Tag Archives: animal testing

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

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.

The BUAV – More Spies, Lies and Inspection Reports

The British Union for the Abolition of Vivisection (BUAV) is a UK anti-vivisection group with a history of infiltrations to labs and unsubstantiated allegations against labs. A newly published report from a government investigation reveals just how far the BUAV bent the truth when they made false allegations against the University of Cambridge last year.

Fool Me Twice

In October, 2014, we wrote about how two separate investigations by the Animals in Science Regulation Unit (ASRU; the Government’s inspection unit) found allegations by the BUAV to be almost entirely groundless. In both cases the allegations had followed an infiltration by a BUAV activist.

The first report investigated the BUAV’s allegations against Imperial College London:

Over 180 individual allegations, made by the animal rights organisation, of non-compliance were investigated. Of these, all were found to be unsubstantiated apart from five formal non-compliance cases which have been completed – one category A and four Category B [none of which involved significant, avoidable or unnecessary pain, suffering, distress or lasting harm to the animals].

A second ASRU report into BUAV allegations against a pharmaceutical company conducting tests on veterinary medicines found:

No non-compliance with authorised programmes of work was detected apart from two minor issues with no welfare implications.
[…]
Our detailed investigations and review of available records and other evidence, does not support the allegations in the investigation report.

So twice last year the BUAV has been found misleading the public with their unsubstantiated claims.

Third Time Lucky?

In the post “The BUAV – Spies, Lies and Videotapes” we discussed an infiltration by the BUAV at Cambridge University. The infiltration and subsequent “expose” regarded research on sheep into Huntington’s and Batten’s disease. The allegations made were that there was “…distressing animal suffering, unlawful regulation by the Home Office, in adequate care of animals and inadequate enforcement by the inspectorate”. The 32-page report by the BUAV was supplemented by a four-and-a-half minute edited video (put together from hours and hours of footage by the infiltrator) but when ASRU officials wrote to them requesting further video footage they might have, the BUAV replied that “there was nothing further they wished to share with ASRU”. One guesses hours of footage of Cambridge University researchers abiding by the laws and regulations was not in BUAV’s interest to share. It also proves that the BUAV’s aim is not to address animal welfare issues at Cambridge, but to score points in their stated effort to “end all animal testing”. This month ASRU released their report into the allegations.

A sheep with Batten’s involved in the study at the University of Cambridge (Image credit: University of Cambridge)

Cambridge had previously provided a strong rebuttal of each the claims made by the BUAV. These claims appear to be a mix of exaggerated information and flatly false information. For instance Cambridge noted:

It is alleged that a lamb had to be euthanized at a UK airport after becoming sick during transit from New Zealand. One of the lambs did appear disorientated on arrival in London, but was cleared by the Veterinary surgeon as being fit to continue his travels. No adverse effects were seen in any of the animals on arrival in Cambridge a few hours later.

ASRU’s report is equally clear about this claim [p.13]:

In summary, we conclude that this allegation is simply untrue in relation to the sheep imported for the Project Licence holder’s research. No animals required euthanasia or were found dead on arrival a Heathrow Airport.

And some of their allegations appear to be of the BUAV’s own making. Cambridge noted:

We are careful to avoid causing stress to the Batten’s disease sheep. As their disease develops, they become confused and can become agitated, particularly when approached by unfamiliar people or surroundings. Thus the animal care team is careful not to isolate any sheep from its flock-mates, allow interaction with strangers, or make sudden or unnecessary changes to their routines. It appears that the BUAV infiltrator not only disrupted their routines in the making of the undercover videos, but also isolated the animals. This will have made the sheep appear more agitated than they are when under routine care.

ASRU have added that [p.13]:

The Establishment has mechanisms in place for whistle-blowing, and it is of note that no animal welfare concerns had been raised by any staff at the Establishment, including the animal rights organisation’s infiltrator…

A similar comment was made in the ASRU report into the Imperial allegations. The conclusion to the ASRU report makes damning reading for anyone who believed in the integrity of the BUAV.

Our detailed investigations, and review of available records and other evidence to do not support any of the allegations made by the animal rights organisation
[…]
None of these allegations has been substantiated nor has any allegation given us further cause for concern with regard to compliance with the requirements of the legislation at this Establishment.

Sound familiar? Once again the inspection reports have found the BUAV telling lies, with their spies and their videotapes.

One additional paragraph in the ASRU report on the University of Cambridge gives an insight into what the inspectors really thought about the BUAV’s allegations:

A small number of the allegations were based on hearsay evidence and we can neither confirm nor deny these. However given the overall lack of substance where relevant evidence was to be found we do not consider it likely that any of these other allegations would be substantiated.

Ouch!

The BUAV

Of the £1.3 million that BUAV spent in 2014 (not including money spent by their three associate companies, Animal Properties, BUAV Charitable Trust and Cruelty Free International), around £200,000 was spent on “Investigations”. Any curious journalist should be asking the BUAV whether they were paying these infiltrators, how much these payments were, and what they expected (video wise) from their employees.

BUAV investigations expenditure 2011-14

To remind people of what we have said before. These are not casual whistle blowers, but people who are working at animal research facilities with the express intention of creating horrifying videotapes. Be it a school, a hospital, a factory or a restaurant, there are few businesses for which you could not create a cleverly edited 5 minute shock video having secretly filmed for hundreds of hours.

One has to wonder how many BUAV infiltrators are in labs around the UK. Moreover, one wonders, how many BUAV infiltration videos were never publicised due to the lack of shocking footage (even after clever editing)?

Speaking of Research

Primate research and twenty years of stem cell firsts

This guest post is by Jordana Lenon, B.S., B.A., Senior Editor, Wisconsin National Primate Research Center and University of Wisconsin-Madison Stem Cell and Regenerative Medicine Center. The research will also be featured this evening in a public talk at UW-Madison’s Wednesday Nite at the Lab. WN@tL: “Twenty Years of Stem Cell Milestones at the UW.”  Details and link are below. Update 1/8/15:  Dr. William Murphy’s talk  can now be viewed at:  http://www.biotech.wisc.edu/webcams?lecture=20150107_1900

As we enter 2015, the 20th anniversary of the first successful isolation and culture of primate pluripotent stem cells in the world, it’s time to look back and see how far we’ve come. Thanks to a young reproductive biologist who came from the University of Pennsylvania’s VMD/PhD program to the Wisconsin National Primate Research Center at the University of Wisconsin-Madison in 1991, and to those whose research his groundbreaking discoveries informed, the fields of cell biology and regenerative medicine will never be the same.

stem cell colonies

Pluripotent stem cells are right now being used around the world to grow different types of cells—heart muscle cells, brain cells, pancreatic cells, liver cells, retinal cells, blood cells, bone cells, immune cells and much more.

Cultures of these cells are right now being used to test new drugs for toxicity and effectiveness.

More and more of these powerful cells are right now moving out of the lab and into preclinical (animal) trials and early human clinical trials to treat disease. The results are being published in peer-reviewed scientific journal articles on stem cell transplant, injection and infusion, reprogramming, immunology, virology and tissue engineering.

Pluripotent stem cells and their derivatives are right now being studied to learn more about reproduction and development, birth defects, and the genetic origins of disease.

Embryonic, induced pluripotent, tissue specific (adult), and other types of stem cells and genetically reprogrammed cells are all being used by researchers due to the open and collaborative environment of scientific and medical enterprises in the U.S. and around the world.

All of this is happening right now because of discoveries made 20 years ago by researchers at the Wisconsin National Primate Research Center.

Here is a brief timeline of stem cell breakthroughs by WNPRC scientists:

  • 1995-James Thomson becomes the first to successfully isolate and culture rhesus monkey embyronic stem cells (ES cells) at the Wisconsin Regional Primate Research Center (PNAS)
  • 1996-Thomson repeats this feat with common marmoset ES cells (Biol Reprod).
  • 1998-Thomson publishes the neural differentiation of rhesus ES cells (APMIS).
  • 1998-Thomson’s famous breakthrough growing human ES (hES) cells is published in Science. (This research occurred off campus, with private funding.)

Many subsequent stem cell “firsts” were accomplished by scientists who conducted lengthy training with James Thomson or Ted Golos, reproduction and development scientists at the Wisconsin National Primate Research Center. These highlights include the following accomplishments by Primate Center researchers:

  • 2003-WNPRC Post-doctoral trainee Thomas Zwaka achieves homologous recombination with hES cells. A method for recombining segments of DNA within stem cells, the technique makes it possible to manipulate any part of the human genome to study gene function and mimic human disease in the laboratory dish (Nature Biotechnology).
  • 2004-WNPRC Post-doctoral trainee Behzad Gerami-Naini develops an hES model that mimics the formation of the placenta, giving researchers a new window on early development (Endocrinology).
  • 2005- WNPRC scientist Igor Slukvin and post-doc Maxim Vodyanik become the first to culture lymphocytes and dendritic cells from human ES cells (Blood, J Immunol).
  • 2005-WiCell’s Ren-He Xu, who completed his post-doctoral research at the WNPRC, grows hES cells in the absence of mouse-derived feeder cells (Nature Methods).
  • 2006-WiCell’s Tenneille Ludwig, a graduate student/post-doc/assistant scientist through the Primate Center with Barry Bavister, then James Thomson, formulates a media that supports hES cells without the need for contaminating animal products (Nature Biotechnology). Co-authoring the work is another former Primate Center post-doc, Mark Levenstein.
  • 2007-Junying Yu, WNPRC and Genome Center, in Jamie Thomson’s lab, grows induced pluripotent stem cells, or iPS cells. (Science). These are genetically reprogrammed mature cells that act like embryonic stem cells, but without the need to destroy the embryo.

Researchers at all of the National Primate Research Centers continue to make advances in this remarkable field of research and medicine. A few more milestones include the following:

  • 2007- Shoukhrat Mitalipov at the Oregon National Primate Research Center successfully converted adult rhesus monkey skin cells to embryonic stem cells using somatic cell nuclear transfer (Nature)
  • 2012- Shoukhrat Mitalipov at the Oregon National Primate Research Center generation chimeric rhesus monkeys using embryonic cells (Cell)
  • 2012-Alice Tarantal at the California NPRC successfully transplants human embryonic stem cells differentiated toward kidney lineages into fetal rhesus macaques.
  • 2013-Qiang Shi at the Texas Biomedical Research Institute and Gerald Shatten at the University of Pittsburgh – and previously with the Oregon National Primate Research Center and Wisconsin National Primate Research Center – genetically programs baboon embryonic stem cells to restore a severely damaged artery.
  • 2013-Shoukhrat Mitalipov at the Oregon National Primate Research Center produces human embryonic stem cells through therapeutic cloning, or somatic cell nuclear transfer (Cell)

NPRC Stem Cell Timeline 01.06.15

Before all of this happened, we must note that non-primate mammalian embryonic stem cells were first successfully isolated and cultured in 1981, by Martin Evans and Matthew Kaufman at the University of Cambridge, England. That breakthrough occurred almost 35 years ago. Jamie Thomson studied mouse embryonic stem cells in Pennsylvania before working on primate cells.

Even before that, in 1961, Ernest McCulloch and James Till at the Ontario Cancer Institute in Canada discovered the first adult stem cells, also called somatic stem cells or tissue-specific stem cells, in human bone marrow. That was 55 years ago.

So first it was human stem cells, then mouse, then monkey, then back to humans again. Science speaks back and forth. It reaches into the past, makes promises in the present, and comes to fruition in the future.

In every early talk I saw Jamie Thomson give about his seminal stem cell discoveries in the late 1990s and early 2000s – to staff, scientists, to the public, to Congress, to the news media – he would explain why he came to UW-Madison in the early 1990s to try to advance embryonic stem cell research. In large part, he said, it was because we had a National Primate Research Center here at UW-Madison, and also that we had leading experts in transplant and surgery at our medical school. After he joined the WNPRC as a staff pathologist and set up his lab, first he used rhesus and then marmoset embryos before expanding to cultures using human IVF patient-donated embryos off campus with private funding from Geron Corporation in Menlo Park, California.

Human And Mouse EmbryoIn these early talks, Jamie included images (see above) showing how very differently the mouse blastocyst (a days-old embryo, before implantation stage) is structured from the nonhuman primate and human primate blastocysts concerning germ layer organization and early development (ectoderm, mesoderm and endoderm). He also was able to show for the first time how differently stem cells derived from these early embryos grow in culture. In contrast to the mouse ES cells, the monkey cells, especially those of the rhesus monkey, grow in culture almost identically to human cells.

At the time, Thomson predicted that more scientists would study human ES cells in their labs over monkey ES cells, if human ES cells could become more standardized and available. Yet he emphasized that the NPRCs and nonhuman primate models would continue to play a critical role in this research, especially when it would advance to the point when animal models would be needed for preclinical research before attempting to transplant cells and tissues grown from ES cells. Both predictions have come true.

Jamie closed his talks, and still does, with this quotation:

“In the long run, the greatest legacy for human ES cells may be not as a source of tissue for transplantation medicine, but as a basic research tool to understand the human body.”

This simply and elegantly reminds us how basic research works: Many medical advances another 20 years from now will have an important link to the discoveries of today, which have their underpinnings in that early research in Jamie Thomson’s lab 20 years ago. It will become easy to forget where it all started, when many diseases of today, if not completely cured, will become so preventable, treatable and manageable that those diagnosed with them will spend more time living their lives than thinking about how to survive another day.

Just as I did not have to worry about polio, and my children did not have to worry about chicken pox, my grandchildren will hopefully see a world where leukemia, blindness, diabetes and mental illness do not have the disabling effects or claim as many young lives as they do today.

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WN@tL “Twenty Years of Stem Cell Milestones at the UW”

http://www.uwalumni.com/event/wntl-twenty-years-of-stem-cell-milestones-at-the-uw/

January 7 – 7:00PM – 8:15PM CT
Location: UW Biotechnology Center 425 Henry Mall, Room 1111, Madison, WI 53706
Cost: Free

Speaker: William L. Murphy, Stem Cell and Regenerative Medicine Centerwnatl_williammurphy

Don’t miss this fascinating talk covering stem cell milestones at the UW. Professor Murphy will talk about the work of his team at the Stem Cell and Regenerative Medicine Center, where they are creating biological materials that could radically change how doctors treat a wide range of diseases.

Bio: Murphy is the Harvey D. Spangler Professor of Engineering and a co-director of the Stem Cell and Regenerative Medicine Center. His work includes developing biomaterials for stem cell research. Specifically, Murphy uses biomaterials to define stem cell microenvironments and develop new approaches for drug delivery and gene therapy. His lab also uses bio-inspired approaches to address a variety of regenerative medicine challenges, including stem-cell differentiation, tissue regeneration and controlled drug delivery. Murphy has published more than 100 scientific manuscripts and filed more than 20 patent applications.

Beagle Freedom Project Uses Former Research Dogs to Spotlight its Anti-Research Campaign

Today’s guest post  is by Dr. Cindy Buckmaster, chair of Americans for Medical Progress.

Activists at the Beagle Freedom Project (BFP) continue to gather support for their agenda to end animal-based research – and some in the research community are unknowingly helping them.

Many of you have seen recent TV news items or read news articles that feature beagles said to have been saved from laboratories where they never had a toy, played with other dogs, or experienced kindness and love from people in research settings. The Beagle Freedom Project uses the limitations of the news media to create this one-sided and false impression of the lives of research dogs.

Individuals at research institutions interested in rehoming post-study animals are approached by adopters representing themselves as private citizens, eager to adopt dogs retired from research. These applicants don’t indicate that they are working with the Beagle Freedom Project. We know of several institutions that have fallen prey to this misrepresentation by the BFP: within days of adoption, their freely released animals are listed as ‘rescued’ by BFP, along with the activists’ usual anti-research propaganda.

As Chair of the Board of Directors of Americans for Medical Progress, as well as an animal lover and someone who directs an animal care program for a major research center in the US, I would like to tell you the real story.

dog, animal testing, animal experiment

Beagle in research

These dogs are NOT ‘rescued’ from research facilities. They’re voluntarily released by the lab animal caregivers who love and cherish them. Research institutions have been rehoming dogs for years, over forty in some cases, without ‘help’ from the Beagle Freedom Project.  That’s how BFP acquired these dogs to begin with: they adopted them from research animal caregivers who were fooled into believing that the adopters’ only intention was to provide research dogs with a good home. The truth is that these dogs were adopted for use as props to support an animal rights agenda that is harmful to public health and safety.

Readers should be aware that BFP is led by animal rights activists, including Kevin Chase (formerly Kevin Kjonaas) who was convicted and served several years in prison for violating the Animal Enterprise Protection Act. Kevin Kjonaas is the Director of Operations of BFP. The Founder and President of BFP is Shannon Keith. Ms. Keith was one of Kevin’s defense attorneys during his domestic terrorism trial. She also produced and directed “Behind the Mask”, a film released in 2006 that glorifies the Animal Liberation Front, a group known for illegal animal rights activity.

The bottom line is this: BFP personnel and associates misrepresent their intentions to the research institutions they target and then deceive the public about the condition and treatment of dogs in research. Why? To demonize the scientific quest for cures that you and I demand.

The welfare and well-being of research animals and our animal care programs are inspected and evaluated by local and federal authorities multiple times per year. Moreover, most of us VOLUNTEER for an intense accreditation review by international experts every three years to ensure that we are providing our animals with the best quality of life possible. A review of the photos and video BFP itself offers of recently released dogs reveals the truth behind BPF’s deception. The dogs’ body condition and coats are gorgeous because they receive top notch nutrition and veterinary care while they are with us. They’re friendly because they have enjoyed socialization and playtime with other dogs and with our caretakers who adore them. The public fails to see this with their own eyes because they have been brainwashed by animal rights extremists for decades…and they seem to prefer drama over the truth.

Tell me something: Why would people who allegedly care so little about these dogs, as BPF claims, offer them for adoption? It’s not a trivial process. Records of animal health and release have to be generated, and adopters have to be located and screened. If our institutions really wanted to hide their ‘dirty little research secrets’, why wouldn’t they just euthanize all of these dogs, rather than risk ‘exposure’ by offering them to the public, as has been suggested by BFP?

Our dogs are offered for adoption because we love them and are grateful for their contributions to human and animal well-being. We want these heroes to live long, healthy, fun lives with loving adopters who have the patience and information needed to help them adjust to their new families. What is heartbreaking is that some of our institutions have closed their adoption programs because they were either exploited directly by BFP, or they don’t know who to trust anymore.

When are you and I going to hold the Beagle Freedom Project accountable for caring more about its agenda than our precious heroes?!

We all love these dogs and we all wish that they weren’t still necessary for the development of treatments and cures for conditions like cancer, Hepatitis C and Ebola. For now, they are still needed. Until we find a better way – and we are working on it – this research will continue to improve the lives of our friends, families and pets. The public is grossly misinformed about the care of animals in biomedical research and thus, unwittingly, people are supporting agendas that will harm them and their loved ones. Our faith is with our fellow citizens – but they must hear both sides of this issue, presented fairly. The media has an especially critical role in getting this right and they have, in most cases, fallen short of the mark. I am hopeful that they will do better by our citizens in the future.

Cindy Buckmaster, PhD, CMAR, RLATG; Chair, Americans for Medical Progress

See also:

http://speakingofresearch.com/2013/11/26/jerry-the-beagle-and-the-liberation-that-wasnt/