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NHMRC

Professor Elias Zerhouni

Professor Elias Zerhouni is the Director, National Institutes of Health, United States of America. He has been leading a change of agenda for the NIH and has developed a roadmap for research. In this vodcast he speaks about the future directions of the NIH and opportunities for collaboration.

Professor Elias Zerhouni: Thank you, and I want to really thank you for hosting us and also being extremely transparent, open to criticism, critiques and also suggestions. We can give a lot of them because after we've gone we won't have to pay for any of it. So what I would like to do really is give you a historical perspective about where NIH was and what are the forces that are really dictating a transformation of how we think about the relationship between fundamental research, health and the wellbeing of our public in terms of health.

In 1797 the US Government created a navy hospital because of the public health issue that was presented by the navy—the seamen who came back with many diseases. This is the first example of the government in the United States trying to address a public health problem. Then the history that I have studied in terms of how this organisation evolved to become the US Medical Research Agency, with $29 billion, proves to me that there is a profound link between scientific advances and public health requirements and organisational structure.

So what happened in 1887 the government changed the mission of the predecessor of the NIH into what we call the National Hygiene Laboratory. Why? Infectious diseases were a real problem, a public health requirement, a public health imperative, and science had changed at that time because the germ theory of disease through Pasteur's work and Koch's work in Europe. And obviously an organisational change was needed. New methodologies were needed. New scientists needed to be trained with new skills. And what happened is the then director or the first director of the NIH went actually to Paris and stayed there to learn about bacteriology.

1930 comes about—we're not suffering as much from infectious diseases in the modern world. We're suffering from cancer and heart disease. And the American Chemical Society said, 'You know, science is advancing. We now understand that biochemistry is going to be key to understanding biological systems and therefore we need to change the way we think about fundamental research in health.' And the American Chemical Society then promoted the idea of a National Institute of Health based on science.

That triggered a 20-year expansion of the number of institutes, with the National Cancer Institute coming about, and in 1945 President Roosevelt said, 'You know, our understanding of the fundamental life processes require us to increase the national investment, because it will be impossible to change health and health care and have a healthy nation unless we understand the fundamental principles of biology.' And this is what led to the expansion of the National Institute of Health. Where are we now? $29 billion, 24 institutes, some focused on cardiac disease, some focused on cancer and stages of life like ageing. But the constant is this: Progress can only occur if you allowed fundamental research to advance in a balanced way with the utilisation of that fundamental research and translating it into real benefits and applying it to the health system.

So having a comprehensive view and a policy was the key to progress that was made. Sixty per cent of our budget is spent on basic research, 25 per cent on translation, 15 per cent on clinical research. Why? Because the private sector companies and the rest of the country spends money in an inverted pyramid, with only 15 per cent on basic research. But the key here is competition and freedom of inquiry. So we have a system whereby any scientist can propose a project and be reviewed and be funded for about four to five years and then renewed if appropriate. Eighty-five per cent of our budget goes to universities and research centres, and this is how we fund science. Ten per cent our budget is spent at the NIH on, for example, developing new vaccines, ensuring the safety of the blood supply, doing primal research in very advanced protocols, for example for cancer and so on. And 1 per cent of our budget is now spent on what I call strategic communications. You need to be able to communicate with multiple constituencies to be effective in health or health research or fundamental research. So our websites now are the most queried websites in the United States—2.5 million hits a day, over half of which are from the public. And we've sort of become the trusted source of information, and that really tells you that as an organisation you have to have a scope of mission that allows you to tie the components of this research together.

Having said that, let me talk to you for a few minutes about what I see as the challenges and opportunities of science. Clearly if you look at our health care systems, costs are going to go out of sight. They're going to grow higher and faster than GDP. Ageing of the population is going to drive this. A shift from acute to chronic diseases is already here. Seventy-five per cent of our expenditure is on chronic diseases, and growing. It's clear that the current models are not sustainable. And no-one has the perfect answer. So when you don't have an answer, you know that your knowledge is just not sufficient. You have to accelerate your acquisition of new facts, new knowledge, and implement that. But how do you do this in today's terms?

One of the things that Warwick was mentioning is what is the construct, what is the fundamental strategy that we need to follow as a society, as a world, in trying to promote better knowledge for better health. So we asked ourselves that question and what was really obvious was that again as science changes and public health imperatives change, you need to change your organisational structure to achieve those goals. So we looked at that, and what was very obvious was that we have underestimated as scientists the complexity of biology. When I was Dean for Research at Johns Hopkins Medical School, we had predicted there would be about 140,000 genes in the human genome and every one of those genes would be coding one or two proteins and each one of them had a function. This sort of linear model was disproved essentially by experience.

You can see, for example, that pharmaceutical companies have an enormously difficult time in developing new drugs that are innovative, and the reason is very simple: We do not understand the complex biological pathways that are interacting with each other. Fundamentally we've done very good research over the past 50 years to understand the components of biological systems—DNA and ribosomes—and how you translate proteins and so on. But what we do not know, what we do not understand—we understand the hardware—is the software, if you will, of how all these things are integrated. That is the frontier right now in science. We call that systems biology. Some people call it that way, others call it complex biology. And we need new scientists, we need an integration of the physical and biological sciences to be able to model and understand and experiment on these complex systems. That will come in parallel with unique opportunities and genomic sciences, understanding the variability across human populations and susceptibility to particular diseases. So that's a very important topic.

How do you enable science to tackle the degree of complexity of the problems that we're dealing with? You need new methodologies, you need nanotechnology, microfluidics, computing expertise. You need large databases, you need an enormous amount of infrastructure. And you need to enable the best and brightest scientists to explore completely different pathways to discovery. That means being very open and very welcoming of change, so when somebody comes up with an idea, the reaction in the culture should not be 'Why would you want to do this?', because the response should be 'Why not do it.' Because, frankly, I have to tell you, as the director of the NIH, I can assure you that we know less than 10 per cent of what we need to know to be effective in health care. We really have a lack of knowledge at the most fundamental level, which really also means that it is an enormous opportunity for those with vision and the willingness to break barriers—barriers between disciplines, barriers between organisations—and really explore what I call research themes of the future, self-assembly of people who wouldn't talk to each other normally needs to happen. And you can see, actually, breakthroughs that are due, essentially, to the fact that people who were in silos start to talk to each other and really make significant breakthroughs.

The leader, for example, at the Broad Institute of MIT and one of the best-funded scientists, is Eric Lander. Eric Lander has never touched a pipette in the laboratory that I know of. He is a mathematician. He worked at the Harvard Business School. He had a very advanced degree in mathematical models and systems, and he is now the unquestioned leader at the Broad Institute, at the genome institute, at MIT. It tells you that we do need a much greater integration across discipline, but we also need to rethink how we deliver translational and clinical sciences and how we train people for these fields, and these are the topics that my colleagues are going to talk to you about.

But the message that I think I want to share with you is this: There is no greater risk right now in science than to stop taking risks, and to keep doing what we've been doing for the past 50 years, thinking that that dogma will drive to success. We need to experiment with many more avenues of research. We need to free people and provide the freedom and the funding for people to explore new frontiers in a way that is not hampered by either culture or tradition. So that's our message.