The briefing by Greenpeace is certainly confusing. It is difficult to distinguish the science from the claims of Greenpeace, who say this new scientific evaluation shows that the GM maize ‘should not have been approved in the EU or elsewhere’. But the abstract of the paper itself only states that ’it cannot be concluded that [this variety of GM maize] is a safe product’.

Predictably, the BUAV claims that the animal data simply ‘raise more questions than they answer’. Of course, as we have pointed out many times, there is no guarantee of perfect extrapolation to humans in every case of animal toxicity studies. Nonetheless, they give valuable information to be taken into account for regulatory decision-making. BUAV is guilty of deliberately confusing the scientific evidence with the risk evaluation process, which is a political judgement based on the best scientific data available.

It’s also been stressed many times before that impartial, evidence-based science advice is but one element of political decision-making. The evidence also shows that animal studies have proved invaluable in helping to protect people from hazardous chemicals.

"The primary reasons most often cited to explain the growth in the use of zebrafish are a comparison of the animal relative to mammalian models in its fitness for the purpose (the primary purpose being the description of human development and disease).”
Evolution of Standards in the Care and Use of Zebrafish, Chris Obenschain and Steve Aldrich in Animal Lab News Jan 2007

and (ii) they are a hardy species that can be bred and maintained in a variety of conditions.  Therefore labs have developed their own procedures and conditions (1); some of which will be less ideal than others and so place extra stress on the fish.

This is a shining example of how seriously scientists and researchers take animal welfare – after all, members of the public care less about fish than cute furry animals, but scientists consider the needs of all species that they use regardless of the fluff factor.

This consideration – unsurprising from a community that works largely to alleviate human suffering – benefits people by producing good science: once the optimal environment is identified (i) labs can standardise conditions to make their results comparable (cutting down repetition of experiments), and (ii) stress can affect the results of an experiment meaning that the effect of the factor you wish to investigate may be masked or interfered with.

So aside from the ethical justifications (which would be sufficient reasons to improve the welfare),
Good welfare = better science = faster delivery of treatments

I look forward to hearing the conclusions of the LASA meeting.

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(1) It is important to note that generalised standards of care do exist – zebrafish are vertebrates and fall under existing legislation – but currently less is known about their care requirements compared with well-established lab models such as mice. 

‘In the South Seas there is a cargo cult of people. During the war they saw airplanes with lots of good materials, and they want the same thing to happen now. So they’ve arranged to make things like runways, to put fires along the sides of the runways, to make a wooden hut for a man to sit in, with two wooden pieces on his head to headphones and bars of bamboo sticking out like antennas—he’s the controller—and they wait for the airplanes to land. They’re doing everything right. The form is perfect. It looks exactly the way it looked before. But it doesn’t work. No airplanes land. So I call these things cargo cult science, because they follow all the apparent precepts and forms of scientific investigation, but they’re missing something essential, because the planes don’t land.’

The first mention I saw of Cargo Cult science was in Saturday’s Bad Science column in The Guardian by Ben Goldacre, in which he has another pop at ‘nutritionist’ ‘Dr’ Gillain McKeith

‘Maybe this pamphlet is just a shortened and simplified version of [Gillian McKeith’s] PhD text, but if it is at all based on her thesis it is not a good advert for that as a scholarly work. Inside is what I could only describe as Cargo Cult science: she’s going through the motions, but the content, only closer inspection, is like an eerie parody of an academic text.’
Bad Science, Ben Goldacre, The Guardian 3 February 2007

Then Channel 4 aired the theories of the extraordinary Dr Aubrey De Grey on Saturday evening in Do You Want to Live Forever? (If you follow this link, you don’t get any information about the programme, unfortunately). He calls his theories – which do not seem to have been tested by any real experimental science – SENS (Strategies for Engineered Negligible Senescence). Anyway, half watching this programme, which made a reasonable stab at debunking De Grey’s ‘science’ there was a sequence showing the South Seas cargo cult – probably a re-creation.

De Grey’s theories do have some relevance to animal research, in that they don’t yet involve any. Calling De Grey a ‘well-informed flake’, Thomas Sutcliffe in today’s Independent TV review (unfortunately I couldn’t find it online) says:

‘It doesn’t help Dr De Grey’s standing with the bench scientists (the people who do the hard grind with fruit flies and rhesus monkeys) that his disciples range from the wilder frontiers of scientific prognostication.’
Thomas Sutcliffe’s TV review, The Independent, 5 Februay 2007

But wait a minute ... De Grey co-founded the Methuselah Foundation and the Methuselah Mouse Prize: ‘the premiere effort of the Methuselah Foundation and is being offered to the scientific research team who develops the longest living Mus musculus, the breed of mouse most commonly used in scientific research.’

How to define the longest living and thus trigger the award? Unfortunately I couldn’t work it out from a quick read of the website – life’s too short to get stuck into in all this Cargo Cult nonsense, I thought. I’ll just stick to debunking the antivivisection Cargo Cult.

It refers to the 5th World Congress on Alternatives and Animals Use in the Life Sciences in Berlin where a declaration was signed to bring about a global commitment to end primate experiments. The statement was signed by animal rights groups predominately, including ADI and NAVS. However, in December 2006, following a major independent review, the Weatherall report of the Academy of Medical Sciences, the Medical Research Council, the Royal Society and the Wellcome Trust was published. Some of the UK’s leading scientists reported that there is a strong moral and scientific case for the regulated use of non-human primates in research. I quote: `There is a strong scientific case for the carefully regulated use on non-human primates where there are no other means to address clearly defined questions of particular biological or medical importance.’ The key point is that whilst an eventual cessation of animal use can be an agreed aspiration, an immediate ban would have serious adverse medical and scientific impacts and would stop vital research into diseases like Parkinson and Aids.

The Declaration also claims that primates are the closest relatives of humans, sharing 98% of human DNA. Frankly, this is a quite meaningless statement. In 2005 the Nuffield Council on Bioethics report on the Ethics of Research involving animals’ wrote: `Knowledge about the percentage of shared DNA has limited application in helping to decide whether or not an animal experiences pain in ways similar to humans. We also share significant amounts of DNA with mice (96%) and fruit flies (70%) and indeed with crops such as bananas (50%). Having genes in common is information that is of limited relevance with respect to assessing welfare.’

The Declaration also falsely claimed that the very existence of primates is threatened by the bush meat, laboratory, entertainment and pet trades. It is clear that the authors of the Declaration do not know that the two most common species in research are the marmoset and the macaque monkey. The marmoset monkey is bred entirely in Europe. A significant proportion of the macaques are also purpose bred or from an area where they are a non-indigenous species that has a negative impact on indigenous flora and fauna. The authorities in those countries thus require active management of the non-indigenous species. None of these monkeys is listed as endangered by the Convention on International Trade in Endangered Species and the impact of research use is trivial compared to habitat destruction or the bush meat problem.

One would wish that politicians would inform themselves and listen to experts and scientists more closely before they sign a declaration filled with false claims. 

The central conclusion of the report is that ’none of the pre-clinical development studies that were performed with TGN1412 predicted a safe dose for use in humans, even though current regulatory requirements were met‘. This included all the ‘alternative’ methods which antivivisection groups like to promote. For example, it was noted as a ’striking observation‘ that TGN1412 was ineffective when simply incubated with whole human blood or in other tests.

The Expert Scientific Group looked in great detail at the role of animal experiments in pre-clinical testing. They were rightly honest about both the benefits, and the limitations, of such studies. But their conclusions could not be more clear-cut. The group state that:

Most, if not all, new medicines arise from biological insights gained from well-designed animal studies. Important information can be learned about the intended pharmacological response of a new medicine, and its potential for adverse reactions, from studies in animal models.

Animal studies taking due regard of the three ‘Rs’ remain necessary for many aspects of pre-clinical development of novel agents including testing of ‘off-target’ and ‘on-target’ toxicity and understanding the fundamental biology relevant to a new medicine and its target molecules in the human. The key point we want to make is the importance of deciding what can be learned from animal studies in the pre-clinical development of a new medicine, and what limitations there might be when it comes to predicting the response, and dose-response relationship, in humans.

It is clear from the report that there remains much work to be done to elucidate the predictive value of the animal model for responses in humans. For example, the Expert Scientific Group sees possible value in using genetically modified animal cells, tissues or whole animal models, or cellular chimeras, to evaluate responses to human-specific agents. It is likely that we are only at the start of a whole new understanding of the relevance of animal models to these new biological agents. But to rule out animal studies now, as the antivivisectionists wish, would be a disaster.

Some of the other interesting findings in this report relate to ’a number of discrepancies‘ identified in the conduct of the clinical trial. For example, the company involved (Parexel) failed to complete the full medical background of a trial subject in writing. It is strange that when occasionally animal studies are found to be poorly designed or conducted, the whole relevance of animal research is questioned by some commentators (see for example our earlier blog on the Guardian article and BMJ paper claiming that many animal tests are ‘badly flawed’). But when clinical trials are poorly conducted, it’s obvious that they simply need to be improved.

Clean drinking water and effective sewage disposal are of enormous benefit to public health, but in my book they are not a medical milestone because only the consequence, not the originator, is medical in nature.
Prof Carl Djerassi, The pill: emblem of liberation, BMJ 2007 334:15, doi: 10.1136/bmj.39051.582546.94

Quibbling aside, the fact that two-thirds of the milestones reference or rely on animal research in some way validates (once again) the contribution such research has made to human health(1).  The remainder include new techniques such as MRI(2), developed through the ingenuity of scientists, which are aiding the research community’s commitment to the 3Rs.
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(1) and at a similar proportion to other recognition of important biomed research – 70% of the Nobel Prizes awarded for Physiology or Medicine relied heavily on, or involved, animal research.
(2) and even this is used in some research done with animals.

‘many scientists who work on animals have complex takes on the issue. But they are not often willing, or encouraged, to express these feelings. Some of this is directly due to fear of animal-rights extremists; some is an indirect effect of the polarized atmosphere that surrounds the issue. In some labs, at least, scientists feel pressured to keep quiet about the grey areas of debate, lest they undermine the official mantra.’

RDS is not quite sure where this pressure comes from, or what the ‘official mantra’ is, but we assume it is a dig at pressure groups such as ourselves! So it is good to know that, with absolutely no input (or pressure!) from RDS, 99% of the researchers polled rated animal research as essential or at least necessary. Many also commented that scientists needed to engage more with the public and discuss animal research more openly. Less than half of those involved in animal research, however, said they did so. If more did so, a larger majority of the public might also move to the view that animal research is essential or necessary.

Nature introduced the feature by characterising the debate as polarised: ‘the voice of the middle ground has been lost’. However, when the vast majority of biomedical scientists appreciate the necessity of animal research, and the antivivisection and animal rights groups only call for outright bans (see also Mark Henderson’s excellent piece in The Times on Saturday) it is difficult to see where the middle ground lies.

The problem is that the differences between animals and humans always confound the results of these tests and radical new treatments like these desperately need testing with something far more accurate, relevant and reliable than animals.

However this official report states:

pre-clinical tests performed in human and animal cells, and in animal models, failed to predict the human response to the starting dose of TGN1412 given in the trial.

Perhaps the absence of further histrionics from these groups may be because even they realise that logically they should now call for a ban on these cell tests … because these also failed! We await such a BUAV press release with baited breath!

Delve deeper into the report and you are struck by the sheer volume of non-animal data used for safety assessment. Again this rubbishes claims that the pharmaceutical industry does not use these non-animal tests. The reports’ overall conclusion on the use of animals is:

Animal studies taking due regard of the three ‘Rs’, (refinement, reduction and replacement of animals in testing) remain necessary for many aspects of pre-clinical development of novel agents including testing of ‘off-target’ and ‘on-target’ toxicity and understanding the fundamental biology relevant to a new medicine and its target molecules in the human. Most, if not all, new medicines arise from biological insights gained from well-designed animal studies. The key point we want to make is the importance of deciding what can be learned from animal studies in the pre-clinical development of a new medicine, and what limitations there might be when it comes to predicting the response, and dose-response relationship, in humans.

No wonder the media, such as the BBC, now steer well clear of BUAV etc, and realise that including their views is not ‘balance’ but merely promulgates junk science.

Second it is great news about a 12 year sentence for Donald Currie. A dangerous criminal has been taken out of circulation. The sentence of a ‘life sentence with a licence for life’ is exactly what is needed. Anybody who has seen people with his views and approaches (and many have seen this on recent TV programmes ) will realise that they are un-reformable.

Let’s hope the parole board recognises this as well!