Tag Archives: journalism

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.

How to Make $75,000/Year Writing (And Hate It)

I’ve gotten some good feedback on the previous post, in which I disclosed my science writing income from the past decade and a half and explained where those numbers come from. Now it’s time to delve a little more deeply into it. Here’s the graph again , this time prettified with a line over the bars:

Profit from science writing, 1998-2012.

Profit from science writing, 1998-2012.

The first thing a business-minded person will notice is that all of the numbers are positive. Unlike most ventures, my sole proprietorship has run in the black every year of its existence. That’s less a credit to my financial acumen than it is to the low entry barriers in this field; anyone with a computer and a phone can hang out a shingle as a science writer, and the checks from just a few articles will cover the office costs.

The second thing everyone will notice is the year 2005. Yes, I made about $75,000 from science writing that year. It was the last year my income exceeded my wife’s. That brings me to an important digression.

Laura and I started dating in 1995 and married in 2000, a few days after she’d graduated from the Columbia University College of Physicians and Surgeons. Contrary to popular belief, doctors do not step straight out of medical school and onto the gravy train. In fact, these days many of them never encounter anything remotely resembling a gravy train. We moved to Philadelphia that summer for her to start residency, which is to medicine what postdoctoral training is to science: an extended period of overwork and underpay, as part of a population of indentured servants without whom the rest of the enterprise could not function. We both made about the same amount for the next several years, but she worked much harder and had vastly more responsibility than I. My income stayed relatively consistent in those years, because I had a good assortment of regular clients providing regular work. Some years were a bit better, some a bit worse, but the average was adequate.

In 2003 Laura changed residency programs, so we moved back to New York. Two years later we started the lengthy, intrusive, and costly process of an international adoption. We were also paying off Laura’s student loans and of course living in one of the most expensive cities in the world. Our debts started piling up. Her income wasn’t negotiable, but it seemed that mine might be. I turned my job into a game, and decided to see how much I could make as a freelancer if I focused on nothing but money. The answer was $75,000.

In 2005, I was raking in more than I’d ever made before. And I was miserable. I pitched stories to any editor who would return my emails. I accepted assignments on any topic, no matter how dull or annoying I found it. I didn’t do anything outright unethical, but I came close. I spent most of my days hammering out text I didn’t care about. Even the fun, interesting stories for my regular clients started to annoy me. I became that guy – the one who hates his job but loves his paycheck. In the evenings, I drank.

After a year at that pace, I started to question my worth as a writer and even as a person. I had gone into this field because I thought the world needed better explanations of science. How does writing another stringer about intellectual property legislation for a throwaway trade rag feed that goal?

Midway through 2006, I was burned out. Fortunately, I also had an ideal excuse for turning away the editors who were now calling me every week: our adoption finally came through. In November Laura and I flew to China and brought home an amazing little girl. As children do, she dismantled our lives completely and reassembled them into something entirely different, and in most ways superior to anything that had come before. Those throwaway stringers may not have helped anyone understand science any better, but by making this possible they were worth every second I had spent on them.

The next couple of years were just about ideal. I still did a few of the crap jobs out of a sense of loyalty to the clients who’d been sending me that work, but by then Laura had finally finished her residency and fellowship and taken a position as an attending physician here in western Massachusetts. I didn’t have to do unpleasant gigs just to make ends meet anymore. My income shrank, but so did my liquor bill.

2008 brought the Great Recession and the simultaneous (though largely unrelated) death throes of much of the print media industry. Newspapers had been hemorrhaging money and staff for a few years already, but now the ax started to fall at magazines, even some of the niche publications I worked for. Meanwhile, nonprofits saw donations plummet, which put one of my biggest clients on the brink of bankruptcy. Freelance budgets are very easy to cut.

Those problems hurt my bottom line, but not my lifestyle. The cost of living here on the unfashionable side of Massachusetts is low, and with a wife who’s now well-employed and a daughter needing frequent attention, I’ve felt little urgency to return to the salt mine. These days, I focus on jobs that genuinely interest me. That leaves me enough free time to provide all of the services of a stay-home spouse, while still bringing home some of the bacon.

As I hope this story illustrates, “making a living as a freelance science writer” has as many definitions as there are freelancers. A handful of writers will hit the jackpot, perhaps in the lottery system we call book publishing, but most of us will bump along from article to article, making very modest profits while suffering the slings and arrows of an outrageous business model. With a lot of effort – and too much Scotch – you might be able to beat the average in this game. I don’t recommend trying.

15 Years of Income as a Freelance Science Journalist

I’ve been pondering – no – obsessing over this post for longer than I’d care to admit. On the one hand, I think it would be very useful for people considering a career in science journalism to get a direct view of the field’s financial realities. Income is the elephant in the room whenever I talk to aspiring writers. Of course anyone can simply Google “average income science writer,” and find a set of figures, but are those numbers really correct? Do they apply to freelancers as well as staff writers? How much does it vary from year to year? Has the death of newspapers and decline of magazines changed it? The simplest way to answer all of those questions and more would be to open my own books. I’m a sample of one, but I can provide very detailed data for that one, and I consider myself pretty average in most respects.

On the other hand, I’m an American man. My culture has programmed me since birth to believe that my net worth is the primary, if not the only, determinant of my value as a human being. That message was filtered through the upbringing of a Southern gentleman, through which I also learned that it is impolite to discuss one’s income, or for that matter anything to do with money, in public. If you’re rich you’ll make people feel uncomfortable, and if you’re poor it’ll sound like you’re begging. Where I come from a man disclosing his income is in the same position as a woman posing nude; it’s only appropriate in very private settings. Yes, of course I know that’s all wrong. Valuing men for their money and women for their bodies are constructs of an oppressive patriarchy, and as an enlightened 21st century feminist moderate Democrat I should reject that paradigm … yadda yadda yadda.

But it still gives me the creeps, okay?

As a result, I usually answer questions about my income with vague comparisons or outright evasions: “Last year I made about as much as a public school teacher,” or “You can make a living at it, but don’t go into it for the money.”

Lately, though, I’ve decided that disclosing this information would probably benefit others more than it would harm me. So here are the data.

Inflation-adjusted profit from freelance science writing, 1998-2012.

Inflation-adjusted profit from freelance science writing, 1998-2012.

You’ll notice that I labeled the graph “adjusted profit,” not “income.” That’s because I run a business, and the appropriate way to think about business income is in terms of profit and loss. The “adjusted” part is adjusting for inflation. These figures are in 2013 dollars. I used the handy online calculator from the Bureau of Labor Statistics because I’m in the US, but analogous tools are available for other currencies.

Side note to all journalists: always adjust for inflation when comparing money figures over time. Otherwise you may crank out idiotic stories saying “Prices for X are at all time highs!” when in fact the price of everything is almost always at an all-time high.

Even after adjusting for inflation, the profit figures aren’t exactly comparable to income you might get from a regular paycheck. Every expense that’s directly related to my work is a business cost. If you’re on a salary and you buy a new home computer, your income doesn’t change. When I buy a new computer, it’s a business expense that reduces my total profit for the year by that amount. My Internet bill, a portion of my mortgage and home expenses (because my office is in my house), and other items also count against profit. That said, profit from my sole proprietorship is the closest analogue to income in the regular paycheck-based world.

I also rounded the figures to the nearest $10 to make it impossible to back-calculate my exact income to the dollar from this graph. If you’re planning to post similar data I suggest you do the same, as one’s income for prior years sometimes pops up as a “security question” for tax and banking purposes.

Having established where the numbers come from, what do they mean? What the hell happened in 2005, for example, and what about 2010? How does one adapt to an income that can swing up and down so wildly? What about health insurance and retirement savings? I’ll delve into those questions in a later post. Right now, I need to go put on some more clothes.

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]

Sentient Spambots vs. Journalism

As a blog owner, I get a lot of spam. Of course my automatic filters weed out the usual ads for anatomical enlargement, financial offers from alleged Nigerian clergy, and suggestions to earn advanced degrees from diploma mills, but in recent years a new category has cropped up, and it’s getting harder and harder to classify it.

Consider the infographic link spammers. These folks use standard online tools to create some marginally interesting illustration, then promote it to any blogger who covers even tangentially related topics. The infographic includes code that helps direct traffic to another site, helping them increase their search engine rankings. I haven’t posted any of these, partly because I’m not into running other people’s ads for free, and partly because the graphics tend to be gimmicky, often misleading representations of questionable data. All the ones I’ve received have included links to “get your degree online” types of sites, which are themselves just extended advertisements for diploma mills. So as an evolutionary byproduct of their efforts to circumvent ever-more-sophisticated filters, the University of Phoenix’s spambots have finally achieved sentience.

Recently, though, I got a note that’s pushed this trend even further, to the point that it’s right next door to legitimate journalism:

Hello,

I help maintain the site [name similar to Diploma-Mills-R-Us.com], and I am writing to let you know about an article we have created that shares essential information on the 2012-2013 Flu Vaccine. You can view part 1 here: [link, to which I’ve added a nofollow tag].

As you may already know, it is flu season and as the seasons change, the weather gets colder and many people start feeling under the weather. The article offers guidance and information on how and why you should get the vaccine and the effects it may have on your health.

We’re trying to spread the word about this article, and hopefully spread awareness on this subject as many people today are still not getting their flu vaccine and having to pay the consequence. So, if you find it to be useful and interesting, and think others would too, I’d be thrilled if you would share it with your readers, or anyone else you think could benefit from it.

The linked post rehashes information that’s easy enough to find elsewhere, but it isn’t a simple copy-paste job. The author actually created original content, summarizing an important issue and promoting public health. My only real objection to it is that the sponsoring site exists solely to sell dubious training programs for healthcare practitioners.

I can’t get on too high a horse about that, though. Most of the publications my colleagues and I write for make a significant amount of their money from advertising, and for many of them (“controlled circulation” trade magazines, virtually all news web sites) it’s the only revenue source. All of my clients are diligent about maintaining a firewall between the advertising and editorial departments, so the former never directly influences the latter. Reduced to its essence, journalism’s business model is to draw readers to original, independent, useful content, and pay for it by showing them some ads at the same time. The main distinction I see is that at “legitimate” news outlets the content is viewed as the primary product, and the ads as a sort of necessary evil. For sites like the one above, the ads are the main point, and the original content is just eyeball bait. It’s largely a question of intent.

In practical terms, the problem with the latter model is that there are certain types of stories that, while highly relevant to the target audience, could never be permitted to appear there. For example, I wouldn’t expect an unbiased investigative report on the business practices of online degree programs from a site whose existence depends on them. Similar conflicts can arise at traditional news publishers of course, but keeping a diverse stable of advertisers mitigates them, and a business philosophy that values content for its own sake tends to discourage serious abuses.

While I don’t expect the spammers to make the final step in this journey and turn themselves into legitimate journalists, I can’t help wondering whether we’re living in a version of this xkcd comic.

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.

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

Unleashing the Ferrets of Fear

The second of two controversial papers on H5N1 “bird flu” came out yesterday, and if you didn’t hear about it, it wasn’t for lack of publicity. Not only did journalists get the usual embargoed access to the paper at the beginning of the week, we also got a whole package of related commentary and an invitation to a high-powered press conference with the lead researchers, the journal’s editor, and other luminaries. Even before this week, people were leaking information about the new results like Julian Assange on a bender.

I considered working up a whole post on this research and scheduling it to come out when the embargo expired, but besides being snowed under with paying work, I knew that such a post would probably disappear in the noise. Instead, I just waited for my friend and TWiV co-host Vincent Racaniello to put up his summary and analysis, which I expected would be excellent. It is, so go read it now if you haven’t already. I’ll wait.

Unfortunately, the bad reporting on this topic also appeared right on schedule. Here, for example, is The Telegraph’s take on the work:

Headline: Bird flu pandemic just “three mutations” away, scientists show

A bird flu pandemic may be close to being a real threat after scientists discovered the virus is already just “three mutations” away from evolving into a strain which would be able to pass from human to human. Avian H5N1 influenza can currently only be transmitted to humans from birds, meaning it cannot spread quickly through the air between large groups of people. But a recent study at Cambridge University shows that there are strains already existing which are just “three mutations” away from being passable form one human to another.

You know what the problem is here? Rhetorical vomit. There’s a lot of it in the world, from political bumper stickers to fear-mongering headlines. Just like real vomit, it takes only seconds to splatter out into the world, and anyone who sees it can’t help but notice and be affected. It’s also contagious; when we see vomit, we want to. We can’t help it. It grabs us at a visceral level, and leaves our conscious minds struggling to catch up with a more reasoned response. When that finally happens, the cleanup takes far longer than the hurl, and it’s very difficult to erase the original impression.

But there it is, pooling on the floor, sticking to the couch, and stinking up the room. And now that reporters like The Telegraph’s Richard Alleyne and Nick Collins have spoiled lunch with that mess, someone has to get out the mop and clean it up. Fine.

Let’s begin by understanding the requirements for a new flu pandemic, starting from an influenza strain that infects birds. First, the virus needs to adapt to a point where it can transmit efficiently from one human to another. Humans are very different from birds, so that’s going to take some mutating and selecting. Second, it has to retain enough virulence that we actually need to worry about it. A virus can be highly transmissible without being a major concern. Cytomegalovirus infects half of the world’s adults, but odds are you’ll never know you have it. Finally, a pandemic flu virus needs to encounter an immunologically naive human population. That’s a serious hurdle that keeps getting higher. For example, if you had the 2009 H1N1 “swine flu” or got the vaccine against it, there’s a good chance you’re now also immune to the dreaded 1918 flu. If a lot of people are similarly cross-immune to some newly mutated H5N1 strain, the pandemic will fizzle.

In the new studies, researchers found that H5N1 flu has to undergo at least five separate mutations from its ordinary bird form in order to be transmissible through the air from one ferret to another. Ferrets aren’t people, but they’re a bit closer to us evolutionarily than birds are. Looking at isolates of H5N1 that have appeared so far, we see that two of those five mutations have already occurred in nature. The Telegraph’s story appears to be discussing an extension of those findings, in which some of the same scientists used mathematical modeling to gauge the potential for wild H5N1 strains to pick up the remaining three mutations, based on our current understanding of influenza biology. Like all mathematical modeling studies, that work is useful for telling us what our assumptions mean. It does not tell us what will actually happen.

So are we three mutations away from a pandemic? There’s no way to tell. We appear to be three mutations away from obtaining a strain of H5N1 that could be aerosol-transmissible between ferrets, but not lethal to them. We don’t know whether the same mutations would enable the virus to transmit between humans. We don’t know whether it would be virulent. We don’t know how much of the population would be susceptible to it.

We don’t even know how likely it is that the remaining three mutations found in these studies could ever occur in nature. Any of the numerous selective pressures on viruses in the wild could prevent them from making those changes. So far, despite infecting at least several hundred (and probably many more) humans, H5N1 flu hasn’t managed to make the jump. Have we just been extremely lucky, or does this streak of failures point to an underlying biological barrier that keeps bird flu in birds? Nobody knows.

The new H5N1 flu papers do tell us a lot, and they represent vitally important work. We now know some of the types of changes that can make a bird influenza virus aerosol-transmissible in a mammalian host. We also know that H5N1 has the potential to contribute genes to a future pandemic virus, and might even have the ability to spark a pandemic on its own. We should keep an eye on that, try to take reasonable precautions against it, and keep studying H5N1 and other flu viruses to get a better idea of what they’re capable – and not capable – of doing. In the meantime, I encourage my fellow editors and journalists to keep a bucket handy.

Yay, We Captured an Endangered Fish!

Welcome to “How to Miss The Story, Fisheries Edition.” Today’s lesson features a cheerful report from Boston’s CBS affiliate, with the upbeat human-versus-nature headline “Hanover Canoers Capture 6-Foot Sturgeon With Their Bare Hands”:

HANOVER (CBS) – Four young women made the catch of a lifetime while they were canoeing in the North River in Hanover. They pulled in a six-foot sturgeon with their bare hands. The fish, according to experts at New England Aquarium, weighted about 75 pounds. The women told WBZ-TV they first spotted the endangered fish struggling along the surface of the river and said it appeared to be dying. The women said the fish died on the canoe ride back to shore.

The women alerted the Massachusetts Division of Marine Fisheries and the Environmental Police.

The rest of the piece goes on in the same feel-good vein: the strong female protagonists tried valiantly to help, and while this fish was beyond saving, it’s great that sturgeon have made it into this stretch of formerly polluted water. There’s even a nice photo of two of these attractive young women smiling as they show off their catch, which is lying dead on a tarp in front of their canoes. Just lovely.

It seems the word “endangered” didn’t ring any bells for the reporter, who also apparently failed to call either of the enforcement agencies mentioned in the story. So let’s do the fact-checking WBZ-TV should have done.

First, we’ll see what MassWildlife has to say about Atlantic sturgeon. Three clicks on their website brings us to a convenient set of plain English summaries of the fishing regulations, in which we find this helpful table:

Massachusetts fishing regulations (excerpt).

Massachusetts fishing regulations (excerpt).

Okay, so in Massachusetts, sturgeon season is … never. Elsewhere in the regulations, we learn that it’s illegal to take any kind of fish out of the water without a fishing license, or to attempt to catch a fish that’s not in season. If a licensed angler accidentally hooks an endangered fish, the only correct course of action is to release it immediately, and by “immediately,” they mean “immediately.”

Even if these ladies didn’t know the law (and it’s pretty clear they didn’t), what the hell were they thinking? “Gee, here’s a huge fish that looks like it might be sick. Let’s haul it out of the water, dump it into the bottom of our canoe, and take it to shore – that should help it feel better, right?” But then, as the poor creature lay on hot fiberglass in an environment where it couldn’t breathe, it died. Go figure.

The real story here took all of five minutes to figure out, even if we started with no information about endangered species regulations. The next step should be to revise the article, starting with the headline, which should read “Ignorant Canoeists Kill Endangered Fish, Then Brag About It.”

Cargill Lawyers Hard at Work

Here’s an interesting press release from UCLA. It’s not so interesting scientifically – it’s just another study showing that excess fructose in the diet is probably a bad idea. What caught my eye, though, was the lengthy blurb at the top:

[Correction: Paragraph 5 of this release was changed from an earlier version to reflect that the study focused on fructose generally, not specifically on high-fructose corn syrup; that high-fructose corn syrup is not necessarily “six times sweeter” than cane sugar; and that Americans consume approximately 35 pounds of high-fructose corn syrup per capita annually, not “more than 40 pounds.” The researcher’s quote in Paragraph 6 has also been changed slightly to avoid the implication that the study focused solely on high-fructose corn syrup.]

Sounds like someone’s lawyers and PR flacks are keeping a tight watch.