Sunday, March 23, 2008

The 3Rs

I doubt that there is a single Institutional Animal Care and Use Committee (IACUC) that does not pay lip service to the notion of Russell and Burch's 3Rs. The University of Wisconsin, Madison, for eaxample says:
UW-Madison is committed to "the Three R's"

Reduction--using the least number of animals necessary for statistically valid scientific results

Replacement--using non-animal alternatives (i.e., cell culture) or choosing a species lower on the phylogenetic tree (i.e., mice instead of monkeys)

Refinement--choosing methods and experimental procedures that minimize pain and distress in research animals (i.e., using laparoscopic techniques rather than laparotomy; defining endpoints as early in a disease process as possible)
Presumably, though I've been unable to find any clear regulatory statement to the effect, an experiment or study that could use human subjects, paid or volunteer, without significant risk, should do so rather than using animals. This seems like a reasonable interpretation of the 3Rs.

In other words, if a scientist can ask a human subject to follow a point of light with their eys, and then, say, beep a horn to see whether their attention is distracted, they should do so rather that conditioning a monkey to follow the point of light while restrained and working for a drop of liquid to overcome their fluid deprived thirst. One method is humane and the other is much less so. The 3Rs suggest that the use of humans in some studies is more ethical than using animals.

So, I was bothered by UW-Madison researchers who chose to - and were allowed to - use monkeys in a study that seems to have been more or less risk-free. I don't understand why human volunteers or paid participants weren't used.

I've posted the question at the PLoS article comment page, I've written to the editors of PLoS, and to Daniel J. Kelley, but have received no reply. My question is this: what characteristics of this study made it necessary to use animals, monkeys in this case, rather than human subjects?

If there is no good answer, then this seems to violate the spirit of the 3Rs and potentially, the letter of the Animal Welfare Act.

Automatic physiological waveform processing for FMRI noise correction and analysis Kelley DJ, Oakes TR, Greischar LL, Chung MK, Ollinger JM, Alexander AL, Shelton SE, Kalin NH, Davidson RJ. PLoS ONE. 2008.

Waisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin, Madison, Wisconsin, United States of America. [To whom correspondence should be addressed: E-mail:djkelley@wisc.edu]

Functional MRI resting state and connectivity studies of brain focus on neural fluctuations at low frequencies which share power with physiological fluctuations originating from lung and heart. Due to the lack of automated software to process physiological signals collected at high magnetic fields, a gap exists in the processing pathway between the acquisition of physiological data and its use in fMRI software for both physiological noise correction and functional analyses of brain activation and connectivity. To fill this gap, we developed an open source, physiological signal processing program, called PhysioNoise, in the python language. We tested its automated processing algorithms and dynamic signal visualization on resting monkey cardiac and respiratory waveforms. PhysioNoise consistently identifies physiological fluctuations for fMRI noise correction and also generates covariates for subsequent analyses of brain activation and connectivity.
Some more lip service:

"I consider myself a welfarist and think that animals need to be used only when absolutely necessary and under the most humane conditions.” From: Straight talk with… Frankie Trull. VOLUME 14 | NUMBER 2 | FEBRUARY 2008 NATURE MEDICINE

"The IACUC decides whether the researchers may conduct a study involving the use of animals and the parameters of such use. Some of the questions considered by the IACUC are: ... whether animals are absolutely necessary to achieve the result." From: Columbia University.

"What is often not realised is that scientists have strong ethical, economic and legal obligations to use animals in research only when absolutely necessary." From: The Research Defense Society (RDS).

1 comment:

Anonymous said...

Hi... well my guess is that the data have actually been acquired for the purpose of a completely different study, and as they wanted to have some correction for physiological artefacts, they coded it and made available the code in this way, squeezing an extra publication out of it and helping the wider research community. Because - in my view not only is such a study not risky in human subjects, but mainly it is generally much cheaper and easier to use human volunteers - so even if they did not care about 3Rs, they would be crazy to go into all the hassle around animal research to check a method generally intended for human scanning anyway. That said, I did not read all the details of the article. If you really want to know the truths, look oout for conference and journal publications from that group using strikingly similar data!