With the Pro-Test Italia rally only 2 weeks away, there is a growing movement against the widespread misrepresentation of science in Italy. To counter this, two members of Pro-Test Italia – Giulia and Federico – have set up “Italy United against Scientific Disinformation“. They will hold a set of public talks around Italy on June 8th 2013, one week after Pro-Test Italia hold a rally in defence of medical research using animals. Click on the image below to share it on Facebook.
The new organisation intends to debunk scientific misinformation wherever it exists. This includes issues surrounding vaccinations (and the myth that it causes Autism), stem cell research and of course the use of animals in biomedical research.
The group provided Speaking of Research with the following message:
“Italy United against Scientific Disinformation” is a mega-project. A very ambitious grass-roots initiative, it is the brain child of two young members of Pro-Test Italia , who worked together to reach out to the community, and found that there are many good people who share their ideals and were willing to join them.
Starting with a budget of zero, and in record time, the project already involves events in several Italian cities and volunteers from all over Italy, with more joining every day.
At the heart of this movement are young science enthusiasts, who are fed up with the way that the Italian public are being manipulated.
Are you fed up with how science is condemned by ordinary people, who prefer to be carried away by phantasmagorical conspiracy theories, despite all the contrary evidence?
If the problem was limited to merely erroneous beliefs it would be tolerable, but in Italy legislative measures are often taken based on mistaken beliefs, so research also suffers many limitations (funding cuts, incorrect regulations and so on). As a result of this we witness daily the phenomenon of brain drain, which afflicts our country severely.
Science is our future. Everything starts with the correct scientific information, but in Italy this is sadly absent from public discourse.
Young people have thus decided to involve their universities and their teachers, to involve associations, to call on the experts, who together will expose the most common misconceptions in this country!
On June 8 we will all unite against misinformation, unite for science, and above all unite for the future of our country.
Giulia and Federico
So stand up and be counted in support of science. Such events will no doubt play an important part in the developing public dialogue about how Italian politics and media interact with important scientific issues.
Speaking of Research
42 thoughts on “Challenging Scientific Dishonesty Across Italy”
”Success in federally funded drug discovery initiatives has had a checkered history. As one example, while the 1971 National Cancer Act gave the National Cancer Institute a charter to cure cancer, the incidence of this disease in the United States remains the highest in the world, with a death rate that has remained unchanged for over 50 years (193.9 per 100,000 in 1950 vs. 193.4 per 100,000 in 2002). This lack of progress is both surprising and disappointing given the billions of dollars spent over the past 40 years on improving treatment options, reducing cancer-related behaviors, such as smoking, and increasing efforts in early detection (Aggarwal, Danda, Shan Gupta, & Gehlot, 2009). Many are now coming to the realization that, as in other therapeutic areas, the greatest limitation for identifying new drugs for treating cancer are the deficiencies in the animal models used for testing NCEs [new chemical entities, also referred to as new molecular entities or NMEs] (Aggarwal et al., 2009) . . .
A major hurdle in the translational medicine undertaking is the fact that most preclinical animal models of disease generally lack predictive value with respect to the human condition under study. Indeed, the false positives that result from the present generation of animal assays are a major cause of NCE attrition in the clinic either because of lack of efficacy or the appearance of unacceptable side effects that were not detected preclinically [in animals]. While there are notable, albeit retrospective, exceptions (Zambrowicz & Sands, 2003), this weakness in the conventional drug discovery process has not been resolved with the use of transgenic animals which themselves contribute additional confounds that further complicate data interpretation.”
[Enna, SJ, M Williams (2009) Defining the role of pharmacology in the emerging world of translational research. Advances in pharmacology 57:1-30. 10.1016/S1054-3589(08)57001-3. http://www.ncbi.nlm.nih.gov/pubmed/20230758.%5D
Was going to stop…but I couldn’t help noticing ALFVperVendetta had posted a bunch of anti-vaccine propaganda…I think it’s called jumping the shark! He/She even brought in the VAERS database, well known as one of the least reliable sources of data on adverse events in existence…a resource that’s to be handled with care if ever there was one. Science blogger Orac has written many posts that discuss the problems with VAERS database and how it is misused, here are just 2 examples.
”The ability of recombinant DNA to provide nearly unlimited access to human proteins resulted in a second approach that is also common today—target-based drug discovery. Here, therapeutic targets are selected using insights gained most often from biochemistry, cell biology and model organisms. Small molecules are identified that modulate the targets (often by small-molecule screening) followed by optimization and clinical testing. Although this is a robust process, the common failure of candidate drugs in late-stage clinical testing, owing to unforeseen toxicity or lack of efficacy, reveals limits in our ability to select targets using surrogates of human physiology, such as in vitro assays and animal models.”
[Schreiber, SL, AF Shamji, PA Clemons et al. (2010) Towards patient-based cancer therapeutics. Nat Biotech 28:904-906. http://dx.doi.org/10.1038/nbt0910-904%5D
”Furthermore, the compound attrition rate is negatively affected by the inability to predict toxicity and efficacy in humans. These shortcomings are in turn caused by the use of experimental pre-clinical model systems that have a limited human clinical relevance . . . Animal models are today important tools to detect adverse effects of compounds but are costly and their clinical relevance is widely debated. In fact, animal models are about 50% effective in predicting human toxicity to the liver, heart and during development.”
[Björquist, P, P Sartipy, R Strehl et al. (2007) Human ES cell derived functional cells as tools in drug discovery. Drug Discovery World:17-24]
….50%!!! What a wonderful predictivity of response…..doesn’t it?
“Thus the lifetime feeding study in mice and rats appears to have less than a 50% probability of finding known human carcinogens. On the basis of probability theory, we would have been better off to toss a coin…”
[Salsburg D. The lifetime feeding study in mice and rats–an examination of its validity as a bioassay for human carcinogens. Fundam Appl Toxicol. 1983 Jan-Feb;3(1):63-7]
”the predictions from animals fail when a compound is tested in humans”
[Dr Don Ingber, director of Harvard University’s Wyss Institute of Biologically Inspired Engineering, Building an Organ on a Chip, MIT Technology Review, July/August 2012 – http://www.technologyreview.com/demo/427992/building-an-organ-on-a-chip%5D
”An over-reliance on animal models at an early stage is now thought to be the biggest cause of failure at phases 2 and 3 [clinical trials]. Using animal models is not producing efficacious human medicines.
Human tissue research presents the most exciting and advanced approaches that medical science currently has to offer… It is time for the use of human tissue to become the gold standard for the pharmaceutical industry.”
[World Pharma 2011 vol 1 p132: http://tinyurl.com/65vds25 – http://www.tissue-solutions.com]
Have a nice evening Blue Sky science… ^_^
Toxicology isn’t really my field, and I have to say that when I do read toxicology reports I have the eerie sensation of being transported back to the 1980’s. Tt’s a field that really doesn’t seem to kept up with developments in the rest of biomedical research. This is important to understand because animal rights activists like to confuse “Animal testing” with “Animal research” when the sort of preclinical safety testing they refer to is very different to the studies that make up the majority of animal research https://speakingofresearch.com/2013/01/17/animal-research-is-not-animal-testing/
NIH Director Francis Collins clearly understands this difference, and is absolutely correct in arguing that there is an urgent need to develop better technologies for per-clinical toxicity testing – though the really big shift will not be from animals based tests to non-animal based tests but from a system that detects and measures toxicity to one that predicts toxicity based on impact of a chemical on biological functions. It will be years before the new systems are ready to replace all the current tests, but the scientific and technical knowledge has reached the stage where it’s realistic to believe it’s possible and to start developing those systems (indeed a few are already quite far along in development).
This certainly does not mean that animal research will not still be necessary, as Francis Collins knows very well as he himself was very recently (just before he became NIH director) involved in research that used GM mice to evaluate new therapies for the rare developmental disorder Progeria
And here’s another ALFVforVendetta quote that caught my attention because it refers (though you wouldn’t know it from the way the quote is presented) to a paper that highlights an increasingly important kind of animal study in cancer research. His/Her quote is:
“The development of antineoplastics is a large investment by the private and public sectors, however, the limited availability of predictive preclinical systems obscures our ability to select the therapeutics that might succeed or fail during clinical investigation. [Cook N, Jodrell DI, Tuveson DA. Predictive in vivo animal models and translation to clinical trials. Drug Discovery Today. 2012;17(5/6):253-60]”
All you have to do it look at the abstract in PubMed to see how out ALF friend might be stretching things a bit http://www.ncbi.nlm.nih.gov/pubmed/22493784
It is worth quoting the concluding remarks of this paper in their entirety, which follow a discussion of the different animal models of cancer now available, both the older models (such as the NCI 60 xenografts) and the newer ones that are a closer model of real cancer.
Selecting the most appropriate in vivo model is essential during the drug development process to enable accurate modelling of therapeutic efficacy. By developing innovative preclinical trials using sophisticated animal models that recapitulate the human malignancies in question, we might be able to advance the field of drug discovery, and improve success rates for potential novel therapeutics in clinical trials. Figure 1 illustrates the approach we have taken in the KPC mouse model of pancreatic cancer .
Hurdles remain, however, and no model is going to be able to perfectly recapitulate the human situation. Historically, the majority of Phase 1 trials have admitted patients who were heavily pretreated with multiple different chemotherapeutics and targeted agents. Unfortunately this situation would be difficult to reproduce in the mouse, due to feasibility, time and money, and individualised patient responses to prior treatment. Some laboratories do manage to study therapeutic resistance, but this is only possible in models where initial sensitivity to an agent is dramatic enough to enable the development of acquired resistance .
Early stage clinical trials are now being designed with more emphasis on the biological effects of therapeutics, incorporating validated biomarkers as endpoints, and utilising an adaptive approach for analysing information in real time . Window studies and Phase 0 trials are becoming increasingly popular, encouraging further insight into novel therapeutic mechanisms of action at an early stage of development .
Pharmaceutical companies have been reluctant to delay any Phase 1/2 trials while awaiting outcome of preclinical trials, potentially taking many years to complete. With recent encouraging Phase 3 results, correlating with earlier GEMM preclinical studies 48 and 49, the pharmaceutical industry might now decide that it is appropriate to invest additional resources into better designed preclinical trials with predictive animal models. For this to happen close collaborations are required between industry and academia, enabling animal and drug transfers between organisations, and divulging of expert knowledge each possesses. This would ultimately lead to a swifter, hopefully successful, translation to the clinic which, in the long term, would actually be cost-effective compared with the failure of a therapeutic late in its development.”
So what this paper is about – as are most of the papers concerning animal models of cancer that ALFVperVandetta refers to above is – is the development and more widespread use of better experimental models of cancer, including newer animal models. This move towards more rigorous animal models of cancer has been underway for some time, and ties in very well with the availability of a wealth of data from the various “omics” studies, as a post on the Speaking of Research blog a couple of years ago highlighted https://speakingofresearch.com/2011/03/25/mice-help-scientists-to-understand-the-cancer-genome/
“If you look at the millions and millions and millions of mice that have been cured, and you compare that to the relative success, or lack thereof, that we’ve achieved in the treatment of metastatic disease clinically, you realize that there just has to be something wrong with those models.”
[Dr. Homer Pearce, who once ran cancer research and clinical investigation at Eli Lilly and is now research fellow at the drug company, agrees that mouse models are “woefully inadequate”]
”Mouse models that use transplants of human cancer have not had a great track record of predicting human responses to treatment in the clinic. It’s been estimated that cancer drugs that enter clinical testing have a 95 percent rate of failing to make it to market, in comparison to the 89 percent failure rate for all therapies . . . Indeed, “we had loads of models that were not predictive, that were [in fact] seriously misleading,” says NCI’s Marks, also head of the Mouse Models of Human Cancers Consortium.”
[Building a Better Mouse, The Scientist, April 1, 2010, http://www.the-scientist.com/?articles.view%2FarticleNo%2F28860%2Ftitle%2FBuilding-a-Better-Mouse%2FflagPost%2F48454%2F%5D
”Change is needed. Thirty years of experience with subcutaneous xenografts, human tumors implanted under the skin of the mouse, have satisfied few because so many drugs that cure cancer in these mice fail to help humans. A 2004 analysis in the Journal of the American Medical Association showed that only 3.8% of patients in phase I cancer drug trials between 1991 and 2002 achieved an objective clinical response — and the response rate is declining. Almost all drugs tried in humans work against subcutaneous xenografts in mice. “How many more negative data do you want? It’s very depressing.”
[Realistic Rodents? Debate Grows Over New Mouse Models of Cancer, Journal of the National Cancer Institute, Vol. 98, No. 17, September 6 – http://jnci.oxfordjournals.org/content/98/17/1176.full.pdf%5D
Wow AlfVperVendetta, I see you are good at the old half truth and misrepresentation game.
I don’t have time so address you entire Gish gallop, but one sentence that you misquoted sums it up, when you write:
” “The fundamental problem in drug discovery for cancer is that the [animal] model systems are not predictive at all.” [Gura T. Cancer Models: Systems for identifying new drugs are often faulty. Science. 1997 Nov 7;278(5340):1041-2]”
Your insertion of the word “animal” is what gives you away, because if you actually read the article by Gura et al. what they are actually pinpointing is a problem with the tumour cell lines used to screen potential anti-cancer drugs, and specifically the NCI 60 library of cells that were developed for use in screening – in both in vitro tests and in mouse xenograft studies. In many cases these cell types are not good models of “real” cancer cells. In particular Trisha Gura actually points to a study of type of in vitro assay called a clonogenic assay, and how comparison with studies in mice revealed it’s weaknesses.
“Both drug screeners and doctors also use another cell culture method, the so-called clonogenic assay, to sift through potential anticancer drugs. They grow cell lines or a patient’s tumor cells in petri dishes or culture flasks and monitor the cells’ responses to various anticancer treatments. But clonogenic assays have their problems, too. Sometimes they don’t work because the cells simply fail to divide in culture. And the results cannot tell a researcher how anticancer drugs will act in the body.
What’s more, new results from Bert Vogelstein’s group at Johns Hopkins University School of Medicine add another question mark about the assay’s predictive ability. Todd Waldman, a postdoc in the Vogelstein laboratory, found that xenografts and clonogenic assays deliver very different messages about how cancer cells lacking a particular gene, p21, respond to DNA-crippling agents. Radiation, like many of the drugs used to treat cancer, works by damaging the cells’ DNA. This either brings cell replication to a halt or triggers a process known as apoptosis in which the cells essentially commit suicide. Waldman wanted to see how p21, one of the genes involved in sensing the DNA damage and halting cell replication, influences that response to radiation.
In the mouse xenograft assay, Waldman and his colleagues found that the radiation cured 40% of the tumors composed of cells lacking p21, while tumors made of cells carrying the gene were never cured. But this difference was not apparent in the clonogenic assay, where the radiation appeared to thwart the growth of both dispersed tumor cell types. “We showed this gross difference in sensitivity in real tumors in mice and in the clonogenic assay,” Waldman says.
He suggests that the different responses in the two systems have to do with the fact that a subset of p21 mutants die in response to radiation, while cells with the normal gene merely arrest cell division. Either way, the dispersed tumor cells in the clonogenic assay will fail to grow. However, in the xenograft tumors, which consist of many cells in a solid mass, the arrested, but nonetheless living, p21+ tumor cells may release substances that encourage the growth of any nearby tumor cells that escaped the effects of the radiation. But tumor cells lacking the p21 gene die, and because dead cells cannot “feed” neighboring tumor cells, the entire tumor may shrink.”
Hi Blue Sky Science. I’m sorry for my ”half truth and misrepresentation game”, but I carry just what is reported by experts on the topic debated.
For example about cancer disease and poor contribution of animal models how do you can argue that animal models can be a valuable contribution to human responses when we know toady that cancer drugs have a success rate of only 5%?
”Indeed, because oncology drugs have a success rate of only 5%, it is clear that animal models are only marginally effective.”
[M.B. Esch, T.L. King and M.L. Shuler, The Role of Body-on-a-Chip Devices in Drug and Toxicity Studies, Annu. Rev. Biomed. Eng. 2011. 13:55–72 (doi:10.1146/annurev-bioeng-071910-124629)2010]
Also prof. Weinberg has been clear on this topic:
“One of the most frequently used experimental models of human cancer is to take human cancer cells that are grown in a petri dish, put them in a mouse–in an immunocompromised mouse–allow them to form a tumor, and then expose the resulting xenograft to different kinds of drugs that might be useful in treating people. These are called preclinical models, and it’s been well known for more than a decade, maybe two decades, that many of these preclinical human cancer models have very little predictive power in terms of how actual human beings. Despite the genetic and organ-system similarities between a nude mouse and a man in a hospital gown, the two species have key differences in physiology, tissue architecture, metabolic rate, immune system function, molecular signaling, you name it. So the tumors that arise in each, with the same flip of a genetic switch, are vastly different. A fundamental problem which remains to be solved in the whole cancer research effort, in terms of therapies, is that the preclinical models of human cancer, in large part, stink. Although drug companies clearly recognize the problem, they haven’t fixed it. And they’d better, if for no other reason than [that] hundreds of millions of dollars are being wasted every year by drug companies using these models.”
[Fortune, March 22, 2004, Why We’re Losing The War On Cancer – And how to win it -http://money.cnn.com/magazines/fortune/fortune_archive/2004/03/22/365076/index.htm]
Go home Alfredo, you’re drunk. History will simply crush liars.
Andrea, i’m fine…don’t worry for me boy, thank you. ^_^
Dear mister holder, you really speaks of ”misinformation” referring to the antivivisectionist scientific culture? Ah Ah Ah….good humor Tom. :D
So, Thomas Hartung, Claude Reiss, Kathy Archibald, Costanza Rovida and many of their colleagues are not scientists, they are against scientific progress….right?
History will tell who will be right.
Greetings from Italy mister Holder.
Well no… developing alternatives is part of what scientists do. But yes.. arguing that we animals cannot possibly contribute to human health despite evidence to the contrary, and/or misleading the public to think we can do away with animal research without any serious implications for our ability to develop new therapies and cures is unscientific.
Dario, as a title of BMJ article, but where is the evidence thata animal research benefists humans? (Pound et al 2004, BMJ). Today we know that 9 on 10 drugs designed and tested succesfully on animals in pre clinical phase fail in next step in the clinical phase on humans because they are toxic or lack of effectiveness for human health. [Lester Crawford, FDA* Commissioner, Innovation or Stagnation, Challenge and Opportunity on the Critical Path to New Medical Products, 2004 – http://www.who.int/intellectualproperty/documents/en/FDAproposals.pdf%5D. Animal models do not provide sufficient predictability in human responses [Peter J.K. van Meera, Marlous Kooijmanb, Christine C. Gispen-de Wiedc, Ellen H.M. Moorsb, Huub Schellekensa, The ability of animal studies to detect serious post marketing adverse events is limited, Regulatory Toxicology and Pharmacology Volume 64, Issue 3, December 2012, Pages 345–349 – http://www.sciencedirect.com/science/article/pii/S027323001200181X%5D, [Greek R, Menache A, Systematic Reviews of Animal Models: Methodology versus Epistemology, Int J Med Sci 2013; 10(3):206-221. doi:10.7150/ijms.5529 – http://www.medsci.org/v10p0206.htm%5D, [Perel et al 2007, Comparison of treatment effects between animal experiments and clinical trials: systematic review, BMJ 2007; 334 doi: http://dx.doi.org/10.1136/bmj.39048.407928.BE – http://www.bmj.com/content/334/7586/197%5D, [Hackam & Redelmeier, Translation of research evidence from animals to humans, JAMA 2006; 296(14): 1731-2 – http://www.animalexperiments.info/resources/Studies/Human-healthcare/Highly-cited-studies.-Hackam-et-al-2006./Translation-Hackam-et-al-2006-JAMA.pdf%5D, [Dr. Francis Collins, Director of the National Institutes of Health (NIH), U.S. to develop chip that tests if a drug is toxic. Reuters, October 6, 2011 – http://www.reuters.com/article/2011/09/16/us-drugs-chip-idUSTRE78F5KX20110916%5D…this is scientific evidence.
Where is the evidence?! Just look around… open your eyes… it is everywhere!
Are you vaccinated? Are your children? Or your pets?
The fact that modeling disease is animals is a difficult scientific problem does not mean it is impossible. Success is not easy to come by, but when we do achieve success the benefits are enormous and far reaching.
If you are truly concerned about the welfare of animals why don’t you start a crusade against prosciutto instead of interfering with live-saving medical research?
Dario i have my eyes really open, and you?
Vaccines did you say? ”Use of murine models to study the immunobiology of infectious diseases, such as malaria and herpes simplex virus, has severely skewed our understanding of immune control of these pathogens in humans, and it could be argued that over reliance on these model systems may have slowed progress in the development of effective vaccines against many human pathogens. Confidence in these model systems has eroded, as we now know that there are significant differences in human physiology and the immune regulatory pathways from these animal models. Indeed, clinical testing of the anti-CD28 monoclonal antibody TGN1412 illustrates this very well… In spite of these significant limitations, we continue to invest huge resources in conducting immunology studies using transgenic murine models, and many of our colleagues often feel highly defensive when questioned on the validity of their model systems… we hope our colleagues will join us in lobbying respective Governments and their funding agencies to invest in human immunology research, which will have important implications for human health… how long can we justify investing
millions of dollars of taxpayers’ funds on delineating the murine immune system, which in most cases has limited application for human diseases.”
[Dr Rajiv Khanna and Dr Scott R Burrows, Australian Centre for Vaccine Development, Queensland Institute of Medical Research, Human immunology: a case for the ascent of non-furry immunology, Nature-Immunology and Cell Biology (2011) 89, 330–331; doi:10.1038/icb.2010.173 – http://www.nature.com/icb/journal/v89/n3/full/icb2010173a.html%5D
Are your children vaccinated? Are you?
This is very interesting, have a good grief to you dario. [Stephanie Seneff, Robert M. Davidson, Jingjing Liu, Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure – http://groups.csail.mit.edu/sls/publications/2012/entropy-14-02227.pdf%5D
Multiple studies, from various countries, have found no link between autism and vaccinations… but I take form your response that this means you, your family and pets are all vaccinated, correct?
”Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines.” ……Those from M.I.T. …what a ”unscientific” .culture. :D
The study in my reply have found link between autism and vaccinations, you can ask to M.I.T. researchers if you want…and this is not the only one. 51% of new drugs in post marketing phase are harmful for people [Moore T.J., Psaty BM. e Furberg CD. Time to act on drug safety. JAMA, 279: 1571-1573, 1998], 106.000 people die every year in U.S.A. for ADRs [Starfield B, Is US Health Really the Best in the World?, JAMA. 2000 Jul 26;284(4):483-5. – http://silver.neep.wisc.edu/~lakes/iatrogenic.pdf%5D, and 197.000 in U.E. [European Commission, Brussels, 10 december 2008, Strengthening pharmacovigilance to reduce adverse effects of medicines – http://ec.europa.eu/health/files/pharmacos/pharmpack_12_2008/memo_pharmacovigiliance_december_2008_en.pdf%5D….it’s correct dario? ”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.” [Mike Leavitt, Secretary of Health and Human Services, FDA, FDA press release 12 January 2006], ”Half of drugs that work in animals may turn out to be toxic for people. And some drugs may in fact work in people even if they fail in animals, meaning potentially important medicines could be rejected.”
[Dr. Francis Collins, Director of the National Institutes of Health (NIH), U.S. to develop chip that tests if a drug is toxic. Reuters, October 6, 2011 – http://www.reuters.com/article/2011/09/16/us-drugs-chip-idUSTRE78F5KX20110916%5D….correct?
A bunch of half-truths and out-of-context statements, as always the case with animal rights activists. It is doubtful you read, let alone understood, the articles you cite. You are too fixated in your personal Vendetta… Again, it is surprising that you fight the development of medicines more than the development of prosciutto.
I know those articles very well, maybe you don’t want to accept the evidence inside them…..as usual with an animal research supporter.
It’s a simple question of intellectual honesty dear dario…..remember it.
”it is surprising that you fight the development of medicines more than the development of prosciutto”….great intellectual opinions, congratulations. :D
However, thanks for this debate on the issue debated. Have a good day.
ALFvforvendetta – you’re pumping out half truths that SR has already debunked. For instance your argument about 92% of drugs failing can be fully explained here:
Claude Reiss has been thoroughly discredited by the scientific community: during his time at the academic journal Biogenic Amines, he allowed articles by his friend Jarrod Bailey from anti-vivisection campaigning group Europeans for Medical ‘Progress’ to get published in the journal without peer review (http://www.thescientist.com/news/display/23184/). Peer review is a process where scientists read each other’s work prior to publication to make sure facts and methods have been checked and are scientifically sound. Abandoning it allows people to publish lies or misleading information that are legitimised by the reputation of the journal. The editor of Biogenic Amines said of Claude Reiss: “After his 2 years stay in the editorial board, he did lots of harm to the journal and we all forced him to resign.
Nonetheless, there are a very small minority of scientists who are against animal research. Such scientists have spread much misinformation about the use of animals in research.
Tom, Claude Reiss was a Director of Research for 35 years of CNRS of Paris, he’s a scientist with a many scientific papers in peer review….so…why this prejudices? Just for his opinions against animal research? It’s very superficial….
On the scientist article we read:”British supporters of animal research have called on the journal Biogenic Amines to retract a pair of articles they claim were motivated by antivivisection philosophy, not science.”…”british supporters of animal research” are all ”scientific community”? :D ….and again in this article about peer review of Dr. Jarrod Bailey:”In an Email response, Parvez told Festing that the journal aims to publish a variety of papers after peer review, and that the philosophy of the author did not enter into the equation.”…..i hope that this is clear about this article on the scientist. :)
No Tom, nothing of personal….the reality is very different of your personal point of view…and many people today knows this, don’t worry. Have a good day Mister Holder.
”“If there was an animal model good enough to substitute for people, we would not have a 92% failure rate in clinical trials,”
[Prof. Thomas Hartung, US NAS panel member and director of the Center for Alternatives to Animal Testingnature, CAAT of Johns Hopkins Bloomberg School of Public Health in Baltimore, U.S.A., Nature call him ”leading scientist”, in an article of Elie Dolgin, Animal rule for drug approval creates a jungle of confusion, Nature Medicine 19, 118–119 (2013) doi:10.1038/nm0213-118
Published online 06 February 2013 – http://www.nature.com/nm/journal/v19/n2/full/nm0213-118.html%5D
A clearly ridiculous claim given that there is an 86% failure rate of human trials – does this mean that humans are a bad model?
Go back and actually read that essay – it shows that people like Hartung are employing nothing but spin in their use of the 92% statistic
Tom, the best model for humans is human…
”Traditionally, the choice of which candidate compounds to take forward into development has been based on pre-clinical data. However, lack of predictivity of the human clinical situation in the models used has led to poor decision-making, and the later in the development process that such mistakes are realised, the more costly and time-consuming it is to correct them. Furthermore, compounds that may have made perfectly good drugs, have been dropped due to poor pharmacokinetics in animal models. Accelerator mass spectrometry (AMS) is an ultra-sensitive detection technique that can be used to quantify carbon-14. By administering very small amounts of (14)C-labelled compounds, AMS can be used to obtain human clinical data very early in the drug development process. Such studies: a) can be helpful in understanding human pharmacokinetics using microdosing; b) can provide early human metabolism information, to validate the choice of animal species used in pre-clinical safety testing and identify unique or disproportionate human metabolites during Phase 1; and c) can provide fundamental human pharmacokinetic data, including absolute bioavailability, by facilitating a scientifically optimal and cost-effective study design. The provision of these clinical insights at the earliest possible opportunity can lead to improved decision-making, and therefore can reduce the time and cost involved in the drug development process.”
[Seymour M, The best model for humans is human — how to accelerate early drug development safely, Altern Lab Anim. 2009 Sep;37 Suppl 1:61-5 – http://www.ncbi.nlm.nih.gov/pubmed/19807205%5D
Hartung is a honest scientist and i think that he don’t uses the statistics for his personal interests….maybe someone else make this dear Tom.
ALF – you’re not saying anything groundbreaking. Microdosing is very widely used. Many research institutions get human microdosing involved at the same time as some animal preclinical studies because it has useful information. HOWEVER, microdosing is still very limited, it tells you nothing of the efficacy, or side effects of a drug. Drugs also behave very differently at minute doses as they do at very high doses. So the information is useful but incomplete. Animals are part of the process of completing that information.
You have also failed to engage with the misleading use of the 92% stat – especially given the point that 84% of drugs passing early human trials fail later on.
Animal models are not useful in the process of development of new drugs and as reported by the researchers and by men of the competent institutions are rather the cause of failure in experimental trials.
When evaluating the predictive value of methods, practices, or tests for use in biomedical science, positive predictive value (PPV) and negative predictive value (NPV) > 0.90 are sought.
Salsburg stated: “Thus the lifetime feeding study in mice and rats appears to have less than a 50% probability of finding known human carcinogens. On the basis of probability theory, we would have been better off to toss a coin…” [Salsburg D. The lifetime feeding study in mice and rats–an examination of its validity as a bioassay for human carcinogens. Fundam Appl Toxicol. 1983 Jan-Feb;3(1):63-7]
The general attitude in the drug development-related sciences reflects the empirical evidence. Cook et al:
Over many years now there has been a poor correlation between preclinical therapeutic findings and the eventual efficacy of these [anti-cancer] compounds in clinical trial [ohnson JI, Decker S, Zaharevitz D, Rubinstein LV, Venditti JM, Schepartz S, et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer. 2001 May 18;84(10):1424-31] – [Suggitt M, Bibby MC. 50 years of preclinical anticancer drug screening: empirical to target-driven approaches. Clinical cancer research : an official journal of the American Association for Cancer Research], The development of antineoplastics is a large investment by the private and public sectors, however, the limited availability of predictive preclinical systems obscures our ability to select the therapeutics that might succeed or fail during clinical investigation. [Cook N, Jodrell DI, Tuveson DA. Predictive in vivo animal models and translation to clinical trials. Drug Discovery Today. 2012;17(5/6):253-60]
Reuters quoted Francis Collins, Director of the US NIH, as stating that: “about half of drugs that work in animals may turn out to be toxic for people. And some drugs may in fact work in people even if they fail in animals, meaning potentially important medicines could be rejected.” [http://www.reuters.com/article/2011/09/16/us-drugs-chip-idUSTRE78F5KX20110916%5D], Alan Oliff, former executive director for cancer research at Merck Research Laboratories in West Point, Pennsylvania asserted in 1997: “The fundamental problem in drug discovery for cancer is that the [animal] model systems are not predictive at all.” [Gura T. Cancer Models: Systems for identifying new drugs are often faulty. Science. 1997 Nov 7;278(5340):1041-2]
In 2006, then U.S. Secretary of Health and Human Services Mike Leavitt declared: “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.” [FDA Issues Advice to Make Earliest Stages Of Clinical Drug Development More Efficient. FDA; 2006], Zielinska, writing in The Scientist supported the above, stating:
”Mouse models that use transplants of human cancer have not had a great track record of predicting human responses to treatment in the clinic. It’s been estimated that cancer drugs that enter clinical testing have a 95 percent rate of failing to make it to market, in comparison to the 89 percent failure rate for all therapies… Indeed, “we had loads of models that were not predictive, that were [in fact] seriously misleading,” says NCI’s Marks, also head of the Mouse Models of Human Cancers Consortium…” [Zielinska E. Building a better mouse. The Scientist. 2010 April 1;24(4):34-8]
”For example, a new medicinal compound entering Phase 1 testing, often representing the culmination of upwards of a decade of preclinical screening and evaluation, is estimated to have only an 8 percent chance of reaching the market.[…] The main causes of failure in the clinic include safety problems and lack of effectiveness: inability to predict these failures before human testing or early in clinical trials dramatically escalates costs.” [Lester Crawford, FDA* Commissioner, Innovation or Stagnation, Challenge and Opportunity on the Critical Path to New Medical Products, 2004 – http://www.who.int/intellectualproperty/documents/en/FDAproposals.pdf%5D
” In recent years, there has been an explosion of scientific discoveries made possible through technologies such as genomics, advanced imaging, nanotechnology, and robotics. These scientific advances can help produce more and better medical products—not just drugs, but biologics such as vaccines, and devices such as pacemakers.
But the efficiency for scientific discoveries being translated into medical products is very low—in fact, it’s worse than it was 10 years ago. For example, new drugs go through three phases of progressively rigorous testing, or clinical trials, to show their safety and effectiveness before FDA will consider allowing them on the market. Today, new compounds that make it through Phases 1 and 2 of clinical trials fail 50% of the time in Phase 3 compared to a 20% failure rate 10 years ago.
In FDA’s view, new science is not being used to guide the medical product development process in the same way that it is accelerating the discovery process. The path that a medical product takes from development to mass-production and availability to the public—what we call the Critical Path—has become increasingly challenging, inefficient, and costly.
Many of the scientific tools used today to predict and evaluate safety and effectiveness, as well as to manufacture products, are decades old. They are time-consuming, cumbersome, and imprecise. They may fail to predict specific safety problems that ultimately halt development.”
[Janet Woodcock, M.D., FDA’s Deputy Commissioner for Scientific and Medical Programs and Chief Medical Officer, The Critical Path: Making Medical Products Better, Faster, and Cheaper – http://www.fda.gov/forconsumers/consumerupdates/ucm061234.htm%5D
Over 1000 drugs that reached the market were discovered to result in hepatotoxicity. [Makarova SI. Human N-acetyltransferases and drug-induced hepatotoxicity. Current drug metabolism. [Review]. 2008 Jul;9(6):538-45]
“One of the most frequently used experimental models of human cancer is to take human cancer cells that are grown in a petri dish, put them in a mouse–in an immunocompromised mouse–allow them to form a tumor, and then expose the resulting xenograft to different kinds of drugs that might be useful in treating people. These are called preclinical models, and it’s been well known for more than a decade, maybe two decades, that many of these preclinical human cancer models have very little predictive power in terms of how actual human beings. Despite the genetic and organ-system similarities between a nude mouse and a man in a hospital gown, he says, the two species have key differences in physiology, tissue architecture, metabolic rate, immune system function, molecular signaling, you name it. So the tumors that arise in each, with the same flip of a genetic switch, are vastly different. A fundamental problem which remains to be solved in the whole cancer research effort, in terms of therapies, is that the preclinical models of human cancer, in large part, stink. Although drug companies clearly recognize the problem, they haven’t fixed it. And they’d better, if for no other reason than [that] hundreds of millions of dollars are being wasted every year by drug companies using these models.” [Prof. Robert Weiberg, professor of biology at MIT and winner of the National Medal of Science for his discovery of both the first human oncogene and the first tumor-suppressor gene, Fortune, March 22, 2004, Why We’re Losing The War On Cancer – And how to win it -http://money.cnn.com/magazines/fortune/fortune_archive/2004/03/22/365076/index.htm]
”The value of animal studies to assess drug safety is unclear because many such studies are biased and have methodological shortcomings. We studied whether post-marketing serious adverse reactions to small molecule drugs could have been detected on the basis of animal study data included in drug registration files. Of 93 serious adverse reactions related to 43 small molecule drugs, only 19% were identified in animal studies as a true positive outcome, which suggests that data from animal studies are of limited value to pharmacovigilance activities.”
[The ability of animal studies to detect serious post marketing adverse events is limited, Peter J.K. van Meera, Marlous Kooijmanb, Christine C. Gispen-de Wiedc, Ellen H.M. Moorsb, Huub Schellekensa, Regulatory Toxicology and Pharmacology Volume 64, Issue 3, December 2012, Pages 345–349 – http://www.sciencedirect.com/science/article/pii/S027323001200181X%5D
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