The latest edition of Nature Medicine (volume 14, number 8, August 2008) has an interesting and thoughtful editorial on the use of nonhuman primates in research. We welcome this heavy-weight journal playing its part in the debate.

The editorial recognises that there are ethical issues involved, and that the use of nonhuman primates has long been a contentious issue. Nonetheless, its conclusion is that ’the solid scientific case that can be made to support the use of monkeys and apes in research must take precedence over ethical arguments until the latter can be settled for good‘.

Nature Medicine debunks the myth that there can be realistic alternatives to all use of nonhuman primates in research. As it points out, ’in vitro and computational strategies might be powerful, but they cannot shed as much light on the complex interaction between cells and organs as the use of whole animals can‘. It also finds it hard to see how ’in vitro approaches by themselves can supplant the use of nonhuman primates in the evaluation of drug safety‘.

Of course, the editorial recognises that nonhuman primates would not be regarded as the first port of call. In some cases other species such as dogs, ferrets and pigs could be used instead. But similar ethical issues apply in principle to the use of these species as well. There are no easy answers. But the number of nonhuman primates used in research projects is always a very small fraction of the number of people affected by the disease under investigation. Judgements have to be made. It is just a question of getting the balance right.

The winners of the Daily Telegraph young science writer awards were announced today. In the category for 15- to 19-year-olds, Arron Rodrigues, was the ‘stand-out candidate’ for his piece describing use of nanotechnology to successfully treat cancer in mice. Not afraid of his difficult and doubly contentious subject matter, Arron started:

For every 5,000 drugs that enter pre-clinical testing in the US, on average only five are ever tested on humans, and only one approved for use. This puts into context the many ‘magic bullet’ treatments that we hear so much about. However, as a result of promising lab results, Nanospectra Biosciences has gained approval to ‘commence a human trial in patients with head and neck cancer’ this year using ‘AuroLase Therapy’.

He continued:

The pioneering research was led by Dr Jennifer West at Rice University in Texas, before the technology was licensed to Nanospectra, based in Houston. West’s laboratory exposed mice with cancerous tumours to tiny ‘nanoshells’ and a special laser, which beams light similar to that used in your TV remote ….

This year saw another increase in the use of fish in animal experiments, according to the latest Home Office report. A large proprotion of these used GM zebrafish, which are evidently an increasingly popular animal in biomedical research.

Animalresearch.info has some interesting information on the use of zebrafish in experiments.

Looking back through the headlines RDS has picked up, there have been some interesting breakthroughs thanks to zebrafish - just in the past few months research has hinted at a cure for Huntington’s disease, offered hope for children with Menkes disease, and given us more understanding of hearing disorders.

It’s good to know, that even with this increase, there’ll still be vital consideration given to the environment of the fish - as a previous blog entry can attest!

For more information on the details of the 2007 report, take a look at the RDS website. 

RDS has long accepted the need for continuous improvement in the design and analysis of all types of research. This goes especially for animal research, which is our area of concern and has ethical indications. The concept is partly enshrined in one of the 3Rs, namely ‘reduction’, which implies getting the most useful information out of research projects whilst using the least number of animals.

The group SABRE has launched a website to ‘facilitate discussion about the methods used to design and evaluate animal studies in medical research’. We support such attempts at dialogue, and hope it takes off. So far there are few posts.

SABRE includes links to a number of references, which it points out are not endorsed by the group. This raises an interesting question. We clicked on four references at random, and three of them were by Andrew Knight—a well-known antivivisectionist. All were claiming to be systematic reviews which demonstrate that animal models don’t work. This individual is hardly likely to come to any other conclusion.

The whole point of systematic reviews is to use a defined methodology to improve the analysis of existing research, so as to ensure a better foundation for future research. At some stage we could need a methodology to sort the poorly-conducted reviews from the rigorous ones!

Number 10 Downing Street recently responded to an antivivisection-inspired e-petition calling on the Prime Minister to ‘ignore the petition that supports animal testing.’

It continued ‘because if they bothered to investigate hard enough they would already know that a) there are modern and more effective methods like computer models and tissue research and b) that 92% of drugs tested on animals are still found to be inappropriate for humans....’ This e-petition got 386 signatures by mid-June.

We blogged the 92% nonsense here, and have addressed the pseudoscience around so-called ‘alternatives’ many times.

The original pro-research petition got over 3,000 signatures and called on the government to support animal research - we blogged the very supportive government response to that here.

If ever there was an example of a single technology which antivivisectionists quote as a successful alternative to animal studies, it is functional magnetic resonance imaging (fMRI). The Dr Hadwen trust even organised a presentation about this research method from an Oxford University Professor at their recent meeting in Brussels.

As we have pointed out many times, the failure of antivivisectionists to accept the limitations of some of these alternative methods of research is frankly dishonest. Fortunately, there are more credible sources than animal-rights literature.

Nature journal this week carries an extensive review of what we can do and what we cannot do with fMRI. RDS certainly acknowledges the view of the author that MRI is the most important imaging advance since the introduction of x-rays. However, as the review points out, ‘fundamental questions concerning the interpretation of fMRI data abound, as the conclusions drawn often ignore the actual limitations of the methodology’.

The concluding sentences of the review are particularly strong, albeit rather technical:

‘Today, a multimodal approach is more necessary than ever for the study of the brain’s function and dysfunction. Such an approach must include further improvements to MRI technology and its combination with other non-invasive techniques that directly assess the brain’s electrical activity, but it also requires a profound understanding of the neural basis of haemodynamic responses and a tight coupling of human and animal experimentation that will allow us to fathom the homologies between humans and other primates that are amenable to invasive electrophysiological and pharmacological testing. Claims that computational methods and non-invasive neuroimaging (that is, excluding animal experimentation) should be sufficient to understand brain function and disorders are, in my opinion, naive and utterly incorrect’.

Today the well-known primatologist Dr Jane Goodall called for a Nobel prize for advancing medical knowledge without experimenting on animals, as reported in the Guardian. This rather misses the point. Since about 70% of Nobel prizes in medicine or physiology involve the use of animals, it is already the case that around 30% do not.

The issue is also discussed on the Guardian ‘comment is free blog’, coinciding with the launch of a report by animal protection groups across Europe calling for greater efforts to replace animal experiments across Europe.

We would all wish to see alternative methods developed that could fully replace the use of animals in research. With current scientific knowledge it cannot happen yet. But this is an area of potential common ground between the scientific community and the animal protection movement. At a meeting held at the European Parliament in Brussels, we heard of the many examples of new technologies which have replaced animal studies, or could do so in the future. Much progress has been made already, and there is much more to be done. 

The news in the Times that monkeys have been genetically engineered in the US to contract Huntington’s disease (HD) highlights the continuing ethical dilemmas of animal research. There cannot be any doubt of the suffering of the animals, although it is not pain itself which is a major feature of HD.

It is presumably this suffering, rather than genetic engineering per se, which led the RSPCA to ‘completely condemn’ these experiments. But that is only one side of the story. As always, a modicum of balance is necessary before making a judgement for society as a whole. The other side of the coin is that many people still suffer with HD. Indeed, because of such neurodegenerative diseases, it is likely that the number of monkeys used in research worldwide will rise in future years.

It is true, as the RSPCA points out, that there are other methods of research. But they have limitations and are not satisfactory. In the absence of greater information about the likelihood of scientific and medical benefits from such research, we cannot give a verdict on this particular research. We hope our colleagues in the US have done as good a job as we would wish to see in carefully assessing and weighing the potential benefits against the harms to the animals. This would be the very least we would expect.

The UK may be looking towards a future without parents fretting about their children catching meningitis, universities no longer having to put together contingency plans for outbreaks amongst amorous students, and the elderly not succumbing to this vicious disease. Reports last week of the successful preliminary clinical trial of a vaccine, shown to produce strong responses to the bacteria causing meningitis B, have raised hopes of eradicating meningitis from the UK and Europe.

The vaccine, MenB, was injected into 150 babies at 2, 4, 6 and 12 months of age, and triggered an immune response when tested against 3 strains of meningitis B. After the 4th dose, the immune response was 100%, 98% and 93%. When you hear these exciting and hopeful results, it’s easy to overlook the years of research that have led to this discovery when such results are published. Progress against this disease has depended heavily on animal studies.

Animals have helped us understand the disease, and test potential treatments and vaccines, so much so that the last decade has seen the UK vaccinated against Haemophilus influenzae type b (Hib vaccine), meningitis C, and a vaccine that offers immunity against the most common causes of pneumococcal meningitis.

Novartis, the company involved in producing the new MenB vaccine, continues to be the focus of a sustained campaign from anti-vivisection campaigners - in fact a whole week of action has been promised from the 26th May by one particular group. With such hope of getting rid of the disease, it is a wonder they don’t quieten down a little, and just let the scientists get on with their fight against one of the world’s deadliest killers.

A new publication, Responsibility in the use of animals in bioscience research, lays out the expectations of the main UK funding bodies for the use of animals in research.

The guidelines outline legal aspects of UK research involving animals, and information on how the 3Rs should be applied. It is the first time major UK funders—the NC3Rs, BBSRC, NERC, MRC and the Wellcome Trust—have collaborated in this way. Dr Vicky Robinson, chief executive of NC3Rs, comments: ‘the NC3Rs is delighted that these major funders speak with one voice on such an important issue for the scientific community.’ Further information is available from the NC3Rs website.

It can be downloaded directly by clicking here. (Adobe PDF File, 542kb)

The Independent newspaper today ran a front-page story about the success of initial results from trials of a gene therapy treatment to treat a rare form of hereditary blindness. The article pointed out that the technique had already been shown to work in animals.

But what are the implications?

Only last week the Independent ran a front-page story about the lack of hope in finding an HIV vaccine. This they said was despite many years of tests in animals—some of which showed positive results but subsequently failed in humans.

100 years ago today RDS was announced to the public. A letter in the national press on 24 April 1908 said: ‘A Society has been formed with the name of the Research Defence Society, to make known the facts as to experiments on animals in this country; the immense importance to the welfare of mankind of such experiments and the great saving of human life and health directly attributable to them.’

In 1912, RDS even had a ‘shop’ in London.

In 1908 (as we know from BBC One’s Casualty 1907) life expectancy in the UK was about 45 years, and Paul Ehrlich and Ilya Mechnikoff were about to win the Nobel Prize for research on magic bullets they called antibodies.

Key points that Lord Cromer, founding president of RDS, made in his letter 100 years ago are just as fitting today, for instance: 

‘The great advance that has been made during the last quarter of a century in our knowledge of the functions of the body, and of the cause of disease, would have been impossible without a combination of experiment and observation.’

Our centenary year also marks significant anniversaries of other medical developments related to animal research:

There has been a steady and sustained rise in openness about animal research from many of our leading research institutions in the UK.

This reflects partly the extremely effective government and police action to tackle animal rights extremism, for which we are extremely grateful. It also reflects a commitment from many more individuals in the scientific community to engage in an informed debate about animal research.

It is critical to point out that animal research is not a separate activity to the rest of biomedical research. Rather, is an integral part of the research effort to advance knowledge and ultimately develop new treatments and cures for patients. It is one of many important elements of the UK science base.

We give special mention to two major funding institutions in the UK, for their commitment and contribution to greater openness: the Wellcome Trust and the Medical Research Council.

Almost hidden by acres of UK media coverage of the (at times hysterical) debate about hybrid human animal embryo research, I was interested to spot a small item about HIV vaccine research. It was in the Financial Times this morning, based on a Reuters report. Last month we blogged about leading scientists calling for HIV vaccine research to go back to basics, including animal research. Now, according to Reuters, the US government has acted:

The US government has announced a major overhaul of its effort to produce an AIDS vaccine, stressing a return to basic scientific research after the failure of a key clinical trial last year.

Government officials at a summit with AIDS scientists pledged to prioritise spending on lab work and animal tests rather than expensive, and thus far disappointing, large-scale vaccine trials on humans. ‘We need to turn the knob in the direction of discovery. That is unambiguous,’ said Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who convened the meeting outside of Washington.

Let’s hope, for the sake of patients, that sense will also prevail in our current scientific/political/ethical/religious/media preoccupation with hybrid embryo research.

There is every indication that the more sophisticated and nuanced debate about the future challenges of animal research, which we have been hoping for, can materialise.

Last month our new Chairman, Professor Colin Blakemore, outlined in profile in the Times Higher Education Supplement the new approach to the debate which RDS will take.

This was followed up by an article in the New Statesman online by the Director of the RDS outlining the challenges ahead.

Finally, a detailed and extensive editorial has been published (as a pdf) in Alternatives to Laboratory Animals (which is the Journal of the Fund for the Replacement of Animals in Medical Experiments) outlining how we see the new arguments unfolding.

With many of the animal rights extremists in jail or awaiting sentencing, now is the time to improve all aspects of the debate, and of course the science, 3Rs and animal welfare as well.