Monday, January 5, 2009

Novelty in Science

Last week, Comrade PhysioProf asked how people go about generating novel scientific concepts in their field. I've been bogged down in the lab and didn't get a chance to sit down to respond until now. Most people responded suggesting that they either apply new methodology to an old problem or follow up on the most unusual or demanding data. While I think that is a key element, I would like to introduce another possibility: capitalizing on the diversity of nature.

I don't work on model organisms. In fact, one might argue that I do the exact opposite. My work thrives on finding the odd balls and misfits and trying to understand why they are the way they are and how they got to be that way. I don't mean chasing down spiny echidnas or duck-billed platipi, more like collecting and working with groups of organisms that you likely don't even know exist. It can be a painful way to proceed when so many major techniques can only be used when you have a basic knowledge of the organism. When you are starting from square one with a bug (generically speaking, not an insect) that has never been described before, or from which only basic descriptive details are known, there is a steep hill to climb before there is a big pay off.

Of course the flip side of that is the possibility (probability) that you stumble across something totally novel. As an example, take the case of the malaria pathogen, Plasmodium. The actual pathogen has been know for a long time and, as one might expect, been the subject of intense research since it was first isolated. TEM studies had shown an unusual organelle in Plasmodium of unknown function, which was termed the apicoplast (because this organelle is shared in other members of Apicomplexa, such as Toxoplasma, as well). It was unclear what the organelle did, but people hypothesized that it was involved in infection.

Combining established methodology and contemporary evolutionary hypotheses regarding the evolution of the group that includes apicomplexans, an international group showed conclusively (McFadden et al. 1996. Nature 381:482 - no link because of age of the paper) that the apicoplast is a relic plastid (chloroplast). Not only did this indicate that the apicomplexans evolved from photosynthetic algae into some of the nastiest pathogenic bugs out there, but it also provided a novel way to attack malaria without human side effects. If you can target drugs to plastid genes, there is no concern that human genes will get caught in the crossfire.

Now, if you have traveled to a country where malaria is a problem and taken the drugs, you are probably thinking "Bullshit, I took Chloroquine and there were certainly side-effects." That's true, mainly because of the difficulty in specific drug targeting into the apicoplast, but this avenue remains one of the most promising opportunities to prevent and even eliminate malaria at some point in the future.

So, novelty in science, for me, comes from exploring the strange and unusual things that have evolved all around us. There is no shortage, I can assure you, and there are probably fewer people studing 90% of eukaryotic diversity than there are studying a single human cell line. In fact, of this I am sure. If what got you into biology was not how blood flows through the body or that you wanted to hug dolphins one day, it's time to realize that animals are boring and plants are just dry algae. Get into to the literature a bit and see what else is out there.

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