In response to our tweet yesterday, a member of the animal experimentation community, Lars Dittrich, has today cited the Olson study, claiming it proves that animal testing holds predictive value for humans.

The Olson study is a favourite of animal modelers, but it fails on every account. Our senior doctor Ray Greek addresses the false claims made by the Olson study, below, in his peer reviewed paper written with Dr. Niall Shanks: Are Animal Models Predictive for Humans?

Below we quote a section of Shanks and Greeks’ paper, summarising the Olson study’s main errors. For those wanting to read Shanks and Greeks’ complete analysis please visit this link,  scroll down – or type in ‘Olson’ in the ‘find box’.

BEGIN QUOTE

‘The Olson Study, as noted above, has been employed by researchers to justify claims about the predictive utility of animal models. However we think there is much less here than meets the eye. Here’s why:

1. The study was primarily conducted and published by the pharmaceutical industry. This does not, in and of itself, invalidate the study. However, one should never lose sight of the fact that the study was put together by parties with a vested interest in the outcome. If this was the only concern, perhaps it could be ignored, however, as we will now show, there are some rather more serious flaws.

2. The study says at the outset that it is aimed at measuring the predictive reliability of animal models. Later the authors concede that their methods are not, as a matter of fact, up to this task. This makes us wonder how many of those who cite the study have actually read it in its entirety.

3. The authors of the study invented new statistical terminology to describe the results. The crucial term here is “true positive concordance rate” which sounds similar to “true predictive value” (which is what should have been measured, but was not). A Google search on “true positive concordance rate” yielded twelve results (counting repeats), all of which referred to the Olson Study (see figure 5). At least seven of the twelve Google hits qualified the term “true positive concordance rate” with the term “sensitivity” – a well-known statistical concept. In effect, these two terms are synonyms. Presumably the authors of the study must have known that “sensitivity” does not measure “true predictive value.” In addition you would need information on “specificity” and so on, to nail down this latter quantity. If all the Olson Study measured was sensitivity, its conclusions are largely irrelevant to the great prediction debate.

4. Any animals giving the same response as a human was counted as a positive result. So if six species were tested and one of the six mimicked humans that was counted as a positive. The Olson Study was concerned primarily not with prediction, but with retroactive simulation of antecedently know human results.

5. Only drugs in clinical trials were studied. Many drugs tested do not actually get that far because they fail in animal studies.

6. “…the myriad of lesser “side effects” that always accompany new drug development but are not sufficient to restrict development were excluded.” A lesser side effect is one that affects someone else. While hepatotoxicity is a major side effect, lesser side effects (which actually matter to patients) concern profound nausea, tinnitus, pleuritis, headaches and so forth. We are also left wondering whether there was any independent scientific validity for the criteria used to divide side effects into major side effects and lesser side effects.

7. Even if all the data is good – and it may well be – sensitivity (i.e. true positive concordance rate) of 70% does not settle the prediction question. Sensitivity is not synonymous with prediction and even if a 70% positive prediction value rate is assumed, when predicting human response 70% is inadequate. In carcinogenicity studies, the sensitivity using rodents may well be 100%, the specificity, however, is another story. That is the reason rodents cannot be said to predict human outcomes in that particular biomedical context.

The Olson Study is certainly interesting, but even in its own terms it does not support the notion that animal models are predictive for humans. We think it should be cited with caution. A citation search (also performed with Google on 7/23/08) led us to 114 citations for the Olson paper. We question whether caution is being used in all these citations.

Conclusion

Mark Kac stated, “A proof is that which convinces a reasonable man.” Even though the burden of proof is not on us to prove animal models are not predictive, we believe we have presented a proof that would convince a reasonable man.

There are both quantitative and qualitative differences between species. This is not surprising considering our current level of knowledge vis-à-vis evo devo, gene regulation and expression, epigenetics, complexity theory, and comparative genomics. Hypotheses generate predictions, which can be then proven true or false. Predict has a very distinct meaning in science and according to some is the foundation of science itself. Prediction does not mean retrospectively finding one animal that responded to stimuli like humans and therefore saying that the animal predicted human response nor does it mean cherry picking data nor does it mean occasionally getting the right answer.

When a concept such as “Animal models can predict human response” is accepted as true, it is not functioning as a hypothesis. We have referred to this as an overarching hypothesis but could have easily referred to it as an unfounded assumption. An assumption or overarching hypothesis might in fact be true but its truth must be proven. If a modality such as animal testing or using animals to predict pathophysiology in human disease is said to be a predictive modality, then any data generated from said modality should have a very high probability of being true in humans. Animal models of disease and drug response fail this criterion.

In medicine, even positive predictive values of .99 may be inadequate for some tests and animal models do not even roughly approximate that. Therefore, animal models are not predictors of human response. Some animals do occasionally respond to stimuli as do humans. However, how are we to know prospectively which animal will mimic humans? Advocates who maintain animals are predictive confuse sensitivity with prediction. Animals as a group are extremely sensitive for carcinogenicity or other biological phenomena. Test one hundred different strains or species and one is very likely to react like humans. But the specificity is very low; likewise the positive and negative predictive values. (Even if science did decide to abandon the historically correct use of the word predict, every time an animal-model advocate said animal species × predicted human response Y, she would also have to admit that animal species A, B, C, D, E and so forth predicted incorrectly. Thus justifying the use of animals because animal models per se to make our drug supply safer or predict facts about human disease would not be true.)

Some have suggested we should not criticize animal models unless we have better suggestions for research and testing [27]. It is not incumbent upon us to postpone criticizing animal models as not being predictive until predictive models such as in silico, in vitro or in vivo are available. Nor is it incumbent upon us to invent such modalities. Astrology is not predictive for foretelling the future therefore we criticize such use even though we have no notion of how to go about inventing such a future-telling device.

Some have also suggested that animal models may someday be predictive and that we should so acknowledge. While this is true in the sense that anything is possible it seems very unlikely, as genetically modified organisms have been seen to suffer the same prediction problems we have addressed [16, 81, 82, 83, 84, 85, 86, 87] and, as mentioned different humans have very different responses to drugs and disease. Considering our current understanding of complex systems and evolution it would be surprising if one species could be used to predict outcomes in another at the fine-grained level where our study of disease and drug response is today and to the accuracy that society demands from medical science.

There are direct and indirect consequences to this misunderstanding of what prediction means. If we did not allow on the market any chemical or drug that causes cancer, or is teratogenic, or causes severe side effects in any species, then we would have no chemicals or drugs at all. Furthermore, there is a cost to keeping otherwise good chemicals off the market. We lose: treatments perhaps even cures; the income that could have been generated; and new knowledge that could have been gained from learning more about the chemical. These are not insignificant downsides. Since we now understand vis-à-vis personalized medicine that even humans differ in their response to drugs and disease and hence one human cannot predict what a drug will do to another human, it seems illogical to find models that are predictive using completely different species from humans. If we truly want predictive tests and research methods (and we do), it would seem logical to start looking intraspecies not interspecies.

Have you heard our senior doctor’s radio interview which is currently being shared on social media?

Please click the video below to hear Dr. Greek explain how today’s medical knowledge understands that each human patient is entirely different and unique. Dr Greek refers to the very varied effects of a mouse model – which actually killed several patients – to illustrate the now widely recognised medical position that one size no longer fits all: we have truly entered the age of personalised medicine, where each human patient is understood to be the sole owner of his or her personal genetic profile, for which treatments can now be tailored to suit, exactly.

All medical research funding needs to go towards this advanced human-based knowledge and research – away from now the proven damaging effects of animal models.

We are delighted that Ricky Gervais and Peter Egan have been spotlighted by K9 Magazine this month, in their continued call for a public science hearing to judge claims: that animal experiments can predict the responses of human patients.

Read the article with Ricky Gervais.

Ricky and Peter are photographed with a beautiful ex-laboratory dog called Scarlett, who is joining the science-based campaign FLOE, as Beagle Ambassador.

Thank you K9 Magazine for all your help; thank you Ricky and Peter for this life-saving focus.

Ricky Gervais says:

“Meeting Scarlett and sensing her painful past will stay with me forever. Like all dogs she is incredibly gentle with a heart of gold, but the horrors of two years in a toxicology laboratory are etched in her eyes and body language. This was clear, even in the relatively short time I spent with her. I’m delighted to have signed an Open Letter calling for animal experimenter Prof. Colin Blakemore to face the world’s leading medical opposition to such experiments, in a public science hearing judged by independent experts. I want people to be able to understand how these shocking experiments are now proven to also fail humans.”

Read the Open Letter signed by Ricky and Peter, including signatories Chris Packham and Dr. Jane Goodall. The letter is addressed to leading advocate of animal models for human patients – Prof. Colin Blakemore – and asks him to agree to a rigorous public scientific debate, judged by independent experts from the relevant fields of science: a debate now called for by over 100 MPs.

 

 

The National Centre for 3Rs (NC3Rs) promotes an animal testing legislation policy called the 3Rs – ‘reduce, refine and replace’ –  established in 1959 for ‘humane experimental technique on animals’.

The 3Rs is now enshrined in the outdated Animals in Scientific Procedures Act , which entirely ignores current scientific knowledge proving that animals have never held predictive value for the responses of humans, in disease research and medical testing. [1-4]

Predictive value in science means getting the answer right around 90 – 95% of the time.

For a test to be accepted as having predictive value by our hospitals and GPs, that test needs to predict the correct outcome for patients around 90-95% of the time. Examples of such tests include those to diagnose if a patient has cancer or HIV AIDS. Animal testing entirely fails to meet this standard. Nine out of ten potential new medicines fail to reach the market shelf because tests on animals are not capable of predicting the responses of humans, in clinical trials. Pharmaceutical companies write about this failure of animal models in their drug development process, openly and often in the scientific literature.

In toxicology testing alone – where rats and Beagles are used to measure the toxicity levels of potential new human medicines – the animal test outcomes correlate with humans around 31% of the time: that’s less than a toss of a coin and worse than guessing. The National Cancer Institute has said we have lost cures for cancer because such studies in rodents have been believed. [5]

There is no doubt that the wider scientific community – outside the vested interests – agree that animals have never held predictive value for humans. But the 3Rs community continue to ignore this, calling for ‘alternatives’ to a method that has never existed. The correct medical term for human-based research is ‘viable’ – this is not an alternative: animal testing is not an interchangeable alternative with human-based research, which has a track record of success.

The 3Rs also calls for a worthless scientific endeavour to be reduced and refined. For more details on the human medical catastrophe which is the 3Rs, please visit this page.

For an example of how animal modelers use the 3Rs to maintain false science, please visit this tweet, below:

148 MPs have now signed four Parliamentary EDMs calling for a science hearing to judge and end animal experiments

These MPs include Jeremy Corbyn MP, Tom Watson MP, Zac Goldsmith MP, Caroline Lucas MP, Diane Abbott MP, Sir Edward Leigh MP, Tim Farron MP and Nigel Dodds MP.

To ask your MP to sign the current EDM please type in your post code at this link .

References

  1. 1. BMJ 2014; 348: g 3719  (available here)
  2. 2. Shanks N, Greek R Animal Models in Light of Evolution Boca Raton: Brown Walker Press; 2009.
  3. 3. Shanks N, Greek R, Greek J: ‘Are Animal Models Predictive for Humans?’ Philos Ethics Humanit Med 2009, 4:2
  4. 4. Lumley CE, Walker S Lancaster, Quay, editors, 1990, ‘Clinical Toxicity – Could it have been predicted? Post-marketing experience’, 57–67; Heywood R. Animal Toxicity Studies: Their Relevance for Man.  
  5. 5. Gura T: ‘Cancer Models: Systems for identifying new drugs are often faulty’. Science. 1997, 278 (5340): 1041-1042. 10.1126/science.278.5340.1041.

We are delighted that Paul O’Grady has joined Ricky Gervais, Peter Egan, Dr. Jane Goodall and many others in signing the Open Letter to Prof. Colin Blakemore, Britain’s leading advocate for the false scientific concept that animals are able to model human patients, in disease research and medical testing.

The Open Letter, below, calls for Prof. Blakemore to agree to debate his position in the rigorous science hearing called for by EDM 66 now supported by over a hundred cross-party MPs who have signed 5 EDMs to this effect.

Dear Prof. Colin Blakemore,

A freedom of information request provided your letter to the Planning Inspectorate, recommending the extension of a Beagle Breeding Farm at B&K Universal in Grimston Hull. The farm will purpose breed around 2,000 dogs annually, destined for painful and traumatic laboratory experiments – typically involving dogs being force-fed chemicals in experiments lasting ninety days with no pain relief or anaesthetic. According to current medical knowledge the results of such experiments are not capable of predicting the responses of human patients, a position highlighted by The British Medical Journal in its Editor’s Choice, June 2014. Over a hundred MPs, to date, have signed Parliamentary EDMs to hear this evidence in a public scientific debate, overseen by independent judges from the relevant fields of scientific expertise. In your letter, you claim to have ‘always tried to engage with those who oppose animal research and take proper account of their objections’, and that it is ‘unacceptable’ that research ‘is impeded or prevented by extreme action’. We therefore call upon you to agree to participate in the thorough scientific debate, as called for by the Parliamentary EDMs and their growing support.

Yours sincerely,

Ricky Gervais, Chris Packham, Peter Egan, Paul O’Grady, Dr. Jane Goodall DBE, Lesley Nicol, Jill Robinson MBE, Jane Fallon, Rick Wakeman and Rumer

Colin Blakemore declined to be interviewed but released a statement in response to the Open Letter, in which he promoted the misleading 3Rs which is an ethical policy for ‘humane experimental technique on animals’.

Louise Owen, founder of the science-based campaign FLOE, was able to respond to Colin Blakemore, live on the BBC, you can listen to her interview below:

 

We have launched a new petition asking TV ‘Supervet’ Noel Fitzpatrick to close down his misleading ‘Humanimal Trust’ and agree to participate in the scientific debate called for by Parliamentary EDM 66.

Noel Fitzpatrick has formed the ‘Humanimal Trust’ which promotes the false medical notion that animal experiments can predict the responses of human patients, in disease research and the safety testing of new human medicines. Noel is using naturally occurring illnesses in his veterinary patients and applying that data to humans, to conform to the misleading 3Rs Govt.  policy – which ignores current medical knowledge by asking for the numbers of lab animals to be merely reduced. Make no mistake: whether they are veterinary patients or lab animals, the same science applies: animals do not hold predictive value for humans.

Given that there is an ethical issue here too, reducing animal numbers does not address those individual dogs, cats, primates and rodents still left lingering in laboratories after their numbers have been reduced.

In May 2016, the Humanimal Trust submitted incorrect science evidence to Parliament’s Science and Technology Committee, in order to secure funding. Our medical Board has written a detailed blog about this, not to be missed, you can read that here.

For examples of the harm and fatalities caused to human patients, by trying to apply data from animals, please visit this link .

For a brochure on why you don’t go to the vet when you are sick, please visit this link. 

Rudolph Virchow, advocate for ‘One Medicine’, opponent of Evolution and the Germ Theory of Disease

It’s worth mentioning that the Humanimal Trust cites a 19th century physician, Rudoplh Virchow, as one of the earliest advocates of ‘One Medicine’. Virchow also made the mistake of opposing Darwin’s Theory Of Evolution and never relented in his opposition. In 1877, Virchow said that the idea that man had descended from apes was an attack on society’s moral foundations and he voiced his opinion that teaching Evolution should not be permitted in Germany’s public schools. This was then acted upon by the Prussian education policy in 1882, when it was forbidden to teach natural history lessons. Virchow also opposed the Germ theory of Disease. Virchow’s own belief was that cells became diseased as a result of internal processes resulting from imbalances in the body. Virchow was partly correct: imbalances in the body can lead to cells malfunctioning and becoming diseased. However, cells can also become diseased when they are attacked by microorganisms. Virchow was wrong to oppose the Germ Theory. Virchow also opposed life-saving evidence for cleanliness and hygiene when examining human patients. Ignaz Semmelweis was the doctor in charge of a birthing ward in Vienna, Austria. In 1847 he showed that if medical staff washed their hands before examining patients, death rates dropped dramatically. Many scientists, including Virchow, dismissed Semmelweis’s work as rubbish. Semmelweis died in tragic circumstances in 1865 following the ongoing unreasonable rejection of his work by other scientists. A very large number of unnecessary deaths were caused by the dismissal of Semmelweis’s work.

139 MPs , to date, have now signed four Parliamentary EDMs calling for a rigorous science debate, judged by independent experts from the relevant fields of science – to stop the funding of animal experiments and ‘One Medicine’, now proven to also fail humans. To ask your MP to sign the current EDM simply type in your post code at this link and send your letter today!

Watch the Science Lecture

This insightful and accessible science lecture guides the viewer step by step through how and why using veterinary patients – or lab animals – to try and predict human outcomes has no scientific basis whatsoever: a MUST SEE!

Please sign and share our new petition asking Noel Fitzpatrick to close the Humanimal Trust, or agree to the EDM 66 science debate; sign and share at this link.

The New Statesman publishes our piece today, about the vital need for a rigorous public scientific debate – judged by experts from the relevant fields of science – about claims that results from animal experiments can predict the responses of human patients, in medical research and drug safety testing.

The New Statesman piece closes by printing the Open Letter to kitten experimenter Prof. Colin Blakemore, signed by Ricky Gervais, Chris Packham, Peter Egan, Dr. Jane Goodall DBE, Jane Fallon, Lesley Nicol, Jill Robinson MBE, Rumer and Rick Wakeman. This letter calls upon Prof. Blakemore to agree to participate in the thorough scientific debate, as called for by 138 MPs, to date, who have signed four Parliamentary EDMs calling for this vital science hearing. The hearing will stop the funding of worthless animal models and speed up cures for humans, by re-directing valuable finance to state-of-the-art human based methods, which are viable – not ‘alternatives’.

To read the New Statesman article, please visit this link.

To read why human-based research is viable – not an ‘alternative’ to animal testing – please visit this link.

If you live in the UK you can ask your MP to sign EDM 66, calling for this science hearing. Simply type in your post code at this link and send your letter today.

Ricky Gervais and Chris Packham have joined Peter Egan in leading celebrity signatures on an Open Letter to Britain’s main advocate for animal experiments, Prof. Colin Blakemore – infamous for sewing kittens’ eyes shut, in experiments that he falsely claimed shed light on the human brain.

To read the full statement by science-based campaign FLOE please visit this link.

Press this week include dog magazines ‘Tails’ and K9 Magazine, tweets below:

The Hull Daily Mail (HDM) covered this story on 10th October, and published the Open Letter to Colin Blakemore. The HDM is the main newspaper in Yorkshire, where B&K lab Beagle breeders are based.

YOU CAN HELP!

Six new MPs have signed Parliamentary EDM 66 this week, calling for the Open Letter’s rigorous science hearing. To ask your MP to sign the EDM simply type in your post code at this link.

 

Patients Campaigning For Cures raise awareness of the vital moral issue of human suffering and death, caused by the now proven failure of animal experiments to help in the search for effective treatments and cures. This human aspect is often overlooked in questioning the morality of animal experiments.

This week, the PR company for animal experimentation, ‘Understanding Animal Research’ (UAR) not only lied about current science, but were additionally exposed by panellist Giles Fraser as failing to uphold a consistent moral position about animals, on the radio programme Moral Maze.

138 MPs, to date, are now calling for UAR to submit the name of their scientist for a rigorous public medical debate  – overseen by independent experts from the relevant fields of science – about false claims that laboratory animal models can predict the responses of human patients. Evidence from this medical hearing can then be submitted to decision makers in order to revoke a 70 year old outdated law, which still requires animal testing, despite its now proven failure.

Scientists from the wider community, outside the animal-based research sector, are increasingly reporting on the failure of animal models for human patients, including the Editor in Chief of the British Medical Journal and pharmaceutical companies. And today, current understanding of evolutionary biology and complexity science has delivered Trans-Species Modeling Theory, which explains how and why animals fail as predictive models of humans.

To ask your MP to sign the current Parliamentary EDM simply click on the image below, to type in your postcode and send your letter today: