Tag Archives: NIH

University of Wisconsin responds to dishonest petition attacking psychiatric research

What do you do if your university is the target of an aggressive publicity campaign that distorts and misrepresents the work of one of your most highly respected scientists? What do you do if hundreds of thousands of people sign a petition calling for a research project to be cancelled, even though the petition contains numerous errors of fact? What do you do if a media campaign, backed by several of the world’s largest animal rights groups threatens to undermine academic freedom and the research evaluation process at your University?

Do you ignore it? Do you give in? What do you do?

Infant rhesus monkeys playing in nursery. Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

Infant rhesus monkeys playing in nursery. Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

These are questions that the University of Wisconsin -Madison has faced in recent weeks as a change.org petition that seeks to end a research project led by Professor Ned Kalin, chair of the University’s Department of Psychiatry. The petition, backed by many animal rights groups across the world, including PeTA and HSUS, has gathered more than 300,000 signatures

So did UW-Madison give in? Did they simply ignore the petition?

No, they did something much better.

UW-Madison issued the response below rejecting the erroneous claims made by the author of the petition, Dr Ruth Decker, and defending Professor Kalin’s right to undertake important research. Just as importantly they defend the right of the scientific and medical experts at UW-Madison and the NIH – and not the misinformed mob – to decide which projects should be approved and funded.

We commend UW-Madison on taking this strong position in support of science.

Responding to Ruth Decker’s change.org petition

Since September, many people have taken interest in a University of Wisconsin–Madison study on the impact of early life stress on young rhesus monkeys. Thousands have added their names to a petition on the website change.org, calling for an end to the work, and we appreciate and share their concern for animals.

But we don’t appreciate the way petition’s author, Dr. Ruth Decker, misrepresents the research. By piling up mistakes, myths and exaggerations, and omitting important information, she asks well-meaning people to speak out with little understanding of the real science and the long, deliberative process through which it was approved.

This isn’t fair to the people who signed the petition, or to UW–Madison psychiatry professor Ned Kalin and the scientists involved in the work, or to the millions of people who suffer from mental illness for whom available treatment methods offer little relief.

The truth is of little concern to activists who wish to end animal research, no matter the benefit to humans and animals. We don’t share that sentiment. We prefer people make their judgments on animal research with a fuller understanding of the research — of both its costs and potential benefits.

So, if you have read the change.org petition, please also consider these corrections and additional information:

  • This is not a repeat of experiments UW–Madison psychology professor Harry Harlow conducted as many as five decades ago, some of which subjected animals to extreme stress and isolation. The methods for the modern work were selected specifically because they can reliably create mild to moderate symptoms of anxiety in the monkeys. They were chosen to minimize discomfort for the animals, and to minimize the number of animals required to provide researchers with answers to their questions.
  • There is no “solitary confinement.” The animals live in cages with other monkeys of their own age, a method of care called peer rearing. This method is often used when mothers reject their infant monkeys, which happens regularly in situations from nature to zoos to clinical nurseries with first-time mothers or following caesarean-section births. In a group setting, even veterinarians would have difficulty distinguishing the peer-reared animals from those that that were maternally reared.

The purpose of peer rearing is not to demonstrate that removing a monkey from its mother causes anxiety, a common misconception we have heard from people who have signed the petition.

Again: peer rearing was chosen because it is known to produce mild to moderate anxiety symptoms. With a group of animals predisposed to anxiety raised in a controlled setting, researchers can use state-of-the-art techniques to observe and measure even very subtle differences in brain chemistry and structure. Those chemical and anatomical differences may suggest new treatments — via nutrition, exercise, meditation, drugs or another approach — for people suffering from mental illness.

  • The animals in the study are not “terrorized,” and do not experience “relentless torture.” Most of their time is spent as a house pet would spend its days — grooming, sleeping, eating and playing with toys, puzzles and other animals.

On occasion, to assess the monkeys’ level of anxious temperament, they are observed under two anxiety-provoking conditions. The first involves the presence of an unknown person who briefly enters the room, but does not make eye contact with the monkey. The second involves the monkey being able to see a snake, which is enclosed in a covered Plexiglas container in the same room, but outside the monkey’s cage.

After each event, the animal’s brain activity is monitored by a non-invasive functional magnetic resonance scan, and blood samples are taken. The stress the monkeys experience is comparable to what an anxious human might feel when encountering a stranger or a snake or a nurse with a needle.

  • No one was “left out” of the review by UW–Madison oversight committees. Several university committees spent a great deal of time assessing Dr. Kalin’s anxiety research, and each committee found it to be acceptable and ethical. These were groups of researchers, veterinarians and public representatives tasked with considering animal research on ethical grounds, and with ensuring potentially beneficial research will subject the fewest animals to the least invasive measures.

As the petition notes, an animal rights group took allegations about the committee process to the U.S. Department of Agriculture. What the petition does not mention is that USDA conducted an investigation in August in response to that complaint. Inspectors found the complaint lacking merit, and the process to be entirely within compliance with federal regulations.

And, as with all animal research on campus, specially trained veterinarians will care for the monkeys involved and ensure that all the work is done in accordance with federal regulations enforced by the National Institutes of Health and the USDA.

The decision to study animal models to understand human psychiatric disorders is not made lightly. Roughly a quarter of the people in the United States, including children, suffer from mental illness. Their conditions subject them to immeasurable disability and dysfunction. And the worst outcome, suicide, is increasing and already among the leading causes of death in adolescents. To develop effective treatments that may alleviate the suffering of millions, it is necessary to understand the root cause of psychiatric illnesses.

In this case, the human suffering is so great that Kalin, the National Institutes of Health and UW–Madison’s review committees believe the potential benefit of the knowledge gained from this research justifies the use of an animal model.

More information on the anxiety and depression research is available at animalresearch.wisc.edu.

Related posts:

Child health benefits from studies of infant monkeys – Part 1

Harlow Dead, Bioethicists Outraged

Speaking of Research

Child health benefits from studies of infant monkeys – Part 1

Health research with nonhuman primates takes place at many universities and research institutions in the US, among them centers funded by the National Institutes of Health (NIH).  A broad range of research aimed at better understanding maternal and child health takes place at these centers and depends, in part, upon humane, ethical scientific studies of infant monkeys.

A sample of the research areas and findings are highlighted below and provide a view of the value of developmental research. What even a short list shows is that the scope of scientific and medical research that informs pediatric health issues is large. It ranges from autism to childhood diabetes to leukemia to mental health to stem cell therapies.

Together, the findings from studies of infant monkeys have resulted in a better understanding of prenatal, infant, child, and maternal health. The scientific research has resulted in basic discoveries that are the foundation for a wide range of clinical applications and have also improved outcomes for premature and critically ill human infants.

Infant rhesus monkeys playing in nursery.  Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

Infant rhesus monkeys playing in nursery. Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

Studies of monkeys are a tiny fraction of all animal studies and are only conducted when studies of fish, mice, rats, or other animals are not sufficient to address the scientific question. Like all nonhuman animal studies, those of young monkeys are subject to rigorous ethical evaluation by scientists, by federal review panels, and institutional review boards that include veterinarians and members of the public.

The decision to conduct a study in nonhuman animals is one that rests on weighing both the potential benefit the work may provide and any potential for harm. The research below provides many specific examples of how and why the studies are conducted and their benefit. For each and every study, scientists, review panels, and ethics boards also consider the potential for harm that may result to the nonhuman animals that are involved. Whether there are any alternatives to the animal study is a requirement of the US system for ethical review and oversight. If there is no alternative, reduction in potential for harm is explicitly addressed not only by a set of standards for animal care, housing, handling, environmental enrichment, and medical care, but also by including only the number of animals needed to answer the scientific question. (You can read more about the review process, regulation, and care standards here and here).

Like other studies of nonhuman animals, those in young animals require serious and fact-informed ethical consideration. At the most fundamental level they challenge us to evaluate how we should balance work that ultimately can help children, the harm that may result from a failure to act, potential harm to animals in research. Consideration of how to balance the interests of children, society, and other animals is not an easy task. Nor is it one that is well-served by simple formulations.

Primate studies of early development have, and continue, to contribute valuable new insights and discoveries that improve the health and lives of many.  The examples below, from NIH-funded research programs across the US, demonstrate how the work contributes to public health.

Sources:  National Primate Research Centers Outreach Consortium. For more information about the NPRCs, see:  http://dpcpsi.nih.gov/orip/cm/primate_resources_researchers#centers

EXAMPLES OF PEDIATRIC RESEARCH WITH MONKEYS

Autism

Cerebral Palsy

  • One outcome of premature birth and accompanying brain injury can be Cerebral Palsy (CP). To date, studies at the Washington National Primate Research Center’s (WaNPRC) Infant Primate Research Laboratory (IPRL) have described the metabolome of normal birth and discovered new acute biomarkers of acute hypoxia‐ This multi‐modal approach will increase the likelihood of identifying reliable biomarkers to diagnose the degree of injury and improve prognosis by tracking the response to treatment after neonatal brain injury. (http://www.ncbi.nlm.nih.gov/pubmed/22391633, http://www.ncbi.nlm.nih.gov/pubmed/21353677)

Childhood Leukemia

  • Wisconsin National Primate Research Center (WNPRC) scientists James Thomson and Igor Slukvin turned diseased cells from a leukemia patient into pluripotent stem cells, providing a way to study the genetic origins of blood cancers as well as the ability to grow unlimited cells for testing new drugs for chronic myeloid leukemia, childhood leukemia and other blood cancers. (http://www.news.wisc.edu/18933 and http://www.ncbi.nlm.nih.gov/pubmed/21296996)

Diabetes and Childhood Obesity

  • Normal and obese marmosets were followed by Suzette Tardif at the Southwest National Primate Research Center (SNPRC) from birth to 1 year. At 6 months, obese marmosets already had significantly lower insulin sensitivity and by 12 months, they also had higher fasting glucose, demonstrating that early-onset obesity in marmosets resulted in impaired glucose function, increasing diabetes risk. (http://www.ncbi.nlm.nih.gov/pubmed/23512966)
  • Infant marmosets were followed by Suzette Tardif at the SNPRC from birth to 1 year. Feeding phenotypes were determined through the use of behavioral observation, solid food intake trials, and liquid feeding trials. Marmosets found to be obese at 12 months of age started consuming solid food sooner and drank more grams of diet thus indicating that the weaning process is crucial in the development of juvenile obesity in both NHPs and human. (http://www.ncbi.nlm.nih.gov/pubmed/23512878)

Diet

Environmental threats

HIV/AIDS

  • Scientists at the CNPRC developed the SIV/rhesus macaque pediatric model of disease, to better understand the pathogenesis of SIV/HIV in neonates and test strategies for immunoprophylaxis and antiviral therapy to prevent infection or slow disease progression. Drug therapies used to prevent the transmission of HIV from mother to infant were developed in nonhuman primate models at the CNPRC, and are now being successfully used in many human populations to protect millions of infants from contracting HIV. (http://www.cnprc.ucdavis.edu/koen-van-rompay/)
  • Development of topical vaginal microbicides to prevent babies from contracting HIV from their mothers during delivery was advanced by Eva Rakasz at the WNPRC and her collaborators. Dr. Rakasz was also a member of the National Institutes of Health study section, Sexually Transmitted Infections and Topical Microbicides Clinical Research Centers. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032991/, http://www.who.int/hiv/topics/microbicides/microbicides/en/)
  • In a model of mother to child transmission, research at the WaNPRC and the ONPRC has shown that neutralizing antibodies can block infection at high doses and prevent disease and death at lower doses in one-month old monkeys exposed to a chimeric SIV that bears the HIV Envelope protein. Human monoclonal antibodies currently in clinical trials are in testing alone and in combination with drug therapy in this primate model as a less toxic alternative to supplement or supplant drugs in newborns. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952052/, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807376/)
  • In women who are HIV positive, prenatal consumption of AZT is useful for reducing the risk that the unborn fetus will contract HIV. Research done at the WaNPRC IPRL demonstrated that the effects of AZT on maternal reproduction and infant development were minimal and at the doses studied, no significant adverse health effects from prenatal exposure to AZT were predicted for pregnant women. (http://www.ncbi.nlm.nih.gov/pubmed/23873400, http://www.ncbi.nlm.nih.gov/pubmed/8301525)
  • A goal of Yerkes National Primate Research Center (YNPRC) infectious disease researchers is to identify the sources of the latent HIV reservoir so targeted cure strategies can be developed. A first step is to develop a novel model of SIV infection and cART treatment of nonhuman primate (NHP) infants to interrogate the SIV reservoir. The development of such a model will greatly facilitate future studies of SIV reservoirs and the design and testing of novel reservoir-directed therapeutic strategies before scaling to clinical trials in HIV-infected patients.
  • YNPRC infectious disease researchers found the percentage of CD4+CCR5+ T cells was significantly lower in all tissues in infant sooty mangabeys (SMs) as compared to infant rhesus macaques (RMs) despite robust levels of CD4+ T cell proliferation in both species. The researchers propose that limited availability of SIV target cells in infant SMs represents a key evolutionary adaptation to reduce the risk of mother-to-infant transmission (MTIT) in SIV-infected SMs. The researchers are applying their findings toward reducing the more than 300,000 cases diagnosed in children each year. (http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003958)

Huntington’s Disease

  • YNPRC researchers have successfully created a transgenic, preclinical animal model of Huntington’s disease (HD). These animals, when followed from infancy to adulthood, show progressive motor and cognitive associated with neural changes similar with the disease patterns seen in humans. Not having such a model has been a major roadblock to developing effective therapies for the disease.
    (http//www.ncbi.nlm.nih.gov/pubmed/18488016; http//www.ncbi.nlm.nih.gov/pubmed/24581271)

Lung Development and Function

  • CNPRC research discovered a link between an infant’s temperament and asthma– research is leading towards the screening, prediction and prevention of lung disease in children. (http://www.ncbi.nlm.nih.gov/pubmed/21536834)
  • Research at the CNPRC has shown that exposure to high levels of fine particle pollution (e.g. wildfire smoke) adversely affects both development of the immune system and lung function(http://www.cnprc.ucdavis.edu/long-term-impact-of-air-pollutants/)
  • Childhood asthma research by the CNPRC focuses on understanding why children are highly susceptible to asthma, with the goal of identifying predictive biomarkers and discovering preventive treatments. These studies use a novel rhesus monkey model of house dust mite sensitization to investigate the pathogenesis of allergic asthma in pediatric and adult asthma. The goal is to define the relationship between pediatric asthma, development of mucosal immunity in the respiratory system, and exposure to the house dust mite allergen. (http://www.ncbi.nlm.nih.gov/pubmed/21819959)
  • Eliot Spindel at the ONPRC has shown that large doses of Vitamin C can protect developing lungs from the damage caused when mothers smoke. This work has been duplicated in clinical trials. (http://www.ncbi.nlm.nih.gov/pubmed/15709053)

Kidney Disease, Organ Transplants, Lupus

  • WNPRC scientists and surgeons at UW Hospital successfully tested a new compound, mycophenolate mofetil, in combination with other drugs in monkeys and other animals, and then in human patients in the 1990s. Their work has saved the lives of patients needing kidney or other organ transplants. These new therapies have also kept patients with chronic kidney diseases, including lupus nephritis, which strikes many children and teens, from needing transplants. (Hans Sollinger, Folkert Belzer, Stuart Knechtle, others.) (http://www.ncbi.nlm.nih.gov/pubmed/8680054, http://www.ncbi.nlm.nih.gov/pubmed/9706169, http://www.ncbi.nlm.nih.gov/pubmed/8821838


Memory Impairment

Polycystic Ovary Syndrome

Puberty Disorders

Prenatal and Mental health

  • Studies at the WaNPRC IPRL have provided important and therapeutically relevant information on the fetal risk associated with maternal exposure to antiseizure medication in infants born to women who have epilepsy (Phillips & Lockard, 1985, 1993). (http://www.ncbi.nlm.nih.gov/pubmed/23873400)
  • Human and animal studies at the SNPRC revealed that the intrauterine environment can predispose offspring to disease in later life. Mark Nijland showed that maternal obesity can program offspring for cardiovascular disease (CVD), diabetes and obesity. This study revealed significant changes in cardiac miRNA expression (known to be affected in human cardiovascular disease) and developmental disorders in the fetuses of obese baboons. (http://www.ncbi.nlm.nih.gov/pubmed/23922128)
  • Studies in the WaNPRC IPRL have demonstrated that prenatal exposure to relatively high levels of ethanol (alcohol) was associated with significant changes in the structure of the fetal brain. (http://www.ncbi.nlm.nih.gov/pubmed/23873400)
  • Recent findings from nonhuman primates studied by Ned Kalin at the WNPRC suggest that an overactive core circuit in the brain, and its interaction with other specialized circuits, accounts for the variability in symptoms shown by patients with severe anxiety. The ability to identify brain mechanisms underlying the risk during childhood for developing anxiety and depression is critical for establishing novel early-life interventions aimed at preventing the chronic and debilitating outcomes associated with these common illnesses. (http://www.ncbi.nlm.nih.gov/pubmed/23538303, http://www.ncbi.nlm.nih.gov/pubmed/23071305)
  • Developmental studies with nonhuman primates at the YNPRC have revealed that neonatal dysfunction of the amygdala, a key brain structure, has long-lasting effects on the typical development of brain circuits that regulate behavioral and neuroendocrine stress, resulting in long-term hyperactivity.  These findings may provide clues on the neural source of HPA axis dysregulation found in autism spectrum disorder, schizophrenia and affective disorders.  (http://www.ncbi.nlm.nih.gov/pubmed/23159012, http://www.ncbi.nlm.nih.gov/pubmed/24986273, http://www.ncbi.nlm.nih.gov/pubmed/25143624)

Preterm Birth and Neonatal Outcomes

  • Current research at the ONPRC incorporates studies directed at understanding the mechanisms of parturition, with emphasis on therapeutic interventions for preterm labor associated with reproductive tract infections and the prevention of subsequent adverse neonatal outcomes. Intra-amniotic infection by genital Ureaplasma species is a predominant cause of early preterm birth. Preterm infants often have life-long health complications including chronic lung injury, often leading to asthma and neurodevelopmental disabilities such as cerebral palsy. Research by ONPRC’s Dr. Grigsby has shown that administration of a specific macrolide antibiotic delays preterm birth and reduces the severity of fetal lung injury and most importantly central nervous system injury. Recently Dr. Grigsby has expanded the infant care facilities at the ONPRC with the addition of a specialized intensive care nursery (SCN); this has enabled new research initiatives to expand beyond the maternal-fetal environment to a critical translation point between prenatal and postnatal life. This one-of-a-kind nursery has the look and feel of a human neonatal intensive care unit and supports the cardiopulmonary, (including mechanical ventilation), thermoregulatory, and nutritional needs of prematurely born infants. (http://www.ncbi.nlm.nih.gov/pubmed/23111115, http://www.ncbi.nlm.nih.gov/pubmed/24179112)

Regenerative Medicine

  • Studies at the CNPRC have advanced the understanding of developmental timelines in the kidney, and applied these findings to new protocols and tissue engineering approaches to someday regenerate kidneys damaged by obstructive disease. (http://www.ncbi.nlm.nih.gov/pubmed/23997038)

Stem Cells and Gene Therapy:

  • The first pluripotent stem cell derived clinical trials to treat childhood blindness are now underway, using stem cell technologies discovered using monkeys first, then humans, by WNPRC scientist James Thomson in the 1990s-2000s. (https://clinicaltrials.gov/ct2/results?term=juvenile+macular+degeneration+stem+cell&Search=Search, http://www.ncbi.nlm.nih.gov/pubmed/18029452, http://www.ncbi.nlm.nih.gov/pubmed/9804556, http://www.ncbi.nlm.nih.gov/pubmed/7544005
  • To successfully treat human disease with stem cells, physicians will require safe, reliable, and reproducible measures of engraftment and function of the donor cells. Innovative studies at the CNPRC have revolutionized the ability to monitor stem/progenitor cell transplant efficiency in fetal and infant monkeys, and have used new noninvasive imaging techniques that demonstrated long-term engraftment and safety. (http://www.ncbi.nlm.nih.gov/pubmed/24098579)
  • Studies at the CNPRC have proven critical in gaining approval for investigational new drug (IND) applications to the FDA and conducting first-in-human trials of (1) an expressed siRNA in a lentiviral vector for AIDS/lymphoma patients,, and (2) achieving the overall goal of utilizing adeno-associated virus (AAV) expression of human acid alpha-glucosidase in 3 to 14-year-old Pompe patients who have developed ventilator dependence.

Tuberculosis and HIV

  • Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. SNPRC scientist Marie-Claire Gauduin and colleagues have successfully established an aerosol newborn/infant model in nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Aerosol versus intra broncho-alveolar Mtb infection was studied. After infection, specific lesions and cellular responses correlated with early Mtb lesions seen on thoracic radiographs were observed. This model will also allow the establishment of a TB coinfection model of pediatric AIDS. (http://www.ncbi.nlm.nih.gov/pubmed/24388650)

 

Animal welfare inspectors clear UW-Madison cat research of PETA allegations, important hearing research continues

A second federal agency charged with oversight of animal research has completed a thorough investigation of an animal rights group’s complaints about sound localization research with cats at the University of Wisconsin. Summary of the result:  “there was no direct noncompliance with the PHS Policy or serious deviation from the provisions of the Guide for the Care and Use of Laboratory Animals.”

We have written previously (here, here, here) about reviews conducted by the United States Department of Agriculture (USDA). This time the report is from the National Institutes of Health (NIH) Office of Laboratory Animal Welfare (OLAW).  Once again, the complaint by PETA is based on hundreds of pages of records that the animal rights group received from the UW via open records requests.  In response to these complaints both federal agencies have sent teams that include veterinarians to look at the animals, records, and research at UW-Madison.

new graphic - AR cycle 10.07.13 ajbIn addition to the USDA and OLAW reviews, during this period the NIH institute funding the sound localization project, the National Institute on Deafness and Communication Disorders (NIDCD), also took action. NIDCD suspended one part of the research— but not the entire project— from April-September 2013 when the final report was issued. Whether the suspension was the result of PETA’s allegations is not clear. What is clear is that the NIH and scientific community have long supported and valued this specific research and– more broadly–  the contribution of animal models to success in this field and advances in scientific understanding and human health. The PI of this work, Professor Tom Yin, has been funded by NIH for many years. As is the case of all NIH-funded research, a competitive expert scientific panel provides rigorous critical analysis of the proposed science. Only a small fraction of proposals are identified as valuable, worthwhile, and likely to succeed. In this case, the PI’s research was deemed justifiable and worthy following scientific review, NIH review, and IACUC review. Furthermore, the scientific contributions Yin’s work is evident in many ways. For example, it is widely cited in the field (e.g., over 5000 citations of his scientific papers). Yin discusses the targeted research in these videos:

In brief, Professor Yin’s laboratory conducts fundamental basic research that has resulted in better understanding of complex brain function and how hearing works. By using a combination of electrophysiological recordings, anatomical studies and behavioral studies, the lab is studying the mechanisms used by the brain to put together inputs from the two ears to improve hearing. The scientific discoveries have public benefit because they provide foundational understanding with broad applicability. Knowing how the brain integrates sound received by both ears and how that allows for localization of sounds is an important part of work towards improving the quality of life and functioning of millions of people with hearing impairment.

Many types of research in this area require recording and studying a real functioning brain, there are no non-animal alternatives. Cats are among the best animal models for this work for a number of reasons. Among them: most of the information we have about the auditory system comes from studies in cats, they are nocturnal hunters with excellent sound localization abilities, and what we know about the cat’s nervous system shows that it is very similar to that of humans. The importance of cats and other animal models to research in this field is widely acknowledged, including by this year’s Lasker-DeBakey Clinical Medical Research Award, and particularly the work of Graeme Clarke, which laid the foundations for the development of multichannel cochlear implants through studies in cats and rats.

As we have discussed previously, consideration of the use of animals in research includes not only weighing its potential benefits, but also evaluation of the animals’ welfare. The welfare of all of research animals is a priority and one that is ensured through the careful efforts of research, veterinary, and animal care personnel. Furthermore, oversight of animals’ care and treatment occurs at individual, institutional, and federal levels. A small number of cats (less than a dozen) participate in UW-Madison’s sound localization research. The cats are healthy and well-adjusted to their work, play, and living environments as was documented in the OLAW report. In that report, external reviewers who had thoroughly reviewed the lab and records, examined the animals, and interviewed the animal care and veterinary personnel, research staff, and scientists were satisfied with the animals’ condition and treatment.  Potential for pain or suffering is minimized through careful efforts: Surgery is performed under deep anesthesia, just like surgery for humans. Infections are a risk, but they affect the animals only a fraction of the time they are in study. Furthermore, infections are caught early through extensive and careful monitoring, treated immediately and resolved quickly in all but a very small number of cases. In no cases are they allowed to be untreated or to cause suffering or unrelieved pain.

OLAW’s summary conclusion, released September 30, confirmed that the research and animal treatment were appropriate: “there was no direct noncompliance with the PHS Policy or serious deviation from the provisions of the Guide for the Care and Use of Laboratory Animals.” Furthermore, the report concluded that PETA’s specific allegations were unsupported. The report also acknowledged UW’s efforts to continue refinement in the animals’ care and treatment:  “OLAW found that while the specific allegations did not accurately reflect the entire clinical and research condition of the cats, changes were made to enhance the care of the animals and potentially improve research outcomes.” Furthermore, the report includes many extremely positive descriptions of the animals’ condition and care.

UW responded:

“The OLAW investigation is the third review of the lab and its animal subjects by the federal government, all instigated by PETA within the past year. To date, none of the many allegations of mistreatment made by the organization to the U.S. Department of Agriculture or OLAW have been substantiated. ‘Contrary to the misleading claims made by PETA, the conclusions cited in the OLAW report reflect our view that the animals in the study are in excellent health, are well treated and cared for, and used to further important research in an appropriate and humane manner,’ says Dan Uhlrich, UW-Madison associate vice chancellor for research policy.  ‘Significant university and federal resources have been repeatedly redirected to respond to these unfounded allegations. This is a questionable use of scarce and valuable public resources, which we feel damages the best interests of the public, science, affected researchers, and the dedicated animal care and veterinary staffs responsible for the health and wellbeing of our animals.”

The OLAW summary report, including 36 appendix exhibits, can be found on their website. The UW has also shared detailed information about the research, the reviews, and the animal program with the broad public via its website, release of hundreds of records, and videos in which the scientist and others speak about the value of the work and how it is conducted.  In other words, as we’ve noted before, there are many venues for the public to learn more about the work, its conduct, and the detailed process of regulatory oversight.

What was PETA’s response?

Hint:  It did not include acknowledgement that OLAW, USDA, and the University of Wisconsin gave serious consideration to PETA’s complaint, performed a thorough investigation, and provided a detailed, specific public response on each of the allegations that the animal rights group raised. Nor did PETA’s response include an acknowledgement that perhaps they were wrong.  And nothing in their public responses indicated – front and center – that PETA’s mission and objective is to end all animal research. PETA’s position is fundamentally absolutist. Regardless of animals’ welfare and regardless of the consequences for the public that benefits from responsible, ethical and humanely-conducted animal studies, PETA is opposed to all use of nonhuman animals. Thus, there are presumably no conditions under which PETA would find laboratory animal research acceptable. (We welcome correction from PETA if this is a misrepresentation of their position.)

It is not surprising then that, as reported in the Wisconsin State Journal, PETA’s spokesman did not accept the OLAW conclusion, but rather vowed:  “This campaign is going to continue until that lab is empty and there are no cats in it,’” Goodman said without specifying the group’s next steps.”

PETA’s next steps in its quest to close the laboratory will probably include some of the characteristic stunts for which they are famous. At the UW this has included small protests on campus, the PETA mobile billboard truck driving around Madison, and an actor and PETA staffer gaining media coverage for disruption and arrest at a UW System Board of Regents meeting. Review of their campaign strategy thus far provides a few other clues for what to expect at the UW and elsewhere. For example, last week PETA set up at the campus job fair to recruit for an “undercover investigator.”  PETA’s Jeremy Beckham netted a local television interview with the tactic. Not a new tactic for animal rights groups, as seen in this campaign directed at Oregon Health Sciences University several years ago.

As we’ve written before however, focusing on these stunts and underestimating the broader gains that PETA has made and that negatively affect science and public interests can be a mistake.  In the case of this campaign and all of the associated events, two things in particular are worth notice by the broader community.  First, the way in which PETA used the openness of records and the public responsiveness of the regulatory process to feed their campaign; and second, the use of emotive tactics that encourage harassment of scientists and others in research institutions. The graphic above captures the general strategy used by many activist groups, highlights the costs, and raises a number of questions. In particular, one question that merits serious discussion is how to better assess the full range of actual costs and critical evaluation of realized benefits to animal welfare, science, and public interests.

Despite the conclusion of multiple federal reviews that failed to support their allegations, PETA is continuing to smear the research and to promote petition and email campaigns to the NIH, UW-Madison, and others. As one of the exhibits in the OLAW report shows, the NIDCD received 562 phone calls and approximately 190,000 emails about cat research. While that represents a tiny fraction of the American public and likely includes many form messages, its inclusion in the OLAW report suggests it may have been relevant to the NIH’s response.  No doubt that number increased after PETA linked a form email to its mixed martial arts assault on scientists videogame in order to encourage players to complain to NIH about the UW research.  Of course the game also encourages players to entertain the idea of harming scientists. As we’ve seen before, these highly emotional tactics can have the general effect of eliciting threatening and disturbing messages from those who follow PETA. For example, this recent tweet:

Beth Carter 10.5.13 tweet

The PETA campaign and response following the USDA and OLAW reports makes their objective clear once again:  to end research and close labs. Nothing new there. The question to ask now however, is how research institutions, scientists, federal agencies, and the public should respond to campaigns like this. In particular, this set of events provides additional strong evidence that there is little broad value in engagement with groups that have a singular agenda and little interest in serious dialogue, accuracy, or acknowledgement of the complex issues and choices in animal research conducted for public benefit.  For scientists and research institutions interested in dialogue and better understanding of animal research, using that time and energy to communicate directly with the public about their research, why they are doing it and what it involves makes more sense.

More here:

http://speakingofresearch.com/2012/09/20/defending-science-and-countering-falsehood-at-the-university-of-wisconsin-madison-2/

http://speakingofresearch.com/2012/10/12/as-predicted-uw-cleared-peta-caught-lying-again/

http://speakingofresearch.com/2013/02/08/a-lesson-in-hypocrisy-as-peta-cries-foul-over-one-cats-death-while-secretly-killing-hundreds-more/

The Double Life of Dr. Lawrence A. Hansen

Dr. Lawrence A. Hansen has a double life he is proud to publicize in his writings and interviews.

On one hand, he is a neuroscientist at one of the finest institutions in the country — the University of California at San Diego.  On the other hand, he is a member and a mouthpiece for People for the Ethical Treatment of Animals.

PeTA, of course, is an animal rights organization that holds the view that all living beings have the same basic right to life and freedom. A corollary of this position is that  animals cannot be used by humans in any way, including their use in scientific research designed to advance human health and medical knowledge.

Dr. Lawrence Hansen regularly attends the Society for Neuroscience Annual Meeting, where he joins his PeTA colleagues in order to protest the organization’s stated goal of broadening support for animal research.”

He has  written numerous opinion pieces (for example, here, here and here) asserting with confidence that animal research will not lead to any advancements in human health, that the experiments are unnecessary because they can be conducted in human volunteers, and that the treatment of the animals in our nation’s laboratories amount to torture.

Image

Dr. Lawrence Hansen (left) demonstrating at the Society for Neuroscience meeting. He is accompanied by PeTA’s Justin Goodman (right).

Dr. Hansen is wrong on all counts.

Animal research has contributed widely to human healthMultiple layers ensure the welfare of animals during experimentation. Methods do not exist today that would allow scientists to study the cellular and molecular mechanisms underlying disease in human volunteers non-invasively. This is what is really required to understand the evolution of a disease in a living organism and how we can interfere with its development. Indeed, a recent poll by the journal Nature revealed that nearly 92% of scientists agree with the statement “animal research is essential to the advancement of biomedical science.”  The  fact is that there are no current alternatives — otherwise, they would be used.  This is the reason the scientific consensus on the topic is nothing short of overwhelming.

Being wrong is just one problem with Dr. Hansen.  The other is the level of hypocrisy required for a scholar like him to criticize animal research while simultaneously being involved in the work.  Specifically, Dr. Hansen is a co-author in animal studies that use transgenic mice to model Alzheimer’s disease in humans: here, here, here and here.

Justification for all these studies relies on the notion that one can model the disease in mice in ways that might be relevant to human patients — an idea that Dr. Hansen rejects vociferously.  Was authorship on these studies forced upon him?

Perhaps Dr. Hansen will argue that he played a minor role in these studies, merely providing resources and reagents for the studies?  This seems unlikely, as at least in one instance Dr. Hansen’s role is listed as having “conceived and designed the experiments.”

All these articles list the Neuropathology Core grant (NIH P50 AG005131), of which Dr. Hansen is the responsible Principal Investigator, as partly funding them.  In other words, Dr. Hansen’s own federal grant has funded the animal research he presumably opposes.  (Incidentally, as far as we can tell, the Aims of the grant do not include any animal research.)

Perhaps Dr. Hansen approves only of work with mice but not in other species? If so, it seems he fails to understand the concept of “animal rights.”  The notion that all living beings have a right to live free from all human intervention would render his own work ethically wrong as well.  Or does PeTA make an exception for his mice work?  Maybe membership has its privileges?

Perhaps Dr. Hansen thinks that for some magic reason his work with mice is guaranteed to translate to humans, while findings in other species will not?  One wonders if there something magical about the biology of mice?  If mice can be used to model human disease, why couldn’t other animals? However, it doesn’t seem that Dr. Hansen holds mice work in high regard.  Last year, in an interview, he stated:

“the amoral scientific problem with using rodents as models for neurodegenerative diseases is that rodents do not naturally develop Alzheimer disease or Parkinson`s disease. The only way to get what looks even a little like AD or PD pathology in rats and mice is to make them transgenic — that is, to insert human disease causing genes into the rodents. This does create a Frankenstein-like mutant model with some expression of AD or PD pathology which can be manipulated to make it go away. But reversing artificially induced AD or PD changes in animals that never naturally develop them is a far cry from curing the human diseases. The “cures” that work in the rodents have never worked when applied to humans. 

[...] The species differences that have evolved over millions of years make animal models largely useless, except for the purposes of enhancing scientific careers and attracting lots of grant money.”

If this represents his scientific opinion, why in the world would he participate and fund the very same “unnecessary” experiments that create “Frankenstein-like” animals? Perhaps Dr. Hansen thinks his transgenic animals are under good care and condition, while the other ones down the hall that belong a colleague are being tortured instead?

Perhaps Dr. Hansen believes his studies are restricted to some basic biological process of Alzheimer’s that has no consequence for the human condition?  But then, how would he justify the use of animals?  And why would he write that his work “supports the possibility that modulators of the autophagy pathway might provide potential therapeutic effects.”  Therapeutic effect for mice but not humans?   Again this seems unlikely, as stated that mice do not develop AD or PD pathology naturally, and thus are not in need of any therapeutics.

The fact is that the justification behind his work can be found in the Introduction and Discussion sections within the very same articles he co-wrote.  Dr. Hansen and his co-authors explain, for example, that:

It is important to note that neurogenesis persists in the aged brain; however, its rate declines with increasing age, as revealed by previous studies in rodents (Kuhn et al., 1996Kempermann et al., 1998), nonhuman primates (Gould et al., 1999), and humans (Cameron and McKay, 1999). Despite this natural decline with age, previous studies have shown that the adult brain remains responsive to therapeutic interventions that enhance neurogenesis (Jin et al., 2003Wise, 2003). Understanding the molecular mechanisms involved in AD-related alterations in neurogenesis might help guide the development of new therapies in this direction. 

This is one of several passages illustrating the synergy between human, mouse and in vitro techniques in biomedical research, and highlights the similarities between development of the human disease and its recapitulation in animals models of AD.  These are the very same scientific facts he denies and renounces in his interviews, OpEds, and PeTA demonstrations.

It would be worth for Dr. Hansen to dedicate some effort in justifying his own work with animals, studying a little bit more about the contributions of animal research to human health, and dedicating less of his time demonizing his colleagues for the wrong reasons.

Speaking of Research

Update: There is more discussion going on at DrugMonkey’s blog as well.

Solving the Brain: Animal research at the frontiers of Neuroscience

Regular readers of this blog will be familiar with the important role played by animal research in neuroscience, a post we published to mark Brain Awareness Week earlier this year covered but a tiny fraction of the work being done around the world. Meanwhile some neuroscientists have been thinking big…very big…with the launch of the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative in the USA and the Human Brian Project in the EU, projects that aim to transform neuroscience and accelerate the discovery of novel therapies for neurological disorders. Within the neuroscience world there has been a lot of discussion and debate over whether now really is the right time to launch this initiative,  and whether the budgets allocated are anywhere near large enough to fulfil the ambitious aims, but as the dust settles a little and it becomes clear that these projects will – at least initially – focus on developing research techniques and infrastructure, it is useful to take a look at what is being planned.

Optogenetics is one technology helping scientists to unlock the brain's secrets.

Optogenetics is one technology helping scientists to unlock the brain’s secrets.

In Nature this week Alison Abbott has spoken to several of the main players in these programs in the USA and Europe, and the very first paragraph highlights their ambitious nature.

When neurobiologist Bill Newsome got a phone call from Francis Collins in March, his first reaction was one of dismay. The director of the US National Institutes of Health had contacted him out of the blue to ask if he would co-chair a rapid planning effort for a ten-year assault on how the brain works. To Newsome, that sounded like the sort of thankless, amorphous and onerous task that would ruin a good summer. But after turning it over in his mind for 24 hours, his dismay gave way to enthusiasm. “The timing is right,” says Newsome, who is based at Stanford University School of Medicine in California. He accepted the task. “The brain is the intellectual excitement for the twenty-first century.”

We strongly encourage you to head over to Nature and read the whole article, which provides a great introduction to the different challenges – both scientific and technical – that neuroscientists face, and how they are planning to overcome them.

Alison’s article also highlights the crucial role that animal research will play in this effort, in developing the technologies that the BRAIN Initiative describes:

While these technological innovations have contributed substantially to our expanding knowledge of the brain, significant breakthroughs in how we treat neurological and psychiatric disease will require a new generation of tools to enable researchers to record signals from brain cells in much greater numbers and at even faster speeds. This cannot currently be achieved, but great promise for developing such technologies lies at the intersections of nanoscience, imaging, engineering, informatics, and other rapidly emerging fields of science

New techniques such as optogenetics that allow researchers to precisely control the activity of individual neurons,  CLARITY and  Scale that make tissue transparent so previously hidden connections within the brain become visible, and advanced electrode technology that has allowed the development of neuroprobes that can measure the activity of over a hundred individual neurons simultaneously (earlier versions of which are being used to develop treatments for paralysis), will all play an important role in these programmes, alongside powerful brain imaging technologies and the supercomputers and computational techniques needed to process and make sense of the vast amounts of data that they will yield.

The ambition of these projects is laudable, but it will not be achieved without a lot of investment, and there lies the problem. While $100 million was invested in the BRAIN initiative at it’s launch, this sum was dwarfed by the $1.5 billion slashed from The NIH’s budget by sequestration in March, and promising neuroscientists who might have made great contributions to understanding the brain are no doubt going to be among those whose careers are cut short by lack of funding.  This crisis at a time when we should be looking forward with hope and excitement shows why it is so important to make sure that your political representative understands that to secure future health and prosperity we need #curesnotcuts.

Speaking of Research

Statement on Harvard’s Decision to Close the New England Primate Research Center

Speaking of Research is saddened to learn about Harvard’s decision to wind down operations at the New England Primate Research Center (NEPRC) within the next two years.

Over the years the Primate Center has contributed important discoveries in many fields, including AIDS, Parkinson’s disease, primate retroviruses, addiction, cardiology and stem cells.

The University cited difficult financial times and shifting long-term strategic plans as the reason for the closing.  Meanwhile animal right activists groups fought among themselves to take credit for Harvard’s decision.

Perhaps a combination of both, the planned closure is a reflection of decreasing Federal support for medical research and a growing anti-scientific movement in the United States and elsewhere.

In Harvard’s decision one can find many lessons for the scientific community, NIH and the public at large, which are likely to be the subject of debate and discussion in the near future. The wider research community will need work together with faculty and staff at NEPRC to ensure that Harvard Medical school keeps to its commitment to provide full support to them during this transition, so that vital research programs and gifted personnel are not lost to science.

For now Speaking of Research join others in expressing our surprise and disappointment at these developments, and offer our support for the scientists, staff and others affected by these events.

Speaking of Research

A Public Conversation on Animal Ethics: The good, the bad, and the ugly

The UW-Madison recently hosted a conversation on the ethics of animal research between Rick Marolt, an opponent of animal research, and Robert Streiffer, a bioethicist at the university and member of the Institutional Animal Care and Use Committee (IACUC).

Here are some of my thoughts on this interesting exchange.

The good: Above all, it is good to see a display of open academic dialogue on a controversial topic.  We have tried such a conversation at UCLA in the past with mixed results. This meeting was described as a “conversation” rather than a “debate”.  Such dialogue is a good first step that allow participants to express their positions on the ethics of animal research. In this regard, I think such exercises are a net good and a sign of progress.

The curious: It is perplexing that the conversation centered on the use of a “utilitarian framework” to justify the use of animals in medical research. Why? Because both participants made it clear they are not utilitarians. Instead, they both (wrongly) declared that scientists are, or assumed the only possible justification for their work must be a utilitarian one. The result was that Prof. Streiffer, on more than one occasion, uttered a sentence beginning with “It is because they [scientists] think that..,” while not being clear on what his own ethical framework as Chair of the IACUC has been. Of course, if the participants were seeking an utilitarian justification for animal research they could have invited Peter Singer.

My sense is that scientists hold a wide range of more nuanced views that they certainly include the consideration of benefits, but are not defined by the utilitarian position. Rather than letting someone speak for us, scientists should let our voices be heard, both to explain the science and ethics of the work.

Mind the gap: The discussion centered exclusively on the upper limits of animal research.  In other words, what kind of experiments would one find to be unjustifiable? Marolt and Streiffer probed this issue using a maternal deprivation protocol at UW as a test case. I think this is a good question to ask. At the same time, if one truly want to explore the size of the gap that exists between our respective positions, we must also ask what kind of experiments the critics of animal research would find acceptable and why. This point was altogether ignored and Mr. Marolt offered no examples. Given the ethical principles he cited (see below), I’d guess his answer would be “none at all”. Understanding the gap between opposing views is critical to identify areas of common ground, or lead us to conclude that there cannot be any.

The bad: To a scientist, perhaps the most shocking passage of the exchange came when both participants agreed that “knowledge is not a significant benefit.” Such an insult to reason is deeply troubling because it shows how little the participants know about the scientific process. They also seem not to appreciate the value of negative results (disproving a hypothesis) in scientific inquiry.

Presumably, neither Marolt or Streiffer see much value in proving abstract mathematical theorems, engaging in space exploration, trying to manipulate single atoms, proving the existence of the Higgs boson, or placing a telescope in space to peek into the boundaries of the universe. They are apparently oblivious, for example, as to the origins of the medical imaging technologies such as X-rays, PET, ultrasound, and MRI. (Hint: basic knowledge.)

The inconsistent: Prof. Streiffer explained how he arrived at the conclusion that a protocol under discussion was unjustified based on his cost/benefit analysis. However, he previously stated that he didn’t fully understand how is that the scientists would be analyzing the data to determine the molecular pathways involved in anxiety. How was he able to assess the potential benefits of the work without such understanding?  It is not clear.

The double standard: Mr. Marolt tried to explain his opposition to animal research based on his “moral intuitions.”  However, he is unwilling to accept the use of “moral intuitions” argument from others, demanding instead solid ethical reasoning. He should apply the same high standards of ethical reasoning he demands from scientists to himself.

The “moral intuitions”: So what are Marolt’s moral intuitions? He said that in his view “life matters” and that we should not deprive anyone from the opportunity to life.

Does he mean this in absolute terms? Is he anti-abortion? Does he believe the use of violence to end slavery or free concentration camps was unjustified?  Does he see any situation at all in which taking a life may be justified?

He said that “suffering matters,” and that he feels the suffering of the monkeys in labs while lying in bed at night. I know that those working with animals also feel in such a way, but they also feel for the mothers that fight breast cancer, the children with leukemia, the elderly with Alzheimer’s or Parkinson’s. Their suffering matters to them too.

We all protect our children against enormous suffering by vaccinations that were developed through the use of animals in research.  We recognize the moral dilemma of the work. Not having children of his own Marolt did not have such experience, but he found no shortage of words when it came to offer suggestions as to how others must educate their children on moral issues.

Marolt said that species membership is not morally relevant because “he does not feel that.” Once again, if we accept this justification, those who support the work could simply respond that “we feel otherwise.” But it is unlikely that he would accept such explanation. What we would like to know is why he thinks we owe the same exact level of moral consideration to a mouse as to a human. We are asking for a reason, not a feeling.  Here are some reasons why cognitive abilities matter, as they impact the level of suffering of different organisms.

Finally, Marolt asserted that if faced with a situation where he had to choose between two living beings, a human and an animal, he would save the life of a human. But he explained he would not be able to rationalize his choice.

One can only infer that if Marolt had a better understanding of the science he would  approve of animal research.  Indeed, scientists feel we are in a sort of burning house scenario. Most of us feel that human lives will be lost if we stop the work and that, at present, there are no viable alternatives. We accept we have to live with the uncertainty of the benefits that any one experiment could yield. At the same time we are certain of the benefits of the work as a whole, as proven by medical history.  We are convinced that stopping scientific work with animals means that many areas of medical research would come to a full stop, with tremendous harm done to humans and animals alike.

Rick Marolt, and other animal rights activists like him, have to justify their inaction and their demand to have this type of work abolished. Not with feelings and intuitions, but with moral reasoning. They have not yet produced a compelling argument, and their absolutist, moral intuitions are wrong.