Tag Archives: science

On “Leaving Science”

I follow news about the science job market pretty closely, but perhaps the most reliable indicator I have of it isn’t in my RSS folder or Twitter feed. It’s my inbox. When graduate students and postdocs start to think their future is especially bleak, I start getting more notes from them asking about my choice of an “alternative” career. Many scientists have the naive impression that anyone with a PhD and a laptop can just take up science writing and make a decent living freelancing. I hope my previous two posts have disabused them of that notion.

Now I’d like to back up a bit and address a broader theme that comes up in these discussions: what’s it like to “leave science”? No matter how the question is phrased, the implicit assumption is that a career in basic research is the only valid purpose for earning a PhD in science. Choosing anything else carries a whiff of failure.

It’s not hard to see where this attitude comes from. In any worthwhile PhD program, students and postdocs are surrounded by principal investigators (PIs) who’ve made basic research their life’s work. Of course these people consider science the primary point of the training they provide their underlings – if they thought otherwise, they wouldn’t be where they are. Society has granted the PIs the extraordinary privilege of pursuing their own curiosity for a living. How could anyone want to do anything else?

What most PIs don’t see is that this privilege has costs, and those costs have skyrocketed in recent years. Jordan Weissmann recently provided an excellent and graphic summary of the situation, based on data from the National Science Foundation. According to those data, a biological science PhD graduating in 1973 had a better than 50% chance of becoming a tenure-track faculty member within five to six years. Those are today’s department chairs and deans. They grew up with that reality, and they have a hard time imagining that things have changed much. But things have changed, and radically; a PhD graduating today has less than a 15% chance of becoming a tenure-track faculty member over that time period, and that percentage is still declining. Basic research is now the “alternative” career. Most PhDs will do something else.

This isn’t a recent trend, and it’s not going to go away even if the idiots in Washington manage to fix the current budget clusterfuck. When I was nearing the end of my doctoral work at Columbia in the mid-1990s, the job market was already pretty tough. Many of my colleagues were brilliant and incredibly dedicated scientists, and some of these hard-core folks were heading for second postdocs, having spent more than a decade in “training” positions already. For those who couldn’t imagine themselves doing anything else, the prospect of becoming a PI was worth nearly any sacrifice. Like aspiring actors or artists, they were perfectly willing to forgo both free time and decent pay indefinitely, and dedicate their lives to pursuing their dream.

That wasn’t me.

I loved science and thoroughly enjoyed doing it. Had I graduated in 1973 I most likely would’ve pursued it as a career, but in a labor market that apparently had many more scientists than it needed, I could easily imagine doing something else. I rejected the outdated notion that a non-PI career track would constitute failure. The PhD was supposed to expand my options, not restrict them.

With longstanding interests in public policy and communication, I started looking around for jobs that would combine my scientific training with one of those fields. It didn’t take long to settle on science journalism. When I switched careers, though, I did not “leave science.”

I can’t leave science. It’s part of who I am. A scientist doesn’t punch the clock in the morning, think scientifically all day, then punch out and suddenly think some other way. It’s the same for writers; I didn’t suddenly become one the day I got my first byline. Writing, like science, is a way of thinking, and for most of us in this business it’s part of the way we’ve always thought. I’m a chimera, a scientist-writer currently employed as a science writer.

Of course one doesn’t need a doctoral degree to write science news, but I don’t think my half-decade in graduate school was wasted. Indeed, that training has helped me spot angles, carve out niches, and write stories that I doubt a nonscientist writer could’ve found. I frequently conduct 15-minute interviews that would take an English major an hour to get through, because the source and I share a common, high-throughput language. Even on stories I haven’t covered before, I can often cut a direct path to the background and sources I need to get up to speed. That’s not to say I’m better than non-PhD journalists, just on a different beat. I get jobs they probably couldn’t do and wouldn’t want, and vice-versa. There’s room for all of us.

If there ever stops being room for me, though, I won’t hesitate to change careers again. Doing research at the bench suited me when I was in graduate school, and reporting and writing stories as a freelancer suits me now. As I discussed in the previous post, business hasn’t been stellar lately, but that hasn’t been a major problem. If it becomes one I’ll move on. I won’t, however, stop being a scientist. Or a writer.

Threading the NEIDL

After two long days of shooting and hundreds of hours of editing, the American Society for Microbiology and This Week in Virology are proud to release the documentary “Threading the NEIDL.” This video provides an unprecedented (and probably never-to-be-duplicated) look inside a state-of-the-art Biosafety Level 4 laboratory. BSL-4 labs are the ones that work on the most dangerous human pathogens, and the National Emerging Infectious Diseases Laboratories (NEIDL) at Boston University is the newest facility with labs built to the incredibly strict standards this type of science requires.

As you’ll see, we were able to get a detailed view of the inner workings of the NEIDL because it’s not operating yet. It seems that opening a high-level containment lab in the middle of a densely populated city didn’t sit well with the neighbors, and lawyers and government officials are still haggling over its fate. Meanwhile, this brand-new $200 million building is mostly empty. The silver lining is that the TWiV team was able to get inside and see spaces that would normally be inaccessible to outsiders. We also tried on some BSL-4 suits to see what it’s like to work in that environment, and chatted at length with the scientists who hope to do research in the NEIDL’s containment labs if and when they open.

The video ends on a positive note about the need to study dangerous pathogens, but it’s not a promotional piece. Community objections and BU’s handling of them get some coverage, and we went into more detail about those controversies in the associated podcast episode we released back in September. I’m still not convinced downtown Boston was the best place to stick the NEIDL. However, it does seem to have been built well, and I’d really hate to see a nine-figure sum of NIH funding flushed down the toilet now that the deed is done. Check out the video and make up your own mind:

Betrayals of Trust

I wish I’d been wrong about polio eradication. Really, I do. Against the ever-extending deadlines, outbreaks of vaccine-associated poliomyelitis, and deadly violence, there’s no comfort in having anticipated failure.

Way back in 1997, when Vincent Racaniello and I penned the first major scientific criticism of the World Health Organization’s polio eradication campaign, we were actually naïve enough to think that our objections might make a difference. Instead, we were waved aside and assured that everything would work out fine.

But the goalposts had already started moving. The original plan was to eradicate polio by the year 2000. When Vincent and I wrote our critique of the campaign’s reliance on oral polio vaccine (OPV), the WHO had already adjusted the deadline to 2005. As that year approached, the date slid further. Bill Gates now thinks that his foundation can help the WHO finish the job by 2018, continuing a longstanding tradition of keeping the goal at least five years in the future.

Don’t get me wrong, there is a chance we might eventually eliminate this virus. There’s even a tiny chance we might get it done with just OPV, but I wouldn’t bet a dollar on it, let alone the billions of dollars the WHO’s funders have pumped into that dream.

The problem is that OPV, originally developed by Albert Sabin, contains live attenuated viruses that routinely revert to wild-type, paralytic strains in vaccinated people. It’s the only vaccine in general use that can cause exactly the disease it’s meant to prevent, and it does so in one of every few million vaccinees. For the eradication effort, a bigger problem is that many, if not all vaccinees secrete the reverted virus for some time. Kids take the vaccine, and a few days later they’re pooping out live, potentially paralytic virus. That’s not a big deal if everyone around them is vaccinated, but in areas where vaccine coverage is spotty it can – and does – lead to outbreaks of polio caused by vaccine-derived strains.

There’s no obvious way to end an OPV-only campaign. People with immune disorders can excrete vaccine-derived poliovirus indefinitely. Eradication mandates eliminating OPV because it’s a source of new infections, but if we stop vaccinating then the existing reservoirs of infection will start new outbreaks. That’s why even the eradication campaigners now admit, more than a decade after we told them so, that switching to the inactivated vaccine may be an essential step.

Unfortunately, inactivated polio vaccine (IPV) is much more expensive to make, transport, and administer than OPV. The price differences aren’t noticeable in developed countries with plenty of pediatricians, but they become prohibitive if your goal is to vaccinate the whole world right now. Getting IPV to every child would require building a functional public health infrastructure everywhere, but we can get OPV to them without having to make that commitment.

In other words, the WHO and its supporters have made a deliberate choice to value the quick elimination of a single disease over establishing lasting improvements in public health.

Back in 1995, when I first heard a presentation about the eradication campaign from a WHO/CDC representative at a conference, the rationale was that eradication is much easier to “sell” to developing countries than the hard, unglamorous work of building public health infrastructure. Eliminate polio in five years and you can claim a distinct, easily defined victory. Spend the same time and money building rural clinics and covering urban sewers, and nobody will notice. I was told that polio eradication was an achievable goal that politicians could understand. I also inferred the subtext: that it was the kind of career-defining accomplishment that WHO and CDC officials would love to put on their resumés. I had a problem with that rationale then, and I still do.

I’m certainly in favor of people advancing their careers, and I’d love to see infantile paralysis eliminated from the world. Public health is chronically strapped for cash and people, though, and pouring huge sums and millions of person-hours into a quixotic charge against one disease inevitably entails shortchanging other, more pressing needs.

There’s also another price that’s only become clear recently. In order to make the eradication campaign work, the WHO has enlisted thousands of volunteers all over the world. The Rotarians committed themselves to the effort early, and have provided an astonishing amount of logistical support. But in the last polio-endemic countries, the real ground troops are local volunteers, mostly women, who’ve had a short course in vaccine delivery. These dedicated individuals are motivated by nothing but a desire to help their neighbors. Their reward is a mother’s thanks, a child’s smile … or a bullet:

Nine female polio vaccinators have been killed in two shootings at health centres in northern Nigeria, police have told the BBC. In the first attack in Kano the polio vaccinators were shot dead by gunmen who drove up on a motor tricycle. Thirty minutes later gunmen targeted a clinic outside Kano city as the vaccinators prepared to start work.

Some Nigerian Muslim leaders have previously opposed polio vaccinations, claiming they could cause infertility. On Thursday, a controversial Islamic cleric spoke out against the polio vaccination campaign, telling people that new cases of polio were caused by contaminated medicine.

This is the latest in a string of such killings, but it’s the first I’ve heard of in Nigeria. It’s become fashionable to blame the CIA for causing this spate of anti-vaccinator violence, but as I’ve pointed out before that’s an oversimplification. The latest incident underscores that point.

If any agency is to blame for these deaths, it’s the WHO. They’ve recruited women to do a job that makes them stand out, in places where armed religious fundamentalists fly into a rage whenever women stand out. Then the WHO has trained these women to administer a vaccine that can cause the very disease it’s meant to prevent. When a local cleric claims that new cases of polio were caused by “contaminated medicine,” what are these volunteers supposed to say? He’s sort of right. Finally, all of this is being done in the service of a public health campaign that’s probably doomed. Meanwhile, malaria, tuberculosis, and HIV remain rampant and vaccines for other preventable diseases can’t be distributed because of a lack of infrastructure.

Perhaps it is much easier to convince politicians to back an eradication campaign than to build real public health systems. But it’s not cheaper.

Who’s Afraid of the Big, Bad ORF?

A recent paper in the journal GM Crops and Food has generated an outsized splash in the press, particularly in biotechnology-averse Europe. I won’t reward a muckraking tabloid with a link, but here’s a screenshot that shows the basic theme:

Daily Mail hype.

Oh No, Toxic Genes!

Apparently the genetically modified food crops that hundreds of millions of people around the world have been eating without incident for more than a decade are in fact horribly toxic. But it turns out that the research that triggered this alarm proves no such thing. How did an arcane scientific finding get turned into a completely incorrect, apocalyptic headline? Let’s dig into it like scientifically educated journalists.

If we start by going to the source, we immediately hit an obstacle: there’s the abstract, but if we want to read the paper itself we’re expected to pony up $29. It would probably help a lot if journals made papers about important public policy issues freely accessible by default, but we don’t live in that world yet. Fortunately, journalists have an easy way to get around this: contact the authors directly. The Daily Mail appears to have failed at this, as all of the quotes in their article are from other sources. Other articles on the new work similarly lack any representation by the folks who actually did it.

It’s rare for scientists to blow off reporters completely, but sometimes they can be hard to reach, out of the office until after the deadline, or just uninterested in helping. Perhaps that was the case here. Let’s see. The first author is Nancy Podevin of the European Food Safety Authority in Parma, Italy. When I sent a note to her identifying myself as a journalist and asking for a reprint, she replied minutes later: “Please find the article attached. Please be aware that the content of the article has been incorrectly reflected in recent press articles.”

Not exactly hard to reach. Or reticent.

Alright, let’s dig into the work. Here’s the basic plan from the introduction:

Bioinformatic tools are increasingly being used in the evaluation of transgenic crops. Guidelines, proposed by WHO/FAO19 and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity and toxicity. With this aim, the EFSA GMO Panel has updated its guidance for the risk assessment of GM plants and proposed to identify all new ORFs due to the transformation event. New ORFs are defined as strings of codons uninterrupted by the presence of a stop codon at the insert genomic DNA junction and within the insert. The putative translation products of these ORFs are then screened for similarities with known toxins and allergens.

This is a study done entirely on computer databases, in which the scientists looked for novel open reading frames (ORFs) in the transgenes of modified crops, then checked to see if any of those ORFs match any known allergens or toxins. The existence of an ORF doesn’t prove that it gets transcribed and translated into a stable protein, so we’re still several steps short of reality here, but it’s a useful exercise to define what might be possible. In this case, the investigators are looking specifically at a sequence called P35S, a gene promoter borrowed from cauliflower mosaic virus (CaMV). P35S promotes constitutive (constant) expression of the gene in front of it, so it’s been a popular choice for driving introduced transgenes in genetically modified crops. 54 of the transgenic crop strains currently approved in the US use this promoter.

In its original context, the P35S sequence overlaps with a CaMV sequence called gene VI. That means that the P35S sequence could potentially encode a piece of gene VI. Podevin and her colleague Patrick du Jardin searched the various P35S sequences used in transgenic crops, and identified a couple of ORFs. Remember, this is all on a computer. The paper contains no wet lab experiments showing that these ORFs are actually producing stable proteins in any cell. But let’s assume they do for now.

Translating those ORFs on the computer and searching against databases of known allergens and toxins, the researchers found … wait for it …

Nothing.

That’s right, these hypothetical proteins that might not even exist don’t match any known allergens or toxins anyway. They did an additional test that sets the bar lower, and found that by this standard, one of the putative proteins might be allergenic. But it’s a stretch:

The vector support machines (SVM) in AlgPred indicated on the basis of the dipeptide composition that the ORF that encoded part of P6 might have some allergenic properties. The sensitivity and specificity of this method is 88.87% and 81.86% respectively and should therefore always be used in combination with other tools.

All the other tools, though, found no allergenicity. Having established that there’s essentially no human risk, the authors speculated that there could still be effects on the plants themselves, such as plant stunting and late flowering. Considering that the entire point of most crop biotechnology is to increase yields, it seems unlikely that this applies to any of the current commercial strains, but product developers should probably keep an eye out for it in future strains. Either that, or they could simply follow the authors’ final advice:

The -343 variant [of P35S], identified by Odell and colleagues, contains all of the necessary elements for full promoter activity and does not appear to result in the presence of an ORF with functional domains, rendering it and its related variants the most appropriate promoter variants for avoiding unintended effects.

To put this all in context, plant viruses commonly infect all sorts of crops. One survey (PDF here) found CaMV and its colleagues widespread in numerous types of produce. We’re already eating huge quantities of plant viral proteins – not hypothetical ones, real ones – all the time. If there is an ORF from CaMV gene VI being expressed as a protein in transgenic crops, it’s likely one you’ve digested before, even if you eat exclusively organic food.

So there you have it. This was a research paper that used bioinformatic methods to ask yet again if GM crops are any more dangerous than non-GM crops. It ended up adding to the large pile of established data showing that they are not. Through what can only be described as laziness and ideologically blinded reporting, it served as a handy news hook for stories claiming exactly the opposite.

Update 2013.1.22 12:49: After writing this post, I saw this discussion thread, in which several smart folks make essentially the same points.

Update 2013.1.23 7:07: After Dr. Podevin graciously sent the paper, I pinged her with a few additional questions about the work because, well, that’s what I do. I received her reply this morning:

I have been overloaded with requests for the paper and as I am no longer working at EFSA it is difficult for me to react.

To answer you[r] questions I am not planning to work on this topic further. It is difficult how headlines on toxic genes in GMOs can be seen to be linked to our paper as we concluded that there are no indications for toxicity of the encoded protein. This virus has been infecting Cauliflower and related plants with no recorded health effect.

It should also be noted that this promoter [has] an ORF overlaps with Gene VI but that no functional gene is present. So in most cases this gene fragment will not lead to the production of a protein.

Update 2013.1.24 15:06: I’ve now received a note from the journal publisher as well:

I am the publishing director at Landes Bioscience – and for GM Crops & Food. Thanks for your excellent piece which was just brought to my attention. Would also quickly like to note that we have now made this paper OA, ie, freely available to anyone who wants to download and read. [link]

Do These Stripes Make My Nanoparticles Look Weird?

There’s something interesting happening in the staid world of peer review these days, and a recent set of posts on another site renewed my hope that it could be a positive trend. Raphaël Lévy at the University of Liverpool starts off the first post this way:

Challenging published results is an onerous but necessary task. Today, our article entitled Stripy Nanoparticles Revisited has been published in Small, three years after its initial submission to this journal (3/12/09) and about three and a half years after the first submission (to Nature Materials, 21/07/09).

As its title indicates, the article challenges the evidence for the existence and properties of “stripy” nanoparticles.

That, and a followup post from another nanoparticle researcher, are interesting reading just for the underlying science. Both researchers do a good job describing the techniques for creating and studying these very tiny structures, which could be useful for all sorts of cool engineering tricks. One intriguing characteristic of these nanoparticles is that they can apparently cause certain types of molecules to self-organize into precise patterns of stripes on their surfaces. At least, that was what earlier work had shown. Lévy, however, thinks this stripy pattern is an artifact, the microscopic version of an optical illusion.

On its surface, this looks like a very small controversy in every sense of the word. Who cares whether a few minuscule spheres mixed with some odd chemicals are striped or smooth or bumpy or dancing the hokey-pokey? I’m certainly not qualified to take a stance on the issue, and it’s hard to see any immediate relevance to my life, but seemingly arcane disputes like this drive much of the scientific enterprise. Get the details wrong on stripy nanoparticles, and maybe we can’t build the next generation of computers. We won’t know why it matters until suddenly it does.

The classic quality control system for scientific facts is peer review, in which scientists submit their work to journals, which distribute the paper to anonymous colleagues of the author for independent analysis. If the author’s professional competitors agree that the new findings are significant and probably correct, then the journal will publish the paper. Peer review always has been a deeply flawed system, plagued by academic politics, errors, and inefficiency, but until recently nobody could come up with a better one.

The World Wide Web changed that by design. It’s easy to forget that the whole online ecosystem we now take for granted originated from a scientist’s frustration with paper-based publishing. YouTube, Amazon, Facebook, and their ilk are merely side-effects of a platform built expressly for reporting science. Now, decades later, researchers are finally starting to appreciate the full depth of what the Web can do for peer review. Lévy and his colleagues are part of that trend. Ironically, they still have to combat the perception that the internet is somehow an inappropriate venue for this. A system built for science is now synonymous with shopping, ranting, and porn in many people’s minds.

What I find most interesting about the stripy nanoparticle conversation is that it has the generally civil tone, moderate pace, and narrow scope of classical peer review. There are lots of other examples of this type of “post-publication review” online, but the ones that draw attention are usually as much about public relations as they are about data. Reading the comments on Lévy’s blog, I’m mostly struck by how thoughtful and well-informed they (mostly) are, and how many of the participants genuinely seem to care more about getting the right answer than winning. That’s how it’s supposed to be done. That’s science.

High Fructose Corn Syrup: Hard Questions, Easy Answer

If you’ve read anything about obesity and nutrition in the past few years, or paid any attention to food packages in the supermarket, you’re aware that there’s a bit of a controversy surrounding a sweetener called high fructose corn syrup, or HFCS. By “a bit of a controversy,” I mean a continuously escalating shouting match involving two extreme, opposing views and a whole lot of ambiguous data.

In one corner, we have a few researchers and a lot of foodies who argue strenuously that HFCS is a major cause, if not the sole cause, of the global pandemic of obesity, diabetes, and “metabolic syndrome.” Opposing these advocates is a multi-billion-dollar government-subsidized food processing industry, heavily invested in producing HFCS-laden products, claiming that the stuff is completely harmless and safe. In between are a lot of scientists genuinely trying to figure out a knot of apparently conflicting study results. Meanwhile, the general public would really appreciate some clear answers before it’s time to serve dinner.

Biochemical conversion of fructose to glycogen.

Fructose, in its usual role of torturing biochemistry students while forming glycogen.

The underlying questions in this debate are very hard to unravel, but this is an unusual instance where most of us can simply disregard all of that and make a simple, obvious choice based on sound risk analysis. Here’s why.

The scientific evidence on HFCS is all over the map, contrary to what advocates on both sides would have you believe. There is no clear proof that this stuff is safe, and no clear proof that it isn’t. Instead, we have a whole lot of suggestive, circumstantial evidence that HFCS might be bad for you, and a whole lot of suggestive, circumstantial evidence that it might not. Many anti-HFCS advocates point to the timing of the sweetener’s introduction, as it became prevalent in the global food supply at exactly the same time we started porking up. On the other hand, the same period saw widespread adoption of cable TV and then the internet, a decline in manufacturing and rise in sedentary work in developed countries, a steady decrease in sleep, and so on. Trying to look at this in more detail, a team of scientists recently completed a huge analysis of multinational data sets, and found that nations with high HFCS consumption rates also have relatively high rates of obesity and metabolic syndrome, even when matched for other traits. However, HFCS consumption could simply be a surrogate marker for processed food consumption, and in any case this particular study doesn’t prove much.

Mechanistic analyses have been similarly ambiguous: feeding rats a diet rich in HFCS can cause them to gain weight, but rodent metabolism differs radically from human metabolism. The most rigorous studies in humans have involved isocaloric diets with either HFCS or sugar as the primary sweetener, and found no difference in weight gain. Isocaloric diets are misleading, though. Outside of controlled clinical trials people eat until they’re full, and there are sound biochemical reasons to believe that our satiety circuits may not register the excess fructose in HFCS the same way we register the breakdown products of sucrose. If HFCS-laden food makes you feel less full for a given number of calories, it could prompt you to eat more. But that’s just a theory.

These mud-clear data haven’t stopped some folks from taking strong stances on the issue. I’ve even been guilty of overinterpreting studies that agreed with my preconceived notions at the time, and my wife is entirely sold on the idea that HFCS is liquid evil. More broadly, authors of papers like the new multinational analysis haven’t shied away from hype-enriched press releases, and of course the deep-pocketed industry making the product is guilty of exactly the same behavior. Both sides repeat their mantras (“It’s nutritionally equivalent to sugar,” “Is not,” “Is so…”) while ignoring all evidence to the contrary. The stakes are astronomical, so the screaming is quite loud.

As I said, though, there’s a very easy way out of this discussion. HFCS contains no essential nutrients. It occurs in no staple foods. It is completely unnecessary in anyone’s diet. Unlike some other controversial foods, there is absolutely no reason to consume this one. So don’t. This is a rare case where the risk-benefit analysis contains absolutely nothing in the benefits column. That means any risk, even a theoretical one, justifies avoiding this substance.

It may sound like I’m endorsing the “HFCS is bad” position, and certainly I have domestic reasons to go along with that, but I’m not. I honestly don’t care whether HFCS is bad for me. All I need to know about it is that it’s a diagnostic marker for junk food: if the product contains HFCS, it contains empty calories, was manufactured as cheaply as possible, and almost certainly tastes fake. Some of the same criticisms apply to sugar, but not all. Sugar is an ancient and sometimes necessary preservative, it’s never used as a low-cost option where HFCS would do, and it’s quite hard to run a kitchen without it. I can only cut back on sugar, but I can avoid HFCS entirely.

The dietary impact of eliminating HFCS is all good, even if we ignore the recent studies. Sodas and other sweets made with sugar are uniformly more expensive than similar products made with HFCS, so there’s an instant incentive to cut back on them. Highly processed entrees may contain it, but a meal made from scratch (which often cooks up just as fast as a TV dinner and tastes vastly better) doesn’t. Whether or not HFCS bypasses my satiety circuits, I’ll probably put fewer calories on my plate when I’m avoiding it, and the calories I do consume will automatically skew a bit more toward the nutrient-rich foods every dietitian advocates.

“But what about the poor?” comes the cry in every food discussion. Well, what about them? In the developed world, the days of the starving poor are long gone. Now, poverty correlates quite strongly with obesity. If avoiding HFCS prompts poor people to consume fewer but more nutrient-rich calories, that’s a big step in the right direction. The picture is more complicated in developing countries, many of which are struggling with simultaneous epidemics of obesity and starvation, but even there it’s unlikely that the empty calories of HFCS are helpful. People need food, not Coca-Cola.

To be clear, I’m not advocating any kind of legal ban on HFCS. Legislation and regulation should always rest on sound evidence, and we don’t have that here. However, if more people avoid this sweetener by choice – and both industry data and package labeling suggest that’s the trend – a much more powerful force will decide the issue: the law of supply and demand.

Single Molecule Determines Complex Behavior, Say Scientists

In a groundbreaking new study, scientists at Some University have discovered that a single molecule may drive people to perform that complex behavior we’ve all observed. Though other researchers consider the results of the small, poorly structured experiment misleading, a well-written press release ensures that their criticisms will be restricted to brief quotes buried near the bottoms of most news stories on the work, if they’re included at all.

“This is a real game-changer for our understanding of this complex behavior, which has affected so many lives,” said Wannabe Famous, PhD, who directed the study. Dr. Famous describes the results, which were hyped relentlessly to journalists for a week before being published in today’s issue of A Scientific Journal, as “the Holy Grail of a field that has been trying to link this single molecule to a complex behavior for decades.”

Though he cautions that the findings are too preliminary to be a basis for any specific recommendations, Dr. Famous says that drugs targeting the single molecule could some day help treat patients displaying this complex behavior. “It’s a controversial issue, because of course complex behaviors are what make us human, or at least animal, but for people dealing with the broken marriages, inadvisable purchases, and stained kitchen tiles that this behavior can cause, a workable therapy would be a blessing,” said Dr. Famous.

The new results add to a growing body of evidence that all of human nature rests on a handful of chemical reactions. Researchers initially believed that the widely-acknowledged link between testosterone and carpentry was a fluke, but studies connecting dopamine to scuba diving, and oxytocin to the production of cat videos on YouTube, have drawn more attention to the seductive power of oversimplifications. “We’re really standing on the shoulders of giants,” said Famous.

Other scientists agree, at least when quoted selectively. “Famous’s result is just unbelievable,” said one researcher, who asked not to be named after seeing a draft of this article.

Nonetheless, controversy persists in the field, especially among those whose statements are harder to misconstrue. “This single molecule has a bunch of different functions, most of which we probably don’t even know yet, and there are thousands of other signaling molecules circulating in the body at any given time, so claiming that it’s the sole cause of this complex behavior is just absurd,” said Grumpy Skeptic, PhD.

But Famous remains undaunted, and argues that his results will ultimately stand on their own whether other researchers replicate them or not. “Ten years from now, if you ask someone whose science education consists mainly of skimming news stories, I’m sure they’ll confirm that this single molecule causes this complex behavior,” said Famous.

Political Science

As the shoutfest The Onion fittingly dubbed “The War for the White House” staggers towards its storm-soaked climax next Tuesday, there’s one fundamental question that I don’t think has really been answered yet:

Why are scientists such raving liberals?

Obama Banner

Yes, science moves in that direction too.

We can’t deny that we look that way to the general public. Nature, which is to science what the Wall Street Journal is to investment banking, unabashedly endorsed President Obama for re-election. Sixty-eight Nobel laureates signed an open letter making the same endorsement. If you follow scientists or science journalists on Twitter, your feed will seldom go an hour without someone advocating Democratic policies or candidates. And by the highly polarized standards of our time, voting for Democrats automatically constitutes raving liberalism, as surely as voting for a Republican is diagnostic of reactionary wingnuttery.

Never mind that “scientists” are far from homogeneous. We’re a group whose principal unifying traits are independent thought, distrust of authority, and a love of intense, arcane arguments. We will agree – slowly, grudgingly – to certain broad, general principles, but only in the face of overwhelming evidence. Even then, the “scientific consensus” inevitably contains thousands of small but intense disagreements about the details. Virtually every biologist worthy of the title will concur that complex life evolved from simpler life, and continues to do so, but if you ask whether this particular species diverged sooner or later than that one, or even what the word “species” means, you’ll immediately see taxonomists disemboweling each other. So how can we possibly have a unified political agenda?

We don’t, of course. Talking to scientists is a big part of my job, and when specific policies come up, the conversation inevitably reveals diverse and unpredictable opinions. Scientists in industry sometimes sound like good Republicans, advocating smaller government, less regulation, and unrestrained markets, while academic researchers sometimes favor more government funding, stronger regulations, and less industry involvement, like stereotypical Democrats. Other times it’s the reverse, and the same scientist commonly appears on different sides of the aisle on different issues. Like taxonomists debating the proper classification of a grasshopper, we’re all over the map.

There’s also some diversity in scientists’ assessments of the two major political parties, but in broad, general terms the group leans toward the Democrats. Some have theorized that this is because Democratic candidates are more likely to understand (or at least purport to understand) the complexity and nuances of major policy questions, whereas Republicans prefer pat slogans that oversimplify the issues, and scientists understand that oversimplification is dangerous. I think that’s bullshit. Bumper stickers that proclaim “Healthcare is a human right” are no less jingoistic than “Abortion stops a beating heart.” Both are willfully deceptive oversimplifications.

Nor does either side’s constituency have a monopoly on the rational treatment of data. If you like to ignore the overwhelming evidence that humans are changing the global climate, odds are you vote with the red states. But if you irrationally oppose genetically modified crops, then I’ll bet the donkey is your mascot. Anti-vaccine advocates, animal rights groups, and the anti-psychiatry movement also draw mostly from the left side of the aisle. Indeed, I suspect that if we held a big conference for everyone who advocates profoundly irrational policies, we’d draw a solid Democratic majority.

Given the blatant stupidity on both sides, you might expect scientists to just throw up their hands, pick randomly, and say “don’t blame me, I voted for Kodos.” I know some who do. There is, however, one crucial difference between the two parties, at least in their current incarnations. Considering what I said a few paragraphs ago, I certainly wouldn’t presume to speak for all scientists, but this difference is the main reason my own voting record has favored Democrats, and I suspect others may have reached similar conclusions.

Political parties are like dysfunctional families. Everyone has a few crazy cousins somewhere, so the question is how to deal with them. The Democratic party tolerates but marginalizes its anti-science crusaders. The Republican party hands them the keys. That’s why the Bush administration and Republicans in Congress neutered the EPA, obstructed any meaningful environmental legislation that came up, and hamstrung public health agencies and some branches of research. Their crazy cousins didn’t like what the science was saying, so they banned it. When Obama was elected, he came into office with a commanding majority in Congress. If the two parties were truly equivalent in their stupidity, we would have seen vaccination, genetically modified crops, and animal research in the crosshairs. Instead, the Democrats nodded and smiled at their crazy cousins, then went about enacting (mostly) rational and moderate policies in all of those areas.

I don’t think this comparative Democratic rationality is deliberate. Instead, it stems from the way the two parties operate. The GOP is a carefully engineered political machine, which is why it’s so frighteningly efficient when its candidates gain power. By grabbing a few critical levers, a small, unhinged minority can take control of the whole juggernaut, and that’s exactly what we’ve seen in recent years. The Democratic party is more of an amoeboid organism, sending out pseudopodia in all directions, averaging the inputs from innumerable signals, and finally crawling in a specific direction for a short distance before repeating the whole cycle. It’s slow, inefficient and cumbersome, but very unlikely to run off the rails.

If that sounds like faint praise, it’s because it is. Should the Republicans ever hand the controls over to scientists, do a teardown on their platform, and adopt consistent, evidence-based policymaking as their primary ideology, I’d be thrilled to join them. Until then, I’ll be voting for these folks.

From Immuno-PCR to Peptoids: Why Great Ideas Sometimes Aren’t

From the inbox last month:

Dear Dr. Dove:

Just curious. Do you really think Kodadek’s Cell paper is a good piece of work? The response of the science community to this seemingly amazing news is silence. This usually means that the results of the paper are odd.

Wang fan

Thanks for your note, Wang, and I’m sorry it’s taken me a month to get back to you. This question touches on some much broader issues in science and science journalism, and I wanted to take the time to put together a proper blog post about it. For readers who don’t know the background, here is my original post about Kodadek’s work, in which I unabashedly raved about a novel technique for discovering new disease biomarkers.

I stand by that assessment. The researchers performed an extremely clever experiment, it apparently worked, and they followed up on it pretty carefully. That’s what science is supposed to be about.

So why isn’t everyone using Kodadek’s strategy to find a slew of new biomarkers already? I can think of a few possibilities. One, of course, is that the technique might be a lot harder to perform than the paper suggested. Perhaps it yields inconsistent results for different diseases. Perhaps there just aren’t good biomarkers for some of the diseases we want to study. Or perhaps people are all over this technique, and we just haven’t seen the papers yet – it hasn’t quite been two years, and these studies would take some time. It’s also possible that the method just isn’t as useful as it first seemed. These sorts of problems trip up new ideas a lot more often than even most scientists realize.

Consider, for example, the tangled tale of another biomarker detection scheme: immuno-PCR. Developed by Charles Cantor’s group way back in 1992, immuno-PCR uses the highly effective signal amplification of polymerase chain reaction (PCR) to detect proteins. The technique was supposed to solve one of the biggest problems in biochemistry at the time, which was identifying and quantifying proteins that are present in vanishingly small quantities in a sample, which certainly describes many promising disease biomarkers. Immuno-PCR was much more sensitive than the best available competitor, a technique called enzyme-linked immunosorbent assay (ELISA), and more sensitive protein assays really sounded like just the thing. The new method was poised for greatness.

But it flopped, or at least went to sleep for awhile. In 2008, I wrote a feature article for Bioscience Technology magazine about protein detection methods, and pretty much everyone I talked to agreed that immuno-PCR was a disappointment. Indeed, several companies were trying to develop a replacement that would work better. It turned out that immuno-PCR was just too hard to do properly, so most users gave up on it.

Similar problems befell David Ward and his colleagues at Yale University, who developed an equally clever protein detection system called the rolling circle immunoassay in 2000. Instead of PCR, Ward’s assay relied on a type of amplification called rolling circle replication, which many viruses use. This elegant new technique blew the doors off ELISA; the investigators could detect proteins at single-molecule sensitivity. Rolling circles were supposed to succeed where immuno-PCR had failed, but instead they also landed in the bin.

Some of the techniques developed since then have fared slightly better. A company called Nanosphere, building on work by Chad Mirkin and colleagues at Northwestern University, now has FDA approval for high-sensitivity diagnostic tests based on a nanoparticle detection system that uses DNA “barcodes” to identify individual proteins in a sample. Nanosphere’s technology apparently offers the sensitivity of techniques like immuno-PCR and rolling circles, without the same technical headaches.

While successive groups of scientists were working on these assays, though, advances in completely different protein analysis techniques made antibody-based detection somewhat less relevant. The past decade has seen astonishing advances in protein mass spectrometry, which allows researchers to identify and quantify proteins without having to make antibodies against them first. Why bother with DNA-bound immunological probes when you can simply feed your sample into a box and read a list of the proteins in it on your computer screen?

Meanwhile, we’ve learned more about protein-based assays, especially in medical testing, and it turns out that greater sensitivity isn’t always a good thing. Barcoded nanoparticles can detect previously undetectable levels of prostate-specific antigen (PSA), for example, but a growing body of evidence suggests that PSA testing does more harm than good. Making a bad test more sensitive only makes it a worse test.

Anyone who’s been a science journalist for more than a few years has probably collected a whole slew of similar stories: results that just didn’t pan out. That’s why I always try to discuss the limitations of a new paper as frankly as possible, even in the midst of an unabashed rave.

So what happened to peptoids? It’s too early to tell. Even if the technique proves troublesome, it represents a fresh approach to a question that currently looks important: what bloodstream biomarkers can we measure to diagnose and monitor chronic diseases such as Alzheimer’s and cancer? 18 months ago, peptoids looked like they might be a really cool strategy for exploring that topic. Maybe they still are.

References

1: Sano T, Smith CL, Cantor CR, “Immuno-PCR: very sensitive antigen detection by means of specific antibody-DNA conjugates,” Science, 1992 Oct 2;258(5079):120-2.

2. Schweitzer B, et al., “Immunoassays with rolling circle DNA amplification: a versatile platform for ultrasensitive antigen detection,” Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10113-9

3. Hill HD, Mirkin CA, “The bio-barcode assay for the detection of protein and nucleic acid targets using DTT-induced ligand exchange,” Nat Protoc. 2006;1(1):324-36

4. Thaxton CS, et al., “Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy,” Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18437-42. Epub 2009 Oct 19

Making Your Experiments Easier to Digest

One of the great things about being a science journalist is being among the first to hear about technologies that are cool, useful, and/or downright weird. Today, for example, I learned that the world’s leading manufacturer of artificial laboratory stomachs has released a fascinating new series of videos. You can check out their channel on YouTube, where you’ll find such gems as this brief instructional piece that covers – quite literally – the care and feeding of your artificial laboratory stomach: