Tag Archives: Addiction research

FDA response to Goodall letter found lacking

On September 25, 2017, Dr. Scott Gottlieb , Commissioner of the U.S. Food & Drug Administration (FDA) replied to a scathing letter from Dr. Jane Goodall, where Goodall denounced what she called the “cruel and unnecessary nicotine addiction experiments on monkeys”. We previously evaluated that letter from Goodall and now do the same with Commissioner Gottlieb’s letter.

The FDA Commissioner’s letter starts with an acknowledged appreciation of Goodall’s opinion and a re-statement of the FDA’s commitment to compliance with the rules and guidance governing the use of animals for research. It is indeed admirable that Commissioner Gottlieb places emphasis on compliance with the long-standing regulatory framework and guidance governing animal research in the US. What is unacknowledged in the letter is that all studies involving animals used in research, including the one that Goodall references, are continually monitored with respect to such compliance.

Gottlieb writes:

“After learning of concerns related to the study you referenced, I directed the Agency to place a hold on the research study earlier this month. Accordingly, at this time, all experimentation involving the monkeys in the study you referenced has been halted.”

Several things are surprising about this approach. Foremost, the vague reference to “concerns” when coupled with the failure to mention the review and oversight mechanisms in place, can give a public impression that is confusing. For example, is Gottlieb saying that his response is driven by Goodall and WCW? Speaking of Research, like the scientific community, supports an effective oversight system that has mechanisms for investigation and correction of animal welfare issues. In this letter, however, the Commissioner appears to bow to celebrity opinion, halting an ongoing experiment without providing evidence or acknowledgement of the continual monitoring that surrounds research. In fact, subsequent media coverage of Gottlieb’s response also conveys the impression that the decision was made directly in response to Goodall’s letter.

This is alarming on many levels. There is, for example, no acknowledgement of contact with the research institution’s federally-mandated review board (Institutional Animal Care and Use Committee, IACUC), no mention of the FDA’s process for review of research, or evaluation of records. Instead, the letter suggests that the federal agency’s decision is a bow to celebrity pressure from Goodall, who is acting on behalf of an anti-animal research organization (White Coat Waste, WCW).

Gottlieb continues:

“I asked for a medical team of primate experts to conduct a site visit to evaluate the safety and well-being of the monkeys and to understand whether there are additional precautions needed.”

This statement and the announcement of “halting” the study, absent any other information, imply that animal health and well-being are in immediate jeopardy. The evidence for that claim is not presented. If the animals were in immediate jeopardy, we would expect that the facility’s personnel would be taking action. Whether that is the case or not cannot be ascertained from Gottlieb’s letter. At the very least, the commissioner’s letter should acknowledge any ongoing efforts by his agency’s personnel—including those at National Center for Toxicological Research (NCTR).

Squirrel monkey. Source: Wikipedia Commons.

The letter can leave readers with the several wrong impressions by leaving out any information about the expertise of the existing veterinary, animal care, and scientific staff at the federal facility. Readers may be left with impression that primate experts—including scientists and veterinarians — are absent at the long-standing federal research facility, the NCTR. That is unlikely to be the case. Further, even when people with a high level of expertise and experience are present, adverse events that require thoughtful review and modifications in procedures sometimes occur. Animal research, like all human endeavors, has potential for error. Research teams, IACUCs, and regulatory bodies all play a role in making sure that those errors are addressed and corrected. Thus, in light of full transparency, actions taken by the institutional IACUC, the scientists, and the facility’s veterinarians, along with further information including the timing and venue for a public report of findings before decisions are taken need to be specified.

Gottlieb’s letter continues:

“I also appointed an independent FDA review team, led by senior career experts and with the guidance of primate veterinarians, to assess the science and integrity of the animal research process for this study. I also asked this team to evaluate whether the re-initiation of the study you referenced is necessary to fulfill FDA’s public health responsibilities, or if the study should be halted indefinitely.”

This is one of the more troubling aspects of the FDA commission’s letter as it is unclear whether he is aware that firstly, this study must have gone through rigorous review in terms of scientific merit, evaluation of the risks to the animals being used as well as the proposed benefit to humans, when it was funded. Secondly, the IACUC at this institution will have vetted all procedures being performed on these animals, including consideration of response and correction should an adverse situation occur.

Finally, separate to this letter, but parallel to this issue, an FDA spokeswoman is quoted as stating, “the agency is also considering creating a wider-ranging function that would provide for even greater oversight of the care of animals in the agency’s possession.”

This statement is alarming in its lack of specificity and requires clarification. Does it mean that FDA is conducting a re-assessment of the existing federal structure for reviewing and conducting all animal research? If so, what is the impetus for the review? How is it different from existing policies? Who is involved in the review? What is the process by which public interests in scientific research that informs public health policy will be protected and scientific objectives balanced with animal welfare? How will the public be assured that the full range of relevant expertise is included in the review? There are many additional questions—all raised by the statement, none addressed, as far as we are aware, by any other materials provided by the FDA.

Finally, it is also important, in light of full transparency that the FDA provides an update about its ongoing lawsuit with WCW. The WCW suit appears to have arisen as a consequence of the FDA’s response to a WCW freedom of information (FOIA) request for records about the NCTR research. At this time, it is unclear whether the FDA’s decision to suspend this ongoing and already scientifically-justified funded research is related to this lawsuit. The Washington Post writes:

“Goodall was enlisted in the fight against the monkey tests by the White Coat Waste Project, an advocacy group that says its goal is to publicize and end taxpayer-funded animal experiments. In January, the organization obtained 64 pages of documents on the nicotine-addiction research from the FDA under the Freedom of Information Act. It is suing the agency to get more information on the research’s costs, as well as veterinary records and photographs and videos of the experiments.”

Speaking of Research is not the only organization concerned with the FDA response. The American Psychological Association (APA), the American College of Neuropsychopharmacology (ACNP), and the College on Problems of Drug Dependence (CPDD), have jointly penned their own letter to the FDA demanding a clear explanation for the suspension of the nicotine research project. Part of it is quoted below:

“As you may be aware, Dr. Goodall’s letter to you came at the behest of an organization, White Coat Waste Project (WCW), that is fundamentally opposed to all research with nonhuman animals. Your decision to suspend the research is extremely troubling because it appears to have occurred without any substantive input from experts in the scientific community who have deep knowledge and understanding of research on substance use disorders. Furthermore, the methods and technologies used in this study have been rigorously validated and commonly used in studies of substance use disorders, including research that is funded by other federal agencies, such as the National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA).”

Speaking of Research shares the APA, ACNP and CPDD’s concerns. We hope the FDA will be forthcoming with an explanation of the suspension of the research project in question. We also hope that they will be taking the evidence of experts over the opinions of prominent celebrity scientists and animal rights groups.

Speaking of Research

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.

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

 

 

 

 

 

 

Speaking of Addiction Research

J. David Jentsch is a Professor of Psychology and Psychiatry & Biobehavioral Sciences at the University of California, Los Angeles. He is the recipient of the 2010 Joseph Cochin Young Investigator Award from the College on the Problems of Drug Dependence and the 2011 Jacob P Waletzky Award for Innovative Research in Drug and Alcohol Abuse from the Society for Neuroscience. He is a member of the Speaking of Research Committee and writes his own blog: the Unlikelyactivist.

This post is the full version of a piece originally written for Substance.com under the title “A Scientist Comes Out Swinging at PETA’s Addiction Research Stance”.

Biomedical research seeks to expose biological principles and mechanisms that cause disease in order to advance from a time where medications and treatments were discovered by chance to one where we reason our way to solutions for human and animal health through scientific discovery. Since the founding of the National Institute on Drug Abuse (NIDA) in 1974 (only 40 years ago), immense progress has been made into understanding, at the level of brain cells and molecules, why some drugs are addictive, why some people are particularly prone to addictive behaviors and how to treat drug use disorders. One of the reasons that so much progress has been made so quickly is that animal models for drug abuse are remarkably accurate and informative.

In the clearest example of all, if you place a laboratory rat into a chamber and allow it to trigger delivery of cocaine, methamphetamine, nicotine, alcohol, heroin, etc., into their bloodstream by voluntarily pressing a button, they will do so. Rats will seek out and voluntarily “self-administer” drugs of abuse, just like people do, precisely because of the remarkable similarity in the reward pathways in the human and rat brain, as well as due to the fact that these drugs act upon brain chemicals in nearly identical ways in rodents and humans. Moreover, if you allow rats to consume the drug daily over a long period of time, a subset of them will progressively become “dependent” upon the drug, just the same way a subset of people that abuse drugs do. Dependence is indicated by the fact that the subject loses control over their drug use and continues to use the drug, despite efforts to abstain. Because of these incredible parallels between humans and animals, we now understand the mechanisms by which drugs of abuse produce reward at a deep level, as well as how these agents encourage drug-seeking and –taking behaviors. For example, we now know how parts of the brain like the nucleus accumbens, amygdala and prefrontal cortex participate in the development of drug-taking behaviors, and we know how crucial brain chemicals like dopamine and glutamate are to these phenomena. This information would not have been possible without responsible and humane research involving a variety of animal models – ranging from invertebrates (fruit flies, roundworms) to rodents (rats and mice) to non-human primates (mostly monkeys).

Rat Rodent Addiction Animal Testing Research

It is reasonable to ask why, given these advances and the value of animal models, we have not yet cured addictions. The answer is simple. When NIDA was founded 40 years ago, we actually knew very little about the basic biology of the brain and its relationship to drug abuse. Decades of basic research were required before we knew enough about the brain pathways involved in reward to further understand how drugs acted on these pathways and changed them in response to long-term drug intake. Decades of basic research, still on-going, was and remains required to identify all the genes, molecules and cell processes that drugs act on but which were unknown to us as recently as 10 years ago. Basic research continues in an attempt to fully describe how the hundreds of billions of nerve cells in the brain work together to create behavior and how the tens of thousands of genes in our genome affect the function of our bodies. Coupled with amazing advances in the technology needed to study the brain, this knowledge from basic research will yield unprecedented progress towards treating addictions, as well as other disorders of the brain (from Alzheimer’s Disease to schizophrenia) will be possible.

So, what has research into the biology of addictions done for us so far? In a recent blog post, Katherine Roe from PeTA claims that only one new medication has been approved for the treatment of alcoholism/alcohol use disorders based upon animal research in recent years, that it has only “limited” effect and that animal research has “green-lighted” decades of failed medication trials. Not only are each of these statements factually wrong, the truth that is subverted by her points actually demands more animal research, not less.

Firstly, there are actually three medications approved for the treatment of alcohol use disorders (one is old and two are new). One new drug naltrexone (that blocks opioid systems in brain) was approved in 1994; in 2004, the FDA approved another medication (acamprosate). Both specifically target brain chemical systems discovered to be important to alcohol’s effects though animal research. In addition, the development of both medicines required animal research since they act on molecules in brain that might be unknown at all without basic research studies in rodents and non-human primates.

Secondly, referring to the efficacy of these medicines as limited seems to misunderstand the nature of pharmacology. These medications do not effectively treat everyone that is medicated with them – but then, no drug used for any disease does. That’s not the way pharmacology works. That said, for tens of thousands of people with alcohol use disorders around the world, they achieve and maintain abstinence thanks to one or both of these medications: something that wouldn’t be possible for them without the medicines. For those people, animal research on alcohol addiction has literally saved their lives.

Thirdly, the fact of the matter is that the desperate need for medications for drug and alcohol abuse has led both NIDA and the National Institute on Alcoholism and Alcohol Abuse (NIAAA) to undertake many clinical trials for medications before there was adequate evidence for efficacy in animal models. Many of the failed clinical trials involved these kinds of medicines. Therefore, if one is concerned about the failure of clinical trials (and we certainly should be), we should be calling for more investment in research, including in research involving animal models. Saying that animal research had “green-lighted” every single medication is simply and unequivocally wrong.

It is for all these reasons that the drug abuse research community is incredibly supportive of animal-based research. The pre-eminent professional society in this area – the College on the Problems of Drug Dependence – which includes epidemiologists, neuroscientists, clinical psychologists and psychiatrists and policy experts has published a statement clarifying their position on animal research:

There is an urgent need to know more about psychoactive drugs, particularly those features that lead some individuals to escalate initial use into regular use or dependence.  Research with laboratory animals will play a key role in these and related efforts… The College on Problems of Drug Dependence recognizes the value and importance of drug abuse research involving laboratory animals and supports the humane use of animals in research that has the potential to benefit human health and society. Such research plays a vital role in acquisition of the new knowledge needed to understand and reduce drug abuse and its associated problems.

Because drug and alcohol abuse are diseases with far-ranging health effects, contributing to death from overdose, cancer, stroke and metabolic disease, all of the National Institutes of Health (NIH) have a clear interest in seeing research end addictions. Animal activists’ claims that former NIH director Elias Zerhouni has spoken against the value of animal research are misleading given that he has recently made his opinion clear:

I understand that some have interpreted these comments to mean that I think that animals are no longer necessary in medical research. This is certainly not what I meant. In fact, animal models and other surrogates of human disease are necessary — but not sufficient — for the successful development of new treatments. In short, animal models remain essential to the basic research that seeks to understand the complexities of disease mechanism.

Overall, opposition to animal research on addictions seems to require a deep misunderstanding of basic science research, of the state of current scientific understanding of addictions and their treatment and of basic principles of biology, like pharmacology. It also defies the overwhelming consensus of the scientific and drug abuse treatment community that emphasizes the critical need for more research, including animal-based research, in that effort.

J. David Jentsch

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.

Do animals suffer from human diseases?

A common argument heard against the use of animals in research is that animals do not naturally suffer from the same conditions as humans do.  Thus, the argument goes, it makes no sense to study human disease in animals.

However, my UCLA colleagues Barbara Natterson-Horowitz MD and Kathryn Bowers, authors of Zoobiquity, explain that the opposite is the case. The book along with videos explain how is that animals and humans indeed get many of the same diseases, and how knowledge from animal and human health is being used to improve the well being of both.

For example, often times it is stated that addiction is merely human problem.  But explained in the video below, animals also seek such substances in the wild, often with tragic consequences.

It is thus not surprising that scientists have made tremendous advances to study how substances alter the brain reward circuits that underlie such behavior.  You can learn more about addiction by visiting SfN’s brain facts web-site here.  For more examples of naturally occurring conditions, such as STD, eating disorders and breast cancer, are shared across species watch these other videos.

We should also remember that a disease does not need to occur naturally at a high frequency in animals for studies of animal models of it to be highly informative. An excellent example of this is the study of genetically modified mice, where in just the past week we have posted links on our Facebook and Twitter pages to articles discussing important scientific insights and promising therapeutic approaches by researchers studying the genetic disorder Rett syndrome, breast cancer,  the human prion protein diseases fatal familial insomnia and Creutzfeldt-Jakob disease, and HIV transmission. These examples, and the study of naturally occurring animal diseases mentioned earlier, serve to highlight the need for scientists to use a wide variety of species and disease models as they strive to understand biological systems and develop tomorrow’s medicines.

Speaking of Research

Oregon Scientists seek to understand the roots of Alcoholism

Just a year ago Professor David Jentsch wrote here about the importance of animal research in developing better ways to treat addiction; now Jim Newman of the Oregon National Primate Research Centre (ONPRC) has written in OregonLive about how research in monkeys is helping us to understand alcoholism and other forms of alcohol abuse, which are among leading causes of death, injury and illness in the United States.

In an interview yesterday with ABC20/20 ONPRC scientist Kathy Grant discusses the importance of research on Rhesus macaques in improving our understanding of why consumption of alcohol differs between  individuals, information which she hopes will help to prevent and treat alcohol abuse.

Speaking of Research wish Professor Grant and her colleagues well in their efforts to reduce the damage done to our society by alcohol abuse.

Addiction Research as an Example of Translational Biomedical Research

In science, “translation” embodies the concept that data gathered in one situation is meaningful for data gathered in another. Applied biomedical research seeks to translate laboratory research into effective treatments or cures. It spans many levels of study. In oncology (the field of cancer biology), some individuals study how cancerous cells grown in a dish operate and grow and how best you can destroy them. Others study tumor growth in animal models; they do this because the behavior of cells in a dish does not always fully predict how cancer will grow in a living body. Because we want to understand how cancer occurs and progresses in humans, yet other scientists use epidemiological or imaging techniques to directly study cancer patients. Information gained at one level informs and fosters the understanding of information gathered at other levels. No single experiment or scientist answers everything – it’s the collective work of the larger group of researchers working at all levels that pushes things forwards. This is how translation is made possible.

A hotly debated question in translational research is whether data gathered in animals 1) always, 2) often, 3) rarely or 4) never is meaningful for our understanding of human biology. Though most scientists and clinical practitioners feel strongly that it is often predictive, explicit examples are required to convince the broader public.  Clear evidence of translational value is found in research on the biology of drug addictions – something that I study in my laboratory. A large number of both rats and humans find drugs of abuse (cocaine, heroin methamphetamine, nicotine, etc.), when ingested, to be incredibly rewarding and will engage in significant drug-seeking behaviors to obtain it. In that sense, the study of these drugs’ effects on rats translates well (though not perfectly) to its effects on humans. Importantly, it translates “well enough” to make the rat a useful model organism in which to explore how drugs of abuse take control of some individuals by altering their brain chemistry. We have made excellent progress in this area over the last 15 years.

Of all areas of biomedical research, the study of the brain poses the biggest challenge for translational research because it is this organ that differs most across species. There is no doubt that a mouse’s brain is dramatically different from that of a monkey which is still different from that of a human. But do those superficial differences matter? Not as much as you might think! Let’s go back to the earlier example of drug abuse. Addictive drugs are chemicals that, when ingested, make their way into the brain where they alter the activity of brain cells, consequently changing the function of circuits in the brain that mediate reward. This is why they make people experience euphoria, relaxation and a sense of well-being after they take them. Remarkably, despite obvious differences in the brain, rats also very much enjoy the effects of these drugs. When offered an opportunity, they will take them voluntarily (e.g., press a button to trigger an injection of the drug). Even more impressively, even fish find addictive drugs rewarding. So, actually, despite the superficial differences, there is a huge amount going on in the brain that is similar across model organisms. This is because the anatomical differences between rat and human brains are actually much smaller than what is shared between them: common sets of circuits with similar functions.

This point is crucial. If fish and rats can be used to predict some of the responses of humans to addictive drugs, they can be used in translational research to explore the therapeutic effects of drugs used to treat brain disorders, such as addictions, as well.

It is important, however, to distinguish between what an animal model can reveal and what it cannot. In the case of chemical addictions, animal models can help you to understand the physiological and basic behavioral processes that drugs act on to alter the body. Again, studying the effects of an addictive drug in rats can help us to understand how it alters the reward circuit and how that relates to drug seeking. Here, translation is excellent. At the same time, it does not fully recapitulate the psychosocial consequences of drug taking in people. Because the drug is available for free, rats do not have to steal to get money to buy it. Because they are not expected to show up to work on time and be productive, drug use does not cause them to get fired from their jobs. Because they do not get married, they are not at risk of divorce when their drug-taking behavior gets out of control. Because they do not share needles, they are not at risk of hepatitis C or HIV infection. So, from a biological perspective, study of addiction can be modeled well in rats, but the psychosocial consequences are not. Rat researchers have revealed the neural mechanisms by which addictive drugs act in exquisite detail, and all modern, FDA-approved treatments for drug dependence arose from basic, mechanistic studies in animals (examples include Revia for the treatment of alcohol dependence and Chantix for smoking cessation). Clinical researchers then are able to tell us whether and how these treatments affect psychosocial functions in drug users. In that sense, like our colleagues who study cancer, we integrate study from many levels together to fully understand the biology and psychosocial consequences of drug abuse and its treatment.

It is because research at many levels integrates so well that providers of clinical intervention often closely study and attend to studies conducted in animals. An international society called the College on the Problems of Drug Dependence brings together scientists, physicians and social workers who are particularly interested in solving problems relating to addiction. Here, each attendee carefully studies the results of the other researchers – with studies in humans designed based upon clinical observations, and clinical tests being spurred by rat studies.  There is little doubt in the group – whether one consults patient-oriented researchers or people that examine cells growing in a dish – that studies of living animals are a critical part to the overall translational effort to stem the impact of addictions on affected individuals. Though animal research will not solve all of the mysteries of addiction, or of any complex human disease process, it is a foundational part of most areas of biomedical research and patients, patient advocacy groups and treatment providers overwhelmingly support it.

Regards

David Jentsch