“Oooooh, the Lord is good to me
And so I thank the Lord
For giving me the things I need
The sun and the rain and the apple seed
The Lord is good to me”

At summer camp we learned that Johnny Appleseed travelled around, randomly planting seeds throughout pioneer-era America, thus providing migrants with a source of food and a tasty treat in the rough wilderness. No one told us that apple trees don’t grow true from seed, and that the vast majority produce inedible fruit (don’t worry, this isn’t going to be a metaphor about postdocs from certain labs). What they do create, as we all learn later, is an easy raw ingredient for booze. And that’s why there are songs about John Chapman.

In modernity, we have lost virtually all of the apple diversity that once characterized North America. Not just the sour cider apples, but all of the freak discoveries of something unique, weird, delicious when roasted, keeps all winter, good for soup, good for pie, amazing off the tree but doesn’t last—anything that was interesting enough for people to take cuttings and graft it into their own apple garden. Apples selected for industrial-scale production are not chosen for taste alone, but also how they look in great heaps in supermarkets (uniform size and shape, smooth skin, no brown), how well they survive shipment by truck or ship, easiness of picking, yield per hectare. (I learned this from a guy at a farmer’s market and from Michael Pollan on the radio.)

This sucks. Some of the best apples I’ve ever tasted look like malformed potatoes. You can still find some of these local varietals at farmer’s markets in the eastern U.S., and they are maintained in isolated places or agricultural research facilities, but most never made it west, and the vast majority of apples are just not available to you and me.

>>>Segue alert<<<

Like John Chapman and apples, the relationship between NIH and “health” is not exactly straightforward, and not what most people think. The Johnny Appleseed version is that the NIH is working for the taxpayer to improve the health and quality of life of the good people of America. Yes and no. Let’s leave aside that if aggregate “health” were the actual goal, almost every dollar spent by the NIH would be better spent on prevention, education, regulation of industry, and alleviating poverty. So what is the NIH for?

With the apple story from summer camp, we went from “food to sustain the weary and brave pioneer” (I’m picturing Michal Landon) to “cider to get so drunk that you can briefly forget you live in a hole in the ground and will probably freeze/starve this winter.”  Here, we go from “improving health” to…what? A somewhat more realistic description of the goal of the NIH is not health per se, but the development of biomedical interventions. That’s important, too, and I think non-controversially beneficial.

But the people who have administered the NIH—and this includes the US Congress, believe it or not—have been much smarter and more strategic than this. At least since the post-war period, the NIH has put enormous emphasis on also funding research that has nothing to do with health at all. They have done this by defining the “health” as the the institutes’ ultimate goal. Most suitably-motivated scientists can think of ways their research may ultimately serve the public health interest. And this is not being sneaky, this is exactly why the NIH’s mission statement and goals are phrased this way. So when you feel tinges of guilt for reaching for health relevance that feels tenuous, relax: it’s a feature, not a bug.

Why do this? In part, it’s a recognition that biomedical advances largely depend on fundamental discoveries, and that fundamental discoveries are nearly impossible to engineer. You can’t go looking for them. If you want more of what you have, you cut and splice from existing apple trees—create clones (I am going to torture the crap out of this metaphor). But if you need truly new things, you have to just plant as many seeds as you can. Only once in a while will you get edible fruit, but many of the scientists are actually happiest with the cider. Win-win.

The other reason, of course, is that the NIH represents the transfer of public funds to local institutions across the country—mostly universities, some companies. This means jobs, development, prestige—stuff congress critters love to take credit for. Until relatively recently, even most Congressional Republicans recognized not only the value of basic research but the value of having federally funded basic research programs at the universities in their districts.

But times are tight. Grant success rates are at historic lows. The purchasing power of the typical NIH grant has declined steadily. Too many PhDs are being produced and there aren’t enough jobs. We don’t even know how many postdocs there are. But we know that a much, much smaller fraction will have the opportunities their mentors did to pursue a research career. All sorts of terrible incentives arise from these conditions.

The instinct in tight times is to prioritize. And my fear is that prioritization means NIH leadership making choices about what kind of proximate basic research goals to fund, despite decades of success doing essentially the opposite: funding the best scientific ideas of almost any kind (here is not the place to go into how the CSR often fails at this, but we can accept that this is at least its stated purpose).

The recent BRAIN Initiative report allays some of the worst fears about centralization of resources and top-down mandates of research priorities, but not all of them. We’ll see how it develops.  This is of course life or death for young PIs like myself, who, in the first years of our appointments, are absolutely dependent on the NIH for starting our programs and keeping our jobs. Whether we fit the particular programs or RFAs of BRAINI or not, how will any study section look on the relevance of young neuroscientists who don’t fit the BRAINI mold? Any policy shifts or mandates that narrowly define what the scope of neuroscience research will be could in effect exclude me from funding, and that is the end of my career.

But it’s not just self-interest. It would be a deep mistake for the NIH to try to pick winners in advance, or even narrow the pool. It is still hard for me to see the focus on “neurotechnologies” as anything other than an already massively successful and expanding field staking claim to essentially guaranteed funding at the expense of others. It is a positive feedback loop of resource concentration. The training pipeline and job market dynamics (everyone wants to hire someone fundable!) mean we will endlessly clone and transplant a few lab “types” and create a generation of people working on the same systems with the same technology. And then what? A supermarket with nothing but golden delicious*. As I keep repeating, conformity is the death of creative science, and how the funding system works determines whether conformists thrive or we have an intellectually diverse field.

You can’t pick apple seeds in advance, you have to plant as many as you can. Neuroscience in the Era of Strong Bullshit is already in danger from mono-cropping tendencies, group-think, bandwagons and concentrating resources around particular institutions, technologies, or experimental approaches. I think recording from a million mouse neurons at once sounds kind of cool…go fucking figure it out and publish the results of each step along the way. But I’ll be damned if I’ll agree a priori, “Yes! That must be done! Set aside $200M!”

That’s why this whole thing can feel like an end run around peer review. When you appeal to POTUS to somehow legitimize or put some federal stamp of inevitability and necessity on specific kinds of neuroscience, when you start to make totally unsupported and idiotic equivalencies between neuroscience and space exploration or high energy physics, it starts to sound like a boondoggle. Let’s be scientists, not shysters. Let’s fund neuroscience, but let’s not institutionalize our worst instincts.

*I hate golden delicious.

6 Comments on “Apples”

  1. Bill says:

    You had me at “drunk”.

  2. Comradde PhysioProffe says:

    Speaking of drunk, sounds like the blogger needs to drink more and ruminate about the field of neuroscience less.

  3. rxnm says:

    I do plenty of both, thanks.

  4. jimwoodgett says:

    There’s more diversity of thought on a soccer pitch of 6 year olds chasing the ball than found nin most applicants to such massive RFAs. While grand challenges and aspirational goals are fine, their execution tends to result in group-think conformity due to the necessary collusion and harmonization of the parts of the task. Such major efforts have a proportionately magnified risk of amplified error. When a scientific project becomes so predictable to consider extrapolation by orders of magnitude*, perhaps that should be the domain of machine simulation?

    * The best exception to this I can think of is the genome project where DNA sequence was the empirical unit of discovery that had to be experimentally determined to the last base (OK, 10 years on, to the last 100,000 bases).

  5. Drug Monkey says:

    “Delicious” varietals are not even really apples. I dunno what, but apples they are not. Nasty.

  6. DJMH says:

    “There’s more diversity of thought on a soccer pitch of 6 year olds chasing the ball”

    To be fair, that’s a *lot* of diversity.

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