinesterase inhibitors. And after 6 or 9 months they usually don’t respond at all. So we’re being sort of hoodwinked by industry for the sake of incoming profit. I spent time in industry, I left it to return to academics because I was concerned about some of the ethical issues of industry. But they’re there I think to really help people and to influence health care, they really want to do a good job. I think that personalised medicine, by looking at the genomic sequences, the proteomic sequences of patients will permit us to develop agents that are much more selective, much more efficacious, presumably less toxicity and maybe the cost will be about the same but they won’t be given to patients unnecessarily who aren’t going to respond. So I think we will have an impact on health care costs. HELMUT SIES. Thank you very much for this which considers the so-called rich countries, in the opening discussions on the podium there was also the other aspect of the so-called poorer countries. Where the $1 a day is what it is. And so there are the 2 ends. And maybe many of the questions that came in also addressed this problem between the richer countries and the very sophisticated personalised medicine, genomic analysis and then conclusions and therapeutic results from that. And on the other hand what is one going to do as we heard also last night with the millions on malaria, tuberculosis and so on. And that is a contrast we could address and maybe the best way to do that in this discussion, go to the questions. So thank you Ferid for this, because of time reason maybe Hans has kindly sorted these questions and maybe if you voice them. HANS JÖRNVALL. Many of the questions are very concrete and more short-term and several are essentially one word answers. So I put up 2, the first one is from Greg Allusian in USA and from Ching Tong in Shanghai China. One question is then which is the most important discovery during the next 10 years. And the more specific question which we haven’t mentioned thus far is the other one from Ching Tong, what about antibodies, we heard that all diseases have expression changes intrinsic or extrinsic and we heard about 35% of all cancers can be infectious background. Antibodies, will that be a future. What in 10 years, what antibodies. HELMUT SIES. Who would like to respond to that. PROFESSOR MARTIN EVANS. Well it’s often said that it took 25 to 30 years before monoclonal antibodies from the discovery to the clinic, to the widespread application. And of course they are now being widely applied, not only as antibodies in common form, you know antivirus something this but also things like Herceptin, specific, using the antibody, the protein engineering techniques to give you a high molecular rate, very specific drug. So yes, they are being used a lot. And of course I think the other side of antibodies, the antibody question is immunisation. And of course we heard Harald zur Hausen yesterday. HELMUT SIES. Aaron. PROFESSOR AARON CIECHANOVER. Yeah certainly antibodies can, am I heard, I’m not sure... HELMUT SIES. I think you are. PROFESSOR FERID MURAD. I would agree, that antibodies are going to be very beneficial, but they’ve got to be humanised, you can’t administer foreign proteins to people. PROFESSOR AARON CIECHANOVER. Yeah I’m heard, I’m being heard, I cannot hear myself. Yeah antibodies are already in the market and very successfully so. Take for example Herceptin for the EGF receptor. In the case of mutated EGF breast cancer, take for example Humira, the anti TNF alpha antibodies. So humanised antibodies are there and there will be more of them, if you heard recently for malignant melanoma (inaudible 28.03) new antibodies coming on. Obviously humanised antibodies we need to think so, if we think about the future we need to section it into small molecules and proteins, not only antibodies but proteins. And certainly also the antibodies are going to be personalised because we are going to profile the patients, in the case of breast cancer we want to know whether the patient is EGFR mutant positive or negative. And only the positive patient can get Herceptin and the negative one it will be a complete waste. So in that sense I think that antibodies are falling very nicely into the new development of personalised medicine. PROFESSOR MARTIN EVANS. But one problem is they’re very expensive, much more expensive than small molecule drugs. HELMUT SIES. Yes, so one can hope that with increased usage that price will come down and in retrospect hopefully in a few years it will just appear that what we are doing now, that this one size fits all therapy that will be then over and be more personalised and on a short term basis available. PROFESSOR FERID MURAD. Well having come from industry I can tell you that prices do not necessarily relate to volume, it relates to what the market will bear. HELMUT SIES. Could be wishful thinking, you are right, yes. PROFESSOR AARON CIECHANOVER. But I think that you know part of the price as Ferid just pointed out, is because of the law suits culture that we’ve all, mostly in the United States, but then infiltrated Europe and now going further. Take for example a drug like Vioxx, a very successful anti-inflammatory drug that went off the market because of a law suit, because of several myocardial infarctions, fantastic drug that helped millions and millions of people. So when the shares of the company went down and Merck really went into huge trouble. So I think that limitation of law suits and making medicine less defensive because the physicians are trying to protect themselves by covering the patients with lots of tests. So this changing culture will help to reduce prices because the prices charged are really unreasonable. HANS JÖRNVALL. Several questions also concerns cancer and several are a bit sceptical but we will reach it. So the first question is a general one, can cancer ever be cured, will we get a pill against every RNA antibody or something against every type of cancer and the second question is in new avenues, might aquaporins or telomerises or translational medicine be a way to find further cancer treatments. PROFESSOR PETER AGRE. Let me take that, at least the first swat. I think the notion that there’s going to be a simple answer to cancer is very unlikely. I mean does anybody really believe that, raise your hand, I don’t want to humiliate anyone but it’s a very complex group of disorders. But we already have a lot of information to prevent cancer. And that’s where I think policy makers can help. So in the United States during my adolescent time, surgeon general finally announced what was obvious to physicians for a long time, cigarette smoking is severely deleterious to health due to cancer and heart disease. And a fairly relentless campaign which was blocked by the tobacco companies, they fought this tooth and nail. But finally the education in the schools has reduced smoking in the United States from about 40% of adults to 20% of adults, still 20% is not acceptable. It’s not something we like but imagine how much benefit there has been. And the Mayor of New York city, Michael Bloomberg who is a benefactor of my university disclosure, initiated a policy in New York city really restricting cigarette smoking in the city of New York. Tremendous response from the restaurateurs, the tavern owners, this will ruin everything. But in fact their businesses have flourished and during his tenure of New York city 300,000 fewer smokers in New York city. So there are things that could be done without a miracle drug and the same thing goes for colon cancer, probably to some degree prostate cancer, melanoma, there are things we can do to protect ourselves right now HELMUT SIES. The lifetime aspect. PROFESSOR FERID MURAD. The market for tobacco use in the United States as fallen, mostly in the adults, it’s growing in the younger people and it’s growing in the foreign markets. HELMUT SIES. Yes, like Harald zur Hausen said yesterday, the lifestyle aspect and cancer is nutrition and other aspects of it, that means just education of the general public is also important point. PROFESSOR MARTIN EVANS. May I put in a comment here. I’m a trustee of a charity, Breakthrough Breast Cancer, which really supports research on breast cancer and also I’m afraid translation as well but the motto is ‘a future free from the fear of breast cancer’, very carefully crafted, we do not believe it’s going to be free from breast cancer, but we think there are lots of things which can be done to mitigate it from, you know a fearful lethal disease to a controllable disease. And I think that that’s true of many other cancers, that we are making advances on controllability and treatment, not necessarily on removal. HELMUT SIES. We’ll have 2 more questions here and then after that we’ll open up for the microphone. So whoever is planning to please be ready then. HANS JÖRNVALL. So the next 2 perhaps concerns specific infectious diseases like malaria and other big diseases, should we aim at getting a big lab, a centre against malaria, a centre against some of the other diseases, a global lab, that’s a question, it’s unmarked so I don’t know from which country. HELMUT SIES. And the other question is regarding the resistance, have we any hope of finding a specific means against resistance, other than finding additional drugs all the time. PROFESSOR PETER AGRE. Well I think on Thursday, Thomas Steitz is going to talk we’ve already heard Ada Yonath so the understanding of the structures of ribosome’s are giving us the opportunity to design new medications which we hope will be very effective. But based on past experiences if these medicines are abused, put in animal feeds and the like, their long term usefulness will decline. So again I guess I’m harping the same message here, intelligent use of medicines will be very important. The rapid spread of antibiotic resistance is astonishingly fast. In just one generation very potent medicines are now rendered almost useless and we have the emergence of killer organisms, metasonal resistant, staphylococcus aureus, a disease that was under control. So I think the public policy makers will have a lot to say with whether these new medicines are going to be useful and actually save the lives that they’re intended to. PROFESSOR FERID MURAD. I think Peter one of the things that’s happened and I’m sure you know is that doctors are not using the drugs properly, they’re treating too short periods of time, they’re not using multiple drugs. Like TB, TB was treated effectively some years ago and then we started using one drug at a time and that’s not the way to do it so we’ve got resistance now, it’s a really serious problem. PROFESSOR PETER AGRE. Ferid I don’t think that was the doctors, I think again that was a policy decision to save money by not having public health nurses observe the TB patients, taking their medicines. They stopped taking them. and the same thing is true of a lot of things, in malaria taking Quinine once you feel well, it’s a horrible medicine, you stop taking it. So I think there are things we can do to reinforce this I believe. HELMUT SIES. There is one aspect regarding cancer that was completely unexpected to me, when we talked this morning. Ferid, I asked you about nitric oxide, what's the next generation, of course we all know about Viagra and things but there is something that I really found very interesting, could you please elaborate on that. PROFESSOR FERID MURAD. I’m going to divulge all my secrets and create more competition with these young people. HELMUT SIES. Well as much as you like. PROFESSOR FERID MURAD. I typically work on multiple projects with a large laboratory, that’s the way I function. And almost all the projects are very high risk, going off in new directions which I find exciting and fun if you solve the problem. But sometimes we go up blind alleys and get lost and back off. Some years, when my interest with cyclic GMP started along time ago, probably almost 4 years ago, one of the things we looked at was cancer and I realised there might be a relationship between cyclic GMP and tumours. But we didn’t have the tools to pursue it properly, it was descriptive work, we hadn’t purified the enzyme, we didn’t have cDNA’s, we didn’t have antibodies’. So we dropped it but fortunately our smooth muscle work took off and that’s the way we went. But about 6 or 7 years ago we returned to cancer as well as stem cells thinking that there might be similarities in the systems, and there are. And we’ve been getting tissue from the neurosurgeons at MD Anderson, glioblastoma cancer which is a horrible cancer. The mortality is about 70% within 2 years, Ted Kennedy died with it, some of my friends have died with it. And we’ve learned from our work during the last few years in the laboratory that we can slow the growth, not kill it but slow the growth by elevating cyclic GMP levels in these tumours in a variety of ways. And we could take these human tumours and stereotactically put them back in the brains of nude mice, athymic mice, and look at their survival rates. And if we genetically treat the cells to make more cyclic G the survival increases 4 fold. So now I’m almost ready to go do a clinical trial somewhere in Asia, I suspect Taiwan. I’d love to get it done. HELMUT SIES. These are these unexpected things, like of course also with aquaporins and malaria, we heard this morning how that might work. So we are very interested in future aspects there. This might be a good moment to open up for questions from the floor. There are microphones, is there anyone who would like to ask a question, if not we have more ammunition here. Is there anyone who would like to, yes please. Could you say your name and your country, where you are from and then a brief question please. Question. Sonet from India and my research interests are HIV. And recently it has been worked out that since pathogens multiplicate exponentially you cannot rely on drugs and consider them on linear scale of reduction of infection or reduction of replication. And antibodies in terms of HIV, there is much more mutations and antibodies just do not work as well as drugs do. So in such cases how would the drug industry go about it and how would the doctors go about administering regimens. It’s a question I would guess especially for Dr. Peter Agre and Dr. Murad, thank you. PROFESSOR PETER AGRE. Antibodies are not something I’m an expert at. But I think we have to be a little careful, the question then turned to the drug companies and frankly that’s where the medicines come from. I mean it’s obvious, there’s a person in the United States named Patch Adams who goes around, he’s kind of light hearted and he suggests that we could make medicines in our basements. Well I wouldn’t want any loved one that I know to take insulin made in his basement. We’re stuck with this mechanism and frankly they respond to opportunities. Big pharma were small unknown companies in the past. In 1921 when insulin was discovered they could use it to treat hyperglycemia in dogs until an unknown pharmaceutical company named Ely Lilly in Indianapolis took it on and purified enough of it to use in patients. And among the first patients treated was a 14 year old girl within weeks of death who lived another 60 years. So the outcomes can be fantastic. In terms of the antibodies I just didn’t catch that part of the question, maybe somebody else up here did. PROFESSOR FERID MURAD. You’re right, I think what we do as scientists, often fundamental scientists is discover the molecular target, the pathway, the detailed biochemistry and then we learn how to manipulate that pathway or that target with various chemicals off the shelf or out of catalogues or collaborating with medicinal chemistry laboratories. A variety of ways it can be done. But to really move that drug into the market it requires an industry with all of the talent, to do toxicity, to do drug synthesis, to come up with pathways of synthesis at much cheaper costs, to get the cost of goods down. It’s a very complicated process, it’s not, I learned an awful lot doing it. Industry deserves what it earns, honestly for all the effort they put into it. I wish that some of the drugs were not quite so expensive however, but they’re entitled to it. HELMUT SIES. Shall we go to the next question please. Question. Hello, my name is Philip, I’m from the United States, my question is related to instances of, talk about public policy, particularly in terms of the food industry and nutrition, you all talked about how the bacterial resistance to antibiotics has been rising because of how patients have been treated but a big reason why we have bacterial resistance is because of the use of antibiotics in food for breeding livestock. Do you all think that it’s important for people in the medical industry and the scientific industry to play a larger role in public policy and to become more vocal in that arena so as to better drive the policy in directions that will help bring down disease rates like diabetes and bacterial resistance. PROFESSOR PETER AGRE. Yes, Philip you should run for office, I will vote for you. PROFESSOR MARTIN EVANS. There is one problem though, regulations are on a national and sometimes super-national basis but I’m afraid bacterial resistance and other disease problems are totally international and it’s difficult to regulate. PROFESSOR FERID MURAD. Yes, society pays the bills, they pay my salary, all our salaries, it comes from all the tax payers in your country. We have a right to keep them informed and we’ve got to tell them what we’re doing and we need a variety of people to deliver that message and to influence the legislatures to give us the resources to do more research to create more, to solve more problems. PROFESSOR MARTIN EVANS. But it is a mater of regulation isn’t it. PROFESSOR FERID MURAD. Oh you’ve got to work within the regulations, absolutely. PROFESSOR PETER AGRE. It works in some societies, you have very old purity laws here in Germany and the public would not accept unregulated additions to the food sciences, so it’s not like this is unacceptable to the population, it’s an education issue. PROFESSOR FERID MURAD. As you know dealing with embryonic stem cells has been an issue now for some years in the US, finally it’s come around and I think it’s opened up a little bit. But for a while in Texas at least the legislatures were trying to pass a bill to put me in jail for working on embryonic stem cells. Fortunately it didn’t pass. HELMUT SIES. The United States has over 50 states, 52 states, Europe has 28 next year and that is quite a difference, so in the legislation of this kind of activity. And even in nutritional regulations and so on and in other parts of the world there is a big challenge there. Shall we go to the next question here, it’s nice that we have a handful of more questions but make it short please. Question. Good afternoon, I am Doctor (inaudible 45.16) from Pakistan. So my concern is that, thank you for mentioning that there should not be medicine for the rich only but for all. So I believe with respect to the first slide, in addition to the 4 P’s if you are able to add a C for cost effectiveness, then I believe that countries like Pakistan would be able to make use of advancements in biomedicine and become part of a brighter future. That’s the only comment I have so I hope you will all make efforts for that, thank you very much. HELMUT SIES. Very well taken comment, is there any further comment to that. In addition to that C there is another one, that Sir Martin mentioned previously, that is risk benefit, that is also a very important further addition to the 4 P’s as well. PROFESSOR MARTIN EVANS. Absolutely yes and some of that risk is not just risk of toxicity to an individual patient but the sort of thing we’ve been hearing about like antibiotic resistance spread across the whole population of the world. There are big population risks as well as local risks. HELMUT SIES. Please. Question. Hello, my name is Gillian from China, the IPS cells or we can say the induced pluripotent cells’ emergence as new cell type for personalised medicine but there are some concerns about its use such as introduction of foreign genes and oncogenesis and I have a question for Professor Evans, what's your opinion about the advantage of IPS cells and what's the future of IPS cells in regenerative medicine in your eyes, thanks a lot. PROFESSOR MARTIN EVANS. The question is what's the future for IPS cells, well of course we don’t know but I think that it’s very likely that IPS cells with all the caveats and published problems at the moment, whether they are exactly equivalent to ES cells, I think that functionally they are equivalent. So what we have there is the ability from an individual biopsy, from an individual patient to create a pluripotential cell line. I’m not talking yet about whether it’s practicable in terms of expense and time but it’s certainly feasible scientifically at the moment. And that means that if we have methodologies and I say if at the moment, if we have methodologies from going from a pluripotential culture to particular stem or precursor cultures that will treat a particular tissue, then that could be totally personalised. Now that is a huge advance in my opinion on a one size fits all mega block drug policy for cells which I don’t think works and I think it does bring in problems that you suggested of inappropriate treatments and cross infection. However the advantage of a single source is it can be very carefully checked for infection. The advantage of a personalised source is that probably the infection doesn’t matter at all because if it’s there it’s already there and it’s a risk of 1 patient, not a risk of 10,000. HELMUT SIES. Ok the next one over here. Question. Hello, good morning, my name is Tiago Rodrigues, I’m Portuguese and I’m working in Cambridge UK. I would like to know your opinion about, in my opinion a taboo, mainly in the area of so-called first world, the psychiatric diseases, how are they important and how this personalised medicine can be applied to them and how can the decision makers and the policy makers face this question that is so important, mainly here in Europe and in the United States, thank you. PROFESSOR PETER AGRE. I would like to reiterate the importance of this question because I think the cost to society of the diseases of addiction, smoking, drinking, overeating, other compulsive behaviours are probably half of the health care budget. I mean type 2 diabetes is now an epidemic in the United States because of these things and I’m not sure policy makers are going to be so effective, they can do some things. But this is probably, if I were to answer the question, in the next decade where will the big discoveries, this could be I think an area of huge need, may not be easy. But these are very costly in terms of the needs of society, particularly in the developed countries. And as the underdeveloped countries get wealthier they have the same problems. HELMUT SIES. In order to do justice to those that have written the questions we would like to return back to some of those. HANS JÖRNVALL. Many of the question remaining concern economy and those who have and have not. And the first one is then on personalised medicine, several are afraid that it will increase rather than decrease health imbalance of the world. That is of course a general concern but that is one question related to economy. The other is whether the biggest problem perhaps is food, water and energy shortage and what prevents us, will we need to make drastic laws like the countries who have food give it to those who do not have and those who have food eat too much and those who do not have sufficient eat too little. PROFESSOR FERID MURAD. Let me try to answer part of it, Peter is probably better for this. But the mortality in the United States increased dramatically with the development of antibiotics. You know the average life expectancy in the late 1800’s was probably 35 to 40 years. Now it’s about 70 plus. And most of that is attributable to antibiotics. Now we’re making progress in other areas as well. But if you look at the poor countries, the third world countries, whenever they have a natural disaster, whether it’s a flood, a hurricane, an earth quake or whatever, they are in serious trouble because the infrastructure is borderline. The water gets contaminated, the sewage is all over the place and they all end up with all sorts of diarrheal diseases. And more than a couple of million people per year die because of that, mostly children and elderly people. Now I think if we were to invest in those infrastructures and train them in how to purify their water and safeguard the pipelines or whatever, we could eliminate an awful lot of that. And that’s not medicine and pharmacology, that’s just common sense I think. PROFESSOR PETER AGRE. I agree entirely, Ferid, and I think Bill Gates earlier this week touched on this. The world wealthiest or second wealthiest man is putting a lot of resources into making pure water available, it is a huge issue. And I just talked very briefly this morning, arsenic toxicity is sort of hypothetical in the developed world, but in Bangladesh and eastern India, it’s endemic. WHO calculates 140 million individuals in that part of the world are drinking arsenic toxic water every day with an epidemic of hepato-cellular carcinoma. So it’s a huge issue, diarrheal diseases also. PROFESSOR FERID MURAD. With the Haiti hurricane I believe more than 120,000 or 130,000 people died from cholera. I’m surprised that there’s not a lot of mortality in Japan right now, I was expecting it to take off. But I don’t think it has, I haven’t heard that it has. PROFESSOR MARTIN EVANS. I suspect that’s because Japan is a better organised society at a higher level to start with. PROFESSOR FERID MURAD. Exactly, they probably have better infrastructure. PROFESSOR MARTIN EVANS. Yes and the greatest improvement in public health in Britain was the Victorian introduction of a sewage system. PROFESSOR FERID MURAD. And in many countries they dump it right out in the lakes. PROFESSOR MARTIN EVANS. That’s right, so it could be spread around a bit. HANS JÖRNVALL. And then perhaps some questions personally to each, some many researchers. When they come from country that do not have all resources and they now see all resources, when they go home what should they do in their country. And the second thing also personalized, if you submit a paper to a journal to get it more evenly something, should we evaluate it, should we have doubled-lined refereeing system or not. PROFESSOR PETER AGRE. I think the statement was when the person from a developing country returns to his country, first off I think that return is a very important issue, because many don’t return, the opportunities are not as rich and yet having worked with young people. Like Sandor who is here at this meeting is an example of getting trained in state-of-the-art western medicine with the ambition of returning to the home country is something very admirable and we should reward that and emphasise that. As far as resources, sharing has never been easy for humans, HELMUT SIES. Of course some countries are better off than others in doing this like China has now the big program to have people come back into China after the training somewhere else and some countries can afford that now and that’s very good. HANS JÖRNVALL. And no word on the double blind referee. PROFESSOR MARTIN EVANS. They’re blind already, that’s the trouble with them. PROFESSOR PETER AGRE. I think the problem with referees is always reviewer B, he’s the one that gets you, I’d like to meet that guy. Hans Jornvall. I think this covers largely the questions we have received HELMUT SIES. Very good, we had more questions but there is also something in basic chemistry one learns in the process there is initiation, there is propagation, there is also termination and I think we are about at a time that we have to find a proper process to terminate our discussion. Is there any final statement that any of the panel would like to make. PROFESSOR FERID MURAD. Another very serious discussion with the physicians and those who want to be physicians is when do you give up and stop treating an elderly patient who is burning all the resources. You know most of the resources, probably 80 or 90% go to the last decade of life and we’re treating patients I think inappropriately sometimes, prolonging life another 6 or 12 months at huge costs and demands to the system. And you know we’re all doctors, we were told to keep life, people alive. But we’ve got to think differently perhaps. HANS JÖRNVALL. There was in fact a question on this and there was a question whether we should have a max cost per person. HELMUT SIES. I think some of that will be addressed on the Isle of Mainau on Friday morning on the podium discussion, especially with the demographic and the ageing process by experts on that field. Aaron you had a comment. PROFESSOR AARON CIECHANOVER. The problem is we always as I said, we are facing societal problems, take for example a drug that is called Avastin, that is used in the terminal stages of colorectal carcinoma, that elongates life by a few weeks, the cost is 10’s and 10’s of thousands of dollars, so this pertains also to the question that Ferid just raised. But on the other hand as physicians we are facing families and who are we to determine what are 3 weeks in the life of somebody. So there are no clear answers to all this huge problems and maybe we do need to decide where are the big slices of money that are going to so-called wasteful places and try to save on them. But we should always remember that medicine at the end of the day is a profession that deals with human life. PROFESSOR MARTIN EVANS. I think Aaron is quite right but there is another aspect to that and that’s the one which is I think lurking in the background of this discussion and that is that the relationship that you’re talking about of the physician with his patient is a one-to-one relationship and you’re talking about an individual. However what we really want is health for the population and the best health for all the individuals in the population and that’s where we run into problems with rich and poor. Or we run into problems with societal needs against private individual needs and it’s a very difficult situation but I think it’s one which needs to be thought out. And I think it needs to be at least considered when for instance particular treatments are being approved. PROFESSOR PETER AGRE. I think the end of life issues are ready for an entire discussion in themselves. It is true that those last weeks are where the dollars flow. The problem is having run intensive care units, are these the last weeks or can we get this loved one to Christmas or to graduation and there’s always a human side and it’s difficult, it’s very difficult. PROFESSOR FERID MURAD. I’ve been involved in treating a couple of family members with cancer, they’ve come to me for advice as to where to go, I don’t treat them but I advise them where to go for their treatment and who to go to. And we’ve been reasonably aggressive with a couple and the reason I was aggressive is because they had a company, a private family company and I thought if I could extend their lives 6 or 9 months that I could make a huge difference in their planning, their estate planning, their families, their businesses. So there are times when you do this and other times you have to ask yourself is it worth doing or appropriate to do, it’s not an easy decision, very difficult. HELMUT SIES. I think most of the comments made, this dichotomy or maybe imaginary dichotomy between basic research and applied science or translation medicine was underlying and both have their place and I would, if I would have to make a concluding remark on this I would say there is room for both and especially that we are open and not only be directed as agencies or so but also do not direct ourselves too specifically, be open to adapt. Maybe we have heard 2 wonderful lectures just before this panel discussion, be adaptive even if it is lock and key but there should always be room for change and for adaptation and for evolution of thought and hopefully also results. Maybe with this I would like to thank the panellists and the audience, I’m sorry we could not accommodate all written question and all potentially all oral questions but thanks for your input from the audience as well. End.

Panel Discussion (2011)

Panel Discussion "Biomedicine: The Future" (with Nobel Laureates Agre, Ciechanover, Evans and Murad)

Panel Discussion (2011)

Panel Discussion "Biomedicine: The Future" (with Nobel Laureates Agre, Ciechanover, Evans and Murad)

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