Wednesday, November 12, 2014

Public Health Relevance Statements vs. Actual Translational Potential

“Research on the brain is surging,” declared the New York Times the other day:

Yet the growing body of data — maps, atlases and so-called connectomes that show linkages between cells and regions of the brain — represents a paradox of progress, with the advances also highlighting great gaps in understanding.

So many large and small questions remain unanswered. How is information encoded and transferred from cell to cell or from network to network of cells? Science found a genetic code but there is no brain-wide neural code; no electrical or chemical alphabet exists that can be recombined to say “red” or “fear” or “wink” or “run.” And no one knows whether information is encoded differently in various parts of the brain.

Yet we still understand so little, they say. And most people don't care.

The Public Find Brain Science Irrelevant and Anxiety-provoking, based on the outcome of a small qualitative study of 48 London residents (O'Connor & Joffe, 2014):

The Brain Is Something That Goes Wrong

Though the brain was ordinarily absent from participants’ mental landscapes, there was one route by which this habitual inattention could be ruptured. The second theme articulates the finding that for many, neurological pathology was the only aspect of brain research that held clear personal relevance. This foregrounding of pathology constituted the brain as a vulnerable, anxiety-provoking organ and anchored brain research in the domain of medicine.

So people may not care about the brain, unless something in theirs is broken. When they'll find it's important that doctors know how to fix it. And perhaps realize this knowledge comes from basic research.

This adds new meaning to the Public Health Relevance Statement required for NIH grant applications (see p. I-65 of this PDF):
For NIH and other PHS agencies applications, using no more than two or three sentences, describe the relevance of this research to public health. In this section, be succinct and use plain language that can be understood by a general, lay audience. If the application is funded, this public health relevance statement will be combined with the project summary (above) and will become public information.

Anyone can look up grants at NIH RePORTER and read the Public Health Relevance Statement for each. Not that most people will be doing this. But what might they find for a basic science grant that studies invertebrates? Say the central pattern generating circuits found in the crustacean stomatogastric ganglion, which controls the rhythmic muscle contractions that grind and move food through the gut? Here's one:
Public Health Relevance Statement: Mental illness may result from relatively minor imbalances in circuit parameters that nonetheless result in significantly disordered functions. To understand what kinds of circuit parameters when perturbed lead to mental illness, it is necessary to understand how different neuronal excitability and synaptic strengths are in normal healthy brains, and how individual neuronal processes compensate for each other.

I chose this example because the Principal Investigator, Dr. Eve Marder, has done such groundbreaking work on neuromodulation and circuit dynamics over the duration of her illustrious career. Last year she was awarded the $500,000 Gruber Neuroscience Prize for Pioneering Contributions to the Understanding of Neural Circuitry:
...Early in her career, Marder revealed that the STG was not "hard-wired" to produce a single pattern of output, but that it was a remarkably plastic circuitry that could change both its parameters and function in response to various neuromodulators while still maintaining its morphologic connectivity. This discovery marked a paradigm shift in how scientists viewed the architecture and function of neural circuits, including those in the human brain.
. . .

More recently, Marder's research has focused on how neural circuits maintain stability, or homeostasis, over long periods of time despite constantly reconfiguring themselves. This research has broad implications for the study of many neurological diseases linked to dysfunctional neural circuitry, such as schizophrenia, depression, epilepsy, post-traumatic stress disorder (PTSD), and chronic pain.

What if PIs were required to provide a detailed description of how their findings will actually lead to new treatments? It's one thing to say “our findings will have broad implications for the study of many neurological diseases” but quite another to explain exactly how this this will happen, even if you're studying humans (not to mention if you're studying a system of 30 neurons in the crab gut). The down side here is that the public might expect too much “Hey, why haven't you cured Alzheimer's yet? Haven't we, the taxpayers, given you billions of dollars?”

On the other hand, politicians are falling all over each other saying, “I'm not a scientist, but...” I'll go ahead and make ignorant policy decisions and second guess independent peer review of grants. So it's critical that neuroscientists can communicate the “broader implications” of their work and yes, how their research may eventually lead to improved treatments for brain diseases.

For that reason, I've been pondering the relative translational potential of neural engineering, pharmacological, and regenerative medicine approaches to neurological and psychiatric disorders... We'll see what (if anything) I can come up with, at least from a comparative perspective.

Cheesy Bench to Bedside Image Credit: UAMS

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At November 14, 2014 8:41 AM, Anonymous Anonymous said...

I actually think Dr. Marder did a nice job expressing the public health relevance of her grant.

At November 14, 2014 8:56 AM, Anonymous Kamran said...

In my opinion Dr. Marder did quite a nice job of summarizing the public health relevance of her proposal. Judging proposals by their "actual translational potential" is a dangerous path that could lead to the stagnation of scientific progress. Many modern tools of medicine (radiography, MRI, ultrasound, etc.) were not discovered because of their translational potential. I wouldn't put the onus entirely on scientists for a failure to communicate. Your acute observations illustrate the extent of the problem. You state perfectly that "The Brain Is Something That Goes Wrong." How many public citizens will actually be interested in reading the Public Health Relevance Statement, even if it's perfectly eloquent?

At November 14, 2014 2:21 PM, Blogger The Neurocritic said...

I do agree that her statement is well-written. One concern is that the requirement to oversell one's basic research -- whether with these Public Health Relevance Statements or with university press releases and other media communications -- sets up unrealistic expectations about the timeline of clinical advances. But then maybe my concern about the public caring about any of this is overblown. So then trying to explain the value of basic research to the public is a lost cause.

My other worry (and hopefully this is overblown too) is about political interference in the funding of basic research. Some notoriously anti-science politicians are in highly placed positions in the US. Lamar Smith, chair of the House Committee on Science, Space, and Technology, has been railing against "frivolous" social science research. And Senator Tom Coburn complained about funding for robosquirrel, calling it "an example of wasteful government spending."

And this: Republicans put 'national interest' requirement on US science agency:

Key members of the US House of Representatives are calling for the National Science Foundation (NSF) to justify every grant it awards as being in the “national interest”. The proposal, which is included in a draft bill from the Republican-led House Committee on Science, Space, and Technology that was obtained by Nature, would force the NSF to document how its basic-science grants benefit the country.
. . .
But the bill ... would place an extra burden on NSF programme directors by requiring them to publish justification for each grant award on the foundation’s website.

Here's my favorite part of that article:

Others say that predicting the broader impacts of basic research is tantamount to gazing into a crystal ball. John Bruer, president of the James S. McDonnell Foundation in St Louis, Missouri, and former co-chair of an NSF task force that examined broader impacts, thinks that the requirement should be eliminated. He says that scientists often make something up to fill that space on NSF grant applications because they cannot predict what will come of their work. “All scientists know it’s nonsense,” says Bruer.

Hopefully these ignoramuses won't turn their sight on basic neurobiological research in worms and crabs and deem it deficient in "actual translational potential."


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