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I've heard from animal rights activists that experiments on animals are not necessary because we can get the same or better results from cell culture experiments.

An example of that claim is this excerpt from a comment on a blog:

2) According to the former scientific executive of Huntingdon Life Sciences, animal tests and human results agree “5%-25% of the time.”

3) Among the hundreds of techniques available instead of animal experiments, cell culture toxicology methods give accuracy rates of 80-85%

Posted in the comments section on Respectful Insolence

I don't want to focus on the exact numbers given here, but on the general issue of toxicology testing using animals and cell cultures. Determining the safety of new chemical compounds, drugs etc. is a major use of animal experiments, I'll focus my question on these toxicological studies.

Can cell culture methods effectively replace animal experiments for toxicological studies?

Sklivvz
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Mad Scientist
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    I think "toxicology" should be added to the title. – Rusty Mar 31 '11 at 16:29
  • At the very least, we certainly wouldn't have learned nearly as much about ethology (animal behavior) without keeping at least SOME animals in captivity... 'Study' does not necessarily equal 'be cruel to'. – Joseph Weissman Mar 31 '11 at 16:50
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    Since this is just my opinion as an environmental chemist, I'm not going to list it as an answer. Cell culture toxicology is definitely a worthwhile tool for determining some aspects of toxicology, but in my opinion it cannot replace animal experiments for the 'entire picture' so to speak. Some animal tests can be better applied to human physiology than others, this is true. But the whole point of toxicologists isn't just what's toxic to us as humans. It's also a matter of what's toxic in the environment to other animals - and the test animals we use are good 'representatives' – Darwy Mar 31 '11 at 16:54
  • Some tests require live animals. For example, tests on [suspended animation](http://labs.fhcrc.org/roth/) – DampeS8N Mar 31 '11 at 16:56
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    for other species which are particularly vulnerable in the environment. Daphnia magna, Danio rerio, etc - these are all well studied animals in toxicology (just to name two), whose physiology is well known and understood. I'm currently testing nanomaterials (ZnO, Ag, and CNT's) and their toxiological effects on Daphnia - there is SO much we don't understand about how these new materials can effect organisms in the environment - and ultimately us. – Darwy Mar 31 '11 at 16:57
  • Are the 5-25% and 80-85% figures are measuring the same thing? It is difficult to tell from the blog comment. – Henry Mar 31 '11 at 17:28
  • Specific type of research being referenced here?In the development of veterinary medicines,obviously animal experiments are needed.In medical trials,it would depend on the quality of the animal model available,for instance we don't have a very good animal model to test new antidepressants,so it would be debateable,but in some other areas,we have reliable animal models(think Harvard Oncomice) which have yielded critical information.And with chemicals like DCA,different results are observed in vitro,in vivo, in animals and in human trials making each step necessary to determine toxicity. – Monkey Tuesday Mar 31 '11 at 19:27
  • I've made it more explicit that I want to restrict the question to toxicologic studies like those required for drug approval. – Mad Scientist Mar 31 '11 at 19:36
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    The issue still remains that pharmaceuticals end up in our waters; whether or not they're the original compound or a metabolite that we've excreted. Unfortunately the drug studies often don't take into consideration what percentage of the drug ends up in the environment. – Darwy Mar 31 '11 at 21:02
  • @Darwy I'm not sure how to work an environmental impact consideration into the course of a clinical trial that already costs in the +100 million range.Especially given the sheer amount of variables at work,which would vary with each individual drug,prevalence of use,geographically localized water filtration and sewage processing issues,indigenous wildlife, etc. I think you raise a good point,and environmental impact is a relevant field of study,but should probably be its own question here. – Monkey Tuesday Mar 31 '11 at 22:04
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    @Monkey Again, I'll refer to nanotechnology: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695593/ They're using nanomaterials in a clinical trial for chemotherapy - it has great promise for treating cancer; but it's a big ?? as to what's going to happen to the CNT's after they've eliminated the cancer cell. It's not just an environmental consideration (assuming the CNT's are excreted) - the CNT's are still in the body - what do they do to the liver? To the kidneys? Will they cause lymphatic issues? Arthritis? An in vitro experiment can't answer it all. – Darwy Mar 31 '11 at 22:27
  • @Darwy, you make a great point,and nonotech for chemo is particularly relevant.However, it's almost a singular case, it's a novel line of therapy (which functions like nothing ever before) and that definitely requires rigorous study evaluating the totality of its impact,since it's obviously unkown at this point.I was simply saying it would be difficult and possibly redundant to apply that line of reasoning to other drugs, such as new macrolide antibiotics, opiate-derived painkillers or things which we already understand the biomechanics of. – Monkey Tuesday Mar 31 '11 at 23:49
  • @Darwy I'm sure you know that back in the 70's anyone using genetic engineering methods to research human DNA had to use a P4 lab(the same used for Ebola Zaire).That's because the tech was new and unestablished,so the precautions were reasonable.Today, you can run a PCR just about anywhere. Nano may go this same route(especially since the Daphnia you are studying it in duplicates genes at 3x the normal rate and represents its own anomaly),they may not. You are right to push for caution, I just don't think we should extrapolate that same logic to all products in testing. – Monkey Tuesday Apr 01 '11 at 00:26
  • @Monkey I'd agree with you regarding opiates, but not the macrolides due to their penchant for inhibiting the cytochrome P450 system. – Darwy Apr 01 '11 at 06:37
  • @Darwy.I have a feeling we could keep at this for quite a while, but I think we've gotten into specifics that aren't exactly on topic anymore. I mean most people probably won't care about comments this specific. Keep up the good work. You seem to know your stuff. Cheers. – Monkey Tuesday Apr 01 '11 at 09:54
  • Hehe, in all honesty cellular tox isn't my forte. I ran screaming like a little girl from biochem as much as possible - I tend to focus much more on the environmental aspects of things but of course, you can't ignore one in favor of the other. – Darwy Apr 01 '11 at 14:45
  • @Darwy: Agreed :) – Monkey Tuesday Apr 01 '11 at 22:57
  • A cell culture isn't an entire organism, therefore studies on them don't reflect the effects of a substance on an entire organism. Logically therefore they can't replace studying an entire organism for at least some purposes. – jwenting Apr 18 '11 at 13:47

2 Answers2

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Ok, now with the edited question I'm going to weigh in.

No. Cell culture methods cannot effectively replace animal experiments for Toxicological studies.

While it will make some advances in toxicology, notably helping ensure products are safer when they come to market, it still doesn't give the 'full picture' of the life of a compound. They do wonders for xenbiotic compounds at the cellular and genetic level, but they cannot encompass all aspects of the toxicological picture.

Let's consider the in vitro tox screening for Ibuprofen.

In vitro studies have been done re: Bilirubin toxicity. (http://journals.lww.com/pedresearch/Fulltext/2009/04000/Ibuprofen_Augments_Bilirubin_Toxicity_in_Rat.6.aspx)

Other cytotoxic studies have been performed with rainbow trout and cellular cultures:

http://onlinelibrary.wiley.com/doi/10.1002/tox.20410/abstract

Does this compound bioaccumulate? Is it Biomagnified? These questions can't be answered via a cellular study.

Does this compound produce metabolites?? (yes!) - what is the process of degradation by the organism? How are the compounds excreted from the organism? Is this compound stored in fat? Are the metabolites stored in fat?

If you're curious about the metabolites of Ibuprofen in water, here's an example: http://www.ncbi.nlm.nih.gov/pubmed/15212901

A single cellular culture array cannot answer all the pertinent questions. It gives us an excellent picture of cellular disruptions, genetic impacts and such, but cannot compensate for the entire physiology of a test subject.

Darwy
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Your citation only apply to toxicology but your general question doesn’t original question wasn’t. So I’ll pick the remaining part.

Animal experiments are unfortunately (still) necessary. Most of the fundamental research today is conducted on animals and for the foreseeable time this will remain so.

Cell cultures and mathematical models are entirely inadequate in most fundamental research since we don’t know what to model. Just consider embryology which studies the developmental processes that lead to an adult animal. Understanding these processes is fundamental for our general understanding of biology and consequently future medicine.

Unfortunately, a big part of this research consists of mapping the embryology by cutting apart mouse embryos to take tissue samples (e.g. Mouse atlas).

This is true of basically every biological and clinical research. I’ll give two examples to illustrate this.

  • Diabetes mellitus is today one of the most prevalent diseases, an epidemic, and one of the major causes of death in the developed world (source: CDC). A lot of research goes into understanding it – and most of this research uses animal models – more precisely, mouse models (examples: 1, 2, 3, …).

  • Muscle development is regulated by a host of proteins. One of them is myostatin. Research into this protein could lead to cures for muscular atrophy which is ultimately the cause of death for several diseases such as DMD – Duchenne muscular dystrophy.

The information gained through these experiments cannot be replicated otherwise. In fact, there’s a big incentive for the industry and governments to use cell cultures or models instead – because they are vastly cheaper than experimenting on live animals. Industry interests and animal rights interests perfectly align in this regard so we can be fairly confident that the industry and public research are indeed doing their best to replace animal experiments by other methods.

Sklivvz
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Konrad Rudolph
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    Hi Konrad - please reference your answer. Thanks! :-) – Sklivvz Mar 31 '11 at 20:01
  • I think the question isn't really about the value of animal experiments for fundamental research but about the value of animal experiments for pharma toxicology tests. Could you add something about the issue of testing for toxicology? – Christian Mar 31 '11 at 21:00
  • Why the double negative in "not unnecessary"? – dbkk Apr 01 '11 at 04:51
  • @dbkk Because I’m directly negating the question, which asked after “unnecesary”. – Konrad Rudolph Apr 01 '11 at 08:50
  • @Sklivvz That’s tricky – the above is the underlying assumption of modern biology, I could cite any number of textbooks on biology and medicine but most don’t actually mention this explicitly (as far as I’m aware), they just mention study results with the relevant outcomes, and these studies invariably use animal testing. I prefer citing the research which relies on these methods – which I’ve done, “Mouse atlas”. – Konrad Rudolph Apr 01 '11 at 08:54
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    @Christian I really prefer not to. The issue of toxicology is *really* muddied (http://www.theskepticsguide.org/archive/podcastinfo.aspx?mid=1&pid=290). I don’t feel competent enough to comment. Furthermore, as I’ve explicitly noted in my answer, the original question did *not* exclusively ask about toxicology research. – Konrad Rudolph Apr 01 '11 at 09:00
  • @Sklivvz I did a rewrite. Better? – Konrad Rudolph Apr 01 '11 at 09:25