What's "beaver" in Spanish?

Nature reports this week on how the beloved Canadian beaver has outworn its welcome in Tierra del Fuego, where 50 of the things introduced in the 1940s bred like rodents will, and now number about 100 000. As intended, it it did provide a substantial fur market for the indigenous people, but had devastating consequences for the local flora and fauna. They are now looking into ways of "eradicating" the beavers. One hopes they don't import a pile of foxes or something.

While traveling in New Zealand a couple years ago, I met a guy at the hostel who had been touring through Australia. He told a story about some guys he met in a small town up in the northeast. When asked what they did fun for fun, these guys said they "go on a catshoot," by which they meant they would drive around (perhaps in varying states of intoxication) and shoot at cats with BB guns. While this sounds cruel and appalling at first, I later learned that cats were a huge problem in the rainforests there. Escaped domestic cats bred over time have become fearsome predators and unbalanced the already wonky ecosystem (what with all the cane toads, pigs, foxes, rabbits and whatnot). Which just goes to show that country people know what's good for the country everywhere you go, even if they sometimes seem like freaky rednecks.

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Small bits of news: Nature reports that biotech giant Invitrogen (who have just finished buying Millipore, Upstate, Chemicon, and maybe several other firms) have offered about US$6.7 billion for Applied Biosystems, another giant in the industry. One is reminded of beer companies, or Microsoft. Canada will partner with California in a $100 million investment into research on cancer stem cells, which will cement our positions as world leaders in this field; strategically it looks like a smart investment, and says that cancer is back in vogue with funding agencies. Scientific American reports on another important step in killing the nature vs. nurture worldview, and what one of the study's authors very cleverly refers to as "genetic nihilism."

This kind of thinking, in which one assumes that genes dictate our lives and there's nothing we can do about, is reminiscent of destiny (or divine purpose) vs. free will debates that have raged through history (and to my admittedly primitive understanding of such things, there's still no conclusive winner). Genes don't change in their sequences over the course of life, but the ways they are structured, "read," regulated, and affect our lives is very much open to input from a surprisingly wide variety of sources. Trust me, I'm doing a whole doctoral thesis on it. Not to say that every gene can be turned up or down so easily, but very good evidence is accumulating that simple things like proper diet and regular exercise can push gene expression in certain directions, which are usually considered good for the animals involved in terms of any number of health indicators.

So what we're saying as biologists, just to make it absolutely clear: Genetics rule our lives. Genetics do not rule our lives. Any questions?

The more things change...

A round of the science news reveals an equally brilliant follow-up to last week's article about drinking during pregnancy: Scotsmen show that pregnant women shouldn't be smoking pot either. What's a poor girl to do? Doctors complain about a bottle of pills called "Placebo" on sale in the US for $6/bottle (50 pills). They're right - Smarties would be way cheaper, equally damaging to your child's psyche, and, hey, if you're going to be a crap parent then you might as well go all out.

The story that most catches my eye is this one about differences seen in brain scans of homo- and heterosexual subjects. The first question I always think to myself when I read about research like this is "Why do people want to get themselves embroiled in this?" The research I do involves rats and cell cultures, not people and highly-charged issues like homosexuality and sexual arousal. I'd be scared of running a lab with so much emotional impact on people, not to mention counting on a Conservative government for funding.

I don't do brain scans, so I can't comment on this paper to the depth I could on something way less interesting (but I will inevitably end up talking about on day). But it all looks legit - there's a whole body a of research showing that men have asymmetrical brains (enlarged right hemisphere) compared to women, and these guys show differences in resting activity patterns and connectivity. However, we'll all be lot more impressed when researchers can look at a brain scan without seeing the patient and be able to predict whether they were looking at a straight or gay representative of a given sex. And why not? A group published last month on a study where they successfully predicted nouns the subjects were thinking about by their brain scans.

One of the most interesting things about the study was that subjects asked to sit and rest in a PET scanner to measure brain activity. They saw plenty in an area called the amygdala, which tends to go active in times of emotional arousal. Which is nice, because maybe it means that gay or straight, men and women are more alike than we like to think sometimes - scientific evidence suggests that either a) everyone gets nervous around doctors whilst in a brain scanner, or my preferred explanation b) left to our own devices, we all think about sex.

The Mirror of the Terminator is Still Bad News.

I don't mean to keep ragging on the English, but who was the genius that decided to name the British Military's new communication satellite network "Skynet?" We can only hope that, actually no, they've never seen Terminator 2, what an unusual coincidence that is... (uncomfortable laugh). Otherwise officers in the British Army have a worryingly dark sense of humour.

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Wired reported yesterday on the fruits of a relatively new "drug" discovery processes that might lead to new migraine meds. What is most interesting about the story is the "drugs" in question, which aren't like drugs at all. The problem with most drugs, particularly in neuropharmacology, is that they are "dirty," as we call them - they bind to many biological targets, which can make their mechanisms of action difficult to understand. This technique sidesteps that difficulty in a very innovative fashion.

Proteins do the work of cells, which is to say absolutely everything you do, and their structures are what is being coded for within our so-called "genetic code" that lies along DNA strands. Genes are "read," and transcribed to an intermediary between DNA and protein known as "messenger" RNA. This mRNA takes the message to another region, where it is translated into a protein. Another kind of RNA - RNAi - was discovered fairly recently and the subject for which the Nobel Prize in Medicine was given to Mello & Fire in 2006. In theory, they are used by cells to shut down the mRNAs of one or many specific gene(s) so they are never translated, providing a potentially much more selective and rational approach to drug design compared to pharmacology.

The neatest thing that these guys did was their homework - trust me when I tell you that mRNA is a bitch to work with. In the body, it seems to be a very dynamically regulated process, and things called RNase can break the mRNA down quickly. RNase is everywhere outside of cells, and if you're not careful when doing work with mRNA, you will find it's all been eaten at the end of your experiment. This is why we convict killers on DNA rather than RNA evidence.

This company, however, took advantage of a strange property of molecules - stereoisometry - and designed mirror-image molecules of the sugar backbones of our RNA molecules. Think of it this way - your left hand is a mirror-image of your right hand. While they are identical, you can't make them overlap. Our bodies can't digest these mirror-image sugars, but they should still bind to their target mRNAs. Which, in theory, would make them a brilliant medium for drug discovery and could provide much-needed new insight into understanding human mental health and disorders thereof.

If I had money, I would probably invest in these guys, assuming they have stock available. They just got a pile of money from Eli-Lilly to do this, too...

Keith Chen rules. Bumblebee women less so.

I was going to blog about something else, but something really stupid piqued my interest instead.

First, a tour of the science news - British researchers prove once again that size isn't everything - unsurprisingly to us neuroscientists, intelligence seems to have a better correlation to synapse number (the connections between brain cells) and complexity than simple brain size. Leading journal Nature shows it's behind the times (the New York Times, at least) by reporting that an Italian group has shown that monkeys can understand money; Keith Chen has been doing this for years as reported here. Finally, the Swiss have gone bugf#$k nuts, as evidenced by a new law prohibiting the use of research techniques that may sacrifice the dignity of creatures, which apparently includes the dignity of plants.

So on to the stupid part. I was fortunate enough to travel to England in April on the boss' tab, where I spent a couple days with friends before I headed on to a conference. England had some minor culture shock associated with it - but I enjoy drinking in public, arguments, sarcasm, cask ales and so forth. What I don't like, and call me sexist if you will, is women drinking like blue-collar alcoholic middle-aged men (particularly if they have a beer gut to match).

So that helped to explain to me this gem from the BBC, published March 26 2008(!), declaring that drinking during pregnancy might be a bad idea. You would think this was a no-brainer, but apparently not - this British woman gave birth during a pub crawl (any bets on her alcohol intake?), claiming she didn't even know she was pregnant. Tragically, the baby boy weighs only 2 pounds and has about a 50/50 chance of living. No punch line here, folks, unless you count the fact that she was dressed as a bumblebee at the time, which is significantly more sad than funny, p < 0.05.

My brother and I bitch every year that we haven't come anywhere near as far along as some futurists/sci-fi writers believed we would have by this time (It's 2008! Where's my damn flying car?!), but the Brits are just getting around to banning drinking during pregnancy. I guess it's nice to see the colonials pulling ahead of empire... but I still want my friggin' flying car.

Win Ben Stein's Esteem? Forget it.

I'm sad today.

One of the things I find most upsetting about living in this modern era is the sheer vacuousness of our role models, who - for reasons completely beyond me - are mostly entertainers. We have pro athletes that can barely string 4 sentences together (and in a post-game interview, they tend to be the same ones in every sport, from every athlete); musicians who will hold court on any subject that comes to mind (third world debt relief and seal "hunting," for example); and actors with IQs somewhere around ground floor levels. We refuse to take our lead from intelligent, educated, or even plain reasonable people.

For this reason, I used to admire Ben Stein. Best known as Ferris Bueller's teacher and host (and usual winner) of Win Ben Stein's Money, Stein is smart, well-spoken and educated. Despite having been a speechwriter for Nixon and Ford, I always had a great respect for him as possibly the only actor able to beat geeks (not just average members of the general public) on a trivia show. I mean, have you ever seen "Celebrity Jeopardy"? These people are downright idiots.

However, Ben Stein has stupidly decided to mire himself in the old creationist debate by starring in a new movie called "Expelled: No Intelligence Allowed." Which is an odd subtitle to any film made in Hollywood - intelligence hasn't been allowed in these films since before I was born. Basically, the film is creationist propaganda, another desperate ploy for enhanced legitimacy of this disturbing movements.

Now, I could send you to Ben's wikipedia article, where a quoted conversation seems to indicate this guy just has a huge hate-on for science: "science leads you to killing people." Or I could send you to his blog posting for said film, full of bizarre assertions like "Some of the greatest scientists of all time, including Galileo, Newton, Einstein, operated under the hypothesis that their work was to understand the principles and phenomena as designed by a creator. Operating under that hypothesis, they discovered the most important laws of motion, gravity... and even economics." Of course economics has a creator, Ben. It's a human phenomenon designed by humans for humans. If God made economics, it might actually work - though probably not. But these are ad hominem arguments, and as such aren't really arguments at all.

Importantly, Ben talks about how Creationists and Creationist ideas are suppressed by Big Science and all the mean, mean men with Ph.D.s and decades of learning behind their belts. Suppression was what the Church did to Galileo when he started talking about Copernican astronomy - and good thing, too, because God knows what a malarkey that turned out to be.

Suppression is possibly the wrong word to use in this context. Scientists, on a whole, demand proof (which is why economics is not so much a science as a complicated way of not understanding certain phenomena). If a group of editors refuses to publish "Creationist" ideas because of a lack of scientific rigour, or a lack of concrete experiments suggesting an underlying theory that will in turn bring out testable hypotheses, Creationists cry "Suppression!" I wish I could do this when my articles get bounced from Nature, and then get all kinds of media attention, grant money, and fame for being a failure in science.

Because that is Creationism, in a nutshell - a failure in science. Or a pseudoscientific success if you will. Science's demands are quite simple: 1) Make observations. 2) Develop testable hypotheses based on these observations. 3) Carry out the tests and revise hypotheses. 4) Repeat until dissertation is finished, or death occurs. Creationism flies through checkpoint 1, but splatters itself against the concrete wall that is number 2. You can't test hypotheses about God, and therefore God has no place in science. You can be a religious scientist - many of these exist, and have their own particular ways of reconciling their faith with their occupation. Anomalous, yes. Suppressed, hardly. But God has no place in the science classroom or its theories.

But this is what we get for looking to celebrities for guidance of any kind instead of people with an actual education and experience in the topic at hand. No, we go for the good-looking ones who can throw a ball REALLY hard. We get the Tom Hankses of the world to endorse our presidential campaigns, and the Tom Cruises of the world are allowed to give the North American public medical advice on the Oprah bloody Winfrey show.

We get what we deserve...

Do the drugs do what now?

I was a little startled to read this editorial in Nature this week, which chides the media for reporting that antidepressive medications simply don't work after the publication of a meta-analytical study finding little-to-no differences in relief from depression when drugs were compared to placebo.

What is special about this paper is that the authors had to file Freedom of Information Act litigation to get the relevant data for the study. A meta-analysis is a study of studies, so to speak (hence meta-), that uses the data from many different experiments and compares all of the results to get a very good idea of whether an effect is really there or not. They literally had to subpoena drug companies and/or the FDA for the results of clinical trials so they could perform their analyses.

What they found wasn't particularly encouraging. They looked at all 47 clinical trials submitted to the FDA for the 6 most "popular" antidepressants from 1987-99. Over 10% (5 trials) didn't even report the improvement scores on psychological tests (Hamilton Depression Index, for example) after drug treatment. Another 7 were incomplete, and knocked 2 drugs out of their study. Happily, in 35 trials covering 4 drugs (including Prozac and Paxil), all of the drug-treated patients showed improvement. However, that improvement was not so much better than the placebo effect that they could be recommended as clinically efficient drugs.

The Nature writers berate the media for "...miss[ing] that the placebo effect can be remarkably strong in psychological and neurological disorders, especially in mild depression." This startled me because it completely misses the point, and I generally expect more from the Nature editorial board. The placebo effect is, in fact, remarkably strong in psychiatric disorders. It may likely be why the concepts of both the double-blind clinical trial and the placebo exist in modern medicine. But if a drug's effects aren't better than a placebo, then the drug doesn't work. It is as simple as that.

If I wrote for Nature I would have attacked from a more different angle, and you can bet the drug companies will: there is nothing simple about these drugs. There is nothing simple about neuropsychopharmacology. Sometimes the drugs work, sometimes they don't. The problem is that depression comes from a wide variety of neuropsychiatric dysfunctions, not just one. Some drugs are going to be efficacious in some of those situations, some will not. Drugs do help a large number of patients suffering from depression, but those who have recovered with pharmacological help will tell you it takes time to find the right drug and dosage. So hoping to respond properly on your first course of a given antidepressive therapy is perhaps ambitious.

But I'll try taking it a step further - the more we talk about "depression," the longer it's going to take us to solve the variety of neurobiological problems that underlie this term. We are talking about of myriad of things when we talk about depression, and until we start being able to devise better correlations between particular symptoms and the biology underlying those particular symptoms - to further develop a knowledge base and a language to talk about depression in a meaningful way - we won't ever have medications that work better than placebo.

I find this most interesting from a population health policy perspective. The study shows that placebos work almost as well as the drugs in all but the most severely depressed patients, and only because those patients get much worse on placebo but improve on medication. What this seems to suggest is that every patient initially presenting with depression should get a placebo (almost the same effect at a fraction of the cost), and those that are severely depressed will get worse rather than better after several weeks. Once you've identified them, they can have the "real" antidepressants. Our health care system would save tens of millions of dollars, and we wouldn't be pulling any more scientific fraud than the FDA has been since 1987...

UPDATE: I spoke with a psychiatrist who runs antidepressant trials, who tells me the 6-week follow-up point used in this study corresponds to the maximal response in the placebo group - scores taken at 10 weeks of treatment would have been much different. Which, of course, continues to beg for the following question: Why did the FDA license the drug on that data?

Why does "gate" mean scandal?

Here's an amusing take on governmental incompetency from David Wilkins, the US ambassador to our great country. He thinks that a leaked memo from our government detailing how Barack Obama is talking out both sides of his mouth about NAFTA cancellation is tantamount to Canadian interference in US elections. To Ohio voters, who are losing jobs under the current NAFTA agreements, he's saying that he'll scrap NAFTA. But his economic adviser, Austan Goolsbee told the Canadian Consul General Georges Rioux that no such plans were in place.

I'd like to ask a couple questions at this point:

1. Since when does the US care about anything Canada does or says? Thinking that we have influence and pressure to bring to bear in the US election is more than a little far-fetched. In fact, it would likely be the other way around - "I'm votin' Bush, 'cuz those Canadians hate that guy." Frankly, we don't care who wins the election now that Bush is out.

2. Why would we be supporting NAFTA anyways? Despite numerous decisions by NAFTA governing bodies that softwood lumber tariffs are unfair, they remain unchanged. We've never profited under NAFTA, even when we've won decisions. Go ahead and scrap NAFTA! Let's get a real regulatory body in place or scrap the thing altogether. The US would be foolish of course, as the original NAFTA was drawn up under the shadow of overwhelming US economic power. See what the new agreements look like now that some pundits are predicting economic collapse.

3. Who is surprised about politicians lying straight to our faces like that?

4. What does it even matter when the next president is going to be John McCain anyways?

5. Since when do the Americans need our help in election interference, and why would we do it for free when Diebold gets paid for it?