Monthly Archives: September 2017

Research Roundup: Drawing closer to curing the organ transplant shortage, using dengue antibodies to minimize the effects of Zika virus and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • Scientists grow bullish on pig-to-human transplantsResearchers give hope to those desperately waiting for an organ transplant. Although the technical skill in organ transplant has been well developed, minimizing the immune response for organs transplanted from one species to another has not. Recently, researchers have been able to lessen, although still not eliminate, the dangerous immune response that transplanted pig organs cause in monkeys. At the University of Munich, a cardiac surgeon, Paolo Brenner, reported results of the first animal to hit a milestone for determining whether a xenotransplantation approach is safe enough to try in humans. According to Immunologist David Cooper, University of Alabama in Birmingham, the new immunosuppressant drug regimens, genetically engineered pigs, and the use of gene-editing tools has increased the ability to safely transplant organs from one species to another. This leads to the possibility of, at least, temporary organ transplants while a patient is waiting for a human organ to be available. This can improve the quality of life for those awaiting kidney transplants and even extend the life for those with more urgent needs for life saving organ transplants.

Genetically engineered pigs produced in Munich, Germany, were recently used in a record-breaking baboon heart transplant. Credit: Jan-Michael Abicht

  • Common antidepressant found to reduce belly fat in older mice. Visceral fat, as compared to subcutaneous fat, is generally considered to be deadly, being linked to heart disease and type 2 diabetes. New research suggests that it is inflammation of immune cells which may lead to the accumulation of visceral fat, for example in the belly area. Christina Camel and her team at the Yale school of Medicine used young and old mice, isolated the macrophages from within the fat tissue, and then sequenced DNA from these cells. They found the macrophages in the older mice expressed more genes that prevent catecholamines, a set of molecules that spread signals between nerve cells. “The genes do this by activating an enzyme that suppresses these neurotransmitters. The boosted activity of this enzyme in aged immune cells in the belly fat of older mice effectively block signals telling the body that there is fat there that is available to burn for energy.” The drug used to accomplish this was “a common antidepressant called clorgyline, which is given to some people because low levels of catecholamine have been linked to symptoms of depression.” This research was published in the journal Nature.
  • New technique turns mouse brains transparent. Stroke is the leading cause of disability and the second leading cause of death worldwide. During a stroke, the blood supply to the brain is cut off, which prevents oxygen and vital nutrients from reaching cells. To understand this process, researchers typically examine 2D images of brain slices under a microscope. Now, a new technique has been developed where a fluorescent gel is injected into the hearts of mice and pumped through the body. The brain is then removed and soaked in chemicals, which leave the brain completely transparent. A laser is used to illuminate the fluorescent gel and provide a 3D image of the entire brain. In the brains of mice that had a stroke, researchers could see how the blood supply is cut off, and how surviving blood vessels reorganize. This research was published in the Journal of Cerebral Blood Flow & Metabolism.

Image source: Antonino Paolo Di Giovanna et al./CC BY-NC-ND 4.0.

  • Transplants of stem cells “cure” anemia in mice. Chronic kidney disease affects 30 million humans in the USA alone. Anemia is the decrease in total red blood cells. People whose kidneys are damaged can develop anemia, as the kidneys are responsible for making the hormone erythropoietin (EPO) that is key to triggering the production of red blood cells. This means the patient lacks enough red blood cells to carry oxygen around the body as effectively. In the present study, stem cells from human cord blood were induced into becoming pluripotent cells that were then coaxed into becoming cells that produce EPO. The cells were transplanted in the kidney cavities of mice with a form of anemia. Within 4 weeks, EPO levels were 20 times higher than those in controls. “Just one transplant of the human EPO-producing cells treated kidney anaemia in mice, keeping their haemoglobin levels in the normal range for the remaining 7-month lifespan of the animals,” says Kenji Osafune, of Kyoto University in Japan, who led the team. This research was published in the journal, Science Translational Medicine.
  • Anti-Dengue Antibody protects against Zika Virus Infection. Dengue and Zika are caused by related viruses, and as such, Professor Diamond and co-authors reasoned that an antibody, EDE1-B10, that prevents dengue disease may do the same for Zika. To accomplish this they infected nonpregnant adult mice with Zika and then administered the EDE1-B10 antibody in as series of experiments. They found that that for the antibody to effectively protect fetuses from Zika infection, it must be administered soon after infection.“Such a goal may be unrealistic clinically because women rarely know when they get infected,” the scientists noted.“However, giving women the antibody as soon as they know they are pregnant could provide them with a ready-made defense against the virus should they encounter it.” This research was published in the journal Nature Immunology.

 

Canada sees rise in animal research numbers in 2016

The Canadian Council on Animal Care is the national peer-review organization responsible for setting, maintaining, and overseeing the implementation of high standards for animal ethics and care in science throughout Canada.  Yesterday it released the 2016 statistics describing the numbers and species of animals utilized in science.  It shows that 4,308,921 animals were used in research in 2016. The report also included statistics regarding the purpose and severity of the research procedures.

CC-BY speakingofresearch.com

Animals used in research in Canada in 2016. Click to Enlarge

CCAC certified institutions utilized 4,308,921 animals in 2016, representing a 20.7% increase over 2015.  While the vast majority of Canadian institutions report animal use numbers to the CCAC, it is unclear if the general trend of increasing animal use number is reflective of an actual increase in the number of animals participating in studies or rather that more institutions are participating in the CCAC certification process.  Further information on the CCAC can be found here.

CC-BY: speakingofresearch.com

Fish were the most utilized species representing 1,602,547 (37.2%) of all animals.  This was consistent with the 2014 data but a change for the 2015 statistics that saw mice as the primary species.  Mice still saw a 7% increase to 1,500,156 (34.8%) animals.  While different from many other countries cattle maintain their position as the third most reported species with 526,249 (12.2%).

Fish, mice and cattle together represent 84.2%, with rats and birds making up a further 10.2%. Dogs (15,093), cats (8,526) and primates (7,556) together continue to represent less than 0.8% of all animals used in science in Canada.  It is worthwhile noting that these numbers also include 30 cephalopod invertebrates but do not include other invertebrate animals that are also extensively used in research, such as the fruit fly Drosophila Melanogaster and nematode worms.

Trends

CC-BY speakingofresearch.com

The trend over time in animals used in research in Canada. Click to Enlarge.

Animal studies have been increasing steadily among CCAC members over the past twenty years – more than doubling over the time period. This may reflect similar increases in biomedical research funding by the Canadian Institutes of Health Research (CIHR is not the only organization funding biomedical research in Canada).

Severity

Severity of Animal Procedures in Cananda - Animal Experiments 2016 Table

Severity of animal research in the Canada in 2016. Total number of procedures is higher than number of animals due to reused animals being counted more than once.

In comparison to the 2015 statistics, there was an overall total percentage increase of 7.4% to 38.5% of animals in the lowest severity category.  This category would include the breeding or animals that were anesthetized and did not wake from procedures.  Animals experiencing mild severity (ie. a blood sample or injection) saw a drop of 6.6% to 30.8%.  While animals representing moderate (ie. surgery with appropriate pain control) and severe (ie. pain-related research) remained relatively consistent at 28.5% and 2.2% respectively.  The purpose of animal experiments was for basic research (57.2%); development of products or appliances for human or veterinary medicine (14.1%); studies into human and animal diseases or disorders (12.9%); education and training (9.7%); and finally regulatory tests (“animal testing”) (6.1%).

Michael Brunt

Source of Canadian Statistics: https://www.ccac.ca/en/news-and-events/news/2017/explore-the-ccac-animal-data-report-2016.html

See previous years’ reports:

Speaking of Research response to FDA announcement regarding nicotine research

For immediate release

Speaking of Research response to FDA announcement regarding nicotine research

Late on September 25, as reported by the Washington Post, the US Food and Drug Administration (FDA) made the startling announcement that it has suspended a nicotine research project involving non-human primates; the goal of this research is to build a better scientific approach to preventing and treating smoking and its associated health complications. The FDA has not yet provided evidence or clear justification for why they took this action. This lack of transparency is concerning not only for halting an important research program that had the potential to improve human health, but also for the welfare of the animals involved.

The FDA yesterday began a review of animal welfare at the National Center for Toxicological Research (NCTR) where the research was conducted. The reason given for the review is four animal deaths that occurred over an unspecified time period. Whether the deaths were associated with the research procedures is also unspecified. While it is not clear when the deaths occurred, the article and timing of the announcement followed closely after publicity from a letter by celebrity primatologist Jane Goodall to the FDA Commissioner, stating her opinion that the research should be halted. Furthermore, Dr. Goodall has aligned herself with an anti-animal research group, The White Coat Waste Project, which perpetuates the notion that research addressing the health problems associated with substance use disorders, including problematic tobacco use, in animals is unethical. Together, these events raise the extremely disturbing possibility that the FDA may have relied on claims provided by individuals with no scientific background or expertise in addiction science to make their decision, rather than on sound scientific evidence.

In an open letter posted at Speaking of Research on September 22, dozens of scientific experts, including the many of the nation’s leading scientists conducting research into drug abuse and alcoholism, expressed deep concern over Dr. Goodall’s egregious and unscientific remarks.  Research into the biological effects of nicotine using primate models has, and continues to be, critical for understanding and development of medications for tobacco use, which is unquestionably a major public health problem worldwide.  That this research could be halted due to political reasons is outrageous, and speaks to the influence of a group opposed to animal research and their celebrity allies over science that impacts the health and care of our citizens.

Dr. J. David Jentsch, a spokesperson for Speaking of Research said:

“Speaking of Research condemns the lack of transparency surrounding the decision to halt important research into understanding addiction.  We call on the FDA to provide much greater transparency on this issue, including a full explanation as to why they have cancelled the studies, and information on the findings of any and all inspections of the NCTR facility leading up to this decision.  

“We are gravely concerned over the influence that Jane Goodall and the animal rights organization The White Coat Waste Project appear to have over FDA research. Animal research remains a critical component of our understanding of disease and the development of new treatments to tackle them. The FDA must be led by the advice of the research community, not from those minimal understanding of key scientific issues.”

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Squirrel monkey.

Mice and the Mycobiome: How Animal Models Will Help Us Understand the Microbial World In Our Gut

Rebecca Drummond, PhD, is a post-doctoral scientist working at the National Institutes of Health, USA. Dr Drummond’s research aims to understand why some people get fungal infections and others do not. To do this she must understand how the immune system prevents fungal infections and the risk factors that make an infection more likely. In this blog, Rebecca explains how mice can help us to understand how bacteria and fungi can affect the immune system and development of gut-related disorders, like irritable bowel disease (IBD).

Our intestines are home to billions of microbes, which help digest food and maintain a healthy immune system. These microbes, known as the ‘microbiome’, are a mixture of bacteria, fungi and viruses, and individual species can have a huge impact on the health of our gut. The bacteria in our microbiome has been studied for decades, using samples from human volunteers and mice. While human research has allowed us to make connections between microbiome patterns and disease, it’s the work with mice that actually help us understand the fine details of how bacteria in our gut may cause or prevent disease. In contrast to research on gut bacteria, research into the fungal population (the ‘mycobiome’) within our intestines has lagged behind. This is because this branch of life is often underappreciated and misunderstood, but this is now beginning to change and recent studies indicate that the mycobiome can profoundly impact the health of our gut.

Since fungi are common inhabitants of our intestines, one of the major interests in the field is how these intestinal fungi affect the health of our gut and what harm they might do if they ‘escape’. Fungal infections are one of the hardest to diagnose and treat, killing more than 2 million people every year and are also responsible for exacerbating other diseases like asthma and inflammatory bowel disease (IBD). Yet, fungi receive a surprisingly small amount of attention in the news and research community.

Microscopy image of fungi in a mouse intestine. Yeast cells interact with the cells of the intestine (epithelium) and mucus. Image courtesy of Dr Simon Vautier, NIH.

It’s therefore important to understand how our immune system handles fungi and prevents an infection. It’s well accepted that some species of bacteria in our gut can promote healthy intestines (probiotics or ‘good bacteria’ – you’ve probably seen these sold in yoghurt at the supermarket), while other bacteria can cause stomach ulcers. It’s therefore reasonable to assume that different fungal species might have similar benefits or health risks, and some recent research has shown that this is the case. For example, inflammatory bowel disease (IBD) is a condition where the immune system attacks the intestine for reasons that we don’t yet fully understand, and it’s long been known that proteins in our blood (antibodies) that stick to a fungus called Saccharomyces cerevisiae (anti-S. cerevisiae antibodies: ASCA) correlate with the incidence of IBD. So, if you have IBD, it’s likely that you have more ASCA in your blood. Moreover, mutations in genes that are needed to activate immune responses against fungi have been repeatedly linked to IBD and an overgrowth of fungi in the gut. Studies using samples from IBD patients have shown that a disturbance (‘dysbiosis’) of the mycobiome is a common occurrence in IBD; patients with IBD have increased amounts of a fungus called Candida albicans, and the ratio between different fungal species is not normal in IBD patients compared to people who have never experienced IBD.

It’s therefore important to understand how our immune system handles fungi and prevents an infection. It’s well accepted that some species of bacteria in our gut can promote healthy intestines (probiotics or ‘good bacteria’ – you’ve probably seen these sold in yoghurt at the supermarket), while other bacteria can cause stomach ulcers. It’s therefore reasonable to assume that different fungal species might have similar benefits or health risks, and some recent research has shown that this is the case. For example, inflammatory bowel disease (IBD) is a condition where the immune system attacks the intestine for reasons that we don’t yet fully understand, and it’s long been known that proteins in our blood (antibodies) that stick to a fungus called Saccharomyces cerevisiae (anti-S. cerevisiae antibodies: ASCA) correlate with the incidence of IBD. So, if you have IBD, it’s likely that you have more ASCA in your blood. Moreover, mutations in genes that are needed to activate immune responses against fungi have been repeatedly linked to IBD and an overgrowth of fungi in the gut. Studies using samples from IBD patients have shown that a disturbance (‘dysbiosis’) of the mycobiome is a common occurrence in IBD; patients with IBD have increased amounts of a fungus called Candida albicans, and the ratio between different fungal species is not normal in IBD patients compared to people who have never experienced IBD.

Candida albicans is found as a yeast in our gut. Image from Wikipedia

In human studies like this, we can only ever make assumptions from this type of data, but it is difficult, if not impossible, to determine causality. It’s not clear whether the mycobiome dysbiosis in IBD patients is a cause of the IBD, or a consequence. To help understand these sorts of correlations and make sense of them, we can use mice as a model system. Mice are commonly used for immunology research because the immune system is similar between different species of mammals; mice have the same types of immune cells that carry out similar functions as their human counterparts. We know this because mutations in genes that are important for preventing IBD or fungal disease cause similar diseases in mice as they do in humans. Mice also provide us with a way of obtaining samples of intestine tissue, since it would be difficult to find human volunteers for such research which would also suffer from the lack of laboratory controls. The complexity of the gut also means that we can’t use petri-dishes, because we simply can’t model the thousands of interactions happening in the gut in a petri-dish.

We can also breed mice so that they have no bacteria or fungi in their intestines. These are known as ‘germ-free’ mice and are particularly useful for studies that want to analyze how an individual species of bacteria or fungi affects the intestinal immune system and our metabolism; something that isn’t possible to do in humans. To give an example, if you take germ-free mice and feed them the yeast S. cerevisiae (the one that ASCA binds to and indicates IBD), you can make the symptoms of IBD worse. Researchers showed that this was because S. cerevisiae caused a build-up of uric acid as it grew in the intestine. Uric acid activates our immune cells so they become over-excited and start to attack the intestine, basically causing symptoms of IBD. These types of experiments can help us understand the possible mechanisms resulting in IBD and the roles our microbiota might play in the development of this disease.

Germ-Free Animal Facility. Animals are bred and kept within isolator units to keep them sterile from outside bacteria, fungi and other microbes found in the environment. Photograph courtesy of Yasmine Belkaid, NIAID, NIH.

In addition to looking at individual species, we can also use mice to understand relationships between bacteria and fungi living together side-by-side in the gut. Changing the amount of fungi in the gut, by introducing a new species in the diet or depleting lots of fungi at once with antifungal drugs, subsequently changes the amounts of different bacteria in the gut. The same is true when you do the opposite experiment – antibiotic treatment (which kills off the bacteria, not the fungi) causes fungi in the intestine to grow like crazy, a phenomenon known as a fungal bloom. These blooms are thought to be one of the ways a patient could contract a dangerous blood-poisoning fungal infection called systemic candidiasis, which if treated, still only has a 50/50 chance for survival.

So, if fungi can exacerbate IBD and be a potential source for blood-poisoning, should we be treating patients with antifungal drugs to prevent this? For IBD at least, mouse models suggest that this strategy won’t work. Mice treated with antifungal drugs weren’t helped at all – they actually developed worse IBD after treatment than mice that were left untreated. This was because the antifungal drug treatment doesn’t completely get rid of all the different species of fungi in the gut. Instead, you get rid of some species, and the remaining fungi (which are resistant to the drugs) start to grow and takeover. This is what we call a dysbiosis of the mycobiome, and we’ve seen it before – in patients with IBD.

The number of papers discussing the mycobiome has seen a 10-fold increase since 2013, indicating that awareness of fungi and fungal infections is on the rise. More research is needed to understand our relationship with fungi and this critically depends on using animal models, without which we wouldn’t have learned how the fungi and bacteria in our guts exacerbate diseases like IBD. By better understanding this, we can begin to decide what to do about it and develop treatments for the future.

Rebecca Drummond

Research Roundup: Mouse model of bipolar disorder shows promise, fighting cancer with Polio and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • Genetically modified mice show promise for studies of bipolar disorder. Human bipolar disorder is characterised by alternation between manic (hyperactive) and depressive (hypoactive) states, but many of its symptoms can be alleviated by treatment with lithium. A new study from Johns Hopkins University discovered that mice engineered to lack the protein ankyrin-G show manic-like states, characterised by over-excited activity and reactions, which could be ameliorated by lithium treatment. Moreover, repeated stress resulted in alternation between “mania-like” and “depression-like” status, reminiscent of human bipolar disorder. Ankyrin-G is a neuronal protein involved in the initiation of action potentials (electrical pulses used by neurons to communicate messages). “To our knowledge, this is the first robust mouse model of bipolar disorder based on a genome-wide significant risk factor for the human disorder”, said Christopher Ross, M.D., Ph.D., professor of psychiatry and behavioral sciences at Johns Hopkins.  This research was published the journal PNAS.
  • Turning “bad” fat into “good” fat could treat obesity. There are two types of adipose tissue in mammals: white fat and brown fat. Brown fat is considered “good” because, unlike white fat, it is metabolically active and burns calories to generate heat. In contrast, white fat simply stores energy and deposits around the waist, hips, and thighs. Scientists discovered that blocking a protein called PexRAP caused white fat in mice to be turned into “beige” fat, a new type of fat in between white and brown. Beige fat acts more like brown fat and may protect against obesity. Mice that were born without the PexRAP protein had more beige fat, were leaner than their littermates, and burned more calories even when they consumed the same amount of food. If PexRAP can be blocked in human fat cells, people with obesity, which represent 9% of the US population, may have an easier time reaching a healthy weight. This research was published in Cell Reports.

  • Blocking a signaling molecule in brain cells can stop the spread of aggressive brain tumors. Certain human brain cancers called high-grade gliomas are incredibly deadly with five year survival rates for some types around 10 percent. Researchers at Stanford University have uncovered a molecule that when deleted can halt the progression of these tumors. This signaling molecule, called neuroligin-3, had been shown in previous experiments to cause gliomas to grow. Working off of this knowledge, scientists put glioma cells in the brains of mice that had the neuroligin-3 gene and those whose gene had been deleted. They discovered that the cancer cells grew in the brains with neuroligin-3, but growth was halted in the neuroligin-3 deficient mice. Two inhibitors of neuroligin-3 had already been developed and so the researchers tested in mice whether either or both of these drugs would similarly halt the progression of the tumors. And they did. The senior author on the article, Michelle Monje, MD, PhD, stated, “We have a really clear path forward for therapy; we are in the process of working with the company that owns the clinically characterized compound in an effort to bring it to a clinical trial for brain tumor patients.” This research was published in the September 20th edition of Nature.
  • Fighting cancer with Polio.  In recent years, scientists have invested their interest in modified viruses, such as oncolytic viruses, which are optimized to kill cancer cells without damaging healthy tissue surrounding the cancer cells. One of these viruses is an engineered version of poliovirus, however it has been unclear how this virus manages to kill the cancer cells without harming the healthy tissue. This week, a study published in Science Translational Medicine, determined that the modified poliovirus, PVSRIPO, actually stimulates the natural immune system to specifically target the cancer cells. Normally, the immune system slows some types of tumor growth and inhibits tumors from becoming problematic, but when the immune system is suppressed this system no longer works. PVSRIPO seems to overcome immunosupression and may open doors to further cancer research targeting immunosupression.

Molecular model of poliovirus. Photo credit: Karsten Schneider/Science Photo Library

  • Ethical concerns growing after genome editing of human embryos. This week the journal Nature published results of experiments that used CRISPR-Cas9 to modify the DNA of a human embryo. They found that the gene OCT4 could steer cell fate as a fertilized egg starts to divide and proliferate. Another study, published just last month in Nature, used the same CRISPR-Cas9 method to correct specific genetic mutations in early stage human embryos. Both studies provide important insights into the biology of human embryos, and may pave new methodologies for in-vitro fertilization (IVF). Concerns are growing however because such gene-editing methods could lead to permanent modifications, and we do not yet understand the safety, accuracy, and feasibility of genome editing as a clinical tool. Thus, although this research is exciting and promising, much basic research and ethical discussions are necessary before we can take advantage of it.
  • A new antibody is able to attack 99% of HIV strains, according to studies in primates. The collaboration between NIH and the pharmaceutical Sanofi involves combining three “broadly neutralising antibodies” to create a “tri-specific anibody” which is able to tackle 99% of HIV strains. Dr Fauci, noted, “Combinations of antibodies that each bind to a distinct site on HIV may best overcome the defences of the virus in the effort to achieve effective antibody-based treatment and prevention.” Twenty-four monkeys were involved in the experiments, and none of those that received the antibodies developed an infection when they later received the HIV virus. Clinical trials are now planned for next year. This research was published in Science.

Jane Goodall and White Coat Waste are wrong about nicotine addiction research

This open letter is from scientists and leaders in the addiction research community.  If you’d like to join the signatories listed below, please do in comments at the bottom of this article. Please also share with others with an interest in research on addiction.

Smoking – and nicotine addiction – are sometimes easy targets for criticism by many people. For others, addiction is a mental health issue of deep concern, affecting one in seven Americans during their lifetime, often resulting in immeasurable suffering and even death.  There are many reasons that addiction can be an easy target and perennial candidate for ridicule. One is that some believe addiction is “simply a matter of weak willpower,” evidence of a “moral failing,” or some other character flaw. In this, we see parallels to medieval beliefs that schizophrenia, bipolar disorder, and depression were due to witchcraft, demonic possession, wandering uteruses, and weak moral character.

Addiction is a brain disorder

Through decades of scientific study of the brain, behavior, genetics, and physiology, we now know that addiction is a complex disorder affected by neural function, genes, and the environment. We also know – at a specific level – about the brain chemistry and circuits that increase the risk for and play a role in addiction—including smoking. Unfortunately, there is still a lot we do not know, including questions such as: Why are some individuals vulnerable to addiction and others not? Why does relapse after any kind of treatment occur at such phenomenally high rates? Why do drug abusers persist in seeking and taking substances that so clearly will lead to incarceration, poverty, even death?

It is these gaps in knowledge – along with empathy for those suffering because of addiction—that lead the nation’s health research agencies to actively support addiction research. Yet, there are others who seek to end this lifesaving research. For example, a months-long campaign by the anti-animal research advocacy group White Coat Waste Project targeting nicotine addiction research recently got a boost from Jane Goodall, the celebrity primatologist known for research on chimpanzee behavior. This marks yet another high profile pairing of Goodall and groups fundamentally opposed to all nonhuman animal research. Here, Goodall wrote to the head of the US Food and Drug Administration (FDA) about research on nicotine addiction in monkeys conducted at the FDA’s National Center for Toxicological Research (NCTR).

Addiction costs the US billions each year

What Goodall claims is that the research is a misuse of taxpayer’s money because of her belief that ‘the results of smoking are well-known in humans’, and that the same research can be done in humans. Both statements are shocking, no less so because they come from a prominent scientist whose very profession is based on reporting facts.

Even a cursory glance at the state of tobacco use in the US gives some clues as to why statements like this are irresponsible: According to the National Institute on Drug Abuse (NIDA), tobacco use kills approximately 440,000 Americans each year. Given the White Coat Waste Project’s interest in saving the taxpayer’s money, the estimated economic impact of tobacco use, including everything from healthcare costs to cigarette-related fires, is almost $200 billion per year (see NIDA Research Report Series online, 2012). So, clearly nicotine addiction remains a significant public health problem and it is quite evident that we do not understand this disorder well enough to eradicate it—current treatments basically have just slowed it down. There is much work to do.

Outright wrong: the FDA nicotine research Goodall targets is not taxpayer funded

There is another blatant inaccuracy in Goodall’s letter to the FDA, namely, the very idea that this is a fraudulent waste of taxpayer’s money. In fact, the funding source for NCTR nicotine research is the Center for Tobacco Products (CTP), which was established to oversee implementation of the Family Smoking Prevention and Tobacco Control Act of 2009.

What is important here is that CTP funding comes from “tobacco user fees” charged to manufacturers of tobacco products. In other words, no taxpayer’s money is funding this research. How can the public trust any claim by Goodall and White Coat Waste if even this basic fact was ignored?

Why research with humans cannot answer the full range of questions

What is lost in the simple formulation that Goodall uses is the fact that research with humans cannot answer fundamentally important questions that are basic to progress in understanding, preventing, and treating addiction. Species other than humans take drugs. The fact that monkeys and rodents “self-administer” drugs in a manner similar to humans provides scientists with an extremely valuable model of drug addiction. The discovery of the “reward center” in the brain, the role of the chemical dopamine, even the basic principles of many behavioral therapies for addiction—all of these basic findings come from studies with monkeys and/or rodents self-administering drugs. In fact, the discovery that nicotine is the primary ingredient of tobacco products that contributes to their addictive properties, as well as the designation of nicotine as a drug of abuse, relied on self-administration studies. And yet, we are just at the beginning of understanding addiction as a brain disorder (rather than a simple moral failure or a series of bad decisions).

Instead of using monkeys in nicotine addiction research, Goodall suggests that ‘smoking habits’ can be studied ‘directly’ in humans. These two scenarios are entirely different—you don’t study ‘smoking habits’ in monkeys (who generally don’t go to the local gas station for some smokes). Smoking habits are an incredibly important part of nicotine addiction, but studying nicotine self-administration has entirely different goals. For example, the NCTR researchers are interested in brain changes following nicotine taking in adults and adolescents. What the monkey experiments allow them to do is isolate just nicotine (burning tobacco creates approximately 7000 chemicals)

and study its effects in a highly controlled environment. This approach allows the researchers to draw much firmer conclusions about effects on brain function than could ever be obtained in people smoking cigarettes. To treat nicotine addiction, we have to know precisely what nicotine does to the brain, and we need to do this in a systematic, carefully controlled manner.  We also need to know, however, what all the other chemicals are doing in order to understand the “real life” situation.  Studying nicotine alone provides a platform for going about doing those types of studies, eventually recreating the real life experiences of the tobacco abuser.

Absolutism is different from consideration of animal welfare

Research in laboratories with animals is conducted humanely, ethically, and under careful oversight guided by federal and state laws, regulations, guidelines, and by institutional policy.  Importantly, it is unclear what evidence Goodall and White Coat Waste have for any serious violations of regulations at the FDA facility. It may be the case that Jane Goodall and White Coat Waste are opposed to animal research that is conducted in order to benefit human health. That is a different argument, however, than saying that addiction research is unnecessary, that human studies are all that is needed, or that the animals are abused. We in the scientific community wholeheartedly support ethical, humanely-conducted research on addiction to nicotine and other drugs of abuse, which is in the public’s interest. At the same time, we condemn this irresponsible and factually-challenged assault on research at the NCTR.

Conclusion

We, the undersigned, support the careful, considered and regulated use of primates in addiction research. While respecting Dr. Jane Goodall as an eminent primatologist—known for her knowledge of chimpanzee behavior in the wild—we do not believe she has the necessary expertise to intervene into the scientific questions of addiction research and neuroscience. Addiction is a major public health issue worldwide, and requires and deserves close scientific scrutiny, some of which will require the use of animals.

James K. Rowlett, Ph.D., Professor and Vice Chair for Research, Department of Psychiatry & Human Behavior, University of Mississippi Medical Center

Jack E. Henningfield, Ph.D., Vice President, Research, Health Policy, and Abuse Liability, Pinney Associates, Inc. and Professor, Department of Psychiatry, Johns Hopkins University School of Medicine

Marina Picciotto, Ph.D., Charles B.G. Murphy Professor of Psychiatry and Professor in the Child Study Center, of Neuroscience and of Pharmacology, Deputy Chair for Basic Science Research, Dept. of Psychiatry, Deputy Director, Kavli Institute for Neuroscience, Yale University

Travis Thompson, Ph.D., L.P., Professor, University of Minnesota; Past President of American Psychological Association Division of Psychopharmacology and Substance Abuse; Past Member, College on Problems of Drug Dependence Executive Committee

Charles P. France, Ph.D., Robert A. Welch Distinguished University Chair in Chemistry, Professor of Pharmacology and Psychiatry, University of Texas Health Science Center- San Antonio

Michael A. Nader, Ph.D., Professor of Physiology, Pharmacology, and Radiology and Director, Center for the Neurobiology of Addiction Treatment; Co-Director, Center for Research on Substance Use and Addiction, Wake Forest School of Medicine

Thomas Eissenberg, Ph.D., Professor of Psychology (Health Program) and
Director, Center for the Study of Tobacco Products, Virginia Commonwealth University

Nancy A. Ator, Ph.D., Professor of Behavioral Biology, Johns Hopkins School of Medicine

Roger D. Spealman, Ph.D., Professor of Psychobiology, Department of Psychiatry, Harvard Medical School

Kathleen A. Grant, Ph.D., Chief and Senior Scientist, Division of Neuroscience, Professor, Dept. Behavioral Neuroscience, Oregon National Primate Research Center

Alan J. Budney, Ph.D., President, College on Problems of Drug Dependence, Past President, Division of Psychopharmacology and Substance Abuse (28) and the Division on Addictions (50) – American Psychological Association, Professor, Geisel School of Medicine at Dartmouth

Peter W. Kalivas, Ph.D., Professor and Chair, Department of Neuroscience, Medical University of South Carolina

Marilyn E. Carroll, Ph.D., Professor of Psychiatry and Neuroscience, Department of Psychiatry, University of Minnesota

Craig A. Stockmeier, Ph.D., Professor, Dept Psychiatry & Human Behavior, University of Mississippi Medical Center

Janet Neisewander, Ph.D., Professor, School of Life Sciences, Arizona State University

Mary E Cain, PhD, Professor of Psychological Sciences, Past President for Behavioral Neuroscience and Comparative Psychology, Kansas State University

Wei-Dong Yao, PhD, Professor, SUNY Upstate Medical University

Lance R. McMahon, PhD, Chair and Professor of Pharmacodynamics, College of Pharmacy, University of Florida

Michael N. Lehman, Ph.D., Professor and Chair, Department of Neurobiology and Anatomical Sciences, Chairman of the Board, UMMC Neuro Institute, University of Mississippi Medical Center

Donna M. Platt, Ph.D., Associate Professor, Department of Psychiatry & Human Behavior, University of Mississippi Medical Center

Michael A. Taffe, Ph.D., Associate Professor, The Scripps Research Institute

Linda J. Porrino, PhD, Professor and Chair, Wake Forest School of Medicine

Kevin B. Freeman, Ph.D., Associate Professor, Department of Psychiatry & Human Behavior, University of Mississippi Medical Center

Mei-Chuan Ko, Ph.D., Professor, Wake Forest School of Medicine

Sally L. Huskinson, Ph.D., Instructor, Department of Psychiatry & Human Behavior, University of Mississippi Medical Center

Mark Smith, PhD, Professor, Department of Psychology and Program in Neuroscience, Davidson College

Daniel C. Williams, Ph.D., Associate Professor, Director, Division of Psychology, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center

Eric J. Vallender, PhD, Associate Professor, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center

Matthew Banks, PharmD, PhD, Assistant Professor of Pharmacology and Toxicology, Virginia Commonwealth University

Paul May, Ph.D., Department of Neurobiology & Anatomical Sciences, University of Mississippi Medical Center

Juan Carlos Marvizon, Ph.D., Adjunct Professor, UCLA, VA Greater Los Angeles Healthcare System

Catherine M. Davis, PhD, Assistant Professor, Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine

Klaus A. Miczek, Ph.D., Moses Hunt Professor of Psychology, Psychiatry, Pharmacology, & Neuroscience, Tufts University, Department of Psychology

Wendy J. Lynch, Ph.D., Associate Professor of Psychiatry and Neurobehavioral Sciences, University of Virginia

Michael T. Bardo, Professor of Psychology, Director, Center for Drug Abuse Research Translation (CDART), University of Kentucky

Xiu Liu, MD, PhD, Professor, Department of Pathology, Associate Director, Graduate Program in Pathology, University of Mississippi Medical Center

Katherine Serafine, PhD, Assistant Professor of Behavioral Neuroscience University of Texas at El Paso, Department of Psychology

Robert L. Balster, PhD,  Butler Professor of Pharmacology and Toxicology, Research Professor of Psychology and Psychiatry, former CoDirector of the Center for the Study of Tobacco Products, Virginia Commonwealth University, Richmond, VA

David Jentsch, Ph.D., Professor of Psychology, Binghamton University

William W. Stoops, Ph.D., Professor, University of Kentucky College of Medicine

Jack Bergman, Ph.D., McLean Hospital / Harvard Medical School

Barry Setlow, PhD, Professor, Department of Psychiatry, University of Florida College of Medicine

Doris J. Doudet, PhD, Professor, Dept. Medicine/Neurology, University of British Columbia

Leonard L. Howell, PhD, Professor of Psychiatry and Behavioral Sciences, Emory University

S. Stevens Negus, PhD, Dept. of Pharmacology and Toxicology, Virginia Commonwealth University

Carrie K. Jones, Ph.D., Director, In Vivo and Translational Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University

 

 

 

 

 

 

The Problem With Jane Goodall’s “Expert” Opinion

On September 7, 2017, Dr. Jane Goodall wrote a scathing letter to Dr. Scott Gottlieb, Commissioner of the U.S. Food & Drug Administration (FDA) denouncing what she called the “cruel and unnecessary nicotine addiction experiments on monkeys” occurring there. The letter, which relies on the repeated use of opinion versus fact-based arguments by Goodall, is not just problematic, it’s downright dangerous.

This is not Goodall’s first time lending her name to various efforts by animal rights activists opposed to federally-supported biomedical and behavioral research, despite her lack of expertise or relevant credentials. Goodall has often partnered with animal rights groups to attack life-saving science. In March 2016, she supported a campaign by the Animal Justice Project to stop preclinical trials of a new malaria vaccine. In September 2016, Goodall joined Cruelty Free International (CFI) to co-author a letter attacking the use of animals in neuroscience research (to which a counter-letter, signed by 400 prominent experts in the field, was published). In February 2017, Goodall worked with For Life on Earth to call out Prof. Roger Lemon, a notable Professor of Neurophysiology, to criticize his comparative work with both humans and non-human primates.

Squirrel monkey. Source: Wikimedia Commons.

As detailed here, her most recent letter to the FDA, in partnership with The White Coat Waste (WCW) Project, a conservative-leaning animal rights organization devoted to the elimination of animal research, relies on the repeated use of opinion rather than empirical observations or rigorous study to arrive at sweeping – and dangerous – conclusions.  

The problems

We’ll tackle this letter in particular, though past letters signed by Goodall and other notable figures like David Attenborough, are similarly flawed and should be similarly scrutinized.

  • No relevant credentials or expertise: This one bears repeating. Although this should be obvious, to many it is not. Though she possesses a PhD and is described as an expert on chimpanzees, Goodall’s “expertise” ends there. She does not possess an advanced degree pertinent to the field of addiction research, and moreover she has never conducted research in a biomedical research facility. Thus, her first-hand knowledge of the methodology and oversight in these types of studies is questionable at best. Would you consult a cardiologist for questions about your car’s transmission?  Or, conversely, consult an auto mechanic about your open heart surgery? In fact, Dr. Goodall appears to recognize this. For example, in her video targeting Prof. Roger Lemon, midway through the video Goodall notes: “I don’t have the scientific medical knowledge to take issue with Professor Lemon” before going on to demand he debate pseudoscientist, Dr. Ray Greek. The problem here is that the weight given to Goodall’s opinion is directly related to impressions of her expertise and credentials. This issue of ethics of expertise is an important one. Goodall herself may not be directly claiming to be a neuroscientist, or an addiction researcher, but one of the reasons that her opinion may be thought valuable in these campaigns is because she is a scientist. As as scientist, it is worth considering whether Goodall should be upfront about her lack of expertise in the topic at hand. In fact, Goodall’s conclusion that the research is “unnecessary” and that “the results of smoking are well-known in humans” are opinions, rather than statements based in evidence and expert analysis.

    “I don’t have the scientific
    medical knowledge…”
    – Jane Goodall

  • “I have been told that…”: This should immediately set off alarm bells to anyone reading Goodall’s letter. Forget what comes after that – who has told her what she describes? As we have noted in the past, it’s crucial to know the starting assumptions of those engaging in a conversation, and the assumptions must be spelled out. In this case, it is no secret that Goodall has worked with The White Coat Waste (WCW) Project, a conservative-leaning animal rights organization devoted to the elimination of animal research (this starting position itself is dangerous, as described below). The WCW’s site itself states, “On the heels of WCW’s new lawsuit against the Food and Drug Administration (FDA)…Dr. Jane Goodall has joined WCW’s campaign to expose and end this wasteful project.” Put simply: Goodall appears to rely only on information provided to her by animal rights groups to make the case in her letter.
  • Factual inaccuracies: Probably because she appears to rely on the distorted information from WCW, Goodall’s letter is full of multiple inaccurate statements. One example is when she writes, “Not only is it extremely cruel to restrain the monkeys.”  In reality, empirical evidence—that is data – show that restraint devices used in such studies do not cause severe stress to the animals, because they are slowly trained to be familiar with and calmly enter and remain in the restraint devices. Despite her scientific background—which should result in knowing that evidence and citations matter—Goodall cites no evidence for her claim that restraint is “extremely cruel.”
  • Sweeping assumptions: At least two glaring assumptions stand out in Goodall’s brief letter.
    1) Goodall writes, “To continue performing nicotine experiments on monkeys when the results of smoking are well-known in humans – whose smoking habits can still be studied directly – is shameful.” There are several problems with this statement. The first is that Goodall assumes that the monkey studies examining the neurobiology and physiology of nicotine addiction is the same thing as studying smoking habits in humans. Someone with expertise in this field should know these are false equivalencies. The only other plausible explanation is that she is choosing to ignore the fact that these two are not the same thing. The FDA describes on its webpage that nicotine research will inform about the toxicity of tobacco products as they continue to change by manufacturers, about how changes in tobacco product characteristics (e.g., aerosolized chemicals, often including nicotine, found in e-cigarettes) impact addiction, and about the changes in cell function/physiology after tobacco exposure. These types of findings are not readily available from studying humans’ smoking habits. 2) Near the end of her letter, Goodall writes, “I’m sure that most Americans would be horrified to learn that their tax dollars are paying for this abuse.” Again, Goodall makes major assumptions without citing any sources of data. We can just as confidently say that we’re sure most Americans would be glad to know their tax dollars are being used in highly-regulated research studies that address the health of current and future generations.

The dangers

  • Calls for de-funding life-saving research: The most recent nicotine delivery methods, e-cigarettes, have not yet been well studied for their health effects, yet they represent a major public health concern. We do not yet know all the ways in which nicotine in e-cigarettes affects the brain. Studies such as those conducted by the FDA in animals, including monkeys, will teach us how these new delivery methods affect the brain and body, which will in turn lead to recommendations for regulation of these products and potential treatments for addiction. Despite these life-saving benefits, Goodall and WCW call for an end to this line of research in their letter. This explicit threat should ring alarm bells for any citizen concerned about public health. But this is not the first time animal research opponents have called for an end to beneficial research. Just a week ago, the Secretary of the Department of Veterans Affairs (VA), Dr. David Shulkin, had to make a plea to the United States Senate to not end life-saving canine research after a campaign by – you guessed it – WCW called for an end to this line of work. Think about that. The VA Secretary had to lobby the U.S. Senate to save a life-saving research program for veterans.

  • Threats to the advancement of scientific knowledge: As if threats to life-saving research weren’t enough, animal rights campaigns that rely on “experts” like Goodall are also threatening to end – or have already ended – scientific programs geared toward broadening and enhancing society’s basic knowledge of the way the world works, from the toxic effects of vapors in e-cigarettes to the safety of new vaccines to the communication between neurons to mechanisms of stress resilience to…the list goes on. This type of basic knowledge is crucial before life-saving treatments can be developed. This implicit threat should ring alarm bells for any citizen, period.