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Q. [Regine Kollek]: We also have to consider the historical development in science itself. I don’t know whether you remember, when the Human Genome Project started, the major players in the field really put forward all sorts of messages. Like - once we have analyzed the genome, we will be able to cure cancer, and to understand this and that. Then, we had the editorials from Nature and Science that we would even be able to solve the major social problems, and so on and so on. This was really put forward massively to the public and the politicians in order to get funding for the project. What we have to deal with right now is some sort of aftermath of this kind of message. What do you think?

A. [Papassotiropoulos]: I partially agree. In a sense, there was a kind of hype, as is always the case with human beings. If there is a new methodology that seems very efficacious, of course, there will be a hype. But not everything these colleagues said was wrong. The information from the HGP really helped to identify the drugs, which are absolutely efficacious. Think about some of the cancer drugs that are related to human genetic information, antibodies, and so forth. So there is a certain face value in claiming this. However, the hopes you might initiate when saying such can sometimes be quite disproportionate. This is our role - to dampen the optimism a bit or to show now what we think is the right way to go. Keeping in mind that this is a changing landscape, in a year from now I might be giving a completely different talk: that the real value of human genetics is prognosticating... whatever. I don’t think that will be the case, but it is a changing landscape nevertheless.

Q. [Manuel Battegay]: Can you speculate a little bit about the delta, between the group results and the individual results? In the workshop this morning, we heard about epigenetics and activating and silencing genes. Will we be able to measure this on a large scale as well?

A. [Papassotiropoulos]: It really depends on the phenotype. I do think the addition of epigenetic information will be of tremendous importance in cancer, for some cancer phenotypes. There, you have the source or organ in your hands and you can really measure the tumor. It is a completely different story in neuroscience. Here, I don’t think epigenetics will always help, at least in some neuroscience-related phenotypes, e.g. depression and anxiety. The tissue is difficult to get. But there are some neuroscience-related phenotypes where this epigenetic approach might work, so I would not be only pessimistic.

Q. [René Spiegel]: Some 10 days ago, we had Dr. Kurzweil talk here in Basel about futuristic things. He projects things into a few years, 10 years, and 20 years, to tell us what he thinks what will happen. He believes he will live a thousand years because he is taking all these measures to prolong his own life. Now Andreas, you tell us that it is absolutely impossible to get down to the individual level with genome-wide association studies. But what drives you in this research, I am sure, is the hope that we get down to the individual level. Isn’t it just a matter of calculating power, to dissect this complexity of individuals, genes and interactions, to really get down to the individual level?

A. [Papassotiropoulos]: You are asking, in fact, what is the core of my message. What drives me is to know biology, to learn biology, this is number 1. Two, perhaps someday to identify mechanisms related to diseases of human cognition, and when it comes to the individual level, to prediction: As a scientist I don’t think we will be able to get predictive values, sensitivity and specificity, beyond 80% in any neuropsychiatry-related complex phenotype, whatever we do with human genetics, even if we scan the entire genome. Then comes the question, what do you need this 80% for? So, we need to talk about the consequences of this 80%. I hope to reach individual levels of prediction when it comes, for example, to questions of response to a certain medication. But to predict who will have good memory 30 years from now is ridiculous. You cannot predict this at an individual level with sufficiant accuracy; you would need sensitivity and specificity levels well above 90% to be able to truly predict this kind of phenotype, which is influenced by nongenetic factors such as the environment. We are just unable for most phenotypes, whatever we do, to pass over a certain limit of sensitivity and specificity.

Q. [Klaus Lindpaintner]: Could you speculate: one of the overall themes of this conference is how will patients and their families deal with this prognostic information? We know from studies in Huntington’s families that some individuals will do very well with it and some might not. This might influence the amount of information, or the ‘right to know’ or the ‘right to NOT know’. Can you speculate if there might be some sort of phenotype, biochemical or genetic, that can say who is more likely to deal with the information better?

A. [Papassotiropoulos]: Absolutely, there is already a phenotype, which predicts how people respond to this. It has to do with whether you are Greek or Swiss! The way to deal with this information is different in Greece versus Switzerland. This is a prognostic marker at the group level. But honestly, for these kinds of very personal information, I don’t think we will ever get down to the individual level. It is complex. This is the difference between group and individual.