Nobel Prize 2015 – Protecting People against Parasites!

The 2015 Nobel Prize in Physiology or Medicine has been awarded to scientists whose research has led to therapies that have saved hundreds of millions of people around the world from parasitic diseases that can otherwise cause disability and death.

William C. Campbell and Satoshi Ōmura shared one half of the award “for their discoveries concerning a novel therapy against infections caused by roundworm parasites”, while Youyou Tu was awarded the other half “for her discoveries concerning a novel therapy against Malaria”.

Portraits of the winners of the Nobel medicine prize, shown on a screen at the ceremony in Stockholm. Photograph: Jonathan Nackstrand/AFP/Getty Images

Portraits of the winners of the Nobel medicine prize, shown on a screen at the ceremony in Stockholm. Photograph: Jonathan Nackstrand/AFP/Getty Images

In the press release announcing the award the Nobel Assembly at the Karolinska Institute highlighted the impact of the therapies that were developed thanks to the work done by these three scientists, Avermectin in the case of William C. Campbell and Satoshi Ōmura, and Artemisinin in the case of Youyou Tu.

The discoveries of Avermectin and Artemisinin have fundamentally changed the treatment of parasitic diseases. Today the Avermectin-derivative Ivermectin is used in all parts of the world that are plagued by parasitic diseases. Ivermectin is highly effective against a range of parasites, has limited side effects and is freely available across the globe. The importance of Ivermectin for improving the health and wellbeing of millions of individuals with River Blindness and Lymphatic Filariasis, primarily in the poorest regions of the world, is immeasurable. Treatment is so successful that these diseases are on the verge of eradication, which would be a major feat in the medical history of humankind. Malaria infects close to 200 million individuals yearly. Artemisinin is used in all Malaria-ridden parts of the world. When used in combination therapy, it is estimated to reduce mortality from Malaria by more than 20% overall and by more than 30% in children.

For Africa alone, this means that more than 100 000 lives are saved each year.

The discoveries of Avermectin and Artemisinin have revolutionized therapy for patients suffering from devastating parasitic diseases. Campbell, Ōmura and Tu have transformed the treatment of parasitic diseases. The global impact of their discoveries and the resulting benefit to mankind are immeasurable.

Animal research played a key part in the development of these therapies, as the Nobel Prize press release has pointed out.



In the case of Avermectin, after  Satoshi Ōmura had identified a series of bacterial cultures that produced a variety of antimicrobial agents, including the bacteria Streptomyces avermitilis which  showed promise against parasitic roundworm infection in mice, in 1979 William C. Campbell and colleagues identified a particular component produced by S. avermitilis called Avermectin B1a which had a broad efficiency against roundworm infections in a wide range of domesticated animal species, including cattle, sheep, dogs and chickens. Following this the team developed a modified form of Avermectin B1a known as Ivermectin, which was entered into clinical trials following positive tests in animal models of parasitic infection, and has since gone on to become a key treatment for parasitic infections – particularly the nematode worm infections that cause River Blindness and  Lymphatic Filariasis (the extreme manifestation of which is known as elephantitis) – and is on the World Health Organization’s list of Essential Medicines.



Ivermectin, and other members of the Avermectin family of therapies, are also widely used in veterinary practice, and their development and use is a good example of the One Health principle in action. You can learn more about the discovery of the Avermectins and Artemisinins in the advanced material Avermectin and Artemisinin – Revolutionary Therapies against Parasitic Diseases produced by the Nobel Assembly.

In 2011 we took a look at Professor Youyou Tu’s research that led to the development of Artemisinin therapy for malaria, and the key role played by mouse models of malaria infection,  in a post entitled “George is OK: Thank the men who stare down microscopes!”

While the news reports don’t state which drugs Cloony took to beat malaria, It is most likely that he was treated with artemisinin-based combination therapies (ACTs), which became available in the late 1990s and are now in widespread use.  If that is the case, he has benefited from mouse studies done in China the late 1960s and early 1970s when over 100 traditional herbal remedies were screened in a rodent model of malaria for anti-malarial activity (1). Eventually “Project 523” scored a hit when Professor Tu Youyou identified an extract of the plant qinghao, scientific name Artemisia annua, which had good anti-malarial activity, leading to the development of the artemisinin-based anti-malarials which have become the first-line treatment for malaria in the past decade.

We congratulate this years Nobel laureates in Physiology or Medicine, their research has improved the lives of hundreds of millions of people across the world over the past 3 decades, and will continue to do so. We hope that their success continues to inspire scientists around the world to rise to current and future public health challenges!

Speaking of Research

UK Government defends Beagle Breeding facilty

As early as 2013 we discussed why it made sense, from an animal welfare perspective, for the UK to approve the expansion of the B&K beagle breeding facility. The UK currently imports 20% of dogs used in research (the rest are bred at UK breeding facilities). The expanded facility in Hull hopes to reduce the numbers bred abroad, reducing the number of animals bred far away from the UK Home Office inspectors, and which must endure long flights at a young age to reach their destination. The Oppose B&K campaign, now joined by a number of other high profile animal rights groups, has fought the decision in the courts and through protests on the streets, but in July 2015, planning for the expanded breeding facility was approved by the Government. Since then, there has been a rash of protests and petitions.

Laboratory DogsWe wrote an article shortly after the decision to explain why we thought people were wrong to oppose the new breeding facility, saying:

Surely it is better to breed them here in the UK, where we have some of the highest standards of laboratory animal welfare in the world and where our facilities can be easily monitored by the Animals in Science Regulation Unit inspectors? The new breeding facility offers animal welfare standards above and beyond those demanded by the Government. Dogs will be kept in socially housed groups in multi-level pens which can be joined together to create larger runs for the animals. All the animals will have toys and enrichment in their enclosures, and will interact with trained laboratory technicians every day. It is this sort of investment in animal welfare we, as an animal-loving nation, should embrace

An official UK Government e-petition (which demands email verification and address details) reached 15,000 signatures (compared with around 500,00 for a petition which can be more easily manipulated). This prompted an official response from the Government. It is excellent, and well worth a read:

The use of animals, including dogs, in research is a vital tool for the development of new medicines and technologies. In order to ensure animals are protected, we have a rigorous regulatory system.

Planning ministers assessed the application’s planning merits and granted it permission on those grounds. The decision letter fully explains the reasons for this decision. The letter and related Inspector’s report can be viewed at:
Home Office regulatory safeguards
The use of animals in scientific research remains a vital tool in improving our understanding of how biological systems work both in health and disease which is crucial for the development of new medicines and cutting edge medical technologies for both humans and animals, and for the protection of our environment.

The Government has a strong commitment to maintaining a rigorous regulatory system under the Animals (Scientific Procedures) Act 1986 (the Act). Guidance can be found here:
The regulatory system ensures that animal research and testing is carried out only where no practicable alternative exists, and that suffering is kept to a minimum. This is achieved through applying the principles of the 3Rs which require that, in every research proposal, animals are replaced with non-animal alternatives wherever possible; that the number of animals used is reduced to the minimum needed to achieve the results sought; and that, for those animals which must be used, procedures are refined as much as possible to minimise their suffering.

All applications for research to be conducted are assessed by Home Office Inspectors. The harm benefit assessment conducted provides advice to the Home Secretary that the likely harms are justified by the expected benefits. Only after completion of this process will the Home Secretary consider granting a licence for the proposed work to go ahead. All Inspectors hold either veterinary or medical qualifications and are specially trained. Proposals must also have been considered by the research establishment’s Animal Welfare and Ethical Review Body.

Once a licence is granted, establishments are regularly inspected for compliance with their licence and the legislation.

The breeding and use of dogs in the UK
On occasion this research requires the use of dogs, mainly purpose-bred beagles. Dogs are accorded special protection under the Act and licences are only granted where justified where the specific results sought can only be achieved by using a dog.

All animals, including dogs, must be housed in accordance with the Code of Practice published by the Home Office: This sets standards for the housing, environmental enrichment, socialisation and exercise required for dogs in UK facilities. These standards are also regularly checked and monitored by Inspectors during often unannounced inspections.

Where it is essential to use dogs in research, it is better for their welfare that they should have been bred in facilities which meet the UK’s high standards and which are located close to the place where the dogs will subsequently be used. This minimises the potential stress of lengthy transport.

Currently less than 0.1% of animals used in research in the UK are dogs. Of these, more than 80% of the dogs that underwent procedures in 2013 were used in applied studies for human medicine or dentistry. Dogs are also used extensively in veterinary research to better understand naturally occurring diseases and to develop treatments and preventatives such as vaccines. Around 2% are used in fundamental biological research.

Following a Government ban in 1998, no animals have been used in testing cosmetics in the UK. The use of any species is also not permitted for the development or testing of alcohol or tobacco products as well as offensive weapons. During 2015, the Government is also implementing a ban on the testing of household products on animals.

Many people are understandably concerned what happens to animals, particularly dogs, at the end of scientific procedures and we are keen to encourage re-homing where appropriate. In deciding whether a dog should be re-homed, consideration of its welfare must be the first priority. It must be free from suffering and the likelihood of future suffering and it must have been adequately prepared to adapt to the new home environment. The types of studies that dogs are currently used for mean that the majority cannot be re-homed as it is often necessary to collect essential post mortem data at the end of a study. Such data is critical to achieving the scientific outcome for which the licence has been granted to enable the benefit of the research to be realised. Further information can be found on the Animals in Science Regulation Unit’s website:

This clear, informative response shows exactly how a Government should be approaching the animal research issue – openly, but with the clear message that such research plays an important part in the health of a nation.

Speaking of Research

OLAW investigates Primate Products, Inc. and praises staff who care for animals!

This one comes with a helping of déjà vu! On Friday, the National Institutes of Health (NIH) Office of Laboratory Animal Welfare (OLAW), published the results of an investigation into Primate Products, Inc. a facility in Hendry County, South Florida that breeds monkeys for medical research, including NIH funded research. The OLAW is the federal body responsible for monitoring compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals that regulates animal research funded by US Government Offices and Agencies – including the NIH – and the breeders that supply animals for the research they conduct. The OLAW report (which you can download here) detailed the results on an investigation which was prompted by complaints submitted by the animal rights group PETA after one of their employees infiltrated Primate Products.

In a statement accompanying the publication of OLAW’s findings, as reported by, the federal agency commended Primate Products administration and its:

“dedicated and caring staff for promptly and thoroughly addressing all of the noncompliant items,” wrote the office’s Axel Wolff in an email. “We now find that your program is operating appropriately under monitored self-regulation … We appreciate your forthright communications and prompt responses to all questions and hereby close this investigation.”

The report cleared Primate Products of many allegations made by PeTA.  The report also noted the efforts of Primate Products to address some breaches of regulations and to ensure that care provided to the animals meets the highest standards. Most of these were small technical changes to update training, reporting, or animal handling procedures, but also included the erection of an electric fence to prevent further intrusions following an unprecedented  incident when a wild bear broke into the facility and killed several monkeys.

Cynomolgus monkey, one of several monkey species supplied for scientific research by Primate Products. Image: André Ueberbach

Cynomolgus monkey, one of several monkey species supplied for scientific research by Primate Products. Image: André Ueberbach

PETA’s allegations were reminiscent of the case a couple of years ago during PETA’s campaign against hearing research that involved cats at the University of Wisconsin – Madison, where after a thorough investigation the OLAW cleared the researchers and University of the allegations made by PETA. They also remind us of the incident 5 years ago when another animal rights group (Stop Animal Exploitation Now) used leaked photos of monkeys undergoing appropriate veterinary care following fighting among group housed macaque monkeys (a normal, if infrequent, behaviour for the species) to make lurid allegations against Primate Products. On that occasion the USDA investigated the allegations, and cleared Primate Products of any wrongdoing, with USDA spokesperson Dave Sacks commenting:

It was a clean inspection report…there was nothing found that was against animal welfare regulations…Group housing of primates is allowed in the animal welfare regulations…with the mindset that’s more closely adapted to how they live in the wild. These animals do various fighting among themselves for hierarchy…so that will carry through to how they are housed…But if in those housing situations, if there is a monkey that gets injured, we require the facility to provide adequate care.”

As we’ve noted before, there’s a pattern in this. Animal rights groups have become adept in using infiltrations and Freedom of Information (FOI) record requests as the basis for (often spurious)  complaints to the USDA or OLAW that they then use to gain publicity and organize campaigns against individual researchers, and raise funds for future “investigations.” It’s a tactic that isn’t limited to animal rights activists of course. Not far away from Hendry County, Dr. Kevin Folta, a University of Florida professor who studies plant genetics and who is a dedicated science communicator, has been targeted by a vicious FOI-driven campaign by opponents of genetic modification of crops. It’s a campaign that is clearly aimed at silencing someone who was a strong voice for science, and an illustration of how Freedom of Information can be used to attempt to suppress the Freedom of Speech of scientists at government funded Universities.

Given the risk that those targeted by campaigns such as PETA’s against Primate Products might decide to stay quiet, it’s reassuring to note that Dr. Jeff Rowell, a veterinarian and President of Primate Products, has a great record of explaining the work done by Primate Products and how it supports important research in Universities and other biomedical research institutions across the USA. An interview he gave to a local journalist earlier this year is a good example of this willingness to engage with the public.

Primate products

These latest  PETA allegations are unlikely to be the last made by animal rights groups against Primate Products, but it is heartening that the regulators are willing to take an honest and objective look at the evidence. In the meantime we hope that Jeff Rowell and his colleagues at Primate Products will continue to be vocal advocates for science, just as their work supports crucial medical research across the nation.

Speaking of Research

National Primate Centre shows off its monkeys

We were sent some wonderful pictures of monkeys (mainly macaques) to share with our readers. Thank you to Kathy West and the California National Primate Research Center (CNPRC) for these pictures. Images like this play an important part in letting people see the conditions that animals are kept in at their research facilities. These photographs are from the large outdoor corrals where most of the primates are kept at CNPRC.

CNPRC uses primates in important medical and scientific research and has a huge array of accomplishments to its name. These include:

  • Due to our development and testing of tenofovir (PMPA), HIV-infected mothers can give birth to HIV-free infants and HIV-infected people can live long and healthy lives. Tenofovir has become the key ingredient of successful prophylaxes, and is the most commonly used anti-HIV drug in the world.
  • Our research found a link between environmental tobacco smoke exposure and adverse effects on prenatal, neonatal and childhood lung development, cognitive function, and brain development
  • Our research has advanced the understanding of developmental timelines in the kidney, and applied these findings to new protocols and tissue engineering approaches to regenerate kidneys damaged by obstructive disease.
  • Novel development of therapies at the CNPRC are being used to treat patients with Alzheimer’s Disease.  Ongoing research is demonstrating that reversal of damage and restoration of brain function is possible.
  • Our 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

These images are shared on a Creative Commons BY-NC-ND Licence (see below). Please ensure you attribute to

Creative Commons License
Rhesus macaque at California National Primate Research Center ©UC Davis/CNPRC by is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Permissions beyond the scope of this license may be available at

Speaking of Research

Guest Post: Why science needs to improve

Jeremy BailooToday’s guest post is from Jeremy D. Bailoo, PhD, a developmental psychobiologist in the Division of Animal Welfare at the University of Bern, Switzerland. He is currently involved in research which examines the manner by which we house and care for animals and its relevance to animal welfare and how it affects experimental results. He is particularly interested in providing empirically based procedures for refining animal housing.

Why science needs to improve

In a recent article in the Huffington Post, Professor Marc Bekoff and Dr. Hope Ferdowsian outlined their reasons for believing that science does not need mice. Their article was written in response to an editorial in the New York Times which advocated for the need for female mice in laboratory research. Bekoff and Ferdowsian made a number of interesting points and cited relevant supporting literature. However, their response presented only certain aspects of the issues involved. In this piece I will deconstruct the arguments levied by both sides. I will refrain from critiquing information that was not accompanied by a citation in either article, as these constitute unsubstantiated opinion.

The authors of the New York Times editorial described a new study published in the journal Nature Neuroscience which suggested “that research done on male animals may not hold up for women. Its authors reported that hypersensitivity to pain works differently in male and female mice….If these differences occur in mice, they may occur in humans too. This means a pain drug…might appear to work in male mice, but wouldn’t work on women.” These authors then state that failure to consider gender or sex in research is well recognized and cite the work of Zucker and Berry (2010) as well as the repositioning of interests statement of the National Institutes of Health (NIH) specifying sex as a biological variable in NIH funded research (see here and here).

The NYT editorial framed a well-articulated argument and did not overstate any of the claims that it made. The issue of the underrepresentation of females in biomedical research has been repeatedly highlighted (e.g., here, here, here, here and here) with little change in US science funders’ policy until now. It is important to note that nowhere in this article is it stated that all research in mice is ungeneralizable to females. Indeed, whether a scientific result is generalizable to both sexes is dependent on the phenomenon being studied; and this seems to be the case in particular for pain research in mice.

Mice in a research laboratory. Image courtesy of Understanding Animal Research.

Mice in a research laboratory. Image courtesy of Understanding Animal Research.

In their argument against the use of mice in research in the Huffington Post, Bekoff and Ferdowsian state that “numerous experiments on male and female non-human animals (animals) fail to reliably hold up in humans, and many prominent researchers have argued we need to develop non-animal models in order to learn more about serious diseases from which numerous humans suffer.” It is without question that some (not all) experiments in male and female rodents fail to replicate their results when that same experiment is performed on humans. However, as the ability to falsify and to replicate an experimental result are the cornerstones of the scientific method, failure to replicate an experimental result does not imply poor generalizability of an animal model to the human condition. I have recently co-authored an article on this topic demonstrating that meta-analytic studies have revealed that the reporting of criteria related to experimental design and conduct in some biomedical animal experiments is poor. The reasons why the result of an experiment conducted in non-human animals may fail to be replicated in humans is a consequence of complex processes that cannot and should not be trivially summarized by the statement “we need to develop non-animal models in order to learn more about serious diseases from which numerous humans suffer.”

In support of their argument, Bekoff and Ferdowsian cite the article “Mice Fall Short as Test Subjects for Some of Humans’ Deadly Ills”. In summarizing this article, Bekoff and Ferdowsian imply that because C57BL/6 mice (a single strain of 16 classified as Tier 1 in priority for investigation) do not seem to be able to model sepsis in humans, then all mice fail as a model of human disease. This is a logical fallacy, and a quick google search leads to very interesting responses to this article. Some are in favour of this piece (e.g., here) while others quickly identify flaws with the logic (e.g., here and here). Indeed, in the original article, the authors state “The study’s findings do not mean that mice are useless models for all human diseases.”

Next, Bekoff and Ferdowsian make the claim that the former director of the National Institutes of Health, Elias Zerhouni has lost confidence in the use of mice to model anything that is related to humans (see here). Bekoff and Ferdowsian fail to cite the clarification or perhaps are unaware of the clarification that was given (see here) in which Mr. Zerhouni states, “In short, animal models remain essential to the basic research that seeks to understand the complexities of disease mechanism.” As my colleagues at the website Speaking of Research have put it: “Animal models are essential to developing new medicines. They are, obviously, not sufficient on their own – cell cultures, human studies and computer models (among others) are also crucial methods used alongside animal models.”

The next paragraph with a citation states “Even experiments involving similar nonhuman species have shown that studies in mice, rats, and rabbits agree only a little more than half of the time (please see Hartung and Rovida 2009)”. Careful reading of this citation, however, does not yield this information. Indeed, nowhere in this article are any of these claims made. More interestingly, the cited article states, “no acceptable alternatives to reproductive-toxicity testing (in animals, my emphasis) have emerged, or are likely to be validated by 2018. Computational approaches are also limited by the complexity of reproductive toxicity and because half of the REACH chemicals are mixtures, inorganic, salts or contain metal atoms, rendering toxicity less predictable”. Thus, rather than supporting Bekoff and Ferdowsian’s arguments, it would seem that Hartung and Rovida advocate for the use of animals in toxicological research because there are no good alternatives.


Laboratory mouse. Photo courtesy of Understanding Animal Research.

Bekoff and Ferdowsian then state, “Attitudes toward animals are also changing, and now is the time for action. As per a recent nonpartisan Pew Research Poll, a solid 50 percent of people surveyed now oppose the use of animals in laboratory experimentation — an all-time high in the public opinion research literature.” This is indeed alarming and is the reason I have spent many hours researching these data. It is time that active scientists speak up for their science and break the cycle of misinformation that is spreading throughout our society.

In their penultimate paragraph Bekoff and Ferdowsian indicate that many may be incredulous in realizing “that mice and rats aren’t animals but a quote from the federal register does in fact read, “We are amending the Animal Welfare Act (AWA) regulations to reflect an amendment to the Act’s definition of the term animal. The Farm Security and Rural Investment Act of 2002 amended the definition of animal to specifically exclude birds, rats of the genus Rattus, and mice of the genus Mus, bred for use in research” (Vol. 69, no. 108, 4 June 2004).” It is worthwhile to note the date of this citation, June 2004 – 11 years ago. Much has changed in those 11 years and much will continue to change in the future. As science progresses, the type of animals used in research, the manner in which they are used, and their care will be continually scrutinized by scientists and the public. As a result, animal care, use, and corresponding regulations will continue to be adjusted. Moreover, animals used in research (including birds, rats, mice) are covered by Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals since 1985 while guidelines for the care and use of laboratory animals have been critically considered since 1963 and have been continually updated as new information becomes available. Ferdowsian and Bekoff are either ignorant of current US regulations governing research or are deliberately being disingenuous.

These authors conclude that “there are numerous non-animal alternatives that are extremely reliable (please also see), and it’s about time they are used.” Again, where is the evidence for this? As I have outlined in this commentary, Bekoff and Ferdowsian have not provided sufficient evidence to come to this conclusion. Moreover, the statement that many non-animal alternatives are currently available and reliable requires careful deliberation. An example of such deliberation can be found here. The unsubstantiated statement that alternatives exist and are reliable does not make it so. Currently, such research and methods complement, rather than replace, research in non-human animals.

Thus, it would seem that the argument levied by Bekoff and Ferdowsian that science does not need research with mice is misleading. Poor reproducibility of experimental results is a problem in biomedical research. Indeed, it is a problem with science in general (e.g., here, here and here). To address the question “does science need mice”, one would have to: 1) examine the fields of science which use mice, 2) identify whether the science is performed with experimental rigour (design and conduct), and then 3) evaluate whether the findings obtained from these rigorous experiments are reproducible. By and large, the scientific community is still at step 2. As I mentioned previously, many fields which conduct research using mice report results that are irreproducible. The current cause ascribed to these failures is poor experimental design and conduct. This insight is gained by analysing whether information related to experimental design and conduct in published manuscripts and experimental applications are reported. For many fields of study employing the use of rodents, we cannot even begin to evaluate the effectiveness of a model because the manner in which the study was reported was poor. It is worth emphasizing that poor reporting of aspects of a study related to experimental design and conduct does not necessarily imply that a study was conducted poorly. Ascertaining this information would require interviews for each published article in question; a Herculean, if not impossible, feat. As highlighted in my recent paper, many solutions have been put forward to improve the manner in which we execute and report experiments but until these are endorsed and enforced, science in general will not improve. And that also applies to research using humans as subjects.

Jeremy D. Bailoo, Ph.D.

The opinions expressed here are my own and do not necessarily reflect the interests of the the University of Bern or the Division of Animal Welfare at the University of Bern.

What happens when an animal rights activist tours an animal research lab?

What would you do if an activist group, whose Facebook wall features the extremist group the ALF, asked to tour your labs? While many people would ignore their request, the University of Guelph (Canada) invited the individual in to tour the facility and answer their questions.

Animal Rights Compliance Facebook page

Animal Rights Compliance Facebook page

A post on the Animal Rights Compliance Facebook page on the 12th September 2015 states that they believe in “The complete abolition vivisection, animal research or drug testing cosmetics, testing of consumer products on animals. Infractions need to be dealt with by fines and minimum incarceration times.” So one might not expect a glowing review on Facebook when the (anonymous) individual reported back.

See transcript of picture at the bottom of this post

See transcript of picture at the bottom of this post

Instead we get an honest account of a research institution which is working hard to improve animal welfare. Huge congratulations to the University of Guelph, and particularly Mary Fowler, the animal facility manager, as they once again show that openness trumps misinformation. The report shows how many people, including activists, are unaware of conditions in labs and can be surprised and impressed when they discover how animals are really treated.

“Mary was very transparent with the University’s policies and I was given a tour of where, currently, only 6 dogs are housed. I was impressed with several issues; The University has extensive dogwalking/caregiving procedures, as well as adoption policies using staff, students and volunteers. It works in co-ordination with the local and area Humane Societies. My understanding is that their treatment models are evolving all the time, with the replacement of live animals with other means whenever possible. Another example is that spay and neutered pets are regularly returned to the Humane Society for adoption. “

A full transcript exists at the bottom of this post for those who cannot see the image. Credit is also due to the unnamed activist who toured the facility and reported back – it’s great to see people be willing to go in with an open mind and report back honestly on what they saw.

Read more about how the University of Guelph gets involved in outreach activities about their animal research through public engagement, internal communication and tours. Also, read their public statement on animal research.

Major advances in the health of humans and animals can be attributed to research using live animals. As an institution, the University of Guelph supports the principle that animals may be used in science only where necessary and where there are no alternative means that will produce the same results to benefit the health of humans and animals.

The University of Guelph has a long history of conducting innovative, multidisciplinary research with partners at other universities, government, and from the private sector. Through partnerships with the Ontario Ministry of Agriculture and Food the university plays a key role in research and teaching in the life sciences and agriculture. With a broad range of species, from laboratory rodents to farm animals, fish and wildlife, the University of Guelph has one of Canada’s largest and most versatile animal care and use programs. The University continues to be on the leading edge of animal-based science, the training of highly qualified personnel, and the promotion of welfare and health advancements for animals and humans through research and teaching

Visitors to the open house at the University of Guelph Central Animal Facility learn about research and environmental enrichment over lunch. Credit: Janet Gugan

Visitors to the open house at the University of Guelph Central Animal Facility learn about research and environmental enrichment over lunch. Credit: Janet Gugan

Speaking of Research


If the image from the activist did not come up on your computer, here is a full transcript.

MEETING WITH MARY FOWLER, MANAGER, ANIMAL FACILITIES OFFICE OF RESEARCH, University OF Guelph, Sept.16/15: I had the pleasure of meeting with Ms. Fowler today, at my request, as I was inquiring about the University’s policies on using live animals. esp. dogs in research. Mary was very transparent with the University’s policies and I was given a tour of where, currently, only 6 dogs are housed. I was impressed with several issues; The University has extensive dogwalking/caregiving procedures, as well as adoption policies using staff, students and volunteers. It works in co-ordination with the local and area Humane Societies. My understanding is that their treatment models are evolving all the time, with the replacement of live animals with other means whenever possible. Another example is that spay and neutered pets are regularly returned to the Humane Society for adoption. It is also my understanding that the University does not do such vivisection procedures as cosmetic testing. While we would all like to see all animals cage-free, I would say a greater good appears to being served when animals are treated with respect and given some sort of a life, then adopted out, on average between 6-8 months. I am not sure how else Vets could learn to save animal lives. The point recognized, I think, is that there is a general agreement about needless animal suffering. Thanks again to Mary and her staff.

Truvada prevents HIV infection in high-risk individuals! A clinical success built on animal research

In the past two weeks we’ve learned of a major advance in ongoing efforts to halt the spread of  HIV, two separate clinical studies have reported that a daily regimen of a pill called Truvada as a pre-exposure prophylaxis (PrEP) is highly effective in preventing infection in high risk groups. This success is a result not just of the dedication of the clinicians who conducted these trials, but also of a series of pivotal studies conducted in non-human primates more than a decade ago that laid the scientific foundations for them.

In the first study of more than 600 high-risk individuals conducted at Kaiser Permanente in San Francisco, which was published in the journal Clinical Infectious Diseases, researchers found that Truvada – a combination of the anti-viral drugs tenofovir and emtricitabine – was 100% effective in preventing infection.  In the 2nd  study, called the PROUD study and published online this week in the Lancet, of more than 500 high-risk men undertaken in 13 sexual health clinics in England Truvada reduced infections by 86%.

Truvada prevents HIV transmission in high-risk individuals. Image: AFP / Kerry Sheridan

Truvada prevents HIV transmission in high-risk individuals. Image: AFP / Kerry Sheridan

These results have been greeted with enthusiasm in media reports, with headlines such as “Aids vanquished: A costly new pill promises to prevent HIV infection” , “A pill designed to prevent HIV is working even better than people thought” and  “Truvada Protected 100 Percent Of Study Participants From HIV: This is exciting!”. It’s worth noting that these are not the only trials to show the potential for Truvada to block HIV infection, earlier trials in Kenya, Uganda and Botswana also showed that it could substantially reduce infection rates, including in heterosexual couples where one partner was HIV positive and the other was not. There has been some concern that those taking Truvada would be less likely to take other safe sex measures – such as using condoms – but the results of the PROUD study showed no difference in acquisition of other sexually transmitted infections between those who started Truvada treatment immediately and those who delayed for 1 year, suggesting that they did not engage in riskier behavior as a consequence of taking Truvada.

Thanks to a multi-pronged approach to preventing HIV infection, combining barrier methods such as condoms,  Highly Active Antiretroviral Therapy (HAART) to lower viral load in infected individuals, and the use of antiviral medications to prevent mother-to-child transmission, the spread of HIV infection has slowed dramatically in many regions of the world, and pre-exposure prophylaxis with Truvada certainly has the potential to help reduce it further.

As we applaud the researchers who conducted these first real-world evaluations of Tenofovir in high-risk populations, it is also a good opportunity to remember the researchers whose work led us to this point. One of those pioneers is Dr. Koen Van Rompay, a virologist at the University of California at Davis who played a key role in the early development of Tenofovir and  its evaluation in pre- and post- exposure phophylaxis in macaque models of HIV infection. In 2009 Dr Van Rompay wrote an article for Speaking of Research explaining how important animal research was to the early development of such HIV prophylaxis regimes, and how important it continues to be as scientists develop ever better treatments, which we share again today:

Contributions of nonhuman primate studies to the use of HIV drugs to prevent infection – Koen van Rompay

Since the early days of the HIV pandemic, as soon as it was clear that an effective HIV vaccine would still be years away, there has been considerable interest in using anti-HIV drugs to reduce the risk of infection following exposure to HIV (so-called prophylaxis). Animal models of HIV infection, especially the rhesus macaque, have played a major role in developing and testing these treatments.

The development of HIV drugs to treat HIV-infected persons has shown that many compounds that are effective in vitro (i.e., in tissue culture assays) fail to hold their promise when tested in humans, because of unfavorable pharmacokinetics, toxicity or insufficient antiviral efficacy. The same principles apply to the development of drugs to prevent HIV infection. The outcome of drug administration is determined by many complex interactions in vivo between the virus, the antiviral drug(s) and the host; with current knowledge, these interactions cannot be mimicked and predicted sufficiently by in vitro studies or computer models.

Testing different compounds in human clinical trials is logistically difficult, time-consuming and expensive, so only a very limited number of candidates can be explored in a given time. Fortunately, the development of antiviral strategies can be accelerated by efficient and predictive animal models capable of screening and selecting the most promising compounds. No animal model is perfect and each model has its limitations, but the simian immunodeficiency virus (SIV) of macaques is currently considered the best animal model for HIV infection because of the many similarities of the host, the virus and the disease. Non-human primates are phylogenetically the closest to humans, and have similar immunology and physiology (including drug metabolism, placenta formation, fetal and infant development). In addition, SIV, a virus closely related to HIV-1, can infect macaques and causes a disease that resembles HIV infection and AIDS in humans, and the same markers are used to monitor the disease course. For these reasons, SIV infection of macaques has become an important animal model to test antiviral drugs to prevent or treat infection.

Studies in rhesus macaques first indicated that Tenofovir could block HIV infection. Photo: Understanding Animal Research

Studies in rhesus macaques first indicated that Tenofovir could block HIV infection. Photo: Understanding Animal Research

Different nonhuman primate models have been developed based on the selection of the macaque species, the particular SIV strain and the inoculation route (e.g. IV injection, vaginal exposure) used (reviewed in (33)). These models have been improved and refined during the past two decades. For example, SIV-HIV chimeric viruses have been engineered to contain portions of HIV-1, such as the enzyme reverse transcriptase (“RT-SHIV”) that the virus requires in order to multiply or the envelope protein (“env-SHIV”) that the virus needs if it is to escape from a cell and infect other cells, to allow these models to also test drugs that are specific for HIV-1 reverse transcriptase or envelope (28, 35).

Many studies in non-human primates have investigated whether the administration of anti-HIV drugs prior to or just after exposure to virus can prevent infection. The earliest studies indicated that drugs such as the reverse transcriptase inhibitor zidovudine (AZT), the first approved drug treatment for HIV, were not very effective in preventing infection, but a likely reason for this was the combination of a high-dose viral inoculums used, the direct intravenous route of virus inoculation, and the relative weak potency of drugs at that time (2, 4, 13, 19, 20, 36). The proof-of-concept that HIV drugs can prevent infection was demonstrated in 1992 when a 6-weeks zidovudine regimen, started 2 hours before an intravenous low-dose virus inoculation that more accurately represented HIV infection in humans, protected infant macaques against infection (29). These results were predictive of a subsequent clinical trial (Pediatric AIDS Clinical Trials Group Protocol 076), which demonstrated that zidovudine administration to HIV-infected pregnant women beginning at 14 to 34 weeks of gestation, and continuing to their newborns during the first 6 weeks of life reduced the rate of viral transmission by two-thirds (10).

Since then, a growing number of studies have been performed in macaques to identify more effective and simpler prophylactic drug regimens. These studies generally used lower virus doses, sometimes combined with a mucosal route of virus inoculation that mimics vaginal or anal exposure responsible for the majority of human HIV infections. These studies demonstrated that administration of some newer anti-HIV drugs, including the reverse transcriptase inhibitors adefovir (PMEA), tenofovir (PMPA), and emtricitabine (FTC) that prevent the virus from multiplying in the infected cell, and the CCR5 inhibitor CMPD167 that stops the virus from binding the CCR5 receptor on the cell surface and entering a cell in the first place, starting prior to, or at the time of virus inoculation, was able to prevent infection, though with varying success rates (3, 4, 16, 24, 25, 31, 34, 35). Only very few compounds such as the reverse transcriptase inhibitors tenofovir, BEA-005 and GW420867, and the CCR5 inhibitor CMPD167, were able to reduce infection rates when treatment was started after virus inoculation. For those drugs that were successful in post-exposure prophylaxis studies, a combination of the timing and duration of drug administration was found to determine the success rate, because a delay in the start, a shorter duration, or interruption of the treatment regimen all reduced the prophylactic efficacy (5, 11, 21, 22, 26, 27, 31) , information that has guided the design of subsequent clinical trials.

While some of the compounds such as GW420867 that showed prophylactic efficacy in the macaque model are no longer in clinical development (e.g., due to toxicity or pharmacokinetic problems discovered later in pre-clinical testing), the very promising results achieved with tenofovir have sparked further studies aimed at simplifying the prophylactic regimen. Several studies in infant and adult macaques have demonstrated that short or intermittent regimens of tenofovir (with or without coadministration of emtricitabine) consisting of one dose before and one dose after each virus inoculation were highly effective in reducing SIV infection rates (15, 30, 32).

The demonstration at the beginning of the 1990’s that anti-HIV drugs can prevent infection in macaques has provided the rationale to administer these compounds to humans to reduce the likelihood of infection in several clinical settings. Antiviral drugs are now recommended, usually as a combination of several drugs, to reduce the risk of HIV infection after occupational exposure (e.g., needle-stick accidents of health care workers) and non-occupational exposure (e.g. sex or injection-drug use) (6, 7). As mentioned previously, drug regimens containing zidovudine and more recently also more potent drugs such as nevirapine have proven to be highly effective in reducing the rate of mother-to-infant transmission of HIV, including in developing countries (10, 14, 17), and save many thousands of lives every year . Because the short nevirapine regimen that is given to pregnant HIV-infected women at the onset of labor frequently induces drug resistance mutations in the mother that may compromise future treatment (12), tenofovir’s high prophylactic success in the infant macaque model has sparked clinical trials in which a short tenofovir-containing regimen was added to existing perinatal drug regimens to reduce the occurrence of resistance mutations and/or further lower the transmission rate (8, 9, 18, 30, 32).

Scanning electron micrograph of HIV-1, colored green, budding from a cultured lymphocyte. Photo: C. Goldsmith Content Providers: CDC/ C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus

Scanning electron micrograph of HIV-1, colored green, budding from a cultured lymphocyte. Photo: C. Goldsmith Content Providers: CDC/ C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus

Because an efficacious HIV vaccine has so far not been identified, the concept of using pre-exposure prophylaxis also as a possible HIV prevention strategy in adults has gained rapid momentum in recent years. The promising prophylactic data of tenofovir (with or without emtricitabine) in the macaque model (23, 32, 35, 37) combined with the favorable pharmacokinetics, safety profile, drug resistance pattern and therapeutic efficacy of these drugs in HIV-infected people, have pushed these compounds into front-runner position in ongoing clinical trials that investigate whether uninfected adults who engage in high-risk behavior will have a lower infection rate by taking a once daily tablet of tenofovir or tenofovir plus emtricitabine. The results of these ongoing trials are highly anticipated. An overview of the design, status and challenges of these trials which are currently underway at several international sites and target different high-risk populations can be found on the website of the AIDS Vaccine Advicacy Coalition (1, 23).

In conclusion, nonhuman primate models of HIV infection have played an important role in guiding the development of pre- and post-exposure prophylaxis strategies. Ongoing comparison of results obtained in these models with those observed in human studies will allow further validation and refinement of these animal models so they can continue to provide a solid foundation to advance our scientific knowledge and to guide clinical trials.

Koen van Rompay DVM Ph.D. is a research virologist at the California National Primate Research Center at UC Davis.

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