Tag Archives: primate

Zika research in nonhuman primates critical as fears among pregnant women, families grow

Jordana Lenon, B.S., B.A., is the outreach specialist for the Wisconsin National Primate Research Center and the Stem Cell & Regenerative Medicine Center, both at the University of Wisconsin-Madison. In this guest post Jordana talks about WNPRC research on Zika virus.

Wisconsin National Primate Research Center scientist David O’Connor is emphasizing using “as few animals as possible” to answer research questions that desperately need answers as the world watches Zika virus cause birth defects and raise fears among pregnant women and their families across the warmer Americas. These answers, O’Connor expects, will move him and his collaborators at the University of Wisconsin-Madison, Duke University, in Brazil and beyond forward as they learn more each day how Zika virus may be operating inside of infected pregnant women and their newborns, and could cause potential lifelong impairments we don’t even know about yet.

Researchers at the Wisconsin National Primate Research Center perform a fetal ultrasound on a pregnant rhesus macaque, in their quest to learn more about the link between the Zika virus and birth defects. (Images by Justin Bomberg, UW-Madison Communications)

Thanks to research using rhesus macaques, whose immune, reproductive and neurological systems are very similar to ours, the answers are starting to come in. Furthermore, O’Connor and his Zika Experimental Science Team, or “ZEST are sharing their raw research data through an online portal with the public – including of course and very importantly other Zika researchers. Their goal is to share data openly, to eliminate as many impediments as possible to spurring collaborative work around the globe to solve the Zika crisis.

David O'Connor, professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison, is pictured on April 19, 2016. (Photo by Bryce Richter / UW-Madison)

David O’Connor, professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison, is pictured on April 19, 2016. (Photo by Bryce Richter / UW-Madison)

Just how severe a problem are we looking at? O’Connor gave some perspective during a public lecture on the UW-Madison campus this week. While HIV – another pandemic virus he has studied exhaustively over the past 20 years – costs society about $400,000 per patient over their life spans, Zika virus impairments in newborns could cost between $1-10 million per patient (using US dollar estimates) over their life spans. Recent studies in macaques found that the Zika virus persisted for up to 70 days in the blood of pregnant female monkeys – much longer than the 10 days it remained in either males or non-pregnant females – this increases the chance of severe birth defects being found in babies.

There are already more than 300 pregnant women in the US with laboratory evidence of Zika. This number is growing daily. Infections in the US are largely being attributed to pregnant women picking up the virus while traveling outside the country: Zika is hitting hard right now in Puerto Rico, infecting nearly 50 pregnant women per day, as Aedes aegypti mosquitos, which can transmit viruses such as dengue and Zika, spread and move northward this summer from South to Central America, to the Caribbean and into the United States. Because Zika is also sexually transmitted, its borders of infection are not limited to places where the mosquitos live and bite.

Mother and infant rhesus monkeysThere is hope, however. A new experimental vaccine has shown to protect mice with just a single dose. Scientists from Walter Reed Army Institute of Research, the Beth Israel Deconess Medical Center and Harvard Medical School found two different vaccines effectively protected 100% of mice from the virus. This compares to a control group which were unprotected and all caught Zika after being exposed to the virus.

Jordana Lenon

See the team’s latest research updates on the ZEST web portal site.

View the Wednesday Night at the Lab lecture on Zika virus that Dr. O’Connor gave July 6 on the UW-Madison campus, including his responses to several questions about the virus, immunity, pregnancy, and vaccine development.

Debating Animal Research in Australia

The Ethics Centre, an independent not-for-profit organisation in Australia, held its second IQ2 debate on the motion: “Animal rights should trump human interests“. Supporting the motion was shark attack survivor, Paul de Gelder, animal lawyer, Ruth Hatten, and philanthropist Philip Wollen. Opposing the motion was ethicist Dr Leslie Cannold, Commissioner at the Australian Centre for International Agricultural Research, and primate researcher Professor James Bourne. See more about the speakers.

A vote was taken before and after, with a huge swing of over 30% of the audience switching over to “against” the motion, in part due to the wonderful speech by Prof Bourne. 

Opinions of audience at IQ2 debate on animal rights

Click to Enlarge

As an animal researcher, Prof James Bourne focused on the use of animals in medical and scientific research. He is the Group Leader at Monash University’s Australian Regenerative Medicine Institute and a Senior Fellow with the federal government’s National Health and Medical Research Council (NHMRC). James’ work with NHMRC is exploring regenerative therapies for babies with brain injuries. 

Below we produce a transcript (with permission) of his speech, which contributed to the massive swing in audience opinion.

Thank you, good evening.

Like many of you I am appalled at our age of factory farming, our wilful blindness to exploitation, our rampant self-interest as a species and the seemingly inevitable destruction of every sphere of our environment.

But like all scientists I am also an optimist.  I hold true that medical research using animal models, and let me be clear – experimenting on animals themselves – is necessary in many areas of medical research if humanity wishes to improve life – life for both humans and animals.

There are two points I am grateful to convey tonight:

  1. The use of some animals in medical research remains necessary. Remembering for every monkey in research over 4 million are used in the food and dairy industry.
  2. Medical research on animals should only occur within a regulated ethical framework directed at the welfare of the animal.

I find myself here tonight after a relatively sudden and unexpected journey that began recently when the scientific community in Australia heard of a Green’s private member’s Bill in the Senate seeking to ban the importation of non-human primates for research purposes.

As a scientist whose work utilises monkeys I knew that a ban on importation would lead very quickly to a level of in-breeding in Australian facilities that would render valuable research impossible and force it into countries known for their unregulated practices.

James Bourne at the IQ2 debate. Image from www.ethics.org.au

James Bourne at the IQ2 debate. Image from http://www.ethics.org.au

I was motivated to enter this political debate because despite the woes and wrongs of our contemporary age, reason is still the best chance humanity has to right those wrongs and improve our world.

Reason always comes off second-best in the face of fear and suspicion. Fear and suspicion characterises much of the debate about animals in research and is cloaked in deliberate and wilful misinformation.

Images of horrific animal experiments undertaken in the 50’s regularly feature today in animal rights literature, even though these experiments have been outlawed for many years.

The Bill, defeated as it was, recycled many myths about animal experimentation… dangerous myths that computers and petri dishes can replace animals, that experiments inflict unnecessary cruelty and suffering, that baby monkeys are every day being ripped out the arms of their dead mothers in the jungle by poachers and then traded through unregulated corrupt profiteering to end up being tortured by mad scientists addicted to outdated scientific models.

The fact that a proposal of this kind can even be seriously considered today is evidence that the scientific community has not only been cowed into burying its collective head, but as a body-politic we are only a few steps away from reverting to a darker age where the quality of life – for both humans and animals – will be considerably lessened.

Indeed, while humanity is making ever more incredible scientific advances, regular polling shows a growing and alarming public disagreement about basic scientific facts, including human evolution, the safety of vaccines and whether human-caused climate change is real.

But let me indulge here in some very recent examples of why I believe non-human primate research is important.

Recently researchers infected monkeys with the Zika virus because it is the closest scientist can get to understanding in real time what is happening when humans are infected with this virus.

In 2015, the world witnessed the worst epidemic of the Ebola virus to date. Monkeys were treated with an antibody isolated from a human Ebola survivor and developed almost complete protection against a lethal dose of Ebola.

And yet opponents of animal research argue that knowledge gained from monkey research is inapplicable to humans.  This claim is utterly and dangerously false. Anyone that argues that insights gained from animals are meaningless, is either poorly informed or knowingly untruthful.

The political reality, however, is that the imagery and language peddled by animal research opponents is utterly confronting.

The facts, if you care to accept them, are:

First, non-human primates used for research in Australia are sourced from regulated breeding facilities overseas. They are not taken from the jungle.

macaque monkey animal research israel

An example of an overseas primate breeding facility.

Second, All animal research in Australia is conducted under the strictest scrutiny and follows the principles of reduction, refinement and replacement known as the 3Rs. Under these principles, animal-based research is only approved by a qualified animal ethics committee, which includes members of the lay public, welfare organisations and veterinarians.

Third, Non-human primates are used only in exceptional circumstances – when no other model is possible – as a last resort – when finding an answer simply cannot be provided by another animal model, cell-based system, computer modelling or human experimentation.

While we make incredible advances every day in computer technology, there is currently, and unfortunately, no alternative approach that can replicate the vast complexity of human disorder and disease.  Researchers are, however, continuously looking for non-animal based alternatives and this has already led to a significant reduction in the number of non-human primates used in research in Australia.

Furthermore, every researcher understands the great duty of care they must apply. Minimising the risk of pain and distress is of utmost importance when designing a study.

However, researchers remain hesitant to speak out as history tells us that this can have significant repercussions on the individual and the research program. I fear with recent activist developments in Europe, global scientific advances in health have been retarded.

You might find my work abhorrent, but it is framed in the highest possible duty of care to the animal and it seeks to address critical challenges in global health. If we proceed down a path to banning animal research – it is not only the science that will suffer but also, more importantly, the patients who would have benefitted from the outcomes.

I believe in a utilitarian sense, much like our speakers tonight, that in suffering the animals are our equals.[1]

So I cannot, and never will, defend factory farming, zoos and circuses or horse and dog racing, but ask you to please consider that in the face of this determined movement to stop all animal experimentation to remind ourselves that animal based medical research is driven, in Australia, by compassion and that the motivation to understand and improve our world – for all life – should always triumph over suspicion and fear.

Thank you.

James Bourne

[1] Eminent Australian moral philosopher, Peter Singer (Animal Liberation, 1975), paraphrasing utilitarian philosopher Jeremy Bentham (1802)

Interview: How our outreach experiences have changed!

In this Q&A post, we visit with Jordana Lenon, B.S., B.A., the outreach specialist for the Wisconsin National Primate Research Center and the Stem Cell & Regenerative Medicine Center, both at the University of Wisconsin-Madison. Jordana reaches her 20th anniversary working at the Primate Center this year. Here, she reveals how different her job is today from when she first began.

Speaking of Research (SR): How has your job changed in the past 20 years?

Jordana Lenon (JL): When I began in 1996, I was in charge of the newsletters and developing the center’s website. That was it. Today, face-to-face outreach events, mostly for K-12 groups, along with news media relations, is most of my job. I still edit the newsletters, but we are actually reaching more people we need to reach with our social efforts. And by that, I don’t mean social media, I mean in-person engagement. In the past five years alone, we’ve met with more than 35,000 students, teachers and community members through mostly school family science nights, science festivals, and visits both on campus and out to the schools and civic groups.

WNPRC outreachSR:  How have you advertised your outreach programs?

JL: First, the UW-Madison Campus Visit Program receives most of our on-campus requests. They promote all the science and other campus venues the public can visit on the university’s website. Second, the UW Madison Science Alliance outreach team has an awesome family science night Google docs sign-up sheet that teachers, parent volunteers and we campus presenters can access, which helps immensely with planning and logistics. Third, the power of good old word of mouth and referrals, from teacher to teacher, or from one civic organization chapter to another, cannot be underestimated.

SR: Are there any challenges to orchestrating so much outreach?

JL: Yes. This is the first year that I’ve had to postpone scheduling more than a few visits to the Primate Center Learning Lobby or Stem Cell Learning Lab. Demand is so high, with daily requests right now, that even with volunteers we just can’t meet it. I suppose that is a good problem to have! I would love it if more people would schedule visits in the Fall, because spring, especially April, fills up so fast.

SR: What is the most rewarding thing about your outreach efforts?

JL: Two things, actually. One is that more and more UW scientists and students have volunteered to help each year. This means a great deal to me, because I know how busy they are, how many different directions they are already being pulled in. When I see their faces, their looks of satisfaction, and hear from them how much fun it was afterwards, how great the students’ questions were, how smart the students were, and that they really “get” how important it is to share what they do and what the Primate Center or Stem Cell Center does, that is just an indescribable feeling. Another cool thing I’ve noticed over the past 20 years is that, when I began presenting, people didn’t know much about the Primate Center, where it was or what we did. They didn’t know about our research programs and how we take care of our animals, how dedicated our scientists, students, vets, animal caretakers and other employees are. There was always someone in just about every group who expressed strong feelings against research with animals. Today, it’s more like, “Yes, we’ve visited the Primate Center before and we wanted to come back again with another school group… what you do is so amazing… we support what you do… we know it’s not easy… my friend has Parkinson’s… my son has diabetes… I have MS… I just read you are working on Zika virus… I didn’t know stem cell research really took off here… I have a friend who worked at the Primate Center… I had no idea what you did before this visit… thank you…

Jordana Lenon takes a tour of the new Madison Science Museum with Ellen Bechtol, museum staff member. Behind them is one of the Why Files Cool Science Image Contest winners, of marmoset embryonic stem cells forming neurons, submitted by Primate Center scientists and students in 2015. http://whyfiles.org/category/cool-science-images/

Jordana Lenon takes a tour of the new Madison Science Museum with Ellen Bechtol, museum staff member. Behind them is one of the Why Files Cool Science Image Contest winners, of marmoset embryonic stem cells forming neurons, submitted by Primate Center scientists and students in 2015. http://whyfiles.org/category/cool-science-images/

SR: Are all the audiences so supportive?

JL: Most, but not all. And that’s okay. I want to know what people are thinking, what they know, what they don’t know. I want to answer questions, or find out the answers if I don’t know them. I learn a great deal from my audiences. Most of the complaints and concerns I get these days are from people expressing to me that it is taking too long for more stem cell research “breakthroughs” to get into the clinic. Rarely do I get someone in my groups anymore who tells me that they are an animal rights supporter (versus animal welfare). This may be because activists of all beliefs are using social media more to express their views. I am definitely seeing that our audiences have many more informed questions than when I first began. I think science education, blogs, shows, pro-science websites and social media are also helping, especially with the younger generation. More people are understanding the connections between the medicines and vaccines they take, and that it all began at some critical step along the way with biomedical research and humane animal care. Also, that the research benefits animals as well as people.

The hardest thing to tell people is why the research takes so much time. People are being wooed by these “miracle stem cell cures” on line, for example. So a large part of my job is explaining how research works, how to search clinicaltrials.gov, and what patients should be asking their doctors. But now that I’ve been here 20 years, myself, I can cite research that was ongoing when I began and that is now in clinical trials or even FDA-approved medical treatments and is saving millions of lives.

I am living proof, myself: UW-Madison scientists and physicians used several animal models, including our Primate Center monkeys, to develop new therapies for systemic lupus erythematosus in the 1980s through the early 2000’s. This research is why I am alive and healthy today. Twenty years ago, most patients with SLE were not expected to live a normal lifespan. Even surviving from year to year with this autoimmune disease usually meant forgetting about work or any real quality of life. People are still dying from lupus, but prognoses are getting better every year.

SR: Anything you’d like to add, plans for more outreach development?

JL: Well… I would like to do more social media… but I’m too busy being social to do it!

SR:  Thanks for your stories. Thanks for sharing the important work that you do!

JL: You’re welcome. We had 10 outreach events last week alone, so this week, I have a little more time to write and catch up on email… and get off my feet for a while!

Read more here:  https://www.primate.wisc.edu/wprc/outreach.html

Open Letter to the Australian Senate regarding a proposed bill to ban the import of primates

The following letter has been sent to the Committee Secretary of the Senate Standing Committees on Environment and Communications regarding the Environment Protection and Biodiversity Conservation Amendment (Prohibition of Live Imports of Primates for Research) Bill 2015. This proposed bill would ban the Australian research community from importing primates for use in biomedical research. The following is a segment of the proposed amendment:

Australian Bill

We encourage the scientific community to leave comments of support for our letter in the comment section below.

Dear Committee Secretary,

Nonhuman primate research has played an important role in many medical breakthroughs, from the polio vaccine to the development of life support systems for premature babies.

Studies with nonhuman primates are a small fraction of basic, behavioural, and biomedical research; however, they are critical to scientific research that seeks to address health issues of grave concern to the public. Nonhuman primate research includes studies relevant to understanding, preventing, and treating a range of diseases including, Alzheimer’s, Parkinson’s, stroke, HIV/AIDS, hepatitis, anaemia and a multitude of mental health conditions.

Thanks to research on primates:

  • Polio has been eradicated from Australia, saving tens of thousands of children from crippling disability
  • Thousands of Australians have had Deep Brain Stimulation to alleviate the symptoms of Parkinson’s
  • Over 20,000 HIV positive Australians can live a relatively normal life thanks to the development of antiretrovirals
  • Australian children can be vaccinated against Hepatitis B, diphtheria, measles, mumps and rubella

Measures to constrain nonhuman primate research in Australia puts future medical breakthroughs in jeopardy.

Australian law already bans the use of wild caught nonhuman primates for research (as does the EU). Such laws should continue to be actively enforced to uphold animal welfare standards, but importantly, should not be expanded to prevent important nonhuman primate research being conducted.

Preventing researchers from importing nonhuman primates could prevent scientists from responding to public health issues or new areas of biomedical research in Australia and beyond. The domestic supply of nonhuman primates may be able to provide for most of the needs of the scientific community, but also risks constraining it. Any future Australian research would be limited to species of monkeys currently bred in Australia’s three breeding colonies, effectively restricting the animal models available to the biomedical community.

Research conducted with nonhuman primates is strictly regulated. All research must be approved by Animal Ethics Committees, who apply the 3 Rs framework to ensure that animal studies are Replaced wherever there is a non-animal alternative, Refined to ensure animal suffering is minimised, and Reduced to ensure that as few animals are used as is necessary to produce scientifically viable results. Animal welfare remains a high priority for the scientific community – with animal care personnel and veterinary staff providing round-the-clock care for their wards.

Yours faithfully,

Speaking of Research

Inês Albuquerque
Jeremy Bailoo, Ph.D
Prof Mark G Baxter
Prof Allyson Bennett
Paul Browne, Ph.D
James Champion
Paula Clifford
Amanda M. Dettmer, Ph.D
Prof Doris Doudet
Jazzminn Hembree RLATG
Tom Holder
Prof J. David Jentsch
Juan Carlos Marvizon, Ph.D
Kimberley Phillips Ph.D
Prof Dario Ringach
Simon R Schultz, DPhil

One step closer to a vaccine for cytomegalovirus: Monkeys transmit CMV the same way as humans

Today’s guest post is by Jordana Lenon, Wisconsin National Primate Research Center and Kathy West, California National Primate Research Center.

PregnantWomanResearchers at Duke and Tulane take the lead, the National Primate Research Centers provide critical resources and expertise in this first-ever proof of CMV placental transmission in nonhuman primates.

Researchers now have a powerful new model for working on a vaccine for cytomegalovirus, or CMV, which is the leading infectious cause of birth defects worldwide.

Now, for the first time, a nonhuman primate CMV has been demonstrated to be congenitally transmitted similar to congenital HCMV infection. The discovery was published this week in the high impact journal Proceedings of the National Academy of Sciences and reported in The New York Times and Science Daily, among other news outlets.

Rhesus macaque mothers can transmit CMV across their placentas to their unborn infants, discovered the teams of co-senior study authors Sallie R. Permar, M.D., Ph.D., Duke University, and Amitinder Kaur, M.D., Tulane University. The lead author was Kristy Bialas, a post-doctoral fellow at the Duke Human Vaccine Institute.

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

The finding establishes the first nonhuman primate research model for CMV transmission via the placenta. The macaque reproductive, developmental, and immunological systems are highly analogous to those of humans. Thus, scientists can now utilize the biologically relevant RhCMV system in a controlled scientific setting to try to find new pathways towards an HCMV vaccine.

“A huge impediment to CMV vaccine development has been our lack of ability to determine what immune responses would be needed to protect against mother-to-fetus transmission,” said Permar, of the Duke Human Vaccine Institute in a Duke Medicine news release Oct. 19.

“It means that we can now use this model to ask questions about protective immunity against congenital CMV and actually study this disease for which a vaccine is urgently needed,” said co-senior author Kaur, of the Tulane National Primate Research Center in a Tulane University release Oct. 19.

The rhesus monkey model for HCMV persistence and pathogenesis has been developed over the past 30 years by co-author Peter Barry, Ph.D., California National Primate Research Center (CNPRC) core scientist, and co-developer of the rhesus intrauterine pathogenesis model with Alice Tarantal, Ph.D., CNPRC core scientist. Barry has recently shown that there is a strong immune response in rhesus monkeys to a potentially paradigm-shifting approach to HCMV vaccine design, and contributed important expertise and resources to this current research.

CNPRCrhesus,K_WestUCD, 4

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

The work highlights the collaboration of Duke University researchers with experts in rhesus immunology and virology at the National Institutes of Health National Primate Research Centers. Contributing authors also included David O’Connor, Ph.D., and Michael Lauck, Ph.D., experts in macaque virology, pathology and genetics at the Wisconsin National Primate Research Center, Xavier Alvarez, Ph.D., at the Tulane National Primate Research Center, and Takayuki Tanaka, D.V.M., Harvard Medical School and the New England National Primate Research Center, which provided macaques for the study. Additional authors’ contributions are included in the Duke news release.

The research was funded by National Institutes of Health (NIH) Office of the Director, NIH National Cancer Institute, NIH National Institute of Allergy and Infectious Diseases, NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Derfner Children’s Miracle Network Research Grant.

Reference:

Kristy M. Bialas et al. “Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission” Proc Natl Acad Sci U S A. 2015 Oct 19. http://dx.doi.org/10.1073/pnas.1511526112

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

 

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]