Saturday, August 23, 2008

Keep your eyes in your head

There's currently a debate over at Thus Spake Zuska about the mysterious grey area where a glance at a breast becomes an unwelcome stare. So far the main talking points seem to be:

-It's biological, people can't help looking at an attractive person
-Humans are sexual creatures and it's unreasonable of society or anyone to expect people to leave their personal foibles and bad habits at home
-People shouldn't be so easily offended, AKA Some women like it
-People should cover up in burkas if they are so incredibly gorgeous

Zuska has done a wonderful job of dispelling the last of these: In countries where women do wear burkas, they get much more harassment than they do in countries with more liberal clothing policies. As to the other three...

It's biological, people can't help looking at an attractive person
Lots of things are biological, and yet we train ourselves out of them in polite company. Adults are potty-trained, eat food with silverware, wear clothing outdoors and in mixed company, and bathe themselves, all means of overcoming natural biological things that are offensive to polite society. You don't get a pass on those, so why should I give you a pass on where you rest your eyes? Practice the good habit of looking someone in the face, always, until you get it right. If prolonged eye contact feels uncomfortable, look at a spot beside their ear, gaze into a notebook or coffee cup, or look to one side while you talk. You can help it. If you can master the art of not picking a wedgie in public, then you can learn to look at someone politely. The added bonus of this good habit is that people truly feel like you are listening intently to them, even if you're only contemplating the pimple on their nose. Male or female, when someone feels like they are being listened to intently, they usually feel a lot better about your conversation even if they did all the talking.

Humans are sexual creatures and it's unreasonable of society or anyone to expect people to leave their personal foibles and bad habits at home
It's not unreasonable. It's just not, and there's an end of it. You don't pick your nose, pick your butt, squeeze pimples or masturbate in public, and those are perfectly reasonable expectations. If you want to know someone better, ask them out for coffee or beer. If you absolutely must know if they are generally attractive on the outside, use the miracle of peripheral vision or look from a respectable distance such that no one could tell if you were checking out boobs or merely trying to recognize the person. It's just not that hard. It's bad for your career to flirt at work anyway.

People shouldn't be so easily offended,
Some people are offended. If you offend people, it's very easy for you to be labeled That Guy in your social circle, in which case you will have to make some friends outside your circle because no one wants to hang out with That Guy, and it's so much easier to cut That Guy out of activities than it is to deal with angry, offended people making the occasion uncomfortable for everyone. Arguing that they should not be offended is missing the point entirely: They are offended no matter what you intended. Your choices consist of finding a new workplace, finding new friends, or apologizing for the offense and making a concerted effort not to do it again. "No one should mind my disgusting lack of socialization" is not a viable option here.
AKA Some women like it
And some don't. Yes, there are people out there who have a higher bullshit tolerance than others, bless their hearts. I'm sure not one of them, and I'm not alone. Some people are into all sorts of fetishes and bad habits that others find perfectly repulsive. The difference is, they know that their bad habit/fetish is not everyone's cup of tea, and keep that to themselves in mixed company. This is why the good Lord created the VCR, the DVD player and the internet, so you can keep your voyeurism in the privacy of your own home.

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?

Friday, August 1, 2008

Anthrax researcher dies

I'm actually quite interested to see how this case turns out. So far every article posted on CNN, BBC, etc. have been very lite on facts. Although I did some work for ECBC (the Fort Detrick bioweapons center) myself as a contractor, I didn't know Dr. Ivins.

From what the half-arsed articles say, the FBI's case is basically, "he swabbed some areas without getting official approval first, and it turned out the swabs did find anthrax in those areas, where it wasn't supposed to be." They declare this highly suspicious on the grounds that he should have gotten approval first.

O RLY? What if, say, his results demonstrated that the Fort Detrick containment system was a joke, and that there was no place safe in the whole building from the bugs they had stored there, and that the senior management knew this and put all the workers and contractors in danger on a daily basis because it would be Too Expensive to pack up the hazards, ship 'em to CDC, and re-engineer the whole entire lab complex from the ground up? What if his results would have caused a major scandal for the organization and about a zillion lawsuits? What if his boss, upon receiving Dr. Ivins' request for permission to swab those areas, realized what havoc a positive result would wreak, and therefore said Absolutely Not?

Anyone who thinks that senior managers don't knowingly pull shenanigans with highly dangerous stuff hasn't been out in the working world long enough. Talk to an environmental engineer who does fieldwork and Due Diligence for chemical company acquisitions. Talk to the industrial hygienists who clean up after regular everyday hazards in coal mines, chemical plants and steel mills on a daily basis. Just two years ago, about an hour up I-95 from me, a big paint manufacturer went kaboom, leaving naught but a giant crater where the building used to be. Turned out that management and their process engineers had knowingly created a faulty flammable liquid handling manufacturing method that resulted in the explosion. Miraculously, no one was killed, only injured. It would not surprise me one bit to find out that USAMRIID managers calculated the risk of what could happen if it turned out the cooties had indeed escaped the lab, and turned Dr. Ivins reasonable and concerned request down. And then decided to throw him under the bus. Unfortunately, government officials and senior managers with a lot of money and their own personal careers at stake, really don't have a great track record on accountability and integrity. They've got a great track record for scapegoating though. That's just the working world for you.

And sadly, I don't know that Agent Scully, with all her science, actually works at the FBI. You have to be a bit of a specialist even as a scientist to understand why a microbiologist might go around swabbing stuff after their boss told them it was a bad idea, and then understand what the molecular diagnostics mean and how to interpret them. Did the FBI have such a specialist review the sequencing results thoroughly, including the bioinformatic logarithms of the computer program used to analyze them, and troubleshoot accordingly? Were the sequences double-checked by some other method? What level of identity was considered a reasonable match, and how was that acceptable mismatch level calculated? Were they working from theory or from a library or what? Did the FBI know to ask this stuff? Or did they just take Dr. Ivins' boss' word for it that everything was done properly? Did they seize the notebooks and samples and try to re-create the results? If not, why not? I would think that the very first step in such an investigation would be to figure out who might be telling a tall tale, especially who might have a vested interest in blaming someone whose career is conveniently over, but then again I am not a criminal investigator. I don't even play one on TV.