Dr Jack E Dixon, Vice President and Chief Scientific Officer, Howard Hughes Medical Institute
HHMI Vice President and Chief Scientific Officer, Dr Jack E Dixon, offers an illuminating insight into the valuable work undertaken at the institute that puts its emphasis on people, not projects, and has cemented its position at the forefront of global biomedical research
Could you summarise the mission of the Howard Hughes Medical Institute (HHMI)?
I think the Howard Hughes has long carried out basic biomedical research to help human kind. That has been our approach from the beginning. We have focused on people, as opposed to projects, and this has served us well. The freedom we have given our investigators to pursue important scientific problems has served us well and generated significant discoveries.
HHMI plays a powerful role in advancing biomedical research and science education in the U.S., spending $730 million on research and distributing $101 million in grant support for science education in 2009. What improvements and developments has this money enabled?
What we care about most is how scientific discoveries can influence human health for the better, even though it may take a long time for those discoveries to have a direct impact. Two recent Nobel Prizes, both in chemistry, illustrate this point. But there are literally dozens of examples.
Roger Tsien, an HHMI investigator at the University of California, San Diego, shared the 2008 chemistry prize for research that has enabled scientists to use a jellyfish protein to visualise proteins in action in the cell. This has yielded many important insights about biological processes, but Tsien and others are now trying to create a new generation of fluorescent proteins that could be used to guide surgeries or illuminate cancerous tumours.
More recently, Thomas Steitz, an HHMI investigator at Yale University, shared the prize in chemistry for his work in describing the structure of the ribosome, the molecular factory that manufactures proteins in the cell. This turns out to be incredibly important in designing a rational approach to the development of new classes of antibiotic drugs.
Why does appointing scientists as Hughes investigators, rather than awarding them research grants, ensure that HHMI is guided by the principle of ‘people, not projects’?
My response is twofold. The first reason is a pragmatic one. The HHMI is a medical research organisation and that means we must engage in the direct conduct of medical research with our own scientists. The second is more philosophical. We believe that long-term flexible support provides an important complement to other sources of funding. By giving individuals enormous freedom and flexibility – instead of insisting on a rigid set of aims, such as one might have in a research grant – we have been able to foster creative, groundbreaking research and enabled our investigators to move in new directions.
Could you explain the role of the Collaborative Innovation Awards and what benefits this four-year pilot programme has brought to selected Hughes investigators and scientists outside HHMI?
The Collaborative Innovation Awards represent an effort by the Hughes to tackle problems that are bigger than could be addressed by any one lab, bringing in additional talent into the pool of HHMI investigators to work on mutual problems of interest to the group. There are several interesting things in progress, for example in the area of epigenetics or the reactions that switch parts on the genome. A team led by Catherine Dulac at Harvard University has revealed how genetic contributions from a mother or father affect an offspring’s behaviour. Working with mice, they have identified more than 1,300 genes that are active in the brain that exhibit a significant bias as to which gene copy is active – the one inherited from the mother or the one inherited from the father. Before this, scientists had identified fewer than 100 genes in the mouse brain that had been imprinted. A more complete understanding of genomic imprinting may lead to findings with direct medical importance because several diseases, including multiple sclerosis, are linked to imprinted genes.
What international work is HHMI encouraging and do you hope to expand programmes like this in the future? What developments has your support facilitated in the field of HIV and tuberculosis, including pathogenesis, diagnostics, therapeutics, vaccines, and prevention?
There are three things that we are doing in the international arena. We are supporting foreign graduate students who are training in the U.S. We are also taking a new look at our international research scholars programme, and have decided to focus on scientists who are at an early stage in their careers in a focused group of countries. Lastly, and perhaps most significantly, we are collaborating with the University of KwaZulu-Natal in Durban, South Africa, in the development of the KwaZulu-Natal Research Institute for Tuberculosis and HIV to tackle these two diseases. In addition to building a research facility, we are using the skills of two investigators – Bruce Walker and William Jacobs – in developing the programme. William Bishai, an accomplished TB scientist who is currently on the faculty at Johns Hopkins University, has recently been recruited to lead the initiative.
In what way does the scientific project at the Janelia Farm Research Campus complement HHMI’s investigator programme? What specific interdisciplinary research is pursued in this facility?
Gerry Rubin, who oversees the activities of the Janelia Farm Research Campus, would tell you that the work is largely collaborative in nature, with research groups being kept small with the intent to encourage collaboration. It also has a very active visitors programme that includes HHMI investigators – as well as scientists from around the world – so we have created an extraordinary network. For example, we have just purchased a new cryo-electron microscope instrument that will be housed at Janelia Farm so that it can aid many of our structural biologists and shared among a wide array of scientists.
As for the scientific aims at Janelia Farm, I would describe it as one of the great experiments that we have undertaken focused on one of the great scientific challenges of the century – understanding the neural circuitry that enables complex behaviour. It is going to be particularly interesting to see how bringing together groups of people in widely-ranging fields to attack common scientific problems will bear fruit, to see what interesting new things are produced by the alignment of these individuals. I think Gerry Rubin has recruited a terrific set of people who are just launching their programmes in the early stages of their interdisciplinary activities.
How important is dissemination to the continuing development of international collaboration between scientists?
Our policy is to make publications, research tools, and information freely available to the greater scientific community. That is one of the cardinal paradigms by which we operate, because we believe it is essential for the health of the scientific community in the U.S. and beyond.
What criteria do you use to allocate funding? How challenging a task can this sometimes be?
Our criterion for funding is, in general, scientific excellence. Having said that, some areas of research are more expensive than others. Some investigators rely heavily on instrumentation and we have gone to great lengths to support them – for example, by developing beam lines to assist our x-ray crystallographers. Others work with yeast and that is relatively inexpensive when compared with mice or other higher organisms. So we evaluate excellence and the specific programme. Our flexible funding model allows us to fund new ideas that investigators have or new discoveries that they make in the course of their research activities.
In terms of your success to date, what would you highlight for special attention?
We feel that we have, as an organisation, been fortunate that many of our investigators have been recognised with honours that include the Nobel Prize, Lasker Award, and membership in the National Academy and in other learned societies. That is one measure of success. But there have been many major discoveries over the past several decades, and others whose importance has yet to be fully understood.
By what means is the HHMI grants programme fusing teaching and research, reflecting the Institute’s commitment to inspiring and educating a new generation of scientists?
We have, for many years, provided support to liberal arts colleges and research universities to enable development of programmes that give students a first-hand experience of research. But I would like to highlight one initiative that connects our programmes in scientific research and science education. We call it the Exceptional Research Opportunities Program or EXROP. It focuses on giving students who are disadvantaged or from groups underrepresented in the sciences access to the best research labs in the country. These are mentored experiences in HHMI labs and we work hard to maintain an ongoing connection with these talented students. The initiative is relatively small, but has had a powerful impact – the percentage of students who stick with science is high and we are just beginning to see the first group complete their PhD training.
HHMI funds initiatives to transform undergraduate and graduate education by engaging students in discovery research. What is the nature of these initiatives and how are they encouraging students to see science differently?
Speaking personally, I can tell you that I worked in a lab when I was an undergraduate and it was probably the single most important experience that contributed to my scientific development. It lets you get a realistic feeling of the complexities of science and the thrill that you get when you discover something new. That is what we endeavour to enable through many of our programmes, we work with outstanding institutions to give young people the opportunity to do cutting-edge science, whether it is the laboratory, in journal clubs, or in classrooms led by committed scientist-educators who fire their imagination.
If you had to outline one achievable target for the future of HHMI, what would that be?
I think that one of our major goals is to remain one of the premier funders of scientific research in the U.S. To achieve this goal, we are constantly evaluating our investigators and the advisors we use to review our investigators. We also seek to recruit and retain the very best scientists possible. In recent years, we changed the selection process to allow individuals to apply directly to become HHMI investigators and early career scientists. This eliminated institutional restrictions that may have made it difficult for some scientists to be considered by HHMI and helped broaden the pool of potential candidates.
Would you like to discuss any other area of the Howard Hughes Medical Institute?
One thing I would add is that we have been extremely fortunate to have extraordinary leadership over many, many years. This starts with our Trustees, medical and scientific review boards, as well as the people who work at the organisation.