Category Archives: Science News

Research with dogs develops an artificial pancreas to treat diabetes

White Coat Waste is a conservative animal rights organization devoted to the elimination of animal research. Its first target is biomedical research conducted using dogs at the US Department of Veterans Affairs (VA). Unfortunately, this campaign is gaining traction. While White Coat Waste is supported mainly by Republicans, some Democrat representatives like Dina Titus (Nevada) and Ted Lieu (California) have expressed their support. In view of that, it is important to highlight the remarkable achievements of dog research at the VA and the tremendous loss that its cancellation would be for Veterans and the general public. 

Diabetes is a nasty disease that affects millions of people worldwide and continues to increase. It is a metabolic disorder in which the body becomes incapable of controlling the blood levels of glucose, either because the pancreas fails to produce enough insulin (type 1) or because cells in the body fail to respond to insulin (type 2). Untreated, diabetes can lead to cardiovascular disease, stroke, kidney disease, neuropathic pain, gangrene of the extremities, amputations, blindness, and death. In 2014, 422 million people had diabetes worldwide (8.5% of the population). These numbers have more than tripled since 1980 (108 million; 4.7% of the population) and continue to increase due to poor dietary habits and lack of exercise. The annual number of deaths worldwide was estimated at 4.9 million in 2014. The incidence of diabetes is particularly high in the USA and other developed countries, but it is increasing fast in Asia and Africa. In the USA, diabetes has a high impact in Veterans: one in four patients receiving care at the US Department of Veterans Affairs (VA) has diabetes. This makes it a high priority for medical research at the VA.

People with serious cases of diabetes need multiple daily injections of insulin. Failure to administer the insulin appropriately can lead to kidney failure, amputations, blindness, coma, and even death. However, the dose of insulin has to be tuned to the needs of the body. To do this, patients measure the glucose level in their blood by drawing blood from their fingers using needle sticks. This has to be done several times a day in order to calculate and inject insulin according to the blood glucose levels. An artificial pancreas has been developed at the VA to help improve the outcomes for diabetic patients. This device measures glucose in the blood in real time and automatically administers the right dose of insulin. This technology will dramatically improve the patient’s quality of life and reduce life-threatening complications. It would also tremendously reduce diabetes-related healthcare costs.

The artificial pancreas uses a reconfigured smart phone as part of its system. Image by UVA

This research project was initiated decades ago by Dr. Seymour Levin, a VA endocrinologist who specialized in diabetes and was horrified by the large number of VA patients who needed amputations because of problems with properly administering insulin to treat their diabetes. He obtained funds from the Mann Foundation. In the early 1980s, the Mann Foundation created a company called MiniMed Technologies to design an insulin pump that patients could wear throughout the day. MiniMed Technologies used dogs at the VA diabetes laboratory to test prototypes of this pump. In the early 2000s the company was acquired by Medtronic, which has been fully supporting this research project ever since. No taxpayer money has been used for it, a detail that seems to be important for White Coat Waste.

Taking advantage of new computer technology, the device being developed incorporates not only an insulin pump but also a glucose sensor and software to calculate the amount of insulin to be injected into the blood according to the glucose level. This makes it a true artificial pancreas. Working with dogs allows researchers to do the pre-clinical testing of the artificial pancreas required for approval by the USA Food and Drug Administration (FDA) at the same time that the hardware and the software are refined and improved.

Why use dogs for this research project? Animals like mice, rats or guinea pigs are too small for the devices being tested and their blood volume is not large enough to allow for frequent blood sampling without causing them harm. On the other hand, dogs have been an important model for metabolic studies and can replicate human diabetes quite well (much early research into diabetes and insulin relied on research in dogs). They can also be used for long-term studies lasting years, which are not possible in rodents. The sensors and catheters implanted in the dogs are the same ones to be used in humans, and the dogs adapt very well to wearing them. Dogs also like interacting with humans and can be trained to go along with these painless procedures without needing to be anesthetized or restrained. Other large animals like pigs and sheep were tried and were found to be far less suitable than dogs for this work.

The standard procedure consists of having the dog rest on a soft bed, unrestrained. Glucose sensors are inserted under the skin and an insulin pump is attached via a subcutaneous catheter (similar to a human patient using these devices). The procedures are painless and the dog soon becomes habituated to them. The dog is given a small amount of glucose solution to raise its blood-glucose level in order to see how the experimental sensor, software, and pump respond. Blood samples are then tested on a large and expensive glucose analyzer to see how well the sensor is working.

The dogs in the VA diabetes research project are very well cared for, and the diabetic ones are maintained on insulin pumps. Pet dogs sometimes develop diabetes as they age. Just like humans, they develop cataracts, kidney problems and all the other complications of diabetes. Even when they are given insulin injections under a veterinarian’s care, they all die within 1-2 years. In contrast, the diabetic dogs in this research program are maintained free of symptoms by the insulin pumps and live at least a decade with no cataracts or other diabetes complications. Non-diabetic dogs are adopted out at the end of the study period whenever feasible.

dog, animal testing, animal experiment

Beagle in research

On September 28, 2016, the FDA approved the first artificial pancreas, the Medtronic’s MiniMed 670G System, intended to automatically monitor blood-glucose levels and adjust basal insulin doses in people with type 1 diabetes. The pre-clinical testing of this device was all done on dogs at the VA diabetes research laboratory. However, the research project is ongoing and much work remains to be done. If it is canceled due to political pressure from White Coat Waste, it would be a huge loss for Veterans and the millions of people worldwide who need more reliable ways to treat their diabetes.

Juan Carlos Marvizon, Ph.D.

References:

  1. Grosman B, Voskanyan G, Loutseiko M, Roy A, Mehta A, Kurtz N, Parikh N, Kaufman FR, Mastrototaro JJ, Keenan B. Model-based sensor-augmented pump therapy. J Diabetes Sci Technol. 2013 Mar 1;7(2):465-77.
  2. Loutseiko M, Voskanyan G, Keenan DB, Steil GM. Closed-loop insulin delivery utilizing pole placement to compensate for delays in subcutaneous insulin delivery. J Diabetes Sci Technol. 2011 Nov 1;5(6):1342-51.
  3. Panteleon AE, Loutseiko M, Steil GM, Rebrin K. Evaluation of the effect of gain on the meal response of an automated closed-loop insulin delivery system. Diabetes. 2006 Jul;55(7):1995-2000.

Research Roundup: Cholesterol vaccine in mice, zebrafish & osteoporosis, new cytomegalovirus treatment, and more!

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

  • Human trials of cholesterol-lowering vaccine are underway after success in mice. This vaccination is designed to stop fatty deposits from clogging arteries — reducing the effects of a form of cardiovascular diseases known as atherosclerosis. This vaccination targets a protein called PCSK9 that allows low density lipoprotein (LDL; “bad cholesterol”) to accumulate in the arteries. In mice, this treatment reduced LDL levels up to 50% over 12 months. This vaccination provides promise of a simpler way “to target high cholesterol and ultimately reduce people’s risk of heart disease.” An editorial on this research was published in the European Heart Journal.

Blocked arteries impede blood flow. Source: Getty.

  • Zebrafish, genetics and osteoporosis. The zebrafish’s ability to regenerate body parts, including scales and fins, has led to their involvement in the study of bone physiology and repair, as well as the identification of treatments for human bone diseases. Researchers at the University of Malta are working with zebrafish as a model to investigate osteoporosis, specifically the genetic factors that may contribute to the disease.  Dr Melissa Marie Formosa, a researcher involved in the project ‘Genetics of Osteoporosis’, writes, “The ultimate aim of genetic research remains that of elucidating the best treatment options based on the person’s genetic make-up and predicting disease outcome in susceptible individuals.”

Healthy bone, left, and osteoporosis, right. Source here.

  • An alternative explanation for loss of consciousness during anaesthesia was published this week in PLOS Computational Biology. Scientists typically speculate that when animals and humans are given anaesthesia, communication between brain areas is disrupted thus leading to loss of consciousness. Although such speculations have been previously tested and suggested to be true, the logic behind such speculation is questionable. Specifically, communication only seems to decrease when less information is available to exchange, thus loss of information should “reduce” rather than “disrupt” communication between brain areas. With these thoughts in mind, German neuroscientists measured brain activity in two ferrets over 3 trials of anaesthesia and recovery — increasing the amount of anaesthesia each time. Their measurements suggested that the ferrets’ brain activity was more subdued when anesthetized, but it didn’t seem communication was disrupted. Rather, the brain areas that send communication signals were less active, and the brain areas that receive communication signals were just as active as normal. This brings into question our current understanding of the mechanisms behind anaesthesia, and will be a starting point for future research in this area.

Lab-housed ferrets. Source: NC3Rs.

Image of mice courtesy of Understanding Animal Research

  • Drug used to treat anxiety found to be effective against the effects of cytomegalovirus (human herpes 5), which can cause major birth defects such as microcephaly, seizures, developmental disabilities, and deafness. Approximately 50% of all humans over the age of 40 harbour the cytomegalovirus and approximately four in 1000 babies suffer massive defects as a consequence. Mice treated during the first three weeks of life with valnoctamide — a drug used in the treatment of anxiety — were found to have reduced levels of the virus available for entry to the brain, to have restored timely acquisition of neurological milestones, and to display rescued motor and behavioral outcomes. Given the pervasiveness of this virus and its debilitating effects, and also that there is no vaccine against this virus, this work is extremely timely and promising. This study was published the Journal of Neuroscience.

Cytomegalovirus (CMV) virus. Source: J. Cavallini.

Research Roundup: Monkeys and face recognition, animals advance AI, sugar to treat heart disease, and more!

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

  • New study challenges our current understanding of how the brain recognizes faces. We can often pick out a face or a person in a crowd (e.g., finding Wally/Waldo), but the cellular mechanism via which this occurs has remained poorly understood. Using rhesus macaques, these researchers investigated which neuronal cells are responsible for facial recognition. By varying aspects of the face systematically (e.g., shape, distance between the eyes) and measuring 205 neurons in 2 animals, researchers found that each neuron responded to a specific combination of facial parameters rather than the face itself, using fMRI. In other words “the neuron is not a face detector, it’s a face analyser”, says Leopold. The brain “is able to realize that there are key dimensions that allow one to say that this is Person A and this is Person B.” Subsequent replication and extension using more subjects is warranted, but these findings provide an exciting new avenue of research with regards to face processing. This research was published in the journal Cell.

    Macaque. Source: Kathy West. CNPRC.

  • Researchers are using animal cognition to make advances in artificial intelligence.  Harvard assistant professor David Cox and his team are studying the rat visual cortex by training rats to play a complex object discrimination video game. While the rats are learning the video game, a 2 photon excitation microscope images neural activity in the visual cortex. These images are then used in conjunction with microscopic images of brain tissue slices to make digital maps of of the visual cortex. The hope is that these neural circuits could become maps for artificial neural networks and next generation artificial intelligence. Check out this video on “How to Digitize a Rat Brain”!
  • Artificial intelligence system detects pain levels in sheep. Researchers at the University of Cambridge have developed an artificial intelligence (AI) system which uses five different facial expressions to recognize whether a sheep is in pain, and to estimate pain severity. Building on earlier work which teaches computers to recognize emotions and expressions in human faces, Dr. Krista McLennan developed the Sheep Pain Facial Expression Scale (SPFES) in 2016, which can recognize pain with high accuracy. In the current study, Dr. Peter Robinson and colleagues developed machine learning techniques to reduce the time required for humans to learn to use SPFES, as well as the confounds of human bias in interpreting facial expressions. Researchers trained the AI model with a small dataset of about 500 photographs of sheep, and early tests showed that the model could estimate pain levels with about 80% degree of accuracy, indicating the system is learning. The next steps for the researchers will be to train the system to detect and recognize sheep faces from moving images, and to train it to work when the sheep are in profile. Ultimately, this research will lead to better pain detection and faster medical attention. The research was presented June 1 at the IEEE International Conference on Automatic Face and Gesture Recognition in Washington, DC.

    Face detection in sheep. Source: Liu et al., 2017, University of Cambridge

  • Lifelong protection from allergies a possibility? When your body comes into contact with a foreign particle, for example, pollen, your immune system kicks into play, producing antibodies (Immunoglobulin E). These antibodies travel to these foreign cells, attempt to “neutralize” them and in this process – triggers an allergic reaction. In order to quickly identify and mount a response to foreign particles that your body has encountered before, the body uses “memory” T cells. However, in some cases, this “memory” may be an “overreaction” of the system and once this “memory” is formed it is virtually impossible to be removed. In the present study using
    mice
    , researchers tackled this issue and were able to desensitize these memory cells which overreact to allergens using therapeutic gene transfer. Approximately 50 million American suffer from some form of allergic disease and this research, which is in pre-clinical trials, provides some hope of treatment. This study was published in the journal JCI Insight.

  • Type of sugar may treat atherosclerosis, mouse study shows. Researchers at the Washington University School of Medicine in St. Louis worked with mice prone to atherosclerosis, clogged arteries due to the buildup of plaque, and found that when injecting trehalose, a natural sugar, the immune system “cleans up” this plaque.  Babak Razani, MD, PhD, an assistant professor of medicine, and his colleagues showed that trehalose activates TFEB, a molecule that then.goes into the nucleus of macrophages and binds to DNA. This turns on specific genes and leads to additional organelles that act as “housekeeping machinery.”  Babak says, “Trehalose is not just enhancing the housekeeping machinery that’s already there,” Razani said. “It’s triggering the cell to make new machinery..”  Trehalose is a mild sweetener and FDA approved for human consumption.  Plaque degradation is not seen when administered orally.  Researchers hope to study trehalose as a potential therapy for atherosclerosis in hopes to find a way to protect its  housekeeping properties when given orally.

    Cross section of mouse aorta with a large plaque. Source: Ismail Sergin

 

 

 

Last surviving member of Pittsburgh polio vaccine team dies at 96

Dr. Julius S. Youngner, the last surviving member of the team that developed the Salk polio vaccine in the 1950s, died in his home on April 27 at the age of 96.

Yougner - Image by University of Pittsburgh

Dr. Julius Youngner. Photo courtesy of University of Pittsburgh

Dr. Youngner, like many scientists, pursued a passion to help people via his love of the scientific method.  His own experiences as a child recovering from numerous infectious diseases, including severe pneumonia that almost killed him at age 7, inspired him to pursue a career in science — specifically, virology.

His interest in infectious disease led him to join Dr. Jonas Salk’s vaccine team at the University of Pittsburgh in the quest to fight polio. Polio crippled an average of 1,000 children every day in more than 125 countries during its peak.  The polio vaccine ended this serious illness that plagued the United States from the late 1800s to the mid-20th century.

Dr. Youngner made three critical advances in the polio vaccine research, much of which relied on research with animals. He first devised a way to break down monkey cells so the team could grow large quantities of poliovirus in the lab. He then developed a way to inactivate the virus so it could be safely injected as a vaccine, and finally, he developed tests to determine the vaccine’s effectiveness in the first human patients. The number of polio cases went from an average of 35,000 a year before the vaccine to fewer than 2,500 two years later. Today, polio is virtually eradicated in the United States and much of the world.

Since his polio work, Dr. Youngner made other major advances in virology and immunology, continuing to rely on animal models. Youngner was the first to demonstrate that non-viral agents could trigger interferon infection in animals, and his research team devised a novel approach to antiviral therapy. By demonstrating that the live, attenuated virus vaccine for influenza A interacts with wild-type influenza to confer protection, rather than inducing a protective immune response, Youngner and his team demonstrated that this type of vaccine, tested in animal models, has the potential for significantly reducing morbidity and mortality associated with influenza.

A comprehensive obituary of Dr. Youngner, including his work on the Manhattan Project and his feud with Dr. Jonas Salk, was published on April 28 by the Pittsburgh Post-Gazette.

Research Roundup: An artificial womb for preemie lambs, umbilical cord protein enhances cognition, smartphones to control diabetes, and more!

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

  • An artificial womb has successfully kept premature lambs alive. Extreme prematurity — infants born at 22 to 23 weeks gestation — is a leading cause of infant mortality, and infants who do survive often have serious disabilities like cerebral palsy or major cognitive deficits. Researchers at the Children’s Hospital of Pennsylvania have developed a first-of-its kind artificial womb that mimics the uterine environment, and have found in studies of lambs that this womb allows the premature lambs to grow normally inside the womb for 3-4 weeks. The thought is that treating the preemies more like fetuses than newborns by extending normal gestation may give them a better chance of survival. The artificial womb, pictured below, is a fluid-filled transparent container that simulates how fetuses float in amniotic fluid inside the mother’s uterus. The womb is attached to a mechanical placenta that keeps blood oxygenated for the fetus. Over the four weeks of study, the lamb fetuses grew to open their eyes, grow wool, breathe, and swim. Human trials are still several years away, though the research team is already in discussions with the Food and Drug Administration. The study was published in Nature Communications and is freely available for download.

  • New research finds that at least one third of all gut nerve cells are replaced weekly. The gut contains the second largest nervous system in the body, the enteric nervous system. Similarly to the number of viable eggs that a woman is born with, it was a once held scientific belief that the gut nerve cells we’re born with are the same ones that we die with. Using healthy adult you mice, and a variety of modern techniques, this study confirmed previous research findings of ongoing neuronal cell loss because of apoptosis (cell death) — although total neuronal numbers remain constant. This observed neuronal homeostasis was found to be maintained from dividing precursor cells that are located within myenteric ganglia. Mutation of these adult precursors led to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Since gut nerve cells were thought to remain unchanged across time, it has limited our understanding and treatment of diseases which affect the gut. These results “enable a new understanding of the pathogenesis of enteric neuromuscular diseases as well as the development of novel regenerative therapies.” This study was published in the Proceedings of the National Academy of Sciences.

  • A new study finds that protein found in human blood makes mice smarter. Previous research investigating the effects of young blood on aging animals has generally focused on within (same) species comparisons. In this study, researchers investigated the role of a human umbilical cord plasma and its effects on aged mice — in particular with respect to hippocampus and behavioral measures of cognition. These particular measures were investigated as impairment is observed in older individuals. They found that human plasma, injected in mice, was associated with revitalization of the hippocampus with increased levels of gene expression there. Additionally, they found that behavioral measures of cognition were also improved. The protein tissue inhibitor of metalloproteinases 2 (TIMP2), was found to be implicated with these positive changes. This study has been published in Nature.

    hippocampus

    Schematic of the hippocampus. Source.

  • The European Ombudsman rejected a complaint by the “Stop Vivisection” European Citizens Initiative that they had not received adequate reasoning behind the decision by the European Commission to reject the initiative in July 2015. “Stop Vivisection” wanted to repeal the European animal research regulation, Directive 2010/63/EU and replace it with a proposal to speed a ban on such practices. The ombudsman noted that the Commission has complied with its duty to explain, in a clear, comprehensible and detailed manner, its position and political choices regarding the objectives of the ECI “Stop Vivisection””.
  • A new study uses your smartphone to control symptoms of diabetes. In a good example of multi-disciplinary translational medicine, and using “a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology” researchers based at the Shanghai Key Laboratory of Regulatory Biology “engineered a technological infrastructure enabling smartphone-assisted semiautomatic treatment of diabetes in mice.” Hydrogel capsules, containing cells that could produce “mouse insulin” in vivo and which contained wirelessly powered infrared LEDs were implanted in mice. Smartphones were then used to control this implant causing it to secrete “mouse insulin” as needed. Researchers were able to maintain glucose homeostasis over several weeks in the diabetic mice. This study provides a step toward translating cell-based therapies into the clinic. It also highlights that even though this technique was developed in vitro, safety and efficacy trials in animals are needed before they can be used in humans. This study was published in the journal Science.
Apr27_2017_ShanghaiKeyLabOfRegulatoryBiology_DiabeticMouseSmartPhone2447847722.jpg

Photo courtesy of Shanghai Key Laboratory of Regulatory Biology

Open letter: Private workshop on the “necessity” of monkey research does not represent broad public interests or the scientific community

This weekend there will be science marches around the globe. Scientists and science proponents will gather to provide a visible sign of support for work that benefits the public, the environment, and the world in innumerable ways. The march has been highly publicized  – rightfully so, because it serves as a reminder that scientific research and scientists can be threatened in a variety of ways that can have consequences with breadth and depth that should be of concern for society as a whole.

This week there will also be another event that has potential for consequences for science and public health. But it is neither a public event, nor one that has been publicized.

The private event is a workshop titled, “The necessity of the use of non-human primate models in research.” The workshop is supported by Johns Hopkins University and is organized by Prof. Jeff Kahn in the Berman Institute for Bioethics, with participants that include philosophers, bioethicists, a leader of the Humane Society of the US, veterinarians, and scientists– all by invitation only (see roster in workshop agenda below). Its stated goals and approach are: “To help address the issues of the use of NHPs in research, we are convening this working group to examine the science, ethics, and policy aspects of the use of NHPs in biomedical and behavioral research and testing, with the goal of identifying consensus findings, conclusions, and recommendations. The focus of the working group will be to evaluate the current and potential future uses of NHP models, drawing on the approach used in the 2011 IOM Report “Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity” (IOM, 2011).

The group lists as their objective: “The product(s) of the working group process will be a report or series of reports based on the working group’s expert analysis, which will include principles and criteria for assessing the necessity of the use of NHPs in research.” (emphasis added)

Detail is here: Animal Working Group Meeting 1 Briefing Book

In other words, the working group, privately convened, is intent on replicating the 2011 IOM process applied to chimpanzees in order to produce their own principles and criteria for assessing nonhuman primate research broadly. This process should cause grave concern for scientists and for the public who rely on research conducted with nonhuman primates.

The scientific community has publicly weighed in on the necessity of primate research. Most recently, the National Institutes of Health convened a working group to consider nonhuman primate research and concluded “that the oversight framework for the use of non-human primates in research is robust and has provided sufficient protections to date.” Similarly, a letter from over 400 scientists, including Nobel Laureates, rejected a claim from notable public figures that neuroscience research with non-human primates is no longer useful. The hundreds of scientists argued that, “primate research was still critical for developing treatments for dementia and other debilitating illnesses.” (https://www.theguardian.com/science/2016/sep/13/brain-experiments-on-primates-are-crucial-say-eminent-scientists)

Consideration of the ethical justification for research and of the care for animals in research occurs at many levels and in public space. Public health, including the interests of patients and of society as a whole, is integral to those decisions. The scientific community provides expert knowledge about what types of studies are needed for progress in the basic understanding of biology, brain, behavior, and disease and also about how to move forward with new prevention, intervention, and treatment to address health challenges. Funding agencies, such as the National Institutes of Health, are charged by the public to make decisions about science and do so through a process that involves multiple layers of expert review. Federal agencies also oversee research and standards of care for humans and animals involved in studies and provide opportunities for the public to comment on standards and to benefit from decisions.

The private workshop has the appearance of being secretive while also directly opposing the processes in place for responsible public decision-making. As such, it appears to be yet another attempt to influence decisions about science without adequately representing either public interests or the breadth and depth of expertise in the scientific community. Without adequate scientific representation the workshop conclusions cannot be taken as adequately representative of the current state of scientific knowledge. Without adequate representation of the public agencies that safeguard societal interests in scientific and medical progress the workshop conclusions cannot be taken as representative of fact-informed, balanced consideration of research.

Finally, without consideration informed by understanding the fundamental characteristics of the scientific process, the workshop conclusions will only reflect an agenda biased to reach a particular conclusion. As it is framed, it appears that the question of “necessity” is one that cannot account well for the role of basic research, of uncertainty, and of the difference between decisions based in a particular set of values and decisions about the best scientific course of action to answer questions and advance understanding of human and animal health.

For all of these reasons, the reports emanating from this private workshop must be critically examined with healthy skepticism, rather than taken as an authoritative account. We remain concerned that the products of a workshop will serve to advance an agenda that is harmful to public interests in scientific research.

[Note:  If you would like to sign on to this letter please add your name to the comments].

Signatories,

Christian Abee, DVM, DACLAM, Professor and Director, Michale E. Keeling Center for Comparative Medicine and Research, Univ. of TX MD Anderson Cancer Center

Jeremy D. Bailoo, PhD, University of Bern

Allyson J. Bennett, PhD, University of Wisconsin-Madison (Member and former chair, American Psychological Association Committee on Animal Research Ethics)

Michael J. Beran, PhD, Psychology Department and Language Research Center, Georgia State University

James Champion, Morehouse School of Medicine

Julia A. Chester, Ph.D., Associate Professor, Department of Psychological Sciences, Purdue University

Linda C. Cork, D.V.M, Ph.D, Emeritus Professor of Comparative Medicine, School of Medicine, Stanford University  (Senior member of the National Academy of Medicine;  Diplomate of the American College of Veterinary Pathologists)

Robert Desimone, Ph.D., Director, McGovern Institute for Brain Research at MIT, Doris and Don Berkey Professor of Neuroscience

Doris Doudet, PhD, University of British Columbia

Marina Emborg, MD, PhD, Associate Professor, Department of Medical Physics; Director, Preclinical Parkinson’s Research Program, Wisconsin National Primate Research Center, University of Wisconsin-Madison

Lynn Fairbanks, PhD, Emeritus professor, Department of Psychiatry & Biobehavioral Sciences, Semel Institute, UCLA

Charles P. France, Ph.D., Professor, University of Texas Health Science Center-San Antonio

Patrice A. Frost, D.V.M, President of, and signing on behalf of, the Association of Primate Veterinarians

Michael  E. Goldberg, MD,  David Mahoney Professor of  Brain and Behavior in the Departments of Neuroscience, Neurology, Psychiatry, and Ophthalmology
Columbia University College of Physicians and Surgeons,  and Senior Attending Neurologist, New York Presbyterian Hospital. (Past chair, Society for Neuroscience Committee on Animal Research)

Katalin M. Gothard, MD, PhD, Professor of Physiology, The University of Arizona

Kathleen A. Grant, PhD, Professor, Oregon National Primate Research Center

Sherril Green, DVM, PhD, Professor and Chair, Department of Comparative Medicine, Stanford Medicine

Nancy L. Haigwood, PhD, Director and Professor, Oregon National Primate Research Center, Oregon Health & Science University

Keren Haroush, PhD, Assistant Professor, Department of Neurobiology, Stanford University

William D. Hopkins, PhD, Professor of Neuroscience, Neuroscience Institute, Georgia State University

J.David Jentsch, PhD, Professor of Psychology, Binghamton University

R. Paul Johnson, MD, Director, Yerkes National Primate Research Center

Joseph W. Kemnitz, Ph.D., Professor, University of Wisconsin-Madison

Robert E. Lanford, PhD, Director, Southwest National Primate Research Center, Texas Biomedical Research Institute

Kirk Leech, Executive Director, European Animal Research Association

Jon Levine, PhD, Director, Wisconsin National Primate Research Center; Professor of Neuroscience, University of Wisconsin-Madison

Alexander Maier, Ph.D., Assistant Professor, Department of Psychology, Vanderbilt University

Juan Carlos Marvizon, PhD, Adjunct Professor, David Geffen School of Medicine at UCLA

Earl K. Miller, Ph.D., Picower Professor of Neuroscience, The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology

John H. Morrison, PhD, Director, California National Primate Research Center, Professor, Department of Neurology, School of Medicine, University of California Davis

Michael Mustari, PhD, Director, Washington National Primate Research Center and Research Professor, Department of Biological Structure, University of Washington

J. Anthony Movshon, University Professor and Silver Professor, Center for Neural Science, New York University

William T. Newsome, Harman Family Provostial Professor, Stanford University, Vincent V.C. Woo Director, Stanford Neurosciences Institute
Investigator, Howard Hughes Medical Institute

Melinda Novak, PhD, Professor of Psychological and Brain Sciences, University of Massachusetts Amherst

Kimberley A. Phillips, PhD, Professor of Psychology and Co-Director of Neuroscience, Trinity University; Affiliate Scientist, Southwest National Primate Research Center, Texas Biomedical Research Institute

Peter J. Pierre, PhD, Behavioral Services Unit Head, Wisconsin National Primate Research Center, University of Wisconsin-Madison

Dario Ringach, PhD, Professor of Neurobiology and Psychology, University of California Los Angeles

Marcello Rosa, PhD, Professor of Physiology, Monash University, Melbourne, Australia

James Rowlett, PhD, University of Mississippi Medical Center (Chair, American Psychological Association Committee on Animal Research Ethics)

Mar Sanchez, PhD, Associate Professor of Psychiatry and Behavioral Sciences, School of Medicine; Yerkes National Primate Research Center, Emory University (Chair, Society for Neuroscience Committee on Animal Research)

Jeffrey D. Schall, Ph.D., Bronson Ingram Professor of Neuroscience, Department of Psychology, Department of Ophthalmology & Visual Sciences, Director, Center for Integrative & Cognitive Neuroscience, Department of Psychology, Vanderbilt University

Igor I. Slukvin, MD, PhD, Wisconsin National Primate Research Center, University of Wisconsin-Madison

David A. Washburn, PhD, Professor of Psychology, Georgia State University

Robert Wurtz, PhD, Scientist Emeritus, National Institutes of Health

 

Thomas Starzl (1926-2017) – The man who saved countless humans using animal research

Dr. Starzl, a pioneer in the field of surgery and the “father” of organ transplantation in humans, was the first surgeon to perform a human liver transplant.

The liver is a remarkable organ, although more specifically it is a gland. It is essential to the functioning of the human body and is involved in metabolism, the production of hormones, detoxification — to name a few of its many functions. Unlike some of the other organs in the human body — of which we have two, such as the kidneys — there is no redundancy for the liver. For example, if one kidney fails the other kidney can compensate for the loss of function, and in many cases people with one kidney can live a normal life. In contrast, in cases of liver failure the only way to continue living would be liver transplantation; although in the short term — usually while waiting for a liver transplant — liver dialysis may be used. However, the liver is quite remarkable, and unlike many other organs possesses the capacity to regenerate, even if as much as 50 to 75% of the organ is damaged. Chronic liver disease, lasting more than six months, is debilitating and if not assessed early and treated (where possible) leads to death. It is estimated that over 50 million people are impacted from chronic liver disease.

Dr. Starzl’s work on human organ transplants was based on his earlier fundamental (basic) research in dogs. Unaware then of the potential application to humans, Dr. Starzl was investigating the role of nutrient rich blood and its contribution to liver health. Dr. Starzl formulated this question based on a lecture by Dr. Stuart Welch in 1957, who described an experiment where he had grafted an extra liver into a dog. In this experiment, blood left the grafted liver via the same system as the original liver, while the system bringing blood to the liver was different. Dr. Starzl hypothesized that the reason Dr. Welch’s transplant failed was a consequence of the different blood supply which brought blood to the liver.

Image courtesy of the University of Pittsburgh

In his subsequent investigations, Dr. Starzl developed and refined several liver transplant procedures in dogs — with his first success (survival after the operation) occurring in 1958. Between then and 1963, when the first human liver transplantation occurred, much research was being performed into immunosuppression by Dr. Roy Calne — also in dogs. This research was integral to the organ transplant field. Without understanding immunosuppression, the body would reject the donor organ; rendering the transplant useless. This pioneering work, in conjunction with Dr. Starzl’s own work, led to the first attempt at a human liver transplant in 1963. This first transplant was not successful, with the patient dying during the operation. Subsequent operations also resulted in patient death within a few weeks. However, those deaths provided evidence that the donor liver was able to function in the recipient’s body.

Dr. Starzl continued to refine and update his method, later moving his investigations to pigs — grafts from pigs were better tolerated by the human recipient. Then in 1967, he reopened his program and performed the first successful human liver transplant. Mortality after the procedure decreased over time, and “more than half of the liver-transplant patients who underwent surgery in 1998 were alive ten years later, and in 2009, almost 50,000 Americans carried a transplanted liver” (Lasker Foundation).

In 2012, Dr. Starzl and Roy Calne were honoured with the Lasker Award for their pioneering work in liver transplantation – “an intervention that has restored normal life to thousands of patients with end-stage liver disease”.

Complete liver replacement in the dog. The fact that the recipient was a dog rather than a human is identifiable only by the multi-lobar appearance of the liver. Image from University of Pittsburgh

Dr. Starzl was a brilliant scientist with a prolific career; over 2200 articles, 26 honorary degrees, and thousands of lives helped/saved by his work. We have previously written about this here; discussing him receiving the Lasker award. Similar to that post, we recommend reading about Dr. Starzl and his remarkable life here. We also encourage our readers to reflect upon his work, and the remarkable progress that was made using non-human animals for research. In particular, much of his pioneering work was derived from fundamental research investigating surgical procedures in dogs and his later work, refining the method, involved other non-human animals: pigs and baboons. It is often difficult to estimate the prospective benefit of research performed in non-human animals — but Dr. Starzl’s work is a great example of the potential reach of such research.

Jeremy Bailoo