Category Archives: Science News

Lung cancer immunotherapy, from PD-1 knockout mice to clinical trials

This morning many news outlets, including the BBC, covered a very promising development in lung cancer therapy; the successful clinical trial of the cancer immunotherapy Nivolumab in 582 patients with advanced lung cancer. While the extension of survival was modest in most patients, it is to be remembered that these were patients with advanced lung cancer, which is notoriously difficult to treat, so to see the survival time doubling in some patients was quite dramatic. Future trials will examine whether greater benefits are seen when Nivolumab is given earlier in the course of the disease.

Dr Alan Worsley, Cancer Research UK’s senior science information officer, told the BBC that harnessing the immune system would be an “essential part” of cancer treatment, and adding:

This trial shows that blocking lung cancer’s ability to hide from immune cells may be better than current chemotherapy treatments. “Advances like these are giving real hope for lung cancer patients, who have until now had very few options.”

Nivolumab works by blocking the activation of the PD-1 receptor protein found on the surface of many of the immune cells that infiltrate tumours. Another protein named PD-L1 binds to PD-1 and initiates a regulatory pathway that leads to the immune response being dampened down. Usually this is a good thing as it maintains immune tolerance to self-antigens and prevents auto-immune damage to healthy tissue, but unfortunately many solid tumour cells, such as lung cancer cells, also secrete PD-L1, and by activating PD-1 can evade destruction by the immune system. By blocking PD-1 Nivolumab turns off this protective mechanism and allows the immune cells to detect and destroy the tumour cells.

X-ray of a lung cancer patient. Image credit: "LungCACXR" by James Heilman, MD - Own work.

X-ray of a lung cancer patient. Image credit: “LungCACXR” by James Heilman, MD – Own work.

So how was this discovered? This is where the knockout mice come in. Scientists had observed in the 1990’s that PD-1 was highly expressed on the surface of circulating T- and B- immune cells in mice, but didn’t know what role PD-1 played, suspecting that it may be involved in increasing the magnitude of the immune response. To examine the role of PD-1 researchers at Kyoto University in Japan creates a knock-out mouse line where the PD-1 gene was absent, and observed that this lead to some immune responses being augmented. In a paper published in 1998 they reported than rather than being an activator of the immune response PD-1 was actually involved in dampening down the immune response (1).

Subsequent studies in a range of PD-1 knockout mouse strains over the next decade explored the role of PD-1 in regulating the immune system, and also demonstrated that its ligand, PD-L1, could block immune-mediated tissue damage (2).  At the same time as these studies were taking place other research was demonstrating that PD-L1 was produced at high levels by tumour cells, first in   renal cell carcinoma in 2004 (3), but later in many other solid tumours including in lung cancer (4), and that this expression was associated with a decrease in the immune response to the tumour and a poorer prognosis.

This raised an obvious question: would blocking PD-1 improve the immune response against these tumours?

Work was already underway to find out. A paper published in 2007 by scientists from Nara Medical University in Japan demonstrated that blocking PD-L1 binding to PD-1 with monoclonal antibodies enhanced the immune response against established tumours in a mouse model of pancreatic cancer and acted synergistically with chemotherapy to clear the tumours without obvious toxicity (5). Subsequent studies with other monoclonal antibodies in a range of mouse and in vitro models of cancer showed similar results, including the humanized monoclonal antibody MDX-1106, now called Nivolumab, which was obtained by immunizing mice which had been genetically modified to produce human antibodies with human PD-1 (6).

Laboratory Mice are the most common species used in research

Cancer Immunotherapy – adding another accomplishment to an already impressive CV!

MDX-1106/Nivolumab showed promising results in a phase 1 trial against metastatic melanoma, colorectal cancer, castrate-resistant prostate cancer, non-small-cell lung cancer, and renal cell carcinoma, and following larger clinical trials (7) it was approved by the FDA for the treatment of melanoma that cannot be removed by surgery or is metastatic and no longer responding to other drugs, and more recently for metastatic squamous non-small cell lung cancer.

The story of the development of anti-PD-1 cancer immunotherapy is an illustration of how basic or fundamental biological research in animals informs medical science, and drives the discovery of new therapies. As cancer immunotherapy begins to transform the treatment of many previously untreatable cancers, it is well worth remembering that this revolution has its origin in the hard work of countless scientists working around the world, many of whom could only have guessed at the time where their efforts would eventually lead.

Paul Browne

References:

  1. Nishimura H1, Minato N, Nakano T, Honjo T. “Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses.” Int Immunol. 1998 Oct;10(10):1563-72. PubMed: 9796923
  2. Grabie N, Gotsman I, DaCosta R, Pang H, Stavrakis G, Butte MJ, Keir ME, Freeman GJ, Sharpe AH, Lichtman AH. “Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart.” Circulation. 2007 Oct 30;116(18):2062-71. PubMed 17938288
  3. Thompson RH1, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, Krejci KG, Lobo JR, Sengupta S, Chen L, Zincke H, Blute ML, Strome SE, Leibovich BC, Kwon ED. “Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.” Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-9. PubMed:15569934
  4. Zhang Y1, Huang S, Gong D, Qin Y, Shen Q. “Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer.” Cell Mol Immunol. 2010 Sep;7(5):389-95. doi: 10.1038/cmi.2010.28. PubMed: 20514052
  5. Nomi T1, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H, Nakamura S, Enomoto K, Yagita H, Azuma M, Nakajima Y. “Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer.” Clin Cancer Res. 2007 Apr 1;13(7):2151-7. PubMed:17404099
  6. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL. “Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.” J Clin Oncol. 2010 Jul 1;28(19):3167-75. doi:10.1200/JCO.2009.26.7609. PubMed: 20516446
  7. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. “Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.” J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. PubMed:24590637

The Contribution of Animal Experiments to the Control of Disease

Jack Botting Animal ResearchDr Jack Botting (1932-2012) was a keen advocate of informing the public about the important role of animals in research. Following a successful career in pharmacology, Dr Botting became the Science Director for the Research Defence Society (RDS), an organisation which would later merge with the Coalition for Medical Progress to form Understanding Animal Research. During his five years at RDS, he wrote many essays for the newsletter on the contribution of animal studies to our understanding of diseases and treatments, as well as address many of the activists pseudoscientific claims denying the role of animals in modern medical developments.

Recently, his wife, Renia Botting, collated his essays and published them in a free-to-all online book. Across nineteen essays, Jack Botting explains the contribution of animal experiments to the treatment of infectious diseases, the development of life-saving procedures, and the creation of drugs for organic diseases. See the chapter overview below:

Animals and Medicine - The contribution of animal experiments to the control of disease

You can read the whole book by clicking here. Choose either “Read the pdf” or “Read the HMTL” to view the whole book for free in two different formats.

Renia Botting writes in the introduction to the book:

“One of the most damaging aspects of antivivisection campaigning was that they had started to hijack the scientific argument, claiming that animal experimentation was scientifically misleading, “a failed technology” etc., and that an examination of the research behind major medical advances showed that non-animal techniques were crucial and that the animal experiments had contributed nothing, or worse still, held up progress. Antivivisectionists were deliberately shifting the debate from the traditional “science vs animal welfare” argument to a “scientific” debate giving their arguments a cover of scientific respectability.

To respond to this style of campaigning, Jack was given the specific task of reviewing the research behind the major medical advances and writing non-technical reviews explaining the role played by animal experimentation. His work effectively put an end to this aspect of antivivisection campaigning. The articles which Jack wrote at that time have been collected in this book.”

It would seem that Jack faced the same challenges we do now in correcting misinformation put about by animal rights groups, as “scientific antivivisection” is sadly still up to its old tricks – if under new guises. His essays address many of the exact same myths that we have worked to debunk. For instance when discussing the development of penicillin, Botting directly answers the animal rights claims that it would never have been further developed if guinea pigs were used in initial tests; when discussing similarity in drug reactions he looks at claims that aspirin has teratogenic effects in rats. The book is well worth a read, especially for anyone who is new to this debate.

Animals and Medicine: The Contribution of Animal Experiments to the Control of Disease by Jack Botting.

Zebrafish: the rising star of animal models

Today we have a guest article by Jan Botthof, a PhD Student at the Cambridge University Department of Haematology and the world renowned Wellcome Trust Sanger Institute. Together with the EMBL-European Bioinformatics Institute – with which it shares the Genome Campus a few miles south of Cambridge – the Sanger Institutes is one of the World’s top centres of expertise for genome research. As EMBL-EBI’s associate director Ewan Birney highlighted in a recent article for the MRC Insight blog, by studying the biology of a wide variety of model organisms – including humans and zebrafish among many others – the more than one thousand scientists working on the Genome Campus a gaining critical insights into biology that are advancing 21st century medical science.

When most people think of animal research, they imagine mice, rats or maybe fruit flies. However, other models are increasingly being used in addition to the more traditional organisms. The number of zebrafish (Danio rerio) in particular is steadily increasing in biomedical research each year. You might be wondering why scientists are using fish instead of animals more closely related to humans for their studies. Let’s have a look at some of the advantages of the zebrafish to explain this matter. This list is obviously not going to be comprehensive, because many advantages are field-specific and quite technical, but it should give you an idea why researchers might want to choose fish over other animals.

The zebrafish, a rising star star of medical research.

The zebrafish, a rising star star of medical research.

First of all is something that makes zebrafish more attractive to scientists who pressed for time, such as PhD students wanting to graduate punctually (like me!): zebrafish reproduce at a rapid rate. Each female can lay several hundred eggs each week, which will develop into mature adults in about three months. This is especially useful if you need to breed a large number of animals very quickly, or when you want to cross several lines with modified genes. Rapid breeding also greatly reduces the time it takes to introduce novel genetic modifications into the animals, as several generations are required before a stable modification of the gene in question is achieved. This makes zebrafish a very efficient species for research.

4-day old zebrafish embryo.

4-day old zebrafish embryo.

Another really useful trait of zebrafish is that their embryos are relatively large and initially transparent. This makes it easy to manipulate the embryo, which is very helpful if you are injecting various substances to modify their properties. In my case, I’m using a technique called CRISPR-Cas9 to very precisely switch off certain genes, but there are many other applications.  An added advantage is that you can treat these embryos chemically to stop pigmentation from forming, making it very easy to study early embryonic development (Figure 1). Moreover, the embryos are permeable to many chemicals and drugs – making them ideal for screening large numbers of toxicology samples or drug candidates.

The zebrafish genome has been fully sequenced, which is a must-have for model organisms nowadays.  This effort showed that their genome is remarkably similar to the human one, with at least 70% of human genes having a zebrafish equivalent – a figure that is even higher when only disease-causing genes are considered. There are also efforts underway (by the same group that sequenced the zebrafish genome, which coincidentally happens to be right next to my research group) to mutate every single gene in the zebrafish genome. This can be very helpful if you study a certain gene and wonder what happens to the whole organism when it is lost – and having such large scale resources can save the wider research community huge amounts of time and effort.

Apart from fish with mutations in specific genes, there are also numerous lines containing genes from other organisms (transgenic lines). Usually the proteins encoded by these genes are fluorescent and are used to mark specific cells, as we can control (at least partially) in which tissue a protein is made. One of these is called green fluorescent protein or GFP (originally from a jellyfish). Using techniques such as GFP it is possible to visualize changes in specific cell populations in real time in living animals. Just to give you a personal example: I study blood development, so naturally I want to look at the different types of blood cells. Depending on what cell type I want to look at, I can select an appropriate zebra fish line, where this type is labelled. For an example, have a look at Figure 2, which shows early blood cells during embryonic development labelled with GFP. As these fluorescent proteins come in different colours, it’s possible to look at two or more different cell types at the same time.

A recent advance is the generation of fully transparent adult zebrafish, aptly named “Casper” after the popular cartoon ghost. You can look up the freely available original paper here if you want to see what these fish look like. Of course, scientists are not making transparent fish just because they look cool, but they are very useful tools for research. One application is the easy study of tumour metastases, as the cancer cells are just much easier to spot in transparent fish. Adding fluorescent labelling as described above can make this technique even more powerful.

Usually when we use zebrafish, we take advantage of the fact that many fundamental processes have been evolutionary conserved between fish and humans. Because of these similarities, we can use zebrafish as a model for what happens in humans. Sometimes differences between animals and humans can be more telling though. For example, many animals can regenerate much more efficiently than humans (you might have heard about the ability of salamanders to regrow lost limbs or tails) and this is also true to some extent for zebrafish. One very well studied research area is heart regeneration. Humans are unable to regenerate heart muscle tissue, which is of course problematic when parts of it die off during a heart attack or following injury. In contrast, zebrafish can use stem cells to regenerate the lost tissue – if we could induce a similar process in humans, it might help treating people recovering from cardiac injury. The British Heart Foundation is funding important research in this particular field through its “Mending Broken Hearts” campaign. In the even longer term, it might be possible to adapt similar principles to other tissues and thereby help in treating a variety of injuries.

The regenerative capacity of zebrafish isn’t only interesting for medical research, but it has a very practical advantage: you can cut a tiny part of the tail fin off and use it to extract DNA from the tissue. Then, the mutation status of a specific gene can be determined, which is essential when you want to know whether an animal is a carrier for the mutation you are interested in. The fin then grows back within two weeks, so the animal is not harmed.

Lastly, I just want to mention some financial considerations. Animal research in general is really expensive, which is one of the reasons why alternatives are used whenever possible. These costs are largely determined by how much effort and space is required to house, feed and care for the animals. Of course, this makes large or exotic species especially expensive, so they are used less often. However, even rodent colonies can cost quite a lot of money to maintain. Zebrafish require much less space per individual, are relatively inexpensive to feed , and it’s also relatively straightforward to ship animals (usually as embryos) between labs. This facilitates collaborative research and reduces the number that need to be used, since they don’t have to recreate the same genetically modified line all over again.

In conclusion, zebrafish have a lot of useful characteristics that make them very practical and useful model organisms, which explains their rising  popularity among researchers.

In the next article of this series, I’m going to have a closer look at zebrafish care, as well as daily work in a fish facility and some of the rules and regulations surrounding fish welfare.

Jan Botthof

En Passage, an Approach to the Use and Provenance of Immortalized Cell Lines

This guest post is by Lisa Krugner-Higby, DVM, PhD.  Dr. Krugner-Higby is a scientist and also a research veterinarian within the Research Animal Resource Center at the University of Wisconsin-Madison. Dr. Krugner-Higby’s research is in development of extended-release formulations of analgesic and antimicrobial drugs. She previously worked in anti-HIV drug development.

I am always fascinated by the idea promoted by some animal rights activists – repeated in many versions and for many decades – that all preclinical biomedical research can be conducted using in vitro cell culture. I have never found one of them who has spent much time working with cell culture. On the other hand, I have spent approximately seven years of my life working with cell cultures, looking at the stainless steel back wall of a laminar flow work station day after day. One thing I can say about immortalized cell lines, or cells that reproduce indefinitely, is that they are not alive in the same way that a mouse is alive.

 

Cell culture

Cell culture

The first thing that a graduate student learns when they begin to work with cell culture is how to take cells that have overgrown the sterile plastic flask they inhabit and put them into a fresh flask with fresh growth medium. It’s called ‘splitting’ the number of cells and ‘passaging’ them into a new home. Split and passage, split and passage… I knew that with every passage, the cell line became a little more different than normal cells and even a little more different than the original cell line. The remedy for this type of genetic drift was to freeze low passage cells in liquid nitrogen and re-order the line from the repository when the low passage stocks were depleted. I was careful with my sterile technique, cleaned the laminar flow hood, and used a new sterile pipet every time in order to avoid contamination of my cells. Unfortunately, the day came when I opened the incubator door and the flasks were black and fuzzy with fungus, and all of my carefully tended cells were dead. An anguished conversation with the tissue culture core technician revealed that this happened every Spring in North Carolina when the physical plant turned on the air conditioning for the year, blowing a Winter’s worth of fungal spores out of the ductwork and into the air. She recommended doing other things for about 6 weeks until the spore load had blown out of the ducts. I have had other cell line disasters in my scientific career: the malfunctioning incubator thermostat that turned a colleague’s two months’ worth of cell culture growth into flasks of overheated goo or that generally reputable vendor that sold us a case of tissue culture flasks that were not properly sterilized resulting in clouds of bacteria in the warm, moist, nutrient-rich environment of the incubator.

I never thought to ask, in those early days, if the cells that I fussed, worried, and wept over, were actually the cells that they were supposed to be. Raji Cells, A549s, U937s, I knew them all, worked with them every day, and never doubted that they were the cells that I thought that they were. I knew that some cell lines had been contaminated with the HeLa cell line. HeLa cells are very hardy and could spread quite easily from one flask to another. But I thought that was in the past. It turns out that there was more to the story than I realized. Cell lines have a provenance, like paintings or other works of art. They have an origin, a laboratory where the line was first isolated and propagated. From there, it may have been distributed to other laboratories and to repositories like the American Type Culture Collection or ATCC. Some cell lines are used by only a few laboratories, and some become used very widely and in a large number of biomedical disciplines. Whereas some paintings are intentionally forged, many cell lines have now been shown to be unintentionally forged. A recent article in the journal Science estimated that 20% of all immortalized cell lines are not what they were thought to be1.

Download original file2400 × 1999 px jpg View in browser You can attribute the author Show me how Multiphoton fluorescence image of cultured HeLa cells with a fluorescent protein targeted to the Golgi apparatus (orange), microtubules (green) and counterstained for DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. National Institutes of Health (NIH).


Multiphoton fluorescence image of cultured HeLa cells with a fluorescent protein targeted to the Golgi apparatus (orange), microtubules (green) and counterstained for DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. National Institutes of Health (NIH).

We now have better methods of identifying cell lines by their DNA, called short tandem repeat (STR) profiling, and scientific journals are beginning to require this testing for cell lines prior to publication. Currently, 28 scientific journals require STR profiling to establish cell line provenance prior to publishing a manuscript from a particular laboratory. Some scientists are also beginning to create catalogs of contaminated cell lines in an attempt to quantitate the damage done by some misidentified, but widely studied, cell lines. The same Science article, notes that the International Cell Line Authentication Committee (ICLAC) maintains a database of misidentified cell lines that now numbers 475 different lines. A cell line geneticist, Dr. Christopher Korch, recently estimated that just two of the immortalized cell lines that were found to be misidentified, HEp-2 and INT 407, have generated 5,789 and 1,336 articles in scientific journals, respectively. These studies cost an estimated $713 million dollars and generated an estimated $3.5 billion in subsequent work based on those papers1. This is because the usual trajectory for testing a new therapeutic modality, especially in cancer research, is to test a compound or technique in cell culture. It will then be tested in mice that express a tumor derived from the cultured cancer cells. If those studies are successful, the compound and/or technique undergoes further toxicity testing in other animal models before entering its first Phase I trial in human volunteers.

A lot of compounds that show early promise in cell culture and in cell line-injected mice turn out not to have efficacy in animal models or in human patients. Sometimes this is simply a matter of the compound being too toxic to organs or cell types that are not represented in the initial cell culture. Often, the reason why particular compounds or strategies fail is not known, and most granting agencies are not keen to fund laboratories to find out why things don’t work. I have wondered if the failure of some compounds or techniques is in part due to misidentified cell lines. I have also wondered if it is a reason why testing in animal models, particularly in animal models with spontaneously-occurring tumors, is necessary.

Testing anti-cancer compounds in models of spontaneously-occurring tumors in animals and/or testing in human tumor cells taken directly from patients and injected into mice (the ‘mouse hospital’ approach) is more time and resource intensive than screening in immortalized tumor cell lines. This approach, however, has the advantage of knowing that the investigator is not just treating misidentified HeLa cells in error. It is always necessary to go from in vitro cell culture models to in vivo animal models to confirm the viability of a therapy.

Science makes claim to no enduring wisdom, except of its method. Scientists only strive to be more right about something than we were yesterday, and efforts are underway to weed out misidentified cell lines. But the fundamental issues behind cell line misidentification highlight one of the reasons why we should not rely on immortalized cell lines without animal models, and why granting agencies should fund more studies to try to identify the disconnect between the results of in vitro and in vivo studies when things do not go as planned. That is a part of good science and part of creating better cell culture models to refine, reduce, and sometimes replace the use of animals in biomedical research.

Lisa Krugner-Higby, DVM, PhD

1) Line of Attack. Science. 2015. Vol. 347, pp. 938-940.

Interview with a Primate Researcher

In the last few months, Italian animal rights activists have conducted a campaign against animal research, in particular against primate research. This is despite the important role that primates have played in breakthroughs in stem cell research and neuroprosthetics, among other things. Nonetheless, activists continue to try to claim such research is useless. In particular, they targeted Prof. Roberto Caminiti, a leading neurophysiologist at the University La Sapienza in Rome, and his research team, accusing them of animal mistreatment. Earlier this year students and scientists at the University rallied round Prof. Roberto Caminiti, his team, and his important research.
To answer some of the activists accusations, Pro-Test Italia has produced a video with Prof. Caminiti to illustrate why primate research is so important in the field of neurophysiology and brain-computer interface, and why animal models remain essential for this kind of research. Pro-Test Italia have also made an English version of the video:

It’s important to spread this video outside of Italy to both explain to the public what is going on, and to encourage other primate researchers not to remain hidden but to be clear about the important research that they do. Researchers should be proud of the important work they do in contributing to medical developments for everyone.

Marco

American Psychological Association supports NIH primate researcher Stephen J. Suomi

Research conducted within the National Institutes of Health (NIH) intramural program has been the focus of a PETA campaign over the past several months. Elements of the campaign mirror tactics PETA has used elsewhere to generate media coverage, fundraising, and emails or phone calls to the NIH. The campaign recently reached beyond newspaper, bus, and metro advertisements to include a congressional request to NIH to provide a review of the research.

The American Psychological Association (APA) responded on January 22 with strong statement of support for the scientist and research under attack by PETA.

APA 01.22.15

APA’s letter to the congress members, in its entirety, reads:

“In December 2014 you were one of four members of Congress who sent a letter to Dr. Francis Collins, Director of the National Institutes of Health (NIH), requesting that his office commission a bioethics review of a research program directed by the world renowned researcher, Dr. Stephen J. Suomi. On behalf of the American Psychological Association and its Committee on Animal Research and Ethics, I am writing to provide a broader scientific perspective on this research. As you are likely aware, the request you received was a part of a sustained and well publicized campaign against Dr. Suomi’s laboratory by the organization, People for the Ethical Treatment of Animals (PETA), in support of its mission to put an end to research with nonhuman animals.

Your letter stated that prominent experts have raised concerns about the scientific and ethical justification for these experiments. We believe that the facts do not support PETA’s public statements about this research. Over the past three decades, Dr. Suomi and his collaborators have made significant contributions to the understanding of human and nonhuman animal health and behavior. Dr. Suomi’s work has been critical in understanding how the interactions between genes and the physical and social environments affect individual development, which in turn has enhanced our understanding of and treatments for mental illnesses such as depression, addiction, and autism.

Dr. Suomi and colleagues found that like humans, monkeys share similar variants of genes that make an individual more vulnerable to mood and personality disorders; however, genetics interact with experience in determining such disorders, and mother-infant dynamics in particular have a large influence on later development. Dr. Suomi has successfully produced monkey models of depression and excessive alcohol consumption and his studies provide insight into modes of treatment. Through his work on neonatal imitation, Dr. Suomi discovered potential early signs of atypical social development in monkeys, which has informed the search for screening methods and treatments for autism in human children. Further, through his work on the development of attachment behavior to a caregiver, which is crucial for infant survival in both humans and other animals, Dr. Suomi’s research has had a tremendous impact on the standards for the welfare of nonhuman animals in captivity.

Cover PNAS monkey pic 2

The specific study targeted by PETA was designed to investigate the long-term effects of fluoxetine (Prozac) in children. Given that drugs are typically tested only on adults, the effects of this commonly prescribed anti-depressant on children were unknown. Thus, in response to overwhelming concern raised by parents, physicians, and others involved in child and adolescent health about the safety of this medication for children, Dr. Suomi and his colleagues began a study with baby monkeys to elucidate the effects of fluoxetine in children. Contrary to PETA’s repeated claims that animal research has not improved human health and that modern non-animal research methods are more effective, there are, in fact, no viable non-animal alternatives for identifying the causes of and treatments for disorders that affect the brain and behavior. Studies with a wide variety of nonhuman animal species have been and continue to be integral to basic and applied research on health.

Laboratory animal models generally provide the most scientifically rigorous means of studying normal and abnormal behaviors in order to better understand their underlying mechanisms and to remedy disorders. Monkeys are the ideal model for the work that Dr. Suomi does, because they share approximately 93% of human DNA, they live in social groups with similar mother-infant dynamics as humans, and they develop more quickly than humans. Moreover, the monkeys in Dr. Suomi’s studies are treated humanely, following strict guidelines set forth by the Animal Welfare Act and overseen by numerous entities including the NIH Office for Laboratory Animal Welfare (OLAW), the United States Department of Agriculture (USDA), the Association for the Assessment and Accreditation of Laboratory Animal Care, International (AAALAC), and institutional animal care and use committees. And given that Dr. Suomi is an intramural researcher at NIH, you can be certain that his research animals receive premier quality of care.

I understand that it may sometimes be difficult to weigh the qualifications and varying conclusions of “dueling experts,” but let me assure you that Dr. Suomi is a highly regarded member of the APA and the psychological science community at large, as well as a highly sought-after expert in the field of pediatric medicine. In addition to providing information to the U.S. Congress, Dr. Suomi has testified at the World Health Organization and addressed the British House of Commons about the implications of his scientific findings.

Based on the conviction that research with nonhuman animals is a necessary component of basic and applied research on health, APA strongly supports humanely conducted, ethically sound, and scientifically valid research with nonhuman animals. For nearly 100 years, through its Committee on Animal Research and Ethics, APA has promoted informed, serious, and civil dialogue about the role of nonhuman animal research in science. If you should be asked to take further action against Dr. Suomi, I hope you will make it a point to seek out additional information before making a decision. My staff stand ready to provide you with additional information, including assembling experts for a staff briefing or assisting you in any other way on this issue.”

***

The complete statement can be found here:  APA Suomi-letter 01.22.15

 

70 year old professor retires and closes lab, PETA claims victory

The retirement of a highly respected senior neuroscientist at the center of a sustained recent publicity campaign by an animal rights group generated a victory claim on Friday when PETA realized that their target had retired. The retirement came after a productive and award-winning 40 year research and teaching career. University of Wisconsin-Madison neuroscience Professor Tom Yin’s research led to breakthroughs in understanding how the brain processes and localizes sounds. The highly cited research was continuously funded by the US National Institutes of Health because it contributed fundamentally important new knowledge that is the necessary building block for advances in medicine and science that involves hearing. We have written about Professor Yin’s research previously, for more information see here, here, here.

Yin’s sound localization research was the target of a sustained and multi-dimensional attack by PETA over the past three years. The campaign had provided rich opportunities for stunts, attracted celebrities, generated media attention, and undoubtedly brought in many donors for animal rights groups.

Metro bus displaying PETA ad. Image: Wisconsin State Journal.

Metro bus displaying PETA ad. Image: Wisconsin State Journal.

The scientist’s retirement is unlikely to provide obstacles to PETA’s continued success in using the research for fundraising appeals, as was indicated by the group’s immediate response. Despite the obvious fact that the retirement of a 70 year old scientist is expected, rather than unusual, PETA promptly claimed responsibility and announced that they had secured a victorious end to their campaign.

PETA’s tactic may well serve as a model to other groups because it offers a solid opportunity to claim effectiveness of their campaigns. If so, we might expect to see other scientists seemingly within the realm of retirement age appear as targets of major campaigns that involve bus ads, celebrities, and stunts that misrepresent the research. (Or perhaps they could simply claim all retired scientists did so not as a result of age, or the natural conclusion of long and productive careers, but rather in response to campaigns by those opposed to the research.)

Despite the scientist’s retirement and the lab closing, it seems unlikely that PETA will retire the photos of research animals and misleading claims about Yin’s work that were the center of PETA’s campaign. It is more likely that the campaign will continue to be used by PETA to attract attention and donors, with the promise of more victories in ending research.

PETA also took a page from other animal rights groups that claim credit for the retirement of research animals, despite the fact that it is the scientists and research institutions that find adoptive homes and retire the animals. Like many research institutions, the University of Wisconsin-Madison finds adoptive homes for animals that are no longer in research and whose care and safety can be assured in a home setting. In this case, four of the five cats that were part of Professor Yin’s research were retired into private homes. This is in stark contrast to the PETA policy at its Norfolk, VA shelter of killing on average 2000 dogs and cats per year (http://www.nytimes.com/2013/07/07/us/peta-finds-itself-on-receiving-end-of-others-anger.html)

The university, like other research facilities, does not use those adoptions as a vehicle for media attention. By contrast, retired research animals are often featured as centerpieces in fundraising campaigns by animal rights groups. We have written about this previously in the context of a controversial campaign by Beagle Freedom, in which the animal rights group appropriates credit for research facilities’ successful adoption programs. In general, the focus of the adoption programs is on successfully placing the animals. Even the NIH and federal government, while providing over $30 million for retirement of research chimpanzees and committed to tens of millions more for their lifetime support, do so without sustained high-profile media campaigns. Similarly there are rarely press releases from the UW-Madison announcing the animal adoptions or the lab closing due to the scientist’s retirement.

PETA seized the opportunity for their own press release and claim of victory after they realized what had happened. How did they find out? Simply by reading the records that the university regularly sends to PETA and other animal rights groups in response to their regular open records requests. PETA was no doubt pleased by their discovery. Not only could they claim victory for the retirement of the 70 year old scientist, they could also continue to claim PETA themselves were responsible for the research animals’ retirement.

The victory claim is PETA’s central rationale for continued used of the images and claims that were at the center of their campaign. There is little doubt that they will not be retired; rather they are likely to be used for a long time to convey the impression of a success. The question is whether those who hear the victory claim might wonder whether there is anything surprising about the retirement of a 70 year old scientist. Others might be curious enough to learn more about the remarkable accomplishments of that scientist over his 40 year career (see here for more information). In light of current campaigns against other scientists, the question will also become whether PETA has highlighted a new path that paves the way for higher likelihood of being able to claim an unearned victory.