Tag Archives: animal testing

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.

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.

***

_______________________________________________________

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/

Child health benefits from studies of infant monkeys – Part 1

Health research with nonhuman primates takes place at many universities and research institutions in the US, among them centers funded by the National Institutes of Health (NIH).  A broad range of research aimed at better understanding maternal and child health takes place at these centers and depends, in part, upon humane, ethical scientific studies of infant monkeys.

A sample of the research areas and findings are highlighted below and provide a view of the value of developmental research. What even a short list shows is that the scope of scientific and medical research that informs pediatric health issues is large. It ranges from autism to childhood diabetes to leukemia to mental health to stem cell therapies.

Together, the findings from studies of infant monkeys have resulted in a better understanding of prenatal, infant, child, and maternal health. The scientific research has resulted in basic discoveries that are the foundation for a wide range of clinical applications and have also improved outcomes for premature and critically ill human infants.

Infant rhesus monkeys playing in nursery.  Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

Infant rhesus monkeys playing in nursery. Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

Studies of monkeys are a tiny fraction of all animal studies and are only conducted when studies of fish, mice, rats, or other animals are not sufficient to address the scientific question. Like all nonhuman animal studies, those of young monkeys are subject to rigorous ethical evaluation by scientists, by federal review panels, and institutional review boards that include veterinarians and members of the public.

The decision to conduct a study in nonhuman animals is one that rests on weighing both the potential benefit the work may provide and any potential for harm. The research below provides many specific examples of how and why the studies are conducted and their benefit. For each and every study, scientists, review panels, and ethics boards also consider the potential for harm that may result to the nonhuman animals that are involved. Whether there are any alternatives to the animal study is a requirement of the US system for ethical review and oversight. If there is no alternative, reduction in potential for harm is explicitly addressed not only by a set of standards for animal care, housing, handling, environmental enrichment, and medical care, but also by including only the number of animals needed to answer the scientific question. (You can read more about the review process, regulation, and care standards here and here).

Like other studies of nonhuman animals, those in young animals require serious and fact-informed ethical consideration. At the most fundamental level they challenge us to evaluate how we should balance work that ultimately can help children, the harm that may result from a failure to act, potential harm to animals in research. Consideration of how to balance the interests of children, society, and other animals is not an easy task. Nor is it one that is well-served by simple formulations.

Primate studies of early development have, and continue, to contribute valuable new insights and discoveries that improve the health and lives of many.  The examples below, from NIH-funded research programs across the US, demonstrate how the work contributes to public health.

Sources:  National Primate Research Centers Outreach Consortium. For more information about the NPRCs, see:  http://dpcpsi.nih.gov/orip/cm/primate_resources_researchers#centers

EXAMPLES OF PEDIATRIC RESEARCH WITH MONKEYS

Autism

  • In a major advance, California National Primate Research Center (CNPRC) research defined a link between maternal auto-antibodies and increased risk of a child having autism (http://www.cnprc.ucdavis.edu/maternal-antibodies-linked-to-autism/)
  • Research at the CNPRC has focused on oxytocin and vasopressin in social bonding and male parental care, as well as on the effects of early experiences on the development of these behaviors. Studies have begun on the long-term effects of oxytocin; a new treatment is already being used in children with autism without an understanding of the long-term effects. (http://www.cnprc.ucdavis.edu/unknown-effects-of-long-term-oxytocin-use-in-children/)
  • Using an innovative approach to imaging the brain, scientists at the CNPRC have significantly enhanced our understanding of the etiology of autism by mapping the location of receptors for oxytocin, a hormone that is linked with social behavior. http://www.cnprc.ucdavis.edu/improving-models-to-understand-the-etiology-of-autism/
  • CNPRC scientists have shown that monkeys exposed to a maternal mock infection in utero exhibit signs of inflammation within the brain four years later, which is a response that is similar to that observed in human patients with schizophrenia and autism.  Nonhuman primate models are essential for understanding the effects of maternal inflammation during pregnancy, as they provide critical information on individual susceptibility and vulnerability of specific gestational time points. http://www.cnprc.ucdavis.edu/mothers-immunity-linked-to-brain-inflammation/

Cerebral Palsy

  • One outcome of premature birth and accompanying brain injury can be Cerebral Palsy (CP). To date, studies at the Washington National Primate Research Center’s (WaNPRC) Infant Primate Research Laboratory (IPRL) have described the metabolome of normal birth and discovered new acute biomarkers of acute hypoxia‐ This multi‐modal approach will increase the likelihood of identifying reliable biomarkers to diagnose the degree of injury and improve prognosis by tracking the response to treatment after neonatal brain injury. (http://www.ncbi.nlm.nih.gov/pubmed/22391633, http://www.ncbi.nlm.nih.gov/pubmed/21353677)

Childhood Leukemia

  • Wisconsin National Primate Research Center (WNPRC) scientists James Thomson and Igor Slukvin turned diseased cells from a leukemia patient into pluripotent stem cells, providing a way to study the genetic origins of blood cancers as well as the ability to grow unlimited cells for testing new drugs for chronic myeloid leukemia, childhood leukemia and other blood cancers. (http://www.news.wisc.edu/18933 and http://www.ncbi.nlm.nih.gov/pubmed/21296996)

Diabetes and Childhood Obesity

  • Normal and obese marmosets were followed by Suzette Tardif at the Southwest National Primate Research Center (SNPRC) from birth to 1 year. At 6 months, obese marmosets already had significantly lower insulin sensitivity and by 12 months, they also had higher fasting glucose, demonstrating that early-onset obesity in marmosets resulted in impaired glucose function, increasing diabetes risk. (http://www.ncbi.nlm.nih.gov/pubmed/23512966)
  • Infant marmosets were followed by Suzette Tardif at the SNPRC from birth to 1 year. Feeding phenotypes were determined through the use of behavioral observation, solid food intake trials, and liquid feeding trials. Marmosets found to be obese at 12 months of age started consuming solid food sooner and drank more grams of diet thus indicating that the weaning process is crucial in the development of juvenile obesity in both NHPs and human. (http://www.ncbi.nlm.nih.gov/pubmed/23512878)

Diet

Environmental threats

HIV/AIDS

  • Scientists at the CNPRC developed the SIV/rhesus macaque pediatric model of disease, to better understand the pathogenesis of SIV/HIV in neonates and test strategies for immunoprophylaxis and antiviral therapy to prevent infection or slow disease progression. Drug therapies used to prevent the transmission of HIV from mother to infant were developed in nonhuman primate models at the CNPRC, and are now being successfully used in many human populations to protect millions of infants from contracting HIV. (http://www.cnprc.ucdavis.edu/koen-van-rompay/)
  • Development of topical vaginal microbicides to prevent babies from contracting HIV from their mothers during delivery was advanced by Eva Rakasz at the WNPRC and her collaborators. Dr. Rakasz was also a member of the National Institutes of Health study section, Sexually Transmitted Infections and Topical Microbicides Clinical Research Centers. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032991/, http://www.who.int/hiv/topics/microbicides/microbicides/en/)
  • In a model of mother to child transmission, research at the WaNPRC and the ONPRC has shown that neutralizing antibodies can block infection at high doses and prevent disease and death at lower doses in one-month old monkeys exposed to a chimeric SIV that bears the HIV Envelope protein. Human monoclonal antibodies currently in clinical trials are in testing alone and in combination with drug therapy in this primate model as a less toxic alternative to supplement or supplant drugs in newborns. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952052/, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807376/)
  • In women who are HIV positive, prenatal consumption of AZT is useful for reducing the risk that the unborn fetus will contract HIV. Research done at the WaNPRC IPRL demonstrated that the effects of AZT on maternal reproduction and infant development were minimal and at the doses studied, no significant adverse health effects from prenatal exposure to AZT were predicted for pregnant women. (http://www.ncbi.nlm.nih.gov/pubmed/23873400, http://www.ncbi.nlm.nih.gov/pubmed/8301525)
  • A goal of Yerkes National Primate Research Center (YNPRC) infectious disease researchers is to identify the sources of the latent HIV reservoir so targeted cure strategies can be developed. A first step is to develop a novel model of SIV infection and cART treatment of nonhuman primate (NHP) infants to interrogate the SIV reservoir. The development of such a model will greatly facilitate future studies of SIV reservoirs and the design and testing of novel reservoir-directed therapeutic strategies before scaling to clinical trials in HIV-infected patients.
  • YNPRC infectious disease researchers found the percentage of CD4+CCR5+ T cells was significantly lower in all tissues in infant sooty mangabeys (SMs) as compared to infant rhesus macaques (RMs) despite robust levels of CD4+ T cell proliferation in both species. The researchers propose that limited availability of SIV target cells in infant SMs represents a key evolutionary adaptation to reduce the risk of mother-to-infant transmission (MTIT) in SIV-infected SMs. The researchers are applying their findings toward reducing the more than 300,000 cases diagnosed in children each year. (http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003958)

Huntington’s Disease

  • YNPRC researchers have successfully created a transgenic, preclinical animal model of Huntington’s disease (HD). These animals, when followed from infancy to adulthood, show progressive motor and cognitive associated with neural changes similar with the disease patterns seen in humans. Not having such a model has been a major roadblock to developing effective therapies for the disease.
    (http//www.ncbi.nlm.nih.gov/pubmed/18488016; http//www.ncbi.nlm.nih.gov/pubmed/24581271)

Lung Development and Function

  • CNPRC research discovered a link between an infant’s temperament and asthma– research is leading towards the screening, prediction and prevention of lung disease in children. (http://www.ncbi.nlm.nih.gov/pubmed/21536834)
  • Research at the CNPRC has shown that exposure to high levels of fine particle pollution (e.g. wildfire smoke) adversely affects both development of the immune system and lung function(http://www.cnprc.ucdavis.edu/long-term-impact-of-air-pollutants/)
  • Childhood asthma research by the CNPRC focuses on understanding why children are highly susceptible to asthma, with the goal of identifying predictive biomarkers and discovering preventive treatments. These studies use a novel rhesus monkey model of house dust mite sensitization to investigate the pathogenesis of allergic asthma in pediatric and adult asthma. The goal is to define the relationship between pediatric asthma, development of mucosal immunity in the respiratory system, and exposure to the house dust mite allergen. (http://www.ncbi.nlm.nih.gov/pubmed/21819959)
  • Eliot Spindel at the ONPRC has shown that large doses of Vitamin C can protect developing lungs from the damage caused when mothers smoke. This work has been duplicated in clinical trials. (http://www.ncbi.nlm.nih.gov/pubmed/15709053)

Kidney Disease, Organ Transplants, Lupus

  • WNPRC scientists and surgeons at UW Hospital successfully tested a new compound, mycophenolate mofetil, in combination with other drugs in monkeys and other animals, and then in human patients in the 1990s. Their work has saved the lives of patients needing kidney or other organ transplants. These new therapies have also kept patients with chronic kidney diseases, including lupus nephritis, which strikes many children and teens, from needing transplants. (Hans Sollinger, Folkert Belzer, Stuart Knechtle, others.) (http://www.ncbi.nlm.nih.gov/pubmed/8680054, http://www.ncbi.nlm.nih.gov/pubmed/9706169, http://www.ncbi.nlm.nih.gov/pubmed/8821838


Memory Impairment

Polycystic Ovary Syndrome

Puberty Disorders

Prenatal and Mental health

  • Studies at the WaNPRC IPRL have provided important and therapeutically relevant information on the fetal risk associated with maternal exposure to antiseizure medication in infants born to women who have epilepsy (Phillips & Lockard, 1985, 1993). (http://www.ncbi.nlm.nih.gov/pubmed/23873400)
  • Human and animal studies at the SNPRC revealed that the intrauterine environment can predispose offspring to disease in later life. Mark Nijland showed that maternal obesity can program offspring for cardiovascular disease (CVD), diabetes and obesity. This study revealed significant changes in cardiac miRNA expression (known to be affected in human cardiovascular disease) and developmental disorders in the fetuses of obese baboons. (http://www.ncbi.nlm.nih.gov/pubmed/23922128)
  • At the CNPRC a new vaccine strategy against HCMV, the “birth defect virus”, has been shown to produce a strong immune response with the potential to prevent a viral infection that causes 5,000 babies yearly to be born with congenital neurological deficits. http://www.cnprc.ucdavis.edu/vaccine-against-hcmv-the-birth-defect-virus-produces-a-strong-immune-response/
  • Studies in the WaNPRC IPRL have demonstrated that prenatal exposure to relatively high levels of ethanol (alcohol) was associated with significant changes in the structure of the fetal brain. (http://www.ncbi.nlm.nih.gov/pubmed/23873400)
  • Recent findings from nonhuman primates studied by Ned Kalin at the WNPRC suggest that an overactive core circuit in the brain, and its interaction with other specialized circuits, accounts for the variability in symptoms shown by patients with severe anxiety. The ability to identify brain mechanisms underlying the risk during childhood for developing anxiety and depression is critical for establishing novel early-life interventions aimed at preventing the chronic and debilitating outcomes associated with these common illnesses. (http://www.ncbi.nlm.nih.gov/pubmed/23538303, http://www.ncbi.nlm.nih.gov/pubmed/23071305)
  • Developmental studies with nonhuman primates at the YNPRC have revealed that neonatal dysfunction of the amygdala, a key brain structure, has long-lasting effects on the typical development of brain circuits that regulate behavioral and neuroendocrine stress, resulting in long-term hyperactivity.  These findings may provide clues on the neural source of HPA axis dysregulation found in autism spectrum disorder, schizophrenia and affective disorders.  (http://www.ncbi.nlm.nih.gov/pubmed/23159012, http://www.ncbi.nlm.nih.gov/pubmed/24986273, http://www.ncbi.nlm.nih.gov/pubmed/25143624)

Preterm Birth and Neonatal Outcomes

  • Current research at the ONPRC incorporates studies directed at understanding the mechanisms of parturition, with emphasis on therapeutic interventions for preterm labor associated with reproductive tract infections and the prevention of subsequent adverse neonatal outcomes. Intra-amniotic infection by genital Ureaplasma species is a predominant cause of early preterm birth. Preterm infants often have life-long health complications including chronic lung injury, often leading to asthma and neurodevelopmental disabilities such as cerebral palsy. Research by ONPRC’s Dr. Grigsby has shown that administration of a specific macrolide antibiotic delays preterm birth and reduces the severity of fetal lung injury and most importantly central nervous system injury. Recently Dr. Grigsby has expanded the infant care facilities at the ONPRC with the addition of a specialized intensive care nursery (SCN); this has enabled new research initiatives to expand beyond the maternal-fetal environment to a critical translation point between prenatal and postnatal life. This one-of-a-kind nursery has the look and feel of a human neonatal intensive care unit and supports the cardiopulmonary, (including mechanical ventilation), thermoregulatory, and nutritional needs of prematurely born infants. (http://www.ncbi.nlm.nih.gov/pubmed/23111115, http://www.ncbi.nlm.nih.gov/pubmed/24179112)
  •  CNPRC investigations into potential effects of long-term binge drinking episodes on later pregnancies in primates demonstrate that binge-levels of alcohol were associated with reduced embryo development, changes in the oocyte and cumulus cell gene expression, and an increase in spontaneous abortion during very early gestation, even after alcohol consumption had ceased. http://www.cnprc.ucdavis.edu/binge-drinking-implications-for-human-health/
  •  A powerful new imaging technique has been developed at the CNPRC that could vastly improve the success of Assisted Reproductive Technologies, including IVF, by increasing the ability to predict which embryos stand the highest chance of continuing to develop normally.http://www.cnprc.ucdavis.edu/predicting-embryo-success-with-in-vitro-fertilization/
  •  Research at the CNPRC has shown a link between sugar consumption in healthy females and disrupted oocyte maturation and in vitro pre-implantation embryo in healthy animals. http://www.cnprc.ucdavis.edu/donec-at-mauris-enim-duis-nisi-tellus/

Regenerative Medicine

  • Studies at the CNPRC have advanced the understanding of developmental timelines in the kidney, and applied these findings to new protocols and tissue engineering approaches to someday regenerate kidneys damaged by obstructive disease. (http://www.ncbi.nlm.nih.gov/pubmed/23997038)

Stem Cells and Gene Therapy:

  • The first pluripotent stem cell derived clinical trials to treat childhood blindness are now underway, using stem cell technologies discovered using monkeys first, then humans, by WNPRC scientist James Thomson in the 1990s-2000s. (https://clinicaltrials.gov/ct2/results?term=juvenile+macular+degeneration+stem+cell&Search=Search, http://www.ncbi.nlm.nih.gov/pubmed/18029452, http://www.ncbi.nlm.nih.gov/pubmed/9804556, http://www.ncbi.nlm.nih.gov/pubmed/7544005
  • To successfully treat human disease with stem cells, physicians will require safe, reliable, and reproducible measures of engraftment and function of the donor cells. Innovative studies at the CNPRC have revolutionized the ability to monitor stem/progenitor cell transplant efficiency in fetal and infant monkeys, and have used new noninvasive imaging techniques that demonstrated long-term engraftment and safety. (http://www.ncbi.nlm.nih.gov/pubmed/24098579)
  • Studies at the CNPRC have proven critical in gaining approval for investigational new drug (IND) applications to the FDA and conducting first-in-human trials of (1) an expressed siRNA in a lentiviral vector for AIDS/lymphoma patients,, and (2) achieving the overall goal of utilizing adeno-associated virus (AAV) expression of human acid alpha-glucosidase in 3 to 14-year-old Pompe patients who have developed ventilator dependence.

Tuberculosis and HIV

  • Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. SNPRC scientist Marie-Claire Gauduin and colleagues have successfully established an aerosol newborn/infant model in nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Aerosol versus intra broncho-alveolar Mtb infection was studied. After infection, specific lesions and cellular responses correlated with early Mtb lesions seen on thoracic radiographs were observed. This model will also allow the establishment of a TB coinfection model of pediatric AIDS. (http://www.ncbi.nlm.nih.gov/pubmed/24388650)

[Updated 01/27/15]

Pregnancy Kits to Ebola Treatment: Medical Tests & Disease Treatments Depend on Animal Products

Antibodies Part 1

There has been considerable discussion on this website about the use of animal studies to develop new medical treatments. But some animal-derived products such as antibodies also play a crucial role in diagnostic tests for some diseases and targeted treatments for others. In the last week, antibodies hit the front pages of newspapers and websites with the news that the ZMapp serum given to 2 Americans aid workers stricken with the deadly Ebola virus was a cocktail of antibodies. Developed through research in mice, the two components of this experimental serum – ZMab and  MB-003 – had only previously been tried in monkeys, but the results were very promising. As of this writing, both aid workers’ conditions had improved.

Mice played a critical role in developing the antibodies used to treat aid workers with Ebola. Tweet this!

Antibodies are proteins the immune system produces to identify and neutralize foreign objects such as bacteria and viruses. Antibodies “recognize” specific proteins, a property that makes them highly useful for a variety of purposes. For instance, antibodies can be used in diagnostic tests to determine whether a protein associated with a particular disease or medical condition is present in a patient’s blood, urine, saliva, or tissues. The home pregnancy test is an example of a diagnostic test that relies on antibodies. These tests detect the hormone human chorionic gonadotropin, a protein that is only present during pregnancy.  Many other medical tests also utilize antibodies; a few examples are:

  1. Tests to look for heart proteins in the blood such as troponin that indicate that a heart attack has occurred.
  2. Tests for the presence of the HIV (AIDS) virus in the blood.
  3. Tests for proteins present in the blood of patients with Lupus, an autoimmune disease where the immune system attacks the body’s own tissues.

A diagram showing the characteristic Y shape of an antibody molecule. It is able to grab two of its target molecules with the ends of the two arms of the Y.

Antibodies can also be used to treat disease. Certain antibodies can neutralize toxins such as snake venom.  Other antibodies are coupled to a toxin or other chemical, such that it is delivered only to cells carrying the protein that antibody recognizes.  For example, some cancer cells generate unique proteins so antibody-coupled drugs can be used to deliver a toxic agent to the cancer cells without harming other cells in the body. Antibody therapies have been effective in treating a number of types of cancer, including Hodgkin lymphoma and non-Hodgkin lymphoma, some forms of skin cancer, and some forms of breast cancer. Now we learn that antibodies may also be effective in treating Ebola.

Unique cell surface proteins on a cancer cell, which can be detected using antibodies.

Unique cell surface proteins on a cancer cell, which can be detected using antibodies.

There are two types of antibodies used for medical diagnostics and treatments: polyclonal antibodies and monoclonal antibodies. Both require animals in their production.

Polyclonal antibodies are produced by injecting the protein of interest (or part of it, called an antigen) into an animal.   Since this is a foreign substance, the animal’s immune system reacts to it by generating antibodies to fight off the intruder. Later, samples of the animal’s blood are removed and the antibodies isolated. Larger animals such as sheep, goats, and rabbits are often used for antibody production because they have enough blood in their bodies that large blood samples can be removed without harming them. Antibodies generated using this method are called “polyclonal,” because they came from many different immune cells known as B cells or B-lymphocytes.

Process for producing polyclonal antibodies

Process for producing polyclonal antibodies

To produce monoclonal antibodies, an animal (often a mouse) is injected with the partial protein or antigen of interest. Antibody-producing cells are later isolated from the animal, often from its spleen. Fast-growing but harmless tumor cells are cultivated in the lab and fused with the isolated antibody-producing cells. This produces a new cell type called a hybridoma that can be grown in the lab. Once it is confirmed that the hybridomas are generating antibodies against the right antigen, these hybrid cells can serve as factories to grow large numbers of pure monoclonal antibodies in the lab.

From: FASEB’s Breakthroughs in Bioscience Series.  Used by permission.

Monoclonal antibody production process

Alice Ra’anan and Bill Yates

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