Brain Alternatives

Extracts from a Report published in Alternatives to Laboratory Animals (ATLA) volume 28 (2000) pp. 315-331

This report is entitled Volunteer Studies Replacing Animal Experiments in Brain Research: Report and Recommendations of a Volunteers in Research and Testing Workshop. The workshop was funded by the Dr Hadwen Trust for Humane Research. Participants included Stephen Swithenby of the Open University.

...it is not necessary to measure the response of every individual neuron. Knowledge at the level of an individual neuron does not always assist in interpreting brain activity at a level of many thousands of neurons, which is the scale of the neural networks involved in most tasks...in the case of medical research...the precision of animal studies may be superfluous if the results are not reliably transferable to humans...

...animal models seldom express the complexity of human disorders...

...(re spatial working memory area in humans) An area was identified...in a more superior and posterior location than in monkeys...

...PET scans with radiolabelled ligands have enabled studies to be made of neurotransmitter fluxes in volunteers...

...US scientists have developed an MRI method that tracks the direction of fastest diffusion of water, thus delineating fibre trajectories...

...The workshop participants concluded that human studies are feasible and appropriate for studying both the systems level and the global level in psychology...

...MRS offers a non-invasive means of measuring the distribution and concentration of several neuronal and glial cell markers and relating these to human brain function in health and disease...

...Imaging of the human brain can already be of immense value in developing CNS drugs, although its potential has yet to be fully explored by pharmaceutical companies...

...one candidate drug was very effective in rodents but did not appear to be active as an analgesic in humans...This was not discovered until clinical trials, after approximately £20 million had been invested...The use of a carbon-11-labelled molecule and PET imaging with volunteers would have determined whether the drug penetrated the blood-brain barrier...

...In medical research, animal experiments may provide data of considerable precision but of variable accuracy, in terms of relevance to the human brain. Human imaging research may produce qualitatively different data from those of animal experiments, which some scientists find difficult to accept...human research overcomes the species barrier – especially significant in drug responses and in functional anatomy...

...Human subjects are easier to train...

...Imaging the human brain has provided new global information about integrated networks, and has identified areas of unexpected relevance, which have taken some research fields beyond the scope of animal studies...

...within strict radiation exposure limits, repeat PET scans can be taken permitting, for example, changes in receptor binding to be measured...

...Imaging is relatively new and research culture can be slow to change...Sometimes, imaging results in humans generate new hypotheses that are still tested on animals, simply because animals have always been used...It is hard to justify this practice...

...pharmaceutical companies can be conservative and bound by regulatory requirements: this is a barrier to change...

...Imaging is now central to some fields, such as cognitive neuroscience...

...Funding...can be difficult to obtain: the pressure is to do research with existing techniques...research councils are dominated by basic scientists who regard animal work as the norm...

...Technology and methodology support staff (such as physicists, computer experts and mathematicians) are essential but, at present, universities make inadequate investment in these areas, even though the continued development of imaging depends on them...

...With animal experiments, it is essential...that a critical appraisal is made at every stage of a project development, especially to ask the following questions: “What is the ultimate purpose of the study?” and “Is it appropriate to address some or all of the key issues in healthy or patient volunteers, or by other non-animal means?” Researchers, funding bodies, Home Office inspectors and ethical review processes all have a responsibility to participate in this ongoing appraisal.

...Certain classes of research, such as cognitive neuroscience, are particularly amenable to the replacement of animals by human studies...

...human studies of disease evolution...particularly with dementia...are revealing the limitations of some traditional animal models...

...The repertoire of radiolabelled ligands for PET research into specific receptors needs to be developed further...

...Various biochemical and pharmacological methods applied to human brain tissue ex vivo can complement imaging of the living brain, thus permitting the replacement of more animal experiments...

...Although the initial capital investment for imaging facilities can be large, once they are established, subsequent human studies can be very productive and can generate data more swiftly than, and often as economically as, animal experiments...

...Methods of interpreting imaging data, such as waveform and mathematical analyses, are being improved, but expert staff are in short supply...Appropriate funding and a career structure would help these staff to be retained and would ensure the continued development of imaging techniques...Multidisciplinary research teams are required...Improvements in career pathways for biologists who want to do clinical studies...would facilitate human studies.