Tag Archives: hype

The DSM-5: What’s Your Alternative?

Last week, Thomas Insel, Director of the National Institute of Mental Health (NIMH) made an announcement that set science bloggers and medicine-watchers atwitter:

In a few weeks, the American Psychiatric Association will release its new edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This volume will tweak several current diagnostic categories, from autism spectrum disorders to mood disorders. While many of these changes have been contentious, the final product involves mostly modest alterations of the previous edition, based on new insights emerging from research since 1990 when DSM-IV was published. Sometimes this research recommended new categories (e.g., mood dysregulation disorder) or that previous categories could be dropped (e.g., Asperger’s syndrome).

The goal of this new manual, as with all previous editions, is to provide a common language for describing psychopathology. While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever. Indeed, symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment.

As a result of the DSM’s shortcomings, Insel says that NIMH will be abandoning this classic manual of psychiatry, in favor of something he calls “Research Domain Criteria.” Under this plan, future psychiatric research will focus on characterizing and treating diseases on the basis of their underlying biology, rather than the DSM’s symptomology.

This drew loud cheers from longtime critics of psychiatry, who are legion. Here at last was a high-profile statement affirming their belief that the field’s “Bible” – and by inference the entire field – is bogus. Many news articles picked up the same angle, but that view vastly overstates what’s actually going on here. In fact, what we’re seeing is just the normal progression of medical science, in a way that should surprise exactly nobody.

Almost every field of medicine has had transitions like this. Two hundred years ago, the germ theory of infectious disease was widely considered absurd. Now we know it is fact, and infectious disease is the most definitive of medical specialties. That doesn’t mean the old knowledge was entirely useless, though; Edward Jenner developed a highly effective vaccine against smallpox without ever understanding its underlying mechanisms.

The DSM catalogues mental disorders the way an early 19th century doctor would’ve catalogued rashes. It’s probably right, and in some cases very right, about a few of them. It’s probably wrong about many more. Psychiatrists I’ve met (and the one I married) generally regard the DSM categories as a necessary evil, not a definitive reference. The “Bible” moniker is a straw man. Nobody likes the DSM, but it serves a purpose and has no obvious alternatives.

And that’s the rub. The NIMH’s brief is research, so they can reject or adopt whatever categories they like for their studies. Nobody shows up there for routine treatment of schizophrenia, or major depression, or bipolar disorder. NIMH should be using the latest neuroscience. The latest neuroscience, though, can’t tell us much about the vast majority of mental disorders, and some of the things it can tell us may turn out to be wrong. We might someday have a blood test for depression, or we might not. We can say with certainty that we don’t have one right now.

Insel’s alternative framework is nowhere near ready for prime time. Until it is, what should we do about the guy who’s running out into traffic to tell people he’s the Messiah, or the woman who is in perfect physical health, but catatonic, or the elementary-age child who can only communicate in screams?

It’s telling that some of the people calling for the death of the DSM-5 are remarkably reticent when it comes to offering alternatives. Perhaps that’s because the more you ponder the problem the trickier it gets. Tell patients with no medical training that the field’s diagnoses are largely theoretical and expect them to appreciate the nuances? Let all of the world’s con-men sell them snake oil? Tell them to come back in a few decades? Or use a deeply flawed framework that at least has a chance of being partly correct?

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]

It’s 2012.12.22: Time For a New Doomsdate

It’s about 30 minutes after the Winter Solstice now, which means the ancient Mayan calendar has officially ticked over to a new year, and thousands of doomsayers are looking a bit foolish right about now. If you’re one of them, don’t despair: I have the updated doomsdate right here for you.

Yes, that’s right, some Wise Old Ones Who Must Have Known Everything Because They Lived A Long Time Ago and Spoke Cryptically have entrusted me with their Great Secret. I know the true final date, the End of Time, the Last Day.

You see, I bought a date stamp about twelve years ago, and I knew right away that it was more than a mere office supply. Sure, this stamp would let me mark dates on invoices I sent, checks I received, bills I paid, and orders I placed or canceled, but it also encoded an end date. Rather than fill all of the available “year” spaces, the Wise Old Ones filled only a subset of them. Why?

Obviously, they meant to communicate something. And the latest year they included on this artifact was 2013. I can stamp all I like until the final day of the final month of 2013, but after that, nothing. They presupposed that nobody, anywhere, would ever want to stamp anything after that date.

39 December 2013: The world will be backordered.

39 December 2013: The world will be backordered.

My own random actions since 2000 have decoded the rest of the message, and revealed our civilization’s bizarre fate. I have answered, canceled, billed, charged, checked, delivered, entered, paid, received, and shipped various stampable items over the years, but there is one option that I have never, ever felt the need to exercise. That action is obviously being saved for last. Very last.

Carefully advancing the stamp to its last possible date, and aligning the action wheel to its only un-inked position, I reveal the terrifying truth. On 39 December 2013, the world will be backordered.

Prepare yourself.

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.

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.

The Day the Science Died

This afternoon, a coalition of influenza virologists released a statement saying that they are voluntarily suspending research on H5N1 “bird flu” for 60 days. This was in response to the Category 5 hype storm that has accompanied the publication of two papers about this virus. My previous post on this topic (and links therein) provides a quick review for those who haven’t been following this story.

I’m of two minds about the new moratorium. As a scientist, I think it’s moronic. H5N1 flu is biologically interesting, and could become a major public health concern if it ever manages to sustain human-to-human transmission. Though its lethality has probably been vastly overstated, there’s no doubt that it is capable of killing at least some people, under some circumstances. The demonstration that it’s possible for H5N1 to adapt to a mammalian host, even one that diverged from the primate lineage many millions of years ago, shows that we need to step up H5N1 research, not halt it.

However, the biodefense industry’s recent push to whip up fear has completely distorted the public’s perception of this issue. Millions of nonscientists are now convinced that the recent virus transmission work was dangerous, perhaps even foolhardy, and that terrorist groups could easily take advantage of the new findings to kill millions. None of that is even remotely true. Unfortunately, people who are in a panic aren’t capable of rationally evaluating the nuances, so the scientists who’ve been trying to defend ongoing H5N1 work are at a disadvantage. Saying they’ll suspend that work is the only reasonable public relations strategy at this point.

Around the same time the moratorium was announced, a partially overlapping group of virologists sent an open letter to the National Science Advisory Board for Biosecurity (NSABB), giving that board a thump on the head. It was the NSABB that started this whole circus, by calling for the new H5N1 publications to be partially censored. In the open letter, the virologists argue that this censorship is unjustifiably hindering scientific progress. They were apparently too polite to say that deliberately omitting data from a publication in response to a nebulous, entirely theoretical “security risk” is antithetical to the whole scientific enterprise, so I’ll do it for them.

The moratorium should help bolster public confidence in the scientists’ ability to address this issue themselves, while the letter to the NSABB lays the groundwork for a productive debate based on reason rather than fear. Hopefully, in a couple of months everyone will be able to calm down and get back to work.

The Biodefense-Industrial Complex vs. Science

I was revving up to post a long rant about the censorship of a new paper on H5N1 influenza, but my friend and TWiV co-host Vincent Racaniello beat me to it. I do, however, have a couple of things to add.

If you’re just tuning in, the short version goes like this: some researchers claim to have isolated a novel strain of H5N1 “bird flu” that is highly transmissible in ferrets, the standard animal model for human flu infection. This triggered a huge round of hand-wringing by various quasi-official groups, claiming that this information could allow some imaginary “bioterrorist” to create The Plague of The Apocalypse. Or words to that effect. Today, the authors of the study announced that they would redact some of the data from the paper to prevent that from happening.

But as Vincent explains in his post:

The article hints that details of the experiments may be made available to influenza virologists ‘with a legitimate interest in knowing them’. Who will decide what constitutes a legitimate interest? And what if a virologist, or another scientist who does not work on influenza virus, has an idea for an experiment and would like the details? Will they be denied because they are not card-carrying influenza virologists? Science often works in unusual ways, and one of them is that difficult problems are often solved by individuals from different areas of research.

In addition, the data have already passed through dozens, perhaps hundreds of hands. There are the folks in the lab who did the work, any collaborators they worked with, the peer reviewers for the papers, anyone at Science and Nature who handled the manuscripts, and of course the sysadmins for every email server connecting all of those geographically distant points. Most scientists don’t have the first clue about information security, so any terrorist who actually wanted these experimental details could probably get them. The only people who won’t have easy access to the data are precisely the folks we want working on this problem.

But why would the terrorists even bother? What the paper shows (allegedly – it still hasn’t been published) is that H5N1 can become contagious in ferrets while retaining its virulence. That certainly could be bad news for weasels who spend a lot of time around poultry farms, but it’s not at all clear what it means for the rest of us. While ferrets are probably the best animal model we have for studying influenza infection, that’s not saying much. Their track record on predicting virulence is particularly spotty; H1N1 “swine flu” is terribly deadly to ferrets, but actually less lethal in humans than most regular seasonal flu strains. There have been quite a few human cases of H5N1 already, so whatever adapting the virus can do in us, it’s already had lots of chances. We’re not dead yet.

If I were a terrorist, I certainly wouldn’t waste my time following up such a weak lead, particularly since there are so many easier, cheaper, more reliable ways to cause terror. How about 1918 flu? It’s unquestionably deadly to humans, and the full sequence – unredacted – came out in 2005. Or anthrax? Or SARS? Nature abounds with nasty microbes.

But why bother with these fickle biological agents at all? Explosives aren’t nearly as hard to work with, and from the headlines it looks as if they continue to serve terrorists’ needs quite well. Finally, let’s remember that most of the official paranoia of the past decade was brought to us by a small group of guys armed with nothing but box cutters, basic flight training, and hatred. How are we going to redact that?

The “Growing” Ham Radio Hobby – Or Is It?

The American Radio Relay League, the main organization representing the US Amateur Radio community, likes to put out predictable press releases trumpeting the hobby’s growth. Back in October, they did it again:

As the third quarter of 2011 came to a close, ARRL VEC Manager Maria Somma, AB1FM, began calculating the number of licensed Amateur Radio operators in the US, as well as the number of new licensees. “At the end of September, I saw that the number of hams in the US was high,” she said. “When I started comparing that number with other years, I found that it was an all-time high.” For the first time, there are more than 700,000 radio amateurs in the US.

Somma said these high numbers mean that hams are upgrading and renewing in larger numbers and staying interested in hobby: “These are compelling statistics and I am thrilled to see the highest number of amateur radio licensees ever!”

Is that really what those numbers mean? Just a glance at the historical data in this press release told me that the ham radio population’s increase wasn’t happening at a smooth rate. In addition, the US population has also grown over the years, so the raw number of amateur radio licensees could keep going up even if relative interest in the hobby were stagnant or declining.

When I started playing with the numbers to figure those things out, the League’s rosy picture started to fade. This graph tells the story pretty well:

Ham Radio in Decline

Ham Radio in Decline

The US population has grown at a reasonably steady rate over the past forty years, averaging somewhere around 10%. Ham radio, however, has been on a roller-coaster ride, from a 50% increase in the 1971-1981 period to a meagre 2.5% rise from 2001-2011. Indeed, the past ten years marked the first period when the ham population grew more slowly than the total population. As a result, the number of hams per 1 million Americans went from 1,402 in 1971 up to a high of 2,427 in 2001. Then, for the first time, it declined.

If we consider that 1991 was the year the US Federal Communications Commission lifted the Morse code requirement for the entry-level amateur radio license, the picture looks even worse. That lift in the 1991-2001 period likely represents the influx of people who’d always wanted to be hams, but were put off by the difficulty of passing the Morse test. Having absorbed all of that extra demand, we went back to a drop that was probably already underway (1981-1991 was almost flat). The data show the opposite of what the ARRL wants to believe.

That’s not a reason to avoid the activity, of course. I love tinkering with radios and electronics, and have no intention of quitting. But let’s stop pretending it’s the hot new thing.

RNAi: Yep, Antisense All Over Again

Yesterday, New York Times reporter Andrew Pollack covered the pharmaceutical industry’s recent rush to the lifeboats of the siRNA/RNAi ship:

When RNA interference first electrified biologists several years ago, pharmaceutical companies rushed to harness what looked like a swift and surefire way to develop new drugs.

Billions of dollars later, however, some of those same companies are now losing their enthusiasm for RNAi, as it is called. And that is raising doubts about how quickly, if at all, the Nobel Prize-winning technique for turning off specific genes will yield the promised bounty of innovative medicines.

In particular, Pollack says companies have been spooked by the apparent side-effects of RNAi:

One obstacle is that the double-stranded RNA snippets, perhaps because they do resemble viruses, can wake up certain immune system sentinels and set off an immune response.

Such responses can be an unwelcome side effect in some cases. In other cases, like in treating cancer or infections, an immune response might be welcomed — but might also obscure whether the gene silencing itself is working.

I recall someone else pointing out exactly that problem a couple of years ago. Since I’m obviously on a roll with predictions here, I’ll throw out another one: the last company standing in the RNAi field – probably Alnylam – will soon be able to buy up all of the relevant intellectual property and talent in RNAi at fire-sale prices. They’ll then restructure into a small, lean operation that will eventually make a modest profit with some niche therapies. In other words, they’ll do what Isis did.

Place your bets.