In recent years, the conversation on medical advances has brought forth a striking observation: new medical treatments have emerged in low numbers despite simultaneous increases in research funding and published findings. Critics blame these stagnant numbers on a lack of translational research at the national level — Stanford, however, stands out as an exception to this trend.
The School of Medicine has spearheaded various programs with the objective of “translating” scientific discoveries into human trials and studies. The Interdisciplinary Translational Research Program (ITRP), for instance, links the basic sciences with clinical science to develop new diagnostic and therapeutic treatments. The program serves as a collaborative breeding ground for medical students, graduate students, postdoctoral fellows and clinical fellows.
“I think we’re a big exception,” said Irv Weissman, director of Stanford’s Institute of Stem Cell Biology and Regenerative Medicine.
“In all honesty, the University top to bottom wants this, to bring in people who are the translationalists who bring not only clinical excellence, but a history of doing and wanting to do clinical trials,” Weissman said.
Still, more could be done.
National Institutes of Health (NIH) appropriations have increased from approximately $3.569 billion in 1980 to nearly $30.860 billion in 2010. In 2010, the Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research approved 21 new molecular entities, down from 26 in 2009.
According to Philip Pizzo, dean of the School of Medicine, looking at dollar values alone can be misleading.
“It is certainly true that funding for biomedical research has been a major resource for the U.S. and has helped make this nation the leader in biosciences,” Pizzo wrote in an email to The Daily. “[But] it is also true that on average that funding has not kept pace with inflation over the last decade.”
“We are looking at bleak funding for research over the next years, below inflation, because of the national economy,” he said.
Medical school experts say that obstacles to translational research and new treatment development come in many other shapes and forms.
Pocketbook, priorities and Big Pharma
In general, scientists obtain funding for biomedical research by submitting grant proposals to the NIH and other agencies.
“NIH is our biggest funder,” said Kathleen Thompson, director of the medical school’s research management group. “They fund a little more than half of the research in the School of Medicine.”
As desirable as it is, federal funding comes with strings attached.
“What their focus is or what their budget is for each institute, and what areas of disease they’re most interested in are typically what’s driving whether or not we do research in certain areas,” Thompson said.
Neurobiology professor Ben Barres thinks that academia needs to look beyond federal agencies to finance translational research, especially given the current funding crisis.
“I would like to see much more collaboration between academia and industry,” Barres said.
“There’s some parts that we are very good at and there are other good parts industry is good at,” he added.
At Stanford, industry funding does exist, but it is small relative to other money sources.
“We do get industry sponsored projects,” Thompson said. “They’re typically in the form of clinical trials, but it’s only about 10 percent of our overall research funding that comes from clinical trials.”
Meanwhile, the medical school’s clinical trial volume has remained fairly flat over the past three years.
“We were almost in the exact same place that we were in the last two years,” Thompson said.
Even when industry isn’t the one paying the bills, the evolution from discovery to treatment still relies on pharmaceutical companies. Once medical findings are published, the idea is to get them picked up by the pharmaceutical industry. Translation to diagnostic and therapeutic applications usually hinges on this latter step.
But Big Pharma hasn’t always been game. Industry players are not too keen about financing research when they do not own the intellectual property rights.
Stanford scientists, for their part, have reservations about industry ties too.
“I think there is a lot of effort going on to try to improve relationships with industry sponsors,” Thompson said. “But there are also issues related to our academic freedom that sometimes becomes an issue with industry sponsors — the right to publish freely [for example]. Sometimes industry sponsors want you to keep certain information confidential and we just can’t do that, that’s not what our mission is.”
In the past, there has been a prevailing bias in favor of “pure” science, rather than research on medical applications and disease treatments. A decade ago, translational science — which often involves grunt work — did not necessarily help the ambitious young scientist who aimed to ascend the university hierarchy.
But at Stanford, a change has come. The Masters of Medicine (MOM) program, started by Barres, is a clear example of this change. Unique to the School of Medicine, the MOM program aims to provide doctoral students with training in clinical medicine to enhance translational research.
“We have this huge interest in our incoming Ph.D. students…20 percent applied to take this program,” Barres said.
He explained that the students accepted to the MOM program “learn about research” and “human biology and human disease.”
That’s not to say “pure” science isn’t important.
“I know from my own work and from being on the faculty here for about 40 years, that we don’t get translational science unless we have people doing pure science,” Weissman said. “Sometimes, like in stem cell research, the pure science discovery can lead rapidly to translation to medical trials and hopefully soon medical therapies.”
For now, the challenge is finding a way to provide interested students with the opportunity to participate in this innovative field.
“The big thing for us is to be able to fund people who want to be in that place in translation,” Weissman said. “So that means instead of the government cutting back on funding, for people who want to do a joint M.D. and Ph.D. degree, we ought to increase it.”
“I don’t know of many people, hardly anybody, who would say, ‘I do pure science and I don’t care about the medical implications,’” he added. “On the other hand…the drive toward translating discoveries is quite recent.”
“Getting the best and brightest people to work on disease is the battle,” Barres said.
On that front, Stanford has already made significant headway.
Ties to a broken healthcare system
Medical advances need to reach actual patients in order to make a difference. Weissman noted that the imperfect healthcare system is another impediment to the development and application of new treatments.
“What has held back the translation of advances in institutions like Stanford to treat the general populace, I would argue, is the lack of a comprehensive medical insurance for all people, rich and poor,” he said.
According to Weissman, the U.S. healthcare system is not national, even with the Obama plan.
“These findings when done at Stanford…wouldn’t budge the statistics, unless everybody adopted them,” he said. “That costs money, it costs the health care system. And in our particular health care system, if you’re uninsured, you don’t get these therapies, largely.”
Prognosis for the future
The future for translational research, especially at Stanford, still shines brightly.
“This is time when people moving into medical research careers will be able to do the most to change the outlook for curing and/or treating serious mainline diseases,” Weissman said.
Furthermore, the benefits of medical progress may simply need a little more time before they are fully felt.
“It is important to know that investments in research need to be considered long-term ones,” Pizzo said. “Discoveries take years and sometimes it’s more than a decade before they progress to a clinical outcome. So the assumption that recent investments will have immediate payoffs is unlikely.
“That said, there have been major advances over the years in clinical medicine because of research funding.”