Monthly Archives: January 2012

Of Mice, Rice, Flies and Men

Animal rights activists often argue that animal models are irrelevant for human medicine, because they are ‘so different’ from us. But in fact some basics are shared across wildly distant species – something that the Nobel Committee acknowledged last year when they gave the Prize for Medicine and Physiology to Bruce Beutler and Jules Hoffmann for discovering the ‘early warning’ signals that set off immune responses in flies, mice and humans.

On Jan. 25 both Beutler, who works at the University of Texas in Dallas, and Hoffmann of the University of Strabourg, France, were at the University of California, Davis talking to a packed house about their work. Joining them on stage was UC Davis plant pathologist Pam Ronald, who studies rice, and Luke O’Neill of Trinity College Dublin, Ireland, who talked about human medicine.

(Watch the presentations here: http://ccm.ucdavis.edu/immunity.html)

L to R symposium speakers Bruce Beutler, Jules Hoffmann, Luke O'Neill and Pamela Ronald, with (far right) symposium sponsor Murray Gardner.

Work in these very different organisms can give insights that advances human medicine. From the basic discoveries in mice, flies and even rice could come new drugs and new approaches to treat heart disease, rheumatoid arthritis, inflammatory bowel disease and other conditions.

Our immune system has two lines of defense. The innate immune system reacts first, attacking invading microbes and triggering inflammation. If that response fails, the adaptive immune system fights back with antibodies and specialized killer cells. Afterward, the adaptive immune system retains a memory that allows a more rapid and powerful response if the same virus, bacterium or parasite comes back.

Only animals with backbones, from fish to humans, have an adaptive immune system. But all animals, including insects, as well as plants, have innate immune systems.

In the 1990s, Ronald (working with rice), Hoffmann (with Drosophila flies) and Beutler (with mice) identified genes for immune receptors that triggered innate immunity in the rice, flies and mice, and found that the genes were remarkably similar despite hundreds of millions of years of evolution.

From this common trigger, plants, insects and animals develop different types of response to invaders.

Activation of the immune system is not always a good thing. It can lead to allergy, inflammatory diseases such as rheumatoid arthritis or autoimmunity, when the body starts attacking its own tissues.

In his talk, for example, Beutler described how his team, working with mice, has isolated genes related to inflammatory bowel disease, while O’Neill talked about the possibility of being able to develop drugs to treat a wide range of diseases linked to inflammation.

The symposium is an annual event sponsored by a fund created by AIDS pioneer and UC Davis professor emeritus Murray Gardner, who previewed in an interview for Sacramento Public Radio Jan. 24 [http://www.capradio.org/168919] At the beginning of the AIDS epidemic in the 1980s, Gardner helped discover viruses similar to HIV in monkeys and cats – animal models that have been of vital importance in discovering drugs to treat and prevent HIV/AIDS.

– Andy Fell

Do your Share – Animal Research Education

School visits about animal research have usually been the domain of animal rights groups like HSUS and PETA, however a new program is set to challenge that. Scott Dobrin and Elizabeth Burnett, with the support of Americans for Medical Progress’ Michael D. Hayre Fellowship, have built a program for schools which aims to address the misinformation put about by animal rights organisations. Welcome to SHARE – Speaking Honestly – Animal Research Education. When I asked them about their program they had this to say.

SHARE helps students form their own opinions on the use of animals in research though a simulated classroom discussion.  It is a teacher-led experience that can be easily carried out in any educational setting with the tools and resources we provide. SHARE is designed for young adults who are still in the process of forming their own morals and values, many of which will stay with them the rest of their lives. Initially developed for both science majors and other college students, SHARE is readily adapted for secondary school audiences.

Through SHARE, students are introduced to animal rights, animal welfare, and animal exploitist points of view. First in small groups, and later as a whole class, students discuss the issues surrounding the use of animals in research by evaluating a sample research proposal. They are asked for their own opinions as well as the concerns they believe a scientist, a veterinarian, and a member of the public would hold, all the while unknowingly acting much like an IACUC. While creating a list of approved guidelines, students see their diverse attitudes revealed in their choices of acceptable animal research rules and regulations. They then are introduced to the concept of an IACUC and come to understand the value that the research community places on animal welfare.

On our website, http://sharehappens.org , you can find all the information you need to facilitate SHARE in the classroom. In addition to logistical tips for organizing the class and teaching tips useful for engaging students, you will find an interactive and detailed lesson plan complete with keys to success, talking points, time checkpoints, and references to the appropriate slides of the included powerpoint presentation. If you need more information on the topic of animals in research, the links page has a listing of several resources, both in support of and opposed to animal research, to read more. It is a one stop shop for facilitating SHARE in the classroom.

We, at Speaking of Research, wish Scott and Elizabeth all the continued success with their program.

Cheers

Tom

An Open Letter to the Laboratory Animal Veterinary Community and Research Institution Administration

The decades following passage of the U.S. Animal Welfare Act in the 1960s are marked with wide-ranging and significant changes to the administration, oversight, and responsibility for daily operations of institutions engaged in laboratory animal research. The intent of the legislation, and the central purpose of the accompanying and continuing changes, is to best ensure the welfare of animals in research.

This goal encompasses all aspects of laboratory animal care— their participation in ethical scientific studies, their humane treatment during daily care and maintenance, and their receipt of the highest standard of clinical care. Do scientists engaged in animal research perform all of these duties?  No. In fact, by law, it is not scientists who have the ultimate responsibility for oversight of all issues involved in animal welfare, but the attending veterinarian and institutional officials.

In practice, there are a range of individuals who share in the responsibility to provide for animal welfare. Many different types of expertise are needed to provide the best management of a laboratory animal research facility. Scientists working with animals have expertise in the topic their research addresses, in the activities that research requires, and in use of animals in research. Depending on their research area, background, and training they may have tremendous depth and breadth of knowledge about the animals’ behavior, psychology, physiology, and other systems. But it takes more than this to accomplish all that is needed to maintain an animal research program.

Animal research programs always include veterinary staff to provide the animals with clinical care. They typically also include animal care staff to provide daily husbandry; behavioral management staff to provide environmental enrichment and animal training; and facility management staff who work with engineers and others to maintain clean and safe environments for the animals. In addition to facility management, clinical care, and daily husbandry there are also divisions of personnel charged with evaluation and oversight of the research, including the Institutional Animal Care and Use Committee, associated staff, and compliance officers. Oversight for the entirety of the animal research program typically rests at the level of university administration.

In sum, the number of individuals and divisions now involved in ensuring laboratory animals’ welfare and humane treatment in ethical scientific studies extends far beyond the scientists most identified with animal research.  What does this mean? It means that there is a great deal of shared responsibility for both successes and the occasional failures in the conduct of laboratory animal science.  It also means that any discussion of continued improvements in the daily activities that affect animal welfare, as well as changes in policies that govern the conduct of animal research, should benefit from teamwork among these different stakeholders.

A Veterinary Technician works with rodents

A huge number of people are involved in animal welfare in laboratories

Finally, it should mean that in public dialogue the voices of scientists and research advocates are routinely joined by laboratory animal veterinarians, university officials, and others who play important roles in laboratory animal research.  This is true even when that research is controversial and has the potential to elicit attention from animal rights activists. All too often, however, few of these voices are raised when the public eye is turned to issues of concern in animal facilities. Rather, in place of thoughtful answers to questions raised by a range of parties—by the press, by animal rights activists, by other scientists, by USDA reports— what is often offered are generic statements that contribute little to understanding of the events and the context in which they occurred. For example, in response to virtually any type of incident, an institution’s response might be along the lines of:  “We follow all regulations and hold animal welfare in highest regard and priority…”

It is long past the time that our community should have abandoned this approach and required more from each of its members and divisions.  To accept anything less is a mistake.  Absence of accurate information, accompanied by the failure of institutions and their representatives to engage in public dialogue, only further erodes public trust.

The intent of the AWA, subsequent legislation and policies, accreditation programs, revisions of guidelines, and continued increases in regulatory oversight is to ensure the best animal welfare and humane treatment possible.  In the rare cases where the apparatuses put in place to achieve this goal fail, sometimes from accident or human error, two things must happen.  First, it is contingent upon all of those involved to immediately work together to identify the reason for the failure and ways to minimize the possibility that it occurs again.  Second, those ultimately responsible for oversight should provide the public with accurate information, explanation, and opportunity for discussion.  At the very least, they should be able to articulate the rationale and their support for the research programs and their contribution to scientific and medical progress.

Are we suggesting that attending veterinarians and institutional officials open their doors for daily chats with animal rights activists?  No, but we do believe that addressing legitimate public concerns and questions about their animal research programs are among the key obligations of those charged with oversight and conduct of those programs.

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

Speaking of Research Committee

The Freedom of Speech Paradox

The world is a complex mix of competing views. Politicians and pressure groups have fought long and hard to find a balance between the desire for free speech, and the need to limit the voices of extremism and irresponsibility within our communities. Few would condemn the arrest of someone who shouts “fire” in a crowded, confined space; however most respect our right to peaceful protest.

Incitement to violence, harassment or intimidation against those of different creeds, lifestyles or  beliefs should not be regarded as acceptable in a modern liberal democracy. The challenge comes in deciding what should be regarded as incitement, and what should not. I believe that a tiny minority of animal rights extremists have crossed the lines of acceptability and to this end I provide two examples – one recent, and one from some years back.

Case 1: Incitement to murder

Jerry Vlasak is an influential player within the extreme end of the animal liberation movement. As press officer of the North American Animal Liberation Press Office he has become one of the mouthpieces of the Animal Liberation Front and the Animal Rights Militia. His position as a role model has not appeared to bring upon any sense of responsibility for his words.

I think there is a use for violence in our movement. And I think it can be an effective strategy. Not only is it morally acceptable, I think that there are places where it could be used quite effectively from a pragmatic standpoint.

For instance, if vivisectors were routinely being killed, I think it would give other vivisectors pause in what they were doing in their work — and if these vivisectors were being targeted for assassination … — and I wouldn’t pick some guy way down the totem pole, but if there were prominent vivisectors being assassinated, I think that there would be a trickle-down effect [...]

And I don’t think you’d have to kill — assassinate — too many vivisectors before you would see a marked decrease in the amount of vivisection going on. (Source)

Now I have little doubt that Vlasak does not intend to murder anyone himself. However it would take only one young, idealistic activist trying to build his reputation and strike a blow for animal liberation to follow Vlasak’s twisted logic into the unthinkable.

Vlasak is not the only person to call for violence against animal researchers (and their families). If the unthinkable was to happen, there would be many animal rights extremists whose words will have played a part in its creation. Nonetheless, surely, there is a moral line in the sand which few if any would be willing to cross, after all the animal rights movement is fundamentally in the business of saving lives (albeit not human ones)? Surely….?

May 31st, 2009, a doctor is shot dead at a church service. It is not the first time he has been shot for his beliefs and line of work, individuals have already called for the death of doctor’s in the same line of work.

The above is not the actions of animal rights activists, but that of anti-abortion extremists. In 2009 Scott Roeder crossed the lines of acceptability and morality and murdered Doctor George Tiller. Such actions were roundly deplored, but little time is spent considering the impact of those that had called for Tiller’s death, and the death of other abortionists. Sadly, many similarities can be found between the tactics of the animal rights extremist movement, and those of the anti-abortion extremists.

Where do we draw the line between Freedom of Speech and Incitement to Violence? This fire at the house of a Pharmaceutical Executive was started by animal rights extremists

Case 2: Naming the targets

The second situation further strains the relationship between freedom of speech and freedom from harassment. What if a known extremist movement does not directly call for the death of its enemies, but instead provides the information necessary to target them. They may not have put the gun in anybody’s hand, but they are certainly showing them where to point it.

Negotiation is Over, a fringe animal rights extremist group has provided such information on a number of occasions. Providing names and contact information for a variety of researchers. NIO’s words are reminiscent of our earlier discussion.

Every time a vivisector’s car or home — and, eventually, the abuser him/herself — blows up, flames of liberation light up the sky [...]

The only effective approaches to veteran abusers appear to be through incendiaries, intimidation, and violence.

Bear such words in mind when you consider that on January 8th 2012 NIO decided to publish floor plans for research facilities at the University of Florida. No threats were published alongside it, but then with a website full of calls to harass and intimidate researchers, they hardly needed to put them in the same post.

Is free speech a sufficient barrier to hide behind when distributing such potentially risky materials. When does one person’s freedom of speech justify infringing on another’s right to live free from harassment?

Before I decided to write this post I received an email from a colleague of a researcher who was under threat. One paragraph particularly stuck with me:

I actually cannot believe a court of law would allow documents of this nature containing names of people who work at an institution to be given to a group of people sworn to kill, torture and terrify them. Their site is already filled with people licking their lips about harassing families and even people discussing murder. I have counted a fair number of people who made implications of going to schools where their kids studies. These clearly are a lot of idle threats but it takes just one person to turn an idle threat into a tragedy.

Just one person.

The comments made by Vlasak and others, the documents and finger pointing of groups like Negotiation is Over, are permitted under the guise of free speech. The effect is a generation of researchers who do not dare to speak up for what they do lest they become the next target. Even though many researchers are not aware of characters like Vlasak, or the particulars of the threats made to fellow colleagues in science, these extremists contribute to a general awareness of a dangerous animal rights movement whom many scientists would prefer not to cross. Furthermore, fear may cause some aspiring scientists to choose different career paths at a time when science plays such a crucial role in the economic prosperity and health of a nation.

The Freedom of Speech Paradox is thus – when people misuse this right, as provided by the First Amendment, in order to intimidate others away from being able to use their same right to defend and justify their work.

Tom Holder

A Proposal for the Labeling of Medicines

In a recent poll conducted by Zogby, 2,100 adults in the U.S. were asked the following question.

Do you agree or disagree with medical and scientific research that requires lab animals?

The results showed  a similar outcome to that of other recent polls.

About 52% of the population approve of animal research in various degrees, about 27% disapprove in various degrees, 15% are neutral and 6% are unsure about their position.

Despite the many polls done on the subject it remains unclear on what grounds do some people object to the use of animals in science.

Is it perhaps that they find the work morally wrong?  Is it that they believe all living beings have the basic rights to liberty and freedom?

Some insight into these questions can be gained by asking the same group of people what would the do in the following scenario.

Suppose you suffer from a leaky heart valve, and that doctors say you have two years left.   You could have a valve replacement surgery that might save your life.  But, in order to obtain the replacement tissue necessary for a surgery, a pig must be killed.

Which of the following statements best reflects what you would do if faces with a similar situation?

Statement A: I would have the surgery.  I think it is ethical.
Statement B: I would have the surgery, but I think it is unethical.
Statement C: I would not have the surgery, but I think it is ethical.
Statement D: I would not have the surgery because I think it is unethical.

Here are the results from the same poll:

Now, if one believes animals have rights they surely ought to be respected.  If you believe a pig has the same basic rights to life and freedom as your neighbor, then you ought to refuse the surgery for the same reason that you would not kill your neighbor to save your own life.

However, only a mere 3% of those asked appear ready to act in a way consistent with such a position.  It is interesting to note that also about 3% of the US population are vegetarian, although most of them do it for health reasons and not ethical objections to the use of animals as food.

Thus, those that oppose research do not appear to do so because of belief that all living beings have the same basic rights to life as that of fellow humans.

Another small minority, 2%, would not have the surgery despite the fact they think such surgical intervention is ethical.  It would appear this group simply is uncomfortable with the notion that pig tissue would be implanted in their human hearts.

About 12% of the group would opt to save their lives despite having ethical objections.  It appears this group feels there is something inherently wrong in killing an animal to allow them to survive and yet, if faced with the situation they would nonetheless go ahead with the surgery.  Arguably, this group realizes that the pig is a living being that we owe moral concern, but that when human and animal lives are at stake, opting to save the human is morally permissible.  Alternatively, they may genuinely opt for behaving in an immoral fashion when it comes to saving their own lives.

Finally, the vast majority, 73% of them, will opt for the surgery without having any moral concerns whatsoever.   None at all.   That is roughly 3 out of 4 people in the US population.

A natural question is then why wouldn’t the same group, at the very least, be in favor of animal research that advances medical knowledge and human health?

One likely possibility is that they fail to see the direct link between research and the therapies and medicines that it produces.  They fail to see that the medicine that will save their lives next time they visit the emergency room will be, in all likelihood, the result of animal research.  They may wrongly perceive basic and translational research as two being completely different things.  The contribution of basic knowledge to human health may be lost in translation.

So, what can be done?

Aside from scientists and physicians reaching out to educate the public on this matters, we could begin by labeling each and every single medication that resulted from basic research in animals with such basic information.  Note that I am not talking about safety testing in animals — which is required by the law.  Instead, I am referring to medicines developed through the identification of molecular targets or the discovery of specific mechanisms with the use of animals in basic research.  In other words, I propose to label medicine as derived from animal research if it actually produced the knowledge that actually allowed scientists to understand how a particular therapy could be developed.

Shouldn’t the public be entitled to know where their medicines come from? Shouldn’t the public be entitled to understand the range of benefits produced by their tax dollars?

What do you think?

Ignorance or Deception?

Animal rights activists may want to start cooling down their engines.

Apparently, by 2050 we can expect the complete elimination of animal use in science.

At least, this is the prediction made by Dr. Andrew Rowan, Chief Scientific Officer of the Humane Society of the United States (HSUS) in a recent article that appeared in The Scientist.

The title of the piece was “Avoiding Animal Testing.  Advances in cell-culture technologies are paving the way to the complete elimination of animals from laboratories”.

The first half of the article focuses on the development and adoption of alternatives to the use of animals in toxicology.  Our public health officials and the FDA have long made the sensible decision to require any company that introduces new chemicals or drugs into the market to provide an initial experimental assessment of their potential toxicity to humans.

This use of animals for such safety screening is typically called animal testing.

Dr. Rowan correctly points out that advances in the development toxicology methods may allow us eventually to relax the regulations that require the use of animals in testing.  But he rapidly moves to insinuate such advances imply that by 2050 we could see the end of animal use in laboratories:

This overall decline in animal use can be attributed to the advent of novel technologies such as improved cell-culture systems and micro-analytic techniques; more sophisticated model systems; improved understanding of signaling and metabolic pathways; and a host of other new methods that allow scientists to answer important questions about the functioning of healthy and diseased tissues without subjecting whole animals to harmful procedures. With a 50 percent decline in animal research since 1975, we are roughly at the halfway point towards the complete elimination of animal research. Thus, we argue that, by 2050, we might finally see the last of animal use in the laboratory, particularly if all stakeholders put their minds to it.

First, the assertion that the total use of animals is systematically declining is not supported by the data.  The slide below, for example, was taken from a recent talk Dr. Rowan gave at the University of Wisconsin.  It shows the total number of animals used has been stable since the mid 80s, with the number of non-genetically modified (Non-GM, faint dashed line) animals decreasing and stabilizing in the 90s (see also data here), while the number of  genetically modified (GM) animals, which are largely mice, has been systematically increasing.

Second, even if correctly asserting that we can expect a diminished need for animals in toxicology testing, Dr. Rowan’s generalization of such trend from a such narrow field to all of biomedical research is groundless and misleading.

Let us be clear, our universities do not engage in animal testing, but in animal research.

What’s the difference?

Scientists are largely concerned with elucidating the basic mechanisms of biological processes in health and disease.  We want to study how cells in our bodies work, how they communicate, how they develop, how they age and how they die.   We want to understand how the brain, our immune system, and internal organs work and how they fail.  And so on…

Why is it critical we develop such an understanding?

Because without this knowledge there will be no hope to combat disease. Indeed, the mission of the National Institutes of Health (NIH) recognizes this fundamental fact in its opening statement,

NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life and reduce the burdens of illness and disability.

Implicit in such declaration is the acknowledgment that it is basic knowledge that drives advancements in human health and well-being.  Basic knowledge of nature is what drives progress.  This point is critical –   translational or applied research would not exist without basic knowledge as the raw material.  Without knowledge there would be nothing to translate nor apply.

Those that declare an imminent end to the use of animals in science are effectively implying that they envisage all basic knowledge needed will be acquired by a certain date, or that we will have methods that would allow us to proceed with studies non-invasively in human volunteers. Dr. Rowan’s statement that “Advances in cell-culture technologies are paving the way to the complete elimination of animals from laboratories” is nothing short of utter scientific nonsense.

Is it possible for Dr. Rowan to be ignorant of the role of animals in scientific research?  Could he legitimately be confused about the difference between safety testing on one hand and the development of therapies and basic research on the other?

This seems highly unlikely giving his academic credentials and the fact that he has served on IACUCs before.  In fact, another slide from his talk, shows him delineating these different uses of animals, and illustrating that animal testing for human safety accounts for merely ~25% of total animal use.

No, Dr. Rowan is not confused at all.  He knows what he is talking about.  This is unfortunate as one can only conclude his article is simply a misguided attempt to deceive the public about the fields in which we might realistically expect science to successfully replace animals in the near future.

And I emphasized science above for a good reason.

As difficult as it is for animal advocates to understand, scientists also believe we will see a day when we can eliminate the use of animals in all animal research.  And the day will arrive because of the hard work, progress and achievements of dedicated scientists, such as this one, and not because of deception of those that want to oppose animal research at all cost.

For HSUS to suggest that all animal research could be eliminated by 2050 is  flatly wrong from a scientific point of view, and utterly irresponsible from a public health perspective.

Fanning the flames of fear

Over the New Year’s weekend, the people of Los Angeles were gripped by a rash of arsons that targeted vehicles and homes. The fires sent people scurrying from bed in the middle of the night, with children in arms, in a desperate attempt to avoid harm. An understandable fear gripped the community, with people parking their cars down the street so that, if the arsonist came, the resulting fire would not spread to their house, risking the safety of their sleeping families.

The string of arsons was, apparently, the action of a single hate-filled man who was determined to inflict his anger on helpless targets. He went out into the night, applied accelerant to cars and set them on fire.

I, like other biomedical researchers in Los Angeles, had a powerful, personal response to viewing these events unfold. It was only 30 months ago that an animal rights extremist, morally blinded by hate and rage, walked through the gates of my yard at 4 am and set my car on fire, risking my life and that of those who lived around me. I can still see the flames when I close my eyes, and I can sometimes still feel the heat of the fire on my face, so I knew very well what these new victims that I watched on television were feeling: fear, panic, sadness and total confusion.

Animal rights extremists torched my car in 2009

The extremist elements that claim responsibility for these actions often indicate that they cause no harm to people; they say that they limit their actions to economic damage (WARNING: link takes you to an animal extremist website). They claim to break windows, steal documents, free animals and – yes – set cars and homes on fire, but they often insist that they do not hurt or injure people.

The claims that they cause no harm are proved hollow by the looks on the faces of people fleeing their burning homes on New Year’s eve. Extremist animal rights elements, like the man who set the New Year’s Eve fires, have one goal – not to cause financial losses to their targets – but to inflict psychological damage in the form of terror. In that sense, their targets are as much the people who have yet to be attacked as they are the individual whose car is on fire.

The events of last weekend underscore the fact that hatred is not unique to animal rights extremists. But it does demonstrate how powerful and insidious these forms of attack can be and how essential it is for our broader civil society to reject the actions of those who use thuggish tactics to achieve their ends of their movement.

Regards,

David Jentsch

On Friday, January 6, KCET, a Southern California PBS station, will re-air the story (‘Testing the Limits’) that addresses the harassment of Los Angeles researchers by local animal rights activists. You can watch it as it broadcasts (2/6 at 830 PM PST; 2/7 at 6 PM PST; 2/8 at 630 PM PST or 2/9 at 1030 PM PST); the program is also archived on their website (click here).