NIH Director talks about the prospects for research in biomedicine

Francis Collins, a scientist known for leading the Human Genome Project, pinpoints areas for potential collaboration with Brazilian researchers. He presented a lecture at FAPESP headquarters.

By Karina Toledo

Agência FAPESP – “I see a lot of students in the audience, and if you came here to find out if there’s any future in medical research, my response is a resounding yes.”

With this sentence, Francis S. Collins, director of the U.S. National Institutes of Health (NIH), began his lecture, “Genomics, Advanced Technology, and the Future of Medicine," presented at FAPESP headquarters on May 22, 2014.

With a bachelor’s degree in chemistry from the University of Virginia and a doctorate in physical chemistry from Yale University, Collins became known between 1990 and 2003 for leading the Human Genome Project, the international effort that aimed to map all the nucleotides that make up the human genome.

From 2003 to 2005, as head of the National Human Genome Research Institute (NHGRI), Collins coordinated a series of other genomics research projects that helped identify the genetic bases of several diseases. In 2009, President Barack Obama nominated him as director of the NIH, the institution that represents the world’s greatest source of medical research funding.

During his lecture at FAPESP, Collins commented on the progress of some of the most ambitious projects the NIH is currently funding, such as the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative.

“The initiative was announced about a year ago by President Obama, and it is a bold mission to bring together experts from several disciplines that do not generally work together, such as electrophysiologists, imaging specialists, neuroscientists and neurologists. Determining how we can work together to understand how the brain works? It’s really a huge challenge,” Collins said.

Another noteworthy initiative is the National Center for Advancing Translational Sciences (NCATS), one of the 27 institutes that make up the NIH. Its mission is to accelerate the process of turning scientific discoveries into new treatments.

“Thanks to advances in the area of genomics, we now know the molecular bases for more than 5,000 diseases, but treatment has only been approved for 250 of them,” Collins commented.

Collins said that one of the ways to reduce costs and the time needed for the preclinical testing that ensures the safety of candidate drugs would be to test for toxicity in human cells “without placing humans at risk.”

“On the basis of significant advances in stem cell technology,” he explained, “it is now possible to attempt to develop a biochip. And once that happens, we can do a skin biopsy, turn fibroblasts into stem cells and then differentiate these cells into any type of tissue we think is important for testing toxicity, such as liver, lung, kidney, muscle or neurons. And then we could take these differentiated cells and print them in 3-D format to create structures that represent human organ systems in which the compounds could be tested.”

Among the promising areas of biomedical research, Collins noted the development of immunotherapies to fight cancer and a universal flu vaccine.

Collins also highlighted studies designed to address the growing problem of antimicrobial resistance to antibiotics. In this area, the NIH director announced the funding – in partnership with FAPESP – of a project aimed at studying Brazilian ants in order to identify antifungal agents that could potentially be used to make new medications. The study will be led by Monica Tallarico Pupo of the University of São Paulo (USP) and Jon Clardy of Harvard Medical School, It was approved under the first call for proposals issued jointly by FAPESP and the John E. Fogarty International Center (FIC), an agency associated with the NIH.

“We’re especially excited about how this project is being funded,” Collins said. “The NIH is funding its portion and FAPESP is funding its portion so there is no bureaucracy, which is always good. We would like to have more projects like these.”

In an interview granted to Agência FAPESP after his lecture, Collins talked about the prospects for future collaboration with Brazilian scientists and about the major advances in medicine that are expected to be made in the coming years.

Agência FAPESP – What expectations do you have for the future as a result of the partnership with Brazil and, more specifically, with FAPESP?
Francis Collins – 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 to be closely aligned with it 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 that will allow 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 this morning 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.

Agência 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?
Collins – 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 even 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] 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 at this point in time. 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. We see that Brazil is taking off in terms of science funding, and this is being translated into talent and ambitious ideas. I don’t know exactly how far this will go, but it’s exciting to be a part of the process.

Agência FAPESP – How important is international collaboration in terms of the current scenario of biomedical research?
Collins – It is critically important. If we really want to take advantage of the world’s best available talent to produce the most encouraging results, 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?

Agência FAPESP – What lessons learned in coordinating biomedical research in the US could be useful to Brazilians?
Collins – 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 the really innovative ideas. Ideas may sound eccentric, but eccentric science also has its place. There needs to be a separate category 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 Awards, the Transformative Research Awards 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 researcher to propose the idea. There needs to be a balance between the bottom-up and top-down approaches.

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

Agência FAPESP – What advances might we expect to see in medicine in the coming years?
Collins – 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 standard treatments. It is also offering avenues for the development of new drugs that are more effective than standard chemotherapy. The number of medications developed in recent years has increased rapidly based on these avenues. It’s really encouraging. If I have 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 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 really delve into it. Just imagine, with appropriate changes in diet and the use of probiotics, you could program 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. We could 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. It’s really tough. 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 test that shows the presence of amyloid plaques. The idea is to intervene early in an effort to avoid the process rather then 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.