Chance Favors the Prepared Mind: Animal Research 101

I just discovered that my blog is reviewed under “Science Career Blogs”.  First, I should point out that I am overwhelmingly honored that anyone thinks I am a scientist of any kind and that it shines through on this mess of a blog.  Second, I’m so pleased with the glowing review!  In honor of this, I’ve decided to write an entry about my sciencey field of interest: laboratory animal medicine and welfare. 

I’m going to go through the questions and misconceptions I hear the most in both my real life, and from my job-related searches of animal rights extremist websites.  I’m making these questions up from memory so it’ll read like a Q&A but the answers are for the reader’s benefit.  I’m going to say up front that it drives me CRAZY when animal rightists don’t cite their sources in a usable way.  I am going to do what I can to source any data that I’ve looked up.  If I don’t cite anything then you should assume that I mean the statement with the understood qualifier “at my institution” or “in my personal experience in research”.   Obviously every institution is different.  I just know what I know from life and work.

Finally, this isn’t going to be a funny or witty post.  The following words and images I use may be disturbing or graphic.  This is your warning.  Also, I do not ever name the institution where I work because I literally fear for my safety after attacks made on the homes, lives, web pages, and reputations of researchers from Berkeley and UCLA.  I live with roommates who have nothing to do with animal research, and so if you have a problem, please leave a comment below or email me directly and I’ll be more willing to discuss the specifics of my experience with you privately.  

Q: What exactly do you do that makes you qualified to say anything about animal research in medical laboratories?

A: I play two roles at work.  I am a research compliance officer and I coordinate the IACUC at my institution.  In the past I have worked on the other side as a bench researcher in a toxicology laboratory at a major university.  We used a rat model.

Q:  According to The Animal Research War by P. Michael Conn, PhD and James V. Parker, PhD, about 50% of polled Americans are convinced that animal research is unregulated.  How true is this?

A: This is so far from the truth it’s not even funny.  If animal research weren’t regulated, I would have no job.  Thousands of others like me would have no job, so it’s about time those of us who work in laboratory animal welfare oversight speak up and justify our jobs!  Here is the rundown:

    Let’s say you are a scientist or a medical doctor and  want to see if Flinstone’s Vitamins have any positive effect on the recovery from stroke.  We already know the toxicity of Flinstone’s vitamins is very low.  We know they are safe because they’ve been tested on animals in the past by the manufacturer and have been shown to be safe.  We even give them to our children.  However, no one has taken a good look at how taking Flinstone’s vitamins after a stroke affects the recovery.  You are just the scientist for the job. 

So you apply for a grant.  A grant is money awarded to an institution to conduct research.  A grant is a full scale written proposal of what you plan to do and why.  You’ll need pilot data.  Pilot data is evidence that a few experiments of this nature have been performed and the data suggests that you are on to something. 

Grant review processes are B-R-U-T-A-L.  Almost all medical research is funded by the National Institutes of Health (NIH) which is supported by the federal government.  Other grant agencies include the Centers for Disease Control (CDC), NASA (remind me to talk about our mice going to space in 2010…SPACE MICE!) and The Department of Defense (DOD).  There are many non-profit research-funding agencies as well.  For example, at my institution we work with the Juvenile Diabetes Research Foundation.  Unless you are independently wealthy and have a few million dollars to spend on your own medical research (some doctors do) then you’ll be sending your grant off to the NIH with about a 10% of receiving approval for funding.  The NIH uses a peer review system so your fellow doctors and NOT bureaucrats will be reading and deciding the fates of these grant proposals.  My supervisor’s husband, a vascular surgeon, does NIH peer review every year.

Any of the above agencies will put your grant proposal up for discussion in what is called a “scientific merit review” This is where they decide if the experiment could lead to health benefits in humans, animals, or both.  While an idea to genetically cross a bunny and a kitten is really cute, it will not stand up to a scientific merit review. 

So let’s say you are one of the lucky ones that receives funding.  Time to start work!  WRONG! Now you need permission from your local institution’s IACUC to do your funded study at that facility.  Which leads me to the next question….

Q:  What is an IACUC? 

A: The Institutional Animal Care and Use Committee (IACUC…pronounced eye-uh-cuck) is a committee of persons at any animal using institution.  _There are requirements for membership.  There must be at least one non-affiliated laypersons (non-scientist), one laboratory animal medicine certified veterinarian (your dog and cat vet won’t count) , and the rest must be made up of qualified (doctoral degree in a scientific discipline) scientists.  The committee meets about once a month.  Sometimes more sometimes less depending on the size of the institution. 

The IACUC reviews animal protocols (the written document that decribes the details of the experiment) and votes one of three ways- approved, disapproved, or approved pending modifications. 

Q:  How hard is it to get the IACUC to approve your protocol?

A: Much to the dismay of everyone I deal with on a day to day basis, it’s not easy.  Much of my job is meeting with scientists and doctors and help them plan their experiments before they even submit their protocol to the IACUC so they are more likely to be approved.  Often first time researchers simply don’t know what  the most humane precautions to take are, or they need help securing veterinary drugs their human medical degrees don’t allow them access to.  That’s where I come in to save the day. 

Q: So how does the IACUC review an animal protocol?

A: First I get it.  Every institution will have someone like me who does the organization of the committee.  The doctors, scientists and laypeople who vote on the IACUC have jobs and lives of their own.  I’m there to deal with the day-to-day issues and document everything tediously to present to the Committee at our monthly meeting. 

So first I get your protocol.  It’ll be about 40 pages long and it’s on a standard form so you can’t dodge the hard questions.  When I receive a protocol I do an immediate screen for the following:
•    Pain Category (will discuss later)
•    Species
•    Hazardous Agents (carcinogens, teratogens, toxic chemicals)
•    Biohazardous Agents (live bacteria, DNA, recombinent DNA, viruses, cancer cell lines, or any sort of stem cell line)
•    Personnel- do I know everyone listed as personnel on this protocol?  If someone is new I stalk them down and find out what their credentials are and what training they’ve had.  I work at a small hospital and I know everyone who works in all of the labs.  Larger places will have an employee database I’m sure.

Then over the next month prior to the IACUC meeting, I rip your protocol a new ass.  I get my big red pen and really go through the whole thing.  I review about 7-12 protocols each month. 

When I’m done I send the protocol with my findings to TWO scientists on the IACUC, a primary reviewer and a secondary reviewer.  I also make sure the PI (principal investigator...person doing the experiement) sets up a phone consultation with our veterinarian.  If you don’t consult with the vet, you get knocked out of the next month’s meeting agenda.  It’s mandatory.  When the two reviewers and the vets have read the protocols they return their comments back to me and I compile my comments, the two sets of reviewer comments, and the veterinarian’s comments into a bound book that I disseminate to the IACUC before the monthly meeting.  During the meeting each protocol is introduced by me and then there is an open forum discussion about the project.  I write down everything that is said.  99.9% of the time the protocol is voted approved pending modifications.  The modifications to be made are the recommendations from the committee, the reviewers, and the vet.

Q: What does the IACUC look for when reviewing protocols?

A: The central dogma to an IACUC is the 3 R’s:
•    Reduction-does the PI use the fewest number of animals possible to still have data be statistically significant?  We make the PIs include a power analysis to show how they estimate the number of animals required (we use the variable “n” to denote number of animals used in each test group)
•    Refinement- has the PI refined his protocol to use the most humane procedures?  Has the PI considered use of an in vitro or computer model?  A written justification from the PI is included in every protocol stating why or why not each of the above is met.
•    Replication- Does this experiment unnecessarily duplicate previous research?  Proof of a web search using pubmed or medline must be shown including what search terms were used.  If someone is already doing the experiment, the IACUC will catch it.  I often double check PI’s internet searches for them.
The IACUC benefits greatly from its veterinarian membership.  They often provide the best advice for performing experiments humanely with the appropriate anesthesia (drugs that induce a lack of sensation) and analgesia (drugs that block the perception of pain)

Q: What are the pain categories?

A: The USDA invented a standardized method of categorizing animals based on the level of pain and distress they will experience as a result of the protocol.  If an animal is going to feel pain even for a fraction of a second, you have to be conservative and file your animals in the highest pain category that will be experienced at any point in the experiment:
•    B: Category B is reserved for breeding animals.  They experience no pain or distress induced by humans.  They are there to breed and that’s it.
•    C: Category C is for animals that will feel momentary discomfort that will NOT be treated with pain managing drugs.  The most pain that should be experienced in this category is that of a routine injection or brief restraint or handling
•    D: Category D is for animals that will experience some pain and distress that will completely be monitored and alleviated by anesthesia and analgesic regimens.  In theory, category D animals should perceive no pain
•    E: Category E is for animals that will experience pain or distress and will NOT be given pain managing drugs.  A scientific justification is required for any PI proposing a category E study.  An example of category E studies are studies where they are trying to test the nature of pain, the efficacy of pain drugs, LD50 tests, and any experiement in which the animal will die without intervention (starvation, disease, dehydration, etc.)  Natural animal deaths do not fall into this category (My boss is a geriatrician and sometimes while aging his rats for his studies on aging, the rats would just kick the bucket naturally…) All category E studies have to be reported to the USDA with their written justifications.

Because medical research universities do not often perform LD50 tests, category E studies are rare in the public sector.  Out of almost 3 hundred active protocols I manage, I have only 1 category E study and 1 that the committee was deadlocked about what category the animals should be placed in.

There is an important distinction that research universities and medical research non-profits don’t typically do these toxicity tests or “LD50 tests”.  LD stands for lethal dose.  Every single product you have in your house has been through an LD50 test.  They’re awful; I don’t think I could oversee one myself.  I don’t have the stomach.  They are very necessary though.  If your child drinks a quarter of a bottle of something under the kitchen sink and uou call the poison control center and they say, “Oh shit, I don’t know how much your child’s body can take before she overdoses and dies.  That research hasn’t been done.  She may be okay or she may die.  Who knows?!” I would imagine that is an even more terrifying answer.

  Pharmaceutical companies invent drugs, not doctors.  They have their own very skilled pharmacologists do this.  These private companies are responsible for the manufacturing of a safe drug.  The Food and Drug Administration (FDA) regulates this process.  If you eat it, drink it, smear it, inhale it, or shove it in to any of your orifices,  the FDA tests it.  You can argue the ethics of testing food, cosmetics, detergents, and all “lifestyle products” on animals but I can’t really field that one.  My focus is on the medical research animal model. 

Okay I’m gonna stop here for now.  I promise I will write more later but I’m cramping and I want to save some energy to write something more light spirited.

Stay tuned for your next installment of Animal Research 101!

Comments

[jeff paul internet millions]

I have read this post. This is very much true. I run a part time internet marketing business
I have been collecting many material on internet marketing and checking out Jeff Paul's
internet marketing tactics. I hope that we can keep each other's contacts so I can
discuss my problems Even I own a blog account. I will mention your post in my blog.

[Anna]

I have been reading your blog for quite a while and though I relate most to your "daily episodes" posts, I wanted to thank you for putting this info out there. I am not a big commenting person, but your desire to explain to us layman is helpful.
This may sound rather odd, but in particular tonight it was good to read something so concrete. I just got over a very shit-tastic relationship moment (we're talking 45 minutes ago) and coming to your site did me good. thanks.

[Sol]

this is very interesting. so you want to become a laboratory animal vet or a cat-dog vet?

[Aubrey]

Great post! I have a few questions. :)
1. Is your job "fun"? It sounds very interesting. I guess I mean, is it satisfying?
2. Is your job hard? What's the hardest part about it?
3. How does one go about getting this job? (Education etc)
4. Do you plan to work towards another job, and if so what job? What other jobs would find this job relevant? (That's not meant to be snarky or anything, I really want to know!)