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EDM 66


We are honoured that our evidence is highlighted in Parliamentary EDM 66, tabled by Kelvin Hopkins MP.

For the EDM's reference to Penicillin please visit this link.

An Invitation to All MPs

The Editor in Chief at the British Medical Journal Highlights the Failure of Animal Experiments to Predict the Responses of Human Patients.

Please Sign EDM 66 which calls for fa air public scientific debate on the claimed predictive value of animal experiments for human patients

The issue of human health and our search to cure diseases is vital to us all. The controversial issue of using animals in experiments has been a heated topic of debate in the media for many years, usually between pro-vivisection scientists and animal advocates.

However, current scientific knowledge now has the evidence to recognise  and explain why using animals to predict human response  to drugs and disease is, in fact, invalid [1].

For tests to be scientifically and medically recognised as “predictive”, they need to have a success rate in the region of at least 90% [2-4] Animal models for toxicity testing have a staggeringly low predictive value for humans: their ‘success’ rate consistently falls within the region of 31%, far less than that required to meet the prediction criteria [5-6].

Not surprisingly, a failure rate of 69% is compounded by the fact that scientists will not know the effect on humans until after the medicines have been applied, [7] thus further highlighting that animal models do not meet the criteria for predicting human response to medicines and disease.

Indeed, 90% of drugs that test well in animals harm or otherwise fail humans, pharmaceutical companies acknowledge the failure of animal models in their drug development process and write about this openly in the scientific literature

EDM 400: Holds the 'Concordat on Openness on Animal Research' to account with Public Scientific Debates In The Spirit Of Open Constructive Dialogue

EDM 400 calls for scientists, who still continue oppose its now known statistics and persist in experimenting on animals, to agree to constructive, public scientific debates with the experts who  illustrate the EDM’s evidence.

Validity: Predicting Human Response

Scientific knowledge has now reached a position where the questions we are asking are highly complex to the point where differences between species outweigh the similarities. With advances in technology we are able to study human disease at the genetic level, and this is precisely where species differences are most pronounced [8].

The causes of most human disease lie in the proteins  the body makes, their regulation and how these proteins interact. Gene expression is responsible for all of these interactions. With systems as complex as humans and non-humans, we now know that even very subtle differences may result in completely varied responses to drugs and diseases [9].

A gene can be removed from members of some species with no consequence,  while members of another would die without it. Some genes cause disease in members of one species, but are harmless to those of another. There is also variation within one given species [10].

Studying genetic variation between humans can convey medically relevant  data  in ways that animal studies cannot. Studying human-based genes will provide us with human-directed knowledge that we need in order to cure our diseases [11].

History: How Did We Get Here?

 In 1847, Claude Bernard institutionalised the modern use of experiments on animals, claiming they were “entirely conclusive for the toxicology and hygiene of man”. By concentrating on non-human animals, Bernard went on to reject the theory of evolution and minimalised the study of the frequency and causes of disease in different groups of people, now known as epidemiology [12].

Here and Now: Why Does It Continue?

Many factors contribute to the continued use of animals as claimed predictive models. A massive financial infrastructure has  arisen, built on the animal model, upon which many businesses and scientists now depend. Some scientists are reluctant to state concerns through fear of committing  career suicide, and are often encouraged to infer “human relevance” from non-human studies [13]. However, some still defend it simply because the animal model is what they were taught to believe in [14].

Evidence: Acknowledgement Of Failures

 As previously stated, the failure rate for animal models falls consistently in the region of 69%. This statistical analysis is not anecdotal. There are no studies in the scientific literature that show evidence to the contrary, including the oft mistakenly cited Olson study. [15].

Examples of how animal experimentation has harmed human health [16].

  • Penicillin stayed on the shelf for over a decade because rabbit tests suggested it would be ineffective in humans.
  • The polio vaccine was delayed by decades because the way monkeys responded was very different from the way humans reacted.
  • Studying strokes and brain haemorrhage in animals has led to multiple medical treatments that worked in animals but that resulted in harm to human patients.
  • Scientists were misled about how HIV enters the human cell because of studies on monkeys.
  • HIV vaccines that protected monkeys have actually increased the risk of contracting HIV in the volunteers that took the vaccine.
  • The flip side of all this is the fact that society has also lost cures and treatments because scientists believed the results from animals.
  • Cancers in mice have been cured but the cures did not work in humans.
  • Babies of mothers who took thalidomide suffered severe birth defects but animals for the most part did not.

Pharmaceutical companies acknowledge the failure of animal models in their drug development and write about this openly in the scientific literature.

Drugs entering Phase I trials have approximately a 9% chance of coming to market [17-20]. Only 5% of cancer drugs that have an Investigational New Drug Application (IND) eventually go to market [21]. Lack of safety or efficacy accounts for approximately 90% of drug failures during clinical trials [22-23]. Both safety and efficacy determinations rely on animal models. Then-U.S. Secretary of Health and Human Services Mike Leavitt stated in 2006: “Currently, nine out of ten experimental drugs fail in clinical studies because we cannot accurately predict how they will behave in people based on laboratory and animal studies” [24]. Jonson et al found that out of 39 anticancer drugs tested on xenograft mice, only one mimicked the response in humans [25]. The National Institute of Cancer has gone on record stating we have lost cures for cancer because studies in rodents have been believed [26]. Visit this link for more examples.

Other Issues: What Are The Other Problems?

Animal-based experiments waste money in that the grants could have funded human-based research and because misleading data in drug development increases the cost of medications. Harmful medications are developed that eventually must be shelved, thus costing more money, and helpful medications are lost because of invalid data from animal models. Animal models also receive the lion’s share of research funding [27].

Valid Methods: The Future Of Medicine

There are very many ways to conduct valid research, including in vitro research on living tissue, mathematical and computer  modelling, microdosing, epidemiology, post-marketing drug surveillance and genetic studies  to encourage personalised  medicine, which involves the ability of  physicians to treat patients individually based on their own unique genetic  makeup. Today we also have stem cell research, gene-based medical research such as pharmacogenetics, toxicogenomics, systems biology, and an important but oft-overlooked area of study is evolutionary biology [28].

VALID SCIENCE: Not Animal Welfare Or Moral Concern

FLOE’s illustration of science, as such, is kept entirely distinct from the separate, moral issue of animal suffering. The medical experts who illustrate this EDM state that animals can be successfully used in science for 7 out of the 9 accepted main ways, failing solely as predictive models for humans. Viable uses include animals as “spare parts”, to study basic anatomy and physiological principles, to train medical students and as bioreactor factories (for example, for the production of insulin) [29]. Even so, for these viable uses there already exist some more efficient, less expensive human biology-based “alternatives” [30].

FLOE: About For Life On Earth

FLOE is an alliance for evidence based medicine,  illustrated by the leading scientific experts against animal experiments as assumed able to predict human responses. The aim of EDM 22 is to initiate public debates; scientist to scientist, while challenging the use of animal models to predict human response to drugs and disease. FLOE comprises a wide range of human health advocates,  led by a Patients and Families Group.

As well as concerns for human health, FLOE recognises those who support its scientific evidence and additionally hold moral concerns for laboratory animals. FLOE is therefore proud to be supported by primatologist and television wildlife presenter Dr Charlotte Uhlenbroek, together with the Beagle Association.

EDM 400: Why This EDM Needs Your Support

Human medicine needs to make a fundamental change from using animal experiments to human-based research. This has already begun, but funding needs to increase in this area.

Given the overwhelming and compelling scientific evidence that animal models are not able to predict human response to drugs and disease - the valid yet unanswered questions regarding the continued use of animal models, the need for accountability, the clear vested interests of vivisection advocates,  the need to put more funding towards valid research methods and the concern that animal experimentation is at an all time high - it is surely crucial that  public scientific debates are encouraged.

INVITATION TO MPS

Please sign EDM 400 and add your voice to our call for public debates, scientist to scientist, in the interests of medical progress for patient safety, and healthy lives. Thank you.

Sources and Further Reading:

  • Shanks N, Greek R, Greek J: Are Animal Models Predictive for Humans? Philos Ethics Humanit Med 2009, 4:2.
  • Shanks N, Greek R: FAQS About The Use of Animals In Science University Press of America; 2009.
  • Shanks N, Greek R: Animal Models in Light of Evolution

References:

1. Shanks N, Greek R: FAQS About The Use of Animals In Science University Press of America; 2009.

2. Shanks N, Greek R, Greek J: Are Animal Models Predictive for Humans? Philos Ethics Humanit Med 2009, 4:2.

3. FDA panel reviews Diabetes Drug linked to dozens of deaths [ http://edition.cnn.com/HEALTH/9903/25/rezulin.review/index.html?iref=allsearch ]

4. Masubuchi Y: Metabolic and non-metabolic factors determining troglitazone hepatotoxicity: a review. Drug Metab Pharmacokinet 2006, 21:347-356

5. Heywood R. In: Animal Toxicity Studies: Their Relevance for Man. Lumley CE, Walker S Lancaster, Quay, editor. 1990. Clinical Toxicity – Could it have been predicted? Post-marketing experience; pp. 57–67.

Spriet-Pourra C, Auriche M. New York. 2 1994. Drug Withdrawal from Sale.

6.  Shanks N, Greek R, Greek J: Are Animal Models Predictive for Humans? Philos Ethics Humanit Med 2009, 4:2.

7.  Salén, Jörn C W. 1994. Animal Models—Principles and Problems. Handbook of Laboratory Science Volume II. Animal Models. 1st edition., edited by P. Svendsen and J. Hau. Boca Raton: CRC Press.

8. Shanks N, Greek R: FAQS About The Use of Animals In Science, Chapter 3 p 47: University Press of America; 2009.

9. ibid Chapter 3 p 45-46

10. ibid Chapter 3 p 46

11. ibid Chapter 3 p 47

12. LaFollette H, Shanks N: Animal Experimentation: the legacy of Claude Bernard; International Studies in the Philosophy of Science, Volume 8, No 3, 1994.

13.  Dr Jim Woodgett Comment in Nature March 2012 [http://www.nature.com/nature/journal/v483/n7391/full/483509a.html ]

14.  Shanks N, Greek R: FAQS About The Use of Animals In Science, Chapter 7 p 96: University Press of America; 2009.

15. Shanks N, Greek R, Greek J: Are Animal Models Predictive for Humans? Philos Ethics Humanit Med 2009, 4:2.

16. Shanks N, Greek R: FAQS About The Use of Animals In Science, Chapter 4 p 63: University Press of America; 2009

17. FDA. Innovation or Stagnation? Challenge and Opportunity on the Critical Path to New Medical Products 2004. Available from http://www.nipte.org/docs/Critical_Path.pdf

18. Sarkar, Susanta K. 2009. Molecular imaging approaches. Drug Discovery World (Fall):33-38.

19. Editorial. 2007. Same old story? Nat Rev Drug Discov 6 (2):97.

20. Paul, S. M., D. S. Mytelka, C. T. Dunwiddie, C. C. Persinger, B. H. Munos, S. R. Lindborg, and A. L. Schacht. 2010. How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nat Rev Drug Discov 9 (3):203-14.

21. Kummar, S., R. Kinders, L. Rubinstein, R. E. Parchment, A. J. Murgo, J. Collins, O. Pickeral, J. Low, S. M. Steinberg, M. Gutierrez, S. Yang, L. Helman, R. Wiltrout, J. E. Tomaszewski, and J. H. Doroshow.  2007. Compressing drug development timelines in oncology using phase '0' trials. Nature reviews. Cancer 7 (2):131-9.

22. Kola, I., and J. Landis. 2004. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3 (8):711-5.

23. Arrowsmith, John. 2011. Trial watch: Phase III and submission failures: 2008-2010. Nat Rev Drug Discov 10 (2):87-87.

24. FDA. 2010. FDA Issues Advice to Make Earliest Stages Of Clinical Drug Development More Efficient. FDA, June 18, 2009 2006 [cited March 7 2010].

25. Johnson, J. I., S. Decker, D. Zaharevitz, L. V. Rubinstein, J. M. Venditti, S. Schepartz, S. Kalyandrug, M. Christian, S. Arbuck, M. Hollingshead, and E. A. Sausville. 2001. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer 84 (10):1424-31.

26. Science; volume 278 Nov 7th p 1041.

27. Shanks N, Greek R: FAQS About The Use of Animals In Science, Chapter 1 p 13: University Press of America; 2009.

28. Ibid Chapter 6 p 75 -76.

29. Ibid Chapter 1 p 1

30. Ibid Chapter 2 p29-33.

Please ask your MP to sign EDM 66. Simply type in your postcode at this link to write to your MP today!

Alternatively you could copy and paste the template letter below.

Remember to include your address and all the References and Resources, after you have signed your letter!

TEMPLATE LETTER FOR YOUR MP

PLACE YOUR NAME AND ADDRESS HERE!

Dear______ MP

I am writing to ask you to please sign EDM 66, which calls for a rigorous and fair public scientific debate between scientists, about best practice in medical research.
Leading scientists, outside the vested interests of animal-based research, are increasingly reporting on the failure of animals as predictive models of human patients.
The Editor in Chief of The British Medical Journal (BMJ), Dr Fiona Godlee, published her Editor’s Choice in June 2014 titled How Predictive and Productive is Animal Research? [1] This article concluded by quoting from the paper it cited:

'If research conducted on animals continues to be unable to reasonably predict what can be expected in humans, the public’s continuing endorsement and funding of preclinical animal research seems misplaced'.

This BMJ article is supported by a growing number of peer reviewed experts from the wider scientific community who agree that animal experiments hold no genuine predictive value for human patients, and are actually now proven to delay the arrival of effective treatments and cures. [2-4]

Pharmaceutical companies also openly acknowledge the failure of animal models in their drug development process, and write about this often in the scientific literature, please visit this link for extensive and referenced quotes. Indeed, the National Cancer Institute has said we have lost cures for cancer because studies in rodents have been believed. [5]
And now, decades of empirical evidence have been placed within current understanding of evolutionary biology and complexity science, to explain why such animal models are failing the search for human treatments and cures; for more information please visit Trans-Species Modeling Theory.

Chronic diseases are rising rapidly

According to an Alzheimer's Society report, the annual economic cost of increasing dementia cases reached £26 billion in 2015. An independent study into multiple sclerosis states that the cost to UK economy of this illness in £1.4 billion. Cancer cases  in the UK alone are predicted to rise from 2.5 million in 2015 to 4 million by 2030 - the cost to the UK economy of cancer alone currently tops £15 billion a year.

Only last summer, a Guardian article was published by award winning oncologist Dr Azra Raza, director of the MDS Centre at Columbia University, who stated this in her TEDx Talk:

“...our system for developing drugs for cancer is essentially broke. We CAN and SHOULD do better. I am here on this stage today really because of a mouse. Earlier this year I pointed out that one of the reasons we are not developing novel therapies for cancers fast enough is that we have been relying way too much on animal models. The fact of the matter is that we cured acute myeloid leukaemia in mice back in 1977, and in humans to day we are using the same drugs with absolutely dreadful results. We have to stop studying mice because it's essentially pointless and we have to start studying freshly obtained human cells".

Penicillin

Surely the most significant medicine of the last century - penicillin - is cited in EDM 66. Discovered by Alexander Fleming, penicillin was delayed for human patients by over a decade because it has no effect on rabbits. Here is Alexander Fleming on animal testing:

‘How fortunate we didn’t have these animal tests in the 1940s, for penicillin would probably never have been granted a license and the whole field of antibiotics might never have been realised.’ [6]

The purification of penicillin, by Howard Florey and Ernst Chain, helped it become the miracle cure which has saved millions of human lives. Here is Howard Florey on the toxicity tests he used:

‘Mice were used in the initial toxicity tests because of their small size, but what a lucky chance it was for in this respect man is like the mouse and not the guinea pig. If we had used guinea pigs exclusively we should have said that penicillin was toxic and we probably should not have proceeded to try and overcome the difficulties of producing the substance for trial in man.’ (Emphasis added) [7]

For a summary history of the discovery and development of penicillin please visit this link.

Dr. Jane Goodall highlights the historical record

Dr. Jane Goodall has released a filmed statement calling for the scientific debate outlined by EDM 66. In her filmed statement, Dr. Goodall highlights a precedent medical ruling in 2002, which stopped Cambridge University building a new non-human primate laboratory. The expert medical Board, which provides the EDM's evidence, secured a ruling  against this laboratory on 'national interest medical and scientific' grounds. Cambridge wanted to build their primate lab on Green Belt land, and therefore had to prove that their experiments were going to be in the 'national interest'. After a two week hearing, the Government inspector refused permission for the laboratory to be built, stating ‘On the basis of the technical input, therefore, I could not conclude that need in the national interest is demonstrated insofar as this pertains to the scientific/medical research and procedures undertaken by the University’. Please visit this link to read more about this landmark decision.

SCIENCE, not ethics or the 3Rs

It should be noted that the EDM must not be confused with ethical debates about animal welfare, including the National Centre for 3Rs (Reduction, Refinement, Replacement) which states: 'The 3Rs are a widely accepted ethical framework for conducting scientific experiments using animals humanely'. Although animal welfare is unquestionably of equal significance and value, ethics about animals cannot enter the EDM's called for debate about medical facts, which, as such, can only ever be about objectively verifiable scientific evidence.
Debate is the cornerstone of our democracy

In his capacity as Patron of the All Parliamentary Group on Animal Welfare (APGAW) acclaimed actor Peter Egan is calling upon MPs to sign EDM 66, highlighting the fact that the conditions for this debate have been endorsed as ‘'well set out and fair” by Britain’s foremost human rights defence barristers, Michael Mansfield QC.

All of us are affected in some way by loved ones who need the absolute best standards medical research has to offer in 2017.

Please support cross-party members who are signing Parliamentary EDM 66, and help its call for fair, rigoruos public scientific debate about this crucial medical issue of such significance, for so many.

Yours sincerely,

 

References

1.BMJ 2014; 348: g 3719  (available here)

2. Shanks N, Greek R Animal Models in Light of Evolution Boca Raton: Brown Walker Press; 2009.

3. Shanks N, Greek R, Greek J: 'Are Animal Models Predictive for Humans?' Philos Ethics Humanit Med 2009, 4:2

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. Gura T: 'Cancer Models: Systems for identifying new drugs are often faulty'. Science. 1997, 278 (5340): 1041-1042. 10.1126/science.278.5340.1041.

6. Parke DV: 'Clinical Pharmacokinetics in Drug Safety Evaluation', ATLA 1994, 22:207-209.

7. Florey H: 'The advance of chemotherapy by animal experiment', Conquest 1953, 41:12.

Resources


Patients Campaigning For Cures

The Science-Based Campaign For Life On Earth

Open Letter by Ray Greek MD: Concerning the Scientific Underpinnings of a Laboratory Beagle Breeding Unit


For Dr. Jane Goodall's filmed statement, calling for a rigorous scientific debate, please visit this link.

For EFMA's medical defeat of the primate laboratory at Cambridge University; please visit this link.

Americans and Europeans For Medical Advancement (AFMA/EFMA)

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Introducing FLOE's Patient, Families and Friends Group. 

FLOE's Introductory Video

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FLOE needs donations to campaign effectively. Please donate to help us reach out from Parliament at the start of this international campaign.

Thank you.

Photo: courtesy of the Toxic Waste Report: Macaque monkey undergoing experiment to 'predict' toxicity in a new human medicine. Around 95% of all experiments on macaques are for this.

Says Dr Charlotte Uhlenbroek, pictured above with an oragnutan in Borneo: "Please help For Life On Earth raise the necessary finance to promote modern science that protects all life on earth by ensuring the principles of evolutionary biology underpin bio-medical research"

Please donate here. Thank you