The Post really screwed this one up, not so much because they took a side on an issue in news piece (this is close to an opinion piece), but because it gets so much wrong and doesn't even address the rest of the story.
Issue 1: Science will save them!
I've been over this before, here and here, but we'll do it again. The Post makes it seem as if we have all this technological advances that can make tests more applicable to humans. Okay, here's how you would make an in vitro system similar to a human: take cell that you want to look at, surround it with other cell types it interacts with from that organ, embed channels to get nutrients, wastes, and other chemicals in and out, then add other organs that interact with that orgen, and systems for communication between different organs, and mechanisms for defense. You see where I'm going with this: the best model for a human is a human. The next best this is logically and scientifically, an animal.
All the in vitro techniques are, and will be, reductionist (i.e. the deal with only very small and specific questions). Why? Because you can't model the human body without building a body. Furthermore, we don't really even understand completely how the body works so how in the heck do you think we can confidently build models when we're unclear about what we're comparing it too. It's like having someone say, "I want you to build a house that is exactly like that one. Oh, I don't have any blueprints, but you can look in some of the windows."
Issue 2: C'mon, don't be so hard.
It makes 4 out of 185 methods approved sound really bad, like ICCVAM was way too harsh. If they were more lax, maybe we'd be reading a story about how some drug has been killing people because a test that didn't work was used. Here's a novel idea for you, maybe the other 181 didn't work.
While we're on this, let's move to Issue 3: Oh, I love Europe, they're the bestest!
First, I don't know of any ECVAM test methods that have been adopted by EU member countries that have been rejected by ICCVAM (that's the US side of things). If anyone knows of one, please post it in the comments. Second, there have been a couple of eye toxicity tests that the EU accepted without validation. The EPA nominated the 4 tests but when the validation was done, it was found that 2 of them don't predict eye tox well enough to be used for regulatory work. Whoops! Guess we should have used the European approach and just taken them based on the existing literature, cause they're all a bunch of socialist liberals who are so far advanced in keeping their citizens safe. Right, right? Geeze Americans, get over the Europe-envy already. Lovey culture, health care, and public transit, no doubt about it, but I'll keep our drug development problems over theirs (and our immigrant problems over theirs, for that matter).
Issue 4: "Animal don't predict what will happen for anything else". Hey blockheads, as far as physiology is concerned, we're animals too. So I guess I do agree with this, 'Plants aren't good predictors of human toxicity'.
Issue 6 In vitro tests are the way of the future, man. Don't be a square!
Yeah, and at one time so were TV dinners, space travel, and dropping acid daily. We flirted with those at one time or another and realized that they weren't really the best idea. The article presumes that non-animals tests can be, and at some point, will be used. It really isn't a given that they will be better. Maybe animals that evolution has linked and produced over millions of years are just better models for each other than what one can dream up in a petri dish in a decade. Maybe not, but you've got to prove it.
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My other big question reading the piece is how many times does Europe rely on American tests? For example, if a product is approved in Europe and animal testing rejects it in the US, I assume it loses approval in Europe. For that matter, how many products are only tested in the US, since we have stricter standards.
Europe can and does take advantage of what happens in the US. That said, there's no reason every country needs to duplicate every animal test for every product, but the animal testing in the US is benefitting Europe.
We don't rely on each others' testing and approvals as much as we (both) ought to. The EU still has a somewhat different philosophy about quite a few things, and thus wants things tested their way, so a lot of stuff gets done twice but slightly differently (at great expense of time and money). There is slow progress in harmonization; a minor update to the U.S. Good Manufacturing Practices (GMP) takes effect this Thursday, whose main purpose is to better harmonize our manufacturing practices with theirs. Each major country's approval processes has some slightly better and some slightly worse aspects than others, but overall the quality level is not much different.
I would be comfortable, and think it would make good sense if we all pretty much decided that if a drug or device gets approval through the full process in the U.S., the EU, Canada, or Japan, that all the rest should be able to approve the same quickly and with little additional testing. I actually think this would be a better approach than trying to completely harmonize the regulations, since no country ever wants to reduce a regulation, so a harmonized system will almost certainly wind up being made up of the most strict interpretation of every possible regulation and be very difficult to meet. Better to recognize that we all have different approaches which are nonetheless roughly equivalent, and let that be OK.
But that would make way too much sense to ever become an official government policy.
PhilB
The brief reference to evidence-based toxicology in the post report was very odd. Evidence based toxicology is a strategy for evaluating different toxicology methods, it is not a toxicology testing method itself. Sure it should be used to evaluate the ability of a particular in vitro or animal test or testing strategy to predict human or environmental toxicity, and that may lead to particular tests being dropped, modified or moved further down the pipeline, but it can't replace a method. This would be like saying that evidence based medicine is a replacement for clinical trials or case reports!
I suspect that the papers being referred to were opinion pieces/reviews expressing a particular authors opinion on evidence based toxicology and how it should be used, opinions which may not be in line with those of mose toxicologists in Europe or anywhere else. Unless we can read those articles it's impossible to tell if the ICCVAM members were unreasonable in their comments.
Surely most of what ICCVAM does is evidence based toxicology? I hope that ICCVAM makes a robust response to the Post article.
In sentiment and policies, Europe is much more bioconservative than the United States.
With a host of biomedical technologies and practices - animal research, therapeutic cloning, genetically modified organisms, water fluoridation, vaccination - Europe is more restrictive and fearful. To be sure, each country has different policies, so these have to be stated as generalities rather than blanket rules.
In addition, Europe is more accepting of homeopathy, a traditional quack therapy. European practices of handling milk products also tend to be more traditional (e.g. less refrigeration) resulting in much higher rates of toxoplasmosis in France compared with the US.
European traditionalism even extends to abortion, which is generally more restricted in Europe than the United States. On the other hand, the state is much more permissive of euthanasia.
"Guess we should have used the European approach and just taken them based on the existing literature, cause they're all a bunch of socialist liberals who are so far advanced in keeping their citizens safe."
That is a common attitude among professional class American liberals, isn't it? I suspect they would reconsider their 'Euro knows best' if they appreciated how knee-jerk biotech-phobic and traditionalist Europe really is.
I have to emphasize that I'm talking about Western Europe, not Eastern Europe. It's not just the Catholic countries either.
Hmm. I wonder what, specifically, these in vitro techniques are that they are referring to. Seeing as how Affymetrix still has most of their proteomics chips *in development* or for custom non-GLP use only. Unless they are referring to the ToxFX suite? But that is only for early pipeline results of HTS hits, and it's pretty cheesy. I mean, I work for Big Pharma, and our competitors use it but they aren't 100% happy with it. We put more $$ into refining our library for toxicity instead of trying to do it on the back end.
Why didn't the WP find some scientists *who actively use* the in vitro techniques and ask them what they think? I mean, I've got a bunch of stuff in my lab that I have, and I use it, but it's not the best and it's not my favorite for various reasons. And a lot of stuff that I bought that was promised to be the Bestest Technique Ever turned out to be not so great. So it goes with all techniques, including tox screening.
Yeah, and at one time so were TV dinners, space travel, and dropping acid daily. We flirted with those at one time or another and realized that they weren't really the best idea. The article presumes that non-animals tests can be, and at some point, will be used. It really isn't a given that they will be better. Maybe animals that evolution has linked and produced over millions of years are just better models for each other than what one can dream up in a petri dish in a decade. Maybe not, but you've got to prove it.
Maybe animals that evolution has linked and produced over millions of years are just better models for each other than what one can dream up in a petri dish in a decade. Maybe not, but you've got to prove it.