Tag Archives: animal testing

Background Briefing on Animal Research in Canada

In February we announced the publication of our US Background Briefing on animal research. Today we are publishing our Canadian counterpart briefing. We hope this will offer journalists, editors and broadcasters who may need to discuss this issue, a handy overview of the facts. Our two-page summary provides key information including the number of animals used for research purposes, the laws and regulations surrounding animal research, and some key questions people have.

Download the Background Briefing on Animal Research in Canada

As with our previous briefing, we encourage those working in universities, pharmaceuticals, and other research institutions, to help share this document when contacting or responding to journalists about research stories relating to their institution. By attaching this background briefing to proactive stories, or reactive statements, it can help ensure that your research is understood within the context of the wider research environment.

Animal Research Canada

We permit anyone to redistribute this briefing providing it remain unchanged, and in whole, with credit to Speaking of Research.

We would like to produce more of these for different countries in the future, to add to our American and Canadian briefings. Those wishing to see a similar briefing for the UK should consult the Science Media Centre’s “Briefing Notes on the Use of Animals in Research”. We thank the Science Media Centre for offering their support in producing our briefings.

Speaking of Research

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

Pictures in need of accurate words: University of Florida animal photos

Pictures of a cat spay clinic misrepresented as a laboratory horror shop circulated the internet recently to support appeals to “end animal testing.” Speaking of Research wrote about it here “Fact into fiction: Why context matters with animal images,” noting the importance of understanding the facts and context for photographs.

This picture was used to misrepresent animal research

This picture was used to misrepresent animal research

In the cat spay clinic case, the photos were from a newspaper article. We have written previously about images of laboratory animals that have made their way to the internet via leaks, undercover operations, and open records release. In all cases, several points remain true. Images are powerful. Providing accurate information about the images is important. It is also true that there are important differences between the sources and ways that images are obtained. Those obtained via infiltrations and undercover operations may be from manipulated situations, or  small fractions of hours of recording, in both cases providing a deliberately misrepresentative view. Photos obtained from institutions via open records release can also be used to misrepresent laboratory animals’ care and treatment and can be the centerpiece in “shock” campaigns. Their value is obvious from even a quick survey of high profile attacks on research, as we’ve written about previously (here, here, here). As in the case of the spay clinic images, conflating veterinary and clinical care with scientific research is also common and further serves to confuse the issues.

Can the laboratory animal research community do a better job of providing context for images of animals?  Yes.

Knowing what the images show and why matters, particularly to people who would like to engage in serious and thoughtful consideration to inform their point of view and judgments. In absence of context and facts, the audience is left without key knowledge and an opportunity to educate is missed. Yet all too often the opportunity is missed and the images remain in public view without comment or context from those who could provide a better understanding of what the photographs show.

In reviewing laboratory animal photographs that appear on animal rights sites, it is obvious that there are generally two types: those from activities directly related to the scientific project and those related to veterinary care or housing and husbandry. In terms of providing context and information, the two differ with respect to their source and which personnel may best explain the content of the photographs.

What does the image depictSome images may be of actual scientific research activities. These may be of animals engaging in an activity directly related to the science question under study. For example, the images may illustrate how animals perform a cognitive or memory task, how they navigate a maze, or how a particular measurement is obtained. The Max Planck Institute for Biological Cybernetics website provides an example of this, with description and photographs of rhesus monkeys and cognitive neuroscience research. Another type of image directly related to the scientific project may be of a surgery or procedure. An example of this is found in pictures of a surgery involved in cat sound localization research (photos here, video here). In each case, it is not particularly challenging to provide additional information and context because the activities are typically also explained in the protocols, grants, and scientific papers about the study.

Images of clinical veterinary care, husbandry, and housing appear frequently in activist campaigns and public view. For example, pictures of routine physical examinations, health tests, unexpected injuries unrelated to scientific procedures, or photos of animals in their normal housing, have all appeared via various sources. Many times– perhaps more often than not– the activity depicted in the images would not be obvious to a lay audience because it remains unexplained.

A common image – tuberculosis skin test

One of the best examples of misunderstood images is found in pictures of an anesthetized macaque monkey with a needle injecting something in its eyelid. The picture circulates the internet with various captions opposing “animal testing.”   What does this picture show?

tb imageIt is a skin test, commonly used in human and nonhuman primates, for early detection of tuberculosis. A small amount of tuberculin (non-harmful) is injected just under the skin. In almost all cases, the primate does not have tuberculosis and the skin remains normal. If the primate—human or not—does have a reaction to the test, indicated by redness and some swelling, it provides evidence of possible tuberculosis infection. That person, or monkey, then receives additional testing and preventive measures for treatment and to avoid infecting and harming others.

Tuberculosis testing is routinely performed as a health procedure in humans who work in hospitals, schools, with children and with others who may be vulnerable. In settings where nonhuman primates are housed, tuberculosis testing is often routinely performed with all human personnel and with the other animals. Why? Because tuberculosis is a rare disease, but one that can be a threat to the animals’ health and thus, precautions are necessary to ensure their health. The difference between human and monkey tb testing is that for humans, the injection is given without pain relief or anesthesia, via a needle inserted into the forearm.

Aside from the momentary discomfort of the injection, the test is painless and without irritating after-effects. In monkeys, the injection is typically given while the animal is anesthetized and is placed just under the skin of the upper eyelid. Why the difference? It is a simple reason—the key to the test is looking for redness or slight swelling. In monkeys, the forearm is fur-covered and it would be very difficult to detect a reaction in an unobtrusive way.

University of Florida monkey pictures

Not surprisingly, the monkey tb test photo is one that seems to appear in an ongoing campaign against the University of Florida. In response to several years of attacks on their animal research programs, public universities in Florida are pursuing new action to shield personal information about their personnel from public disclosure.   We’ve written previously about an ongoing campaign of violent threats, harassment, and protest by local activists (here, here, here).

In parallel to other campaigns, photographs are a centerpiece of the current attacks on animal research. As reported by Beatrice Dupuy in the Independent Alligator:

“Disturbing pictures of primates being examined by researchers are featured on the organization’s website along with posters with quotes like “stop the holocaust inside UF, free the monkeys.” After a three year lawsuit, the organization, formerly named Negotiation is Over, obtained UF’s public veterinary records last April. The researchers named in public records were the first ones to be targeted by animal rights activists, said Janine Sikes, a UF spokeswoman.”

What are these “disturbing pictures of primates being examined by researchers”?

The photographs <warning: link to AR site> are of macaque monkeys that appear to be receiving routine veterinary care or are simply in fairly standard housing. While the activists claim these photos are evidence of maltreatment at the hands of researchers, they likely are mostly of routine veterinary procedures. For example, two appear to be of an anesthetized macaque monkey receiving a tattoo, another two of an anesthetized monkey receiving a tuberculosis test, while others show the reddened skin that rhesus macaques exhibit normally in the wild and captivity. One photo depicts what looks like a stillborn infant macaque. Without context or confirmation, it isn’t surprising that the photographs can be interpreted in many ways.

UF’s spokesperson says: “The university wants to be very open and honest about its research,” … “It wants to stop these personal attacks against our researchers.”

One place to begin is to provide straightforward and accurate context for the images of laboratory animals that have been released. While those with experience in laboratory care of nonhuman primates can view the images and be reasonably certain that they are mostly of clinical veterinary care, it is only the UF veterinary, animal care program, and scientific personnel that can provide accurate information. Other universities have done exactly that when faced with the same situation. In “An Open Letter to the Laboratory Animal Veterinary Community and Research Institution Administration”   we wrote:

“While scientists can address questions about the scientific side of animal research, we need the laboratory animal care and veterinary staff to provide their expertise in service of addressing public questions about clinical care and husbandry.  If they do not, it will be no surprise if the public view of animal research is disproportionately colored by the relatively rare adverse events and the misrepresentations of animal rights activists. Many believe that it is possible—and perhaps acceptable—to ignore this part of reality in order to focus on more immediate demands for time, energy, and resources. Consider, however, that a fundamental part of the AWA, accreditation, regulation, and professional obligation is actually to ensure communication with the public that supports animal research.  Thus, it is our entire community who share a primary obligation to engage in the dialogue that surrounds us.”

We have consistently condemned the extremists who have targeted UF scientists and others with outrageous harassment. Tactics designed to elicit fear and terror do not have a place in democratic society and do nothing to promote fair and civil dialogue about complex issues.

At the same time, we believe and have written often, that the scientific and laboratory animal community, including scientists, veterinarians, and institutional officials should consider that better education and explanation are key to building public dialogue and understanding of research. Furthermore, as highlighted in this case and others, releasing photographs, records, and other materials without providing context serves no one well. Providing straightforward explanation of the veterinary practices, housing, husbandry, and care of laboratory animals not only gives context to photographs, but also should not be that hard to do.

Allyson J. Bennett

More information and resources:

Raising the bar: What makes an effective public response in the face of animal rights campaigns:  http://speakingofresearch.com/2013/02/20/raising-the-bar-what-makes-an-effective-public-response-in-the-face-of-animal-rights-campaigns/

Time for a change in strategies? http://speakingofresearch.com/2013/06/24/time-for-a-change/

A detailed response to a PETA video accusing a primate lab of mistreatment:  http://speakingofresearch.com/2008/07/04/peta-out-with-the-new-in-with-the-old/

Speaking of Research media briefing (pdf):  Background Briefing on Animal Research in the US

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

Background Briefing on Animal Research

Having a full understanding of all the issues surrounding animal research can be a challenge for even science-specialist journalists, let alone general journalists, editors and broadcasters who have to handle many unrelated issues each and every day. Speaking of Research have produced a two-page summary of the key information which general news producers, journalists, presenters and editors, can use to quickly inform themselves about this issue.

Download the Background Briefing on Animal Research in the US

We encourage those working in universities, pharmaceuticals, and other research institutions, to help share this document when contacting or responding to journalists about research stories relating to their institution. By attaching this background briefing to proactive stories, or reactive statements, it can help ensure that your research is understood within the context of the wider research environment.

Media briefing on animal testing

We permit anyone to redistribute this briefing unchanged, and in whole, with credit to Speaking of Research.

We would like to produce more of these for different countries in the future. However, those wishing to see a similar briefing for the UK should consult the Science Media Centre’s “Briefing Notes on the Use of Animals in Research”. We thank the Science Media Centre for offering their support in producing this briefing.

Speaking of Research

Conversation Starter? PETA’s Bus Ads on University of Wisconsin Hearing Research

As predicted, PETA’s ongoing campaign against scientific research at the University of Wisconsin-Madison continues, escalating this week with a striking advertisement on 100 Metro buses. The ad calls for an end to UW research aimed at better understanding how the brain processes sound. A central question is how sound arriving at both ears is combined to allow us to determine the direction of its source with respect to our body. Sound localization ability allows us, for example, to quickly react to an approaching car that we might not have seen. In turn, this kind of basic understanding has provided the knowledge necessary to help people with hearing disorders and to guide the way for cochlear implants. It is the work of a highly respected scientist, Professor Tom Yin, whose discoveries and research have been funded by the National Institutes of Health for decades. His research is publicly funded because the scientific leadership of our country determined that the work is important to serve the public’s interest in advancing scientific understanding and public health. Furthermore, and contrary to PETA’s claims, the  cats are healthy and treated humanely, in accord with federal regulation, as demonstrated by the public reporting of thorough oversight by multiple federal agencies.

Metro bus displaying PETA ad. Image: Wisconsin State Journal.

Metro bus displaying PETA ad. Image: Wisconsin State Journal.

The ads that PETA is running on the buses don’t mention that.  What they do instead is show a picture of a cat, a participant in the research and the phrase “I am not lab equipment. End UW cat experiments.”

The picture is one PETA obtained from an open records request. Video of the research, many pictures, and interviews of the scientists whose research is targeted can be found here. The PeTA ads also don’t mention that both the US Department of Agriculture and the NIH’s Office of Laboratory Animal Welfare investigated PeTA’s complaints and cleared Prof. Yin and UW of any wrongdoing.

We have written previously (here, here, here) in detail about PETA’s sustained efforts to use the federal regulatory system to end the UW’s sound localization research. We’ve also written about their other approaches to generate public and media attention – ranging from celebrity protests at the UW Board of Regents meeting to Bill Maher robocalls to an MMA fighting game where players are encouraged in violence (and sending emails to NIH opposing UW’s research).

Through all of this, PETA has made their position quite clear. Their goal is to end animal research regardless of the consequences for human and animal health, regardless of public interests.

While PETA’s campaigns are marketed as concern about animal welfare, even a superficial analysis quickly shows that it is not their central mission. After all, this is the same group with an abysmal record of killing the cats and dogs in their care.  Furthermore, it seems unlikely that PETA’s investment in various campaigns is proportional to the number of animals involved in different uses. Only a tiny fraction of animals are used in research, in contrast to the vast majority in food, clothing, entertainment, service, and companionship. Yet animal research remains a major investment for PETA campaigns.

What PETA is aiming for when it targets animal research, particularly when it invests so much effort and so many resources to shut down a program involving only a dozen animals is political and obvious. They have selected a target that they believe will capture public emotion and sentiment in a way that serves a broader political goal that otherwise would be difficult to raise public attention and support.

In all of these campaigns, PETA is banking on a couple of expectations. First, that the public will not take the time to learn more about the research. Second, that the scientific, medical, advocacy, and patient groups will decline to engage or counter PETA’s outrageous claims. If, and when, those expectations are no longer met, PETA will lose its power to detract from a serious, civil and public consideration of science, medicine, and animal research.

For that reason, we believe that it is a critical responsibility of our community to continue to provide clear, factual, and responsive engagement to the public—regardless of how silly or wrong PETA’s tactics appear.

In the case of the Madison Metro bus ad campaign, we encourage the public and journalists who are interested in learning about the science– why it is conducted, the discoveries of the scientific team, the clinical applications, and the treatment of the animals—to take the time to learn more. The scientist and the University of Wisconsin have written extensively about the work. They have placed videos, photographs, interviews, papers, and point-by-point responses to PETA’s allegations in public view (more here). In fact, the scientist targeted by PETA for several years has provided a lab tour and interview to a local journalist.

Representatives of the university administration and animal research program have also consistently engaged with the media in a way that goes far beyond boilerplate responses and the university has hosted public discussions that have included contributions from both scientists and animal rights activists. At the time when PETA first made their allegations 65 of Prof. Yin’s colleagues even backed an Op-Ed piece written for the local newspaper. In other words – and no surprise –there is more to the story than a bus shrink-wrapped with a PETA billboard.  UW-Madison has made that clear time and again, with consistent and sustained effort to provide the public with clear, factual information and to engage when questions are asked.  More than that though, they also have a strong track record and commitment to science education and outreach in a great many venues.

While it is tempting to dismiss PETA’s tactics, it is worth public consideration that there is a sure long-term harm of acting on PETA’s commands without understanding the consequences to public interests, public health and the science that serves all of us. The scientific, academic, advocacy, patient, and other communities, on the other hand, know the value of the work that Prof. Yin and his colleagues are doing and can view this latest campaign as yet another time to speak up for the research.

Animal research and diabetes: Now the truth must be told – Part 2

In yesterday’s post we described how animal research contributed to the understanding and treatment of diabetes – most importantly with the discovery of insulin. In this post we address some of the common misinformation that activists are circulating on social media about the role of animal experiments in diabetes research.

a)      One of the most valuable advances in understanding diabetes was made by Dr Moses Barron.

Prior to 1920, many researchers had worked on the relationship between the pancreas (or even more specifically, the islets on Langerhans) and diabetes. Banting and Best were by no means the pioneers in this field.  In the literature review of their February 1922 paper (1), they cited the article of Barron for having inspired their work and allowed them to formulate their hypothesis. They also cited precursor work of Mering & Minkowski, and Sscobolew, amongst many others. Banting and Best made use of groundwork already done before them and used this as support to bring their research to higher heights. This is something very usual in biomedical research, groundbreaking discoveries/advances are never achieved in a nutshell – they all rely on previous precursor work.

b)      Barron explained that his discovery ‘could be made in no other way, not even by experimental ligation of the ducts in animals’

In his November 1920 paper (2), Barron was not speaking about his ‘discovery’. In fact the purpose of the paper (page 1) was to present examples of typical changes in the Islets found in cases of true diabetes together with one histopathology case study of pancreatic lithiasis (formation of stones in the pancreas) and to correlate these findings with those recorded in the literature as obtained in experimental ligation of the ducts in animals.

On page 8 of his paper, while he is describing his 4th case study,  he describes the lesions of pancreatic lithiasis as ‘by their very nature, being of long standing, presents gradually progressive changes in the parenchyma, that could be obtained in no other way, not even by experimental ligation of the ducts in animals”.  This is indeed true as experimental ligation would bring an abrupt obstruction in the pancreatic duct while the formation of stone (lithiasis) would be something gradual and hence bring progressive changes in the functional parts of the pancreas. This has of course been taken completely out of context by activists.

Animal rights activists also conveniently occlude the statement of Barron on the next page of his paper after he finishes describing the case study, that:  “ The study of this case reveals results that are remarkably similar to those found in experimental ligation of the ducts”. Thus the principle impact of Barron’s work was not providing groundbreaking information, the role of the pancreas and the islets of Langerhans in diabetes was already known by the time he published his 1920 paper, but in providing additional evidence that what had been observed in animal studies was also true in humans, and of course in bringing diabetes to the attention of Banting, whose interest in the field was sparked by reading Barron’s paper.

c)       Diabetes was understood and insulin was applied primarily thanks to human clinical study and autopsy.

Prior to 11 January 1922, most of the work done to understand the mechanism of diabetes was on animals (dogs, cats, rabbits). Human clinical studies of pancreatic extracts in the treatment of diabetes were almost inexistent due to problems observed in the preclinical animal studies, and the few clinical studies that had been attempted in the previous decades produced severe adverse effects that prevented the therapy entering clinical use. Toxic reactions due to impurities in the pancreatic extract prevented its application by Banting, Macleod and Best to humans until January 1922, when a sufficiently pure extract was produced to allow human trials.

As for autopsy, it was apparent decades before the paper of Barron from autopsy/surgical findings that the pancreas might play an important role in diabetes, but it was through animal research that the role was confirmed and mechanism through which the pancreas regulated sugar levels was determined. It was only one chance autopsy that indicated to Barron that it was indeed the islets of Langerhans that played an important role in the disease in humans.  The disease that allowed this observation was very rare, in fact, Barron said that this was the first case of pancreatic lithiarsis that he encountered in a series of several thousand autopsies.

The understanding of diabetes and the role of insulin that allowed the development of insulin therapy was obtained from the interplay between crucial discoveries made through both clinical observation and animal research, so assigning primacy to one or the other is nonsensical.

d)      Claude Bernard had by 1895 experimented on dogs and come to the incorrect conclusion that diabetes had nothing to do with the pancreas.

Claude Bernard (who died in 1878 – more than a decade before the discoveries of Von Merin and Minkowski and the discovery of the first hormones) lived in a time where it was generally accepted that diabetes was a disease of the kidney due to the excessive levels of sugar in the urine. In the mid to late 19th century, various scientists had been exploring other possibilities to the cause of diabetes, including Bernard who believed that the sugar present in diabetic urine was stored in the liver as glycogen.  In a series of animal studies in the late 1840’s and early 1850’s Bernard made crucial discoveries about the role of the liver in storing and producing glucose.  He also found – correctly – that the central nervous system was involved in controlling blood glucose concentration by working with rabbits, though he believed that this was through a direct nerve communication between the CNS and liver, whereas in fact the conversion of glucose to glycogen in the liver was controlled indirectly via the hormone epinephrine – produced by the adrenal gland – and then insulin (and of course insulin also affects other tissues as well as the liver). So the situation is not that Bernard concluded that diabetes had nothing to do with pancreas, it is merely that he did not explore this avenue, principally because he did not think that it was possible to surgically remove the pancreas without killing the animal being studied. Bernard’s animal research did not provide a complete explanation of how glucose levels are regulated, but it was the starting point for the key discoveries made over the next 70 years, as Professor J. Sjöquist of the Nobel Committee for Physiology or Medicine of the Karolinska Institute noted in his presentation speech for the Nobel Prize in Physiology or Medicine on December 10, 1923.

It is true that the observation by Tidemann and Gmelin in 1827, that starchy foods are under normal conditions transformed into sugar in the intestinal canal and that this is absorbed by the blood, marks an important advance; but really epoch-making was the discovery of the great French physiologist Claude Bernard in 1857 that the liver is an organ that contains a starch-like substance, glycogen, from which sugar is constantly being formed during life; in the words of Claude Bernard, the liver secretes sugar into the blood.

In connection with his investigations into the circumstances that affect the formation of sugar, Claude Bernard observed that in certain lesions of the nervous system the sugar content of the blood was increased and that the sugar passed into the urine of the animals in the experiments. For the first time, therefore, an appearance of sugar in the urine – a glycosuria, though of a transitory nature – was experimentally produced; and consequently this discovery by Claude Bernard may be characterized as the starting-point of a series of experimental researches into the causes and nature of diabetes.”

e)      Macleod and Banting did not discover insulin as it had been identified and named before their experiments.

It was strongly hypothesized that the pancreas and more specifically the islets of Langerhans were producing a substance responsible for controlling blood sugar levels well before 1920 on the basis of animal research and clinical observations. Various names were proposed for this substance, insulin being one of them as this particular name had its Latin root derived from ‘islets’ (Latin: insula,island), but there is a big difference between inventing a name for a hypothetical substance and actually proving it exists and purifying it.

The quest for insulin was the ‘holy grail’ amongst scientists working in this field. Macleod, Banting and their fellow co workers had devised a series of experiments whereby they proved the hypothesis that insulin indeed came from the islets of Langerhans, they managed to produce an extract containing insulin and purify it to a degree that it retained its potency and efficiency in animal testing. They then further purified it to allow clinical testing, with the same positive results. They even refined their techniques to eventually reduce and replace animals that had to be used in the research and managed to produce the insulin in a stable, pure form in commercial quantities – making it available to the general public for diabetes treatment.

Irrespective of the controversy regarding who identified/named insulin, two things must be considered:

i)                    Almost all the scientists working in this field had been using animals as research models.

ii)                   The work of Macleod, Banting and their team was done over a short time (2 years) at the end of which, this resulted in clinical treatment of diabetes .Their Nobel Prize in Medicine/Physiology was amply deserved as they had according to the will of Alfred Nobel, made a discovery during the preceding year, “that conferred the greatest benefit on mankind”.

f)       Use of dogs was not necessary as human tissue was available

The study of diabetes required whole organisms – not just tissue/organ samples. The complex interactions behind production of insulin and its action in the metabolism of carbohydrates as well as the fact that diabetes affects several organ systems in the body made it crucial that whole organisms were studied. In addition insulin could not be obtained from any source other than as an extract from the pancreas, and human pancreases were not available for this purpose.

Dogs were the preferred animal model in the initial studies on diabetes because of their availability, the fact that their anatomy was well understood, hence making surgical techniques more efficient and most importantly, because at the time they began their experiments a large volume of blood needed to be sampled, thus the research animal could not be any smaller.

While in the course of their work, with newer methods being developed to test blood sugar levels in smaller volumes of blood, the team switched to smaller animals (rabbits). In fact, they acknowledge that the development of such techniques allowed their work to be done more precisely and more quickly.

beagle_UAR

g)      Synthetic insulin was developed in 1936

Synthetic insulin could not be made until a full understanding of its molecular structure was achieved. Sequencing of insulin was achieved in 1958 ; Chemical synthesis was first achieved in the lab in 1974 and it was only in the 1980s that synthetic insulin made by recombinant DNA technology was made available to the public. Until recombinant insulin became available almost all insulin was obtained from cattle, horses, pigs or fish.

h)      Diabetics owe nothing to animal experimenters.

Diabetics owe everything to animal researchers. The basic understanding of the anatomy and physiological functions of the pancreas was made possible thanks to work on animals. Duct ligations and depancreatisation experiments which gave insights into the functioning of the islets of Langerhans and allowed the isolation of pancreatic extracts containing insulin were made on animals. Although later this stage was deemed unnecessary due to the development of alcohol extraction methods, it provided the key stepping stones to the team to better understand the mechanism and properties of insulin, allowing them to move on to better techniques of obtaining insulin from whole pancreas. The testing of the pancreatic extract containing insulin of various degrees of purity had to be tested first on animals before being considered safe enough for humans. Even today, new insulin analogues need to be tested first on animals for efficacy and toxicity before moving on to human trials.

Research in the field of diabetes is still ongoing nowadays. Scientists are working to find alternative routes of insulin administration either by the oral route or by inhaling. Hopefully, in the near future, insulin injections will be something of the past. Work is being undertaken in the field of pancreatic or islet cell transplantation to cure Type I diabetes, including innovative stem cell based therapies that are being developed through animal research. Newer classes of therapy, including insulin pumps and insulin sensitizers that allow more precise control over blood sugar levels are being developed. All this progress relies on the continuing use of animals in the research.

So tomorrow on World Diabetes Day remember the many millions of lives around the world that have  been saved through animal research conducted by scientists over many decades, and also the thousands of scientists around the world who continue to strive to develop even better therapies – and even cures – for diabetes.

Nada and Paul

1)      Banting F.G. and Best C.H. “The internal secretion of the pancreas.” The journal of Laboratory and Clinical medicine, 1922;Vol VII No 5: 251-266

2)      Barron M. “The relation of the islets of Langerhans to diabetes with special reference to cases of pancreatic lithiasis.” Surg Gynec Obstet 1920;31:437-448.

Animal research and diabetes: Now the truth must be told – Part 1

Today we will take a look at the series of discoveries and innovations that led to the development of insulin therapy for type 1 diabetes, and tomorrow we will take a closer look at some of that claims made about this by animal rights activists.

With the World Diabetes Day coming up on 14th November, it is no surprise that activists are targeting diabetics by saying that cures and supportive treatment of this disease owe nothing to research on animals. They as usual, support their claim by a series of misinformation, statements taken out of context and in some arguments, deliberate distortions.

Although the remedy for diabetes was discovered in the 20th century, it is a disease that has plagued mankind since the ancient times. It was first described some 3,500 years ago by Egyptian physicians. Since then, various physicians of different civilizations – Greek, Roman, Indian, Chinese, Japanese and Arabic – have separately recorded descriptions of this disease, with the Greeks giving it the name ‘diabetes’ in reference to the increased frequency of urination that is characteristic of it. The predominant school of thought at that time was that the disease was due to kidney malfunction.

From the 16th to 18th century, diabetes was further described by European doctors, and from the idea that the disease was caused by kidney malfunction, various other hypotheses were also put forward – liver malfunction, systemic disease or even a malfunction of the central nervous system.  Amongst the various hypotheses put forward, one from Dr Thomas Cawley in the late 1700’s, linking diabetes to a damaged pancreas, based on the autopsy of a diabetic patient. During the 19th century evidence for a role of the pancreas in diabetes increased, but it was not clear if the damage seen was related to the cause of the disease or was a consequence of the disease, and how the pancreas might be regulating blood sugar. The pancreas was known to secrete digestive enzymes into the intestines via the pancreatic duct, but it was not clear how this function was related to the proposed role in controlling blood sugar levels.

The first experimental proof that the pancreas played an important role in carbohydrate metabolism and that diabetes could be of pancreatic origin was provided in 1890 by Von Merin and Minkowski  using dogs as research models. Their work showed that if the pancreas was removed from a dog, the animal got diabetes, but if the duct through which the pancreatic juices flow to the intestine was ligated the dog developed minor digestive problems but no diabetes, indicating that the roles of the pancreas in digestion and regulating blood sugar were separate (1). Later Minkowski and French scientist Edouard Hedon showed independently that if the entire pancreas was removed but some pancreatic tissue was grafted under the dog’s skin then diabetes was prevented, thus conclusively demonstrating that the  sugar regulating function of the pancreas was independent from its role in digestion (2).

While the role of acinar cells of the pancreas in the production of digestive juices was well understood at that time,  the small clusters of cells (‘islets’) discovered by Paul Langerhans in the pancreas of rabbits in 1869 still had no function attributed to them.   Dr Edouard Laguesse in 1893 suggested that these ‘islets of Langerhans’ might constitute the endocrine tissue of the pancreas responsible for the glucoregulatory role of this organ. Further evidence for this role came in 1900 from the pathologist Eugene Lindsay Opie, who noted damage to the islets of langerhans in diabetes patients (4). A year later Leonid W. Ssobolew demonstrated that a ligature of the pancreatic ducts in rabbits, cats, and dogs leads to gradual atrophy and destruction of the enzyme-secreting acinar cells, whereas the islet cells remained intact for weeks, with no evidence of excessive sugar in the urine (5).

In 1905, William Bayliss and Ernest Henry Starling, introduced the concept of hormones to designate the chemical messengers of the body’s endocrine glands, following their identification of the first hormone “secretin” through research on the regulation of digestion in dogs (3). Extrapolating on this concept, in 1913, Sir Edward Albert Sharpey-Schafer – another pioneer in the field of endocrinology – suggested that a hormone responsible for lowering blood sugar concentration was being secreted by the islets of Langerhans and he named this hypothetical hormone ‘insulin’. Independently, 4 years earlier, Jean de Meyer, a Belgian physician had produced an extract from the pancreas that lowered blood sugar concentrations and he also, concluded that the extract contained a substance from the islets of Langerhans and he named that hypothetical substance ‘insuline’ (Latin: insula,island).

Once it was clearly established that there was a link between diabetes and the pancreas – more specifically,  a substance produced by the islets of Langerhans – researchers from various parts of the world were focusing on treating diabetes with pancreatic extracts. Several workers including Zuelzer (Germany), Paulesco (Romania), Scott and Kleiner (North America) had all been able to produce pancreatic extracts that often reduced hyperglycemia or glycosuria in animals and, in a handful of cases with mixed results, in humans. However, due to toxic reactions after the initial relief of symptoms and the outbreak of the First World War, their work was discontinued or slowed down. The problem of how to isolate the hormone insulin in a form sufficiently pure for clinical use remained for now unresolved.

On 30 October 1920, while preparing for a physiology lecture, Frederick Banting came across the article by Moses Barron, “The Relation of the Islets of Langerhans to Diabetes, with special reference to cases of pancreatic lithiasis” (6). While doing routine autopsies, Dr Barron had come across a rare case of the formation of a pancreatic stone. Rarer still, the stone had completely obstructed the main pancreatic duct. Dr Barron observed that this obstruction had caused the atrophy of all acinar cells while the islets of Langerhans had remained intact, and he observed that there was a similarity to Leonid W. Ssobolew’s earlier animal studies where the ligature of the pancreatic ducts in rabbits, cats and dogs lead to the gradual atrophy of the enzyme-secreting acinar cells.

If Frederick Banting was alive, I'm sure he'd be writing about his research for us.

The Nobel Prize in Physiology or Medicine was awarded to Banting and Macleod

Although not a researcher (he was a general surgeon and part time lecturer), Banting’s thoughts were triggered by Dr Barron’s article, as he describes in his 1923 Nobel Prize Lecture. He suspected that in the failed attempts of those scientists who were using pancreatic extract to cure diabetes, the digestive enzymes of the pancreas were destroying the active principle responsible for lowering glucose levels. He started thinking about what if the extract came from a fully degenerated pancreas (through duct ligation) – something that no one had tried before.  He brought his idea to John Macleod, department head at the University of Toronto and a leading authority on carbohydrate metabolism. After much convincing, Macleod agreed to provide research facilities including 10 dogs as research animals and overview the testing of Banting’s proposal. He employed Charles Best to be a research assistant to Banting with work starting in May 1921 (7).

The team had to first refine their surgical techniques on dogs – namely to ligate the pancreatic duct in some animals, and in other individuals to completely remove the pancreas. On 30 July, they managed to obtain an extract from a duct-tied dog which was administered to a depancreatised dog that was displaying the symptoms of diabetes. The extract caused a reduction in blood sugar. The experiments were replicated and recorded frequent decreases in blood sugar as well as sugar excreted in urine. The team had experimental evidence of having isolated an extract with antidiabetic properties – they named the extract ‘Isletin’.

They next refined their technique by using a hormone, secretin, to exhaust acinar cells and obtain extracts from the pancreas free from digestive enzyme trypsin, thus bypassing the duct ligation procedure. They also explored the avenue of obtaining pancreatic extract from fetal calves – in which there was no active acinar secretion, hence free from the digestive enzymes. This was successful but still not efficient enough to be appropriate for large scale production. The next advance was to employ an extraction method that used slightly acidified alcohol rather than saline water, as the ethanol could then be evaporated to leave behind the active hormone. With the help of James Collip, a biochemist who joined the team  in early December 1921, they managed to secure the active principle from fresh whole beef pancreas, and Collip even managed to isolate the active principle as a powder, still with impurities but far purer than any previous extracts. This was tested on rabbits as newer methods for blood testing had been developed that required a far lesser volume of blood as sample. These new methods for testing blood sugar levels had been instrumental in the further purification and testing of the extract as it was more precise, more rapid and required  a small volume of blood (hence, smaller animals could be used). After the assay of tests, it was realized that the extract was sufficiently pure for testing on humans.

On 11 January 1922, the extract was administered to Leonard Thompson, a 14 yr old boy with severe diabetes, however, although they recorded a drop in blood sugar levels, it was considered not effective enough.  A second trial on 23 January 1922 with a more highly purified extract prepared by Collip was performed, and this time a more significant blood sugar level decrease as well as glucose excretion level decrease was obtained. In February 1922, 6 more patients were treated, all with favourable results (8). In later papers the active principle was re-named ‘Insulin’.

When moved to industrial production, with the help of the chief chemist from Eli Lilly and Co, Georges Walden, insulin was being produced at greater yields, better stability and much purer than what was obtained before. Diabetic patients were being treated successfully and the team was achieving fame, honours and prizes with the culmination of the Nobel Prize being awarded to Banting and Macleod in October 1923.

Further work by other scientist on Insulin resulted in its sequencing by Frederick Sanger in 1958. Chemical synthesis of the two protein chains of insulin was achieved in 1967. For many years, beef/pork insulin was the only source of insulin until 1974 where Sieber and his colleagues managed to chemically synthesise human insulin. Subsequently human insulin was produced by recombinant DNA technology by scientists working for the biotechnology company Genentech Inc. and in 1982 the first synthetic insulin analog “Humulin” was approved by the FDA. Nowadays more than 300 insulin analogues exist – with differences in their absorption and duration of action characteristics according to the needs of the patients.

Prior to the introduction of insulin therapy, most patients with diabetes died within a year of diagnosis.  Today’s life expectancy for people with diabetes is still lower than that for the general population by about 10 years, but better control is leading to longer and healthier life. Much of this improvement is thanks to animal testing.

Tomorrow, in the second part of this article,  we will take a closer look at some of the specific claims that animal rights activists are making about the role of animal research in the development of insulin therapy for type 1 diabetes.

Nada and Paul

1)      von Mering J, Minkowski O. “Diabetes mellitus nach Pankreasextirpation”. Centralblatt für klinische Medicin, Leipzig, 1889, 10 (23): 393-394. Archiv für experimentelle Patholgie und Pharmakologie, Leipzig, 1890, 26: 37

2)      Hedon E. “sur la consommation du sucre chez la chien apres l’extirpation du pancreas” Arch Physiol Narmal Pathol Vth series 1893; 5: 154-63.

3)      Bayliss WM, Starling EH.”The mechanism of pancreatic secretion.” J Physiol. 1902 Sep 12;28(5):325-53.

4)      Opie EL. “The relation of diabetes mellitus to lesions of the pancreas. Hyaline degeneration of the islands of Langerhans.” J Exp Med 1900;5:527-540

5)      Ssobolew LW. “Zur normalen und pathologischen Morphologie der inneren Secretion der Bauchspeicheldrüse.” Archiv für pathologische und anatomie und physiologie und für klinische medizin 1902;168:91-128.

6)      Barron M. “The relation of the islets of Langerhans to diabetes with special reference to cases of pancreatic lithiasis.” Surg Gynec Obstet 1920;31:437-448.

7)      Rosenfeld L. “Insulin:Discovery and controversy.” Clinical Chemistry 2002 48:12 2270-88

8)      Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. “Pancreatic Extracts in the Treatment of Diabetes Mellitus.” Can Med Assoc J. 1922 Mar;12(3):141-6.

More Charities Doing Animal Research Outreach Right

Cancer Research UK animal Research

Click image to download CRUK’s leaflet

This is the simple message that Cancer Research UK (CRUK) hope to get across in their new leaflet about why they fund and conduct research on animals.

The leaflet covers many important points, including why CRUK uses animal models:CRUK - why we need animals in research

Its efforts to replace animal tests:Replacement - CRUK animal testing

And how animal welfare is maintained:CRUK animal welfare

That such research is needed is made clear by today’s report that deaths from prostate cancer have fallen by 20% in the UK in the last 20 years, due to improvements in the diagnosis and treatment of the disease. While this is good news it highlights the need for further improvement in the treatment of prostate cancer. An example of improving therapies for prostate cancer is the drug Abiraterone (marketed as Zytiga), which was approved for use in advanced prostate cancer in the UK last year, and was identified through research in mice by scientists at what is now a CRUK funded research centre (CRUK was founded in 2002 when the Cancer Research campaign and Imperial Cancer Research Fund merged). Last year also saw the approval of the skin cancer therapy vasmodegib, a drug whose CRUK supported development started with a study of the regulation of development in fruit flies.  This work continues today as CRUK funded scientists make discoveries through animal research that will help to develop the next generation of therapies for a wide range of cancers.

We have previously mentioned the efforts by medical research charities in the UK to discuss their reasons for funding animal research. This includes Alzheimer’s Research UK’s leaflet and the British Heart Foundation’s Mending Broken Hearts Campaign. CRUK’s leaflet is another fantastic contribution by British medical research charities. Sadly, US charities still have some way to go, as we found when assessing the strengths of their position statements.

Speaking of Research

Animal welfare inspectors clear UW-Madison cat research of PETA allegations, important hearing research continues

A second federal agency charged with oversight of animal research has completed a thorough investigation of an animal rights group’s complaints about sound localization research with cats at the University of Wisconsin. Summary of the result:  “there was no direct noncompliance with the PHS Policy or serious deviation from the provisions of the Guide for the Care and Use of Laboratory Animals.”

We have written previously (here, here, here) about reviews conducted by the United States Department of Agriculture (USDA). This time the report is from the National Institutes of Health (NIH) Office of Laboratory Animal Welfare (OLAW).  Once again, the complaint by PETA is based on hundreds of pages of records that the animal rights group received from the UW via open records requests.  In response to these complaints both federal agencies have sent teams that include veterinarians to look at the animals, records, and research at UW-Madison.

new graphic - AR cycle 10.07.13 ajbIn addition to the USDA and OLAW reviews, during this period the NIH institute funding the sound localization project, the National Institute on Deafness and Communication Disorders (NIDCD), also took action. NIDCD suspended one part of the research— but not the entire project— from April-September 2013 when the final report was issued. Whether the suspension was the result of PETA’s allegations is not clear. What is clear is that the NIH and scientific community have long supported and valued this specific research and– more broadly–  the contribution of animal models to success in this field and advances in scientific understanding and human health. The PI of this work, Professor Tom Yin, has been funded by NIH for many years. As is the case of all NIH-funded research, a competitive expert scientific panel provides rigorous critical analysis of the proposed science. Only a small fraction of proposals are identified as valuable, worthwhile, and likely to succeed. In this case, the PI’s research was deemed justifiable and worthy following scientific review, NIH review, and IACUC review. Furthermore, the scientific contributions Yin’s work is evident in many ways. For example, it is widely cited in the field (e.g., over 5000 citations of his scientific papers). Yin discusses the targeted research in these videos:

In brief, Professor Yin’s laboratory conducts fundamental basic research that has resulted in better understanding of complex brain function and how hearing works. By using a combination of electrophysiological recordings, anatomical studies and behavioral studies, the lab is studying the mechanisms used by the brain to put together inputs from the two ears to improve hearing. The scientific discoveries have public benefit because they provide foundational understanding with broad applicability. Knowing how the brain integrates sound received by both ears and how that allows for localization of sounds is an important part of work towards improving the quality of life and functioning of millions of people with hearing impairment.

Many types of research in this area require recording and studying a real functioning brain, there are no non-animal alternatives. Cats are among the best animal models for this work for a number of reasons. Among them: most of the information we have about the auditory system comes from studies in cats, they are nocturnal hunters with excellent sound localization abilities, and what we know about the cat’s nervous system shows that it is very similar to that of humans. The importance of cats and other animal models to research in this field is widely acknowledged, including by this year’s Lasker-DeBakey Clinical Medical Research Award, and particularly the work of Graeme Clarke, which laid the foundations for the development of multichannel cochlear implants through studies in cats and rats.

As we have discussed previously, consideration of the use of animals in research includes not only weighing its potential benefits, but also evaluation of the animals’ welfare. The welfare of all of research animals is a priority and one that is ensured through the careful efforts of research, veterinary, and animal care personnel. Furthermore, oversight of animals’ care and treatment occurs at individual, institutional, and federal levels. A small number of cats (less than a dozen) participate in UW-Madison’s sound localization research. The cats are healthy and well-adjusted to their work, play, and living environments as was documented in the OLAW report. In that report, external reviewers who had thoroughly reviewed the lab and records, examined the animals, and interviewed the animal care and veterinary personnel, research staff, and scientists were satisfied with the animals’ condition and treatment.  Potential for pain or suffering is minimized through careful efforts: Surgery is performed under deep anesthesia, just like surgery for humans. Infections are a risk, but they affect the animals only a fraction of the time they are in study. Furthermore, infections are caught early through extensive and careful monitoring, treated immediately and resolved quickly in all but a very small number of cases. In no cases are they allowed to be untreated or to cause suffering or unrelieved pain.

OLAW’s summary conclusion, released September 30, confirmed that the research and animal treatment were appropriate: “there was no direct noncompliance with the PHS Policy or serious deviation from the provisions of the Guide for the Care and Use of Laboratory Animals.” Furthermore, the report concluded that PETA’s specific allegations were unsupported. The report also acknowledged UW’s efforts to continue refinement in the animals’ care and treatment:  “OLAW found that while the specific allegations did not accurately reflect the entire clinical and research condition of the cats, changes were made to enhance the care of the animals and potentially improve research outcomes.” Furthermore, the report includes many extremely positive descriptions of the animals’ condition and care.

UW responded:

“The OLAW investigation is the third review of the lab and its animal subjects by the federal government, all instigated by PETA within the past year. To date, none of the many allegations of mistreatment made by the organization to the U.S. Department of Agriculture or OLAW have been substantiated. ‘Contrary to the misleading claims made by PETA, the conclusions cited in the OLAW report reflect our view that the animals in the study are in excellent health, are well treated and cared for, and used to further important research in an appropriate and humane manner,’ says Dan Uhlrich, UW-Madison associate vice chancellor for research policy.  ‘Significant university and federal resources have been repeatedly redirected to respond to these unfounded allegations. This is a questionable use of scarce and valuable public resources, which we feel damages the best interests of the public, science, affected researchers, and the dedicated animal care and veterinary staffs responsible for the health and wellbeing of our animals.”

The OLAW summary report, including 36 appendix exhibits, can be found on their website. The UW has also shared detailed information about the research, the reviews, and the animal program with the broad public via its website, release of hundreds of records, and videos in which the scientist and others speak about the value of the work and how it is conducted.  In other words, as we’ve noted before, there are many venues for the public to learn more about the work, its conduct, and the detailed process of regulatory oversight.

What was PETA’s response?

Hint:  It did not include acknowledgement that OLAW, USDA, and the University of Wisconsin gave serious consideration to PETA’s complaint, performed a thorough investigation, and provided a detailed, specific public response on each of the allegations that the animal rights group raised. Nor did PETA’s response include an acknowledgement that perhaps they were wrong.  And nothing in their public responses indicated – front and center – that PETA’s mission and objective is to end all animal research. PETA’s position is fundamentally absolutist. Regardless of animals’ welfare and regardless of the consequences for the public that benefits from responsible, ethical and humanely-conducted animal studies, PETA is opposed to all use of nonhuman animals. Thus, there are presumably no conditions under which PETA would find laboratory animal research acceptable. (We welcome correction from PETA if this is a misrepresentation of their position.)

It is not surprising then that, as reported in the Wisconsin State Journal, PETA’s spokesman did not accept the OLAW conclusion, but rather vowed:  “This campaign is going to continue until that lab is empty and there are no cats in it,’” Goodman said without specifying the group’s next steps.”

PETA’s next steps in its quest to close the laboratory will probably include some of the characteristic stunts for which they are famous. At the UW this has included small protests on campus, the PETA mobile billboard truck driving around Madison, and an actor and PETA staffer gaining media coverage for disruption and arrest at a UW System Board of Regents meeting. Review of their campaign strategy thus far provides a few other clues for what to expect at the UW and elsewhere. For example, last week PETA set up at the campus job fair to recruit for an “undercover investigator.”  PETA’s Jeremy Beckham netted a local television interview with the tactic. Not a new tactic for animal rights groups, as seen in this campaign directed at Oregon Health Sciences University several years ago.

As we’ve written before however, focusing on these stunts and underestimating the broader gains that PETA has made and that negatively affect science and public interests can be a mistake.  In the case of this campaign and all of the associated events, two things in particular are worth notice by the broader community.  First, the way in which PETA used the openness of records and the public responsiveness of the regulatory process to feed their campaign; and second, the use of emotive tactics that encourage harassment of scientists and others in research institutions. The graphic above captures the general strategy used by many activist groups, highlights the costs, and raises a number of questions. In particular, one question that merits serious discussion is how to better assess the full range of actual costs and critical evaluation of realized benefits to animal welfare, science, and public interests.

Despite the conclusion of multiple federal reviews that failed to support their allegations, PETA is continuing to smear the research and to promote petition and email campaigns to the NIH, UW-Madison, and others. As one of the exhibits in the OLAW report shows, the NIDCD received 562 phone calls and approximately 190,000 emails about cat research. While that represents a tiny fraction of the American public and likely includes many form messages, its inclusion in the OLAW report suggests it may have been relevant to the NIH’s response.  No doubt that number increased after PETA linked a form email to its mixed martial arts assault on scientists videogame in order to encourage players to complain to NIH about the UW research.  Of course the game also encourages players to entertain the idea of harming scientists. As we’ve seen before, these highly emotional tactics can have the general effect of eliciting threatening and disturbing messages from those who follow PETA. For example, this recent tweet:

Beth Carter 10.5.13 tweet

The PETA campaign and response following the USDA and OLAW reports makes their objective clear once again:  to end research and close labs. Nothing new there. The question to ask now however, is how research institutions, scientists, federal agencies, and the public should respond to campaigns like this. In particular, this set of events provides additional strong evidence that there is little broad value in engagement with groups that have a singular agenda and little interest in serious dialogue, accuracy, or acknowledgement of the complex issues and choices in animal research conducted for public benefit.  For scientists and research institutions interested in dialogue and better understanding of animal research, using that time and energy to communicate directly with the public about their research, why they are doing it and what it involves makes more sense.

More here:

http://speakingofresearch.com/2012/09/20/defending-science-and-countering-falsehood-at-the-university-of-wisconsin-madison-2/

http://speakingofresearch.com/2012/10/12/as-predicted-uw-cleared-peta-caught-lying-again/

http://speakingofresearch.com/2013/02/08/a-lesson-in-hypocrisy-as-peta-cries-foul-over-one-cats-death-while-secretly-killing-hundreds-more/