The $140 fix

In his State of the Union address to congress on Feb 12, President Obama laid out many ambitions for his next term.  It was a speech to the country and to Congress, and he stated many things he wanted to use the government for, in particular, goosing up the economy in various ways.

Like other  Presidents before him, and perhaps as is necessary given the complexity of his job and the topics he must deal with, Obama relies on lines and catch-phrases and selected data that he's been fed by advisers.  Often, as here, they represent vested interests within the Federal government.  For example, the Education secretary is bound to recommend this or that specific thing to fix our education problems.  The Energy department will recommend equally pressing needs, as will Defense and so on.

One needs to beware of the selectivity and promotional nature of factoids being cited, so as to at least be savvy about what they mean and why they're being cited--and of course to be aware that they are advocacy.  The President can only say, marionette-like, what he's told by people whose judgment he trusts, but they often do the same, passing things down the line to the primary advocates.  Just as lobbyists do provide expertise, along with their advocacy, advocacy isn't entirely self-serving.  But it can come pretty close and in a sense it's the President's, Congress's, and our responsibility to make the judgments about what is being said and what we believe are important.

Must everything we do be crass and venal?
In this context, Obama stated that the effort to 'map' the human genome has 'returned' $140 for every dollar ("--every dollar") that was spent on it.  How great!  But what does that suggest in a not very subtle way? That the science investment has value because it is good for business.  If that's the case, and apparently a great many people feel that it is, why not call it business socialism?  Or a welfare system for businesses and universities?

NIH isn't unique in playing the economy card, as well as the 'you will never get sick if you give us funds' card (and Obama repeated things NIH or others had told him along those lines, too).  It's how our system is constructed, perhaps.

Whether, when, or to what extent investment in NIH leads to a fully functional immortality is separate from the justification of funding on the grounds that it's good for business.  Obama isn't qualified to discuss whether to 'map' the human genome is the best or even a good way to remove disease from the face of the earth.  A State of the Union address may not be the place for subtle discourse.  But if we are just going to justify it on business grounds, we might as well not worry about whether, say, billions of dollars are spent on  projects that don't generate a single result, or projects that use mouse models that are totally inappropriate, or studies that grow ever larger when we know they'll find ever tinier effects, or projects that grow ever-larger research empires at the expense of intellectual freedom and the support of young scientists who could, with different distribution of resources, perhaps think more freely and have an even better chance of making discoveries that, yes, were good for the economy.

Our society perhaps simply can't be made to temper its exaggerations in support of vested interests, but we think that's a shame.  It systematically replaces substance with label, and numbs us from critical thinking.  If every word in our language must be a superlative, we'll all end up in semantic wonderland, like Lake Woebegon, all above average.

Polio deaths

In previous posts I’ve discussed the ways that diseases tend to persist in war-torn regions in ways that they don’t in other places.  For example, vivax malaria persists along the region separating North and South Korea, and Myanmar continues to have malaria even after neighboring nations such as Thailand and China have been relatively successful at controlling malaria.  I would suggest that the reason for this relation between disease and war has a lot to do with the conditions in which people that live in war zones must live.  When people flee an area where war has begun and cram into refugee camps, it’s predictable that there will be crowd- and hygiene-related disease.  Expect problems with intestinal and diarrheal diseases such as cholera.  Furthermore, while dodging bullets it’s probably hard to worry too much about drugs and bugs.  Public health efforts fall to the wayside.  

Frankly, if people would just stop acting like jackasses we would probably have a lot less trouble in our world.  But that’s probably too much to ask for.

Today I’d like to specifically talk about poliomyelitis (polio).  Polio is a viral disease and it spreads extremely easily via fecal and oral transmission.  Many who become infected with the virus never exhibit symptoms; however children under 5 are disproportionately affected.  Symptoms can vary widely, with the worst being paralysis and even death when the muscles necessary for breathing cease to function.  There is no cure for the disease.

Polio was historically a major problem even in Western nations such as the U.S.  By the late 1800s it was recognized as a severe and perhaps growing threat and in the 1950s a successful vaccine was created.  Since then a LOT of progress has been made in the control and even eradication of polio.  Today it really isn’t much of a problem for most of the world.  Or is it?

1963 poster from the U.S., courtesy of CDC and Mary Hilpertshauser

According to the World Health Organization, the only remaining nations with endemic polio are Nigeria, Afghanistan, and Pakistan.  These are places that frequently make the major news for reasons other than disease and probably aren’t on your radar when planning a family vacation (I apologize in advance if I’ve offended people in the tourism industry in any of these places).  But remember that most (around 90%) people are asymptomatic and that we have a highly mobile global population.  So you may not be worried about your kids getting polio while hanging out on a beach in Nigeria, but that doesn’t mean that it can’t wind up in your neighborhood (though most U.S. schools require you to get a vaccine before attending).

Anyway, the reason that I’m writing about polio today is that it keeps popping up in the news, most recently with regard to Nigeria.  Nigeria has been having some trouble lately.  For example, the radical religious group Boko Haram has been terrorizing a good chunk of the country now for several years.  The words Boko Haram can be roughly translated from Hausa to English as “Western education is forbidden”.  These guys REALLY don’t like “modern” Western science, which can be a real problem for people who like to save lives by practicing that modern Western science.  If you haven’t heard of them, keep your ears open because I think you’re going to be seeing their name a lot in the future.  

To get back to the polio story, several religious leaders in Nigeria have warned their followers against becoming vaccinated against polio.  Some have claimed that it will make you infertile while others claim that it will actually infect you with the virus (though I suppose if you’re a Boko Haram follower then viruses don’t exist in the first place).

Obviously this is a public health problem, but things have recently taken a drastic turn for the worse.  In the last week it appears that health care workers who administer the vaccine are actually being targeted by gunmen.  At least 9 were killed last Friday.  While no group has claimed these attacks, they resemble previous attacks that have been attributed to Boko Haram.  Perhaps even more disturbing is that these killings come just a couple of months after similar killings in Pakistan, which also targeted polio vaccinators.  In Pakistan, the Taliban has suggested that health care workers are working with, or actually are, CIA operatives.  (And while this may seem crazy, remember that the CIA did pay a Pakistani doctor to help in the capture of Osama bin Laden).

Clearly this is a pretty terrible situation.  Several organizations have hoped to actually eradicate polio, but clearly this won’t happen if the virus is allowed to persist in human populations.  (The potential for nonhuman hosts might also be an issue here, but getting it out of human populations is a noble cause anyway).  

Furthermore, what does this mean for future public health efforts in this region?  I suppose we can continue to bring outsiders in to vaccinate, but in my opinion it is always better to have local people maintaining public health efforts.  And when the news of this type of violence spreads through regions where it is occurring, I can’t help but think that it will in some ways shape the future of public health in those regions.  The children who are growing up now, who are just beginning to form ideas about what they will do when they are older, are now facing a world where being a medical provider can be a very dangerous thing.  Not everyone who goes into medical practice or public health does so because they have a passionate desire to practice medicine.  Some do it because it’s a relatively OK job and the added benefit of it helping others out gives it a sugar coating.  I worry that, for this type of person, a career giving vaccinations to local people will no longer be on the radar as a future potential occupation.  This could be a tragedy for public health, meaning that it would also be a tragedy for global health.

Concentric circles of causation

Public health has always been a broad discipline, encompassing the study of diseases in populations in all its forms, applied and academic both, and it's getting broader.  The story of the first epidemiologist, John Snow, is well-known -- he suspected that an 1854 cholera epidemic on Broad Street in London was due to a waterborne infectious agent, at a time when it was generally thought that cholera was an airborne disease.  He convinced authorities to remove the handle from the pump on the well that he suspected was the source of the epidemic.  It turned out, of course, that he was right, although the spread of cholera had already slowed by the time the handle was taken off the pump.  So, his contribution was to future public health, not his ill contemporaries.

Epidemiology is the study of patterns of disease in populations -- who's at risk, what's the cause, how to prevent it.  For more than 100 years after John Snow epidemiologists concentrated on proximate single causes or specific exposures -- cigarettes and lung cancer, Legionnaire's disease and Legionella bacteria, HIV and AIDS -- but recently the field of "social epidemiology" has gained some traction. This is the study of the social determinants of health and disease.  The proximate cause of AIDS is HIV, but often, HIV is contracted through drug use and shared needles, or patterns of multiple sex partners.  And, in most places, those at highest risk are poor, so that it's perfectly legitimate to say that poverty causes AIDS.  So, what's the actual 'cause' of the disease?  And, where does Public Health intervene to control it?

There has long been debate over whether epidemiology has a theoretical framework, or whether it is just a set of established statistical methods.  Social epidemiologist Nancy Krieger, in her seminal paper in 1994 called "Epidemiology and the web of causation: has anyone seen the spider?" discussed just this, writing that epidemiology at the time, yes, was interested in the 'web of disease causation' -- what causes disease in populations? -- but was neglecting the search for the spider, the maker of the web.  This paper kick-started the field of social epidemiology.

Krieger wrote:

[This paper] emphasizes why epidemiologists must look first and foremost to the link between social divisions and disease to understand etiology and to improve the public’s health, and in doing so exposes the incomplete and biased slant of epidemiologic theories reliant upon a biomedical and individualistic world-view. 

She's just published a new paper in the American Journal of Public Health, "History, Biology and Health Inequities: Emergent Embodied Phenotypes and the Illustrative Case of the Breast Cancer Estrogen Receptor" in which she argues that health inequities can only be reduced if diseases are considered not just as static biological entities, but within their social and evolutionary contexts, and as individual histories (she calls this broad view of, in this case the estrogen receptor, the "emergent embodied phenotype" -- we can ignore the jargonizing of what is a rather obvious idea).  The paper was brought to our attention by Susan Oyama, who has done some very good work on developmental systems, broadening the understanding of genes in context, among other things.

There's a new field in biology, too; 'systems biology'. This is the study of interconnected biological systems -- metabolic pathways, gene interactions,  cell signaling networks.  This is intended to be a more holistic approach to biology rather than a reductionist one.  The idea is that describing these interactions will help us to understand the 'emergent' traits that are complex diseases.  It is hoped that there will be practical applications -- understanding networks will, e.g., elucidate 'druggable' pathways that pharmaceutical companies can then intervene on, to prevent or cure disease.

Ken and I have often criticized the idea that the new field of 'systems biology' is going to be all it promises.  Like social epidemiology, systems biology is a somewhat self-congratulatory jargonized term whose  proponents suggest the very reasonable idea of taking a broader view of causation, in an attempt to take into account as many factors as possible that might explain how genes function or how traits are made or the causes of a disease.  It's basically a way of enumerating identifiable interactions among components.

So, rather than being satisfied with knowing that mutations in a specific gene on their own cause a particular disease, the idea is to take a larger view:  Enumerate the regulatory pathways or gene interactions (that is, between proteins) so that there are more targets for pharmaceutical intervention.

Seoul from space

Systems biology sounds like a good idea.  A standard, purely additive model of what genes do treats each gene like an independent dose of some effect, and the overall result is just the sum of these effects.  But this is clearly oversimplifying at best, because gene products interact in various molecular ways that need not just be additive.  Instead, sets of genes (their coded proteins, or the proteins that cause a given gene to be expressed) interact with each other -- in 'systems'.

Metabolism is an example in which chains or cycles or hierarchies of interactions pass molecules from one stage to the next.  Even if the interaction networks are the mechanism of action, there is no reason to expect that the effects of variation in the components will lead to simple or additive variation in the result.

However, the temptation (whether explicit or implicit) is to try to rescue complexity by treating networks as self-contained causal units. Take sets of tens or hundreds of genes and treat each as a single causal unit, and magically you've reduced the causal dimensions you need to consider by an order of magnitude!  But this is wishful thinking, and doesn't really simplify causation or the hunt to understanding, because we know that genes contribute to multiple networks, that vary, overlap, and have alternative pathways that are used under different circumstances.

Social epidemiology faces similar complexity.
Broad causal networks may seem to smooth out causal relationships until they look generalizable, but they aren't necessarily any smoother in social than molecular life.  There's a common issue in population sciences called the "ecological fallacy."  This is when an association that is true on the population level is inferred to be true on the individual level.  The county may always vote Republican, or this neighborhood may be a wealthy one, but it can't be assumed that everyone in the county votes Republican, or that everyone in the neighborhood has an income above the average. Or that the neighborhood causes political preference or wealth in a given individual.

Social epidemiology by its nature and objectives searches for population level associations and attempts to infer from those associations causal relationships that apply at the level of the individual. Poverty causes AIDS.  Racism causes stress which causes high blood pressure.  In a sense, as reasonable and plausible as these ideas, and as much as they must reflect causal processes in some way, the ecological fallacy is always lurking, because not everyone with AIDS is poor, and not everyone who is poor gets AIDS, not everyone who has experienced racism has high blood pressure, and so on. And, even eliminating poverty won't prevent further cases of AIDS.

Unlike systems biology, where the idea is to intervene in the networks with targeted pharmacological agents, it's hard to know what to do with the information that social epidemiology is producing.  Public Health is, ultimately, an applied science.  It has very little that could be called real theory, beyond the use of statistical methods to design and evaluate studies -- that is, assuming the kinds of repeatabliity that any statistical sampling requires, similar to saying that every roll of dice has the same probability of coming up 6.  Dice rolls may be repeatable events, but to a great extent, humans aren't.  And as with systems biology, the idea is not just to enumerate interactions but to identify targets of intervention.  But, when the field is identifying "poverty" or "racism" as causal factors, what can be done to intervene? 

Indeed, one might say that at least simple biological systems like the krebs energy cycle or photosynthesis require networks of interactions among a step-wise hierarchy of truly enumerable molecular components in quantitative relationships, and a very high degree of repeatability so they can be studied experimentally and evaluated with standard statistical methods.  But are 'poverty' and 'racism' even serious concepts of similar type?  If not, then current statistical or other study-design methods may simply be inappropriate, too vague, or unable to provide the type of answers we would like to get, especially if we desire to understand causation at the individual level.

Public Health, and epidemiology in particular, has a legacy of successful research and intervention in infectious diseases -- these are 'point source' diseases, with largely replicable causality, and if you cut the problem off at the source, you prevent the disease.  This has its parallels with human genetics, where clearly Mendelian, single-gene disorders are relatively easy to explain.  It's when causation gets complex that genetics -- and Public Health -- get into difficulties.


But, ok, granted, Public Health is a population-level field, and eliminating all cases of a disease has never been asked of it.  But it's curious to see the field seeming to homogenize causation at a time when complexity is a buzzword in other fields.  Though, again, this is quite in line with much of genetics, which has its own legacy of successes with point causation (Mendelian disease), just not so much with complex diseases. And which also mixes population-level effects of particular variants with the ability of those variants to 'personalize' medical care.

Have you seen the photos that Col. Chris Hadfield is posting on his Facebook page?  He's in the Space Station, taking pictures of Earth in his free time and sharing them with the world.  They are stunning.  He photographs cities, regions, large chunks of continents; they are lit up at night or green, or snow-covered, or cloud-covered, or dry-as-a-bone desert, or stretches of ocean during the day.  When he wonders what something is in one of his pictures, he crowdsources the answer.  The other day it was a spot in Tehran that looked curious to him.  It turned out it had once been an airport, and is now a playground, which Iranians told him.

If a region is experiencing drought, that's easy to see from these photos.  But, if there are cracks in the macadam on those long stretches of highway, or a bridge is unstable, or the rivers are polluted, you can't see it from space.  At least, not from these pictures.  You do get the big picture, but you have to zoom in to discover where to intervene to prevent a catastrophe due to crumbling infrastructure.

Social epidemiology may be a lot like Col. Hadfield's photographs -- beautiful descriptions, but so far removed from the individual that it's impossible to actually predict who's going to get sick and why, never mind useful for figuring out where to intervene.  Even identifying the risk factors themselves is notoriously difficult.  And one need not give it a special name, which is often a way we academics have of making their ideas seem new or particularly insightful.  Just 'epidemiology' will do very well--and the point is to include social as well as other potentially causal factors (and, as we hope is clear, we are not just picking on public health rhetoric, because genetics is just as much affected by unnecessary jargonizing).

Public Health is by goals and design a population-based field, and it works well when the message is that cholera is waterborne, so we need to keep our water sources clean, or that vaccination can protect entire populations against infectious disease.  Its methods have saved countless lives.  But, like trying to make risk predictions from  genetic data from whole populations, it's hard to know what to do with these descriptions of the causes of complex diseases from such a distance.

And ultimately,  of course, if we go out enough concentric circles of causation, it's life that is the cause of disease, and the only prevention is death.

Science, jobs, and education

We have recently argued in several posts that the pressures in academia today make funding hard to secure, good science jobs seemingly hard to find, and lead to the churning out of tons of useless research, the support of a large academic welfare system, and increased cheating.  'Research' has been so heavily marketed--and that's the right word for it--by both academia and the media, all thumping like itinerant preachers, that it has become an iconic status symbol and, even, idol of near-religious worship.

We argue that one way or another we should rectify the system.  There are not enough funds for as many people to play this game as want to, or as we lure into when we recruit graduate students.  Exponential growth, and institutions largely serving themselves rather than their  purported societal clientele, will eventually, inevitably, become overcrowded.

We can tolerate overcrowding, somewhat akin to Marx' and Engels' idea of an excess labor pool, kept on hand, but only on the brink of sustenance, to be hired or shifted around as needed.

We still import large numbers of students from abroad, in part because American-trained kids don't want to or are insufficiently trained or motivated for competitive-level science and technological research.  But in part, the foreigners pay full-ride tuition, or they are serfs who work long hours on faculty members' grant projects without complaining.

But there are alternatives.  First and primary, perhaps, is that we have a notoriously faltering (or should we spell it faultering?) K-12 system.  In other countries, the top of the university graduate pool are those allowed into teaching.  To be euphemistic about it, that's not the same here.  And our complacent, self-satisfied society doesn't have nearly the work ethic that more driven societies do.  So, naturally, many of our high school graduates are badly under-trained and under-attituded for serious university level work.

But what about the excess labor pool of PhDs who do, in fact, have a degree in science but who have not been able to compete for university faculty positions?  Some may be not very well qualified and hence not competitive for limited positions, but that's certainly not the problem with all of them by any means.  An obvious solution, we have argued, is to scale back the graduate school mill so it doesn't lure into, and ejest, more than can find employment.  We are overstocked for reasons we've posted about before, including last week.

But there are very important areas where these people could use their training and skills, that would be much, much more important to society than the typical research-mill career.  That would be in science education, especially at the high school level (a PhD would not be relevant for earlier-year teaching, but real solid BS degrees--not degrees in 'education'--would be very valuable, if we could goose up the level of undergraduate teaching to expect more and give more to our students. Junior or community colleges, or small undergraduate colleges, are also places where good teaching could have a major impact.  These jobs can have job security, good health and pension plans, and plenty of time off, so they're not exactly scut-work.  And, they could have a noble position in their local communities if our society re-evaluated what's important.

They don't have the panache, but they have far more punch, than the typical research-mill professor who escapes as much teaching as s/he can, or does it rather perfunctorily.  But as long as we only give status to research careers, because that serves our rather than our students' interests, we will have the system we've created.  Instead, solid Masters degrees that were given only to those who really were masters of their subject, or PhDs not aimed solely at academic research careers, could address many problems, even as the research enterprise continued purring along.

There will be no easy answers until society realizes that miracles from science are costly and few and far between, while the underpinning that can make life better for everyone, even in less than spectacular ways, should command far more of our attention and respect.....and provide good jobs for many good people.

Resistance to glyphosate-resistant weeds

Business and science aren't always a good mix.  Farm Industry News reports that glyphosate-resistant weeds are spreading faster than ever.  The International Survey of Herbicide Resistant Weeds reports: 

There are currently 396 unique cases (species x site of action) of herbicide resistant weeds globally, with 210 species (123 dicots and 87 monocots). Weeds have evolved resistance to 21 of the 25 known herbicide sites of action and to 148 different herbicides. Herbicide resistant weeds have been reported in 63 crops in 61 countries. 

This is, of course, a direct result of genetically modified herbicide-resistant corn, soy, canola and other crops that were built to be resistant to weed killer so that farmers could spray their fields until the cows came home in order to keep down weeds.  The best known such product is Monsanto's herbicide RoundUp, and the RoundUp Ready crops it also engineered.  

Herbicide resistant crops are perhaps an appealing idea -- in year One.  Anyone who knows anything about evolution knew that weeds would likely develop resistance, even as Monsanto assured farmers this wouldn't happen. 

Farm Industry News writes:

The area of U.S. cropland infested with glyphosate-resistant weeds has expanded to 61.2 million acres in 2012, according to a survey conducted by Stratus Agri-Marketing. Nearly half of all U.S. farmers interviewed reported that glyphosate-resistant weeds were present on their farm in 2012, up from 34% of farmers in 2011. The survey also indicates that the rate at which glyphosate-resistant weeds are spreading is gaining momentum; increasing 25% in 2011 and 51% in 2012.

The increase is fastest in the Midwest, though every state is seeing it.  And, the number of species that are resistant is also increasing on each farm.  In southern states, the proportion of resistant weeds is highest -- 92% of farmers reported resistant weeds in Georgia, for example.  

Source: Stratus agri-marketing inc.

In Mississippi, the first weed to become resistant was horseweed, or marestail, in 2004.  Italian ryegrass, waterhemp, Palmer amaranth, Johnsongrass, giant ragweed,  goosegrass and spiny amaranth have followed, according to Corn and Soybean Digest.

It is, of course, costly to spray for weeds; sometimes more than $100 per acre, and according to the Digest, farmers may have to apply herbicides 6 or more times a year.  Thousand-acre farms are not uncommon in the Midwest, and resistant weeds have already put a lot of farmers out of business. And it's not just the cost -- sometimes the problem of resistance is so rampant on a farm that there's nothing that can be done to control the weeds.

Monsanto's RoundUp, of which glyphosate is the active ingredient, was seen by many as almost a miracle when it was first introduced.  It was cheap and killed a wide spectrum of weeds, with no residual effect the following year.  As a result, many farmers used it liberally, and happily.  One such farmer was a cropping farmer in New Zealand where weeds have only now started to be resistant, although resistance is widespread in neighboring Australia. So much for miracles!

New Zealand is now in a position to prevent the spread of resistance -- one way is to use other herbicides on resistant plants.  The problem is that these are not as environmentally friendly (and how friendly glyphosate is open to debate; we've blogged about this before, and the issues haven't changed), or as inexpensive to use. 

But, as a group of researchers write in Weed Science:

It is clear to most weed scientists who are involved in herbicide research, and even those who are not, that the best way to reduce selection pressure for herbicide resistance is to minimize herbicide use. However, the “solutions” that have emerged in most recent meetings on herbicide resistance have usually involved more herbicide use—herbicide rotation, tank-mixtures, PRE- followed by POST-herbicides, “right-rates,” etc. To an unbiased observer, it would appear that many weed emperors are wearing no clothes.

As is being found, to the surprise of no one who understands evolution, the use of different, and more toxic herbicides is creating races of weeds resistant to those chemicals, and it will always be thus.  This is quite comparable to the problem of over-use of antibiotics, and even the use of single rather than combined chemotherapetutic agents to treat cancer patients (that leads to the evolution of resistant cells within the tumor).

And, the weed researchers continue:

Why are so many weed scientists and extension personnel recommending more herbicides to mitigate herbicide resistance problems? One speaker at a 2011 WSSA weed resistance meeting noted that because of his funding sources, it was difficult to talk about real solutions. At the same meeting, another expert suggested that the solution to herbicide resistance “all sits on herbicide diversity.” At a 2010 meeting of Pan-American and European weed scientists, the near-consensus solution for glyphosate resistance presented by speakers was to use glufosinate in the place of glyphosate. Industry strategy to manage glyphosate-resistant weeds is to develop crops with “stacked” herbicide-resistance traits (Green and Castle 2010; Wright et al. 2010). 

It's the likes of chemical purveyors such as Monsanto that got farmers into this mess.  They aren't going to solve it in any rational way.  "Are we as a discipline," these weed scientists ask, "so committed to maintaining profits for the agrochemical industry that we cannot offer up realistic long-term solutions to this pressing problem?"

The real solution, they say, if there is to be one, requires crop rotation with a greater diversity of crops, as that tends to increase the diversity of weeds in a field as well.  Yes, farmers will use herbicides on these weeds, but it will be a range of different ones, and resistance will be slower to develop.  And, farmers should use herbicides far less frequently than they now do, on schedules recommended by, who else?, the herbicide manufacturers.  That would help in the short term.

But, in the longer term, the resistance roller coaster, and dependence on the chemical companies that manufacture both resistant plants and herbicides, needs to slow down.

More research on herbicide alternatives is required. Research on allelochemicals and biofumigants, diverse crop rotations, higher crop seeding rates, intercropping, competitive cultivars and planting patterns, physical weed control, weed seed destruction, and reducing weed seed and vegetative propagule dormancy is crucial for a sustainable future. Combinations of a diversity of tactics in integrated crop management systems augment herbicide-based weed control (Harker et al. 2009) and lengthen the useful life of valuable herbicide tools.

Chemical companies that naturally have, or even that created, vested interests shouldn't be allowed the overpowering influence that enables them to continue to call the shots, because of course it's not in their interest to solve the problem except by more chemicals that depend on evolution not happening.

The problem is not with science per se, nor even with industrial-scale agriculture.  The problem is with overly simple solutions and, equally perhaps, an over-confidence that  industrialized science can itself always evolve a step or two faster than the organisms it's targeting. 

To cut, or how to cut, that is the question

We have criticized the current science funding and approach many times and in many ways here on MT.  Essentially, there is waste, relentless pressure to churn out safe incremental results, and pressure to rely on Big Science for a variety of reasons, some of which have as much to do with careerism as the science itself. The science establishment has been overpopulated in a Malthusian way, even knowingly, and we have noted how and why this understandably leads to various forms of shading of the evidence, including outright fraud.

These are facts that only the most Pollyannish people in science, or perhaps Francis Collins politicking in defense of NIH's budget, would deny.

We have said to the contrary, that grant budgets should be cut substantially.  The objective would be to force investigators to work on more cogent problems, more likely to return useful practical or theoretical results to the society that funds the work, and do that at more reasonable cost.  But we would encourage longer-term funding, and caps on how much any one investigator can have, to spread the wealth.  We know that this, like any such distribution policy, would generate some waste and inefficiency, but it could hardly be more than it is currently, and might increase the chance of real innovative discovery.  Faculty for whom research is part of their job, should be given modest research budgets without having to pass 'peer' review, but accountable instead by periodic demonstration of capable thoughtful work.  Projects, especially big ones, ought to have clear and definitive time limits.  Universities should be weaned off their addiction to grant overhead, and career-building needs to be returned to evaluations based more on originality, depth, and impact than on lobbied, gamed production mills.

But how can it be good to cut funding when it's already so tight?
It has been objected that the probability of funding is already very low--some institutes at the National Institutes of Health are said to be funding only 8% of grant applications--so that cutting could hardly have salubrious effects!  How can we rectify a belief that the system of science is too bloated with the fact that reduced budgets would make it even harder to be funded?

This is a fair question, and the answer isn't simple, but let's try to explain our view, at least.  First, funding is tight perhaps, but the 8% figure doesn't represent the whole story.

A large amount of research support by NIH at least, and probably NSF as well, goes to internally driven programs or projects, perhaps like funding DNA sequencing centers, or to semi-competitive contract bids, or to RFP's.  RFPs are NIH's requests for proposals to address some particular area that they have been convinced need attention; RFP's are drafted with external consultants and in our experience the funding mainly goes more or less predictably to insiders, already established in the field, partly because they're in effect designed or aimed that way, which leaves most proposals coming opportunistically out of the blue and truly far off the fundability mark.

In addition, the low per-proposal rate, whether it's 8% or in fact higher, just leads investigators to submit reams of proposals every year, so that while most proposals may not be funded, most investigators do get some funding.  And if you look at what's funded, you wonder how that could happen if funds were really so tight that only really good science would make the mark.

This same overheated system means less time investigators spend doing any actual work because they're writing so many grant applications, and that leads investigators to routinely overstate what they have done, and to be very safe in proposing what they want to do in the future.  It generates large sets of administrators to handle the processing, etc.  And, of course, to the shading of truth in various ways.  You can't expect otherwise.

Further, there is a very conscious and intentional drive to propose bigger and longer studies on various grounds, some legitimate but many trumped up as rationales, so investigators can manage big groups for long time periods.  Bigger means safer and more status and influence on campus.  You can't fault people for thinking grandly, or seeking more security.  A concentration of funds in Big Science is not good for science overall if it leads to quickly diminishing returns but too-big-to-terminate projects, and this we think is quite common, indeed almost the rule.  The move to 'omics' scale work is very deliberately done and in part for these fiscal and careerist rather than scientific reasons.

Of course, the same, predictably, also drives universities to want more overhead income--universities get a hefty percentage of the budget of just about every grant their faculty members receive, money over and above the grant budget, that goes straight from the funding agency to the university--so there are all sorts of pressures on the system itself to go Big.  There is no reason universities shouldn't keep wanting to expand: in the way we view the world in the business-modeled US and EU, size, growth, and competition are everything.  Investigators who aren't funded can, well, survive however they can survive.  Or not.  Pressures are naturally for 'faculty' to teach less if at all, and do less actual work so they can spend their time and effort on grant-writing.  So naturally we tend to hype every little factoid to the media and publish a relentless stream of (usually never-cited) papers.  Anyone who denies the pervasiveness of this is being disingenuous.

Considering all these factors, however tight funding is it's in part because the system is still bloated without constraints to make people do more focused, accountable, work.  Or to become more efficient.  Or more honest, if it comes to that.

If budgets were cut to the point that NIH and perhaps also NSF and others, had really to evaluate what is most necessary, focused, and likely to yield returns, and to stop things that aren't, and to curb university overhead-greed and administrative overload, and to restrain NIH's and NSF"s own big publicity hype machines, and so on, we could perhaps--perhaps--make things more scientifically efficient.

If we slowed down and scaled back, and made funding more predictable and longer-term, but per capita smaller, and changed to a way of thinking that led to fewer but better-trained graduate students, fewer post-docs, smaller faculty and research staff, smaller and less bloated operations overall, then science might be advanced and perhaps even at a lower cost.  And funding, though more modest perhaps, would be easier to get.

But without real tightening, it is in nobody's interests--certainly not those who accept the Darwinian worldview that life is all about relentless competition and winner-take-all rewards--to change the way they do business.  As it is now, competing more frenetically is the strategy that is perceived to have the best chances of success.

But what about the jobs at stake?
Any cuts will involve threats to jobs and hence draw resistance of whatever sort universities and investigators and other lobbyists can muster.  But there are honorable ways to cut.  Phased budgetary cut-backs could give universities time to adjust.  They could downsize by not replacing personnel who leave or retire, for example.  Phased change that is clearly signaled with enough time to adapt is a proper and feasible way to do things.

A return to more measured expectations and modest but focused work, done in a humanely phased way, could rectify some of the issues and improve the yield of knowledge and 'translatable' results to the public. 

Live chat: Are we doing science the right way?

We posted last week on the recent Science piece by Jennifer Couzin-Frankel about scientific integrity, highlighting the work of Ferric Fang and Arturo Casadevall on what's wrong with science.  Science is following up that piece with a live chat tomorrow, February 7 at 3PM eastern time with Drs Fang and Casadevall.  You can follow it on the Science website, but you can also follow it here.