Category: science

NIH Funding Patterns, Part 2

As a follow-up to my last post concerning NIH funding, I though I’d do a deeper dive into the funding landscape over the last decade or so.  In the last entry, I found that the total amount of money disbursed by the NIH fluctuated dramatically, reaching an apex just after the recession and regressing since.  Over that time, a more pernicious change also occurred, namely an increase in funding inequality at the level of individual grants, as measured by the Gini coefficient.

Grants are the basic unit of the NIH bureaucracy, but they are not the only level of concern.  Another interesting question bears on the individual investigators who receive those grants.  Is funding at the investigator level becoming more uneven?

PI_Gini_over_Time

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NIH Funding is Increasingly Uneven

The Glory of the NIH

When you stop and think about it, the mere fact that the United States government aggressively funds research is a little crazy.  The innovation of government-funded research is new, at least on the scale of world history.  That American taxpayers, many of them hardworking folks with little cash to spare, are willing to fork over a few dollars a year for the purpose of science is not only strange, it’s wonderful.  It speaks to the cooperative spirit that is at the core of government: if we all give a little, our combined charity can move mountains.

And make no mistake, the taxpayer-funded engine of research that is the National Institutes of Health has moved mountains.  A wonderful study came out in 2013 which showed that as funding priorities changed and new institutes of study were created, the disease(s) to which each institute was devoted to curing showed reduced mortality and morbidity.  As an example, as research into heart disease increased (via the creation of the National Heart, Lung, and Blood Institute) the death rate plummeted.  The reduction in mortality and the increase in healthy lifespan pays dividends for the country, not only at an emotional level (delaying the loss of loved ones) but also economically, by increasing the amount of time each worker can contribute their work to society.

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Maxwell’s Demon and Genetic Assimilation

Definitions

Organisms of the same genotype raised in different environmental conditions will sometimes develop different phenotypes, a phenomenon with numerous examples called plasticity.  One of my most recent favorites are caterpillars raised in different seasons who adopt different camouflage patterns, either twigs or flowers to match the environment, in a diet-dependent manner.  Plasticity is important for adaptation, as you might imagine, because it determines the extent of variation available to an organism without genetic change.

Sometimes, an organism will adopt a plastic phenotype when entering a new environment.  If that new environment is invariant, it becomes beneficial for the organism to always express the plastic phenotype.  Over time, so the theory goes, the organism will lose the ability to switch between phenotypes (the plasticity), and only express the phenotype adapted to the newly invariant environment.  This process is called genetic assimilation, and is hotly debated as a pattern of evolutionary change.

The Cost of Plasticity

I would argue that the big question concerning assimilation is whether it is necessary, in the sense of being obligatory or requisite.  Does it have to occur?  One way proponents of assimilation argue that it is necessary is by invoking the idea that there must always be a cost to plasticity, or more broadly, genetic decision making.  No matter the environment, no matter the switch which mediates the plasticity, such a switch must impose a cost on the organism.

If there is such a cost, assimilation will be obviously favored in order to remove that cost when the need for plasticity is no longer present.

Maxwell’s Demon and the Cost of Making Choices

Now I want to turn to a topic which will seem at first entirely unrelated, but which I promise will become relevant.  In the late 1860s, James Maxwell, eminent physicist, conceived of a thought experiment which later came to be known as Maxwell’s Demon.  He postulated a box divided into equal halves, with a door between the halves, and filled with a gas at a constant temperature.  In this box lives a demon, that is to say a hypothetical entity, with the following modus operandi:

  • If the demon detects a fast moving particle, he opens the door to move it into one half of the box (the hot half).
  • If the demon detects a slow moving particle, he opens the door to move it into the other half of the box (the cold half).

Repeating this process many times ought to produce a box in which one half is entirely filled with hot gas and the other half with cold.  (A schematic of this mechanism can be found here.)

The trouble with this demon is that by making this box differ in its heat content by halves, he has just produced usable energy from nothing.  One could imagine a very large box being created in which energy from the hot half was used to drive a generator and create electricity.  If true, Maxwell’s Demon has violated thermodynamics and created energy where before there was none.

Like other thought experiments, the intent was not to break the laws of physics, but to figure out where our understanding of them erred.  Maxwell’s Demon stood up to scrutiny for a long time without being entirely understood, until Leo Szilard put forth an explanation which neatly squared the box’s generated energy such that it became just as costly for the demon to operate the box, yielding a net gain of 0.

Szilard’s insight was that the Demon must consume energy in determining which particles are moving at which speeds.  Szilard showed that the very act of measuring the state of a given particle consumes exactly as much energy as would be gained by moving that particle from one half of the box to the other.  In the long term, the gain of energy would be nothing, and in fact, owing to inefficiency in the demon’s operation, such a mechanism would in fact cost energy.  Thermodynamics confirmed.

The Cost of Information

Szilard’s insight has profound implications on the world.  He showed that the very act of gaining information about the environment necessarily has a cost.

Hopefully, the utility of Maxwell’s Demon is becoming evident.  One of the ways in which genetic assimilation is justified is through the cost of varying phenotype in response to the environment.  Critics of assimilation raise the question of whether there is necessarily a cost, but I think Maxwell’s Demon eloquently demonstrates that any measurement of the environment and decision thereon requires the expenditure of energy.

The analogy to Maxwell’s Demon is not perfect, because the cost of measuring a single particle’s motion is so insignificant as to be negligible in the context of most biological systems.  Despite this, I think there are two lines of evidence suggesting that Maxwell’s Demon is relevant in the context of assimilation.  The first is that the Demon operates at the very limits of efficiency, making perfect measurements of the world at exactly the cost necessary to make those measurements.  Real systems are less efficient, often much less efficient.  Nature is a better designer of mechanisms than us, but even natural systems are profoundly less efficient than the thermodynamic ideal.

Secondly, both the measurement and the subsequent decision are substantially more difficult for an organism.  An organism has to measure a whole slew of variables related to the environment to determine the correct phenotypic response, and often these variables are noisy and befuddling.  Furthermore, the organism has to propagate that measurement throughout a carefully built genetic regulatory network to result in the correctly chosen plastic phenotype.  Between the added complexity of plasticity and the fact that nature doesn’t operate anywhere near maximum thermodynamic efficiency, I believe Maxwell’s Demon is relevant to the cost of genetic assimilation.

More broadly, Szilard and much work after him has demonstrated that information is deeply connected with energy, although the details of that relationship are still to some extent unresolved.  To measure the world, to reliably transduce that signal to other parts of the organism, and to make decisions based upon the signal, must all be treated as energetically expensive acts.  For this reason, there is necessarily a cost to plasticity, and that cost likely makes genetic assimilation an under-appreciated pattern of evolutionary change.