Monday, October 27, 2008

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.

Saturday, October 18, 2008

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.

Wednesday, October 15, 2008

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.

Thursday, October 9, 2008

Fair is fair - Science Under Harper

So it's been awhile. I've been restraining myself because what I really want to write about is the election next week and the US subprime crisis. But I write about science, mostly (go Habs go), and so have tried to avoid these topics, which then keep me from writing. Which brings me to a summary of Canadian science news during Harper's term as Prime Minister. Election- and science-related, which is a big coup for me.

I could bring up that Harper backed us out of the Kyoto protocol, news about which seems to come up in "Science" sections of the news frequently. Seriously, our response to this relatively slow-moving but incredibly serious threat resembles that of FEMA's to Katrina, i.e. to lay back and hope the problem will blow itself out before anybody has to do anything. Harper's environmental plans are simply awful. I don't know if carbon tax is the right way to go, but Harper's plan will lead to increased emissions. Simple as that. Not that Dion's record on emissions was spectacular as Minister of the Environment, but you have to limit the amount of blame you can put at his feet, as he was only there two years.

I have to mention a positive thing - long deserved tax exemptions for graduate students. Graduate students make very little money - averaging under $20 000 annually - so getting that kickback really makes a difference. Plus, it never made sense to me that our government charged taxes on money they gave my boss in order for me to study. Harper actually increased the number of fellowships available to students - in science, anyways, I don't know about anywhere else - which is pretty good. Harper has given modest increases to funding agencies, but any government will have trouble keeping pace with the Chretien Liberals, who did things like increase the budget of the Canadian Institute for Health Research from $289 million to $666 million over 6 years, which is a stunning feat.

Another big thing that Harper got press for was dropping the position of National Science Advisor. This got him condemned by Nature, one of the most important journals in the world. They readily admit that the post was woefully underpowered and underfunded upon its creation by the Liberals, but relegating it from direct Prime Ministerial interaction to a subdivision of some Ministry, and then phasing it out for the Science, Technology and Innovation Council wasn't a step forward. This represents a typically Canadian approach to politics - create 18 jobs where one would do, and give at least 9 to your friends.

But then there some other things I wasn't a fan of. Him opposing safe injection sites when there's a pile of evidence they work. Health Canada started calling for them as early as 2002, and Harper wants to eliminate those few that exist. This is an example where the Prime Minister is refusing to let science shape policy. Him firing the head of the nuclear commission when she shut down a potentially unsafe Chalk River nuclear plant. His then-Environment Minister Rona Ambrose engaging in a little old-fashioned Big Brother-type censorship.

All in all, I think science and technology would fare better under someone that wasn't Harper, and allows science to have a role informing policy, and doesn't engage in downright lying and bullying to advance their agenda. Science should change your policies - it apports new information. That's what it's for, and why the government funds billions in research and development projects. The least we can ask our politicians to do is to take some return from that investment.

Next week - the Nobel Prizes.