Tag Archives: animal research

A Conversation About Beagle Testing

I received an email one morning from James, a Grade 6 student who wanted to know more about beagles used in research and testing for a school project about his passion. He has a pet beagle named Bagel and had recently watched some videos from the Beagle Freedom Project (BFP written about here and here). James was very curious and quite concerned about the beagles that participated in studies in Canada. He requested some information and to visit the Central Animal Facility at the University Of Guelph. James was invited for a tour and the answers to his questions are as follows:

Job Related

  • What is your job and what do you teach at the University?

I am a research animal technician and my job is to advocate for the animals that are under my care. I instruct those who have not worked with animals how to do so in a compassionate, respectful and ethical manner.

  • Why did you become a technician?

I became a technician because I love animals and people. I also love science and love being a part of making discoveries that improve the lives of millions of people and animals

  • My project is on a passion and I am wondering what your passion is?

I’m passionate about a lot! I am passionate about animals that I have the privilege to care for with compassion and respect. I am passionate about the science that continually makes strides towards new therapeutic advancements. I am passionate about alleviating the suffering of our fellow animals and people who agonize with debilitating and painful diseases. I choose this profession in research because it is my passion.

  • What research do you do in your Lab?

The majority of the work that is done in the facility where I work is basic or fundamental science in a wide variety of areas including oncology, neuroscience, animal behaviour and welfare, molecular biology, physiology, immunology, among others.

Michael Brunt and James during the laboratory visit

Michael Brunt and James during the laboratory visit

Animal Research/Testing

  • Why is it important to use animals/ beagles?

Various non-animal research methods are used together with animal studies to reduce the number of animals needed. These methods include antibodies, stem cells, tissue cultures (all in-directly use animals) and computer models. Non-animal methods account for the majority of biomedical research. Nevertheless, there are important research questions that still require animals. For example, in drug development, a large initial group of chemical candidates may be screened using non-animal methods, and only the most promising ones are taken through animal testing and human clinical trials. Before animal studies can go forward, investigators must detail how they have considered non-animal methods, and why they are not appropriate for answering their research question.

  • What kinds of tests are done?

The Canadian Council on Animal Care has 5 classifications for the purposes of animal use (PAU):
PAU1 – Studies of a fundamental nature in science relating to essential structure or function
PAU2 – Studies for medical purposes, including veterinary medicine, that relate to human or animal disease or disorders
PAU3- Studies for regulatory testing of products for the protection of humans, animals, or the environment
PAU4 – Studies for the development of products or appliances for human or veterinary medicine
PAU5 – Education and training of individuals in post-secondary institutions or facilities

  • What happens with your research findings once you are finished a project?

The findings are published in scientific journals that are available on the internet for everybody to access. The knowledge gained could be used to answer other scientific questions or be applied in translational science to develop new therapies or cures for those that are suffering.

  • What do you do with the animals after you have used them for research/testing?

Ultimately, most of the animals involved in animal research are euthanized. This is because the researchers will often need to further study the body – taking tissue samples and other such tests to make sure they get as much data from any animal they use. To euthanize the animals, researchers use a variety of methods such as an overdose of anesthesia (pain killers) or using CO2 so that the animal slowly drifts into a sleep it never awakes from.

Beagle Research/Testing

  • What is your opinion about beagle research?

Animal research plays a vital role in the development of modern medical and veterinary treatments. Much of our understanding about the biological processes in the body, and the diseases that affect them, comes from studies in animals. I believe that animal research should be conducted with the utmost care, responsibility and respect towards the animals. All personnel involved in animal research should strictly follow the pertinent guidelines, regulations and laws.

  • When did beagle testing begin?

Hundreds of years ago to begin to understand blood movement and the interactions of organs.

  • Why are beagles used for testing?

Health Canada requires that all new drugs, medical devices, and procedures first be evaluated in animals for safety before clinical trials involving human volunteers can begin. The most common “product” that is tested using animal models is new medications. Animals are used to determine that the drug shows a reasonable likelihood of working as conceived and to determine unforeseen side effects. For instance, a researcher may find that a new drug to control high blood pressure does so, but there is a possibility of a side effect such as liver damage. That information needs to be known before it is used in clinical trials with humans.

  • How many beagles are used a year?

0.3% of the animals used in Canada in 2011 were dogs. Mice, rats and fish accounted for 78.5% of the animals.

  • Where do you get your dogs?

Our beagles are provided by companies who breed dogs for research, teaching or testing purposes.

  • How are the dogs treated?

With love, compassion and respect.

  • Why don’t some companies let beagles see sunlight play or even touch grass during their testing time?

At our institution our animals go outside for walks every day with their dedicated paid dog walker and our volunteer dog walkers.

  • How many beagles die each year from testing?

I don’t have an answer to that question. In Canada in 2011, 10,199 dogs were utilized in science. However, that isn’t how many were humanely euthanized at the end of the projects. Our institution has adopted 100s of beagles into our community.

James and Bagel

James and Bagel (Photos reproduced with permissions from copyright owner)

Feedback

James and his parents met a number of our animals, including our beagles, during their tour and I asked him to provide some feedback on his experience.

At first I thought beagle research and testing was inhumane, unbeneficial and cruel. But when I went to the University of Guelph my perspective changed and I learned that research and testing is very important and it helps 1000s of humans and animals because of the research on animals. The people treat all the animals to a good life like every other animal in the world. They play with all the animals mice/rats/dogs and turkeys. One of the reasons that they euthanize the animals is to further discover the effects of a drug to make it safer for humans and other animals. All the animals there are well cared for, like the animals are their family. If we didn’t have research and testing we would never have a treatment to help the people suffering with cancer. 1000s of products have helped humans and other animals because of the work done with beagles. How many people would have died without animal research and testing on the drugs to know if they are safe. What I thought about beagle testing at first was nothing compared to what it is now. I now know that it very helpful. Most of the websites that say all the bad things are not aware of all the things the beagles and animals have done for advancing medicines. Another part of my visit included seeing Dr Woods and he told me about the research he did on mice for prostate cancer. They use mice cells because they react to the cancer like the humans cells do. Dogs are closer to humans than mice in DNA and they need to see how much of the drug they can give without it being toxic. All chemotherapy has been tested through rats, mice and beagles before humans. In my opinion all the beagles and animals who are involved in research are Heroes.”

My interview and tour with James demonstrates that everyone must seize opportunities to engage with members of the public. It is a chance to present accurate information about the ethical use of animals in science and allow people to make informed opinions. These instances foster a culture of understanding, acceptance, value and recognition for the contributions animal research plays in improving the lives of millions of animals and people every day. They are opportunities that should not be squandered.

Michael Brunt

Stop vivisection Initiative fails to impress at EU hearing

In March we discussed a new attempt by animal rights supporters to ban animal research in Europe, The Stop Vivisection European Citizens’ Initiative, which was signed by  1.2 million people (half of them in Italy). The initiative calls for “the European Commission to abrogate directive 2010/63/EU on the protection of animals used for scientific purposes and to present a new proposal that does away with animal experimentation”. On Monday 11th May the organizers of the initiative had an opportunity to present it to a joint session of  several European Parliament committees, in a hearing that was also addressed by scientists who spoke in favor of keeping directive 2010/63/EU.

So how did it go?

Well, an editorial in last week’s edition of Nature gave a fair assessment of it when they described the session as “a pretty grey affair” in which the duo who presented the initiative – Gianni Tamino and Claude Reiss – “spoke calmly but unconvincingly” to a half-filled auditorium. A transcript and summary of the key points made by the European Animal Research Association and put together the key points that were said during the meeting (download here) indicates that the initiative is almost certain to fail in its objective of  persuading the EU Commission to repeal Directive 2010/63/EU.

European-Parliament

A look through the EARA report  shows why. Any MEPs (Members of the European Parliament) hoping to hear new evidence from Dr Ray Greek and Dr Andre Menache, the scientific advisors who the Stop Vivisection Initiative organizers had brought along, were in for a  disappointment, as instead they presented a veritable greatest hits of anti-vivisection claims. Their testimony included Dr Ray Greek’s trademark  misrepresentation of what “prediction” means in biomedical research, while Dr Menache reheated the old 0.0004% myth. Surprisingly, these were far from being the worst claims made by supporters of the Stop vivisection initiative. Particularly low points came when MEP, and initiative supporter,  Anja Hazekamp stated that there has been massive increase in animal testing (The EU’s own statistics show the opposite) and when Claude Reiss, one of the organizers of the Stop Vivisection petition, ventured deep into conspiracy theory territory with a claim that there is a patent on HIV treatment that completely cleans the virus from the body, but has not been developed because it is not profitable.

In contrast the voice of science was very ably represented. Professor Francoise Barré – Sinoussi, 2008 Nobel Laureate in Physiology or Medicine for her role proving that HIV causes AIDS, put forward a very strong case for the importance of animal research in advancing medicine, and repeatedly demolished false claims made by anti-vivisectionists, particularly claims that animal research had not made a useful contribution to HIV research and the development of a vaccine against HIV infection. On this she is on safe ground as there is no doubt that animal research has made very important contributions to HIV research and development of therapies (for examples see here, here and here), and while development of an effective vaccine has been slow – because it’s very, very difficult – there has been real progress in recent years, and most HIV experts is that studies in  non-human primate models of the infection have a critical role to play in evaluating potential vaccination strategies.

Francoise Barré - Sinoussi, undoubted star of the EU parliament hearing.

Francoise Barré – Sinoussi, undoubted star of the EU parliament hearing.

Throughout the hearing one very important voice was conspicuous by its absence, that of the patients who rely on medical research. MEP Françoise Grossetête, who spoke in favor of retaining Directive 2010/63/EU, noted in particular that EURORDIS, the organization that represents rare disease patients in Europe, had not been invited to present evidence at the hearing. We hope that the EU commission will now actively seek the advice of EURORDIS and other European patient organizations before making their final decision.

What happens now?

At the hearing the Vice-President of the European Commission confirmed that the Commission will provide a formal response to the initiative by 3 June 2015. On the basis of what we saw at the hearing, and the fact that the majority of MEPS present were in favor of retaining Directive 2010/63/EU, it is a near certainty that the EU commission will reject the Stop Vivisection initiative and retain the Directive.

In 2017 the Directive will undergo it’s first 5 year review, which is likely to focus on its implementation across the EU, but the commission have also promised to organize a scientific conference that year to discuss the validity of animal research. With that in mind it’s good to see that last week’s Nature editorial noted that scientists across the EU are becoming increasingly – and refreshingly – vocal on the need to support animal research as a pillar of scientific and medical progress. In recent weeks we’ve seen thousands of scientists sign a motion of solidarity with a neuroscientist targeted by animal rights extremists in Germany, more than 140 research organizations, patient organizations, medical research funders and scientific associations sign up to a statement in support of Directive 2010/63/EU, Sixteen European Nobel laureates publish an open letter in UK and German newspapers to rebut the Stop Vivisection campaign. We’ve also seen several excellent letters appear in the national press, including a letter in the Times by Steve Ford, Chief executive of Parkinson’s UK, on the importance of animal research, and articles such as that written by Oxford University Duchenne muscular dystrophy researcher Professor Kay Davies.

The Stop Vivisection Initiative may have almost run its course, but the threat to the future of biomedical science in the EU is sadly never very far away. We hope that the current re-invigoration of the European scientific community continues, and that scientists strengthen and expand their engagement with politicians, journalists and citizens in the run-up to 2017 and beyond.

Speaking of Research

Zebrafish: the rising star of animal models

Today we have a guest article by Jan Botthof, a PhD Student at the Cambridge University Department of Haematology and the world renowned Wellcome Trust Sanger Institute. Together with the EMBL-European Bioinformatics Institute – with which it shares the Genome Campus a few miles south of Cambridge – the Sanger Institutes is one of the World’s top centres of expertise for genome research. As EMBL-EBI’s associate director Ewan Birney highlighted in a recent article for the MRC Insight blog, by studying the biology of a wide variety of model organisms – including humans and zebrafish among many others – the more than one thousand scientists working on the Genome Campus a gaining critical insights into biology that are advancing 21st century medical science.

When most people think of animal research, they imagine mice, rats or maybe fruit flies. However, other models are increasingly being used in addition to the more traditional organisms. The number of zebrafish (Danio rerio) in particular is steadily increasing in biomedical research each year. You might be wondering why scientists are using fish instead of animals more closely related to humans for their studies. Let’s have a look at some of the advantages of the zebrafish to explain this matter. This list is obviously not going to be comprehensive, because many advantages are field-specific and quite technical, but it should give you an idea why researchers might want to choose fish over other animals.

The zebrafish, a rising star star of medical research.

The zebrafish, a rising star star of medical research.

First of all is something that makes zebrafish more attractive to scientists who pressed for time, such as PhD students wanting to graduate punctually (like me!): zebrafish reproduce at a rapid rate. Each female can lay several hundred eggs each week, which will develop into mature adults in about three months. This is especially useful if you need to breed a large number of animals very quickly, or when you want to cross several lines with modified genes. Rapid breeding also greatly reduces the time it takes to introduce novel genetic modifications into the animals, as several generations are required before a stable modification of the gene in question is achieved. This makes zebrafish a very efficient species for research.

4-day old zebrafish embryo.

4-day old zebrafish embryo.

Another really useful trait of zebrafish is that their embryos are relatively large and initially transparent. This makes it easy to manipulate the embryo, which is very helpful if you are injecting various substances to modify their properties. In my case, I’m using a technique called CRISPR-Cas9 to very precisely switch off certain genes, but there are many other applications.  An added advantage is that you can treat these embryos chemically to stop pigmentation from forming, making it very easy to study early embryonic development (Figure 1). Moreover, the embryos are permeable to many chemicals and drugs – making them ideal for screening large numbers of toxicology samples or drug candidates.

The zebrafish genome has been fully sequenced, which is a must-have for model organisms nowadays.  This effort showed that their genome is remarkably similar to the human one, with at least 70% of human genes having a zebrafish equivalent – a figure that is even higher when only disease-causing genes are considered. There are also efforts underway (by the same group that sequenced the zebrafish genome, which coincidentally happens to be right next to my research group) to mutate every single gene in the zebrafish genome. This can be very helpful if you study a certain gene and wonder what happens to the whole organism when it is lost – and having such large scale resources can save the wider research community huge amounts of time and effort.

Apart from fish with mutations in specific genes, there are also numerous lines containing genes from other organisms (transgenic lines). Usually the proteins encoded by these genes are fluorescent and are used to mark specific cells, as we can control (at least partially) in which tissue a protein is made. One of these is called green fluorescent protein or GFP (originally from a jellyfish). Using techniques such as GFP it is possible to visualize changes in specific cell populations in real time in living animals. Just to give you a personal example: I study blood development, so naturally I want to look at the different types of blood cells. Depending on what cell type I want to look at, I can select an appropriate zebra fish line, where this type is labelled. For an example, have a look at Figure 2, which shows early blood cells during embryonic development labelled with GFP. As these fluorescent proteins come in different colours, it’s possible to look at two or more different cell types at the same time.

A recent advance is the generation of fully transparent adult zebrafish, aptly named “Casper” after the popular cartoon ghost. You can look up the freely available original paper here if you want to see what these fish look like. Of course, scientists are not making transparent fish just because they look cool, but they are very useful tools for research. One application is the easy study of tumour metastases, as the cancer cells are just much easier to spot in transparent fish. Adding fluorescent labelling as described above can make this technique even more powerful.

Usually when we use zebrafish, we take advantage of the fact that many fundamental processes have been evolutionary conserved between fish and humans. Because of these similarities, we can use zebrafish as a model for what happens in humans. Sometimes differences between animals and humans can be more telling though. For example, many animals can regenerate much more efficiently than humans (you might have heard about the ability of salamanders to regrow lost limbs or tails) and this is also true to some extent for zebrafish. One very well studied research area is heart regeneration. Humans are unable to regenerate heart muscle tissue, which is of course problematic when parts of it die off during a heart attack or following injury. In contrast, zebrafish can use stem cells to regenerate the lost tissue – if we could induce a similar process in humans, it might help treating people recovering from cardiac injury. The British Heart Foundation is funding important research in this particular field through its “Mending Broken Hearts” campaign. In the even longer term, it might be possible to adapt similar principles to other tissues and thereby help in treating a variety of injuries.

The regenerative capacity of zebrafish isn’t only interesting for medical research, but it has a very practical advantage: you can cut a tiny part of the tail fin off and use it to extract DNA from the tissue. Then, the mutation status of a specific gene can be determined, which is essential when you want to know whether an animal is a carrier for the mutation you are interested in. The fin then grows back within two weeks, so the animal is not harmed.

Lastly, I just want to mention some financial considerations. Animal research in general is really expensive, which is one of the reasons why alternatives are used whenever possible. These costs are largely determined by how much effort and space is required to house, feed and care for the animals. Of course, this makes large or exotic species especially expensive, so they are used less often. However, even rodent colonies can cost quite a lot of money to maintain. Zebrafish require much less space per individual, are relatively inexpensive to feed , and it’s also relatively straightforward to ship animals (usually as embryos) between labs. This facilitates collaborative research and reduces the number that need to be used, since they don’t have to recreate the same genetically modified line all over again.

In conclusion, zebrafish have a lot of useful characteristics that make them very practical and useful model organisms, which explains their rising  popularity among researchers.

In the next article of this series, I’m going to have a closer look at zebrafish care, as well as daily work in a fish facility and some of the rules and regulations surrounding fish welfare.

Jan Botthof

Guest Post: Animal models in research are necessary and ethical

The following post was originally published in The Daily of the University of Washington on April 26, 2015. It has been reproduced with permission from the newspaper and the original author. Benjamin Cordy is a neurobiology student at UW, he is also the Editor-in-Chief of Grey Matters Journal – an undergraduate neuroscience journal whose mission is to educate the public and develop effective science communicators.

Guest editorial: Animal models in research are necessary and ethical

On Saturday hundreds gathered in Red Square to voice their opposition to scientific research. At its core, this is the true message of the animal rights movement, which believes that research should never rely on animal models. The march on UW was about stopping science altogether. Is this really the best move for society?

Debates about animal models in research are emotional, contentious, and unfortunately, often fraught with demonstrably false “facts.” This is a serious problem. It is impossible to have a thoughtful conversation about the role of science and medical research in society if a position is based on misinformation and inaccurate beliefs.

Two of the most frequently repeated claims of the animal rights movement are that animal models are not actually useful in science and that there are more effective, humane ways to engage in research. While appealing, both statements are wrong.

The history of science provides countless examples of the utility of animal research. For example, until as recently as 1940 and the development of the “antibiotic age”, a knee scrape, if it became infected, could be a death sentence.

In 1928 Alexander Fleming discovered that when grown in proximity to one another, the mold Penicillim notatum killed the colonies of the often-fatal bacteria Staphylococcus aureus. Unfortunately, Fleming’s test-tube studies failed to show the antimicrobial properties he expected from Penicillin. These results, and the difficulty of isolating Penicillin, ultimately led Fleming to believe that it might only be useful as a topical antiseptic.

Although Fleming’s work showed some promise, Penicillin was not a high priority for antimicrobial researchers. In addition to being very difficult to isolate, its therapeutic properties seemed to be inactivated in blood — making it a poor candidate for treating systemic infections. But by 1940 enough Penicillin was isolated for testing. In a landmark study Ernst Chain and Howard Florey infected eight mice with a deadly dose of Streptococcus pyogenes. One hour later, four of the mice were injected with Penicillin. These mice survived the infection and changed modern medicine forever.

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(Left to Right) Alexander Fleming, Howard Florey and Ernst Chain – Shared the Nobel Prize for Physiology or Medicine in 1945

The amount of Penicillin required to treat a human infection is 3,000 times greater than for a mouse. If animal models were unavailable to Chain and Florey, they would have had to undergo the perfectly unreasonable task of isolating huge quantities of a substance that, as far as they could understand, had no therapeutic value. Simply put, without animal models Penicillin would not have been developed.

Fortunately, the story of Penicillin is not unique. There are literally thousands of medical interventions, drugs, and procedures whose discovery and development required the use of research animals. Modern therapies that require animal models include: vaccines, organ transplants, cancer treatments, HIV/AIDS drug development, and thousands more. The claim that animal models are “bad science” and fail to provide important insights into biological understanding and therapeutic development is dishonest and wrong.

The second position of the animal rights movement is that there are alternatives that are simultaneously more effective and humane. The three most often suggested alternatives are human cell cultures, computer models, and experimentation on human subjects.

Tissue and cell culture experiments are extremely powerful research techniques. Their use provides important insights into the function of individual cells and helps identify potential targets for future therapeutics. However, these studies, by their very nature, can only reveal a fraction of the whole picture. For example, a few cells could never describe the complexity of an entire organ — much less the entire organism. Though important for reducing the number of animals used, these techniques could never replace them.

Computational techniques are another tremendously valuable tool. With mathematical models and data analysis, computers allow researchers to better understand the systems they study. But again, computation is a supplement to animal research, not a replacement. Every computer model has to be validated against data collected from animal research. There is no other way to ensure that a modeling program is accurate.

Furthermore, animal rights activists overestimate the power of computer models. In 2007 researchers were able to simulate a virtual brain of 8,000,000 neurons, roughly the complexity of half a mouse brain. While impressive, this is less than 1/10,000th the number of neurons in a human brain and likely much less complex. The simulation ran on the fastest supercomputer and could only do so for 10 seconds at 1/10th the speed of a real brain. In all, this program required the world’s most powerful supercomputer to model one second of one half a mouse brain. How could a desktop PC possibly predict the behavior of the human brain?

The most troubling alternative proposed by animal rights activists is the use of human volunteers for basic science. In practice, such policies would effectively halt biomedical research. For one, the cost of recruiting and paying human subjects would bankrupt already sparse science funding within months. This of course, assumes that enough people volunteer to participate. Considering that clinical researchers already have difficulty in recruiting people for fairly benign studies, it is highly improbable that eight people would volunteer to receive a deadly dose of Streptococcus pyogenes, for example.

Beyond the practical limitations of using only human subjects, there are serious questions about the morality of doing so. Which population is likely to accept payment for becoming test subjects: the socioeconomically disadvantaged or the wealthy? The argument that humans ought to replace research animals raises real concerns about the exploitation of disadvantaged communities.

It was not long ago that I was sympathetic to some of the positions of the animal rights activists. But, as I learned the science behind biomedical therapeutics, it became clear that because animal models save millions and millions of lives, they are necessary. A powerful research program, which includes the use of animal models, is the responsibility of an ethical society.

Benjamin Cordy, UW neurobiology student

Animal research openness in action – from Cambridge to Florida

Last week we published an article calling on all involved in animal research to speak up for science as animal rights activists held their annual World Week for Animals in Laboratories (WWAIL), writing:

This year, if your university or facility is among those that attract attention during WWAIL, we ask that you join in the conversation by providing protestors, public, and media your own voice.  Whether it is via banners, websites, or talking with reporters– speak up for science and for public interests in advancing scientific understanding and medical progress. Although it may not matter to those committed to an absolutist agenda, it can matter to those who are interested in building a dialogue based in fact and serious consideration of the complex issues that surround public interests in the future of science, health, and medicine.”

The past few days have seen several great examples of just the sort of engagement with the public that we had in mind, including videos form two top universities in the UK that take viewers inside their animal research facilities.

The first comes from the University of Cambridge, who have published a video entitled “Fighting cancer: Animal research at Cambridge”, which focuses on how animals used in research are cared for and how the University implements the principles of the 3Rs. It includes interviews with Professor Gerard Evans of the Department of Biochemistry, who uses mice in studies of lung and pancreatic cancers, and Dr Meritxell Hutch of the Gurdon Institute, who has developed 3D liver cell culture models that she uses to reduce the number of mice required for her studies of tissue repair and regeneration, as well as with members of staff as they care for the animals.

The second example is another video, this time from Imperial College London, which also show how research staff care for the animals used in research, and features an interview with Professor of Rheumatology Matthew Pickering, who studies the role of complement proteins in liver damage in mice.

For the third example we cross the Atlantic to South Florida, where animal rights activists are trying to close down several facilities in Hendry County  that are breeding monkeys for medical research, a service that is hugely important to biomedical research. One of the companies being targeted by the animal rights campaigns is Primate Products, so we were delighted to see Dr. Jeff Rowell, a veterinarian and President of Primate Products, speak up about the vital work they do in an interview with journalist Amy Williams of local news outlet News-Press.com.

Primate products

During the interview Dr. Rowell discusses how the work of Primate Products is misrepresented by dishonest animal rights campaigns, including the inaccurate and malicious allegations made by the group Stop Animal Exploitation Now (SAEN) in 2010. As we discussed in a post at the time, these allegations were based on the deliberate misrepresentation of photos taken during veterinary care of injuries several macaques received in fighting with other macaques when housed in social groups (a normal though infrequent behaviour in the species in the wild and in captivity).

The News-Press.com article also shows that there is still a lot of work to be done to improve openness in animal research, as the three other companies that are breeding monkeys for research in Hendry County refused to speak with the Amy Williams, a shame considering that it was their decision to base themselves in the county that triggered the current animal rights campaign. While they are justifiably nervous of speaking with the press (some journalists and publications are arguably beyond redemption) the truth is that the “No comment” approach works for no-one apart from those who oppose animal research. In speaking at length with Amy Williams, Jeff Rowell has provided an excellent example that his colleagues in Hendry County would do well to follow.

The initiatives we have seen from the University of Cambridge, Imperial College London, and Primate Products over the past few days are extremely welcome, and we applaud them for their efforts. Nonetheless, we acknowledge that the future of medical science will never really be secure until they are the norm rather than the exception.

Before we conclude, it’s worth noting that it’s not just in the US and UK that researchers are beginning to realise the importance of openness in animal research to counter misleading antivivisectionist propaganda. In Italy Prof. Roberto Caminiti, a leading neurophysiologist at the University La Sapienza in Rome whose work is currently being targeted by animal rights activists, was interviewed recently for an excellent video produced by Pro-Test Italia, in which he discusses his primate research and how it is regulated.

Speaking of Research

World Week to Speak Up About Animal Research

Banner at UW-Madison, April 2015.

Banner at UW-Madison, April 2015.

Each April a group of people committed to ending all use of animals for any purpose, including medical and scientific research, orchestrate events for a week they designate World Week for Animals in Laboratories (WWAIL). Among the primary objectives of WWAIL is to generate media coverage via picketing and protests. The event often culminates in World Day for Animals in Laboratories (WDAIL).

WWAIL events are primarily coordinated by Michael Budkie, leader of Stop Animal Exploitation Now (SAEN). Budkie is also known for previous misrepresentation of animal research and its rebuttal by federal agencies. Budkie’s group is funded primarily by the Mary T. and Frank L. Hoffman Foundation, a “Biblically based organization” that believes “our call to mission is to restore God’s original creation intent of a plant based diet (Genesis 1:29-30).”  The  mission of the Hoffman Foundation  is quite clear: “To promote through education the elimination of the use of animals in biomedical research and testing, their use as food, or their use for any and all commercial purposes…

Sit-in at UW-Madison during WWAIL (April 18, 2015).

Sit-in at UW-Madison during WWAIL (April 18, 2015).

SAEN is like other absolutist groups whose position is that no matter what potential benefit the work may result in, no use of animals is morally justified. This extends across all animals – from fruit-fly to primate. Furthermore, all uses of animals, regardless of whether there are alternatives and regardless of the need, are treated identically. In other words, the use of a mouse in research aimed at new discoveries to treat childhood disease is considered morally equivalent to the use of a cow to produce hamburger, the use of an elephant in a circus, or a mink for a fur coat.

WWAIL protests are focused specifically on research. Thus, the sites for protest tend to be universities and other research institutions where scientists engage in work that produces the new knowledge and discoveries that drive scientific and medical progress to benefit humans, other animals, and the environment. The protests also target individual scientists with the kind of “home demonstrations” we’ve written about before (see more here and here).  In some cases the protests target businesses that support animal research.

Although the WWAIL activities vary some each year, they have a few consistent themes:

  • First, the primary objective appears to be media coverage. In fact, a quick view of the “successes” claimed by the primary organizing group shows that number of news stories is the prize accomplishment.
  • Second, the number of people participating in the activities is typically a few to a dozen.
  • Third, most of the materials used in the protests, social media coverage, and news releases reliably rely on outdated, out-of-context images and little reference to the protestors’ broad agenda and position.

We agree that public consideration of animal research is important. Stimulating serious, thoughtful education efforts and inclusive public dialogue about science, public interests, medical progress, and animal research are critically valuable to public decision-making and, ultimately, to global health. Informed decisions based in accurate information and in an understanding of the complex issues involved in animal research are in the best interest of the public, science, and other animals.

For that reason, many scientists, universities, educators, advocacy groups, and individuals engage in public outreach, education, and dialogue about scientific research with nonhuman animals. Their goal is to provide the public with accurate and thoughtful information about the range of issues that bear on decisions, policies, and practices related to animal research. Among those topics are:  how science works, its process, timescales between discovery and application, why animal research is conducted, in absence of alternatives; who benefits and what would be lost if it did not occur;  how animals in research are cared for, how ethical review occurs, and how regulation and oversight function.

None of these are simple issues, which is why there are many websites, books, articles, and interviews on the topic. WWAIL provides a unique opportunity for the research community to help point people towards these resources for education, dialogue, and serious consideration of animal research.

At the University of Wisconsin-Madison, we have one example of how to do just that.  The website referenced in the banner shown in the photos here (animalresearch.wisc.edu) provides extensive information about animal research.  The site provides facts, interviews, videos, photos, and links for those interested in learning more about why animal studies occur, the role that they play in scientific and medical progress that serve public interests, how research is conducted, its ethical consideration, and the practices, policies, regulation and oversight that govern animal care.

By contrast, we have the signs held by those below participating in a WWAIL sit-in at UW-Madison on Saturday.  Among the signs are photos of animals from other decades and other countries.  For example, note the repetitive use of a picture of Malish, a monkey who was involved in research in Israel in 2001 (not exactly relevant to UW).  We also see quotes by an actor and numbers that do not reflect those from UW-Madison.  None of these are difficult errors or misrepresentations to correct; but they probably won’t be corrected in absence of voices and sources to provide accurate information.

Sit-in at UW-Madison during WWAIL (April 2015).

Sit-in at UW-Madison during WWAIL (April 2015).

This year, if your university or facility is among those that attract attention during WWAIL,  we ask that you join in the conversation by providing protestors, public, and media your own voice.  Whether it is via banners, websites, or talking with reporters– speak up for science and for public interests in advancing scientific understanding and medical progress. Although it may not matter to those committed to an absolutist agenda, it can matter to those who are interested in building a dialogue based in fact and serious consideration of the complex issues that surround public interests in the future of science, health, and medicine.

Speaking of Research

En Passage, an Approach to the Use and Provenance of Immortalized Cell Lines

This guest post is by Lisa Krugner-Higby, DVM, PhD.  Dr. Krugner-Higby is a scientist and also a research veterinarian within the Research Animal Resource Center at the University of Wisconsin-Madison. Dr. Krugner-Higby’s research is in development of extended-release formulations of analgesic and antimicrobial drugs. She previously worked in anti-HIV drug development.

I am always fascinated by the idea promoted by some animal rights activists – repeated in many versions and for many decades – that all preclinical biomedical research can be conducted using in vitro cell culture. I have never found one of them who has spent much time working with cell culture. On the other hand, I have spent approximately seven years of my life working with cell cultures, looking at the stainless steel back wall of a laminar flow work station day after day. One thing I can say about immortalized cell lines, or cells that reproduce indefinitely, is that they are not alive in the same way that a mouse is alive.

 

Cell culture

Cell culture

The first thing that a graduate student learns when they begin to work with cell culture is how to take cells that have overgrown the sterile plastic flask they inhabit and put them into a fresh flask with fresh growth medium. It’s called ‘splitting’ the number of cells and ‘passaging’ them into a new home. Split and passage, split and passage… I knew that with every passage, the cell line became a little more different than normal cells and even a little more different than the original cell line. The remedy for this type of genetic drift was to freeze low passage cells in liquid nitrogen and re-order the line from the repository when the low passage stocks were depleted. I was careful with my sterile technique, cleaned the laminar flow hood, and used a new sterile pipet every time in order to avoid contamination of my cells. Unfortunately, the day came when I opened the incubator door and the flasks were black and fuzzy with fungus, and all of my carefully tended cells were dead. An anguished conversation with the tissue culture core technician revealed that this happened every Spring in North Carolina when the physical plant turned on the air conditioning for the year, blowing a Winter’s worth of fungal spores out of the ductwork and into the air. She recommended doing other things for about 6 weeks until the spore load had blown out of the ducts. I have had other cell line disasters in my scientific career: the malfunctioning incubator thermostat that turned a colleague’s two months’ worth of cell culture growth into flasks of overheated goo or that generally reputable vendor that sold us a case of tissue culture flasks that were not properly sterilized resulting in clouds of bacteria in the warm, moist, nutrient-rich environment of the incubator.

I never thought to ask, in those early days, if the cells that I fussed, worried, and wept over, were actually the cells that they were supposed to be. Raji Cells, A549s, U937s, I knew them all, worked with them every day, and never doubted that they were the cells that I thought that they were. I knew that some cell lines had been contaminated with the HeLa cell line. HeLa cells are very hardy and could spread quite easily from one flask to another. But I thought that was in the past. It turns out that there was more to the story than I realized. Cell lines have a provenance, like paintings or other works of art. They have an origin, a laboratory where the line was first isolated and propagated. From there, it may have been distributed to other laboratories and to repositories like the American Type Culture Collection or ATCC. Some cell lines are used by only a few laboratories, and some become used very widely and in a large number of biomedical disciplines. Whereas some paintings are intentionally forged, many cell lines have now been shown to be unintentionally forged. A recent article in the journal Science estimated that 20% of all immortalized cell lines are not what they were thought to be1.

Download original file2400 × 1999 px jpg View in browser You can attribute the author Show me how Multiphoton fluorescence image of cultured HeLa cells with a fluorescent protein targeted to the Golgi apparatus (orange), microtubules (green) and counterstained for DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. National Institutes of Health (NIH).


Multiphoton fluorescence image of cultured HeLa cells with a fluorescent protein targeted to the Golgi apparatus (orange), microtubules (green) and counterstained for DNA (cyan). Nikon RTS2000MP custom laser scanning microscope. National Institutes of Health (NIH).

We now have better methods of identifying cell lines by their DNA, called short tandem repeat (STR) profiling, and scientific journals are beginning to require this testing for cell lines prior to publication. Currently, 28 scientific journals require STR profiling to establish cell line provenance prior to publishing a manuscript from a particular laboratory. Some scientists are also beginning to create catalogs of contaminated cell lines in an attempt to quantitate the damage done by some misidentified, but widely studied, cell lines. The same Science article, notes that the International Cell Line Authentication Committee (ICLAC) maintains a database of misidentified cell lines that now numbers 475 different lines. A cell line geneticist, Dr. Christopher Korch, recently estimated that just two of the immortalized cell lines that were found to be misidentified, HEp-2 and INT 407, have generated 5,789 and 1,336 articles in scientific journals, respectively. These studies cost an estimated $713 million dollars and generated an estimated $3.5 billion in subsequent work based on those papers1. This is because the usual trajectory for testing a new therapeutic modality, especially in cancer research, is to test a compound or technique in cell culture. It will then be tested in mice that express a tumor derived from the cultured cancer cells. If those studies are successful, the compound and/or technique undergoes further toxicity testing in other animal models before entering its first Phase I trial in human volunteers.

A lot of compounds that show early promise in cell culture and in cell line-injected mice turn out not to have efficacy in animal models or in human patients. Sometimes this is simply a matter of the compound being too toxic to organs or cell types that are not represented in the initial cell culture. Often, the reason why particular compounds or strategies fail is not known, and most granting agencies are not keen to fund laboratories to find out why things don’t work. I have wondered if the failure of some compounds or techniques is in part due to misidentified cell lines. I have also wondered if it is a reason why testing in animal models, particularly in animal models with spontaneously-occurring tumors, is necessary.

Testing anti-cancer compounds in models of spontaneously-occurring tumors in animals and/or testing in human tumor cells taken directly from patients and injected into mice (the ‘mouse hospital’ approach) is more time and resource intensive than screening in immortalized tumor cell lines. This approach, however, has the advantage of knowing that the investigator is not just treating misidentified HeLa cells in error. It is always necessary to go from in vitro cell culture models to in vivo animal models to confirm the viability of a therapy.

Science makes claim to no enduring wisdom, except of its method. Scientists only strive to be more right about something than we were yesterday, and efforts are underway to weed out misidentified cell lines. But the fundamental issues behind cell line misidentification highlight one of the reasons why we should not rely on immortalized cell lines without animal models, and why granting agencies should fund more studies to try to identify the disconnect between the results of in vitro and in vivo studies when things do not go as planned. That is a part of good science and part of creating better cell culture models to refine, reduce, and sometimes replace the use of animals in biomedical research.

Lisa Krugner-Higby, DVM, PhD

1) Line of Attack. Science. 2015. Vol. 347, pp. 938-940.