Just before any predictable disaster hits, its almost impossible to take even a medium term view. With the sequester bearing down on us in a couple of days, identifying the immediate consequences is terrifying enough. Just check out the Obama administrations state-by-state list of the grim weeks ahead.

The picture derived from that tally is evil enough, as we all (or should) know by now. In broad strokes, it will slow the recovery, cut economic growth, and act as a persistent drag on ordinary folks attempts to make a better life hell, to pay the rent on the first of the month. But there is a sense, I think, that however crappy conditions may get for the weeks or months before some resolution emerges, matters will return to normal in reasonably short order.

But thats wrong, at least when it comes to the future of science in the United States. The federal government is by far the lead funder for basic scientific research. [PDF; see p. 5] When the funding stream dries up, even briefly, work doesnt just pause for a bit; instead, the blow cuts deeper, past fat, through muscle and into bone. Theres been some coverage of this over the last week or so. For example, in an interview conducted by Dylan Matthews, former NIH director Elias Zerhouni said:

"I think the suddenness of it and the depth of it would be a disaster for research, which is not an activity that you can turn on and off from year to year. Its an activity that takes time. The most impacted are the young, new investigator scientists, who are coming into science, and will now abandon the field of science. There will be a generational gap created.

An average grant is five years long, because science is like that. So think: That means that every one year, only 20 percent of the grants come to their end. So any one year, NIH only has 20 percent of its money available for new grants. At NIH, about half of the grants get terminated at five years, but the rest get to be continued, as you dont want to throw away good research. So the half of it thats left has to go to very promising areas of science, and you have 10 percent left.

If you take 8 percent of that 10 percent, its going to come from new science, new people, young investigators; we are going to maim our innovation capabilities if you do these abrupt deep cuts at NIH. It will impact science for generations to come."

New science, new people, young investigators. Thats the rub. But the issue involves more than the sequester itself. Rather, for at least a large slice of the basic research community, the killing force of the current plan comes from the way it piles on to an already ailing enterprise. Last week I contacted my colleague, Marc Kastner, a physicist, former head of the physics department, and now Dean of the School of Science at MIT which makes him the leader of a some-hundreds of million dollars/year basic research enterprise. The story he told me aint pretty.

For MIT itself the effects, Kastner says, will hurt a lot. The hit to the annual research budget will be about $40 million falling most heavily on the School of Science, which gets 95% of its research budget from the federal government. The effects wont be felt equally across the board. If you run a big lab then you have some room to manouver, Kastner acknowledges. Is ever Eric Lander going to slow down? Hell find a way. But, he says, The rich survive and the poor get devastated. The real question is the next generation.

That is: the sequester wreaks its havoc by striking hardest at particular points in the life cycle of a university researcher. New tenure-line faculty are actually somewhat insulated from the very worst of the pressure. Every agency has set aside money for young investigators, he says,some from private foundations, and a lot from the feds. Cuts in budget strike those dependent on other peoples grants graduate students, post docs and soft-money research scientists but a new faculty hire has somewhat better prospects than most for the first few years.

The rubber hits the road, though, at tenure. MIT, like other leading research universities, generally tenures faculty at around the seven year mark. Researchers achieve tenure on the basis of strong performance in those first years and then after promotion are expected to advance their program through what should be the heart of their productive lives. The tricky part is that it is already enormously difficult to do so. Once tenured, the researcher competes for grants against the entire population, Nobel laureates, National Academicians and all. Theres a reason that the average age for winning your first R0-1 grant is 42 thats up by more than five years since 1980. Add the sequesters cut on top of that existing semi (or more than)-crisis, and you have a circumstance where early-mid career scientists could become even more at risk to career-blasting loss of research funding.

So, add that up: sequester cuts will strike bluntly across the scientific community. The illustrious can move a bit of money around, but even in large labs, a predictable result will be a reduction in the number of graduate student and post - doc slots available and as those junior and early-stage researchers do a whole lot of the at-the-bench level research, such cuts will have an immediate effect on research productivity.

The longer term risk is obvious too: fewer students and post-docs mean on an ongoing drop from baseline in the amount of work to be done year over year, and given that industry has reduced its demand for research-trained Ph.Ds, a plausible consequence is that some, many perhaps, those with capacity to do leading edge science no dummies they will simply never enter the pipeline, shifting instead to some other career that does not demand six years and more of poorly paid training to find that there are no jobs.

But that mid-career trap is at least as troubling: By the time you have a scientist who has done well enough to earn tenure at a research institution, someone the taxpayer, to a very large extent has invested a ton of money, often well into seven figures, into her training and early professional life. If she ends up without that crucial next grant, that money is at risk. The work weve all been paying for doesnt come to a conclusion, and, if our brilliant, mid-thirties investigator finds something else to do, all her time and all that cash are sunk costs, irrecoverable even if Congress relaxes the sequester's bite after a while.

The immediate situation is thus one in which the overall research effort in basic science in the US risks a loss of talent from at least two inflection points in the normal course of a research career. But thats not all. In Kastners genuinely grim account, a certain heedlessness in our leading research institutions, especially among those whove gone all-in on biomedical work, is going to make the problem worse. Over the last several years NIH budgets have doubled, allowing more basic biology and applied bio-medical researchers to get in the game.

Institutions have grabbed the opportunity, and because of the rules about what you can actually charge against overhead on research grants, some borrowed money to build the very expensive buildings in which such work is done. Servicing the loans turns on filling the lab space with grant-getting researchers; the imperative is so stringent that you hear charming phrases like the dollar density of research. (Those researchers insufficiently cash dense get squeezed of space, stuffed into basements and the like.)

The whole scheme turns on continued substantial NIH budget growth. Factor in the sequester and you can bet that there are a number of institutions for whom loss of grants will have a multiplier effect, because of the need to find new cash to pay for debt service on underutilized space. Less institutional cushion means still fewer resources for students and post docs; it limits the possibilities of new hires and so on and the numbers continue to roll in the wrong direction.

Now add one more datum. If you look at the history of US funding [pdf, fig. 2, p. 5] for science over the last fifty years, you see that with the exception of the Apollo years, it remained more or less constant as a percentage of GDP to the 1980s, after which it has experienced a slow decline. Looking at the federal budget going forward, the reality is that as long as health care spending looks to consume its increasing share of both GDP and national budgets, then basic science, like everything else in the federal discretionary budget, is going to remain under pressure. Thus, even without the sequester, there is no shower of gold ready to rain down on the research community.

In that larger frame, Kastner argues, we are now confronting a problem thats been mounting for decades. The meat-axe poised over the biological sciences struck his own field of physics back in the seventies: That was when you heard about theoretical physicists driving cabs. The response? Groups got smaller and post-docs got treated better. (Sic! Even now, physics post docs at national labs get significantly higher pay than new Ph.D post docs in biology, Kastner says.) Something similar is likely in prospect now: Maybe what we need is simply to have fewer graduate students." The issue, brought into focus by the battle over the sequester is that for any of the gambles individual centers may have chanced, ultimately the decision about how much science the U.S. chooses to pursue is a civic one. Right now, Kastner says, "we have over-produced scientists given the investment we are willing to make as a society.

In sum: the reality is that I think the sequester will have a rolling effect on science research Kastner says, but its hard to tell as there are no controls. Thinking parochially for a moment, MIT and similarly well-off, internationally recognized universities will hold up. Not perfectly, not without pain, but still, theyll persist. And certainly, science as a human enterprise isnt going to go away. But thats not the same thing as saying that Americas scientific pre-eminence is invulnerable. There are places around the world which will fill the gap, Kastner tells me as our conversation winds down. Theyre just not necessarily here in the U.S.

Thats one view, acquired from the vantage of the leader of one of the worlds most effective basic research centers. Let me add one more thought from my own, much more modest perch.

Its easy and usually foolish to spin narratives of decline out of a momentary political circumstance. It is true now and looks to remain so for the foreseeable future that the U.S. retains its slot atop the national league tables on all kinds of different measures of power. If the gap between us and the rest of the world is shrinking, compared to the extraordinary circumstances of the post-World War II era, thats a very good thing: it means that the rest of the world is getting richer, healthier, more comfortable.

But that doesnt mean that it is impossible to imagine an actual decline in U.S. power and independence of action.

There are lots of reasons to do science. The one you hear most often, I think, is that human beings are obligately curious. You can make the claim we emerged from our evolutionary past to produce our science-infused civilization because of some confluence of traits that included the willingness to accept risk in the face of the unknown, to ask questions.That has the ring of plausibility to me. You dont become a parent without discovering in your child that drive to find things out.

Then theres the aesthetic quality to science. Theres so much beauty to be found in the systematic investigation of nature from the grandeur of Darwins tangled bank to the iconic force of the Hubble Space Telescopes Pillars of Creation image, made by Jeff Hester and colleagues and on and on and on.

Add to that the simple satisfaction that comes from solving puzzles a reward that motivates more scientists than I first imagined, and that I think may also drive much of the publics hunger for stories of science that one might write with that scientific detective, Sherlock Holmes, perched at the back of ones mind.

But to cut through to the hard cash at the core of this whole crisis, the simple truth is that paying for basic research is a bet a society makes on its future. And it turns out that it is one of the safest wagers around. In the 2007 report linked above, the CBO writes, in predictably dry language, Federal spending in support of basic research over the years has, on average, had a significantly positive return, according to the best available research. (p. 15) Or, to put it a more gaudily, its estimated that the Human Genome Project delivered a return on investment of 141:1 $141 in wealth created for every dollar spent on the job.

No one claims that all basic research posts such glorious rewards, but as MIT president Rafael Reif and former Intel CEO Craig Barrett noted this week in the Financial Times, A report by the non-partisan Information Technology & Innovation Foundation estimates that over those nine years, such cuts would reduce GDP by $200bn and that estimate compares sequestration to a scenario where R&D merely remains at the 2011 rate. If in those nine years the US instead kept R&D spending constant as a proportion of output, the economy would be $565bn bigger. And if it invested in R&D at the same rate as China, that gap would grow to $860bn.

Thus the risk posed by the sequester: it magnifies strains in an already constrained scientific enterprise. And from that, it's not hard to weigh the concept of decline, an actual, lasting erosion of essential national capacity. We can certainly avoid such an unforced error; we can decide to invest more, and more reliably in the future. But we may notand that choice has consequences that arent too difficult to perceive.

Image: Rembrandt van Rijn, The Anatomy Lesson of Dr. Tulp, 1632.