Monthly Archives: April 2015

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.

sss

(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

Animal Research and the 2015 UK General Election

On May 7th 2015 the British voters will flood to the polls to determine the next Government (which for the second time in a row is likely to be a coalition). The political landscape has changed a lot since the 2010 election resulted in a Conservative-Liberal Democrat Coalition, with the rise of several smaller parties including the United Kingdom Independence Party (UKIP) and the Scottish National Party (SNP). The negotiation process of forming a coalition will mean that smaller parties can make demands on the largest parties (Conservatives and Labour) to secure a coalition agreement.

In the last week the parties have released their manifestos, outlining what they promise to do over the next five years if they are elected into Government. Many of the manifestos have specific pledges relating to the use of animals in medical and scientific research (which is supported by around two-thirds of the British population).

Nature and the Guardian have analysis of what the parties and their  manifestos say about science in general, so this article will concentrate on policies specific to regulation of animal research.

UK General Election 2015

The Conservatives Conservative animal research

The Conservatives (or “Tories”) are the larger of the two parties in the 2010-15 ruling Coalition. Their manifesto’s only mention of animal research says:

“We will encourage other countries to follow the EU’s lead in banning animal testing for cosmetics and work to accelerate the global development and take-up of alternatives to animal testing where appropriate.”

This fits the business-focused Conservative messages. The Coalition Government’s 2014 Delivery Plan on “Working to reduce the use of animals in scientific research“, which called for the UK to “develop an international strategy towards the eventual eradication of unnecessary animal testing of cosmetics products, adopting a science-led approach” (2.2.3).

The Labour Party Labour animal testing

Labour is the second largest party in British politics, currently neck and neck with the Conservatives. Their manifesto mentions hunting, protecting dogs and cats, and defending the UK ban on hunting with dogs, but does not mention animal research explicitly anywhere. Separately, Labour released a manifesto called “Protecting Animals“, signed by the Labour leader which expands on the main manifesto, but similarly lacks any specifics on animal research.

During their previous term in government, which ended in 2010, Labour established the National Centre for the 3Rs, and implemented legislation to stop campaigns of harassment and intimidation against scientists by animal rights extremists.

The Liberal DemocratsLiberal Democrats animal experiments

Traditionally third party in British politics, the Liberal Democrats (or “Lib Dems”) were in Coalition with the Conservatives during 2010-15. The last two Home Office ministers in charge of animal research – Lynne Featherstone and Norman Baker, have both been from the party. Their manifesto states (p82):

“Liberal Democrats believe in the highest standards of animal welfare. We will review the rules surrounding the sale of pets to ensure they promote responsible breeding and sales and minimise the use of animals in scientific experimentation, including by funding research into alternatives. We remain committed to the three Rs of humane animal research: Replace, Reduce, Refine.”

Under the 2010-15 Coalition, funding for the National Centre for the 3Rs rose from £5.3 million to over £8 million. The manifesto also uses the word “minimise” rather than “reduce”, so as not to focus on baseline figures, but on the 3Rs – preventing a repeat of confusion over terminology surrounding early Coalition pledges.

The Scottish National PartySNP animal studies

Buoyed by the Scottish Independence Referendum, the Scottish National Party (SNP) look to be mopping up almost all the Scottish seats in (the Westminster) Parliament, and will likely become the third largest party. Their manifesto promises “further animal welfare measures” but does not specifically mention animal research. They separately promise to increase funding for Motor Neurone Disease, which would likely involve animal studies.

While no other party is likely to reach over 10 seats in parliament (of 650 seats), the following parties are still worth mentioning (of these, only the Democratic Unionist Party (in Northern Ireland) is likely to get over 5 seats).

United Kingdom Independence PartyUKIP animal testing cosmetics

UKIP are a relatively new party at the far right of the British political spectrum. While their polling suggests them getting around 10-15% of the vote, they are unlikely to get more than 3 seats in parliament. Their anti-EU platform means they believe that the UK “can only regain control of animal health and welfare by leaving the EU”. Their manifesto calls for:

  • “Keep the ban on animal testing for cosmetics;
  • Challenge companies using animals for testing drugs or other medical treatments on the necessity for this form of testing, as opposed to the use of alternative technology;
  • Tightly regulate animal testing.”

It would appear that UKIP are trying to put in place the existing UK regulatory system. As Chris Magee, from Understanding Animal Research, says:

“these aren’t bad policies – but we know this because they have been working effectively for at least the last 29 years.”

The Green PartyGreen party ban animal experiments

The Green Party have recently surged in British politics, but are unlikely to make gains beyond the single seat they currently hold.

Their manifesto reads like it was written by the animal rights group, the BUAV:

  • “Stop non-medical experiments, experiments using primates, cats and dogs. End the use of live animals in military training.
  • Stop the breeding and use of genetically altered animals.
  • End government funding of animal experimentation, including any that is outsourced to other countries.
  • Provide greater funding for non-animal research methods and link funding to a target for developing of humane alternatives to animal experiments.
  • Increase transparency and ensure publication of all findings of animal research, including negative findings.
  • Introduce a comprehensive system for reviewing animal experiments and initiate a comparison of currently required animal tests with a set of human-biology based tests.”

Four of these pledges have analogues among the BUAV pledges, and it would similarly result in the end of over 80% of animal experiments in the UK. Quite simply, this policy is a disaster for human and animal health. Interestingly, both the leader of the Green Party (Natalie Bennett), and their only MP (Caroline Lucas), have both signed the BUAV’s pledges.

Plaid Cymru 

This party will be contesting all forty parliamentary seats in Wales. They are likely to come out with up to five of them (they currently have three). Their manifesto pledges:

“[T]he introduction of a European-level Animal Welfare Commissioner and adoption at all government levels of the new and comprehensive Animal Welfare law to end animal cruelty.”

The Democratic Unionist Party

Contesting seats in Northern Ireland, and likely to win 5 – 10 seats (currently holding 8), their manifesto does not mention animal research but says:

“[We want] a UK wide charter for animal protection.”

Some predictions (from April 22nd) on the number of seats parties will win. 326 seats are needed for a majority

Some predictions (from April 22nd) on the number of seats parties will win. 326 seats are needed for a majority

Animal Rights Election Activism

There are also various animal activist groups which are working to convince parliamentary candidates (PPCs) to put in place new regulations for conducting animal studies. Those that have contacted candidates include:

The National Anti-Vivisection Society (NAVS) are focusing on household product animal tests (which will be banned from October 2015), and reforming Section 24 (which is already underway).

The British Union for the Abolition of Vivisection (BUAV) are running their “Vote Cruelty Free” campaign, which asks candidates to make six pledges which would effectively destroy British medical and veterinary research. These include bans on GM animals, on “non-medical research” and on the use of cats an dogs.

Animal Aid are calling for an end to all taxpayer money used to fund research involving animals – thereby denying the National Health Service of many future treatments.

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.

Interview with a Primate Researcher

In the last few months, Italian animal rights activists have conducted a campaign against animal research, in particular against primate research. This is despite the important role that primates have played in breakthroughs in stem cell research and neuroprosthetics, among other things. Nonetheless, activists continue to try to claim such research is useless. In particular, they targeted Prof. Roberto Caminiti, a leading neurophysiologist at the University La Sapienza in Rome, and his research team, accusing them of animal mistreatment. Earlier this year students and scientists at the University rallied round Prof. Roberto Caminiti, his team, and his important research.
To answer some of the activists accusations, Pro-Test Italia has produced a video with Prof. Caminiti to illustrate why primate research is so important in the field of neurophysiology and brain-computer interface, and why animal models remain essential for this kind of research. Pro-Test Italia have also made an English version of the video:

It’s important to spread this video outside of Italy to both explain to the public what is going on, and to encourage other primate researchers not to remain hidden but to be clear about the important research that they do. Researchers should be proud of the important work they do in contributing to medical developments for everyone.

Marco