Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Sulfoxides: A Sneaking Affection | Main | Spray-Painted For Success »

August 13, 2009

Animal Testing: A View From the Labs

Email This Entry

Posted by Derek

Why do we test drugs on animals, anyway? This question showed up in the comments section from a lay reader. It's definitely a fair thing to ask, and you'd expect that we in the business would have a good answer. So here it is: because for all we know about biochemistry, about physiology and about biology in general, living systems are still far too complex for us to model. We're more ignorant than we seem to be. The only way we can find out what will happen if we give a new compound to a living creature is to give it to some of them and watch carefully.

That sounds primitive, and I suppose it is. We don't do it in a primitive manner, though. We watch with all the tools of our trade - remote-control physiological radio transmitters, motion-sensing software hooked up to video cameras, sensitive mass spectrometry analysis of blood, of urine, and whatever else, painstaking microscopic inspection of tissue samples, whatever we can bring to bear. But in the end, it all comes down to dosing animals and waiting to see what happens. That principle hasn't changed in decades, just the technology we use to do it.

No isolated enzymes can yet serve as a model for what can happen in a single real cell. And no culture of cells can recapitulate what goes on in a real organism. The signaling, the feedback loops, the interconnectedness of these systems is (so far) too much for us to handle. We keep discovering new pathways all the time, things that no model would have included because we didn't even know that they were there. The end is not yet in sight, occasional newspaper headlines to the contrary.

We do use all those things as filters before a compound even sees its first rodent. In a target-driven approach, which is the great majority of the industry, if a compound doesn't work on an isolated protein, it doesn't go on to the cell assay. If it doesn't work on the cells, it doesn't go on to animals. (And if it kills cells, it most certainly doesn't go on to the animals, unless it's some blunderbuss oncology agent of the old school). The great majority of compounds made in this business have never been given to so much as one mouse, and never will.

So what are we looking for when we finally do dose animals? We're waiting to see if the compound has the effect we're hoping for, first off. Does it lower blood pressure, slow or stop the growth of tumors, or cure viral infections? Doing these things requires having sick animals, of course. But we also give the drug candidates to healthy ones, at higher doses and for longer periods of time, in order to see what else the compounds might do that we don't expect. Most of those effects are bad - I'd casually estimate 99% of the time, anyway - and many of them will stop a drug candidate from ever being developed. The more severe the toxic effect, the greater the chance that it's based on some fundamental mechanism that will be common to all animals. In some cases we can identify what's causing the trouble, once we've seen it, and once in a great while we can use that information to argue that we can keep going, that humans wouldn't be at the same risk. But this is very rare - we generally don't know enough to make a persuasive case. If your compound kills mice or kills rats, your compound is dead, too.

I've lost count of the number of compounds I've worked on that have been pulled due to toxicity concerns; suffice it to say that it's a very common thing. Every time it's been something different, and it's often not for any of the reasons I feared beforehand. I've often said here that if you don't hold your breath when your drug candidate goes into its first two-week tox testing, then you haven't been doing this stuff long enough.

Here's the problem: giving new chemicals to animals to see if they get sick (and making animals sick so that we can see if they get better) are not things that are directly compatible with trying to keep animals from suffering. Ideally, we would want to do neither of those things. Fortunately, several factors all line up in the same direction to keep things moving toward that.

For one thing, animal testing is quite expensive. Only human testing is costlier. In this case, ethical concerns and capitalist principles manage to line up very well indeed. Doing assays in vitro is almost invariably faster and cheaper, so whenever we can confidently replace a direct animal observation with an assay on a dish, plate, or chip, we do. All that equipment I mentioned above has also cut down on the number of animals needed, and that trend is expected to continue as our measurements become more sensitive.

So things are lined up in the right direction. Any company that found a reliable way to eliminate any significant part of its animal testing would immediately find itself in a better competitive position.

And for the existing tests, it's also fortunate that unhappy animals give poor data. We want to observe them under the most normal conditions possible, not with stress hormones running through their systems, and a great deal of time and trouble (and money) goes toward that end. (In this case, it's scientific principles that line up with ethical ones). Diseased animals are clearly going to be in worse shape than normal ones, but in these situation, too, we try to minimize all the other factors so we're getting as clear a read as possible on changes in the disease itself.

So that's my answer: we use animals because we have (as yet) no alternative. And our animal assays prove that to us over and over by surprising us with things we didn't know, and that we would have had no other opportunity to learn. We'd very much like to be able to do things differently, since "differently" would surely mean "faster and more cheaply". None of us enjoy it when our compounds sicken healthy animals, or have no effect on sick ones. Just the wasted time and effort alone is enough to make any drug discoverer think so. There are billions of dollars waiting to be picked up by anyone who finds a better way.

Comments (82) + TrackBacks (0) | Category: Animal Testing | Pharma 101


COMMENTS

1. darwin on August 13, 2009 7:56 AM writes...

Well said Derek. Perfect example is cardiac physiology and potential API effects on one or more ion channels and their complex interactions. One can conduct in vitro receptor binding or other in vitro or ex vivo assays all day long, but until you test the compound in vivo, no one can have full confidence regarding arrythmogenic potential.

Permalink to Comment

2. Sili on August 13, 2009 10:05 AM writes...

Hear! Hear!

Very fair and balanced (in the real sense).

Permalink to Comment

3. SciChick on August 13, 2009 10:17 AM writes...

Derek, what's you take on microdosing? I realize there has not been enough data points to demonstrate whether this paradigm would work, but in the end, if this is feasible, one can imagine the dramatic reduction in animals that are consumed in the early phase preclinical development.

Permalink to Comment

4. BioGuy on August 13, 2009 10:42 AM writes...

All of what you say is true, Derek, however your colleagues are also reluctant to try new methods to reduce animal studies. Case in point. A company I work with, VaxDesign, has an in vitro system that replicates the human immune response to vaccines, immunosuppressants, and other agents. Lots of data. But companies have been extremely slow to adopt this new technology. People do not like change. They like their animal models and are resistant to new methods that could reduce the need for animal tests.

Permalink to Comment

5. Anonymous on August 13, 2009 12:00 PM writes...

BioGuy-I don't know anything about your model but I'd assume that companies are not using because regulating agencies we always have in the back of our minds...what data is acceptable to the regulating agencies. It takes a lot of data to get guidance from the regulatory agencies on new techniques. I'd suggest that your company partner with academia to increase the data out there and fuel the spread of the technology...but again, I don't know anything about your company...perhaps it is already headed down this path. I want to assure you though...that at least where I work no one is closing their minds to new ideas. New ideas are brought in everyday and their utility is discussed thoroughly.

Permalink to Comment

6. Anonymous on August 13, 2009 12:04 PM writes...

addition to previous comment. I know you said there is lots of data on this technique. It probably requires obscene amounts of data. Example...for all of the guidance ICH and USP provide us on residual solvents in our drugs-there are still some common solvents for which they provide no guidance because there is not enough data.

Permalink to Comment

7. Hap on August 13, 2009 12:05 PM writes...

I think the FDA wants a whole lot of data that the nonanimal tests give results correlating to those obtained from animal tests before it approves drugs or clinical data based on them - so drug companies aren't willing to spend lots of money (and the less fungible resource of time) to test whether the nonanimal tests give the same results.

This is something that would be best done by NIH - the test developers don't have the cash, and drug companies aren't going to spend their valuable time and money on a shared benefit. Alternatively, the drug companies would have to validate the alternative tests cooperatively. Probably why they haven't been validated yet.

Permalink to Comment

8. barry on August 13, 2009 12:16 PM writes...

re: microdosing
At one time, I held out huge hope for microdosing to preview the fate of a potential drug in man. Alas, it has grave flaws. No drug distributes to exactly one physiological compartment. A small compartment--that would be utterly negigible at therapeutic dose levels--can totally dominate the pharmacokinetics of a microdose. The data coming back can't be trusted.

Permalink to Comment

9. MTK on August 13, 2009 1:19 PM writes...

Excellent explanation, Derek.

Unfortunately for the really hard-core animal rights folks it won't mean anything. Their belief is based on the concept of "specieism", which is analogous to racism or sexism. The sin in their minds is that we consider some individuals to be of less worth than other individuals solely based on the species of that individual. So any animal testing no matter what the rationale is wrong. The only way to avoid specieism would be to test on humans. And just because other species practice specieism does not justify us practicing specieism. No more so than a group of racists would make it OK for us to be racists.

Good luck dealing with some of these arguments.

Permalink to Comment

10. Cloud on August 13, 2009 1:21 PM writes...

This is indeed a very good post.

If I'm feeling lazy, I tell people we have to test in animals because of Donald Rumsfeld's famous "unknown unknowns". There is so much that we don't even know we don't know....

I've also tried pointing out that the alternative is testing in humans without toxicity data to help us set a safe dose, etc. Usually, that works.

Sometimes, though, it is a lost cause to try to argue with people. One time, someone threw back at me that the smallpox vaccine had been developed without animal testing. Well, yes. Instead, Jenner tested his ideas on a human child of lower socioeconomic status (he injected his gardener's son with cowpox and then smallpox). Luckily, Jenner was right and the boy didn't get smallpox. But what if he'd been wrong?

I explained all of this, and the person thought that this was better than animal testing.

Personally, I'd rather we use animals, even cute ones, than children. Apparently, not everyone agrees with me. That scares me.

Permalink to Comment

11. Riaan on August 13, 2009 2:09 PM writes...

thank you Derek, did not expect you to post a response so soon after my comment.

I have to admit that I may be one of those people who argue the specieism point - as pointed out by another commentor.

What checks and balances are in place to guard against abuse? If this is like any other business I imagine that corners are cut sometimes, people cheat sometimes, big promises are made but what actually happens is a different matter.

And also how many frivolous "comfort" drugs are being developed and tested? Eating too much fat - take this, those lines around your eyes bothering you - we've got a cure for that!

Permalink to Comment

12. BOB on August 13, 2009 2:57 PM writes...

So you would rather live in a world without modern medicine than in one where animals are tested?

In order to live up to these principles you would need to live like Theodore Kaczynski. After all it isn't only medicines that harm the animal world. Do you put gas in your car? Do you live in a house, if so it was stolen from weaker species. What gives you the right to do that?

Permalink to Comment

13. Alig on August 13, 2009 3:37 PM writes...

I used to work for a big pharma company. They had a board for the ethical treatment of animals that set out the guidelines for what procedures could be performed and how the animals were treated. It was serious business. You obeyed those rules the same as OSHA, GMP and FDA guidelines.
Also justification always had to be given to use a higher species. Most experiments are done in rodents.

Permalink to Comment

14. Jose on August 13, 2009 3:38 PM writes...

What about the cyanobacteria? Who still stand up for them and all their brethren? And what about Periplaneta americana?

Permalink to Comment

15. BioGuy on August 13, 2009 4:03 PM writes...

Anonymous - yes of course the replacement of animal studies for regulatory purposes is not even close. Yet many animals are used for research purposes that are not part of a regulatory package. Also, you can submit in vitro data as a supplement in a regulatory application. The goal in the near term is to reduce the number of animals used in research. If an in vitro test correctly predicts human responses to vaccines, then why would you continue to use animals for that same test? Europe gives lip service to this idea but then runs everything through ECVAM which will not validate proprietary assays. The result is that many technologies that could reduce animal research use will never become validated.

Permalink to Comment

16. Riaan on August 13, 2009 4:04 PM writes...

@Bob I prefer to live in a world where harm is not done to others. If it is possible to get closer to that ideal - then do what you can to get closer to it. Just becaue it is hard is no excuse.

Does the fact that somewhere there is a guy bigger and more ruthless than you mean that he can do what he wants with you?

No, as a society we have values that determine what is acceptable for us to do. These eco-nut ideas are simply a new societal value that may (or may not) form part of the future social norm.

Permalink to Comment

17. Hap on August 13, 2009 4:33 PM writes...

As a supplement to testing, in vitro wouldn't seem to be much good - you have to spend extra time and money doing something that you have already done another way, or you have to risk having to redo many of the tests. Only when the in vitro assays well-validated and accepted by the regulatory agencies would they actually be useful as replacements for tests in animals.

What am I missing here?

Permalink to Comment

18. Larry on August 13, 2009 5:15 PM writes...

Great blog. That makes total sense. My question is then at what point is risk allowed assumed okay over reward. At what point do we take humans that have been on "compounds" for awhile and test them. I remember as a teenager I was blood tested once a month for the perscription I was taking, I dont know why but it seems logical ... getting something put in lets see how it affects the body regularyly.
One last thing is there a time when we use something like specific chiropractic and compare it to more and more "compounds" once they make it to the human "models?"

Permalink to Comment

19. Kismet on August 13, 2009 7:23 PM writes...

Riaan, sure you *prefer* to live in that world, but it is not the real world (at least not now as pointed out by Derek).
Either we use animals or people will suffer from our neglect of preclinical research. Even if you argue the speciesism point, you'd have to actually deem other species to be not just equal, but *more* important than humans, if you want us to forgo animal testing.
And don't forget that animal testing can also benefit other animals.

But please elaborate about 'frivolous "comfort" drugs'? Mitigating the damage that obesity does to our society and economy certainly is a worthwhile goal (and, no, obesity is not just a matter of laziness, although it often is).

Permalink to Comment

20. Bored on August 13, 2009 8:08 PM writes...

You know, what is so bad about specieism? We've become hypersensitive to having labels applied to us. If the animal "rights" wacko's truly believed in what they said, they would all practice Jainism.

There is no privileged frame of reference, physically or morally. We are "geocentrists" by the fact that we live on this particular speck of rock and metal. That humans currently OWN the planet is evolution's gift to us. (Or, depending on your persuasion, God's gift to us, or God's gift to us through evolution.)

Makes me want to have a shirt made that says: "Practicing Specieist."

A little courage in the face of these nuts is in order.

Permalink to Comment

21. Morten G on August 14, 2009 6:03 AM writes...

@Riaan
I think you're taking your argument to the wrong place. You can't get untested pharmaceutical drugs but if you want to live without pharmaceuticals then you have plenty of opportunity. But Derek and most people who read this blog is in the business of providing people with proven methods. Animals have weak and diffuse concepts of self and future and that's why we evaluate that where no other method is available it is better to test something in an animal before doing it in a human.
Personally I think that as long as fear and harm is equal or less than what the animal would experience in nature then we are on moral quite solid ground.

Permalink to Comment

22. Phlogiston on August 14, 2009 6:43 AM writes...

Great post. It really captures all the saliant points about animal testing in pharma. I think the biggest contribution of the early animal rights movement has been the awarness towards reducing suffering of lab animals. As pointed out in the post, happy animals make sense scientifically, morally, and financially. I can't think of any scientist who enjoys animal testing, bur we all recognize that we are vastly ignorant of biological systems, hence it is unavoidable. One could be quntitative about it and say that developing medicines which treat a painful condition or saves lives reduces the overall amount of suffering in the world for both the animals and humans who will take these drugs. For all the reasons Derek ellaborated upon, if someone did come up with a validated method which either reduced or mostly eliminated testing, every company who cares about making money would be using it. I know Derek's post will do little to change some of the extremist's minds (perhaps if they had better science education they might understand a bit more), but I do hold out hope that more moderate people will listen. One of the comments mentioned the testing a development of "lifestyle" drugs on animals, like ones for baldness, obesity, male bedroom problems, etc..., but I believe that even in those cases, most of them were designed for other reasons (high blood pressure, depression, etc). I'm not a big fan of these drugs, but I don't believe testing on humans is a very good alternative. This claim that all animals are morally equivalent is stupid. I have little sympathy for a mouse eating my cereal, much as a lion has little sympathy for a gazelle. Besides, where does one draw the line? Is a spider equivalent to a mouse or human?

Permalink to Comment

23. Alig on August 14, 2009 7:04 AM writes...

Did you see the story last week of the old lady who was repeatedly warned against feeding bears from her porch? They found two bears eating her. I couldn't believe what happened next, the cops shot the bears. They didn't read the bears their rights or assigned them attorneys, they just shot them. PETA should be out there protesting against those police officers.

Permalink to Comment

24. Bored on August 14, 2009 7:27 AM writes...

#23 Alig

That was natural selection at work as well. The woman's genes predisposing her to feed bears are now out of the gene pool, and the bear's genes predisposing them to eat stupid humans are, unfortunately, also eliminated.

Permalink to Comment

25. Alastair on August 14, 2009 7:31 AM writes...

One thing that's often overlooked is pest control. I can't remember the exact figures, but in the UK a quick search suggests that about 5 times as many rats are killed by pest controllers as are used in drug research. And how many animals are killed for food? Humans use animals in many ways, drug discovery is one where at the moment we don't have another option.

Permalink to Comment

26. ARPhilo on August 14, 2009 7:43 AM writes...

How about humane pest control, not killing animals for food, AND not using them for research? The idea that all modern medicine would halt without nonhuman animal testing is a complete farce. I do believe that some scientists actually believe this because it is so ingrained in them throughout education. We are all brainwashed in school. I know I really believed that animal research was helping at some time in my life, before researching things further and seeing the deceit running rampant.

It's time to break free from that though and realize that although some methods can not tell us how something will act in a complex system, nonhuman animal testing does not tell us how things will react in the human system! Sure, sometimes there is a correlation, but pointing out a few successes in a mass of failures (causing suffering and death of humans who had things tested upon them after other animals) does not defend such a primitive practice.

Nonhuman animal research is outdated, inaccurate, inhumane, and most of all- DANGEROUS. Nonhuman animal testing does not predict human response enough for us to depend upon it. The sooner scientists realize this, the sooner we can see more medical progress without the torture of nonhuman animals being involved.

To those of you "proud" to be speciesists, that's sad. It reminds me of many other "proud" -ists in other movements. Go ahead and wear your shirts. It will only make the opposition to you look better.

Permalink to Comment

27. MarkySparky on August 14, 2009 8:10 AM writes...

#26/7 ARPhilo,

Congratulations, you hit the homerun of animal testing crankery in one post:

1. Positing an conspiracy of educators to promote animal testing, and relating your own Road to Damascus conversion;
2. Demonstrating a complete lack of understanding of the terms "complex system" and "human system";
3. Admitting that in vitro techniques are of limited utility, then demanding perfectly predictive data from 100% of animal tests;
4. Using the word "torture" means you either have never dealt with an IACUC, or your ideological definition makes "torture" so broad as to be meaningless.

Bonus points for the veiled Godwin in that last bit.

Permalink to Comment

28. Bored on August 14, 2009 8:59 AM writes...

#28 MarkySparky

Ah, but you miss the point. #27 ARPhilo is speaking from the point of view of a privileged frame of reference. Not all of us are so fortunate. Damn! I wish I could always have the moral high ground too...

Permalink to Comment

29. Alig on August 14, 2009 9:06 AM writes...

Also testing in small groups of humans doesn't always predict what happens in large populations, so we should just skip the small studies and immediately dose thousands of people so we don't wate our time.

Permalink to Comment

30. Bored on August 14, 2009 9:40 AM writes...

Alig, you don't take it far enough. Let's do away with drug testing altogether. Let's do away with Pharma! Let's do away with any type of health care of any kind. The animals don't have doctors or drugs, why should we? It isn't fair that humans can fight disease when polar bears can't. It is outright speciesist of us!

The alternative is to create medical schools for dinoflagellates. Of course, the dinoflagellates might have to do drug testing on us one day...

Permalink to Comment

31. MarkySparky on August 14, 2009 9:46 AM writes...

#31 Bored

What about veterinarians, veterinary small molecule drugs, and veterinary biologics?

Permalink to Comment

32. Sili on August 14, 2009 9:54 AM writes...

Some people seem to focus a bit too much on the negative (I do too all the time).

The important thing isn't to convince the ALF &c nuts of our good faith. It's the public we need to relate to. Move the Overton window if you like.

Permalink to Comment

33. MTK on August 14, 2009 9:57 AM writes...

Alig,

I was thinking along the same lines.

The animal rights folks argue that testing in animals isn't very accurate and therefore useless, but they're missing the point. All of the testing in vitro, in animals, and clinical is not about absolute assuredness, but rather risk management. At each step of the way, if something is observed that indicates that the compound does not have enough therapeutic value relative to other effects, it is terminated, because the risk to move forward is too large. Which is exactly why tests are first done in small numbers before moving onto larger numbers.

And ARPhilo, "pointing out a few successes in a mass of failures", fails to capture that in all probability nearly all the compounds that failed to get past animal testing would have caused massive suffering in humans had that step been omitted. So I would deem most of those very successful.

Finally, I don't quite understand why the pharma companies are the subject of all the rage? It would seem to me that Pharma should be third on the list. Should not the protests and acts of rage be directed toward the regulatory bodies which require animal studies? Pharma is doing what's required of them. If one wants to eliminate the animal testing, you have to eliminate the requirement of it for IND or NDA submission first. Second in line would be the legal system. PETA or others should ask Congress to pass a law indemnifying researchers from civil litagation arising from adverse effects seen in clinical trials that were missed due to the absence of animal testing. Changing the regulatory and legal landscape would be vastly more effective than the current strategy and tactics. Somehow I don't see it happening, however.

Permalink to Comment

34. cynical1 on August 14, 2009 10:22 AM writes...

As a vegetarian medicinal chemist, I feel the inclination to put in my two cents. Actually, contrary to the post above, nonhuman testing does tell us something about how it will react in a human system. If 9/10 rats die after two weeks of dosing, it is almost assured to cause gross toxicity in humans as well. If 0/10 rats die, one hopes for the best in humans. It is archaic but not outdated.

I wonder how many animal rights activists have taken prescription or over the counter drugs. If they refuse all drug treatments and would willingly die of an easily cured bacterial infection, then I applaud their convictions. However, anything less would be hypocritical. I don't eat animals because it is completely unnecessary for me to survive. However, I could have easily died from a perforated ulcer if I didn't treat my ulcers (brought on by being a medicinal chemist).

With that said, I also would suggest that the industry has refused basic common sense in early stage research. How many compounds optimized for a 7TM receptor, ion channel, nuclear receptor ect. have never even seen a simple cytotox screen before they go into an in vivo tox study? Anti-infectives aside, how much effort would it be to dose your compounds against an immortalized cell line (CHOs, MT4s, Jurkat, ect.). If I had a scaffold that showed cytotox at 1 or even 10 uM, I'd be looking for a new scaffold. No, it's not perfect but it is easy and a pretty cost effective way to prioritize hits from a screen at a minimum. When I suggested it at my last employer, they looked at me like I had two heads (and they already had the screens up for the antiviral assays). But I have to ask myself how many drug candidates that failed for toxicity reasons would have passed that quick and dirty test.

Just my two cents......

Permalink to Comment

35. Bored on August 14, 2009 10:29 AM writes...

MarkySparky,

Maybe my comments got lost in sarcasm. I was saying, "Where are the animal doctors who are animals? The drugs invented by animals?"

Your point is excellent, though. Humans, by and large, take pretty good care of animals today. (I thus invite some PETA freak to send us a link to some chicken slaughter house.)

Can you pass the honey mustard?

Permalink to Comment

36. stuff on August 14, 2009 10:32 AM writes...

I have a poster on the wall here that puts the numbers in context.

In their lifetime each human (I suspect this is for N. America or Europe) is responsible for:
* Eating 600 chickens, 30 sheep, 30 pigs and 5 cows.
* 8 mice or rats killed in public health actions; and
* 3 mice and 1 rat used in experiments.

Permalink to Comment