"Translational medicine will cause a cultural and logistic change
in the scientific community"

First of all I would like to thank doctor Kelner, for giving us this interview after giving the lecture of translational regenerative medicine in Vitoria. Among other interesting aspects in her curriculum she is now the managing editor of the new born Science Translational Medicine magazine, edited by the AAAS. For our readers could you tell us what is translational medicine?

That is something we thought a lot of about as we were planning this new journal. Translational medicine is research that uses basic science findings from genetics, from immunology, from engineering... takes that big science findings and translates then into treatment or diagnosis for addressing human diseases and thereby improve the life of mankind. That is a broad definition.

When I hear that I think that is more or less what we have always done when applying scientific research to clinical medicine. What is new about it?

I think it is a new area, is which at least some of our working physician scientist need and will to shift their focus a little bit. There has been a philosophy in the last several decades that if we pursue basic science discovery to driven research we will serendipitously discover things that will give us clues and treatments for human diseases. And of course that has been true, oncogenes were not discovered by a physician scientist, oncogenes were discovered by basic researchers. But that approach has a vast and enormous amount of work and is not clear that the technology has been as efficiently used as it could be to apply what we know to diseases. We have new tools now, we have the human genome project, we can do large proteomic studies, we can do enormous gene expression... so we have tools to ask questions that we have never ask before as well. So there has to be an integration of people that understand the biology of human disease and basic science research approaches to get the maximum benefit from intersection of these new tools and can cope problems.

So the necessity of this translational medicine arises, on one hand, from novel heuristic possibilities of basic science and, on the other hand, on the fact that the complexity of these methods does not make them easily applicable. Is there something else that I am missing?

Basic scientist can go trough their entire training, beginning with their training in the medical school and never really understand anything about human disease. So they may work on immunology but they may approach the immunological problems without references to whether that answer to that particular question is likely to help a human patient. For example, I went to hear a talk about a very interesting cell type, and actually these experiments have been done in humans. The postdoc had discovered what was wrong with this patient with immunological disease. And the talk was all about what the mutation was and how this affected the immunological cell type and it was a beautiful work, but at the end I asked the question: "so now we will be able to help this patient?" He said: "Oh, well not really". This is a kind of a silly story but I think is part of the culture. There are gifted physician scientists who move back and forward from one world to the other. They have seen so many patients with a particular disease that they really understand the phenotype and they know enough about the basic biology to think creatively about what must underline that phenotype and ask the right questions in order to understand the disease process.

I did my PhD in the medical school, department of biochemistry, and my boss thought very seriously and said that to became involved in medical problems was prostitution.

Is part of the culture. I think is less common now but…

Another factor I think that is pushing in my view translational medicine is what you mentioned in your lecture about the different social view of science between the scientist that do basic research now comparing with that in the 19th century.

The social contract that scientist has made is that we became public foundations with private funds that will finance our research. But we are not getting the public funds for curiosity driven research, we are getting the public funds in order to help to stick the people in whatever country that is funding the research. We are not in the situation as in England in the 19th century where there was a gentleman scientist that does not depend on external source and he could pursue science for science’s sake. But we do not have that country.

I have said in public more than once exactly the same words. I happen to meet Professor Leloir, Nobel Laureate, Argentinean who died in late 80s and all his research have been supported by his family. And he said to be a biochemist he had to be rich. It is a sort of the conditions. He is the man who found out the essential connections between the sugar nucleotides and their function in the biosynthesis of carbohydrates.

Coming back to translational medicine, is there a birth certificate, do we know when it was born?

That is a good question, I have a very washed and concentrated point of view and I would like to think that it really became a movement under Elias (Zerhouni) and the NIH. But I am not sure that is right, because I remember when an earlier NIH director, and I have forgotten her name, she started talking about that. We really need to make sure that we were addressing the needs of patients. She did not get very far but she was thinking that. And of course not everybody shares her view; it was very difficult politically for her to change the NIH.

Something that I find very interesting about what I have read about translational medicine is the idea of building a software community, something that goes beyond the traditional method of scientist writes paper, editor accepts paper and then other scientist read the paper. Can you tell us something about it?

Yes, that is very interesting because is something we started here when we were talking to people on the community. In fact we heard it first, believe it or not, from a medical librarian, and she said: "what the translational scientist need is a way to find each other, because they need to find the bioengineer who can help them solve the engineering problems. They need to get the geneticists talking to the clinicians to tell them what genes to look at”. So it is a problem of getting people together and that is one reason why we want our journal to be very interdisciplinary, so that people from different fields can talk to one another. In addition the AAAS is starting a new programme which is part of their website science career, called CTSciNet that is nearly for trainees in the translational science. And it is a social networking site, so it actively provides a mechanism by you can go and mine people who are really expert in whatever you are looking for.

Of course this network is very new?

Is even more new than the journal.

And the journal is about 3 or 4 weeks old.

But I think I should say that the NIH has also an effort in this regard. Is not specifically designed for translational medicine but it is designed for science, sort of a giga information band where scientist can register and indicate where they are interested and so they can find each other. It is possible that that may grow to something that can be useful to the scientific community as well.

How does the preventive medicine fit with translational medicine? Or how does prevention fit?

That is a very good question. We result with that when we were thinking about the general purpose. It is obviously part of the story. But that is something that for now we have decided to address in the non research pages of our journal, so long head commentaries and perspectives will go on our commentaries and perspective sections. And ultimately I would like to see preventives coming to the journal as well. Because I think should be an equal putting with innovation.

I was going to ask you about the challenges in translational medicine.

I guess I see it as two main changes. One is cultural, so that basic scientists are taught usually during their PhD training to think about the little problems, or to think about basic research. That is changing. And connections are not taught in their training. How do you value research? That is changing too and I hope is changing enough.

And another think the other issue is the logistics, how do they find each other. I think it should be easier now than it used to be. Now it does not matter if it is in Europe or in California, but the systems are in place and we are hoping to have this areas focusing on certain disease and then bring out this basic scientists to talk.

But some people believe still that in order to make two scientists interact they have to share the same coffee machine for a while.

That is the energy activation area?

Exactly (laughing)

Is it relatively easy to get money to do translational research or is it still considered to be an esoteric subject?

I am not an expert in this, and I just repeat what I heard from scientists. Is better than it used to be but still is difficult. I think the funding mechanism is different from Europe. In the United States although an NIH has funded 38 or 40 of this institutional CTSAs (Clinical Translational Science Awards) which are designed for translational medicine, they are in construction grants. So they are to build the infrastructure to be able to do clinical trials, the infrastructure to be able to store the data, the infrastructure to be able to do the cosseting necessary for contrast the training programs to make sure the conditions they have to make basic research...but then they have small budgets for pioneer studies. But you still have to get main research funding trough the extender R01, NIH funding grants. And those do not have clinicals funds. Those study sections are still oriented to do basic science. At least this is what I heard. I am sure there are exceptions. But I heard the steady section culture has not shifted and I presume it is in the process of shifting but I actually do not know what it is being done to make sure that happens.

I have written one question "when I grow old I want to be a translational doctor". What could or should he or she do? He should contact this famous impossible net? Do you foresee that this should permeate the whole medical education?

I think this is evolving into a separate kind of training. The reason I said that is because the standard way to address this problem, students that are both interested in basic science and clinical science, is to go to MD-PhD programmes. And MD-PhD programmes are plural, are very long and often they do not end up producing a high bright MD- PhD who wants to bridge the gap. They often produce either PhD or an MD who could not be valued with the tedium of research. And I do not what the presenters are at, but I know the data they are build that up. I think this movement is having specified degrees in translational science that maybe they are a little bit different from the master degrees. So I think that people who are truly interested in thinking about both projects will start to emerge from these training programs. I do not know about Europe.

I do not think there is a serious consideration about translational medicine as a specific academic subject. And of course any PhD or MD, the result is that you come with a double degree but you are either a PhD or a MD.

When I was going to graduate school the students who were in the MD-PhD programmes tends to be the smartest students, but usually they were in the MD-PhD programmes because they could not decide which one they want to do and they...

I should have mentioned this before, but we you first discuss the meaning of translational medicine with examples as cancer, perhaps cancer is an example of lack of success of the traditional approach. Because after all, less people die for cancer, that is true, but this is just because of early detection. What we really know about the real thing is very little.

Yes I think that is true and I spend yesterday the day with people in the AECC in Madrid and I talked to several people there about the problem. I think there are many people in the cancer field who wonder whether so much research effort should have been invested in mouse models they proved to not be predictive. And especially I know they actually are thinking about how can we make a better mouse model, which I think is progress. But when you start accepting papers from translational medicine, that is since April, the number of cancer studies submitted is enormous. It is almost like a positive feedback loop where other cancer biologist train another cancer biologist… and of course is such a terrible problem and NCA have a huge budget. And so I wonder if perhaps is overfunded. I am not an expert so, no one should put me on charge of that budget, but form my point of view it seems like there is an awful work and a lot of people who has very poor prognosis when they get cancer.

There are some names that became fashionable suddenly, for instance chemical biology or systems biology. Is translational medicine one of them?

That is a very good question because we are worried about that. We worried about that at the beginning. What does this name? And we tried lots of different ways to express the idea of what we wanted this tribune to be. And that came the closest to be an area to invite other people that we meet. And so that is why we went with that name, but I have heard people say: “is what we used to call preclinical research”.