A very narrow bridge: Translational research

by Joseph Madsen on September 21, 2010

“The whole entire world is a very narrow bridge….and the main thing is not to be ruled by fear.”
–Rebbe Nachman of Breslov, 18th century Ukranian Hasidic mystic

My lab studies hydrocephalus, probably the most commonly treated pediatric neurosurgical condition. Most people think hydrocephalus was solved 50 years ago with invention of the shunt. But the kids I see with brain water problems, and their parents, don’t think the challenge is over. They ask: Why do I keep having headaches? Why do I keep having operations? Hydrocephalus needs new thinking, new imaging, new drugs, new interest. Our patients want us to innovate, and come up with something better.

In an area like hydrocephalus, with only a handful of researchers trying to make the world better, clinical innovation comes up against a rate-limiting step – the high, scary, often shaky bridge between basic discovery and clinical breakthrough. We call this translational research. The really big advances may depend on the folks who can build the bridges between these two peaks, and then delight in living on them.

New drugs, devices, surgical procedures, and (probably most importantly) changes in how we think about a disease process, all need bridge builders and bridge crossers. As with translating from one language to another, translational research requires mastery of two or more vocabularies, two grammars and maybe two cultures to make a conversation possible. But the translational researcher does more: adding ideas, questions and new experiments and discoveries that may fall outside the range of traditional basic or clinical research.

In November of 2006, at a Surgery/Anesthesiology Grand Rounds, I gave a presentation on new ways to think about the physics of pressure and fluid flow in the brain as it relates to hydrocephalus. The late Dr. Judah Folkman was in the audience, and asked a question about a vessel-targeting molecule that he thought might play a role in hydrocephalus.

Dr. Folkman knew how to build bridges, and, judging from his trainees and protégés, he knew how to teach the art. Within weeks we were testing cerebrospinal fluid from patients, and at least the first test supported his conjecture about a new pharmacologic way to treat the condition. Following on his lead has made us think about the responses of the brain blood vessels to these molecules, and more recently, the frilly ciliated cells that line the brain-fluid spaces. I’m as certain as Dr. Folkman was that we will someday see a dramatically different treatment for kids with brain water problems—but we will only see the connection from the bridge.

We need to teach more young docs to live on the bridge, love the view, and not fear. But how do we teach this key skill? Is it even possible?

The two peaks at either end of the bridge are well defined. For a basic-science researcher, the path to the summit might be: Find a laboratory that excels in the techniques of unlocking deep and difficult secrets. Study the techniques with a master. Earn a PhD degree. Rise through a series of grant awards, over years, to run a lab yourself. Publish in Nature and Science.

Training in clinical research takes a different path: Develop a skill set in biostatistics and epidemiology. Find large patient populations to study. Develop strong hypotheses about natural history of disease, response to treatment, cost effectiveness, clinical effectiveness. If you have an MD degree, consider a Masters of Public Health or equivalent degree. Publish in JAMA and NEJM.

The summits of these educational peaks are individually spectacular, and the climb to either summit is difficult and rewarding. The same is true for translational research, except there’s no clearly defined path of travel, and no systematic training approach. It may be hard to find a mentor, research funding and a place to publish, and to get recognition.

Mapping the human genome was a monumental achievement — a seismic thrust of a new mountain peak into the sky. But bridges to the opposite peak have yet to be built, so we still read headlines like this from The New York Times: “A Decade Later, Genetic Map Yields Few New Cures.

Sometimes we can be nudged into action by an unexpected source. Almost two decades ago, when I was a young attending here, I explained slit ventricle syndrome, a kind of shunt problem, to the parents of a young patient, using the same physical explanation that most neurosurgeons still use. The problem was that the mother was an engineer, and the father a professor of physics. He gently replied to me: “You know, Doctor, what you just said does not make any physical sense.”

They were right—and our conventional understanding was wrong. Slowly we realized that our attempts to understand hydrocephalus and shunts required a deeper understanding of dynamic, changing, pulsatile phenomena.  Linking the physics, the biology, and clinical intuition has become a wonderful passion. For me, a high and narrow bridge is a great way to view things.

The last thing patients want is for us to stay off the bridge because the height and wind make it scary. In future posts, I would like to think about the bridges, the builders, and the people who like to live on bridges. We must learn and teach how not to fear.

13 comments

  • David Fleming

    On behalf of parents of children with hydrocephalus, thanks for being out on the bridge. Interesting about transitional research. It seems it warrants a new course of study. Maybe similar to an entrepreneurial MBA program where docs would learn to seek non-traditional paths to discovery.

    • Joseph Madsen

      I am happy you picked up on the point about the challenge of training people to do innovation. I think there really is a role for this, and there are in fact programs that supply MBA education to medical students (such as in combined MD-MBA programs, which I understand are in high demand), and programs to teach biomedical entrepreneurship (as in the BEP program at MIT). I’d leave it to people associated with these programs to comment on how well they get to the heart of teaching the skills for innovation. My own opinion is that certain skills for inventorship and innovation can be learned by practicing docs, among others, and that disseminating such information is a high yield way to move medicine forward.

  • David Fleming

    On behalf of parents of children with hydrocephalus, thanks for being out on the bridge.

    • Joseph Madsen

      I am happy you picked up on the point about the challenge of training people to do innovation. I think there really is a role for this, and there are in fact programs that supply MBA education to medical students (such as in combined MD-MBA programs, which I understand are in high demand), and programs to teach biomedical entrepreneurship (as in the BEP program at MIT). I'd leave it to people associated with these programs to comment on how well they get to the heart of teaching the skills for innovation. My own opinion is that certain skills for inventorship and innovation can be learned by practicing docs, among others, and that disseminating such information is a high yield way to move medicine forward.

  • Laurene

    It is the good news and the bad news that we all get traiend within “disciplines” and subject matter areas. But paradigm shift and changes in thinking seem to occur when we look at subjects and issues form “outside the box,” “from the bridge,” or whatever metaphor captures the concept of observing from a new perspective. What should we be asking from our educators? How do we encourage new researchers, scientists, medical professionals not to follow the money, but to follow their questions, passions, etc?

    • Joseph Madsen

      Thanks, Laurene. My experience is that the happiest professionals are the ones who are following their passions and answering questions which have been bothering them for a long time. Lucky students find mentors who teach them, by example, the value of passion for discovery and translation.

  • Laurene

    It is the good news and the bad news that we all get traiend within “disciplines” and subject matter areas. But paradigm shift and changes in thinking seem to occur when we look at subjects and issues form “outside the box,” “from the bridge,” or whatever metaphor captures the concept of observing from a new perspective. What should we be asking from our educators? How do we encourage new researchers, scientists, medical professionals not to follow the money, but to follow their questions, passions, etc?

    • Joseph Madsen

      Thanks, Laurene. My experience is that the happiest professionals are the ones who are following their passions and answering questions which have been bothering them for a long time. Lucky students find mentors who teach them, by example, the value of passion for discovery and translation.

  • Joseph Madsen

    @Dave–Thank you for picking up on the challenge of educating people to innovate. I'm hoping that by sharing stories of innovators and would-be innovators we can think of new models to encourage inventorship. There are medical/MBA combination programs….perhaps we will hear from folks involved in some of those programs?

  • Joseph Madsen

    @Laurene–I think oftentimes the happiest professionals are the ones who are following their passions and improving the world. The young researchers need to observe this, work out where their passions and aptitudes point, and learn some basic skills (perhaps by means suggested by David in the previous comment) to make it work.

    • Mish Madsen

      I think that's a great point.

  • Jeff Behrens

    I had the pleasure of spending a couple of years with the MIT/Harvard HST BEP program that Dr. Madsen mentions above, and now work in orphan drug development. I found the program invaluable in helping me develop a basic foundation not only in biomedical science, but perhaps more importantly in how translating science itself works (and sometimes doesn’t.) Part of what made my time in the program so valuable was spending time with medical and phd students working together in medical and business classes and learning to speak to each other, communicate in our different languages, and begin to appreciate our respective challenges. I also think there are a number of fascinating and important questions that are worthy of academic exploration as well in this area – why are some innovations “translated” while others are not? What are the characteristics of researchers and labs that are successful at getting their innovations funded? How can we incorporate these kinds of lessons into academic training to help increase translational “output”? etc…

  • Jeff Behrens

    I had the pleasure of spending a couple of years with the MIT/Harvard HST BEP program that Dr. Madsen mentions above, and now work in orphan drug development. I found the program invaluable in helping me develop a basic foundation not only in biomedical science, but perhaps more importantly in how translating science itself works (and sometimes doesn't.) Part of what made my time in the program so valuable was spending time with medical and phd students working together in medical and business classes and learning to speak to each other, communicate in our different languages, and begin to appreciate our respective challenges. I also think there are a number of fascinating and important questions that are worthy of academic exploration as well in this area – why are some innovations “translated” while others are not? What are the characteristics of researchers and labs that are successful at getting their innovations funded? How can we incorporate these kinds of lessons into academic training to help increase translational “output”? etc…

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