Making an Impact

Aerial shot of the HHMI's Maryland headquarters. On a pristine 23-acre campus in Maryland located just a few miles from the National Institutes of Health, a handful of scientists decides how America's richest privately held biomedical research organization should distribute more than $500 million in funding annually. But the Howard Hughes Medical Institute, perhaps America's most prestigious patron of biomedical research, has undergone a changing of the guard at its Chevy Chase headquarters in t

Oct 30, 2000
Eugene Russo

Aerial shot of the HHMI's Maryland headquarters.
On a pristine 23-acre campus in Maryland located just a few miles from the National Institutes of Health, a handful of scientists decides how America's richest privately held biomedical research organization should distribute more than $500 million in funding annually. But the Howard Hughes Medical Institute, perhaps America's most prestigious patron of biomedical research, has undergone a changing of the guard at its Chevy Chase headquarters in the past year--and, as a result, a slight change in funding philosophy as well.

Last January, Nobel laureate Thomas Cech, an RNA researcher at the University of Colorado in Boulder and an HHMI investigator since 1988, became the new HHMI president, replacing Purnell Choppin. Gerry Rubin, an HHMI investigator and professor of genetics at the University of California, Berkeley, who led efforts to sequence the Drosophila genome, came on as vice president for biomedical research. And David Clayton, a senior scientific officer at the institute since 1996, took on a newly created "strategic planning" position as vice president for science development. Clayton and Rubin assumed the duties of Clayton's former position and those of W. Maxwell Cowan, former HHMI vice president and chief scientific officer.

Initially financed by the tens of millions of dollars provided by eccentric billionaire businessman Howard Hughes, HHMI gained the bulk of its endowment in 1985 when institute trustees sold Hughes Aircraft Co., that had been made part of the institute in 1953, to General Motors for $5 billion. As a result, the number of investigators has soared from 47 in 1957 to 350 today and the grants and education programs have expanded considerably. Additionally, seven years ago, the HHMI was able to move into a new multimillion dollar headquarters complete with residence halls for visiting scientists, conference rooms, a private dining area, pool table, bar, and tennis court.

Those now at the helm will have to steer HHMI through a landscape of biomedical research that has changed significantly since Choppin and Cowan joined the institute in the late 1980s. Bipartisan support in Congress continues to forge sizeable National Institutes of Health budget increases. Biotechnology and pharmaceutical companies are carving out ever-increasing translational research niches and attracting more and more top-notch investigators. In the face of such an evolution, Cech, Clayton, and Rubin must decide how the HHMI can make the biggest impact on the research enterprise. "We have a new motto," says Cech: "Steady progress in an established field is insufficient criterion for reappointment as a Hughes investigator."

Thomas Cech

Upping the Ante

Though HHMI has always claimed to be on the cutting edge, the aim now will be to fund research that's a bit riskier, a bit more unproven. Cech and his colleagues expect that by relieving researchers of the pressure and the time-consuming process of applying for grants, they'll provide the time and energy to perform the important research that moves a field forward--not the most practical projects or those that are the most likely lead to publications, but those that have a chance to be truly groundbreaking. And, says Clayton, a bigger NIH budget frees up HHMI for more forward-looking research.

"We can take our risk tolerance up one whole notch because we know that our investigators should be maintaining an NIH grant," he comments. "Anything that the NIH is doing well, we should let the NIH do well and we should do something else," says Rubin. "We have a much smaller bureaucracy, different constituency, and the ability to change directions much more easily." The HHMI prides itself on helping to establish a fledgling research field, then letting the NIH take over on a larger scale. It's something the institute did successfully in the late 1980s with structural biology.

The key, says Cech, is adhering to the HHMI's mantra: "fund people not projects." As a Medical Research Organization (MRO), the HHMI differs from not-for-profit foundations in a couple of significant ways. They are required annually to spend 3.5 percent rather than 5 percent of their assets, which come from investments in the stock market. And, perhaps more importantly, the 350 HHMI investigators currently working at academic institutions all over the country, though funded remotely, are actual HHMI employees with benefits and retirement plans--not grantees expected to work on a very specific project for a specific period of time. About 20 percent of HHMI's spending is, however, given as grants to support international research and science education for precollege students, undergraduates, and graduates.

Reviewed every five years, HHMI investigators are expected to do creative, innovative research, whether their area of focus changes or not. Investigators such as Patrick Brown, a professor of biochemistry and HHMI investigator at Stanford University, and Susumu Tonegawa, an HHMI investigator and director of the Massachusetts Institute of Technology's center for learning and memory, have drastically changed their research projects since joining the HHMI. Brown has moved from studies of retroviral integration to functional genomics and microarray technology. Tonegawa has gone from immunology research on antigen recognition, work for which he won the Nobel Prize in physiology or medicine in 1987, to studies of learning and memory in mice.1

The institute aims to not only fund new fields, but fields that may require nurturing and encouragement. HHMI's latest national investigator competition, completed last May, brought in 48 new investigators from 31 institutions, 12 of them specializing in computational biology. Although certainly not outside the norm--the field has become crucial to things like the annotation of the human genome and protein biochemistry--computational biology, says Rubin, is a field for which universities still have difficulty finding a place. Better resources and funding in the commercial sector have attracted many of the top people in the field. "In many universities, they're somewhat conflicted," Rubin explains. "The biologists aren't sure that these people are biologist enough, and the computer scientists don't think they're real computer scientists because they're too applied. They sort of fall between the cracks." HHMI hopes, says Rubin, to give "the key individuals in the field the kind of resources ... that would make the thought of going into industry less attractive."

Gerry Rubin

Good Patrons

Indeed, organizations such as HHMI ideally serve as the much-needed dutiful patrons of science. "Industry ... is really relying on the academic sector and the patrons, the nonprofits, to provide the trained people for the industrial jobs." comments Cech. "There's a synergy there." Of course, an increasing number of scientists have both industry and academic ties, something that HHMI monitors closely with its investigators. "Many of our host institutions have had a very laissez-faire attitude toward industrial involvement of their faculty," says Cech. "We have chosen to instead require that we look at every contract that is signed and every involvement with the for-profit world that our investigators have."

HHMI asks how many hours per year investigators spend on an industry-related activity, whether there's intellectual property flowing from their lab into a company, and how much stock they own. The institute also limits the amount of time investigators are allowed to consult for biotechnology or pharmaceutical companies, and doesn't allow scientists to both consult for, and collaborate scientifically with, the same company.

Cech, Clayton, and Rubin have spent much of their rookie years contemplating potential new directions for the institute. Aside from taking bigger chances with research projects, Cech also hopes to broaden the relationship of the education and investigator arms, though specifics have yet to be determined. "These two really strong arms have not talked to each other very often," says Cech. He plans to somehow make use of the investigator's ideas, passions, and skills to enhance the grants program while, at the same time, getting students to participate more in the laboratory setting. Cech notes how one investigator approached him, saying he was interested in fostering a better understanding of evolution in his local schools; another wanted to help update the country's antiquated medical school curriculum. The HHMI also plans to eliminate or realign its somewhat dated research categories: cell biology, genetics, immunology, neuroscience, and structural biology. According to Clayton, the titles have lost their meaning as science becomes increasingly interdisciplinary.

Yet Cech, Clayton, and Rubin emphasize that steering the institute in the right direction means operating with little bureaucracy, ensuring close contact and collaborations among investigators and finding areas of greatest potential impact. Institute headquarters holds seven field-specific meetings annually, though all HHMI investigators, regardless of their field, are encouraged to attend. Cech, Clayton, and Rubin have already planned to put a cap on the number of investigators at its current level to keep the numbers manageable, choosing to put any additional money elsewhere.

Buildings on the grounds at the HHMI headquarters.
HHMI leaders also want to fund the areas of greatest potential impact. Despite its large endowment, with roughly one-fortieth of the NIH's budget, the HHMI and other nonprofits must, of course, defer to the government for certain vital enterprises. In particular, Cech, Clayton, and Rubin all hope that much of the budget increase will go toward laboratory equipment and capital construction of medical schools and laboratories, which are in dire need of repair. Hughes currently spends a much higher percentage of its assets on mending the "bricks and mortar" of the scientific enterprise than does the NIH. "There's such a need to rebuild ... the laboratory infrastructure in this country if the [United States] is to stay number one," says Clayton. "It's in the best interest of our society and certainly our economy."

The HHMI, notes Cech, also cannot be the National Science Foundation when it comes to education programs, hoping to reach every community in the United States. Says Cech, "This is the exciting challenge for HHMI, to decide where we can do things that are maybe a little more experimental, a little bit more innovative, a little bit more groundbreaking on a more limited scope. And then find ways to spread the word if we're successful."S


Eugene Russo can be contacted at



1. E. Russo, "Same Labmates, Different Projects," The Scientist, 14[2]:16, Jan. 24, 2000.