Perspectives On Medical Research
Volume 4, 1993
A Critique of Brain Mapping Experiments Using
Animals at the Uniformed Services University of the Health Sciences
Murry J. Cohen
Human brain mapping reveals which brain regions receive sensory information from specific parts of the body. In cases of injury or congenital malformation, brain mapping elucidates the process by which an area of the brain that previously received information from the now-incapacitated body part adapts by developing sensory input from a different body party. This type of brain mapping is known as somatosensory tracking; one of its goals is to study cortical plasticity, the brain's ability to change function.
When performed in a clinically relevant manner--non-invasively, minimizing stress, and only on the species intended to be helped by the experiment's results--brain mapping can be extremely useful. In contrast, invasive animal experiments, such as those conducted by Dr. Sharon Juliano at the Uniformed Services University of the Health Sciences, have not advanced our understanding of human neuroanatomy, neurophysiology, or neuropathology. In Juliano's experiments, cats, kittens, and squirrel monkeys are subjected to the amputation of a digit, surgical brain damage, and other forms of neurological destruction.(1)
Setting complex scientific considerations aside for the moment, the sick and debilitated condition of Juliano's animals suffices to preclude the generation of meaningful data.(2-5) Of the ten monkeys used in the experiments, three died within a day of experimental brain surgery.(2-4) Post-mortem examination revealed the appalling condition of these animals. One was infested with abdominal parasites, dehydrated, and emaciated ("no fat stores");(2) another showed parasitic infection in the colon and lungs;(3) the third had suffered from intestinal parasites and heart disease,(4) In addition, two of the monkeys had previously undergone abdominal surgery:(3-5) one was missing a spleen;(5) the other, his left adrenal gland and kidney.(4) Why were such debilitated animals subjected to surgery? Why was this the second surgery for two of the animals? Surely, such methods are neither humane nor scientifically sound.
Even if the animals had been healthy, the hormonal and immunological changes produced by the stress of being in a laboratory would have precluded the possibility of valid findings. In an interview published in The Washington Post, Juliano stated, "we are not hurting the animals";(6) however, in her grant application she assigned the "level of pain and distress to be imposed on the animals" a value of 3 on a scale of 1-5.(1), Pain and distress alter measurements and confound results because of stress-induced physiological changes.(7) The stress induced merely by the unnatural isolation of these social animals would produce changes in neurotransmitter functions that alter experimental results.
In addition to the problems of disease and stress, Juliano's species choices seem arbitrary and nonscientific. Data from two different species, squirrel monkeys and cats, are to be applied to yet a third species, humans. Will results from the two different species be combined? If the results conflict, which will be considered more valid? If the results agree, to what extent will they apply to humans? It is impossible to know.
Why were cats selected as experimental subjects? Juliano offers four reasons, without once discussing generalizability and applicability to humans.(8) First, cats have previously been used in similar brain-mapping research; second, cats have been used in other types of brain-mapping research, such as amblyopia experiments (see [The Clinical Relavance of Dr. Colin Blakemore's Vision Research] for a critique of such experiments); third, certain brain areas of interest are more "exposed" in cats than in other nonhuman animals, facilitating study; fourth, "the metabolic modular organization of the cat somatosensory cortex has not yet been studied in detail."(8) These four considerations are not appropriate justification for using cats as models for human beings.
Juliano cites prior visual deprivation experiments in which animals, usually cats, were deprived of sight by being blinded, having their eyelids sutured shut, or being kept in darkness. Purportedly, these experiments were conducted to elucidate "lazy eye syndrome" (amblyopia) in humans. Although Juliano does not study sight deprivation, she cites these experiments demonstrating central nervous system plasticity as precursors to her own.(1) But many vision scientists(9-11)--including von Noorden,(12) world-renowned in the field of sight deprivation and an advocate of animal experimentation--have criticized such animal studies because of the neuroanatomic and neurophysiologic differences between cats and humans. (In "amblyopia" research on cats, one major problem is that amblyopia is a disease involving the fovea centralis of the human retina, and the retina of cats contains no such structure.) Juliano completely ignores such interspecies differences.
Why did Juliano choose squirrel monkeys? It is often assumed that all primates closely resemble one another with respect to the parts of the brain that receive signals from specific parts of the body and that monkeys are, therefore, valid models for humans. However, squirrel monkeys differ considerably from owl monkeys in the cortical representations of body surfaces.(13) On what scientific grounds, then, can anyone assume that squirrel monkeys do not differ even more substantially from humans?
Juliano's grant proposal contains no mention of any possible clinical
relevance of her work to humans. Only in a paper published in 1990, four
years after she received her original NIH grant, does she indicate that
her research may possibly advance our understanding of Alzheimer's disease.(14)
The connection between Juliano's research and Alzheimer's Disease is,
to say the least, vague and unconvincing.
Juliano completely ignores new, important, and technologically sophisticated
advances in studying brain structure and function in humans--the CT, PET, and
MRI scans. These imaging techniques, which offer means of directly studying
the brains of people with peripheral neurological damage, are safe and non-invasive,
provide diagnostic information that can directly help patients who participate
in research protocols, and circumvent the problem of interspecies differences
that renders animal experimentation scientifically unsound. In a recent monograph
published by the National Academy of Sciences entitled Mapping The Brain
And Its Functions, the Committee on a National Neural Circuitry Database
of the Institute of Medicine acknowledged that "graphic depictions have
proved to be so useful that greater and greater attention is being paid to
the concept of visualization computing in biomedical sciences."(5)
References
1. Juliano SL (principal investigator). Structural Correlates of Cortical Information Processing. Federal grant application PHS NS-24014, Jul 1, 1989-Jun 30, 1992.
2. Pathology Report, LAM Necropsy No. P-1-88, USUHS Pathology No. 88-37, Jul 31,1989.
3. Pathology Report, LAM Necropsy No. P-3-90, USUHS Pathology No. 90-473, Dec 3, 1990.
4. Pathology Report, LAM Necropsy No. P-4-90, USUHS Pathology No. 90-482, Dec 21,1990.
5. USUHS document dated Oct 7, 1991, signed by HC Holloway (Deputy Dean, School of Medicine), and provided to In Defense of Animals.
6. Anon. Protesters stalk researcher. The Washington Post, June 23, 1991.
7. Barnard N, Hou S. Inherent stress--the tough life in tab routine. Lab Animal l988;17:21-27.
8. Juliano SL, Whitsel BL, Tommerdahl M, Cheema SS. Determinants of patchy metabolic labeling in the somatosensory cortex of cats: A possible role for intrinsic inhibitory circuitry. J Neurosci 1989;9:1-12.
9. Buyukmihci NC. Response to Dr. Blakemore's assertion that work involving nonhuman animals has led to significantly greater understanding and treatment of amblyopia. Perspec An Res l989;l:57-62.
10. Abraham SV. A tribute to Claud Worth. Ann Ophthalmol 1972;4:171-175.
11. Marg E. Prentice Memorial Lecture: Is the animal model for stimulus deprivation amblyopia in children valid or useful? Am J Optomet Physiol Optics 1982;59:451-464.
12. von Noorden GK. Application of basic research data to clinical amblyopia. Ophthamology 85:496-504;1978.
13. Jenkins WM, Merzenich MM. Reorganization of neocortical representations after brain injury: A neurophysiological model of the bases of recovery from stroke. Prog Br Res 1987;71:249-266.
14. Juliano SL, Bear MF, Eslin D. Cholinergic manipulation alters stimulus-evoked metabolic activity in cat somatosensory cortex. J Comp Neurology 1990;297:106-120.
15. Pechura CM, Martin JB (eds). Mapping The Brain And its Functions. Washington, DC, National Academy Press, 1991.
[Note: Juliano's work continues today:
Jablonska B, Smith AL, Palmer SL, Noctor SC, Juliano SL.GABAA
receptors reorganize when layer 4 in ferret somatosensory cortex is disrupted
by methylazoxymethanol (MAM). Cereb Cortex. 2004 Apr;14(4):432-40.]