A few days ago I read a great post written by my brother in ScienceBlogging, PhysioProf on the generation of novel scientific ideas. His post stemmed from a post originally written by Zuska, and PhysioProf noted that one of the ways he generates new ideas is through the generation of novel methodologies. This left your humble domestic and laboratory goddess reflecting on the source of her own methods. You see, in the work that I am doing the problem came first and the method evolved as a way to solve the problem. I work in an area where it is usually impossible to buy a kit or a pre-made apparatus. Everything that we are currently using is stuff that I built and I was very fortunate to have trained in labs where we were taught to draw diagrams, to hook together electrical-type gizmos, use awesome things like solenoid valves and transducers, and to just build really cool stuff. That's part of what excites me about science -- the opportunity to look at an organism and at man-made equipment and to figure out how to integrate the two in a way that allows me to make physiological measurements and describe phenomena. That is, the ability to combine electrical, chemical, and mechanical engineering techniques with awesome surgical skills and generate data.
And I remember the paper that first really sparked a desire to develop novel methodolgy in order to solve a problem. In the 1950s Frederick Kao of the State University of New York' College of Medicine was trying to discern the mechanism that causes hyperpnea during exercise -- hyperpnea being a physiologic increase in ventilation in order to meet an O2 delivery or CO2 clearance requirement. At this point is was known that an increase in blood pCO2 or decrease in pO2 (to a lesser extent) was enough to increase ventilation in a resting animal/human through activation of the central and peripheral chemoreceptors, located in the carotid bodies and brain. However, it was recognized by researchers of this period that the time course of the increase in ventilation seen at rest with simple alterations in blood gases was too slow to explain the much more rapid increase in ventilation noted with exercise. This led folks to postulate that there was some direct neural connection between the exercising muscle and the respiratory centers in the brain that would signal the hyperpnea at the start of muscle contraction. So, 70 years pass, a whole slew of scientists take a crack at this chicken and the egg-style problem, and none of them are able to effectively tease apart the potential neural mechanisms from mechanisms related to changes in blood factors (what Kao calls "humoral" factors).
Then, like a shining beacon of science hope, along comes Frederick Kao (who had been keeping his finger on the pulse of the field) to solve the problem. Kao clearly demonstrated that there is no humoral-, (or blood-) related component that is necessary for the increase in ventilation caused by exercise. To do so, Kao used two dogs as research subjects, deeming one the "neural dog" and the other the "humoral dog." He connected the circulatory systems of the two dogs, joining their carotid arteries and jugular veins, so that the head and neck of humoral dog (the head and neck being where the chemoreceptors are located) was perfused by blood exclusively from the other dog (check our Figure 1 from their paper for a pretty cool diagram of the experiment). Thus, Kao could perfuse the chemoreceptors of the humoral dog with blood from the other dog and specifically test whether there was a factor in blood that increased ventilation during exercise. Kao then simulated exercise in the neural dog by stimulating the hind legs to contract and measured ventilation in both dogs. In essence (and how freakin' cool is this???) Kao incorporated great surgical technique, setting up his one little bypass circuit between the two animals, with some basic engineering to answer his question.
What Kao found was that ventilation in the neural dog, whose blood was perfusing the chemoreceptors of the humoral dog, increased as he expected it would with the onset of muscle contraction. The ventilation of the humoral dog, however, did not change. Thus, Kao was able to conclude that there was no factor in the blood of the exercising neural dog that could explain the increase in ventilation. Since Kao's paper was published, investigators have gone on to describe the presence of C-fibers and metaboreceptors in skeletal muscle and to scrap like mad fiends about which is important in determining the exercise hyperpnea response in health and disease.
But still, 2 dogs 1 circulation. How cool an idea is that?
Medicine & Health
Comments
Brilliant post, Dr. Isis!
physiologic
AUGGGHHHHHHH!!!!!!!!!!!
Posted by: Comrade PhysioProf | January 2, 2009 10:17 PM
I knew that would get under your skin, PP, and backspaced the "al" out just for you....
XOXOXOX,
Isis
Posted by: Isis the Scientist | January 2, 2009 10:18 PM
HAHAHAH! You are so cruel.
Posted by: Comrade PhysioProf | January 2, 2009 10:24 PM
I do find it necessary to occasionally be cruel to my humble worshipers if only to remind them of how very good the have it in my service the rest of the time.
Posted by: Isis the Scientist | January 2, 2009 10:25 PM
This is very nice work.
There is another signaling mechanism for breathing, that of S-nitrosothiols.
http ://www.nature.com/nature/journal/v413/n6852/abs/413171a0.html
It is quite a bit more complicated than hypoxia or hypercapnea and is much less well understood. Part of the complexity is because there are many sources of NO, and under conditions of hypoxia there are many more (via enzymatic (and perhaps non-enzymatic) reduction of nitrite). There are many enzymes that act as nitrite reductases and produce NO. Virtually all of them are strongly inhibited by physiological levels of O2. They are probably inhibited by NO too. Many of these NO effects don't require the presence of actual NO, nitrosylation can occur directly from nitrite during hypoxia without an NO intermediary.
http ://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18835812
Breathing is triggered by a complex summation of multiple signals including CO2, O2, and S-nitrosothiols and other signals not yet fully understood. When levels of those signaling agents get out of whack, the control system gets out of whack too, and may transition into a state of instability, as in Cheyne-Stokes periodic breathing.
It should be noted that being out of breath is not necessarily only due to insufficient O2. People with COPD get notoriously breathless with modest exercise, and that breathlessness is not relieved any better by breathing O2 than by breathing air.
What I find very interesting in this paper
http ://thorax.bmjjournals.com/cgi/content/full/59/8/668
as was pointed out in this response
http ://thorax.bmj.com/cgi/content/full/60/3/257-b
the patients when breathing through a mask had higher work production, longer exercise times than breathing through the mouth with nose clip. The suggestion is made that this may be due to proprioceptive input; however the nose is a major source of NO in inhaled air.
They produced more work with less O2 and less CO2 suggesting increased efficiency of oxidative phosphorylation (maybe I am reaching here, but this is an exercise in hypothesis generation ;) which better regulation of O2 delivery to mitochondria by high NO levels could conceivably mediate. Distributing the load better between mitochondria keeps the average mitochondria potential lower, which reduces slip and increases the efficiency of ATP production.
Relating breathing regulation to asthma and women's health, this interesting paper reports exacerbation of asthma symptoms in the late luteal phase and also increased sensitivity to CO2 during the follicular phase.
http ://chestjournal.org/cgi/content/abstract/104/6/1718
Both of these could be explained by increased NO. Decreased NO in the late luteal phase would increase mast cell sensitivity (perhaps the thing needed to reduce the likelihood of infection during menstruation) and increased NO in the follicular phase would reduce the magnitude of the CO2 signal needed to trigger breathing (because the NO signal is higher, the CO2 signal doesn't need to get so far out of range before their sum triggers breathing).
Posted by: daedalus2u | January 2, 2009 10:56 PM
I love, love, love creative experiments like this one!
Posted by: Coturnix | January 2, 2009 11:28 PM
Nice post, Isis. I really enjoy reading about key experiments done in the past without fancy gizmos and gadgets (even though the latter can also be incredibly cool).
Posted by: sanjiva86 | January 3, 2009 12:36 AM
"Hyperpnea" is the most awesome word EVER. :)
Posted by: The Perky Skeptic | January 3, 2009 8:28 AM
[quote]"Hyperpnea" is the most awesome word EVER. :)[/quote]
Nuh, uh: dyspnea. Now *that's* a motherfucking awesome word!
Posted by: Comrade PhysioProf | January 3, 2009 9:54 AM
Oof. Better hope the PETA types don't hear about this one.
Posted by: hfs | January 3, 2009 10:13 AM
PETA?
In grad school, I once injected liquid soap into a catheterized dog at the conclusion of an experiment, just to see what would happen.
The dog was terminally anesthetized, but still it gasped and wriggled terribly. Most of the time the 'dogness' is lost when the subjects are out when out and on their backs; they become mere dangly lumps of flesh and fur. But that memory of the soap response haunts me terribly.
Posted by: Dave | January 3, 2009 1:46 PM
For fuck's sake, Dave. Do I even need to ask the rest of the class to outline all of the reasons this is horrible?
"Just to see what would happen?"
For fuck's sake.
Posted by: Isis the Scientist | January 3, 2009 2:13 PM
This is a great post!
Posted by: Fia | January 3, 2009 3:33 PM
Dave, I get it that you are a troll. However, if you really did this to an animal I suggest that 1) you need to be psychologically evaluated and get treatment and 2) if a person such as an advisor get wind of these types of actions you would be, and should be, kicked out of your program.
Cruelty to animals is an indicator of a sociopath -- I'm certain that you know this -- and there are strict regulations that apply to the use of animals in scientific work. If your program caught wind that this had occurred, they would likely lose their ability to continue to use animals in grad student training. If you really did this, get yourself some help before you take the next step. For fuck's sake.
Posted by: gnuma | January 3, 2009 4:40 PM
Isis, gnuma: I really did it. But what separates me from a true sociopath is that I feel really bad about it. I also recognize that it could have been really bad for the program had news of my 'experiment' gotten out. Obviously, I was an impetuous youth.
That said, I believe the only thing that really separates my experiment from 'official' exploratory science is that I don't conceal my curiosity in hypothe-speak or conjure up some ex post facto rationale and interpretation.
Does an examination of "short-term physiological responses to dramatic alterations in blood pH" suit you better?
What is the NIH Knockout Mouse Project (http://www.nih.gov/science/models/mouse/knockout/) but a multi-billion dollar exercise in 'seeing what happens' ? With regard to applied biomedical science: What about animal testing? Clinical trials? They're basically all just shrugs of the shoulders and 'let's see what happens'.
Don't get me wrong; I support animal research. But let's not B.S. about what we're really doing.
Posted by: Dave | January 3, 2009 5:02 PM
I had a girlfriend once who had a saying she would use when ever there was a report of a guy (and it was alway a guy) doing something like what Dave just discribed, it was
"Too much time on his hands and no woman in his life to tell him not to do it."
Posted by: daedalus2u | January 3, 2009 5:28 PM
If you really feel bad about it then you will start giving a yearly donation of at least 50 bucks to your local Humane Society. And I still suggest you have your head examined by a licensed individual.
Posted by: gnuma | January 3, 2009 5:36 PM
wtf would possess someone to inject liquid soap into a dog, terminally anesthetized or otherwise?
i did a lot of transcardial perfusions on rats, and that was my absolute LEAST favorite thing i have ever done in a lab. i was incredibly relieved when that part of my work ended.
Posted by: leigh | January 3, 2009 7:56 PM
I've read your blog occasionally, but have never commented before.
Animal experimentation is one of the reasons I decided not to pursue a degree in the biological sciences. I don't think I could bring myself to cause the needless suffering and death of another living being. While I know that there are good reasons for animal experimentation and would not support banning it, I am horrified by much of what I've heard about it.
I do not think Kao's experiment was a "cool idea". I find it deeply disturbing. I want to know what happened to the two dogs involved. Were they separated, and did they survive the procedure? If not, I find it hard to justify the experiment. I hope the results were really bloody important and lead to a cure or something.
I find it confusing that Dr. Isis can gush over Kao's experiment while condemning Dave's. Both seem pretty sick to me.
Posted by: Zetetic | January 4, 2009 3:13 AM
Zetetic,
There are a tremendous number of fields in Biology that do not require animal experimentation. In fact, some of the most mind-blowing discoveries, causing biologists to question what we thought we knew, are happening in non-animal systems. I have been planning on posting about this for a while, but it's going to have to wait until my grants are submitted in a week. In any case, biology is not just zoology, though it feels seems that way.
And Dave, feeling bad about doing something cruel dosn't just make it okay, particularly if you feel "so bad" about it that you think it is a good idea to gloat about it in a public forum.
Posted by: prof-like substance | January 4, 2009 9:03 AM
Zetetic and all, I realized when I posted this paper it might be a bit controversial. We could certainly discuss for weeks the ethics of animal use in research. I gave a very brief overview of the experiment, but I think there are profound differences between these authors' experiment and what Dave did. I would encourage you to look at the methodology of the paper to see the conditions the experiment was performed under in order to minimize the suffering of the animal.
I think it is the responsibility of those performing animal research to minimize the suffering of the animal, and I think many researchers perform experiments with this in mind. With that, I am going to leave Dave's comment in this thread because I think it is an important reminder to us that it is the responsibility of those supervising junior scientists (and ultimately of the PI) to ensure that animal research is conducted ethically in the lab. If anyone believes that Dave's actions were even remotely acceptable, I would encourage them to discuss the ethical use of animals with their PI, to contact their institution's Animal Use and Care Committee for additional training opportunities, review the Association for Assessment and Accreditation of Laboratory Animal Care's (AALAC) resource page, and review The Guide for the Care and Use of Laboratory Animals.
Posted by: Isis the Scientist | January 4, 2009 10:23 AM
As an undergrad, I lived with a friend who was vegan and a member of PETA. We used to have great discussions about animal rights, the societal value of animal experimentation, and alternatives to animal use in research. I think PETA is poorly run by morons, but deep down I actually agree with the philosophy - "A rat is a pig is a dog is a boy"*
I was glad to see Zetetic's comment, because I agree that Kao's experiment is horrifying. I don't care what the justification is for animal experimentation, sometimes it is still horrifying. One of my favorite examples to show clips of (I last did so in a presentation to first year medical students a few months ago) is the infamous 'Experiments in the Revival of Organisms' (Google it, or try wikipedia). It's like a B horror film. And yet what we see here are pioneering experiments (or more likely recreations thereof) in development of the Heart-Lung Machine, which enables all modern major surgery and which has saved countless lives.
It is easy to say all sorts of PC things about animal cruelty and toss around AALAC documents. But don't let that whitewash the truth. Remember that the Nazis got away with the holocaust mainly because they hid the reality from the population and talked about improvements to society**. Animal quarters are also hidden from the public in every institution I've been at. No matter how you slice it, animal experimentation is often insanely cruel stuff. Is it justifiable? Well, that's another discussion.
As a courtesy to Zetetic, I think Isis should explain exactly why the experiments described above were worth it. C-fibers and metaboreceptors were certainly not discovered this way.
*The scientifically-sanctioned version of this is: 'Physiological and molecular conservation across species', which is the fundamental argument for all biomedically-justified animal experimentation.
**I'm sure everyone enjoyed 'The Boy in the Striped Pajamas' this holiday season.
Posted by: Dave | January 4, 2009 12:18 PM
Again, I say that Dave's comments do not realisticly represent the way most scientists conduct research. I again refer you to the resources I suggested if you have concerns.
An understanding of the mechanisms driving normal exercise-induced hyperpnea have been important in understanding how the normal blood gas/ventilation relationship becomes dysregulated in disease and exercise intolerance (ie, congestive heart failure, COPD, metabolic syndrome, central sleep apnea, etc)
Posted by: Isis the Scientist | January 4, 2009 12:41 PM
...
Ah. I see Godwin's Law** has come into play.
As an undergraduate I participated in several live animal studies. We learned much from these studies and all animals were treated as humanely as possible. My kudos to the professor that instilled in us the need to value and treat humanely the subject animals.
...tom...
** Link to an old-school Usenet-focused source ... but it still applies today
Posted by: ...tom... | January 4, 2009 1:24 PM
Wow. Thanks. I didn't think it would happen so tidily, but Isis and Tom both totally demonstrated the evasion I alluded to. Tom definitely gets extra points for invocation of Godwin's law, as if that were a valid argument. Do you feel better about Kao's experiments now that Tom and Isis have labeled me a Bad Man, Zetetic?
Isis is correct in that my comments do not realistically represent the way most scientists conduct research. Most scientists accept the vivisectionist culture of modern biomedical science rather blithely, trotting out AALAC and OLAW documents and dismissing the topic when necessary, exactly as we have seen done here. Have you actually read the laws that govern animal research, Isis? Those regulations have more to do with protection for agriculture and lack thereof for pest species than actual moral justification. What training procedures do you personally enforce in your lab, over and above what might be part of your program? Is your animal care facility location known to the public and accessible for tours? If not, why not? What is there to hide? Are you willing to post a video of your oh-so-humane experiments on the web? If not, why not?
Animal research is a moral grey zone. It is disconcerting to not see any moral introspection on the part of the people who do it, or in the case of Isis' post, cheer it on without explaining why it was justified.
Posted by: Dave | January 4, 2009 1:56 PM
Dave- I agree with some of your points on animal research. Although I must say, I'd never have done that to a dog... seriously, that is more than 'a bit' horrifying.
Then again, in undergrad I lived in a hippie house (cooperative vegetarian/vegan-friendly eco-conscious house).
Part of me emotionally believes that ceasing to be horrified by this type of animal research is a Very Bad Sign. No matter how justified the research might be*. Scientists who can only see How Very Cool The Science Is and not The Terrible Cost of The Research are one of the main reasons why IRBs/IACUCs are so critical.
*and yes, I see a world of difference in the justification of Kao's work and the impromptu soap-experiment
The transparency thing is also a good point, although I don't think you've made it well. There are plenty of good reasons animal quarters are usually out-of-the-way. For one, lots of people are allergic to animals and putting animals where random allergic people will run into them is bad. Obviously, allowing people who haven't been preped into pathogen-free animal housing is also bad for the research and probably the animals. So I think there are very good reasons animals quarters are out of the way that need not have anything to do with concealment...
That said. At my institution, we are technically only supposed to transfer the animals in the freight elevators, in covered cages. This was explained to me as a measure to keep people from being upset that animal work was being done (although some of the allergy concerns also apply).
In general, I think scientists do too much to hide the animal research parts of their work. I realize there are some understandable reasons for that, but it's something that concerns me.
Dr. Isis- it is very difficult to look at the methodology of a paper that is pay-only if you do not have access to it (I don't have access right now). Fruthermore, I know paper writing styles have changed a lot since the 1950s, and they used to include a lot more details... but does the paper explicitly discuss whether this was the least cruel method for conducting this research? If not, I think it's a bit of a cop-out to say 'consult the methods'.
And, if your point is "Kao is better than Dave!" or "properly conducted research is not wanton animal cruelty" I agree with you. But citing AALAC as an "authority" does not free you up from considering the moral implications of any given work. This work of Kao is cruel and horrifying. It may also be totally facinating, groundbreaking science... but I don't think you have conveyed that particularly well. The science has to go beyond "gee wizz that's cool" to justify animal work. You merely give some handwaving thing about "understanding the normal case gives us insight in to *insert important diseases here*". To be clear: Yes. It does. So What? Was it necessary to do this to these dogs to discover X Y or Z that actually helped other dogs or people?
That is one standard we should consider applying. Not just "oh it's importantly sciencey!".
You know how much I like to say it, but seriously, that is a pernicious and absurd flavor of BULLSHIT.
I think that this was an excellent paper to blog about, and I love it when you do sciencey posts (even if, as a nonphysiologist, I am sometimes confused... carotid bodies? I fear the chemoreceptor link did not help very much)... but I think it's unreasonable to sidestep the discussion of the ethical implications here.
(completely side rant: wtf is a scientific paper from 1956 still under copyright? that is just wrong)
Posted by: becca | January 4, 2009 1:56 PM
Ironically, at least in Canadian Universities, many animals are killed because of the stance of animal rights activists. The idea is that animals must be euthanized as quickly as possible after an experimental endpoint in order to prevent undue suffering. So the psych students can adopt their rats (cause even PETA knows that running a maze ought not to be an automatic death sentence) but if you measure a rat's metabolism in a bell jar, too bad Miss Norvegicus, you're toast. Even more oddly, these rats must not be fed to any of the captive animals (such as snakes) even after they are euthanized. Separate rats must be killed to feed the Serpentes. Now there is a movement afoot to remove live animals from herpetology classes (of course those animals must be euthanized as well). Someone at an unnamed university (it has a name, but I won't say it here) actually had their animal care protocol bounced by the ACC Vogons because they did not specify how their fish would have access to drinking water. It only makes sense that someone should be able to graduate with a BSc in life sciences without ever having studied anything, you know, alive. This is the sort of thing that comes from adopting an absolutist philosophy and then taking great pains to not engage any mental faculties for ever after.
Posted by: MattK | January 4, 2009 1:59 PM
Like Zetetic, I found reading about this experiment - especially with the bouncy 'how cool is that' tone used - deeply disturbing. I actually had a nightmare about it last night... lovely. But the occasional gory mental image is something I should expect for continuing to read here when it's absolutely clear that your science involves gruesome stuff with other mammals.
I dropped Biology at school to get out of dissecting the usual bullseye, locust and rat, and when I realised at university that I did want to take some biology courses NOT using animals was a key factor in my choice. But I don't totally oppose animal experimentation, I just ask for ethical treatment of the animals, people to be very careful about 'minimum numbers' calculations, and for alternative methods to be used whenever possible - and I hope that current legislation and control means that the vast majority of scientists work in this way (if only to avoid the paperwork and cost of using more animals than necessary). Although there does seem to be a bit of 'what happens if' with some work, when I read up on it I can usually see the justification.
My current work is broadly at the ecological end of biology, and biology is so much more than physiology/zoology (and genetics!), although you'd sometimes be forgiven for thinking otherwise. For a start - plants? fungi? Plants are so freaking cool...
Posted by: JaneB | January 4, 2009 2:06 PM
As usual, becca, your comments are insightful, but I'm disappointed that you've bought into the 'keep people and animals separated for both of their protection (allergies, etc)' argument. The obvious counter for that argument is zoos, which are the complete opposite of how most research animal facilities are, with regard to public exposure. If zoos don't have to hide their animals and facilities, why do research institutions?
Again -- I support and engage in animal research. But I do so knowing that it is also a big responsibility. Sure, I'm not proud of the soap experiment, but I'm not about to pretend it didn't happen either.
Posted by: Dave | January 4, 2009 2:18 PM
These are the nuanced-type discussions that ethicists and IACUCs routinely have. Dr. Isis is a huge supporter of the power of the IACUC and I have written about this before. I have also written about the responsibility of senior scientists to monitor the work of junior scientists. Was it necessary? Kao's article is taught as a classic paper in respiratory and exercise physiology and has contributed to our understanding of the control of breathing in health and disease. Has it led to advancements in the field? Yes. But the definition of "necessary" is tricky and I fear we could debate that to no end for eons.
I see no problem having this discussion continue here, my humble commenters, provided it remains civil. I appreciate that some of you may not have access to the article to understand "what the investigators did to these dogs" and that this could lead to some speculation about what was done. Kao's experiments were performed under general anesthesia and the animals were not allowed to recover from the experiment. Discussion continue...
And I'm sorry you found my enthusiasm for a novel technique to be bothersome, JaneB. But, I think the innovative solving of a problem and advancing of a field is cool.
Posted by: Isis the Scientist | January 4, 2009 2:26 PM
"Kao's experiments were performed under general anesthesia and the animals were not allowed to recover from the experiment. Discussion continue..."
Same with my soap experiment. Discussion continue...
Posted by: Dave | January 4, 2009 2:44 PM
As extra context/perspective, I should add that my soap experiment -- though obviously unsanctioned -- was performed during participation in a required part of first year veterinary curriculum at one of the country's top vet schools. All dogs were 'pound dogs' -- abandoned pets destined for euthanasia. The last memory my 'soap dog' (a lovely black spaniel) had was of playing (probably for the first time since abandonment), and then being held in someone's arms and comforted as the general anesthetic took hold. Way better than asphyxiating in a puddle of its own urine in a stainless steel CO chamber. Which is how it would otherwise have died*.
So back to Kao...
[Practices have changed since then. I think it's now lethal sodium pentathol. But to be honest I'm not sure...]
Posted by: Dave | January 4, 2009 3:04 PM
becca,
That's not hand waving. That is the point of science, to discover things about the way the world works. A biproduct of that is that improved understanding improves and lengthens the lives of both humans and dogs and other animals (those that potentially receive veterinary care). Nothing about physiology (and physiological medicine) has ever been discovered without the use of animals at some point or other.
So you're saying that we should only use animal experimentation for problems whose solution is already known to have medical relevance? If we already know what the relevance is than we already know the solution and in that case the experiment really would be pointless. You can't predict the utility of certain facts if the facts are not discovered yet.
Posted by: MattK | January 4, 2009 3:06 PM
There in applies the problem in using Dave's example to discuss the current way animal experimentation is done. Dave's experiment was not "sanctioned" or allowed to withstand the scrutiny of an IACUC. Dave is governed by no moral compass but his own. The purpose of the IACUC is consider the ethical and societal implications of an experiment outside of the scientist's desire to see what happens.
You can be inflammed by what he writes, but Dave is just the ultimate Strawman Troll with no greater purpose than stirring up the slime.
Posted by: An IACUC Member | January 4, 2009 3:25 PM
Sorry Dave, I should have perhaps specified... I work at an academic medical center, and my views are shaped acordingly. If I come into a hospital as a very sick patient, I don't want to accidently run into animals that might make me sicker. We don't take very sick people to zoos... we do take them to the building in which my lab is located in.
I'm not saying allergies are always a legitimate reason for seperating animal quarters, but rest assured they can sometimes be.
MattK- "Nothing about physiology (and physiological medicine) has ever been discovered without the use of animals at some point or other." First, that's absurd bullshit. You're saying that the stint I did cloning calcium channel genes into HEK cells and then zapping them on the electrophysiology rig had nothing to do with physiology whatsoever, which is just plain insulting. Your attitude of "if it doesn't have animals it's not Real Physiology" is patronizing and, more importantly, Scientifically Invalid.
Secondly, we can study many interesting physiological questions in humans (in fact, if we want to cure human diseases, sometimes we must study things in humans). There are ethical problems in human research, but given the protections currently in place, I virtually never see any physiology methods in a paper that makes me think "hmm, that sounds too cruel" (actually, I'm more worried about what the psycologists get away with than the physiologists, in terms of human subjects!).
Many, many, many incredibly interesting and important scientific investigations will not in any way involve even the hint of animal cruelty.
Which isn't to say I think we should shy away from doing some experiments which may have a somewhat cruel aspect to them, if and when they are scientifically well designed and are needed to advance the science (as well as carried out with as much care as possible to minimize harm and suffering).
"So you're saying that we should only use animal experimentation for problems whose solution is already known to have medical relevance?" It is true I am most comfortable with animal experimentation in the context of clinical trials. Rest assured, there is a category of animal research where we're pretty dran sure there will be medical relevant (otherwise we wouldn't go to the expense!).
Bottom line Mattk- I don't think that the goal of human knowledge is, in itself, an adaquete justification for cruelty to animals (if it were, Dave's "I just wanted to see what would happen" soap experiment would be perfectly legit).
1) It's not like we've run out of ReallySupercoolScientificQuestions that don't require animal cruelty, so the goal of advancing human knowledge would not be rendered impossible by eliminating all animal research.
2) What would, I believe, be rendered vastly more difficult or perhaps impossible, is the goal of advancing human knowledge about how to cure diseases. This is a very specific subset of scientific questions, and I believe it justifies the use of animals.
Posted by: becca | January 4, 2009 3:42 PM
a lot of animal research is "how does this work?"- like the paper posted above. we have to know how things work to fix them when they're broken. this, however, opens the door to the systematic study of EVERYTHING. i personally think that is good.
should we cease to study the brain (which in many cases, like mine, requires animal work) unless it relates to curing alzheimer's or any other known and identified disease? how about those really rare ones that only affect a handful of people? where shall we draw the line on what is "useful medical knowledge" vs just plain ol' "human knowledge" and who gets to pick?
legitimate scientific experiments are ones that have been carefully designed to maximize the gain for each animal used and reviewed and approved by an outside committee. the committee works for the purpose of balance between animal use and benefit to society.
Posted by: leigh | January 4, 2009 4:16 PM
Becca, this NIH-driven need to relate everything we study in the life sciences to some disease, no matter how contrived the link, is a scourge on biomedicine. We can't let asking "how" replace asking "why?"
Posted by: BioProf | January 4, 2009 4:18 PM
becca,
I suppose I wasn't clear enough about that, and perhaps the emphasis should have been on medicine rather than physiology. Nevertheless, while some aspects of a problem can be approached without any confirmation in an animal's physiology (apologies to any plant physiologists reading this) I'm not sure that any grand resolution can be achieved without investigating it in animals at some point. This last phrase was also in my earlier post and you quoted it so I'm sure you must have read it. The significance of the phrase is that I was not denying that parts of a problem can be investigated at the cellular level through cell cultures or some other way. To suggest that I would claim that your Ca channel work is not related to physiology is a ridiculous straw man characterization.
I absolutely agree.
I detest the idea of farmed science (science that limits scientists to questions specifically sanctioned by someone else' ideas about what is an important or appropriate avenue for intellectual curiosity). Yes I know this is how most science is funded but I disapprove. I think that some methods should be forbidden and so some questions will have to be put off. However, with appropriate analgesia and anesthesia, careful power analysis and use of pilot studies, use of other animal models, cell lines, computer simulations etc I think that still leaves plenty of room. I think that a ban on animal research would kill physiology and stifle, to an extreme degree, medical advancement.
Also, I think that pure science is at least as important as clinical trials. (besides, without theoretical + advanced experimental science there would be little need for clinical trials anyway). What is definitely less defensible is the use of animals for testing cosmetics and similar. Also, I wonder how much the pharmaceutical companies use animals to go on pharmacological fishing expeditions without any particular scientific rationale or goal.
Dave's experiment would still not be legit because it was not published and was never intended to be published. It was also not scientifically rigorous (due small sample size if nothing else). Hence it did not contribute to human knowledge, only Dave's knowledge.
Posted by: MattK | January 4, 2009 4:27 PM
whoa whoa Bioprof- you can always ask "why" in all manner of ways (Look, it's not my fault all these silly physiologists are incapable of seeing 'The Awesome Power of Yeast Genetics'...), but when someone asks you why you are hurting this animal, you need a better answer than "why not? I wanna know stuff!" (see soap experiment). I'm all about knowledge for the sake of knowledge when we aren't talking about the cost. Heck, I'm honestly still pretty in favor of knowledge-for-the-sake-of-knowledge if all you want to spend is my tax dollars and years of graduate student's lives.
MattK- I wasn't trying to set up a strawman in order to have a conveinent argument to attack, I was instead trying to point out that some scientists will legitimately take umbrage at the idea that all physiology must involve animals. I can easily grant that virtually all medically useful scientific progress will depend on animal studies at some point along the line... I think our principles actually aren't totally in conflict in how we might implement them. But I do think you need to think more carefully about what the scientific research world would look like if we reasoned solely by the principles you have put forth (I expect you actually do have some implicit criteria for utility/applicability of scientific work that you just haven't bothered to articulate; this is assuming we were only going off what you've said so far)...
For example, Dave's experiment was not "scientifically rigorous" due to the small sample size. So if Dave had just done this to 11 more dogs, assuming he had also ensured it was scientifically rigorous, then it automatically would have followed that it was morally acceptable? Ahahahaha.
Because, in a very untraditional sense... Dave did just publish the results of his experiment. No one who reads Dave's comment has the excuse of doing it "just to see what would happen". But, truthfully, that is what the world of investigator curiosity driven science (free of moral constraints) looks like in an unusually extreme, but obviously ocassionally realistic, case. It seems... problematic. To me at least.
leigh- I'm not saying I have all the answers on how to judge if particular scientific research offers benefits (in the form of some combination of knowledge and potential applicability to human health) that outweigh the costs (in the form of animal suffering or lives spent). I'm just trying to say I think those are the critical things on each side of the scale.
Posted by: becca | January 4, 2009 4:56 PM
Becca, in the entire field of it here, your statements are the ultimate BULLSHIT. One need not "hurt" an animal in order to ask a question for the sake of asking questions. Using animals does not necessitate hurting animals, although some protocols may require some agreed upon and sanctioned degree of discomfort. It is crucial though that we continue to ask questions for the sake of asking questions.
This is the same simplistic nonsense taught in first year graduate student ethics courses and is exactly the reason, as others have noted, that animal use committees evaluate protocols. You can keep debating hypotheticals and lining up the strawmen, but at the end of the day this debate will continue to go in circles because someone will always be able to invent some hypothetical scenario more horrifying than the next.
Posted by: BioProf | January 4, 2009 5:20 PM
It is categorically impossible to determine what is "necessary" to advance a basic science field in ways that impact human health until after the experiments have been performed, sometimes very long after.
Posted by: Comrade PhysioProf | January 4, 2009 6:30 PM
becca,
I think that 'utility' should be determined by other scientists in the field based on citations or whatever. Scientists should have more freedom to work on what interests them and they can choose how much they toe the line re. 'importance'. I think that importance is difficult to judge except retrospectively, especially by non-scientists or scientists working in other fields. Science is a creative enterprise (with empirical constraints) so scientists should be given more leeway to indulge in creativity and let it take them where it may. I certainly wouldn't presume to tell an artist what to paint.
You're probably right.
There you go again. I said "due small sample size if nothing else" which, to me at least, implies other reasons may/do exist that render it illegitimate from a worthwhile use of animals standpoint. In fact I did give another reason which was publication (I meant in the literature). But, for the sake of argument, I'll give some thoughts about what additional considerations could make it legitimate. First, that there is some reason to believe that the effects of high blood pH was not adequately known and that the experiment had a reasonable chance of being informative. I.e. there was some new knowledge to be gained. Also, I count the fact that the dog was terminally anesthetized in favour of the experiment: it was going to die anyway so the dog is not losing its life in order to answer this question (whatever it is). Of course coupling of experiments would be contingent on a reasonable belief that they would not interfere with each other.
One other thing, I'm not against animal care committees but I think that they seem, in my limited experience, to be run by Vogons that care more about the rules than about what those rules are meant to achieve. The committees' goals should be to ensure that suffering is kept to a minimum and that animals are not used needlessly. Basically they should be there to balance the welfare of the animals with the advancement of science. They should not be in place to keep up appearances for animal rights activists.
Posted by: MattK | January 4, 2009 7:43 PM
Well, I'm glad some other people agree with me, at least in part. As an educated layman I often feel that I should refrain from posting in deference to the experts.
Dr. Isis, I tried to access the article, but I don't have a subscription. I'm probably not qualified to assess the methodology in any case.
Since you probably only know me from the one post, I'll give an extremely brief overview of my background, limited as it is. I was very good at biology in high school (which probably means nothing to anyone, as undergrad students seem to be routinely dismissed by people on most of the blogs I read). I originally wanted to go into veterinary medicine, but became interested in another field and decided to pursue that instead. Bioethics was a large part of my decision. I wasn't sure that I would be able to do things that I would be asked to do, and I wasn't sure I was up to dealing with the debates and issues that would probably come up throughout my career. I decided not to pursue a different biological field because I have always been more of a generalist and the thought of specializing in a narrow field felt too limiting. I did take an undergraduate course in bioethics, which doesn't make me an expert, but did give me a sense of the nuances involved in trying to grapple with some of these issues.
Although I didn't go into the sciences, I have continued to read books, magazines, journals and (recently) blogs to remain informed. I have also volunteered at several vet clinics, so I've been able to observe various operations and procedures. I have regretted my earlier decision not to go into biology. I think many of the reasons for my decision turned out to be less important than I thought at the time. One day I might be able to gather the resources to go back to school, but I'm nearing 30 so I've probably lost a good deal of my potential anyway.
When I was in undergrad, I heard stories about some of the biology classes. I remember one in which everyone was assigned a rat which they then trained to do various tasks, and at the end of the semester they decapitated the rats to see how the learning had affected their brains. (Or that's how it was explained to me, anyway.) What horrified me about that class is that it was repeated over and over again. At least every year, or possibly every semester, a new class killed a new crop of rats. Was it really necessary? Surely, having done the experiment thousands of times, the results were known?
At the same time, I recognize that people can only be trained to work with living tissue by having access to living tissue. You can't learn to operate by looking at the pretty pictures in an anatomy book. You can't learn to prepare specimens without specimens to prepare. If it had been a course in dissection or something, perhaps it would feel more justified.
My personal feeling is that animal experimentation is justified if there are no alternatives methods available. Perhaps in that sense Kao's experiment was necessary at the time. But I still wonder about how important the results were. If it was necessary to join the dog's circulatory systems in order to, oh, cure malaria or something, and millions of lives had been subsequently saved, then it feels more justified. It's hard for me to tell from your succinct explanation of why it was important how important it really was.
However, I appreciate that it's difficult to determine whether an experiment is necessary. I very much support research for knowledge's sake... just not at the expense of lives. I also think that it may be wrong to judge Kao's experiment by the morality of modern times.
It's late and I think I'm starting to go in circles, so I should go to bed. I admit that Kao came up with a very clever way of obtaining his results. But I can't help my visceral disgust with his methods.
Posted by: Zetetic | January 5, 2009 1:19 AM
Sounds like you have a passion and the ability, Zetetic. Which makes you perfect for a career in biology or veterinary medicine. No one knows exactly what they want to do as an undergrad. Most people don't even have a good clue in grad school. Sure, you'll have to put up with some horrible slaughter during training, but in the end one of the following things will happen:
1) You'll understand the rationale for animal use, agree with it, and have a happy life.
2) You see how the evil system works from within, fight it, and change the world.
Those are not bad options.
Posted by: Dave | January 5, 2009 7:23 AM
Dave, you forgot
3) You'll agonize over killing mousies everytime you have to do it, but end up curing malaria to give over the guilt.
That's my plan, at least.
(although, ethical disclosure most malaria researchers won't give: financially, we're better off buying bednets than tackling it from an immunological standpoint. Only $10 and you save a live (or a few!). It's a great bargin! www.nothingbutnets.net)
Posted by: Becca | January 5, 2009 10:39 AM
becca:
1) There are already drugs that very effectively kill plasmodium (and thus cure malaria).
2) People were convinced malaria was on the verge of being wiped out a few decades ago, but then people got all upset about DDT and draining swamps.
3) Your argument for bug nets is like saying the cure for AIDS is abstinence.
4) I don't really have a four, and really there is not much rationale for writing any of the stuff I just wrote, except that you started me on this listy thing and I like lists.
5) Five comes after four.
6) I still think Zetetic might be a great scientist or vet.
Posted by: Dave | January 5, 2009 3:52 PM
1) We're going to be chasing our tails with multidrug resistance of some strains of plasmodium for years. Getting people existing effective drugs is an admirable effort I'm completely willing to get behind. Yet I'm far from convinced it's sufficient.
2) Meanwhile, in this century, we still have birds. Their the pretty chirpy things you'd see if you ever left the dark shadows under your bridge.
3) So you're saying if I send you to Zambia, you don't want a bednet? Suit yourself.
4) Lists are good, but you are wrong about everything else.
5) Except that five comes after four.
6) And possibly the last one. Though, Zetetic- I'd personally (totally selfishly) direct you away from the glutted market that you will be in if you get the PhD and suggest you go toward vet school. This may just be grass is greenerism though. Vets also make awesome scientists, so it's really just keeping your options open; as far as I know you should be plenty able to compete for research funding with a vet degree.
Posted by: Becca | January 5, 2009 7:14 PM
I second #6. The best and most successful scientist I know, whom I also admire greatly, has a DVM but no Ph.D. or M.D. He works on nothing related to anything you'd expect to need a DVM for.
p.s. I like my bridge just fine, thank you. Birds are crunchy.
Posted by: Dave | January 5, 2009 7:43 PM
Thank you both for the support. I would absolutely love to go back to school and study veterinary medicine. Unfortunately, my current degree has zero overlap, so I'd pretty much be back at square one, as if I'd just finished high school. Except that, you know, I took all those biology and chemistry and math classes were over 10 years ago. I could certainly go back for a bachelors degree in biology or zoology or something... but the competition is fierce to get into any of the veterinary graduate programs. I'm not sure what else I'd do with a biology degree, though there are certainly options, and I might find myself leaning toward something completely different once I got there.
The other complicating factor is that I'm currently engaged (to a physicist - I'm marrying into science! Yay!), who happens to be taking his PhD in another country about 2000 miles from where I live, and so we're trying to sort out how to move me there, and pay for everything - I'm not sure I want to start a long educational program right now and increase the amount of time we have to be separated from each other. Everything will sort itself out someday...
More on topic, just because I feel better about posting long digressions if I also include something on topic:
I want it to be clear that I'm not some sort of crazy PETA activist. I jokingly call myself an "obligate carnivore" and assisted with euthanasia when I was volunteering at vet clinics. I would just prefer that all other avenues had been exhausted before resorting to lethal/painful animal experimentation, that the suffering be kept to a minimum, that the sample size is kept to the minimum possible to obtain good results, etc.
Also, I was thinking about this and wondering how the tone of such posts contribute to the public perception of scientists as being potentially unethical. I have heard people argue against stem cell research and other such topics by saying that just because something is possible doesn't mean it should be permitted. Usually these people have a sort of "gut reaction" against the research, just as I do about Kao's dog experiments (and Dave's impromptu soap experiment). Should sentiments like, "How cool is that!" be kept to a minimum or qualified? When someone is jumping up and down with excitement over creating florescent markers with jellyfish genes should they temper their enthusiasm so as not to put off those who find "chimeras" horrifying? I don't know... it's just something I've been mulling around. Mostly I'm coming down on the side of letting the scientists express their enthusiasm however they desire, in spite of the fact that it may sometimes put others off (including myself).
Posted by: Zetetic | January 5, 2009 8:24 PM
Dave,
um, I would say that condoms are a better analogy for bed nets than abstinence is. If I had to guess I would say that it is a lot easier to get someone to sleep under a bed net than to give up sex.
DDT is still used to control malaria carrying mosquitoes in many countries. Most of the malaria mosquitoes in many areas come from anthropogenic water sources (irrigation ponds and canals, old tires etc) rather than wetlands. This is because 1) most people don't live in wetlands and the mosquitoes that are a problem in populous areas are those that exploit those habitats. 2) permanent or semi-permanent natural large water bodies are really crappy mosquito habitat. They are full of predators and some research in North America at least shows that intact wetlands actually decrease the numbers of mosquitoes because they support large numbers of mosquito predators (Odonates etc).
Several years ago I read a study that compared the efficacy of DDT based mosquito control in India to alternative non-chemical controls. The non chemical controls included eliminating anthropogenic stagnant water habitats (such as tires) from around communities as well as stocking irrigation water works with fish which were also harvested for food or for sale. Overall the non chemical methods were cheaper and more effective.
Posted by: MattK | January 5, 2009 9:48 PM
My comments are running a little late, so they may seem out of order, I have been pretty busy. I will try and catch up.
Dave's "experiment" was like the "experiments" of George W. Bush, when he put firecrackers in frogs and blew them up.
http://www.all-creatures.org/aip/nl-3nov2000-frogs.html
It does not meet the definition of research. Research has a specific definition:
Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. (45cfr46.102)
What Dave did was not research. It was not systematic; it was not designed to produce generalizable knowledge. From the description, it sounds like an ad hoc intervention to "see what would happen". What did Dave expect to see? If the only observable was going to be muscular activity in a terminally anesthetized animal, is that a reasonable experimental endpoint? Was the effect that Dave observed due to pH? Detergency? Bacterial contamination?
Animals are property. Wild animals are the property of the owner of the land they are on. Property has no "rights" and so the owner can do anything to it (unless proscribed by law). Animals are hunted; sometimes killed just for sport and sometimes used as food. Their only "value" in that context is for their nutritive value of the parts of their dead body that are used as food and because they represent a moving target and because killing them invokes some primal hunting-gathering-killing emotive state.
I suspect that part of why Dave did what he did was to explore how he would feel doing something terrible to a helpless creature, and he found it made him feel bad. In some ways the rest of us should be thankful that Dave learned that lesson about himself on a terminally anesthetized animal and not on a conscious animal, and especially not on a human being. We should be thankful that Dave has the capacity to feel terrible about hurting a helpless creature. There are some people who don't. There are some world leaders that don't, e.g. those leaders who authorize torture of humans for example.
Exploring one's feelings about doing terrible things to helpless creatures is not something that a person should do alone, but only under quite strict supervision by a trained mental health practitioner. There have been quite good suggestions that Dave should consult such a person. Certainly if he ever has the slightest hint that he wants to further explore his feelings about hurting helpless creatures he should run (not walk) to such a person. It may still be useful to Dave for him to contact such a person and explore his feelings with that person even if he never acts on them again. Contact with such a person may facilitate Dave never acting on them again.
Some cultures use dogs as food, some do not. Some cultures induce dogs to fight each other to the death, some do not. Some cultures race dogs for sport, some do not. Some cultures use dogs as pets, some do not. The animal that Dave used was obtained from a pound for "research purposes", not for other purposes. The animal was never Dave's property, so the right to do anything to it never passed to him. I presume the animals were transferred from the pound to Dave's research institution under a transfer agreement which specified what the animals would be used for and subjected to. I presume that Dave violated that agreement by doing what he did.
Research with live animals is difficult for many reasons. Research with live animals is indispensable for understanding physiology. Things can be learned without recourse to live animal research, many things cannot.
Research difficulties with live animals can be divided into 4 categories; first, the purely practical, cost, upkeep, housing, food supplies, disease prevention and otherwise keeping the animals in a state where they are useful for research. Second, the relevance to the research question, the instrumentation required, tying this particular animal physiology to the existing research base, and extending it.
The third category I will call ethics. The only reason animal experimentation is useful in understanding human physiology is because animals are related to humans, we share ancestors with them and so we share physiological pathways with them. Animals invoke feelings in humans for some of the same reasons that humans invoke feelings in humans. Those feelings are real, and dealing with them appropriately and ethically is important for the mental health of researchers using live animals. It is important that humans not become inured to harming helpless creatures because in some circumstances the motivation to harm other creatures can be displaced onto humans. Killing and torturing animals by an individual is very often a behavior that precedes torturing and killing humans. It was Dave's behavior in harming a helpless creature that led some to (rightly) suggest that Dave may need mental health counseling.
The fourth category I will call political, and it relates to the regulations that must be followed. It is primarily due to politically active individuals that such regulations are in force. Many of those individuals, such as members of PETA and ALF want to see all animal experimentation stopped completely. That research questions would remain unanswered is irrelevant to them. That diseases such as malaria would continue to kill millions of humans each year is irrelevant. That many thousands of times more animals are killed under much less humane conditions for pest control, or as food sources is irrelevant. Some of these individuals use terrorist techniques against researchers using animals in their research, putting them at risk of harm or even death..
Gratuitously harming animals the way that Dave did gives such people ammunition to further their political aims, and also may make them more desperate such that they become willing to do more desperate things, things that risk the safety of researchers working with animals. It may make it more difficult for legitimate researchers to use animals for legitimate research.
When Dave was confronted with his actions, he attempted to divert criticism by bringing up the research involving the production of gene knock-out animals. The research done via gene-knock-outs cannot be done any other way. There is no conceivable substitute for knocking out a gene and producing a phenotype to understand what the phenotype of the animal without the gene is. We know that roughly 2/3 of mouse genes can be knocked out and still produce viable and fertile mice. How and why remains unknown. Unless research on those animals continues, we will never know.
Posted by: daedalus2u | January 5, 2009 9:53 PM
Zetetic,
I don't think so. Maybe on a public forum but even then... Should scientists, who have thought about and discussed the ethical implications of their work, and will continue to do so, have to work it in to every communication that they make like some sort of fine print car commercial disclaimer? Should we not be enthusiastic about our work but instead behave dispassionately in the face of coolness just to make sure that lay people, most of whom have put less thought into scientific ethics than we have, don't think that we're having too much fun? I see no problem with addressing ethical concerns as they are raised but I don't think that we should constantly self-censor our awe a priori.
BTW I never understood how people could find florescent marker gene insertion 'horrific'. It just makes no sense to me.
Posted by: MattK | January 5, 2009 9:59 PM
daedalus2u
As a Canadian, this strikes me as a peculiarly American thing to say. I'm guessing that you mean this as a matter of law rather than a matter of principle, but maybe not.
To paraphrase someone I know: It is understandable that Song Sparrows think that they can own a space of land since they don't know that they are mortal but humans don't have the same excuse.
Posted by: MattK | January 5, 2009 10:27 PM
It is inconceivable that effective research to eradicate malaria can be done without live animal research. The role of each particular experiment in the final "cure" of a disease is difficult to ascertain, and impossible to ascertain before the fact. Without basic research, incremental progress toward treating disease cannot be made.
Kao's paper wasn't just about control of breathing; it was also about the development of a technique (shared circulation system) that has been used in other extremely important physiological studies. Parabiosis has been used to investigate many different aspects of physiology. Some of the signals for breathing are carried by the blood, some are carried by nerves. Kao showed that. By showing that there was neural control, experiments to look for blood borne agents were not needed. He wasn't the first to use the technique, others used it for other things earlier.
In things such as cancer cachexia, the signals that cause the muscles to atrophy are carried by the blood. Cachexia is a terminal symptom of many diseases, heart failure, cancer, liver failure, kidney failure, sepsis, just about any degenerative disease can (when it gets severe) cause cachexia. Is it due to the presence of a signal or to the absence of a signal (low nitric oxide would be my guess ;) Can that signal(s) be blocked or augmented? That question remains unanswered.
Doing research on animals in fragile metabolic states may be easier if a healthy animal is attached to the fragile animal. The healthy animal can act as "life support". That is essentially what nude athymic mice are, mice without an immune system so they don't reject what ever cells get implanted in them.
Posted by: daedalus2u | January 5, 2009 10:34 PM
Daedalus2u said: "Animals are property. Wild animals are the property of the owner of the land they are on. Property has no "rights" and so the owner can do anything to it (unless proscribed by law)."
That sentiment horrifies me more than any experiment, I think. I agree that we treat animals as property, particularly domestic animals, but it is not self-evident to me that this "should" be the case. It disturbs me because it seems to be related to the idea that we "own" the earth or have "dominion" over all creatures and can - nae, we should - exploit them without restraint. I don't know that Daedalus holds such beliefs, or to such an extreme in any case, but I feel wary based on what he said.
Human society is arranged so that treating animals as property is the norm, and it would be very difficult and limiting to change the status quo. While I find it hard to imagine ever giving up our "property rights" over domestic or farmed animals, (certainly PETA's "free them all suddenly" approach is unrealistic), I fail to see how I own the robins or magpies in my yard, just because they happened to land there.
Are humans animals or aren't they? The more we discover about how similar animals are to us, the less morally defensible it seems to own and exploit them. I know there are some movements to give apes "rights", which I have mixed feelings about. There is a continuum of "likeness" between humans and other animals. It seems as hard to find a place to draw the line between "animals like enough to us to have rights" and "animals unlike us who do not have rights" as it is to pinpoint a speciation event. The extreme solutions would seem to be either absolute right over animals or no right at all, but I would like to find a middle ground, if possible.
And I've been interrupted so I forget what else I was going to say. Which is just as well, as I tend to be too verbose.
Posted by: Zetetic | January 5, 2009 11:49 PM
Ah, yes, now I remember... :)
MattK said: "Should scientists, who have thought about and discussed the ethical implications of their work, and will continue to do so, have to work it in to every communication that they make like some sort of fine print car commercial disclaimer? Should we not be enthusiastic about our work but instead behave dispassionately in the face of coolness just to make sure that lay people, most of whom have put less thought into scientific ethics than we have, don't think that we're having too much fun? I see no problem with addressing ethical concerns as they are raised but I don't think that we should constantly self-censor our awe a priori.
"BTW I never understood how people could find florescent marker gene insertion 'horrific'. It just makes no sense to me."
I just wanted to say that I agree with you, Matt. At first I did not approve of the tone Dr. Isis was taking with the subject, but upon reflection I realize that I don't want scientists to have to issue a disclaimer every time they get excited about something.
Also, I live in a very conservative area and most of my friends/family are evangelical Christians. They find many scientific things horrifying, which often baffles me.
Posted by: Zetetic | January 6, 2009 12:02 AM
Zetetic, thanks for appreciating my point of view. I do have to admit that while I feel no twinge at all about jellyfish genes I did have a moment of 'Gah!' about the neural and humoural dogs (although I still thought the science was cool). Even more gruesomely, but probably less of an animal rights issue, are some of the groundbreaking experiments in insect hormonal control of development. Basically, they cut the heads off two cockroaches and connected them with glass tubes (nothing fancy, the just jammed 'em on). Now roaches can live for a couple weeks without their heads, but they do not develop to the next instar. However, if only the front of one of the 'roaches heads was removed (leaving the relevant glands and nervous tissue) it can induce development in a completely headless comrade via haemolymph flowing through the tube. By varying what tissue is removed it is possible to determine what parts are important for controlling insect development.
Maybe I've said too much though... entomology labs won't appreciate my remarks if ALF starts picketing them.
Posted by: MattK | January 6, 2009 12:54 AM
MattK, I feel sorry for the bugs I squish even as I squish 'em, but I do try to give them a quick, clean death. Perhaps my problem is that I have a vivid imagination and can all too easily imagine someone performing gruesome experiments on me. I don't want my head chopped off and jammed onto a tube, so I hesitate before doing such a thing to another, even a cockroach.
Though, it is kinda cool that you can grow a whole new bug and study development that way. Cool but evil? Perhaps. Many cool things are arguably evil.
Am I the only one who thinks about cat-eating aliens when I see the acronym ALF?
Posted by: Zetetic | January 6, 2009 2:21 AM
"That many thousands of times more animals are killed under much less humane conditions for pest control, or as food sources is irrelevant. "
With respect, this is most likely bullshit. I mean, there probably are people out there who are only worried about scientific research, and not worried about factory farming, but rest assured PETA speaks out loudly against factory farming too (and other things... for a flagrantly hilarious example, check out http://www.peta.org/sea_kittens/). Granted, I may have a skewed idea of what "most" people think, since most of the animal-rights concerned individuals I have known have been met through vegetarian co-ops at universities (shockingly, this subset of people were pretty pissed about factory farming, not very concerned about scientific research).
"It is inconceivable that effective research to eradicate malaria can be done without live animal research." Bullshit. Find me some freakin immortalized macrophage and dendritic cell lines that are transfectable and produce IL-12 and then we'll talk about eradicating malaria. Or at least I'll get my darn thesis already.
The rest of what you said I tend to agree with, but I don't think we truly know for sure if animal research is by nature "necessary" or just "useful enough that our cleverest scientific minds can't see a better way".
"There is no conceivable substitute for knocking out a gene and producing a phenotype to understand what the phenotype of the animal without the gene is. "
RNAi baby, RNAi... we'll get there. And with temporal and spatial/cell type specificty control most KO can't dream of...
Posted by: Becca | January 6, 2009 12:00 PM
Becca, they are not only worried about animal research, but they would shut down animal research in a heart beat if they could. They would also shut down farming too. Never mind that the resulting consequence would be the extinction of all domesticated farmed animals. These are the people who have set free carnivores from farms (minks) knowing (I presume they knew) that the mink would soon die of starvation, exposure and by eating each other after they had decimated the local indigenous fauna.
I admit I don't understand their thinking. My presumption is that they don't care about animals per se, what they care about is their feelings about animals. It is not injury to animals that bothers them; it is their feelings about those animals that is important. That is the only way I can rationalize their actions to set free healthy well cared for animals so that they will quickly die under horrendous circumstances. It isn't about the animal experiences; it is about the activists' feelings.
Becca, with all due respect if you had "some freakin immortalized macrophage and dendritic cell lines that are transfectable and produce IL-12 and then we'll talk about eradicating malaria." And you would administer these to humans without live animal testing? What IRB would let you do that? No IRB on this planet (that I am aware of, and I would run from any IRB that would allow it).
RNAi with temporal and spatial/cell type specificty control is knocking out the gene but with temporal and spacial/cell type specificity control. You can't do that except in a live animal.
Living systems are too complex to understand without looking at them as whole systems. If you don't understand that, you have a lot to learn.
Posted by: daedalus2u | January 6, 2009 3:22 PM
"RNAi baby, RNAi... we'll get there. And with temporal and spatial/cell type specificty control most KO can't dream of..."
Oh, becca, Nooooooooooo! RNAi has a LOT of caveats that are generally ignored by non hard-core geneticists. It is great in conjunction with other methods (traditional mutants, pharmacology), but is not a magic bullet.
"RNAi with temporal and spatial/cell type specificity control is knocking out the gene but with temporal and spacial/cell type specificity control. You can't do that except in a live animal."
Oh, dear me, daedalus, you need to brush up on your modern molecular genetics. RNAi never knocks out a gene. At best it is equivalent to reduction in expression. And actually, it is far easier to deliver RNAi to cultured cells than any living animal tissue. And temporal/spatial control for RNAi is a myth that is only true in review article hype or allowed to be written in Cell Press journals. At best, you can drive an RNAi transgene under control of a native enhancer. If you really know how an enhancer works or how to reliably know the complete spatial and temporal expression pattern of one, then congrats on your imminent Nobel prize.
Obviously, I am (in part) a geneticist. Normal sane people are not worked up by this stuff.
Posted by: Dave | January 6, 2009 4:13 PM
Dave, I defer to your greater knowledge. DNA stuff is not something I know much about. I wasn't thinking of the distinction between knocking down and knocking out a gene. If you want to get RNAi into every cell, you have to do it when the organism is a single cell. Becca brought it up as an alternative to doing whole live animal experiments and/or gene knock out experiments which it isn't.
The paper I was thinking about when I made that comment was this (and maybe I confabulated techniques)
http://www.sciencemag.org/cgi/content/full/315/5815/1143
Which is a very cool paper with blindly hot science. It touches on my autism research because I think the final common pathway for loss of MeCP2 to cause autism-like symptoms is via metabolic stress (due to Rett patients being mosaic in DNA methylation readout) which causes low NO. Essentially all the physical symptoms of Rett Syndrome are in pathways involving NO, and are what would be expected from low NO. The instability of breathing in Rett Syndrome is especially interesting giving the topic of this post. That instability looks to me like being due to low NO.
Posted by: daedalus2u | January 6, 2009 5:01 PM
"Becca, with all due respect if you had "some freakin immortalized macrophage and dendritic cell lines that are transfectable and produce IL-12 and then we'll talk about eradicating malaria." And you would administer these to humans without live animal testing? What IRB would let you do that? No IRB on this planet (that I am aware of, and I would run from any IRB that would allow it). "
No no no! I'm not about to start sticking immortalized (cancer prone? eek!) cell lines into people willy nilly.
You see, I want cells for in vitro poking. My in vitro poking skills are so l33t it will allow me to discover a way to modify existing treatments and vaccines so they actually work the way we want them to.
*small voice*
Or at least get me a PhD trying.
"RNAi with temporal and spatial/cell type specificty control is knocking out the gene but with temporal and spacial/cell type specificity control. You can't do that except in a live animal. " Well, technically knocking down != knocking out. My point is that RNAi, in theory would cut down on the number of mice needed to probe gene function compared to knockout mice. I see this working in at least three ways:
*First, if a gene is totally required for life, then controlled RNAi (think like a light with a dimmer switch) allows us to gradually cut the level of protein and see if there is a mild phenotype; without killing the mouse (or at least without simply ending up with a pile of relatively uninformative dead mouse embryos).
*Second, for a subset of genes (not all, for obvious confounding reasons), you could (in theory) use the same mouse and knock down genes sequentially, gleening more information on a per-mouse basis. (random side note: actually, I suspect they'll eventually do some awesome studies in multi-stage cancer progression models with tumor suppressors knocked down with RNAi- this stuff is cool on the sheer "gee whiz" science level too, mousie life considerations aside)
*Third (and probably most signfiicantly), making knockout mice, at least as I understand it, requires a lot of mating (sometimes of heterozygotes) and often 12ish generations of backcrossing. RNAi could (in theory) greatly increase the information per mouse when you factor in all those 'wasted' mice you just used for breeding.
Also, you can do RNAi in plenty of things other than mice. Plants are one thing that would not be "a live animal", to take an obvious one. As Dave points out, RNAi in cell culture (like macrophages? *hope hope*) is not necessarily a technically difficult feat (depending on cell type). Moreover, you can do RNAi in some simple animals and learn some pretty amazing things (random plug for planarians: yay for RNAi in planarians! Neoblasts! Neuroregeneration! Cool things to study! You don't even have to worry about the delivery; planarians will *eat* siRNA in their juicy calf liver. mmmmmmmRNAi)
"RNAi has a LOT of caveats that are generally ignored by non hard-core geneticists." You ever try to get shRNA into a macrophage? Even with a lentivirus? Yeah. I know it's got caveats. And that's not even counting the whole game of "oh let's pretend RNAi = universally more specific than pharmacology and not use multiple independent-sequence targets for the same gene BS I see routinely published in the literature. There are many problems, I admit. And I am not a hard-core geneticist, but I play one for my advisor (since he is radically less interested in those particular nitty gritty than I am). So give me a little credit. I do at least consider some of those issues. Many can be addressed with multiple controls.
But do you think knockouts are a magic bullet? Then explain to me how we should know, a priori whether we can learn more about innate immunity from the MyD88-/- Balb/c mice (which are more suceptible to cerebral malaria than their balb/c 'wt' controls) or from the MyD88-/-C57BL/6 mice (which are less suceptible to cerebral malaria than their C57BL/6 'wt' controls)?
(note to the internets: if anyone knows if people are, inflammatorily speaking, more like B6 or more like Balb/c, I would greatly appreciate knowing this)
Quibble: " And temporal/spatial control for RNAi is a future direction that is currently only true in review article hype or allowed to be written in Cell Press journals."
I fixed that for you. No imagination in those old men, I tell ya.
;-)
(P.S. Dearest Dr. Isis, if you are reading this, please bestow upon your loyal worshipers the strike tag for our html goodness. Love, Becca)
Posted by: Becca | January 6, 2009 5:40 PM
Oh, I almost forgot:
"My presumption is that they don't care about animals per se, what they care about is their feelings about animals. " Most likely wrong. My presumption is that they don't care only about a particular batch of mink that they release, but all the mink in general. If they can terrorize the mink farmers into thinking it's not worth farming them, then mink farming will end and no sad little minklets will be kept in captivity and killed for their furry pelts. It's rather logical, actually. Not that being logical always makes things any less batshit crazy.
Posted by: Becca | January 6, 2009 6:00 PM
Rather logical perhaps but also uninformed. Farm raised Mink will hybridize with wild Mink and lower the fitness of the local population (there is a reason none of the Minks that you see along your local creek are piebald). Besides, most of them die quickly in the wild anyway (but unfortunately not all). Outside of their native range releasing American Mink (Mustela vison) has had devastating impacts on sea birds, water voles, the endangered European Mink (Mustela lutreola) and other animals. Conservation measures usually involve trapping mink (less humane then how they are killed in fur farms) so this is an animal activism FAIL since it is not actually humane and is ecologically disastrous. Also it makes the activists look dumb.
Note that animal activists are not the only ones responsible for releasing mink. Farmers have done it to establish populations for trapping and escapes are not uncommon (anyone with Ferrets will appreciate this).
Posted by: MattK | January 6, 2009 6:59 PM
Wow, this thread is going all over the place. I would like to wrap up my contribution with these thoughts:
1) Be nice to animals; you are one.
2) I think it's fine that Isis expressed enthusiasm for what I agree is a clever experiment, but hope next time she'll take a little more time to better explain why the experiment was worth the freakhouse horror show setup. And then someday I'll post how as an undergrad I was tasked with creating worms that grew a head on each end. Both heads ate and the food piled up in the middle until the animal burst and died. This is actually a fun activity you can do with your kid; no special equipment needed.
3) RNAi is one tool among many. Nothing beats drugs for temporal control and the fact that they inhibit proteins, which is really what people are usually studying functionally. But drugs are not always specific and are hard to deliver spatially. Genetic knockouts & other mutants are good but phenotypes are always genetically accrued. Mis & overexpression allows tissue specificity (somewhat) but also has the developmental caveats. RNAi has advantages of drugs and mutants, but can be very inefficient, and it's tough to differentiate between off-target effects and secondary changes in expression of other genes that follow any perturbation (but which are never talked about or generally even looked for). Most papers from my lab use a combination of knockouts, mis/over expression, RNAi, and pharmacology to perturb whatever we're interested in. It's de rigueur in my particular field and where we publish. Why? Because nobody trusts any one particular technique enough to let a conclusion ride on it.
4) I'm not buying the NO stuff with autism, daedalus. I think there's a more obvious commonality in ASDs. But it's a fine paper you point to.
Posted by: Dave | January 6, 2009 7:47 PM
p.s. No one should defer to my 'greater knowledge'. Remember I am a troll and could just happen to sound authoritative once in a while. Internet message boards are not a reliable information source. Read up on the stuff and make up your own mind.
Posted by: Dave | January 6, 2009 7:50 PM
I meant, in point #3 line 4, "... phenotypes are always developmentally accrued."
See what I mean about anonymous internet boobs being unreliable?
Posted by: Dave | January 6, 2009 7:53 PM
I have no trouble learning from people with greater knowledge than myself, I can even learn from trolls. I don't know that much about DNA stuff, and am not going to take the time to learn it because my NO stuff is a better use of my time.
If you want the real scoop on NO and autism, you have to look at my blog, where I demonstrate that I pwn NO and autism. Rett Syndrome is only "autism-like". Any sufficiently severe NO depletion in utero will result in the autism phenotype. Any chronic NO depletion after birth that is sufficiently severe will result in autism-like symptoms.
My comment about animals being property was strictly related to how they are treated by the legal system (which is law and regulation dependant) not how they should be treated by individual humans (which is complex and is context and relational dependent). My attempt was to show that even from the most pragmatic and non-emotional viewpoint what Dave did was wrong on multiple levels.
Just to be clear, what I said about what Dave did, I did not say so as to try and hurt Dave, but rather to try and help him. To help him understand why he did what he did, and to understand why it was wrong, and why actions like that can have adverse consequences to himself and to others.
I included the comment about GWB because I thought it was relevant. The frogs that Bush blew up with firecrackers were the property of the landowner who owned the land they were on. If Bush had the landowner’s permission, then he did not commit a property crime.
In my opinion, children should not be allowed to torture and kill animals the way that Bush was allowed to do or they will grow up to be someone like Bush, who in my opinion puts the moron in the oxymoron of compassionate conservatism.
Posted by: daedalus2u | January 6, 2009 9:05 PM
"Just to be clear, what I said about what Dave did, I did not say so as to try and hurt Dave, but rather to try and help him. "
You can help more by donating generously to the 'Dave Morality Fund'. All money will be spent in ways that distract me from being cruel to animals. I promise.
Posted by: Dave | January 6, 2009 9:43 PM
"My comment about animals being property was strictly related to how they are treated by the legal system (which is law and regulation dependant) not how they should be treated by individual humans (which is complex and is context and relational dependent). My attempt was to show that even from the most pragmatic and non-emotional viewpoint what Dave did was wrong on multiple levels."
Daedalus, I thought this might have been the case, but as I don't know you I wasn't sure. In a purely legal sense I agree with most of what you said; however, I wonder if wild animals are considered property by law everywhere in the world. It seems the sort of thing that might vary culturally or by jurisdiction.
Posted by: Zetetic | January 7, 2009 1:49 AM