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11Critical Thinking Essays and Websites

If you want to see passion, watch a creation v evolution debate. In the Bill Nye v Ken Ham debate, the inventor of the MRI scanner was very passionate about special creation and a young earth. Watch almost any creation v evolution debate and you will see many very passionate people arguing for creation and against evolution. For even more passion, watch a pro-choice demonstration and observe the interaction between the pro-choicers and the anti-abortionists. Just as appeal to authority is a fallacy so is appeal to passion.

One thing that all sides should agree on is that humans are masters at rationalization. This was very evident in the Nye-Ham creation v evolution debate when Ken Ham was explaining a young earth that was specially created by Jehovah. Ham quoted many facts but then took the facts and distorted them to fit in to his predetermined beliefs. The audience at the debate was also skilled at rationalization. Critical thinkers can usually give many examples of fallacious reasoning such as appeal to authority and post hos ergo propter hoc that they have witnessed on any given day. The problem with critical thinking is applying it to oneself. In any given controversy, each side will say it has critical thinking on its side just as each will probably say it has science on its side. These are unsubstantiated claims and should be treated as such. The answer as to who is right lies in examining the evidence. Massimo Pigliucci addresses this:

A recurring theme of this book is that one cannot simply trust authority no matter how, well, authoritative it may appear to be. There is, unfortunately, no shortcut to using one's brain and critical sense and doing some background research before taking a position. [1] p90

Alan Sokal is Professor of Physics at New York University and Professor of Mathematics at University College London. He is also author of the 1996 article titled “Transgressing the Boundaries: Toward a Transformative Hermeneutics of Quantum Gravity,” which was published in the cultural studies journal Social Text. The article was a nonsensical parody of certain aspects of Post-Modernism and exposed much of Post-Modernisms for its lack of meaning and irrelevancy.

Sokal has published three essays on the website Scientia Salon, which was founded by Massimo Pigliucci. 

If you are interested in critical thinking and science, I strongly recommend the three essays. They contain many points relevant to my position on animal models.

Also on the same website is an article titled: “The strange phenomenon of the cult of facts: three case studies,” by Massimo Pigliucci. I quote from many of Pigliucci’s books and articles and recommend pretty much anything he writes.

A related website is Clearer Thinking. From the website:

Our brains are incredible machines. By using our reason and intuition, we can process complex situations and make excellent decisions most of the time.

But our brains don’t work perfectly. From time to time we all make reasoning errors, and we all make decisions that aren’t the best for achieving our goals. In fact, it is now known that there are certain systematic biases built into the structure of all human brains. Disturbingly, most of the time they operate without us even being aware of them. To date, psychologists, neuroscientists and economists have discovered more than 30 of these biases that regularly occur in human thinking and decision-making.

In order to discuss animal models, from an ethical or scientific perspective, one needs to understand the concepts discussed on these and related websites (see here and here and here). I assure you most of the people that you will argue against do not understand these concepts or have never studied the issue.

Photo courtesy Wikipedia Commons.

References

1.         Pigliucci, M., Nonsense on Stilts: How to Tell Science from Bunk. 2010, Chicago: University of Chicago Press. 


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11Trans-Species Modeling Theory and Dr Ringach

I try not to respond to nonsense from the vested interest groups as there is no end to it and most of it is just the same ol’ same ol’ that I have corrected many times before. I applaud bloggers who essentially deal with the same nonsense day after day seemingly never tiring of correcting the exact same nonsense. Although I disagree with some of them on the value of animal models, I nevertheless appreciate the energy they bring to whatever topic they are addressing.

That having been said, Speaking of research has been publishing a fair amount lately and as I have ignored most of it, I feel I should address the following. Most of what I say below is not new but apparently requires repeating.

Dr Dario Ringach has posted on the Speaking of research web site, an essay titled “Saving Life on Earth.” I suggest everyone read the essay before reading my response. I think reading the entire essay is important in order to appreciate the context of the comments I am going to address. I will ignore most of his comments either because I have addressed them before or because they are obviously immaterial, wrong, or a non sequitur.

Ringach begins with the myth that animal-based basic science research in the biomedical sciences is equal in value to basic research in chemistry and physics: “there is wide consensus that such fundamental knowledge is critical to enhance the health, lengthen life, and reduce the cost of illness and disability in both humans and non-human animals.” See the following for refutation of this [1-19]. The refutation revolves around two facts: 1) animals and humans are examples of complex systems and 2) animal-based basic research simply does not translate to humans empirically. Theory combined with empirical evidence is as good as it gets in science.

Ringach then employs the fallacy known as appeal to authority:

Unfortunately, at this point in time, our methods do not allow to pursue cellular and molecular-level questions non-invasively in human subjects, and this is why part of the work requires the use of animals in research. Accordingly, a recent poll by the journal Nature revealed that nearly 92% of scientists agree with the statement “animal research is essential to the advancement of biomedical science.” (Emphasis in the Ringach essay.)

How many people agree with you and what their qualifications are is immaterial to whether the claim is true. Moreover, there is a difference between a modality being necessary to advance science and the same modality being necessary in terms of finding cures. Science advances every day. Cures are not discovered every day or even every year. References 1-19 explain why this is the case.

Ringach then assumes that animals and humans are simple systems not complex systems:

Any reasonable person would agree a mechanic would be in a better position to fix a car if s/he actually knows the role each part plays, how they fit together, and what can happen if one of them fails.  Similarly, any reasonable person must agree that we would be in a better position to develop therapies and cures if we knew exactly how living organisms work in health, and what happens to our cells and other organs in disease.

The only systems humans can learn exactly how they work are simple systems. Little things like emergence and the whole being greater than the parts place constraints on ascertaining the total knowledge of complex systems. If the level of examination of a complex system can be explained in terms of a simple system, then organisms can also be so studied. But animals and humans, the systems we are interested in studying, are complex systems and the properties we wish to evaluate are located at the level of complex systems. Organisms by definition are complex systems!

Moreover, parts of a simple system , for example pistons in auto engines, are not equivalent to genes. [[20]p39]  This is another difference between complex and simple systems. The way a piston functions does not vary that much between engines but the function of genes vary considerably. [21-31]  Knowing how a mouse cell functions in health and disease is of no predictive value for human cells beyond what can be described in terms of a simple system. We passed that level of understanding decades ago. (For more on complex systems and animal models see:

·      More Misrepresentations, Fallacies, and Other Lies. Part II

·      Complexity and Animal Models

·      Brute Science

·      My article introducing Trans-Species Modeling Theory. (Indeed, Dr Ringach’s entire essay can be dismissed based on what I addressed in the article on Trans-Species Modeling Theory)

Ringach then correctly points out that Trans-Species Modeling Theory has not yet been widely read by the scientific community. Since it was published less than a year ago and contradicts major vested interest groups, this should not come as a surprise to any adult. Ringach follows up on this piece of non-information with an ad hominem stating that the writers of the Trans-Species Modeling Theory article are animal rights activists. The writers could have been aliens, nevertheless Trans-Species Modeling Theory has to stand on its scientific merits, which Ringach does not address, regardless of who wrote it. (Note how many critical thinkers will point this out—zero. Hard to keep a job in academia teaching philosophy if you correct the people bringing in the money.)

Ditto for Shanks and my book Animal Models in Light of Evolution. The book is very technical and I doubt a system based on animal modeling is going to be citing it frequently in their literature. By the way, as I have pointed out many times, I am an animal rightist philosophically but am not currently engaged in any activism, nor have I been so engaged for over a decade. Trans-Species Modeling Theory is a theory in the scientific sense of the word. How many people realize that is immaterial to its ultimate value. I justify why Trans-Species Modeling Theory is a theory in the article. Widespread acceptance is not a criterion.

Those are the main points from my perspective but Ringach goes on and I again suggest you read the entire essay. He also links to an essay by Dr Gorski titled Animal rights activism: Petitions aren’t science. I addressed Dr Gorski’s comments in  Science-Based Medicine Is Having A Little Trouble With Critical Thinking (And Due Diligence).

The petition that For Life On Earth (FLOE) is circulating revolves around a debate between a recognized, well-qualified, spokesperson from the vivisection community and myself. My rules for such a debate can be found here, in the same essay as my response to Dr Gorski. As vivisection activists will not debate me in the scientific literature, a debate with rules such as outlined in that essay are probably as close as society will ever come to seeing the positions of both sides presented and then evaluated by experts. Debates are important because, as Dr Steven Novella wrote: “During a live debate we can see how the candidates think and what they know and believe about scientific issues. They can also be pushed on specific points if they give evasive answers.”

Vivisection activists thrive in a world of limited information and fallacious reasoning. Don’t hold your breath waiting for them to participate in an event where they will be forced to plainly state, supported by references, their position and then have experts in the disputed areas of science judge those positions.

(Image courtesy of Wikipedia Commons http://en.wikipedia.org/wiki/File:Jack_McCall.jpg)

References

1.         Alini, M., et al., Are animal models useful for studying human disc disorders/degeneration? Eur Spine J, 2008. 17(1): p. 2-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17632738

2.         Begley, S., Physician-Researchers Needed To Get Cures Out of Rat's Cage. Wall Street Journal, 2003.

3.         Crowley, W.F., Jr., Translation of basic research into useful treatments: how often does it occur? Am J Med, 2003. 114(6): p. 503-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12727585

4.         Editorial, Hope in translation. Nature, 2010. 467(7315): p. 499. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20881968

5.         Editorial, Must try harder. Nature, 2012. 483(7391): p. 509-509. http://dx.doi.org/10.1038/483509a

6.         Geerts, H., Of mice and men: bridging the translational disconnect in CNS drug discovery. CNS drugs, 2009. 23(11): p. 915-26. http://www.ncbi.nlm.nih.gov/pubmed/19845413

7.         Grant, J., L. Green, and B. Mason, From Bedside to Bench: Comroe and Dripps Revisited, in HERG Research Report No. 30 2003, Health Economics Research Group. Brunel University, Uxbridge, Middlesex UB8 3PH, UK.

8.         Hackam, D.G. and D.A. Redelmeier, Translation of research evidence from animals to humans. JAMA, 2006. 296(14): p. 1731-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17032985

9.         Hampton, T., Targeted cancer therapies lagging: better trial design could boost success rate. JAMA, 2006. 296(16): p. 1951-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17062851

10.       Hurko, O. and J.L. Ryan, Translational research in central nervous system drug discovery. NeuroRx, 2005. 2(4): p. 671-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16489374

11.       Ioannidis, J.P., Materializing research promises: opportunities, priorities and conflicts in translational medicine. J Transl Med, 2004. 2(1): p. 5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14754464

12.       Johnston, S.C., Translation: case study in failure. Ann Neurol, 2006. 59(3): p. 447-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16489618

13.       Kaste, M., Use of animal models has not contributed to development of acute stroke therapies: pro. Stroke, 2005. 36(10): p. 2323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16141431

14.       Leslie, M., Biomedical research. Immunology uncaged. Science, 2010. 327(5973): p. 1573. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20339046

15.       Mankoff, S.P., et al., Lost in Translation: Obstacles to Translational Medicine. J Transl Med, 2004. 2(1): p. 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15149545

16.       Rothwell, P.M., Funding for practice-oriented clinical research. Lancet, 2006. 368(9532): p. 262-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16860680

17.       Smith, R., Comroe and Dripps revisited. Br Med J (Clin Res Ed), 1987. 295(6610): p. 1404-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3690250

18.       Zerhouni, E.A., Translational and clinical science--time for a new vision. N Engl J Med, 2005. 353(15): p. 1621-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16221788

19.       Greek, R. and J. Greek, Is the use of sentient animals in basic research justifiable? Philos Ethics Humanit Med, 2010. 5: p. 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20825676

20.       Cairns-Smith, A.G., Seven Clues to the Origin of Life: A Scientific Detective Story. 1986, Cambridge: Cambridge University Press.

21.       Belmaker, R., Y. Bersudsky, and G. Agam, Individual differences and evidence-based psychopharmacology. BMC Medicine, 2012. 10(1): p. 110. http://www.ncbi.nlm.nih.gov/pubmed/23016518

22.       Durrant, C., et al., Collaborative Cross mice and their power to map host susceptibility to Aspergillus fumigatus infection. Genome Research, 2011. 21(8): p. 1239-1248. http://genome.cshlp.org/content/21/8/1239.abstract

23.       Hunter, K., D.R. Welch, and E.T. Liu, Genetic background is an important determinant of metastatic potential. Nat Genet, 2003. 34(1): p. 23-4; author reply 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12721549

24.       LeCouter, J.E., et al., Strain-dependent embryonic lethality in mice lacking the retinoblastoma-related p130 gene. Development, 1998. 125(23): p. 4669-4679. http://dev.biologists.org/content/125/23/4669.abstract

25.       Miklos, G.L.G., The human cancer genome project--one more misstep in the war on cancer. Nat Biotechnol, 2005. 23(5): p. 535-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15877064

26.       Morange, M., A successful form for reductionism. The Biochemist, 2001. 23: p. 37-39.

27.       Nijhout, H.F., The Importance of Context in Genetics. American Scientist, 2003. 91(5): p. 416-23.

28.       Pearson, H., Surviving a knockout blow. Nature, 2002. 415(6867): p. 8-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11780081

29.       Raineri, I., et al., Strain-dependent high-level expression of a transgene for manganese superoxide dismutase is associated with growth retardation and decreased fertility. Free Radic Biol Med, 2001. 31(8): p. 1018-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11595386

30.       Regenberg, A., et al., The role of animal models in evaluating reasonable safety and efficacy for human trials of cell-based interventions for neurologic conditions. J Cereb Blood Flow Metab, 2009. 29(1): p. 1-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18728679

31.       Rohan, R.M., et al., Genetic heterogeneity of angiogenesis in mice. FASEB J, 2000. 14(7): p. 871-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10783140

 


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11U.K. Professor Dies Of Lung Cancer After Being Told Her Year-Long Symptoms Were "Psychological"

A 37-year-old Canadian professor living and working in the U.K. spent an entire year battling various symptoms like shortness of breath, fatigue, muscle and limb pain, and headaches. All of the symptoms came on progressively, but no doctors took them seriously, and Lisa Smiri was told that she was likely dealing with anxiety or depression. Finally, a year after her symptoms started, a doctor was able to diagnose her, but at that point, it was too late.

Smiri was diagnosed with Stage IV lung cancer in November 2011, and while the diagnosis came as a shock to the Cambridge-educated woman, she says it was also a relief.

“For the last year I'd been battling a range of bizarre and seemingly disparate symptoms that had forced me in September 2011 to go on sick leave from my job as a lecturer,” wrote Smiri in a blog post following her diagnosis. “The diagnosis at the time was anxiety and/or depression. And while I was both anxious and depressed, this was due to the increasingly disabling symptoms that my doctor kept insisting were purely psychological. So I was actually grateful for a medical diagnosis that confirmed there were objective, physical reasons behind my illness. While in some ways this was a terrible surprise, in another it was a huge relief."

Smiri died from metastatic lung cancer in February of last year, and despite her struggles, she left behind a lasting legacy.

“Lisa was a fantastic colleague and friend, a great teacher and researcher and truly inspirational in the way she dealt with her illness,” said Professor Richard Black at the University of Sussex.

Before she died, Smiri took to her blog to share some advice with others who may be experiencing symptoms that are largely ignored by their doctors.

"I can't prove it, and this is just my opinion, but I have no doubt in my own mind that my misdiagnosis was in large part due to the fact that I was a middle aged female and that my male doctors were preconceived towards a psychological rather than a physiological diagnosis,” wrote Smiri. “It is so easy to say that someone's symptoms are 'anxiety' related if they are a little bit complicated, unclear or unusual. Don't repeat my mistakes. You know when something is wrong. Find another doctor that you connect with and who takes your concerns seriously. Get referrals. Get tested. Refuse to be dismissed."


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11Venomous Snake Being Pickled For Three Months Suddenly Awakens And Bites Woman

A Chinese woman was attempting to make a traditional healing liquor from scratch, but after the long process was finally complete, it literally came back to bite her.

Shejiu is liquor made by pickling a venomous snake in a bottle of alcohol. The venom in the snake is neutralized from the process, and practitioners of Chinese medicine say that it has healing properties.

The woman suffers from chronic joint pain, so in order to relieve her symptoms, she frequently takes shots of the shejiu. One day, as the woman opened the top to pour out more alcohol, the snake, which had been pickling in the jar for three months, jump out and attacked her. The venomous snake bit the woman on her finger.

“Before the shejiu could have any effect on me I was sent to the hospital for a snake bite,” said the woman.

The woman was released from the hospital not long after she was bit, and the snake was later killed.


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11Nonsense on Newsweek.com

John Ericson wrote an article titled The Price of Killing Off Animal Testing, which was published by Newsweek.com on February 20, 2014.

Ericson begins by stating that: “Each year, more than 25 million animals are used for scientific research in the U.S. More than 90 percent of those are mice . . .” The actual numbers are unknown but a more realistic estimate would be over 100 million. Even a former editor of Scientific American stated that around 100 million genetically modified mice were used annually in the US. (Mukerjee 2004) So anyone or any organization that claims less than that is clearly biased or uninformed.

Ericson goes on to paint a very black and white picture of animal-based research and testing. He cites the American Association for the Advancement of Science (AAAS) as supporting it and quotes Frankie Trull of the Foundation for Biomedical Research (FBR), as saying the usual: “An immediate end to animal research in the U.S. would be a death sentence for millions of people around the world . . . If you've ever taken antibiotics, had a vaccine, had chemotherapy, an MRI, a blood transfusion, dialysis, an organ transplant, bypass surgery or joint replacement, you have been the beneficiary of research that started with lab animals.” Although these claims are widespread they is also unsupported by a critical examination of the scientific literature along with currently known facts regarding species differences. Moreover it is an example of the fallacy post hoc ergo propter hoc. (See The Strengths and Limits of Animal Models as Illustrated by the Discovery and Development of Antibacterials and Are animal models predictive for humans? for a refutation of some of the above claims. See Trans-Species Modeling Theory for why animals are very poor models for humans.)

Ericson goes on to describe why the elimination of animal-based research would be a blow to “research on neurodegenerative disease” like Alzheimer's disease (AD). This is an odd choice for an example since research with animal models has misled researchers studying AD more often than not. (For example, see Evidence Supports TSMT. See Trans-Species Modeling Theory for a detailed examination of this claim as related to amyotrophic lateral sclerosis (ALS).)

I wrote the following in the comments section of the article:

Animal-based research and testing originated during a time when creationism was accepted as the norm. Under that paradigm, animals and humans were thought to be more alike than different. Today we know better. Animal testing is a failure from a scientific perspective and animal-based research results in something medically useful only a tiny fraction of the time. For more on why animal experimentation is scientifically nonviable see http://www.futuremedicine.com/doi/pdfplus/10.2217/pme.11.89

The reason animal models fail to be of predictive value for human response to drugs and disease lies in evolution and genetic variability. This variability exists even within the same species, for example monozygotic twins.  An article in Developmental Cell by Spector and Mélanie Eckersley-Maslin et al., (Eckersley-Maslin et al. 2014) reveals new reasons for this. A team from Cold Springs Harbor conducted research, which revealed that “some cells activate only one of their two gene copies during development, altering protein yields and raising new questions.” We have one copy of each gene from each parent. Usually both of these copies are activated. But in some cases it appears that only one copy is activated either in development or later. “Random monoallelic gene expression cuts the amount of a protein by half, suggesting that this type of variability may have significant implications for disease.” The researchers found that “monoallelic gene expression is truly a random process.” Spector stated: “It is not deterministic in any way . . . This significant amount of flexibility and randomness in gene expression is important for adaptation as a species evolves, but it is unclear how it functions in organisms today.”

The above differences in genetic make-up are in addition to differences in mutations like single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) and differences in gene regulation and expression, among many others. Just one such difference between species could account for why a disease affects one species differently from another or why one drug affects one human differently from another. Species are defined by thousands of such differences and this is why we can eat chocolate but dogs should not.

The failures of animal modeling are best demonstrated by intra-human variation. A February 26, 2014, Mayo Clinic press release announces: Mayo Clinic Discovers African-Americans Respond Better to Rubella Vaccine. Scientists compared vaccine responses from Somali Americans and Caucasians and discovered that Somali Americans developed “twice the antibody response to rubella.” A non-Somali, African-American cohort also saw a high response and Hispanic Americans exhibited a low response as did Caucasians.(Haralambieva et al. 2014) Dr. Poland, the chair of a Safety Evaluation Committee for non-rubella vaccine trials being conducted by Merck Research Laboratories stated: “The significance of the findings is that in the future we may be able to create vaccines for specific groups or even individuals based on their genomic and other characteristics . . . That may mean adjusting doses for some or being able to treat larger populations with the same vaccine if the dosage is less.”

Vivisection activists should be concerned that the practice they are defending is based on a creation model of life. But they’re not.

(Photo from CDC and Wikiperia Commons http://en.wikipedia.org/wiki/File:Rubella_virus_TEM_B82-0203_lores.jpg)

References

Eckersley-Maslin, MÈlanie†A, David Thybert, Jan†H Bergmann, John†C Marioni, Paul Flicek, and David†L Spector. 2014. "Random Monoallelic Gene Expression Increases upon Embryonic Stem Cell Differentiation." Developmental cell 28 (4):351-365. http://linkinghub.elsevier.com/retrieve/pii/S1534580714000586

Haralambieva, I. H., H. M. Salk, N. D. Lambert, I. G. Ovsyannikova, R. B. Kennedy, N. D. Warner, V. S. Pankratz, and G. A. Poland. 2014. "Associations between race, sex and immune response variations to rubella vaccination in two independent cohorts." Vaccine. doi: 10.1016/j.vaccine.2014.01.090.

Mukerjee, Madhusree. 2004. "Book Review of Speaking for the Animals " Scientific American August:96-7. 


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1110-Year-Old Boy Impaled By Iron Bar Survives (Photo)

Weverton Silva, 10, was called a medical miracle after he was impaled with a 2 foot long metal spike and survived.

The young boy was picking guava fruits on Saturday in the Brazilian city of Macae when he fell from the tree. He landed on an iron bar, which punctured the left side of his body under his armpit and emerged near his right ear.

The bar missed all of Silva’s vital organs and his basic arterial routes. It was removed in one piece after five hours of surgery.

“It is difficult to arrive at a hospital with such a situation and survive,” Dr. Rodrigo Chicralla said. “I think it was just God.”

Silva was discharged on Sunday.

Sources: Metro, NY Daily News


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11Apple Reportedly Held Secret Meeting With Tesla Motors

Apple’s merger and acquisitions chief Adrian Perica and Tesla Motor’s chief executive Elon Musk met last year, suggesting that the iPhone maker may expand its business to electric cars.

Considering Apple has announced plans to better integrate iOS into car dashboard screens and has partnered with Ferrari, it seems likely that the Silicon Valley giant would be interested in Tesla.

The meeting was reported Sunday by The San Francisco Chronicle, which cited an anonymous source. The paper also noted that Apple is interested in medical devices, specifically those that can predict heart attacks.

Apple’s interest in electric cars and medical devices signal that the company wants to expand and take risks beyond the iPad and iPhone, as Wall Street analysts have speculated in the past.

Adnaan Ahmad, an investment bank analyst in Germany, wrote an open letter to Apple CEO Tim Cook in October suggesting that Apple buy Tesla. He argued that the electric car industry could provide long-term revenue growth unlike smartphones and tablets.

“I know this is radical and potentially 'transformative',” Ahmad wrote, “but this would radically alter Apple's growth profile.”

Neither Tesla nor Apple have commented on the alleged merger.

Sources: Market Watch, CNet


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11Husband, Son Leave Leukemia Patient Message In Snow

A son and husband teamed up Sunday morning to leave a heartwarming snow message on the roof of a Chicago hospital parking garage.

“HI MOM GOD BLESS U!” the message, written in snow, reads from a room at Rush University Medical Center.

Tim Hart and his 14-year-old son Will wrote the message for Hart’s wife, who is fighting leukemia.

After finishing the message, Will called his mother and asked her to look out the window. With the help of a nurse, Sharon Hart got out of bed and saw the message outside.

“It was uplifting and it was a proud mom moment to think that my 14-year-old son would do this,” Sharon Hart said.

The message could be seen from 70 hospital rooms across four floors, encouraging both medical staff and patients.

Angela Washek, a nurse at the medical center, said that it was nice to see the good side of health care.

Sources: CNN, NY Daily News


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11Mouse Models Have Failed

Azra Raza, M.D. Professor of Medicine, Director of the MDS Center, at Columbia University recently wrote the following regarding mouse models of cancer. Azra was answering the question: “What Scientific Idea Is Ready For Retirement?”

Mouse Models

An obvious truth that is either being ignored or going unaddressed in cancer research is that mouse models do not mimic human disease well and are essentially worthless for drug development. We cured acute leukemia in mice in 1977 with drugs that we are still using in exactly the same dose and duration today in humans with dreadful results. . . . there are no appropriate mouse models which can mimic the human situation.

Raza quotes Robert Weinberg of the Whitehead Institute at MIT, as stating that the reason people continue to use mouse models are: "Two reasons. First, there's no other model with which to replace that poor mouse. Second, the FDA has created inertia because it continues to recognize these models as the gold standard for predicting the utility of drugs." (See here for more on the comments of Robert Weinberg. I will also address some of his comments on the FAQs section of the new website.) Weinberg’s first reason is fallacious as there are many times when doing nothing is preferred to the status quo of doing something. For example, doing research that is misleading is worse than doing no research at all. Weinberg’s second reason, while true is just an excuse to maintain the status quo. Scientists do not have to use models that do not work just because someone in a different department of the federal government suggests they use mouse models.

But Raza adds a third reason that is more to the point:

There is a third reason related more to the frailties of human nature. Too many eminent laboratories and illustrious researchers have devoted entire lives to studying malignant diseases in mouse models and they are the ones reviewing each other's grants and deciding where the NIH money gets spent. They are not prepared to accept that mouse models are basically valueless for most of cancer therapeutics.

Sound familiar? I wonder if David Gorski MD, PhD agrees with her? (You can read her entire essay at http://www.edge.org/responses/what-scientific-idea-is-ready-for-retirement.) Furthermore, I wonder if any scientists will speak out and support her in this position? I doubt it. Growing a spine could result in their colleagues talking behind their back or the university speaking sternly to them about their tenured position and being a team player. I cannot imagine anyone asking a full professor to endure that kind of horror just to save the lives of few billion human patients.

Raza’s position is consistent with a December 19, 2013 press release from Jackson Laboratory that announced the response to cocaine and methamphetamine differs between 2 substrains of the commonly used Black 6 mouse. The C57BL/6J mice appeared to have a weaker response to the drugs than the C57BL/6N mice. The reason appears to be a single nucleotide polymorphism (SNP) in the gene Cyfip2. The press release states that: “This means that researchers should be very cautious when comparing behavioral data from studies using 6J and 6N strains.” (For more see reference  [1].)

As I have stated many times, when strains of mice differ in their response to drugs and disease and monozygotic human twins do the same, trans-species extrapolation is not going to have any predictive value. (See Trans-Species Modeling Theory for more.) But it will be a hard to convince people of this when they have a vested interest in animal models. And by vested interest I do not just mean a financial interest.

Recently Universities and Science Minister of the UK, David Willetts stated: “Animals are only used when there are no suitable alternatives. But the results we get from research can transform lives and pave the way for new and ground-breaking medical advances.” Needless to say the Science Minister provided no references for this claim and refuses to support a proper debate as I outlined here or even consider the notion that vested interest groups might lie. Willetts supports the status quo as long as he benefits. Moreover, as I have also stated, there are no alternatives to something that is not viable in the first place. There are no alternatives to using animals as predictive models for human response to drugs and disease.

Interestingly, in the same article that Willets was quoted in, Minister Norman Baker was quoted as saying that “the scientific case for developing new techniques that do not involve animals is ‘as strong as the moral one.’ ”

Raza is not the first to point out that mouse models have failed. The list of scientists who have stated more or less the same thing in science journals is long. Despite this, nothing seems to be changing. Perhaps that is because society seems to be under the impression that all scientists support the use of animals as predictive models in drug and disease research. As long as the vested interest groups get to phrase the survey questions, can buy advertising space, have the support of the media, and refuse to debate specific questions in the presence of unbiased experts, this will not change. Must be nice to have that kind of job security.

References

1.         Kumar, V.; Kim, K.; Joseph, C.; Kourrich, S.; Yoo, S.-H.; Huang, H.C.; Vitaterna, M.H.; Pardo-Manuel de Villena, F.; Churchill, G.; Bonci, A.; Takahashi, J.S. C57BL/6N Mutation in Cytoplasmic FMRP interacting protein 2 Regulates Cocaine Response. Science 2013, 342, 1508-1512. http://www.sciencemag.org/content/342/6165/1508.abstract


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11Response To More Comments From Disingenuous People. Part II

Continued from part I.

Magee also points out, correctly, that almost every study we quote also states that animal models are invaluable for medical science to continue. We have addressed this many times including in Animal Models in Light of Evolution (p27):

The FACTS of species differences relevant to the prediction issue are not in question. What is at issue are the INTERPRETATIONS authors place on the facts they refer to. We are justified in citing facts (and quoting researchers who do so) while rejecting interpretations. We cite many examples of the same phenomenon (species difference) to establish that it is a more or less agreed fact. Our point is not to get involved in an endless ding-dong about examples but to suggest that there are other well-established ways to deal with what we see (i.e. evolutionary biology). It matters not to us that those referring to the facts of species differences are also ardent advocates of animal experimentation. What matters are the facts, along with consideration of alternative hypotheses about their significance. We will offer some alternative hypotheses about the significance of the facts we uncover. Science, after all, is as much driven by disputes about the meaning and significance of facts as it is about the facts themselves. We have nothing to apologize for in this regard. (Capitals in original but bold added.)

Since most of the people we quote or cite are themselves animal modelers, it would be a shock if they did not say something positive about their research method. They are entitled to this, but we are also allowed to interpret the very impressive data they present as revealing that animal models have very little predictive value at higher levels of organization such as where drugs and diseases act and to explain why we think our interpretation of the data is correct. Statements against interest, on the other hand, are impressive on their own merit and such statements abound from animal modelers.

Magee also seems to have only minimal understanding of complexity science: “Arguing that animal models are not predictive because life is complex, when there hasn’t been a single death during a phase 1 clinical trial in the UK in over 30 years (and only one serious incident, due to human error), is a bit like arguing that airplanes can’t fly whilst being seated on an airplane at 30,000 feet.” Three points: 1. Data on who has died in Phase I trials is proprietary and any death-based lawsuits are probably settled out of court. Arguments from ignorance (we do not know how many people die in Phase I clinical trials) are not valid. 2. It does appear that in India, where many Phase I trials are done, they have a reasonably high death rate from clinical trials in general. For more on the problems of using animals to determine dose for first in man see [11]. 3. Magee is clearly stating that animal studies are used to confirm safety for first-in-man Phase I clinical trials. This means Magee thinks they have predictive value and are used to predict human response, which is somewhat contrary to earlier statements by Magee. But, many vivisection activists have stated this is true for first in man trials. However, many others claim that animal studies are performed so that all people receiving the drug will be safer. It takes different data to support or negate these claims and vivisection activists rarely provide data. Magee’s reference to first-in-man deaths in the UK being an example of where no data is provided.

Magee goes on, and I have ignored many previous claims, but my main issue with the essay is the same issue I have with almost every critique of the work Shanks and I have published. Our main message has always been some version of the following. From Animal Models in Light of Evolution (p24):

The purpose of this book is to address the ability, or lack thereof, of animals to predict human response and to see what other roles they may have in research and testing. We will argue that claims concerning the great utility of animals as predictive models of human biomedical phenomena are unsupported by evidence and are compromised by both methodological issues and issues arising from basic biological theory.

From Animal Models in Light of Evolution (p358):

Our position can be summarized as follows: Living complex systems belonging to different species, largely as a result of the operation of evolutionary mechanisms over long periods of time, manifest different responses to the same stimuli due to: (1) differences with respect to genes present; (2) differences with respect to mutations in the same gene (where one species has an ortholog of a gene found in another); (3) differences with respect to proteins and protein activity; (4) differences with respect to gene regulation; (5) differences in gene expression; (6) differences in protein-protein interactions; (7) differences in genetic networks; (8) differences with respect to organismal organization (humans and rats may be intact systems, but may be differently intact); (9) differences in environmental exposures; and last but not least; (10) differences with respect to evolutionary histories. These are some of the important reasons why members of one species often respond differently to drugs and toxins, and experience different diseases. Immense empirical evidence supports this position.

Many other such quotes could be produced from all of our writings. I have recently formulated this message into Trans-Specia Modeling Theory (TSMT):

While trans-species extrapolation is possible when perturbations concern lower levels of organization or when studying morphology and function on the gross level, one evolved, complex system will not be of predictive value for another when the perturbation affects higher levels of organization.[9]

All of the above are concise explanations of a very complicated, trans-disciplinary position. I am always amused when I see critiques of the position from people that obviously do not know what some of the words and concepts even mean. If people want to criticize our position, they must first be familiar with it and only one critique [58] has revealed even minimal familiarity. For my response to that criticism see [59]. (I am hoping that author will continue our dialogue.)

There are some that have read and understood the books and articles. Compare their interpretation with what I stated above and with what Magee and others have claimed was the position of the book. Rachel A. Ankeny of the Department of History & Politics at the University of Adelaide, Adelaide, Australia offers a reasonable review of Animal Models in Light of Evolution:

Nonetheless, the authors do an admirable job of situating their discussions against the backdrop of relevant theories and information from evolution theory and systems biology, while at the same distancing their arguments from claims about animal ethics or rights, the typical domain where debates about the validity of animal models have previously occurred. Perhaps most importantly, they do not attempt to take their conclusions too far, and grant that nonhuman animals can be used for some forms of basic biological research where prediction for human health is not the main goal. [60] (Emphasis added.)

Lewis Wolpert also appears to understand the main point of Animal Models in Light of Evolution when he reviews the book:

Animal Models in the Light of Evolution provides persuasive evidence that animal models should be used with great caution when applying the results to human diseases. Mice and other model animals are both similar and different, in their biology, to humans. It is rather technical and not easy reading. [That’s the truth!] . . . Arguments from evolution are used to show the fundamental differences between, for example, rats and humans, as the organisms are too complex for information about one to be applied to the other. The authors discuss this complexity in terms of dynamical systems theory and its mathematical basis and question the possible similarity of such systems in different mammals. Quite small changes can have significant effects. They use such views to raise doubt on just how much genes contribute to an organism's form and function, but their arguments are themselves complex and hard to follow, and there is no persuasive evidence. It is no mystery that mice can differ significantly from humans in their response to drugs.[61]

I could take exception to some of the comments in the above two reviews but at least the two reviewers understood the basis for our position. Comments like the above from Magee miss the big picture either from ignorance or malice.

Wolpert is right—our position is technical, requires trans-disciplinary education, and is not easy. Moreover, it is unpopular as the hierarchy of academia will change dramatically as will salaries. I have presented posters at the largest conferences in evolutionary biology and complex systems. The attendees walk by, read the poster, say they agree with me and ask why I am at their meeting as everyone already knows all this. After all, they say, no one uses animals as surrogate humans in biomedical research anyone. They are only used for basic research. I show them a few grant applications that claim the research project will directly cure humans and they are aghast. So, I ask them to sign a petition that states the following scientists agree with TSMT. They refuse and then they all say the same thing. “No. I agree with you but I would lose my job. My university will not allow us to voice opposition to something that brings in money to the university.” Needless to say, I do not have any of that on tape. But the experts in the two fields on which our position is based agree with us while the basic researchers that use animals use fallacy after fallacy along with obfuscation to try and confuse society and justify their research. They never address our position or the issues that arise out of it. Suffice it to say Magee is not an exception to that rule.

I am happy to correct mistakes made in any of our books or articles and actually appreciate them being pointed out. But I will in the future resist responding to people who are the equivalent of young earth creationists in that they simply do not have enough appreciation of the science to understand why their questions and comments are not even wrong. In the future, if someone wants to engage me in a discussion of TSMT please demonstrate that you at least understand what we are saying by explaining it in your first or second paragraph. Only then will I comment on your issues.

Essays like Magee’s and Gorski’s recent post are why I have also changed my criteria for debates. The recent Bill Nye debate notwithstanding, most science debates would benefit from the rules I list here. I would also suggest the same concepts be employed in debates in the scientific literature. That being said, I welcome the opportunity to engage in a fair and proper debate either in the scientific literature or in a public forum. Once again, I am not holding my breath waiting for a response.

References

9.         Greek R, Hansen LA: Questions regarding the predictive value of one evolved complex adaptive system for a second: exemplified by the SOD1 mouse Progress in Biophysics and Molecular Biology 2013:http://dx.doi.org/10.1016/j.pbiomolbio.2013.1006.1002. http://www.sciencedirect.com/science/article/pii/S0079610713000539

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

11.       Greek R, Rice MJ: Animal models and conserved processes. Theoretical Biology and Medical Modelling 2012, 9(40). http://www.tbiomed.com/content/9/1/40/abstract

58.       Shelley C: Why test animals to treat humans? On the validity of animal models. Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences 2010, 41(3):292-299. http://www.sciencedirect.com/science/article/B6VHP-50NH66T-3/2/adf77c24c844a88e0c8b93547272a7b9

59.       Greek R, Shanks N: Complex systems, evolution, and animal models. Stud Hist Philos Biol Biomed Sci 2011, 42(4):542-544. http://www.ncbi.nlm.nih.gov/pubmed/22035727

60.       Ankeny RA: Book Review: Animal Models in Light of Evolution. Q Rev Biol 2011, 86(September):223-224.

61.       Wolpert, Lewis. 2010. Review of "Animal Models in the Light of Evolution" by Niall Shanks, Ph.D., and C. Ray Greek, M.D. Philosophy, Ethics, and Humanities in Medicine. doi: 10.1186/1747-5341-5-12. http://www.peh-med.com/content/5/1/12

 


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