Angry Toxicologist

Is this about a better environment, animal welfare or about better drug development? Take a guess.

Yesterday NIEHS (National Institute of Environmental Health Sciences) had a little symposium on animal testing to celebrate the 10th year of ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) – gotta love the gov’t and their acronyms. They unveiled (although I don’t believe there was a veil or curtain used) their 5-year plan. Like the NAS report that has previously come out, it’s full of a lot of hope and hooey. Please read my previous post as a primer where I conclude:

Toxicologists will be killing animals for a long time. Not because we like doing it (live animal work is a pain, no one I know likes it), because it’s the only way to know what the heck chemicals do.

Now, what is even stranger, is that NIEHS is just as on board with this. Those associated with the field don’t seem to think about the inherent differences between the types of chemicals that present risks. I’d like to expand on what I said in the previous post about the differences between the environmental concerns and pharma concerns.

Facts that should be kept in mind:
1) In pharma, the scientific burden is on industry. In the enviro world the burden is on the public/gov’t.

2) In pharma, the safety burden must be proved before marketing. For general chemicals, they are marketed before we learn something (if anything).

3) Because of 1 and 2, it is in pharma’s best interest to identify problem compounds as early as possible to save money by not developing that drug.

4) It’s acceptable for a tox screen to have a considerable # of false negatives for pharma, the toxicity will eventually get picked up when they do the full-scale animal tests to support marketing of the drug. It’t not acceptable to have considerable # of false negatives for enviro chemicals because if it passes the screen, it’s done and free to go. This is true vice-versa as well (pharma doesn’t want to chuck promising drugs because of a false positive tox screen, and the enviro chemical will get an additional test). Therefore, an ideal system for a tox screen for pharma and enviro chemicals are at odds.

5) Chemical companies want to do as little testing as possible and also want a system with very low false positives and don’t care about the false negatives much. Exactly the opposite of the public’s interest.

6) Non-animal screens usually only come at a problem from one mechanism of action (it assumes that all toxicants of a certain class act the same way). If we use the screens exclusively, we’ll miss the next time a new class comes along.

7) These alternatives are only screens. As I’ve noted before:

The hubris of these people is stunning to think that they can devise a cell-based screen to predict possible toxicities when we don’t even understand completely how cells work, much less how they interact, much less how millions of processes are interrelated in a whole animal. If we understood all this stuff don’t you think we’d know how to cure diseases and develop drugs that only targeted what you wanted them to target?

What have we learned?
Are these methods and proposed future methods going to reduce the number of animals used? Doubtful. If you applied some screens on all the chemicals in commerce that haven’t been tested before (as has been suggested), you’ll be sure to come up with a couple of new concerns that need to be tested more. Oops, more animals.

Are they good for pharmaceutical development? Yes.

Do these alternative methods really do anything for environmental health? Yes. They weaken it. There are more opportunities for outs for every chemical. Hooray!

What’s the solution?
As I see it, this is a fine agenda for the Pharma world: better development, less cost, fewer animals – everybody(and animal) wins. What gets my back up is the environmental side seeing this as a fine idea. The goal should not be to get all chemicals tested, the goal should be to most effeciently reduce risk. That means going after the chemicals that we’re exposed to. Let’s start with the ones in our blood and move on to those in our drinking water and give those a real test.

PS I hate animal research. I really do, but I can’t see that there are any alternatives. Also, I should admit that I don’t see animals as small furry humans (or in the case of bears, big furry humans); because not everyone does. Hey, at least the Dalai Lama is with me on this one.

Comments

  1. #1 sonyala
    February 8, 2008

    right on AT. I’m with you on this one.

  2. #2 Sandra
    March 6, 2008

    Finally someone who thinks clearly about the argument! I use to say that even if we don’t like the idea, human beings are animals also. Sooner or later, things will be tested on animals: ourselves. And the things will not stop on us.

  3. #3 Jamie
    April 4, 2008

    Not that I disagree with 99% of what you wrote, but are you saying you’d be fine chugging down pills that came out positive in a HERG block screen? After all, it’s “only cells”!

  4. #4 AngryToxicologist
    April 18, 2008

    Jamie,
    Maybe. The thing is, if something is positive in the hERG assay (IC50 less than 10 uM or there abouts), the company would move next to do a cardiovascular study in dogs to confirm as the false negative is huge for a hERG (see #4 above). So there are plenty of hERG assay positive compounds out there but they aren’t risky (hERG only speaks to hazard and badly at that).

    This speaks exactly to my point; if only a hERG assay was done, I wouldn’t feel very comfortable one way or the other. The assay is almost worthless from a risk assessment perspective unless the IC50 is super low, but it’s very valuable as a drug screening tool.

  5. #5 muhabbet
    March 26, 2009

    thanks..

  6. #6 Abercrombie
    November 30, 2009

    Sooner or later, things will be tested on animals: ourselves. And the things will not stop on us.

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