Monday, November 28, 2011

DARPA to the rescue! If civilians have lost interest in developing cures, let the military do it.

Wired magazine reports that the Defense Advance Research Projects Agency (DARPA) is working on a new approach to antibiotics--or post-antibiotics.   As Wired's Katie Drummond writes,  DARPA is seeking proposals that could completely replace traditional antibiotics with a whole new kind of bacteria killer:

Darpa wants researchers to use nanoparticles--tiny, autonomous drug delivery systems that can carry molecules of medication anywhere in the body, and get them right into a targeted cell. Darpa would like to see nanoparticles loaded with "small interfering RNA (siRNA)" -- a class of molecules that can target and shut down specific genes. If siRNA could be reprogrammed "on-the-fly" and applied to different pathogens, then the nanoparticles could be loaded up with the right siRNA molecules and sent directly to cells responsible for the infection.

Drummond allows that it might seem hard to believe that DARPA could pull off something like this, but in fact, the theory has already been proven.  Last year, she notes, researchers were able to engineering siRNA and put it into nanoparticles that were injected into four primates infected with the Ebola virus, thereby arresting the killer disease.

But wait--there's more.   Not only does DARPA seek to bring about this whole new approach, skipping past familiar modes and mechanisms, it is also seeking ways to time-compress the timeline of new cures, from years down to mere days.

So it's a daunting, if enticing, prospect.   DARPA does, indeed, have a big vision.  At a time when most healthcare "experts" talk only of finance and bean-counting and rationing--that is, on the demand-side of medicine--the DARPA wants to jump in on the supply-side of medicine; that is, the creation of actual cures; it's the Pentagon, not the Department of Health and Human Services, that wants to decisively intervene in the course of disease and save lives.  Audacious?  Sure.  Impractical?  Maybe.  Popular?  Absolutely, if it works.   But as Drummond concludes:

If anybody can design a new paradigm for medicine, and a new way to mass-produce it, our money's on the military. After all, we've got them to thank for figuring out how to manufacture the medication that got us into this mess in the first place: penicillin.

Indeed, the military, British and American, was the impetus for the serious development of antibiotics.  The medicinal qualities of the blue-green mould penicillium notatum had been observed as far back as the Middle Ages, but those positive properties were not recorded in a scientific treatise until 1875.  Yet serious scientific inquiry did not begin for another five decades after that.  Alexander Fleming had been a British military doctor during World War One, working in the mud and filth of the trenches, observing firsthand the lethality of infected wounds.   For the next decade, Fleming kept seeking a remedy for infection--until that fortuitous moment in 1928, when he noticed that bread mould was inhibiting bacteria growing in a petri dish.  He called it penicillin.

Yet in the following years, progress remained slow, as Fleming and others at St. Mary's Hospital in London struggled for a decade to purify and extract the antibiotic agent and turn it into a usable drug.  It was not until World War Two that urgent military necessity led to increased funding for Fleming--and to the rapid acceleration of penicillin research and development, mostly in the US.  This heroic story was ably told by Lauren Belfer in her 2010 novel, A Fierce Radiance.  

Vannevar Bush, the director of the Office of Scientific Research and Development--DARPA's predecessor agency--ordered that penicillin research be a national priority second only to the atom-bomb project.   And it worked.  By 1944, penicillin was being produced in the millions of doses by Pfizer, working on a government contract.  As a result of this public-private partnership--this medical-industrial complex, if one prefers--more gains were made in the battle against deadly infection than in all the previous years of human history.

Fleming and two fellow researchers were awarded the Nobel Prize for Medicine in 1945.   As Bush   observed in that same year:

The death rate for all diseases in the Army, including the overseas forces, has been reduced from 14.1 per thousand in the last war to 0.6 per thousand in this war.  Such ravaging diseases as yellow fever, dysentery, typhus, tetanus, pneumonia, and meningitis have been all but conquered by penicillin and the sulfa drugs, the insecticide DDT, better vaccines, and improved hygenic measures. Malaria has been controlled. There has been dramatic progress in surgery.

So while we don't yet know if DARPA's new plan for siRNA will truly work, history tells us that if the military really puts its mind to work on a challenge, that challenge can often be overcome.  Why?   Because the military has a strong claim on national resources--and not just tax revenue.  In the past, to achieve an urgent objective, the military has black-boxed its budgets, dragooned brain power, and bulldozed any and all obstacles.

To cite one germane non-medical example, Gen. Leslie Groves, leader of the Manhattan Project, did not pause over Environmental Impact Statements when he occupied Oak Ridge, Tennessee, and set up a nuclear bomb factory that brought in 75,000 people, and he certainly did not hold public hearings in advance of the 1945 atomic tests at the Trinity site in New Mexico.    Such military mobilization of resources is a hard and Hobbesian process, but it has one virtue: It works.   If the goal is important--and theoretically, at least, the wartime military doesn't have any goals that are not important--then the Manhattan Project sums up the way the process can work to shorten the war, reduce casualties, and guarantee victory.

Similar tales could be told about the wartime (including the Cold War) invention/acceleration of such 20th century inventions as radar, synthetic rubber, aviation, electronics, nuclear power, the internet, and GPS.   As an aside, the fact that each these inventions contributed not only to military victory but also to civilian wealth is yet another bonus of constructive public-private partnerships, and a reminder that the US military has been one of the principal drivers of the American economy all through our history.   And so, too, in the case of DARPA's siRNA project; if it works, we will all owe those defense nerds yet another huge debt.

By contrast, the results for innovation and the economy in the absence of military mobilization can be painfully slow--even deadly slow.  In a free and pluralistic society, every economic activity is eventually surrounded by claimants and rent-seekers of various kinds; these claimants and rent-seekers can be variously described as remoras, barnacles, or lampreys.   That is, they can be mildly symbiotic, a slight burden--or they can be lethally parasitic.

The dismal economic consequences of runaway pluralism were ably described by the economist Mancur Olson in his 1982 book, The Rise and Decline of Nations; Olson went so far as to suggest it was more economically beneficial to lose a war than to suffer the endlessly cumulated sedimentations of special-interest encrustation.  The non-catastrophic solutions to such "demosclerosis"--to recall Jonathan Rauch's encapsulation of the Olson argument--are relatively straightforward; csh solutions include deregulation and an overall opening up of clotted economic arteries.  But as we have seen in our time, it's easier to prescribe those solutions than it is to implement those solutions.

Typically, what's needed is at least some kind of crisis--some wake-up call; a default, if not a  defeat.  Civilian leaders can sometimes make the most of a sense of urgency and crisis--but military leaders always can.

As we have seen in recent decades, bad news on the medical front has not been in any way galvanic--the situation gets worse and worse. Indeed, the worsening seems to be part of a deliberate policy of looting the medical industry to achieve other governmental goals.  

No wonder, then, that we have been losing the war against infection for some time now, and nobody in the US government, other than DARPA, seems to have noticed.  Yes, it might seem to be a strange world when all the agencies and committees that have the word "health" in their title have been allowing the problem to worse, to the point where the number of new antibiotics has fallen by more than 80 percent over the last quarter century, even amidst louder warnings about the rise of deadly "superbugs."   Yet as the historical record shows, even well-meaning civilians have not been able to overcome the cumulative blockages of the trial lawyers, the FDA, and the overall brain-drain and capital-drain out of the pharma sector.

Enter the Pentagon and DARPA, coming from a different world, pursuing different goals.   By no means is the military always a paragon of efficiency, but mission-focused command-and-control does have its bottom-line virtues.   For the most part, the military is able to fend off civilian predations and Olsonian sclerosis, because generals and admirals can invoke national security--and, at a more gut level, the well-being of our fighting forces--in order to push its projects through.

"Compared to war," General George S. Patton said during World War Two, "all other forms of human endeavor shrink to insignificance."   War is, indeed, catalytic; it does unleash vast amounts of public exertion and public forbearance.   But war, of course, is also tragic, even if, as in World War Two, the larger benefits of improved medicine save lives during and after the war.

In a better world, advocates for Serious Medicine, such as a new kind of instantaneous bacteria-killer, would be able to act just as decisively in the fight against microbes as generals can in the fight against men.   That is, we would enjoy the benefits of saving lives without predicating the effort on taking lives.   Until then, however, we can conclude that those generals and admirals care more about the well-being of their men and women than our elected politicians care about the well-being of us civilians.

So yes, someday, we should have a MARPA, for Medical Advanced Research Projects Agency, as a more mission-focused version of the NIH.   We should mimic the military's sense of purpose on the civilian side, without firing a shot.

But until that happens, we should be thankful that we have a DARPA.  


  1. "Darpa wants researchers to use nanoparticles--that can carry ... medication anywhere in the body, and get them right into a targeted cell."
    Ok, good idea Jim. It needs 2 things: 10 x the funding it has now and the rest of the government to stand back out of its way because it is seeking ways to time-compress the timeline of new cures, from years down to MERE DAYS.
    What a wonderful thought and gift to humanity. ....... and the jobs it would create!

  2. Correct me on this if I'm wrong...but I believe when they built Oak Ridge, even the Gov. of Tennessee didn't know it was there....not on any map.