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Francis Collins

Francis Sellers Collins: Now we’re going to learn about the brain

Léo RamosOne of the current jobs of Francis Collins, director of the National Institutes of Health (NIH), is managing the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative, announced by President Barack Obama in April 2013. The project involves neuroscientists, neurobiologists, and imaging specialists – that is, “researchers from a range of disciplines who don’t usually work together,” as Collins enthusiastically put it when describing the initiative during his lecture at FAPESP on May 22, 2014. Difficulties aside, he knows that learning how the brain works presents an irresistible challenge. He also believes that any scientist would want to take part in this ambitious biological research project.

From 1990 through 2003, Collins was one of the leaders of the Human Genome Project. The following two years, as head of the National Human Genome Research Institute (NHGRI), he coordinated a series of projects that helped identify the genetic bases of several diseases. In 2009, in recognition of his scientific expertise and communication and leadership skills, President Obama appointed him director of NIH, the key center for biomedical research in the United States, comprising 27 specialized research centers and institutes and boasting an annual budget of $30 billion. During his lecture, Collins announced the sole project that was selected through a joint call for proposals by the University of São Paulo (USP) and Harvard, the former under the coordination of Monica Tallarico Pupo and the latter under Jon Clardy. Collins, who said he would like to receive more proposals from Brazilian scientists, offered these words as way of advice: “Don’t be afraid to fail. If you’re not failing, it’s because you’re not taking enough chances. Collins granted the following interview to the journal Pesquisa FAPESP and the FAPESP News Agency.

Medical genetics
University of Virginia (BS in chemistry), Yale University (PhD in physical chemistry), University of North Carolina (MD)
National Institutes of Health (NIH)
Scientific production:
512 articles registered on PubMed

The BRAIN initiative will release its final report in June 2014. What are its main findings?
In general terms, I can say it’s a ten-year plan. We want to discover the cell types that form the brain and figure out how they are connected and how they function. I’m sure there will be lots of discussion about the document. We want to hold ourselves accountable and determine whether we’re succeeding or not. I don’t want this to be a project where everybody goes off in a corner and does their own thing. We’ve got to have real goals and be able to show what we’re achieving. The report has multiple components and timetables and a lot of technology. What we need right now is to develop tools to measure the actions of a million neurons at a time, in real time. Nobody has even come close to that yet.

What kind of problems have you run into? Just those involving software? Isn’t it hard to bring scientists from different fields together?
We do need to get the experts around the same table, which we basically did for the Genome Project in 1988-89. Back then, one of the questions was whether people who build instruments and who understand engineering would be able to dialogue with biologists. We got it to work. And now we have the same need to bring together people from this and other disciplines. The difference is that the BRAIN initiative is much more ambitious than the Genome Project and it’s much harder to say when it’ll finally be done.

How do you bring scientists from different specialties together? How do you motivate them? How do you foster dialogue?
What primarily motivates scientists is the opportunity to be involved in a really exciting adventure that’s going to be historic. People will be willing to set other concerns aside and learn the language of other disciplines if they think they’re going to be able to take part in a project like this. It’s going to take strong leadership. There will be times when people don’t get along and they’ll have to be reminded why it all matters. This is all familiar territory because of the Genome Project. I’m confident that it can be done. And it’s so compelling. What scientist who’s alive right now would not want to be a significant part of the most ambitious biological project we’ve ever imagined: the effort to understand the most complicated structure in the universe.

In your lecture, you said Brazil is the NIH’s most important partner in South America. What expectations do you have as a result of this partnership with Brazil and, more specifically, with FAPESP?
Brazil is growing very quickly and lots of resources are being invested in research and in training large numbers of young scientists. I can’t predict where Brazilian science will be in five years, but I want to be sure that we are closely aligned to take advantage of the opportunities that present themselves. I was very happy to announce the joint effort with FAPESP in launching a really good synergistic project that involves a researcher from Harvard University and a researcher from USP. Each of them has the appropriate skills for this incredible project, which may bring a real payoff in the discovery of new drugs. I’m not sure that we could have even imagined such a thing 10 or 15 years ago. One of the reasons why I’m so happy to be here is that it gives me the opportunity to talk to FAPESP leadership about ways to develop ongoing opportunities for this type of joint proposal in which one researcher is funded by NIH and the other by FAPESP.

What do you think about the projects that are being presented under this joint call for proposals? Are you satisfied with the projects that have been submitted?
Yes, but there could be many more of them. We need to promote this and increase awareness about these opportunities. We need to make it clearer that we’re very interested in major projects. Much of what we have traditionally done in partnership with Brazil has been related to infectious diseases, like dengue fever, for example. Yesterday [May 21, 2014], I was at Butantan Institute to see what is being done on our collaboration with that institute. One of the objectives is to come up with a really effective vaccine for dengue fever, something that is desperately needed because the disease is becoming increasingly common. There are a number of opportunities in what’s known as neglected tropical diseases, which I’m happy to say are actually less neglected now. We have a long tradition of working with our Brazilian colleagues with regard to Chagas disease, and there is certainly more that can be done. There is also leishmaniasis, which is becoming more common than Chagas disease. There are also opportunities in HIV-AIDS, with the growing potential for developing a truly effective vaccine. A collaborative effort is beginning to take shape in this area. In every place I visited in Brazil this week, I found a lot of enthusiasm in the area of neuroscience. It would be great if we could figure out a way to do more in this area. There are also cancer and rare tumors that seem to be occurring more frequently in some parts of the world. I do not think there should be a narrow focus, but rather a wide range of opportunities. Some areas, like vaccines, are stronger than others. Then there are some areas that have been developing very quickly.

How important is international collaboration in terms of the current scenario of biomedical research?
It is critically important. If we really want to take advantage of the world’s best available talent to produce the most exciting outcomes, we can’t be limited to country borders. No one country has all the talent. And scientists are good about understanding this, and they work very well together. Another reason is the resources. When faced with a really difficult problem, no country can solve it on its own. Why not join forces and share the costs?

What lessons learned in coordinating biomedical research in the US could be useful to Brazilians?
I think that one of our advantages is having a stringent peer review system, because without it, we would never be able to fund all the research proposals we receive. Having projects reviewed by other experts in the field really helps us decide how to invest the funds. We also need to make choices and define priorities. But we’re learning that this shouldn’t be conducted in a way that squelches real out-of-the-box ideas that may sound a little ‘whacky’, because whacky science is important too. There needs to be a separate portfolio for highly innovative ideas so that they don’t have to compete against well-described projects that will clearly be successful. Otherwise, the latter will always have priority. We have program categories designed for innovators, such as the New Innovator Award, the Transformative Research Award, and the Pioneer Award. In terms of other lessons learned, it’s really necessary for most research to be organized from the bottom up; in other words, it should come from the researchers’ ideas. It’s not good to control this process too much. But there are times when things come up and a single researcher is not able to handle it. In that case, there needs to be leadership, and the scientific community needs to think about how it should be handled. There would be no such thing as a BRAIN initiative if we waited for a single researcher to propose the idea. There needs to be a balance between the bottom-up and top-down approaches.

And always take chances?
Yes, and not be afraid to fail. If you’re not failing, it’s because you’re not taking enough chances.

What medical breakthroughs might we expect to see in the coming years?
Cancer research is advancing quickly, partly because of our ability to identify what is causing malignancy at the individual level. And this is allowing us to increasingly personalize care instead of using a one-size-fits-all approach. It is also offering insights for the development of new drugs that are more effective than standard chemotherapy. The number of cancer medications developed in recent years has increased rapidly based on these insights. If I got cancer today, for example, I would want the tumor to be sequenced in order to see exactly how many DNA mutations it has, and I’d want to look at this new list of cancer-fighting drugs that target specific mechanisms and determine which one will work in my case. Another very encouraging field has to do with microbiomes. This involves studies about the microorganisms that live inside us, and the role they play in diseases. We’re beginning to understand that they are major actors in diseases such as diabetes, obesity and even autism. It’s a unique opportunity not only to understand this relationship but also to interfere in it. Just imagine, with appropriate changes in diet and the use of probiotics, you could reset this microbiome to help rather than hurt the body. This is a huge opportunity, and genomics has made it possible. We understand microbiomes because they have DNA and we can figure out what is there through gene sequencing. Another field I would love to see advance in the coming years and find a way to clinical application is stem cells and cell therapy – use cells taken from an individual and modified into the types of cells needed to treat the liver or kidneys or sickle cell anemia, a disease that very much concerns Brazil. Could we cure this disease by taking a biopsy of a carrier’s skin, turning it into stem cells, and using this very intelligent capacity to edit the genome called CRISPRs [clustered regularly interspaced short palindromic repeats] – in other words, repair the mutation and take these cells, differentiate them into blood cells, and then return them to the patient? I believe we should invest heavily in this area. I see no reason why it wouldn’t work, and the same approach could be taken with many other diseases. Alzheimer’s, for example – I would love to see progress on Alzheimer’s disease in the next five years. We are making significant investments in this area and focusing on people who are not yet experiencing the symptoms of the disease but who know they are susceptible [to the condition] based on their genetic risk or because of a scan that shows the presence of amyloid plaques. The idea is to intervene early in an effort to avoid the process rather than wait for the disease to take hold, when many neurons have already been lost. We need to do something about Alzheimer’s or this disease will become an economic burden on every country because of the aging population. All these areas have potential, but as far as knowing which is more important, I don’t have a crystal ball.