Our report on the WEATHERALL report

We, as PACE members, sometimes have to face the accusation that we have twisted priorities, that we put animal welfare above those of diseased or dying humans, that children would be dying of polio, that miracle drugs could not be developed or high-tech surgical techniques would not be possible, or that AIDS could not be alleviated and soon prevented, were it not for research on non-human primates (sometimes referred to in this text as nhps). We are often told we would quickly change our tune if we had a parent or spouse suffering from Alzheimer's or Parkinson's or a child sick with cancer.

The Weatherall Report was published in December 2006 and was hailed as the first "independent" enquiry into whether there is a convincing case for continuing to use non-human primates in biomedical research. Of course there have been other enquiries on this same issue in recent years but they have been undertaken either by government committees or animal welfare organisations and therefore seen as biased.

The Weatherall enquiry took evidence from approximately 100 organisations or individuals involved in some way with laboratory primates and to be fair to him, Sir David Weatherall FRS FMedSci, himself a leading Oxford medical researcher, tried very hard to dig down to the important issues, attempted to document hard evidence, and made some attempt to confront the ethical dilemmas. But how "independent" was his enquiry?

The report was funded by the Academy of Medical Sciences, the Medical Research Council (then headed of course by “Chimp Enemy Number One”, Colin Blakemore), the Royal Society and the Wellcome Trust (representative of big pharma); and of the 10 committee members, seven were eminent medical research scientists. Is it remotely conceivable that the enquiry could, however broadminded and fair the members tried to be, have concluded that non-human primate research was not justified? And what, then, were its conclusions?

1) In relation to the development of drugs and vaccines for the killer diseases, HIV/AIDS, malaria, TB, schistomasomiasis and hepatitis, Weatherall could find no substantiated referenced evidence of any advances made by using non-human primates. He notes, for example, that 25 years of research on HIV using chimps produced over 30 potential vaccines all of which failed in human trials. This is understandable since, although chimps are closely genetically related to human beings, their physiological reactions are often very different, owing to the 6 million years of evolution which separate our species: six million years in which the human lineage and the chimp lineage adapted to survival in very different habitats, eating very different diets, and challenged by a very different range of pathogens. As a consequence chimps’ metabolism, the proteins and biochemistry of their blood, their endocrine responses, and above all their immune systems are all different from ours, and if used as models can give dangerously misleading results.

2) The treatment of Parkinson's disease (PD) of course was claimed in evidence to the committee as a success story. (Many PACE members might have seen the widely-watched TV ‘debate’ in Autumn 2006, in which Professor Tipu Aziz, a close colleague of Colin Blakemore's, stated that the technique of Deep Brain Stimulation had only been possible through research on monkey brains and produced a symptom-free PD patient from the audience. Many people were convinced by this dramatic case of the value of primate research and so, apparently, was Weatherall.) [Immediately upon publication of the report another Oxford neurosurgeon, Marius Maxwell, in the Oxford Magazine number 259, challenged this conclusion absolutely, stating that all current advances in PD treatment had come from "clinical research of actual end-stage human PD patients" and that Aziz had "rushed to duplicate these studies in the neurotoxin nhp (non-human primate) models". This is a reference to the fact that monkeys do not naturally develop PD, so that before the researchers can start their so-called treatment by drilling into their brains, effects mimicking human symptoms have to be induced using central nervous system poisons i.e. the "neurotoxin nhp model". For a thorough account of the course of PD research with full references, see www.navs.org.uk/media_centre/35/0/757/.

Considering other neural pathologies Weatherall was forced to conclude that there has been no progress on prevention or treatment, after decades of primate research on, for example, strokes or Alzheimer's Disease (both of which, like PD, are not naturally developed by monkeys and therefore have to be induced by deliberate brain damage).

3) Weatherall reports that over 3,000 monkeys were used in 2005 in nearly 5,000 experiments and no fewer than 87% were involved in the toxicity testing of new drugs. Partly this is due to EU legislation, Directive 2001/83/EC, requiring "safety" testing on one rodent and one non-rodent species before human clinical trials are permitted. A bizarre fact revealed in Weatherall's discussion is that pharmaceutical companies developing a drug have to search hard among species to find one which "responds pharmacologically" before they even start the animal testing (!!!) This, to say the least, seems to reveal a ridiculously unscientific circularity.

Despite all this pre-selection, the tragedy of the infamous TGN1412, which had been tested at a hugely higher dosage on monkeys, still occurred. The lessons of this section of the report are clear: the legislation must be urgently changed; and alternative non-animal methods must have vastly more resources put into them.

4) Alternatives to experimental research or toxicity testing on nhps do exist and Weatherall describes them quite thoroughly in chapter 9, worth reading for its informative value:

In vitro (test tube, culture dish) work with tissues from samples, autopsies, biopsies, skin strips, smears etc on cells, molecules, genes, proteins, DNA, RNA;

Computer modelling of systems biology can handle huge amounts of data with which to calculate outcomes, test hypotheses and predict effects;

Microdosing might have saved the 6 young victims of TGN1412 and is probably the most likely candidate to replace nhps in toxicity testing. A miniscule dose of the pharmacological agent to be tested, made slightly radioactive, can produce a imperceptible reaction by the body's systems measurable only by using accelerator mass spectrometry (AMS) but which is predictive of the effects of a larger dose;

Transcranial magnetic resonance imaging (TMS), positron emission tomography (PET), functional magnetic resonance imaging (fMRI) all are ways of viewing what's going on in the human brain down to the firing of tiny groups of neurones, before, during and after various interventions, and could replace entirely the brain function experiments on monkeys which use helmets and implanted electrodes.

The last two alternatives discussed by Weatherall involve mice and other small mammals. The use of transgenic mice is a growing area of biomedical research involving replacing genes or DNA in mouse eggs with human proteins to develop a strain of mice which have human genetic material in every cell. These mice then react as humans to, for example, toxic compounds or can be used as models for testing vaccines. Stem cell research is closely related and involves growing genetically human organs in mice or other mammals.

5) As we said above, Weatherall does attempt to confront the moral issues but most PACE members would, we think, find his reasoning unsatisfactory.

Firstly he argues that "people in general" believe humans have a higher moral status than animals. He ‘proves’ this by the fact that in the imaginary case of a burning hospital building, people would intuitively rescue the human beings before the animals in the lab or the hospital cat. (Surely this is total nonsense. Our guess is that "people in general" would rescue their own family members first on the basis of kinship, then the young before the old on the basis of their right to a life, then the doctors and nurses on the basis of their value to society - and probably if they had a moment's opportunity they would smash open the monkey cages on the way - none of which decisions would imply anything whatsoever to do with moral status. Nor anything to do with any group's suffering being less important.)

Secondly, Weatherall uses the utilitarian argument that suffering to a "small" number of primates (10,000 in Europe per year, 50,000 in the US, up to 200,000 worldwide) is worth the benefits to huge numbers of human beings. (One could justifiably say "Benefits? What benefits? The benefits to humanity resulting from experimenting on nhps are simply not evident from Weatherall's very exhaustive report)!. 6) Finally, Weatherall's conclusions? You've guessed it. Nhp research should be allowed to continue! We have to ponder the pressures on Weatherall and his committee, since after three years of enquiry we defy any reader of the report in full to find a convincing case for medical research using nhps. Here are the reasons he gives:

(i) The unpredictability of research means that new requirements for nhps in the future cannot be excluded (straight from the mouth of our old friend Colin Blakemore no doubt!)

(ii) Banning nhp research in the UK would force researchers overseas

(iii) Research programmes using humans would be too expensive. (This is clearly rubbish. Human volunteers would not be hard to find. Every monkey costs £20,000 to buy and £400 a week to house!)

(iv) The law requires two different non-human species for the safety testing of new drugs. (Then let's improve the law!)

(v) The use of human subjects would "provide more clearcut answers" but would not be "permissible" (why? no law bans the use of human volunteers).

(vi) New drugs and vaccines need to be tested on a "whole complex organism" [irrespective of whether the results are predictive for humans apparently]

7) In summary, the Weatherall report does not provide a convincing case for using nhps to further the progress of medical benefits for human beings. Its conclusions are therefore not a logical outcome of its content and are disappointing. However the report is full of valuable information and is likely to be used as a definitive defence by researchers in the future. "Well Weatherall looked into that and he concluded .......etc". Therefore, we all need to be prepared, by reading the report itself, or at least this short summary of it!

News 07 index