Of Mice, Rice, Flies and Men

Animal rights activists often argue that animal models are irrelevant for human medicine, because they are ‘so different’ from us. But in fact some basics are shared across wildly distant species – something that the Nobel Committee acknowledged last year when they gave the Prize for Medicine and Physiology to Bruce Beutler and Jules Hoffmann for discovering the ‘early warning’ signals that set off immune responses in flies, mice and humans.

On Jan. 25 both Beutler, who works at the University of Texas in Dallas, and Hoffmann of the University of Strabourg, France, were at the University of California, Davis talking to a packed house about their work. Joining them on stage was UC Davis plant pathologist Pam Ronald, who studies rice, and Luke O’Neill of Trinity College Dublin, Ireland, who talked about human medicine.

(Watch the presentations here: http://ccm.ucdavis.edu/immunity.html)

L to R symposium speakers Bruce Beutler, Jules Hoffmann, Luke O'Neill and Pamela Ronald, with (far right) symposium sponsor Murray Gardner.

Work in these very different organisms can give insights that advances human medicine. From the basic discoveries in mice, flies and even rice could come new drugs and new approaches to treat heart disease, rheumatoid arthritis, inflammatory bowel disease and other conditions.

Our immune system has two lines of defense. The innate immune system reacts first, attacking invading microbes and triggering inflammation. If that response fails, the adaptive immune system fights back with antibodies and specialized killer cells. Afterward, the adaptive immune system retains a memory that allows a more rapid and powerful response if the same virus, bacterium or parasite comes back.

Only animals with backbones, from fish to humans, have an adaptive immune system. But all animals, including insects, as well as plants, have innate immune systems.

In the 1990s, Ronald (working with rice), Hoffmann (with Drosophila flies) and Beutler (with mice) identified genes for immune receptors that triggered innate immunity in the rice, flies and mice, and found that the genes were remarkably similar despite hundreds of millions of years of evolution.

From this common trigger, plants, insects and animals develop different types of response to invaders.

Activation of the immune system is not always a good thing. It can lead to allergy, inflammatory diseases such as rheumatoid arthritis or autoimmunity, when the body starts attacking its own tissues.

In his talk, for example, Beutler described how his team, working with mice, has isolated genes related to inflammatory bowel disease, while O’Neill talked about the possibility of being able to develop drugs to treat a wide range of diseases linked to inflammation.

The symposium is an annual event sponsored by a fund created by AIDS pioneer and UC Davis professor emeritus Murray Gardner, who previewed in an interview for Sacramento Public Radio Jan. 24 [http://www.capradio.org/168919] At the beginning of the AIDS epidemic in the 1980s, Gardner helped discover viruses similar to HIV in monkeys and cats – animal models that have been of vital importance in discovering drugs to treat and prevent HIV/AIDS.

— Andy Fell

12 responses to “Of Mice, Rice, Flies and Men

  1. I must say, the UK animal welfare laws include rats, mice, birds and fish, and the sky hasn’t fallen in. It would be useful for them to at least count the use of these animals…

  2. Thank you for the correction, but mice and rats of any genus should be covered under the Animal Welfare Act, along with birds and other vertebrates. Eventually invertebrates should be included. I know the PHS tries to cover the gaps, but not all labs are subject to PHS guidelines, are they?

    Until the AWA is amended so that the definition of “animal” doesn’t exclude approximately 95% of all animals used in science, the language of the law will continue to be like a tin can tied to the tail of animal research. You try to assure people that there is a law that protects lab animals, but then they find out that the law doesn’t cover the vast majority of the animals used, and that doesn’t make you seem very honest or sincere. Ask Congress to amend the law.

    It is appropriate for improvements in lab animal care to be developed and funded from “within the field” or from government agencies. Some animal advocacy groups have funded research into alternatives in the past. The late Ethel Thurston’s organization (A.F.A.A.R. or something like that) put some money into alternatives for the Draize and LD50 tests in the 1980s, and then Procter and Gamble started generously funding the search for alternatives after being persuaded by the late Henry Spira. It isn’t the place of animal charities to pay for environmental enrichment or improving conditions of laboratory animals. For one thing, you wouldn’t let them in the labs to do it.

  3. Kim: There is a slight error in your comments about the regulations. The AWA does not cover mice of the genus Mus or rats of the genus Rattus but it does cover other rodents such as Hamster, Gerbils, Guinea Pigs and mice and rats in a different genus such as Peromyscus. Also, researchers receiving funds from the NIH are required to follow the Public Health Policy on the Humane Care and Use of Laboratory Animals which was mandated by the Health Research Extension Act of 1985 (Public Law 99-158). The PHS policy covers all vertebrate species and you can look at it here: http://grants.nih.gov/grants/olaw/references/phspol.htm. The PHS policy defines an animal as “any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes.”

    Many animal activists point to the AWA and it’s exclusion of some laboratory animals. However it’s important to remember that the AWA has a very broad application because it regulates many institutions, not just laboratory animals. The PHS Policy and the Guide the Care and Use of Laboratory Animals (almost a bible rather than a “guide”) have attempted to fill the gaps in the care of laboratory animals.

    I think it’s also important to know that most work being done in terms of environmental enrichment and improving conditions of laboratory animals are coming from within the field. It’s not like PeTA or the HSUS has given any money towards working on these issues.

  4. I am absolutely NOT a moral relativist. One’s time and culture can explain why something harmful to others is viewed as being acceptable, and perhaps the perpetrators are less culpable because they didn’t (or don’t ) know right from wrong, but that doesn’t make an atrocity any less atrocious. My great-grandparents in Mississippi had slaves, and it was part of their culture and heritage, but it was as immoral then as it would be now. If it was morally fine to have slaves THEN, then they shouldn’t have been forced to give them up because other people believed it was an immoral practice. They did have to give up their slaves, and we live in a better country because of it, but it was a big hardship for them and it changed their way of life and the way they thought about themselves. I am ashamed that my ancestors had slaves, but I often use my familial history as an example of how we all have to adapt and change as we collectively discover new moral truths. My own personal history is not unblemished as far as animal welfare is concerned. I was brought up exploiting animals just as much as the next person of my time and place (the place was Texas: neither then nor now the center of enlightenment).

  5. Kim, while I agree to a point – I find certain methods used years ago entirely unacceptable now – It’s a bit more tricky condemning the past actions. If you’re a moral absolutist (actions are right/wrong regardless of context – this does not change over time) then you can, but if you are a moral relatavist (right/wrong depend on context, and often the belief that right and wrong change over time) then that doesn’t make it wrong THEN.

    Analogy. I think slavery is wrong now. If you have a slave I will condemn you. However, I would think twice before calling every roman nobleman immoral for having slaves – it was morally fine THEN.

  6. It is NOT my belief that most animal researchers today think they should be free of ethical constraints in using animals in harmful experiments and procedures, but that is what “most animal advocates believe,” and historically there is plenty of evidence that animals were very cruelly treated by scientists who did feel free to use animals for all kinds of atrocious things. Animal researchers in the U.S. and Europe are, today, of a different generation and–in my opinion–seem to be eager to demonstrate that they are in compliance with laws and regulations that pertain to animal welfare. Unfortunately, there are inadequacies in the laws and regulations, but they can be fixed if everyone is of a mind to do that. Meanwhile, it is possible that animal researchers need to consider a statement that repudiates animal cruelties perpetrated in the name of science in the past. It might be a meaningful gesture, helpful to both sides of the debate.

    • I have difficulty following what you believe. So perhaps I will tell you what I believe:

      I believe that anyone who bothers to check will know that there are laws and ethical principles that govern animal research. That is fact, not prejudice.

      My personal belief is that most animal researchers strive to meet and even exceed the ethical principles that apply to their work. Some of these people have been my instructors and professors at school, and I have almost unfailingly found them worthy of the confidence I have placed in them.

      • Good if you can’t follow what I believe. It isn’t important, though I have outlined my views in other postings.

        What people who have been your instructors and professors at school do you believe are being maligned by my comments?

        Is it not somewhat disingenuous to state “that there are laws and ethical principles that govern animal research”? The federal Animal Welfare Act (the only law there is in the US that deals with animals used in research) omits from coverage all rats, mice, and birds–something like 90% of all the animals used in research–and labs that use only rats, mice, or birds are not inspected by the USDA APHIS. Further, the AWA does not have any authority over uses of animals in procedures. The AWA was last strengthened by Congress 25 years ago, over strong opposition by animal researchers (many of whom have probably retired by now). NIH guidelines and those of other government funding agencies are better than they used to be, but there are still weaknesses.

        I thought dialogue between animal advocates and animal researchers about these concerns was what you all wanted–rather than “shouting and calling names.”

  7. @ kim bartlett:

    In reply to your belief that animal researchers wish to perform “experiments that cause them physical suffering and/or fear because they are sufficiently unlike us that using them should not be subject to ethical constraint.”

    Can you give us an example of an animal researcher who believes he or she should be able to do research without any ethical restraint?

    Having perused the following links, I find your assertion rather unlikely:

    http://oacu.od.nih.gov/ARAC/documents/Pain_and_Distress.pdf
    http://awic.nal.usda.gov/nal_display/index.php?info_center=3&tax_level=1&tax_subject=310
    http://www.apa.org/science/leadership/care/guidelines.aspx

  8. Only the “vivisection is scientific fraud” group contends that “animal models are irrelevant for human medicine, because they are ‘so different’ from us.” Some of this contingent have (at least historically) not been animal rights advocates or even vegetarians. The late Hans Ruesch was one such person.

    Most animal advocates believe that the problem is that biomedical researchers have wanted it both of these ways: 1) that animal models are relevant for research on human diseases and conditions because they are so much like us; but 2) animal researchers should be free to subject non-human animals to procedures and experiments that cause them physical suffering and/or fear because they are sufficiently unlike us that using them should not be subject to ethical constraint. Need I elaborate on why these positions are contradictory?

    The only resolution is to expand ethical considerations in scientific research to include all species, and to provide for the mitigation of negative experiences such as pain and anxiety in all sentient beings–including but not limited to mice and flies.

    • Kim,

      They are similar to us in terms of their physiology. They are unlike us in terms of their cognitive abilities, mental states, and capacity for suffering, upon which moral status is based. There is no contradiction unless you believe in the equal moral status of all living beings.