Tag Archives: monkey

American Society of Primatologists’ statement of support for NIH primate research

The nation’s largest primatological scientific society, the American Society of Primalogists (ASP), has posted a strong statement sent January 21 in support for the scientist and research under attack by PETA.  The statement can be found on ASP’s website: https://www.asp.org/index.cfm

ASP home page Jan 2015

In its entirety, the letter reads:

“Members of the Board of Directors of the American Society of Primatologists would like to add our comments to the discussion of the validity and effectiveness of non-human primate research as it pertains to human behavior and medicine. Non-human primate research (on monkeys and apes) has had widespread effect on improving the diagnosis and treatment of many adult and childhood diseases. Studies that have employed the judicious use of non-human primates as models for human illness have improved our understanding of such disorders as autism, childhood leukemia, cerebral palsy, and mental health.1 The long-term research of one scientist, Dr. Stephen Suomi, has been called into question as a result of inaccurate, misguided and inflammatory media accounts. Our comments will address Dr. Suomi’s work and the value of non-human primates in understanding human biology, illness and behavior.

Dr. Suomi’s research has focused on the influence of variable environments and genetics on infant development, and by extension variation in adult behavior2. He and his colleagues found that early changes in the degree of attachment between mother and infant have real biological, not only behavioral influences on adult social behavior3. If this finding seems intuitive, it is evidence that the benefits of research have permeated not only the scientific, but also mainstream media4 and literature. Infant subjects are either mother-reared or reared in same-aged groups of monkeys. Infants may undergo temporary isolation during the study5 to facilitate comparison among groups that are reared differently. The goal of much of this research is to mimic separation that every social animal, including humans, undergo during their lifetimes and to understand why individuals respond differently to separation. One such research focus is the development of risk factors leading to mental illness in humans.

The American Society of Primatologists supports research on non-human primates that is carefully designed and employs rigorous research protocols. Dr. Suomi’s research and consistent funding by the NIH attests to his adherence to prescribed protocols and regulations.

Before research can begin, proposals are thoroughly vetted by both their institutional ethical oversight board (in the United States these are called Institutional Animal Care and Use Committees or IACUCs) and by the review boards of granting agencies (e.g., NIH, NIMH, NSF). This very extensive process requires prospective researchers to respond to questions such as those raised in your letter, e.g., your concern about redundant research. Per both the Animal Welfare Act and Regulations (AWARs) and the Public Health Service Policy on the Humane Care and Use of Laboratory Animals (PHS Policy), research funded by federal and state governments, as well as private foundations, must demonstrate that the project they propose will advance knowledge in the field, be relevant to human biology or behavior, and will not duplicate the efforts of previous research. The number of animals used in experiments must also be justified as well as the conditions in which the animals are housed, the duration of the project, and the protocols implemented during experiments. The scientists employed by the NIH have been leaders in the development of safe, effective, and reliable research protocols whether the research is done on mice or monkeys.

Because of the close genetic relationship between humans and non-human primates, monkeys are important models for studying particular biological phenomena, including the research conduct by Dr. Suomi. Nevertheless, non-human primates are rare in laboratory populations making up < 1% of the laboratory animals used in research (Government statistics from 2010, cited in Phillips et al., 20146). Furthermore, species are carefully matched to proposed studies.

We appreciate your attention to this matter, and ask that you please send us a response letting us know the charge to the NIH Bioethics Review Board.

Respectfully submitted,
Marilyn A. Norconk, President; Justin A. McNulty, Executive Secretary; Kimberley A. Phillips,  President-Elect; Corinna N. Ross, Treasurer; Karen L. Bales, Past-President

 

Supporting science: NIH answers PETA

The National Institutes of Health released a statement Monday in support of a well-respected and long-standing primate research program within the NIH intramural program that has been the subject of an ongoing PETA campaign. The focus of the research program, under the direction of Dr. Stephen J. Suomi, is on:

“examining the behavioral and biological development of non-human primates. Primary objectives are to understand how genetic and environmental factors interact to affect cognitive development, as well as develop interventions that can alter developmental trajectories of individuals whose specific genetic and experiential background put them at risk for adverse developmental outcomes. These studies cannot be carried out in humans and require the use of animal studies to carefully separate experience, genetic, and environmental factors. Ultimately, these findings assist researchers in identifying humans most likely to suffer negative effects in at-risk situations and develop behavioral and drug therapies to improve negative outcomes early in life.”

The NIH statement notes the high value of the research program, as assessed by an external board of scientific experts who concluded that the program:

  “has achieved world class, enduring contributions to our understanding of the developmental, genetic, and environmental origins of risk and vulnerability in early life,” and “could be a truly remarkable point of departure for a unified theory describing the biological embedding of early social conditions and their developmental consequences.”

Cover PNAS monkey pic 2For more about the research, the laboratory, and the animals, see:

NIH’s Response to PETA

NIH’s response to the PETA campaign was thoughtful, thorough, and transparent. The response includes a positive assessment of the value of the research in terms of human health relevance and advances in scientific understanding. It addresses why the research in conducted in monkeys and why it is not possible to use alternative methods, or to conduct the work in humans.

The response also includes a serious, fact-informed consideration of the animals’ welfare. Detailed responses from two of NIH’s Institutional Animal Care and Use Committees that conducted an extensive evaluation of the research address each element of the concerns raised by PETA and the scientists supporting them (including, Professors John Gluck, Psychology, University of New Mexico; Agustin Fuentes Anthropology, Notre Dame; and Barbara King, Anthropology, William and Mary College; Lawrence Hansen, Pathology, UC-San Diego).

Furthermore, in response to PETA’s complaint, the NIH undertook an exhaustive review via its Office of Laboratory Animal Welfare (OLAW). Comprehensive responses to each of the concerns raised by PETA are contained in the reports posted on the NIH website. For those who seek more information, facts, and substantive background to inform their consideration of the conduct of the research and the animals’ welfare, we encourage you to read the NICHD IACUC response posted here: NICHD 12.17.15 ACUC_Memo_2_121914

nih statement 01.28.15

Taken together, NIH’s responses provide a strong demonstration of a high level of care and consideration of animal welfare, as well as the risk and benefit balances that are inherent in the conduct of research with both human and nonhuman animals. The response clearly vindicates Dr. Suomi and provides welcome public acknowledgement by the NIH of the importance of his work.

As welcome as the NIH responses are, they are not, however, responses that will satisfy PETA’s absolutist goal of ending all use of nonhuman animals for any purpose, including animal research, but also food, companionship, entertainment, or other uses.

PETA’s complaint about this and other research included language about animal welfare and about alternatives to animal research in order to achieve the same scientific goals. In reality, however, PETA’s position—like that of all absolutists—is not centrally concerned with either viable alternatives to animal studies or with animal welfare. Rather, the position is that no human use of other animals—any animals, whether photogenic and appealing in popular campaigns, or not—is justified, regardless of the outcome or harms. (See here and here for additional discussion.)

As a result, it would seem that no response NIH could give to PETA would be satisfactory unless it was to end all animal research altogether. Or, in the case of a particular project or lab, the only response satisfactory to PETA or other absolutists would be to end that project, or close that lab. At some level then the question to ask may be about the cost: benefit of such responses.

By contrast to the absolute viewpoint, aspects of ethical consideration of animal research that matter to the majority of the broad public and to the scientific community are evidenced by their instantiation in the laws of a democratic society and  in regulatory and community standards, as well as in individuals’  own assessment. These include concern with significant public health challenges and appreciation for the critical role of basic scientific understanding as the foundation for a broad range of advances that benefit the public, other animals, and the environment. They also include acknowledgement of accomplishments and breakthroughs for human and nonhuman health that are accomplished via animal research. At the same time, they include selection of alternatives where possible, attention to animal’s care and welfare, continuing refinements of procedures in accord with evidence, risk and benefit justification, external oversight, and expert scientific evaluation.

In the case of the current NIH campaign and other campaigns against specific animal research there is a well-known pattern. A group like PETA focuses on a research project—usually one involving  animals such as cats, dogs, or primates that will capture broad public interest. The group then uses the highly responsive system of public institutions and government agencies to obtain information, call for investigation, and launch media campaigns to elicit public concern (and donations). The campaigns are typically based in some form of oversimplification and misrepresentation of the research, treatment of animals, availability of alternatives, or value of the science. In the face of public inquiry or media attention, public research institutions under attack typically offer a response focused on the scientific question, accomplishments, absence of non-animal alternatives, and on the animals’ welfare and oversight.

The problem with that pattern is that it ignores the fact that PETA and others’ campaigns are, in many ways, a reflection of a conflict between fundamentally different philosophical viewpoints. These differences cannot be resolved simply by ensuring scientific advances, careful risk and benefit assessment and balance, or high standards for laboratory animal welfare. All the care, training, accreditation, and external oversight in the world will not address the concerns of individuals or groups who are absolutely opposed to the use of animals in research and who believe that no matter the benefit, use of animals in research cannot be justified. Nor will such approaches address those who believe — wrongly, in most cases — that there are existing alternatives to the use of animals in research. Furthermore, each additional layer of oversight and regulation introduced in an attempt to appease those who cannot be appeased may well add substantial administrative hurdles and costs to the scientific effort without achieving meaningful improvements for animal welfare.

From that perspective, and in light of yet another PETA campaign that has resulted in a significant and extensive response from public agencies, the question becomes whether – and what – might be a better path forward. At present, the same path does not look like one that is productive to improving scientific research. Rather, the prediction would be that PETA and other groups will continue to use the transparency and responsiveness of public research institutions to lend steam to popular opinion campaigns that then target individual scientists, laboratories, and institutions. In turn, a great deal of time and energy will go into investigations, responses, and reports that are likely to yield little in terms of animal welfare, little public benefit, little progress to ending animal research, yet potentially high harm to science. At the very least these responses consume resources that would otherwise be devoted to scientific research or practical enforcement of regulations to protect animal welfare.

As we welcome the NIH’s support for Dr. Suomi we must also ask ourselves a question:  How many more cases like this will there be before the leaders of the scientific community take action to prevent the regulatory system from becoming primarily a tool of the animal rights propaganda machine?

Speaking of Research

American Psychological Association supports NIH primate researcher Stephen J. Suomi

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

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

APA 01.22.15

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

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

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

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

Cover PNAS monkey pic 2

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

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

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

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

***

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

 

Primate research and twenty years of stem cell firsts

This guest post is by Jordana Lenon, B.S., B.A., Senior Editor, Wisconsin National Primate Research Center and University of Wisconsin-Madison Stem Cell and Regenerative Medicine Center. The research will also be featured this evening in a public talk at UW-Madison’s Wednesday Nite at the Lab. WN@tL: “Twenty Years of Stem Cell Milestones at the UW.”  Details and link are below. Update 1/8/15:  Dr. William Murphy’s talk  can now be viewed at:  http://www.biotech.wisc.edu/webcams?lecture=20150107_1900

As we enter 2015, the 20th anniversary of the first successful isolation and culture of primate pluripotent stem cells in the world, it’s time to look back and see how far we’ve come. Thanks to a young reproductive biologist who came from the University of Pennsylvania’s VMD/PhD program to the Wisconsin National Primate Research Center at the University of Wisconsin-Madison in 1991, and to those whose research his groundbreaking discoveries informed, the fields of cell biology and regenerative medicine will never be the same.

stem cell colonies

Pluripotent stem cells are right now being used around the world to grow different types of cells—heart muscle cells, brain cells, pancreatic cells, liver cells, retinal cells, blood cells, bone cells, immune cells and much more.

Cultures of these cells are right now being used to test new drugs for toxicity and effectiveness.

More and more of these powerful cells are right now moving out of the lab and into preclinical (animal) trials and early human clinical trials to treat disease. The results are being published in peer-reviewed scientific journal articles on stem cell transplant, injection and infusion, reprogramming, immunology, virology and tissue engineering.

Pluripotent stem cells and their derivatives are right now being studied to learn more about reproduction and development, birth defects, and the genetic origins of disease.

Embryonic, induced pluripotent, tissue specific (adult), and other types of stem cells and genetically reprogrammed cells are all being used by researchers due to the open and collaborative environment of scientific and medical enterprises in the U.S. and around the world.

All of this is happening right now because of discoveries made 20 years ago by researchers at the Wisconsin National Primate Research Center.

Here is a brief timeline of stem cell breakthroughs by WNPRC scientists:

  • 1995-James Thomson becomes the first to successfully isolate and culture rhesus monkey embyronic stem cells (ES cells) at the Wisconsin Regional Primate Research Center (PNAS)
  • 1996-Thomson repeats this feat with common marmoset ES cells (Biol Reprod).
  • 1998-Thomson publishes the neural differentiation of rhesus ES cells (APMIS).
  • 1998-Thomson’s famous breakthrough growing human ES (hES) cells is published in Science. (This research occurred off campus, with private funding.)

Many subsequent stem cell “firsts” were accomplished by scientists who conducted lengthy training with James Thomson or Ted Golos, reproduction and development scientists at the Wisconsin National Primate Research Center. These highlights include the following accomplishments by Primate Center researchers:

  • 2003-WNPRC Post-doctoral trainee Thomas Zwaka achieves homologous recombination with hES cells. A method for recombining segments of DNA within stem cells, the technique makes it possible to manipulate any part of the human genome to study gene function and mimic human disease in the laboratory dish (Nature Biotechnology).
  • 2004-WNPRC Post-doctoral trainee Behzad Gerami-Naini develops an hES model that mimics the formation of the placenta, giving researchers a new window on early development (Endocrinology).
  • 2005- WNPRC scientist Igor Slukvin and post-doc Maxim Vodyanik become the first to culture lymphocytes and dendritic cells from human ES cells (Blood, J Immunol).
  • 2005-WiCell’s Ren-He Xu, who completed his post-doctoral research at the WNPRC, grows hES cells in the absence of mouse-derived feeder cells (Nature Methods).
  • 2006-WiCell’s Tenneille Ludwig, a graduate student/post-doc/assistant scientist through the Primate Center with Barry Bavister, then James Thomson, formulates a media that supports hES cells without the need for contaminating animal products (Nature Biotechnology). Co-authoring the work is another former Primate Center post-doc, Mark Levenstein.
  • 2007-Junying Yu, WNPRC and Genome Center, in Jamie Thomson’s lab, grows induced pluripotent stem cells, or iPS cells. (Science). These are genetically reprogrammed mature cells that act like embryonic stem cells, but without the need to destroy the embryo.

Researchers at all of the National Primate Research Centers continue to make advances in this remarkable field of research and medicine. A few more milestones include the following:

  • 2007- Shoukhrat Mitalipov at the Oregon National Primate Research Center successfully converted adult rhesus monkey skin cells to embryonic stem cells using somatic cell nuclear transfer (Nature)
  • 2012- Shoukhrat Mitalipov at the Oregon National Primate Research Center generation chimeric rhesus monkeys using embryonic cells (Cell)
  • 2012-Alice Tarantal at the California NPRC successfully transplants human embryonic stem cells differentiated toward kidney lineages into fetal rhesus macaques.
  • 2013-Qiang Shi at the Texas Biomedical Research Institute and Gerald Shatten at the University of Pittsburgh – and previously with the Oregon National Primate Research Center and Wisconsin National Primate Research Center – genetically programs baboon embryonic stem cells to restore a severely damaged artery.
  • 2013-Shoukhrat Mitalipov at the Oregon National Primate Research Center produces human embryonic stem cells through therapeutic cloning, or somatic cell nuclear transfer (Cell)

NPRC Stem Cell Timeline 01.06.15

Before all of this happened, we must note that non-primate mammalian embryonic stem cells were first successfully isolated and cultured in 1981, by Martin Evans and Matthew Kaufman at the University of Cambridge, England. That breakthrough occurred almost 35 years ago. Jamie Thomson studied mouse embryonic stem cells in Pennsylvania before working on primate cells.

Even before that, in 1961, Ernest McCulloch and James Till at the Ontario Cancer Institute in Canada discovered the first adult stem cells, also called somatic stem cells or tissue-specific stem cells, in human bone marrow. That was 55 years ago.

So first it was human stem cells, then mouse, then monkey, then back to humans again. Science speaks back and forth. It reaches into the past, makes promises in the present, and comes to fruition in the future.

In every early talk I saw Jamie Thomson give about his seminal stem cell discoveries in the late 1990s and early 2000s – to staff, scientists, to the public, to Congress, to the news media – he would explain why he came to UW-Madison in the early 1990s to try to advance embryonic stem cell research. In large part, he said, it was because we had a National Primate Research Center here at UW-Madison, and also that we had leading experts in transplant and surgery at our medical school. After he joined the WNPRC as a staff pathologist and set up his lab, first he used rhesus and then marmoset embryos before expanding to cultures using human IVF patient-donated embryos off campus with private funding from Geron Corporation in Menlo Park, California.

Human And Mouse EmbryoIn these early talks, Jamie included images (see above) showing how very differently the mouse blastocyst (a days-old embryo, before implantation stage) is structured from the nonhuman primate and human primate blastocysts concerning germ layer organization and early development (ectoderm, mesoderm and endoderm). He also was able to show for the first time how differently stem cells derived from these early embryos grow in culture. In contrast to the mouse ES cells, the monkey cells, especially those of the rhesus monkey, grow in culture almost identically to human cells.

At the time, Thomson predicted that more scientists would study human ES cells in their labs over monkey ES cells, if human ES cells could become more standardized and available. Yet he emphasized that the NPRCs and nonhuman primate models would continue to play a critical role in this research, especially when it would advance to the point when animal models would be needed for preclinical research before attempting to transplant cells and tissues grown from ES cells. Both predictions have come true.

Jamie closed his talks, and still does, with this quotation:

“In the long run, the greatest legacy for human ES cells may be not as a source of tissue for transplantation medicine, but as a basic research tool to understand the human body.”

This simply and elegantly reminds us how basic research works: Many medical advances another 20 years from now will have an important link to the discoveries of today, which have their underpinnings in that early research in Jamie Thomson’s lab 20 years ago. It will become easy to forget where it all started, when many diseases of today, if not completely cured, will become so preventable, treatable and manageable that those diagnosed with them will spend more time living their lives than thinking about how to survive another day.

Just as I did not have to worry about polio, and my children did not have to worry about chicken pox, my grandchildren will hopefully see a world where leukemia, blindness, diabetes and mental illness do not have the disabling effects or claim as many young lives as they do today.

***

_______________________________________________________

WN@tL “Twenty Years of Stem Cell Milestones at the UW”

http://www.uwalumni.com/event/wntl-twenty-years-of-stem-cell-milestones-at-the-uw/

January 7 – 7:00PM – 8:15PM CT
Location: UW Biotechnology Center 425 Henry Mall, Room 1111, Madison, WI 53706
Cost: Free

Speaker: William L. Murphy, Stem Cell and Regenerative Medicine Centerwnatl_williammurphy

Don’t miss this fascinating talk covering stem cell milestones at the UW. Professor Murphy will talk about the work of his team at the Stem Cell and Regenerative Medicine Center, where they are creating biological materials that could radically change how doctors treat a wide range of diseases.

Bio: Murphy is the Harvey D. Spangler Professor of Engineering and a co-director of the Stem Cell and Regenerative Medicine Center. His work includes developing biomaterials for stem cell research. Specifically, Murphy uses biomaterials to define stem cell microenvironments and develop new approaches for drug delivery and gene therapy. His lab also uses bio-inspired approaches to address a variety of regenerative medicine challenges, including stem-cell differentiation, tissue regeneration and controlled drug delivery. Murphy has published more than 100 scientific manuscripts and filed more than 20 patent applications.

Thank You Doctor Salk! (and Drs Enders, Bodian, Landsteiner, Sabin…)

Today’s Google Doodle honours Dr Jonas Salk, who in 1954 created the world’s first effective polio vaccine, which was responsible for launching a campaign that has seen this terrible disease become an increasingly distant memory in most  – though sadly not all – parts of the world.

jonas-salks-100th-birthday-5130655667060736-hp

It’s an opportunity to reflect on the pioneering work of Dr Salk, who was born 100 years today, but we should also remember all the other great scientists whose work made crucial contributions to the development of the inactivated and live polio vaccines.

Salk’s 100yr anniversary: say thank you to those who helped develop the Salk vaccine against polio Tweet this!

Today, in honor of Jonas Salk and all the other polio vaccine pioneers, we are reposting this article, which we first published in 2011.

Albert Sabin and the monkeys who gave summer back to the children.

Albert Sabin has been called “the doctor who gave summer back to the children.”*

Because of his decades of research to develop the oral polio vaccine, children today know nothing of the fear that polio brought to the United States every summer well into the 20th century.  Swimming pools and movie theaters were closed and children were kept inside their homes by frightened parents.  Worldwide, the disease killed millions of people and left legions of others permanently disabled.

Albert Sabin administering the vaccine that saved millions from polio.

Albert Sabin administering the vaccine that saved millions from polio.

We’ve just celebrated the 50th anniversary of the introduction of Dr. Sabin’s vaccine. Estimates suggest that in just its first two years of worldwide use, the vaccine prevented nearly 500,000 deaths and five million cases of polio.  Today, the world is on the brink of realizing Dr. Sabin’s lifetime dream: the eradication of polio from the planet.

The development of the oral polio vaccine required years of extensive research with rabbits, monkeys and rodents.

Animal rights activists long ago seized on a single phrase by Dr. Albert Sabin, and have been using it ever since to try to support their outrageous claim that the developer of the oral polio vaccine(OPV) opposed the use of animals in research.

That phrase, “The work on prevention (of polio) was long delayed by an erroneous conception of the nature of the human disease based on misleading experimental models of disease in monkeys” spoken by Dr. Sabin during a congressional hearing in 1984, has been used in animal rights publications and comments for over two decades.

Dr. Sabin, a member of the Board of Directors of the pro-research Americans for Medical Progress until his death in 1993, spent years working to correct the record.  Here is a letter he wrote to the editor of the Winston Salem Journal, published in 1992.

Winston-Salem Journal

March 20, 1992

The Correct Conclusion

In a recent letter to the Journal (“Misrepresenting Research,” Feb. 20), Dr. Stephen R. Kaufman, the chairman of the Medical Research Modernization Committee, correctly quoted my 1984 testimony before Congress but he drew wrong conclusions from it.  Dr. Kaufman was also wrong when the said “the polio vaccine was based on a tissue culture preparation … not animal experimentation.”

On the contrary, my own experience of more than 60 years in biomedical research amply demonstrated that without the use of animals and of human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans but also among animals.

In my 1956 paper in the Journal of the American Medical Association (Vol. 162, p. 1589), I stated that during the preceding four years “approximately 9,000 monkeys, 150 chimpanzees and 133 human volunteers were used thus far in studies of various characteristics of different poliovirus strains.”  These studies were necessary to solve many problems before an oral polio-virus vaccine could become a reality.

Albert B. Sabin, M.D.

Washington

It is true that in the early years of polio research some lines of inquiry eventually proved unsuccessful. An overreliance on a strain of the virus known as the MV strain that had become adapted to survive only in nervous tissue, and the fact that the Rhesus macaque, while a good model for many aspects of polio, cannot be infected through ingestion via the mouth, led to the incorrect assumption that polio could only infect nerve cells (despite evidence to the contrary from both clinical studies and laboratory studies with other polio strains and monkey species).   These mistakes were unfortunate, though understandable given the fact that virology as a science was in its infancy.

However, these failed attempts do not cancel out the fact that animal research, and research using monkeys in particular, was absolutely crucial to the development of vaccines for polio.  Without it the polio vaccine would certainly not have been developed by the end of the 1950’s, and we might even still be waiting for it.

These vital contributions made by animal research to the development of polio vaccines were not limited to the work of Albert Sabin, and include:

  • The discovery by Karl Landsteiner and Erwin Popper in 1908 that polio was caused by a virus, a discovery made by inoculating macaque monkeys with an extract of nervous tissue from polio victims that was shown to be free of other infectious agents.
  • The subsequent discovery by Simon Flexner  that blood serum from infected macaque monkeys could protect against polio infection.
  • The discovery by Carl Kling and colleagues in 1911, following an earlier discovery that polio virus could be isolated from the lymph nodes of the small intestine of monkeys, that polio virus was present in the throat and intestinal tissues of people who dies from polio. Soon afterwards they isolated virus from the intestines of patients suffering from acute polio, and importantly from family members who did not display the symptoms of polio, establishing that healthy carriers played an important role in spreading the disease. In these studies the presence of polio was demonstrated by injecting filtered fluid from the patients into monkeys, the only method then available to confirm the presence of polio (Introduction to Epidemiology, fifth edition, by Ray M, Merill, Jones and Bartlett Learning).
  • The discovery in the early 1930’s by the Australian scientists Macfarlane Burnet and Jean Macnamara that antibodies against one strain of polio did not always protect macaque monkeys against infection with another strain.
  • The discovery by John Enders, Thomas Weller and Frederick Robbins that the polio virus could be grown in a number of tissue types, not just nerve tissue as previously assumed, a discovery that required the use of mice and monkeys to prove that the cultured virus was indeed polio and still capable of causing paralysis.
  • The determination in 1949 by David Bodian and colleagues at Johns Hopkins University that there were three major families of polio virus, referred to as types 1, 2, and 3, and that a separate vaccine would be necessary for each to give broad protection against polio.
  • The discovery by David Bodian and colleagues in the late 1940’s and early 1950’s that the polio virus entered the body through the mouth, and then needed to pass into the blood stream before it could infect nervous tissue, and that if you could block the infection in the blood you could prevent the virus from entering nerve tissue and causing paralysis. The work of Enders and Bodian paved the way for the development of vaccines by Salk and Sabin.
  • The evaluation by Jonas Salk and his colleagues at the University of Pittsburgh  of vaccine candidates produced by inactivating the virus with formalin under a range of conditions, until a vaccine was identified that was effective and safe enough for human trials.
  • The evaluation by Albert Sabin of hundreds of polio virus strains in hundreds of monkeys and scores of chimps before identifying attenuated strains that were capable of efficiently entering the body through the digestive system and provoking an adequate immune response to protect against the different pathogenic strains of polio while not causing the disease themselves.

It is hardly surprising that those close to Albert Sabin are disgusted with the way in which his views are misrepresented by animal rights activists. Writing for the Wall Street Journal two years after his death Albert Sabin’s widow, Heloisa Sabin, discussed the value of animals to his research.

ANIMAL RESEARCH SAVES HUMAN LIVES

The Wall Street Journal, October 18, 1995

by Heloisa Sabin

Mrs. Sabin is honorary director of Americans for Medical Progress.

That scene in “Forrest Gump,” in which young Forrest runs from his schoolmate tormentors so fast that his leg braces fly apart and his strong legs carry him to safety may be the only image of the polio epidemic of the 1950s etched in the minds of those too young to remember the actual devastation the disease caused. Hollywood created a scene of triumph far removed from the reality of the disease.

Some who have benefited directly from polio research, including the work of my late husband, Albert Sabin, think winning the real war against polio was just as simple. They have embraced a movement that denounces the very process that enables them to look forward to continued good health and promising futures. This “animal rights” ideology — espoused by groups such as People for the Ethical Treatment of Animals, the Humane Society of the U.S. and the Fund for Animals — rejects the use of laboratory animals in medical research and denies the role such research played in the victory over polio.

The leaders of this movement seem to have forgotten that year after year in the early ’50s, the very words “infantile paralysis” and “poliomyelitis” struck great fear among young parents that the disease would snatch their children as they slept. Each summer public beaches, playgrounds and movie theaters were places to be avoided. Polio epidemics condemned millions of children and young adults to lives in which debilitated lungs could no longer breathe on their own and young limbs were left forever wilted and frail. The disease drafted tiny armies of children on crutches and in wheelchairs who were unable to walk, run or jump. In the U.S., polio struck down nearly 58,000 children in 1952 alone.

Unlike the braces on Forrest Gump’s legs, real ones would be replaced only as the children’s misshapened legs grew. Other children and young adults were entombed in iron lungs. The only view of the world these patients had was through mirrors over their heads. These, however, are no longer part of our collective cultural memory.

Albert was on the front line of polio research. In 1961, thirty years after he began studying polio, his oral vaccine was introduced in the U.S. and distributed widely. In the nearly 40 years since, polio has been eradicated in the Western hemisphere, the World Health Organization reports, adding that with a full-scale effort, polio could be eliminated from the rest of the world by the year 2000.

Without animal research, polio would still be claiming thousands of lives each year. “There could have been no oral polio vaccine without the use of innumerable animals, a very large number of animals,” Albert told a reporter shortly before his death in 1993. Animals are still needed to test every new batch of vaccine that is produced for today’s children.

Animal activists claim that vaccines really didn’t end the epidemics — that, with improvements in social hygiene, polio was dying out anyway, before the vaccines were developed. This is untrue. In fact, advanced sanitation was responsible in part for the dramatic rise in the number of paralytic polio cases in the ’50s. Improvements in sanitation practices reduced the rate of infection, so that the average age of those infected by the polio virus went up. Older children and young adults were more likely than infants to develop paralysis from their exposure to the polio virus.

Every child who has tasted the sweet sugar cube or received the drops containing the Sabin Vaccine over the past four decades knows polio only as a word, or an obscure reference in a popular film. Thank heavens it’s not part of their reality.

These polio-free generations have grown up to be doctors, teachers, business leaders, government officials, and parents. They have their own concerns and struggles. Cancer, heart disease, strokes and AIDS are far more lethal realities to them now than polio. Yet, those who support an “animal rights” agenda that would cripple research and halt medical science in its tracks are slamming the door on the possibilities of new treatments and cures.

My husband was a kind man, but he was impatient with those who refused to acknowledge reality or to seek reasoned answers to the questions of life.

The pioneers of polio research included not only the scientists but also the laboratory animals that played a critical role in bringing about the end of polio and a host of other diseases for which we now have vaccines and cures. Animals will continue to be as vital as the scientists who study them in the battle to eliminate pain, suffering and disease from our lives.

That is the reality of medical progress.

 

Animal rights activists are free to express their opposition to the use of animals in research, but they cannot do so by blatantly robbing society of scientific achievements.  This one fact is clear — if our critics had their way, today millions of children would be dead or disabled from polio and other infectious diseases.

* Of course Jonas Salk is equally, if not more, deserving of this accolade.

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

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.

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

  • In a major advance, California National Primate Research Center (CNPRC) research defined a link between maternal auto-antibodies and increased risk of a child having autism (http://www.cnprc.ucdavis.edu/maternal-antibodies-linked-to-autism/)
  • Research at the CNPRC has focused on oxytocin and vasopressin in social bonding and male parental care, as well as on the effects of early experiences on the development of these behaviors. Studies have begun on the long-term effects of oxytocin; a new treatment is already being used in children with autism without an understanding of the long-term effects. (http://www.cnprc.ucdavis.edu/unknown-effects-of-long-term-oxytocin-use-in-children/)
  • Using an innovative approach to imaging the brain, scientists at the CNPRC have significantly enhanced our understanding of the etiology of autism by mapping the location of receptors for oxytocin, a hormone that is linked with social behavior. http://www.cnprc.ucdavis.edu/improving-models-to-understand-the-etiology-of-autism/
  • CNPRC scientists have shown that monkeys exposed to a maternal mock infection in utero exhibit signs of inflammation within the brain four years later, which is a response that is similar to that observed in human patients with schizophrenia and autism.  Nonhuman primate models are essential for understanding the effects of maternal inflammation during pregnancy, as they provide critical information on individual susceptibility and vulnerability of specific gestational time points. http://www.cnprc.ucdavis.edu/mothers-immunity-linked-to-brain-inflammation/

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)
  • At the CNPRC a new vaccine strategy against HCMV, the “birth defect virus”, has been shown to produce a strong immune response with the potential to prevent a viral infection that causes 5,000 babies yearly to be born with congenital neurological deficits. http://www.cnprc.ucdavis.edu/vaccine-against-hcmv-the-birth-defect-virus-produces-a-strong-immune-response/
  • 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)
  •  CNPRC investigations into potential effects of long-term binge drinking episodes on later pregnancies in primates demonstrate that binge-levels of alcohol were associated with reduced embryo development, changes in the oocyte and cumulus cell gene expression, and an increase in spontaneous abortion during very early gestation, even after alcohol consumption had ceased. http://www.cnprc.ucdavis.edu/binge-drinking-implications-for-human-health/
  •  A powerful new imaging technique has been developed at the CNPRC that could vastly improve the success of Assisted Reproductive Technologies, including IVF, by increasing the ability to predict which embryos stand the highest chance of continuing to develop normally.http://www.cnprc.ucdavis.edu/predicting-embryo-success-with-in-vitro-fertilization/
  •  Research at the CNPRC has shown a link between sugar consumption in healthy females and disrupted oocyte maturation and in vitro pre-implantation embryo in healthy animals. http://www.cnprc.ucdavis.edu/donec-at-mauris-enim-duis-nisi-tellus/

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)

[Updated 01/27/15]