Animal models and alternatives?

A topic that I feel wasn't addressed enough in class or even in the forums is the potential impact of human research on the scientific community. It is interesting that we would still subject animals to what we ourselves would never undergo, or at least would never admit to allowing another human to undergo. But by do we believe that we are better than any other animals on this planet? I would agree with Paul Neuman's sentiments last week that the only thing keeping us from using human subjects in place of animals is that we are ourselves human and see too much likeness between the researchers and the subjects. After all, we know that it can and has been done, when the subjects were dehumanised by those who wished to do research.

Besides, we are already participating in human subject medical trials, as was brought up in class. Can we really deny an new drug that seems to cure cancer, just because we don't have decades of research on it to look for potential side effects?

Unfortuantely, as good as animal models are, and as willing as we are to value a human life over that of a lab rat, like is the best model for like. It can take into account any and all abnormalities and differences in the human brain and body, something a mouse or rat could never do.

Another interesting point that was brought up in earlier discussion is relevancy. Should research only be performed when it is absolutely necessary? How do we define what is necessary, and who gets to define that? Most of the medical and scientific knowledge that we have now was garnered in some way from animal research, but looking at exactly how it came about would turn our delicate stomachs today. Was it necessary then? Maybe, but probably not. Is it useful now? Without it, we would be as clueless now as we were in the middle ages. Just a thought.

There is such a wide variety of topics/thoughts to respond to above, that I wanted to pick just a few to touch on that I found most interesting.

First, i wanted to respond to some of the questions posed to those of us who work with animals for our senior research. For context, I work in an Immunology lab that uses mice (we use primary thymocytes for our experiments). On average I would say I use about 2 mice per experiment, though sometimes lysates can be used for multiple blots. This works out to be actually a lot of animals when all is said and done. (Side note: one interesting thing that I thought about when we were doing this is the idea of maturity of the animal-- I dont have as much of a moral issue with using frog embryos but do have to carefully consider my use of grown (young) mice.)

A question posed was: Given your research project, have you honestly as a researcher considered an alternate model? And the answer is yes, I have tried experiments using a non-primary cell type (DO11.10 for those who may be interested). Unfortunately, as is often the case, these cells are just not able to tell us as much as the primary cells can... they don't stain for IMF as well, they dont always react in the same ways that primary thymocytes do, etc. Its frusterating because to have a cell model would be great; it would really relieve the pressure to make sure that everything works, not just for experiments sake but for the sake of sparing more mice.

Another question was: Did you think about the limits of your model before this conversation? I have to admit that yes, this has come up a bit. Ian brought up the environment, and i have to say I hadn't really ever thought about the actual lab setting having an effect. I guess its slightly different for immunology-- to some extent I would almost hypothesize that a lab mouse would be a better model than a wild one simply because our society has become so "germ-free" recently and therefore more lab like for humans. (a stretch I know, but something I hadn't considered). As for other limits, I think whats really important here is not hte limits of our model but how much it can tell us... if we are still learning things about the model-- whether exactly applicable to humans or not-- it means we are still learning things about the system in general. and for me, learning makes it worth it. even if what I learn about murine thymocytes doesn't exactly correlate to humans i think its still valuable because then it gives an interesting comparison-- we could learn all sorts of things about evolution, system interactions in organisms, etc etc.

Another thing of interest that no one has brought up but that I think is really relevant here is the whole idea of knockouts. These are animals that we genetically engineer... often so that they are sick. I often think about this and am pretty conflicted-- I think knockout mice can tell us SO much and have been invaluable for their research contributions. however, isn't this a form of cruelty like we've been talking about? yes these mice may be housed and fed but we are intentionally causing them all sorts of harm in the form of severe illness and function. That doesn't exactly seem like something anyone (anything?) would give their informed consent to... I don't really have an answer. I feel like I couldn't give up knockouts, because they are so useful, but I really don't think that they fit under the "treat animals as best we can" idea. I'd love to hear what others have to say...

Many important and interesting points/questions have already been brought up that I would like to touch on. First off, I think it’s important to note that like many others, I too have worked with animals in a research setting. My first experience was this past summer with mice in a malaria lab, and now I work with mice for my biology senior thesis work. As many have made clear, I think it is crucial to not become completely unaffected by one’s use of animals in research. At the beginning of the year, my lab’s very first lab meeting was about using animals in research: what it means, our previous experience, and how it makes us feel. Keeping these ideas in mind throughout the year has really made a difference for me. I never like sacrificing mice, but hope it is ultimately for a good cause. Also, starting off the year with this mindset has made us all work closer together – we try to minimize the number of mice we have to sacrifice by coordinating who needs cells and when. While this doesn’t necessarily address the basic ethical issues of exploiting animals in research, I think it at least helps me keep an active consciousness about my work and stay continually aware about the animals I use.

The Blue Brain project is absolutely fascinating. I cannot even imagine the work that must be needed to go into creating a functional computer-based brain. However, while I can envision how it may eventually prove incredibly useful in the future as far as scientific research is conducted, I think it has certain unsolvable limitations. It is still going to be a while until it is completed. I would also suspect that when it is finished, ordering one would be quite expensive. And then even if or when we get to that point, its usefulness is limited by how well we can create the program and its software applications (e.g. would researchers buy software that mimics specific drugs in the system or creates lesions or initiates cancers?). I do not mean to make it sound like this is not a worthy endeavor, but it is just so complicated that I think working with animals will always have its value. No matter how perfect this Blue Brain project is ultimately created, there will always be surprises that I think can be discovered and studied in animal research that simply cannot be done on a computational level. Therefore, as Amelia brought up, it is important to realize that there is, and never will be, only one way to do research. Every method or technique will have specific concerns and limitations, but also specific advantages and rewards unattainable by the other methods.

I suspect that reconciling the issues surrounding the use of animals in research will never end. But I think that’s probably a good thing – it keeps us (the researchers) as well as the general public aware of important ethical standards and how we should (and do) treat animals. The debate will and must continue in order for scientific progress to be kept in check. Finding that “line” of what is OK and what is not will always be difficult, but hopefully for the improvement of all animals and scientific progress alike.

In response to Jessica, I have thought about using other models for my pain research when I start in graduate school in the fall. I’m planning to go to Northwestern University for a PhD in Neuroscience and will most likely work with a (well-known) professor who uses both brain imaging techniques for chronic pain conditions and animal models. While visiting, I thought about what answers about chronic pain they have been able to find without using animals, and while they have made some huge discoveries: http://www.jneurosci.org/cgi/content/full/24/46/10410 , it has always been that the imaging work is the first step and then they use rat models to try to confirm and extend their knowledge. I have chosen to stay working with animal models because I feel as though the information you can gain is (at the moment) much more than you can with just using humans (who you usually can’t truly manipulate). This is a paper by the lab that I’m planning to work with which I think points to a great reason to use animal models—through them they have found that chronic pain may in fact be in the cortex-a memory of the pain: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0K-4NJ26SD-5&_user=423519&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000020258&_version=1&_urlVersion=0&_userid=423519&md5=961f08b08ee88a46a6efbc976f29f2e4#

However, Andrea brings up an important point. How good of models are these rats and mice that we use? We accept that they don’t have the cognitive power of primates, and yet often use them for studying learning and memory. The rat chronic pain models, while believed to mimic humans with chronic pain, are never exact. Many chronic pain conditions have no physical origin that can be found—there is not a way, as of yet, to model this type of pain in animals. How could we, since they can’t speak to us? What does this than tell us about pain? I feel as though we admit that there are conclusions that can’t be drawn, and yet we continue to draw them. As researchers we have a responsibility to acknowledge the limitations of our methods, and I think with animal research we must keep in mind that they are not perfect. To draw conclusions to humans (which is what most researchers are trying to do) requires that we make a leap in assumptions. I’m not sure how/will/should this change, but it is something that we need to consider. While rodents may be good models of simple tasks, are we drawing too many conclusions to say that the mice we use as models of Alzheimer’s are just as good? At the same time, how else can research be done? While alternative models may be useful, I think many are a long way off from being even close to the use of animals.

At the same time, self-report in humans also has problems. Basically, there is no perfect way to do research, so we must choose a model and stick with it. Humans, animals, blue brains—all have limitations and all have reasons for use.

This was a common theme in both our discussion and on the forum, but I definitely have fewer moral qualms with the idea of using laboratory animals for research when the research will directly serve to help us (AIDS research, cancer research, etc) than I do with using animals to gain knowledge for the sake of knowledge.  I worked in a lab last summer where they were studying problems with protein transport in rat models of Huntington’s disease, and to do this they had to anesthetize a pregnant rat and use neurons from the brains of the babies.  I had a lot of trouble watching this procedure done, but given the progress that they made in understanding (and hopefully helping people with) Huntington’s, it seemed to be worth it to me.  I was thinking about this in terms of Jessica’s question as to whether researchers really consider alternate models. In the Huntington’s research, for example, I can’t imagine what alternate model would allow you to study protein dysregulation.  Even if you could somehow get humans to donate their brains to research, the neurons would be too mature to be cultivated and studied like the prenatal rat neurons.  At the same time, there are of course limitations to animal models since their brains are obviously not always functionally similar to ours.  Also, to use my experience as an example again, the lab’s results may show what’s going wrong in developing neurons, but how do we know that the same problems exist later in life for people with this condition?  I guess that my personal rational for using animal models of disease is how many advances have been made through this method, even given all the limitations.

The first real discussion of the ethics of laboratory animal use that I had was led by a professor who is personally comfortable using animals in her research.  One of the arguments that I remember her making was that she feels it’s meaningless to talk about “animal rights” because animal species excluding humans are not concerned with the “rights” of others (individuals or species), and if they do not give rights then they don’t deserve to receive them either.  I think this came off harsher than it did when she presented it, but I think the general idea is interesting.  I personally feel like the degree to which an animal is concerned with the “rights” of others varies between species - I don’t feel like humans are the only species who exhibit this characteristic; I feel like dogs probably exhibit it more than flies, and chimpanzees more than dogs.  Maybe this is why to me it’s so much more okay to cause and study genetic deformity in fruit flies than it would be in monkeys.  But, like many other people have pointed out, this still requires drawing a line somewhere between which species are okay to use and which aren’t, and it’s impossible to say where that line is.

Hi guys,

  I wasn't able to make it to class last Tuesday, but from reading the postings so far and the assigned articles it sounded like there was a pretty intriguing discussion about the use of animal models in pyschological and biological laboratories.  Being in a thesis group which uses animals, lab mice specifcally, to carry out our experiment, the ethics surrounding the use of animals is something that I have been confronted with on a fairly regular basis, especially because the nature of our study involves inducing pain.  To be completely honest, I still do not have my feelings on the matter completely pinned down.  I obviously, like I'm sure most others in the class, feel that it is valid to use animals in many laboratory situations such as in exploration and treatment of various human diseases (cancer, AIDS etc)  I thought it was interesting, however, that in one of the articles (and it would seem to me in a good part of most of the articles advocating for the use of animals in research) these types of projects were used too vehemently as a reason to continue all types of animal research.  I think, and I think this was mentioned earlier, that if people are going to make a case for continuing animal research they would almost do better to steer clear of the obvious and instead focus on why other uses of animals in research, especially on the psychological end, where we are attempting to figure out why for instance a specific behavior occurs instead of curing an epidemic, are valid. 

I personally do not have an answer to this question, and I agree with Stephanie that there are pretty widespread differing views on the use of animals depending on whether the animal used is a mouse or a primate.  However, in the end I think that the rules for humane lab protocol shouldnt differ among different species, and in fact, I think this might be a good way of understanding what is humane in lower animals such as mice, by asking ourselves whether we would perform the same procedure on an animal we are perhaps more sympathetic towards such as a primate.

That said, I think one thing that is perhaps neglected at least in theory with respect to the use of animals versus the use of humans is the idea of compensation.  When we use humans in studies, we almost always have to present some type of compensation for their time, whether it be credit for a class or monetary compensation.  I wonder sometimes why it is that animals are not afforded the same type of compensation.  Some may argue that as we are the only caretakers of these animals, and that therefore our feeding, sheltering, and general maintainance of these animals is the compensation that they get for participating in our studies.  However, I would say that compensation, as it is for humans, goes above the "basic necessities" of life, and that therefore the compensation for our animal counterparts should be likewise a reward and not a requirement.  This is really at the crux of why I have very little if no problem with animal research carried out in veterinary programs, as they are eventually benefiting the animal kingdom, and therefore I think provide some type of compensation, if not to the individual animal, to their species, for their participation.  I do still, however, feel some disconnect when it comes to using animals for human-only purposes. 

Thanks to Jessica, Gillian, and Tamara for such a relevant and interesting discussion topic.

I was fascinated by the idea of the "blue brain" and whether a completed human brain would have a consciousness. There is a part of me that just has to struggle with that idea, but perhaps that is simply because this is such a different thing than a real brain. Neurons that emit neurotransmitter molecules are not the same thing as computer microchips that simply link to another microchip in a pre-programmed way, and so I am not convinced that they would be able to ultimately function in the same way. I do not know if there would be a way to learn enough about all of the connections between all of the neurons in the brain and then input that into a computer and build the necessary connections.

However, another option is somehow using genetics. We mentioned in class that it would take far too long to build all of the necessary connections between microchips, but humans build a brain in 9 months. Yes, I realize connections continue to build after that, but it is a pretty impressive feat for less than a years time. I wonder if eventually it could be possible to take a genetic sequence for brain development, run THAT on a computer, somehow getting a human brain as an output. What would that look like? Would it have consciousness?

I also wonder how we would KNOW it had consciousness. Would it be necessary to hook it up to some kind of robotic body? They have been doing a lot of research recently into finding ways for brains to talk, for people who are paralyzed for whatever reason to communicate. They've even found a way to show that someone in a vegitative state can understand speech, and so could there eventually be a way for just a lone brain to communicate as well?

http://news.bbc.co.uk/2/hi/health/5320234.stm

This is somewhat repetitive of what I said in class, but these are the thoughts that I just keep coming back to…

When it comes to research with animals all of the debate seems to boil down to medial pros and moral cons. I (very personally) believe that extremism is highly problematic in every situation, if for no other reason than it promotes close-mindedness and an unwillingness to consider alternatives. I think that either extreme option (discontinuing the use of animals for moral reasons or promoting all animal research just because it’s research) is irresponsible. (Just a quick side note, one of the easiest ways to decrease the number of animals used would be to lower the criterion for publishable results; so many experiments with strong trends are repeated just to get from strong trend to statistically significant.)

In order to prevent the misuse of lab animals, lines have to be drawn. These lines may seem arbitrary and arguments can always be made for pushing the line one way or the other, but as I see it the line is necessary. Whether or not an individual feels comfortable participating in research is a very personal decision that should be made with a consideration of the ethical and moral issues.

That said I was a little surprised and upset at the notion raised in class that people participating in animal research can end up “using animals just to fit in.” That to me seems irresponsible of the individual performing the research. I very much appreciated that my PI encouraged us to think seriously about our feelings on animal research, and I know that this isn’t the case in all labs. At the same time we are all responsible for our own actions and to not think about what you’re doing but rather point fingers at the lab environment is negligent and immature.

I think it’s very natural to feel uneasy about participating in animal research at first, but most researchers in that position are there because they are interested in the research and find it worthwhile. It’s not easy to see a mouse cut open and perfused. (Saline is injected into the circulatory system to flush out the blood and then a fixative is injected to preserve tissues.) But there’s a difference between feeling uneasy about seeing all the blood and having to try something new on an animal despite believing it to be worthwhile, and feeling uneasy about killing an animal because you feel that is morally reprehensible. If you decide that you’re not comfortable with the moral implications and stop participating in the research that’s fine. If when coming under (inevitable) scrutiny for what they do with animals the researcher blames the lab environment, that just seems careless to me.

So to sum up, apparently irresponsibility with regards to animal research is a pet peeve of mine.