The lecture about responsible and reliable research presented by LeBreque sparked a lot of great conversation on the blog about unethical research and how much has changed in the past 50 or so years. Studies like the Tuskegee Study of Untreated Syphilis in the Negro Male resulted in better regulation of things like informed consent in studies involving human subjects in order to try to prevent experimental issues like this in the future. A comment on another blog post how the use of subjects, both human and non-human, is an evolving topic, and it made me wonder whether or not use of animals for scientific research will one day be considered unethical by the majority. I use mouse models in my research, and while I am not happy about it, I understand that they are being used for the greater good of advancing research, even if they are being used without their consent, and regardless of the fact that we are giving them diseases they most likely would not have contracted otherwise.
I decided to look into some of the current concerns related to use of animal research, and found an article posted by the New England Anti-Vivisection Society (NEAVS). According to the article, 24 of the 30 Institutes and Centers that make up the NIH use animals in their research, and about 40% of NIH-funded grants and contracts involve animal research. We use animal models under the assumption that they recapitulate humans biologically, and while we know animal models can represent human diseases and responses well, in many cases the way animals respond to treatment does not mimic human responses. The article gives examples such as how "forcing dogs to inhale cigarette smoke did not show a link to lung cancer; Flosint, an arthritis medication, tested safe in monkeys but caused deaths in humans; and the recalled diet drug fen-phen caused no heart damage in animals, while it did in humans". More than 25 million animals are used yearly in the U.S. in all areas of research, testing, and education, and the article says that statistically, 92% of drugs tested in animal and approved for human trials fail. Outside of drug studies, I would be curious to see how much of the data obtained through use of animals successfully models outcomes or responses in humans.
The article points to how factors like stress, which is often experienced by animals in labs, negatively influences the reliability of animal research data. According to the article, stress influences heart rate, pulse, blood pressure, muscular activity, and hormone level, and can influence results observed in studies. Cost of using animals in research is another issue addressed by the article. Animal research is a multi-billion dollar industry, with interest from the animal importers, breeders, dealers, cage and equipment manufacturers, feed producers, and drug companies. Additionally, purchase and maintenance of animals is expensive. "Rats, mice, and birds are the main animals used, not because they are necessarily the best or most reliable, but because they are relatively inexpensive to buy, easy to manage and maintain, and because they are disposable without much public clamor or concern."
Another point made by this article was related to the development in the last 10 years of using transgenic models for medical research. While transgenic models are great for attempting to remedy the biological differences between humans and animal models, the NEAVS article pointed out that if transgenic models are needed to genetically improve existing animal models, perhaps animal models really aren't justified for research use, because they really don't have biological and/or clinical relevance.
I agree that animal models are not perfect for researching human conditions, but I also cannot think of a non-animal alternative that is a better solution. I also believe that there should be some sort of in vivo model used after in vitro studies before testing drugs or whatever else in humans. The article blames a lack of alternatives on the investigators, but I don't see them offering any alternatives either. I guess time will tell whether animal research is eventually considered unethical, but I don't think that will come until someone comes up with a good non-animal alternative that does not jeopardize progress made with testing human subjects.
Briana, thanks for posting this. There's some interesting ideas in this about the negative side of animal research. However, I agree with you that there are some scenarios in which I can't think of any better alternative than animal studies. In our world of cancer research, there have been so many critical studies done in rodents that have made significant improvements for our understanding of cancer biology and even how we treat patients. I do think that we need to very carefully assess when animals are actually needed in studies; if there is a better alternative available then it should be used. But again, there are many situations where there just isn't a better alternative. I think scientists also need to be honest about the limitations of animal studies and when publishing results admit when and how the animal biology doesn't match human biology, but we can still learn so much more from in vivo studies.
ReplyDeleteI wonder if the majority of the non-scientific community already thinks that animal research is unethical, and just aren't aware of how much of it goes on. However, I definitely agree with what you said about there not being better alternatives to animal research in most cases. It would certainly be unethical to proceed directly into human trials from in vitro studies; if the majority of drugs trialed in animals go on to fail (or even be dangerous) in humans, just imagine how much worse it would be if we skipped straight from in vitro work to humans! I think that the benefits associated with animal research justify its drawbacks.
ReplyDeleteSo true! I think honestly most of the public just thinks of these mouse or "lab rat" experiments being science fiction or perhaps just for testing drugs in. It seems less likely that the public understands the need for animal research and more likely that they just don't realize how many thousands of mice are experimented on just at Emory in a given day!
DeleteThe ‘alternatives to animal research’ is an important point. As anyone who has written an IACUC protocol knows, one of the main purposes of the protocol is to be able to justify use of animals. A key component of this is an alternatives search where you have to provide evidence from the literature that your chosen model, be it rodent, amphibian, cat ect, is the best model, necessary to perform your work and that an alternative, especially a non-animal model, is not available or will not be suitable. To the point of the non-scientific community, I also wonder how aware it is of the considerable efforts made by investigators to ensure the wellbeing of animals and that they are not used frivolously.
ReplyDeleteAs far as looking into the future, I too wonder if animal work will one day be seen as unethical. Animal consumption, be it in its most literal sense as food for nutrition and sustenance or be it in its more abstract sense as pets for entertainment and companionship, has been central to our civilization. Yet as better alternative to animals became available, such as machines to replace animals domesticated for labor, we shifted our use to the alternatives. I imagine that should non-animal models eventually become superior to animals models when people are looking through the ‘retrospectoscope’ they will understand that animal models were our best options at the time and that the utmost care and concern for animal welfare was taken into account (in theory). I further wonder when that day will come, especially given the NIH’s current push for more reproducibility and more extensive animal trails prior to advancement into clinical trials.
I agree with the stance that you take in regards to the use of animal models. Mouse models still represent an important research tool for scientists, especially in my current area of interest, Glioblastoma. Using mice has a number of benefits over in vitro work, even primary patient-derived GBM cells. One of the principle concerns regarding any study of GBM is the role that the microenvironment plays on tumor itself. None of which can be adequately addressed using a cell line. I think the concern over the use of animals in the scientific discovery has been largely exacerbated by the mass media, and without proper education about why scientists use mice, I think the problem will only get worse. There is plenty of research to support the need for mice in the scientific process. Though it is true that humans have suffered from the differences between mice and humans in clinical trials, some leading to death, mice provide a much more powerful model than cell lines.
ReplyDeleteThough I support the use of mice for research, I cannot help but wonder about the ethics behind the treatment of mice. I have done a bit of mice work in the past, and one of the things that have bothered me the most is the sacrificing of mice due to cutting down the numbers of mice in the colony. It is hard to justify the killing of mice in this context, since the mice are not used for any experiment that will benefit humans. I think in this respect, research using mice can be seen as unethical; however I can still justify the use of mice strictly by the results that they can generate. Mice should be used for research as long as there does not exist a better alternative.
It definitely is interesting to wonder if majority of he general public already disapproves of animal research. It is hard to imagine anybody vehemently supporting animal research without cruel motives. From my experience, most people I've met think it's unfortunate that we conduct animal research but at the end of the day simply just necessary.
ReplyDeleteI think that this is where IACUC's incredibly important role does come in. As stated in one of the comments above, it is their role to decide whether the use of an animal in a research study is actually necessary. It is one of the requirements of animal research that all alternatives to animal research have been considered before the use of animal is suggested.
Hence, it is good to know that IACUC meetings are not just attended by scientists and other researchers, but also members of the public. However, having attended some IACUC meetings, it is certainly true that IACUC meetings are predominantly attended by scientists and researchers. Perhaps a shift in this ratio can bring us more towards the right direction.
"The article points to how factors like stress, which is often experienced by animals in labs, negatively influences the reliability of animal research data. According to the article, stress influences heart rate, pulse, blood pressure, muscular activity, and hormone level, and can influence results observed in studies."
ReplyDeleteThen apparently the article did a decent job cherry-picking normative autonomic nervous system functions in response to actual or perceived stressors. While I agree that it is necessary to minimize any untoward stressors when working with animals, I think it's important to keep in mind that presumably all animals will be exposed to the same types of routine "stressors" during the course of an experiment. Exposure to unintended stressors does not have to amount to a negative influence on the results, as the article suggests. This underscores the importance of having control groups built into your animal research so that all animals encounter the same similar unintended stressors (e.g. handling, routine cage changes, etc).
Isn't interaction between treatment and stressors the issue. True, if the experiment was done well, some control groups should get the same stressors as treated groups. But if the stressors interact with the treatment (which seems likely in some cases), the experiment basically tested what happens when the test treatment is administered on a background of cortisol jacked-up animals who could be sleep-deprived, unstimulated, hungry, in pain, or heavily doped. These interactions may be important (or they could be irrelevant). I think it is another caveat to some animal research. Again, is there a better alternative? I argue there is probably not a better alternative, but producers and consumers of the research should be aware of the limitations. Hence, IACUCs.
DeleteAbout IACUCs, however. The portion of the protocol that requires searching for alternatives seems like a great idea. However, I am not convinced how useful it is at getting an investigator to re-strategize to reduce or eliminate animal use. Often, years of resources have been used on method development. That momentum can be difficult to change.
Thank you for posting this. My first reaction was surprise at the fact that all NIH Institutes and Centers do not use animal models, and that a greater number of grants with animal models are not funded. It seems that we are entrenched in the use of animal models, and this does not seem likely to change for a while. Despite this culture, it is astounding to me that "92% of drugs tested in animal and approved for human trials fail". This seems like a great failure on our behalves as researchers. The reason that you exemplify from the article is that stress causes different responses among animals in trials. What else could contribute to this massive difference in response, however? The genetic conservation of genes related to the problem in question is presumably determined before experimentation begins. For example, 60-70% of cancer causing genes are conserved between Drosophila and humans. I am extremely puzzled at the fact that so many clinical trials with positive results in animals lead to negative results in humans. I would like to learn more about how/why that is the case, as it seems that a lot of money and time is being wasted.
ReplyDeleteNucleotide sequence and genetics are no doubt important, powerful determinants of phenotype. But there is lots of wiggle room in 3.1 billion basesgenes are not the whole story.
DeleteAs pointed out in earlier comments, there have been amazingly successful uses of animal models. For example, a form of early on-set retinal degeneration caused by null mutant forms of a gene required for retinoid recycling (RPE65), was replaced by gene therapy in dogs. Voila, the blind dog could see. This treatment has since moved to clinical trial in humans. Many of the first trial participants, like the dogs, had huge improvements in vision. This would have been extremely unlikely without animal experimentation.
If we want our kids and grandkids, etc, to get the best medical science can offer, responsible animal research is necessary. Mutations happen. Life happens. People are going to get diseases that suck. We have the ability to try to help that through animal research.
This was a great read, you brought up many great points regarding animal research. This especially hit home for me since our lab uses rats (almost on a daily) for our research projects. We have mother rats which are brought to us pregnant and we used their neonatal pups to collect heart cells for primary cell culture. We cannot use the mothers heart because the adult cardiomyoctyes do not culture. Then we use the mother rats for other studies. Overall, we use an animal for a significant number of our projects. I have had to perform the invasive surgeries to retract the tissue desired and often I wonder if each animal is being maximized. In the sense that I hope we are acquiring the maximum data from each animal. Another random thought, I wonder with the advancements in technologies if we are able to move away from animal models and move into 3D printed tissues?
ReplyDeleteI really enjoyed your post. This is such a loaded question, with so many factors to consider. Many scientist, myself included attempt to find a link between our research and human disease and health. Scientist process many tools like cell culture, mathematical predictors among others; however, the scientific community expects to see the physiological relevance of an experiment performed in a cell line. When I tell non-scientist that I work with animals I often get the questions "don't you feel bad for them?" or "isn't there other ways to figure out those questions". And what can you say without sounding like a detached or cruel scientist. Often, I have to explain that we make sure that the animals are well taken care of, that we use the minimal number we need and that these experiments are necessary to progress with the treatment of disease. Additionally, animal work is highly regulated by the IACUC, NIH and the Emory DAR. In reality I know that animal models are not perfect and that can be misleading and not work in humans; however, it is necessary to use that hypertension drug in a mouse before we attempt to give it grandma.
ReplyDeleteNo organism will behave, react and interact with treatment the same way; however, animal models allow us to have a starting point for a better understanding of scientific questions.