In these troubled times...

I've been committing adultery on this blog, by which I mean I will soon be writing a blog for the research institute where I work. However, being a public institution, they made me promise I wouldn't talk about politics on that blog and stick to science. So as long as there are still politics, I will still feel the need to rip on policy in this space.

Take the new federal budget, for example. Now, I'm not going to talk about Harper's bold-faced lie last fall that there would be no deficit for Canada this fiscal year. Nor will I rail on the other parties for not pushing the Government hard enough to create a great budget. No, here I'm going to stick with the science part of the budget, particularly the health research part. Because I hate it.

Shocking, I know.

The CBC generously refers to the budget as a "mixed bag" for science. The best news is the $2 billion to repair and expand existing facilities. Working in labs that don't have a) water dripping on experiments from pipes above, b) ceilings falling on machines worth a quarter-million dollars, and c) luxuries like proper ventilation and working temperature controls will be highly beneficial for Canadian science. This infrastructure spending will also help create jobs through construction projects, many of which will also be funded through the $1 billion the government is giving for green energy and the $750 million for the Canadian Foundation for Innovation, which offer key grant competitions for institutions needing to upgrade equipment and research infrastructure.

Other perks in the budget include some $87.5 million for new scholarships for students - although Science magazine reports that "an unspecified chunk" will go to business-related degrees. There's $351 million for Atomic Energy of Canada, which is probably overdue seeing as how Harper fired the head of the Nuclear Safety commission last year when she deemed the Chalk River reactor was unsafe, and another $110 million or so for the Canadian Space Agency - Marc Garneau's presence in Parliament makes it hard to keep cutting that program.

What most of the budget wonks don't say is that the feds are only providing about half of the promised $2 billion in infrastructure spending here - universities will be expected to raise the other half through municipal and provincial governments and potentially even private or corporate investors. Which means that some of that cash may never show up, particularly for small universities in "have-not" provinces that are struggling as it is.

The bad news doesn't end there. The budget also shaves about $150 million from the main Canadian funding agencies - CIHR, NSERC, and SSHRC. This is close to a 10% hammering, and will only serve to shave down the already outrageous odds of winning a grant. They are also gutting the funding for Genome Canada, which is a brilliant project that brings the cutting edge of genetics research techniques to universities across Canada. They are a major supporter of the provincial genome projects, some of which - such as Génome Québec - are extremely successful in their own right. While they had already been promised about $240 million over 4 years, the current budget allots them absolutely nothing. Not a sausage.

Now, in these troubled economic times, yadda yadda yadda. In these troubled times, the US is injecting some US$3.5 billion to their National Institutes of Health alone; and tens of billions more for other science organizations. Note this not a reduction in spending or in grant money, which is what Canada seems to think was the right thing to do. A mere 5% of the $3.75 billion set aside for infrastructure and such would provide for all of the money being cut from the granting agencies.

It's nice to have renovated labs, but if there's no grant money with which to fill those labs, these billions in infrastructure expenditures are little better than federal make-work projects. Frankly - particularly here in Quebec - the money might be better spent on the roads.

Smarter, faster, stronger

A stunning opinion piece in Nature on Monday encouraging the use of cognitive-enhancing drugs, which has been all over the news and brought me to remember a problem I have with Ritalin. I'll have you know this is completely different from having a Ritalin problem. I'm not saying I don't believe in ADHD, although I do believe it is over-diagnosed, but I'm not getting into that. What I want to get into is Ritalin. And most of what we have in the way of ADHD drugs.

The simple fact of the matter is that these drugs are cognitive enhancers. They're a couple of chemical steps removed from amphetamines (speed), which are well-known for improvement of certain parts of thinking - short-term memory and attention particularly. Now, the ADHD drugs seem to work in a select number of specific areas of the brain whereas the speedball drives an entire neurotransmission system into overdrive (to make a gross oversimplification), but people without ADHD still see an enhancement of performance on tests of cognitive performance when they take Ritalin. That's why people buy it illegally during exam periods.

I'm about to make a brutal analogy here, so cover your ears - this is like letting Special Olympics athletes go to the other Olympics, but doped up on whatever performance-enhancer is big right now. No, really. My problem with Ritalin is that gives improvement on performance of tests that we use to diagnose ADHD in in both controls and ADHD patients. We're not treating ADHD necessarily - just improving performance on diagnostic tests, performance on which corresponds closely to that on academic exams.

Most of us are already users of cognitive enhancers. During my undergrad I smoked 15-20 cigarettes and swilled maybe 2-4 litres of coffee daily (thankfully, I've since cut down on both significantly). Both nicotine and caffeine are clinically proven enhancers of performance on pretty much any cognitive task you could name. We drink Red Bulls and coffee to make us sharper, we take sleeping pills to help us calm down, we take alcohol to enhance our social performances.

Which brings us back to the topic of the editorial that brought me to this piece in the first place. Why shouldn't we use drugs to become more intelligent? In what way is this possibly a bad thing? There are side effects; many not as bad as are present in a large number of other commercially available drugs (especially alcohol and tobacco). Why shouldn't my doctor, my lawyer, my accountant, my Member of Parliament and my future kid's teacher be on these drugs all the time?

Personally, I think that the means here don't require justification by the ends. There's no ethical dilemma about taking vitamins, or antioxidants, or coffee. We already use pharmacology to improve our quality of life in so many ways, and I see this as no different than taking drugs for anxiety, diabetes, or metabolic syndrome. Better living through pharmacology is still better living, and I don't think anybody should have a problem with a better life.

Science cuts and general news

From the news:

• Interesting article on anti-aging drugs from Wired, where scientists think that this new class of drugs might be the key to fighting cancer, diabetes, Alzheimer's, and just about everything else under the sun.
• A great piece in CBC suggesting that forward-facing strollers are bad for a child's social and verbal development. This makes a lot of sense: kids of stroller age have brains that are designed for learning about faces and language.

From the InterWeb:

• Wired's 10 favourite biology videos. Just awesome (except the PCR song - man, I hate the PCR song). I'll be commenting on at least one or two over the next while.
  

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According to this CBC article, Statistics Canada reported Thursday that federal spending in science and technology is about to drop for the first time in 5 years, which is about the same time we elected Paul Martin to a minority government. Now admittedly these cuts seem small - about 3% - but this represents hundreds of millions of dollars lost for funding science and innovation in this country.

I don't think this is a good idea, but I'll declare a conflict of interest being a scientist who would like to be employed in Canada. Even still, it seems natural that investment in alternative energy production will create domestic skilled jobs desperately needed by Canadians. Of course, it would cost money now, and it will be years before we see any real return from this investment. But unlike investing in shady debt trading - asset-backed commercial papers, or subprime mortgages - this economic activity would create real wealth, and by that I mean jobs, clean energy, and Canadian businesses with a head start in a globally important industry.

Garneau vs. Goodyear

The Opposition Liberals have named their new Science critic, and it is former astronaut and generally awesome guy Marc Garneau. This is a good move by the Libs, as Garneau actually has a Doctorate in engineering and therefore knows something about science. Oh yeah, and he was the first Canadian in space, with almost 678 hours over three trips total. That's mad geek cred right there.

Gary Goodyear may not be as well-known as Marc Garneau, but is our newly-appointed Minister of State - Science and Technology (I know, what kind of title is that?). Wikipedia lists him as a physiotherapist and doctor of chiropractic, having graduated from an established college that engages in multidisciplinary research and involves about 4500 hours of coursework. However, I couldn't find him in PubMed so I don't think that he's ever actually performed research.

I'd like to see some more Ph.D.s in our legislature's ranks. People that actually understand the cutting edge of their science and can talk about research in a meaningful way. Harper's treatment of science hasn't been cruel, but it hasn't been kind, either. But I'd like to see someone that can actually sell the importance of research through their experiences to the Prime Minister and the Canadian people. It will be interesting to hear Garneau defend the Canadian Space Agency from further budget cuts.

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Economics rant. Feel free to skip.

Bush was at the G20 summit last week talking about how free markets need to remain free, and that this is how global economic progress will be made.

Let me point out three perfectly obvious things. First of all, the U.S. is not interested in free markets. That's why we have things like NAFTA, to make sure that American economic interests get certain advantages. This is not necessarily a bad thing (for the US, at least), but it is definitely not a free market. Secondly, the government is spending up to $700 billion to bail banks out of bad business practices. The very definition of capitalism and free markets demands that governments not engage in massive market manipulation. Thirdly, the only way to have prevented the current economic meltdown would have been to actually regulate the banks and what they were doing, which is also not a free market approach.

Alan Greenspan, former head of the Federal Reserve (and by extension the US economy) said he made a key error during his tenure - "I made a mistake in presuming that the self-interests of organizations, specifically banks and others... were best capable of protecting their own shareholders and their equity in the firms." In other words, he assumed that the banks would follow base capitalist economic assumptions: turn profits, perform due diligence, cover their asses. But they only got one out of three on that quiz, and a suddenly socialist US government is now paying them truckloads of money - skyscrapers full, actually - for this colossal failure to do their jobs.

This is not a free market approach, which just goes to show that capitalism and free markets don't work, and never have. Not that socialism does, but I'm sick of hearing about the power of free markets when 1) there aren't any, and 2) the closer we go towards a free market, i.e. the less closely government regulates, the worse things get.

Transsexuals, farts, stem cells and memory manipulation. Just another day...

From the news:

• Australian study finds correlation between transsexuality and the gene coding a male hormone (androgen) receptor. Apparently, the long version of the gene has a less efficient product, and was found significantly more often in 112 male-female transsexuals compared to 258 control subjects. Which makes me wonder what this finding means to transsexuals, if anything at all...
  


• Solomon Snyder, an interesting character in the history of neuroscience, stands behind a study linking the stink-inducing chemical in flatulence and blood pressure. Apparently the foul smell, hydrogen sulfide, can lower blood pressure significantly. Reported with a sort of childish glee by both the BBC and the CBC (and others)...
  


• While Britain relaxes certain stem-cell laws, it is pointed out that Canada is the about the only country in the world that does not currently allow the use of animal eggs in the production of human embryonic stem cells. I would bet a hefty sum of cash that stem cell technology will cure at least some neurodegenerative disorders within my lifetime. However, it is up to legislators to determine whether it will be 10 years from now or 25...
  

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A very interesting piece from CBC reports on scientists who seem to succeed at wiping a specific memory from a rat. They do this by using mice who have a very fancy piece of genetic engineering on board. The scientists built a gene construct where they could make a certain protein become more abundant in certain areas of the brain through pharmacological manipulation. Then they tested if a mouse could remember a certain place by shocking him there, and seeing if he shows behavioural signs of fear the next time he gets put there.

By overexpressing the protein in question when the mouse was put back in the chamber, the researchers could effectively make the memory disappear. Now, as we all know, memory is a strange thing. It consists of four processes that we call "acquisition," "consolidation," "storage," and "retrieval," which we could equally call "getting," "coding," um, "storing," and "remembering." But it's more complicated than that - when a memory is brought back from storage to become part of conscious thought, it has to be re-encoded, and stored. Even worse, it becomes flexible while we remember it - numerous studies show memories are influenced by current emotions and knowledge, become mixed up with the present.

Instead of altering the memory, the overexpression of this protein (αCaMKII for those keeping track) seems to destroy the memory when it's being remembered, perhaps with a sort of excessive brain "noise" level that obliterates the memory signal during the process of recalling it. This paper is a tome, so I haven't been through it very thoroughly, but it's in an amazing journal (Neuron) and looks pretty watertight. Really an amazing study.

That being said, this is a bit of what a former colleague of mine calls a "sledgehammer" approach, because it lacks precision as a tool. Gene expression is affected through an enormous population of cells, so it could be the case that more than the memory being recalled is affected . Other limitations make it extremely tough to try pulling this off using similar methods in humans. Firstly, the behaviour is not very sophisticated, even for a mouse. More importantly, human memories - particularly the bad ones - are probably richer and more complex than those of mice, and will be consequently harder to "knock out."

The best part, however, is this very wise comment by senior author Joe Tsien: "All memories, including the painful emotional memories, have their purposes. We learn great lessons from those memories or experiences so we can avoid making the same kinds of mistakes again, and help us to adapt down the road."

Good advice, and wise words for the future of memory manipulation.

Glowing rats & adventure!

The other Nobel Prize I felt qualified to comment on was that awarded for chemistry, where researchers were honoured for the discovery of green fluorescent protein (GFP), which is a protein native to jellyfish and, as implied by the name, can glow green. Now green glowing proteins may not seem like a big deal, but this discovery also brought about fundamental changes in the way we do biology (although the use of luciferase, a light-generating protein from fireflies, was also a big step along the same direction).

In my last post I talked about using the HIV virus a "shuttle" for genetic material, able to insert genes into a host's DNA after infection. Now, if you wanted to look at whether your cells were infected or not, a great way to do that would be to make the virus carry GFP. If you want to know whether a gene is being expressed, you can make a construct that has the same regulatory regions as your gene of interest, but make it code GFP. Instead of performing time-consuming experiments to measure expression, you can literally just look. And then there's the "Brainbow" mice, which have genes for several fluorescent proteins in their neurons. Their stunning pictures (amazing gallery here) will drastically change neuroanatomical methods forever.

Discoveries of this magnitude, like the discovery of the HIV virus, are huge not because of any single aspect of the discovery, but also for the development of tools that literally change the way science is done. The same thing was true of Mello and Flame's Nobel last year for the discovery of RNA interference. This was such a paradigm-shifting discovery that the committee gave out the Nobel to what must be two of the youngest researchers to ever be considered for it, and a discovery that was barely a decade old; normally the Nobel is reserved for the final coup-de-gras of a senior scientist's long and storied career (like Kandel, Greengard and Carlsson in 2000). It heartening to see the Nobel going to researchers who are changing the ways we do science, rather than given out as an honorarium, like a degree to PhD students who've been chugging along as best they can for the last decade.

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Most interesting thing I've read this week: in high school, I was taught about a 1953 experiment by a guy named Miller, which remains one of the most fascinating I've ever heard of. He designed a closed system with an atmosphere similar to what was, at the time, believed to comprise the early Earth's atmosphere - methane, ammonia, carbon dioxide and such. He introduced some sparks and water vapour, and voila - found a couple of amino acids were produced, perhaps giving some insight into abiogenesis (how life came from inorganic precursors).

Miller died last year, and the researcher who inherited his labs and equipment found a series of tubes marked "experiments 1952-1953." He took some vials from the very same experiment and subjected it to much more advanced analysis than was available at the time. These researchers found dozens of organic compounds Miller was unable to detect, lending great support to the original experiments.

While today we acknowledge that the early atmosphere of the planet was not exactly what was envisioned in 1953, this experiment is a fascinating example of a sort of adventurous scientific spirit that I don't think is as prominent today as it was 50 years ago, and I think science is probably the worse for it.

Viral Marketing

Well, no surprises for me in the election, which frankly makes me sad, actually. I am predicting that the Libs will have a new leader by November 2009 (if not sooner) and will force another election 18 months or so thereafter. Not really Dion's fault, but he didn't help himself much. It was very telling that the separatist leader Gilles Duceppe is significantly more comfortable in English than the Liberal PM hopeful.

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I wanted to speak briefly about the Nobel Prizes this year, or at least those in medicine and chemistry - I don't know enough about physics to even begin to comment on that work. And of course, the Nobel Prize in economics is really the Swedish Central Bank Prize in memory of Alfred Nobel, because economics isn't so much a science as it is a crapshoot.

The Nobel Prize in Medicine went to a number of people (details here) for work on viruses, two of them for the discovery of the HIV virus. It was a little shameful that a certain other party didn't get some credit, but the Nobel can only be given to 3 people, and he doesn't seem as broken up about it as it might be.

What you probably don't know about the HIV virus is how it blew away the biology community when they discovered how it worked. It is literally capable of taking its own genetic information and downloading it into the hard drive of your genome. Then your own cells start manufacturing the virus and it spreads. It uses a special enzyme for this, known as reverse transcriptase, which itself allowed the development of a process called RT-PCR, one of the most important tools in the field molecular biology.

Now, AIDS and other retrovirally-transmitted diseases are important enough on their own to merit consideration for a Nobel, but an important development in recent years has made the discovery even more important. Since this virus can insert genetic material, scientists wondered if they could use the virus as a tool to put genes into mammalian cells.

I wouldn't be talking about this if it was unsuccessful. The virus has been extensively genetically engineered to be able to carry genetic payloads into cells that it can infect, without replicating new virus and harming the host. Today, I myself use a heavily modified version of the AIDS virus to insert genes into rat brain cells and perform experiments looking at how certain genes affect the expression of other genes.

The importance in this case wasn't just the discovery of the viral agents, or showing that these agents caused much more serious diseases. These things were vital contributions to medicine. This discovery went on to reverberate through the field of biology and changed the way we do experiments and perform the science. There are few nobler things that could have been honoured.

Soon - the chemistry Nobel, another (related) paradigm-shifter.