Saturday, August 9, 2008

Animal rights activists firebomb university scientists

Winning hearts and minds.

Disclaimer: I have done animal research in the past on rats, mice and squirrels, although I don't do that currently. I raise cage-free, extremely spoiled chickens in my barn, and occasionally have to cull them if they are injured or ill beyond recovery. I fish regularly, and eat local venison when they feast on my garden. I have no compunctions about killing wasps, mosquitoes, aphids, slugs, wireworms, or any other garden pests. I keep an extremely spoiled dog and several cats. So I probably qualify as Evil as far as animal rights go.

In my experience, the animal rights folks--and I know many, my mother included--don't have an awful lot of experience working with actual animals. They specifically don't want any, either, which seems odd to me, since a horrible lot of animals end up in rescue situations where they could use some love and support from a hairless monkey with compassion and time to spare. In a sort of circular logic, I can see this, if you're starting from the point that it's wrong to domesticate animals at all for any reason. That this first point is obviously wrong doesn't seem to matter to them--is it also wrong to wear clothing, cook food with fire, eat with silverware or take birth control? We've domesticated ourselves to a large extent, too. I guess it's OK to domesticate yourself because you're doing it to yourself, but that argument also applies to human babies and plants--is it wrong to eat any kind of tomato that isn't a landrace, or eat maize in any form, or consume the many Rosaceae derivatives that have been domesticated these past few millennia? Or is that OK because plants aren't sentient? How do you know for sure they aren't sentient, though? Lots of things don't look like animals but really are, and other things that look sentient really aren't at all. You end up with the whole epistemology question again.

True story: I had a philosophy professor once, a seriously involved animal rights activist, who said that we should all use traditional Chinese medicine because it's so much kinder to animals. Yeah, she really said that. And many of the animal rights people I know feel that we should use something other than animals because there are all these alternative ways of doing things out there. Only, in actual point of fact, when you ask them what specifically these ways are and how they've been validated, because our animal rooms are damn costly and a real pain in the arse to staff, they haven't got any answers.

Quite frankly, I don't think many scientists really enjoy doing the animal work. I don't know any who wouldn't rather use something else if they possibly can. Petri dishes don't need fed on weekends, they don't bite, they cost about a buck, one tech can manage about a thousand of them, and you get results in a couple of days rather than a couple of months or a couple of years. Here's the alternatives we've got and their relative drawbacks:

Genomics: There are several techniques in genomic analysis and transcriptome analysis. The most developed one is probably the AffyChip system. Error rates for the Affy system are about 10%; that is, 10% of the hits you get as "gene expressed/present in this sample" are wrong. To some extent you can correct by using longer oligos, better computer algorithms, but really you do have to run RT-PCRs to confirm hits. The initial capital equipment investment is not small either. And the fundamental problem is, this only tells you about genes, and genes aren't everything. There are several other levels of molecular control, which an Affy system will tell you nothing about.

Proteomics: There are several proteomics workbenches on the market. They also have some nasty error rates. The proteomics problem is, there are a couple million proteins in any human and they can all have their own subtle differences even with the same transcript. So most people focus on a single tissue. However, this often produces as much gobbledegook as actual data, as proteins tend to be very subtle things rather than the simpler on/off mechanisms that genes have.

Metabolomics: We don't have any good models yet. We just don't. Although folks have been trying for many years to cobble together models of the pathways, they are still not good predictors and at best can only work with extremely simple control loops. Whole people aren't simple.

Tissue culture: OK, so let's say I add Drug X to my dish of human liver tissue to see how it behaves. My liver tissue is immortalized through various means; how do I know that the immortalization process (whether through viral transfection or creating lesions in the DNA or by creating hybridomas) didn't screw up the metabolic processes? Because it usually does, to some extent. But let's take it for granted that this liver culture is pretty good, and also that the lack of an epithelium to affect uptake and diffusion isn't a problem. Even assuming that my liver tissue culture will do a decent approximation of first pass kinetics, how do I know that other tissues won't be affected by the metabolites? Do I test all the thousands of tissues in a human? We don't have cultures for all of them, but we do have cultures for many of them. We do, in fact, have high throughput systems and liquid handling mechanisms that we could probably test a couple thousand tissues in triplicate on a gradient. That still doesn't tell me whether or not all the tissues working together will behave the same way.

And the error rate due to the immortalization process is cumulative. Cell cultures drift over time, in many cases over a fairly short time--say, three months. It's the nature of immortalized tissue to drift genetically, because it hasn't got the control mechanisms to correct its own genes. Worse that that, tissue cultures can be very delicate things. You've seen news stories about Compound X that "kills cancer in tissue cultures"? Everything, except possibly sterile heat-treated fetal calf serum, will kill a cancer cell in a tissue culture! Other cancer cells in the same bloody dish will kill their neighbors in tissue culture! The mere shear stress of pipetting the cells up and down too often kills cancer cells in tissue culture, but that doesn't mean that if you ride enough roller coasters you won't get cancer. Tissue cultures are not stable critters.

Co-culture in a reactor to produce complex systems: Sometimes these are advertised as "growing organs," but they're more like growing a piece of an organ rather than the whole thing. Again, you've got a piece of a cancerous growth in a highly-oxygenated, extremely artificial condition. It may share a proteome with a human tissue, but it sure doesn't quantitate expression the same way.

So, we could use some other tools. Hey, animal rights folks say we should develop them, and I agree. I don't like having to wait two months for Drug X results, either. It seems to me that since animal rights groups have many dedicated people and get plenty of donations, that they should establish some cell & molecular biology scholarships and fellowships, fund a grant or ten, and develop us some better tools. I would love, LOVE to have a metabolomics in silico model of a human, to start with, and that only requires a bunch of textbooks, a UV-Vis spectrometer, some Sigma-Aldrich reagents and a couple of good computer programmers. If I had a couple of good engineers and didn't have to work full-time, I'd do it myself. Most of my colleagues have been begging our bosses to let us do it, but they are fussy about having us focus on curing cancer and stuff, they don't want us to spend a lot of time developing tools as we are not a tool-making company. You could sell such a model for a small fortune to various drug companies, thereby eliminating much animal suffering and experimentation, as well as earning a living and being able to quit your day job. The cost of the grant to fund it would be, oh, let's put it at $125,000/year for three years, meh, round it up to $500,000. Surely some animal rights group has $500,000 to spare? Isn't that, like, a fraction of their advertising budget?

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