Remixing memories

I'm thinking that The Globe and Mail has been checking out my blog, seeing this article from earlier in the week talking about the things from my last post. Particularly how other countries are pumping money into research while Canada is cutting. Interestingly, they interviewed my PhD supervisor, who is apparently "one of Canada's top scientists".

I'm pleased how closely his opinions follow mine, and that they're publishing them in the Globe and Mail. I'm a bit disturbed about being so similar to my boss, though. I'm also disturbed that he apparently has fantasies of moving to Signapore...

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A genetic therapy approach to treating AIDS that I blogged about last summer is currently recruiting for its first clinical trial. This is pretty incredibly quick, but it seems very safe - take some of a patient's blood, take out the T-cells, culture them, insert the gene, grow a whole pile of the modified cells, and then return them to the patient. This follows on the footsteps of another successful trial of gene therapy for AIDS treatments.

The risks of these treatments seem minimal. The gene transfer isn't contagious to other cells, and the T-cells come from the patient's own body so there should be no risk of rejection. Assuming the cells aren't grown in an animal serum, which could induce a rejection response in patients. But I imagine these guys know what they're doing.

Of course, the guys injecting a Russian boy with stem cells also knew what they were doing, and they knew the risks. Turns out they lost this bet - the kid developed extensive tumours throughout his nervous system. While this was a predicted potential side effect, I don't think anyone was expecting this to go so spectacularly wrong.

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If there's one thing I've been wanting to blog about this week, it's this story about using a heart medication (propranalol, a beta-blocker) to "block bad memories." People are going buck-wild about this - I even saw it on Facebook (I have some geeky friends). But the study is not all it's cracked up to be.

The researchers conditioned people to be "afraid" of spiders by showing them pictures of spiders and then shocking them, a Pavlovian paradigm that couples a neutral stimulus (spider) to an averse stimulus (shock), and transfers the unpleasant feeling associated with the shock to the spider. The drug was able to reverse this conditioning, so people no longer had an adverse response to the spiders. And now it's being touted as a treatment for PTSD and anxiety disorders.

First of all, I would like someone to explain to me and a couple of war veterans exactly how shocking someone while looking at pictures of spiders is anything remotely like traumatic experiences like losing a limb in a firefight or having your friend's brains blown out all over you. Or even like being in a car crash.

Secondly, even something like a phobia against an object (say, spiders) isn't like a conditioned association. In fact, it's the opposite. The reason it's a phobia is precisely because it's an unconditioned and irrational fear of an object. Show me a trial with arachnophobics on propanalol viewing pictures of tarantulas and I don't think we'll see such stunning claims being made.

The idea is that when we remember things, we take the representation out of long-term storage in our brains and move it into "working memory," a sort of RAM buffer memory for your brain. When we're done with it, it gets re-programmed back into the long-term storage. If we can remove the bad associations from the memory before we code it back into long-term storage, then we can remove some of the anxiety and pathology that comes from remembering it.

I, for one, am not sure that this will work. I think that removing a simple conditioned association is a lot different from removing the particularly vivid memories that many PTSD patients have, and that the emotional component of these memories is much more intense than a simple shock to the finger. I think the biochemical underpinnings are significantly more complicated than simple noradrenaline release as well. That being said, we can condition men to respond sexually to an old boot, but again I would argue that this neither a complex behaviour nor particularly difficult to accomplish. Now if we could do it in women, then we'd be on to something.

I'm not sure what it will take to "erase" these memories, but I refer you back to an earlier post I made on memory manipulation and Joe Tsien's quote: "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."

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My other blog, for those who are interested, is up. The first post is enititled "Douglas Zombies Need Brains." And if that doesn't pique your interest, then I don't want you reading it anyways.

Blowing Ourselves (another bubble)

I was amused a couple months ago by this comic from Jorge Cham at phdcomics.com, which depicts a graph of changes in enrollment to grad studies over time superimposed over the unemployment figures. The correlation is incredible.

Being all in fun, you'd be excused for thinking the artist was just exploiting a quirk of statistics to get a laugh. But then you see Nature reporting exactly the same thing last week and realize that it's not funny, thousands of people think that getting a Ph.D. is worth money. Many people accept this as true, but I think you'd have a hard time convincing Bill Gates or Warren Buffet of that. Or me, for that matter.

For their sakes, I hope that a good portion of these thousands are working on M.B.A.s rather than Ph.D.s, particularly in science. Nature also had a feature last week about two very successful US scientists closing their labs because their funding has simply dried up. An editorial in the same issue points out that "The career crisis is especially stark in the biomedical fields, where the number of tenure-track and tenured positions has not increased in the past two decades even as universities have nearly doubled their production of biomedical doctorates. Those who do land jobs in academic research are struggling to keep them..."

All that to say professors doing academic research in their ivory towers are being as hard hit by the budget cuts, loss of endowment funds and general financial crisis as anyone else. And they don't get severance packages in the millions of dollars. Even still, I guess starting a doctorate is a bit like signing a 4-6 year contract at a meagre (but fairly secure) salary, and maybe some kind of health coverage, which is better than a lot of American citizens can say.

Maybe it is the smart move. Presumably, you set yourself up for a better job by working on an advanced degree during the recession, which will be a couple years long anyways. Good jobs should become available as we begin blowing ourselves another economic bubble to drive unsustainable expenditure - I predict some kind of -tech bubble, be it bio-, nano- or green-. Plus, it won't be long before some genius figures out a new way to create money out of nothing now that subprime mortgages are bust.

But bubbles always burst. That's why they're bubbles. When the economy crashes, it does so like a plane. It doesn't care if you're Richie Valens, the Big Bopper and Buddy Holly; or how many fancy-pants letters there are after your name. There will be blood.

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.