Tag Archives: animal research

I Pro-Test for Science

Please leave your messages of support including your full name in the comment section at the bottom of the page (no sign up necessary). We must show our fellow scientists that they have our support. Names in the comment section will be added to the signatures at the bottom of the post.

When researchers are harassed and intimidated for carrying out their work, we must consider the whole scientific community to be under threat. We may not always be available to stand shoulder to shoulder with our colleagues, but we can still offer our strength and support from afar.

At UCLA, the scientists and their community are standing up to end the home demonstrations that have targeted their colleagues for many years.  As Professor David Jentsch writes

For more than a decade, the streets in front of the homes of UCLA researchers have been the scene of regular, brutal, vitriolic and hate-filled campaigns by animal rights hooligans. …  We have decided to act, with our voices, our messages of scientific progress and – most importantly – with the unity of our community.

Speaking of the successful first counter-demonstration at a home protest Professor Dario Ringach writes:

… it should not come as a surprise to anyone that after a decade of harassment, intimidation and threats,  we have decided to mount counter-demonstrations when these animal right terrorists show up at our homes.

These activists now have the shameless audacity to play the victim of this encounter. Incapable of understanding the message, they are now recruiting more misguided individuals to join them in their fanatical crusade and come back to harass us at our homes on February 15th.

We will be there to meet them once more and convey one simple message,

We are not going to take it anymore!

Colleagues and friends – please take a moment to leave a message of support for the brave UCLA scientists who have been subjected to fire bombs, home harassment, threats to their children, and relentless fear-campaigns for over a decade by animal rights activists, yet continue their work to advance science.  It may be difficult to imagine what this is like, and easy to imagine is an issue that is someone else’s– one that will never be yours– but it is not. It is an attack on public interest in scientific progress, in medical progress, civil dialogue, and democratic ideals. Our community is often silent in the face of attacks. We can change that and we really must.

I am Pro-Test

For those who think that this is about animal welfare, about specific types of research, about whether or not invasive research in nonhuman animals is justified, or about some other distinction among the wide range of issues concerning captive animals, it really is not.

We ask you to please read David Jentsch and Dario Ringach’s posts (here, here, here), watch this video, and get better look at what is happening.

These are our colleagues and scientists who bravely defend their work, who engage in public dialogue, who lend their voices to serious, fact-based consideration of ethical issues. Consider whether you really believe that the actions taken by the animal rights groups represent a best path forward.  If you do not, please take a minute to comment in support of the UCLA scientists and share with others who can be there to stand with them. Even if you cannot be in LA to stand with them, you can offer a comment in support and let the public know that home harassment is the wrong path.

Please leave a comment including your full name to be added to the list below.

We should all be Pro-Test. Now it’s time to say so.

Speaking of Research

Counter-demonstration. When: February 15, 10:15am sharp!
Where: Franz Hall Lobby @ UCLA (near Hilgard and Westholme)  http://maps.ucla.edu/campus/


Allyson J Bennett
Tom Holder
Chris Magee
Pamela Bass
David Jentsch
Dario Ringach
Jacquie Calnan
Paul Browne
David Bienus
Andy Fell
Jim Newman
Prof Doris Doudet
Gene Rukavina
Prof Bill Yates
Christa Helms
Jeff Weiner
Justin McNulty
Alice Ra’anan
Jordana Lenon
Jae Redfern
Melissa Luck
Claudia Soi
Kevin Elliott
Brian L Ermeling
Teresa Woodger
Joanna Bryson
John Capitanio
Dennis J Foster
Juan Carlos Marvizon
António Carlos Pinto Oliveira
Dawn Abney
Michael Brunt
Wayne Patterson
Greg Frank
Jim Sackett
Davide Giana
Paulo Binda
Emiliano Broggi
Marco Onorato
Cardani Carlo
Pasquele Franzese
Diana Gordon
Janet R Schofding
Rick Lane
Lorinda Wright
Jamie Lewis
Judy Barnett
Martha Maxwell
Stacy LeBlanc
Deborah Donohue
Paula Clifford
Cindy Buckmaster
Diana Li
Ashley Weaver
Jayne Mackta
Giordana Bruno Michela
Agata Cesaretti
Enrico Migliorini
Kim Froeschl
Daniele Mangiardi
Liz Guice
Myrian Morato
Patricia Zerbini
Michael Savidge
Jefferson Childs
Kimberley Phillips
Anne Deschamps
Dario Parazzoli
Robert M. Parker
Agnes Collino
Alberto Ferrari
Igor Comunale
Kristina Nielsen
Marco Delli Zotti
Megan Wyeth
Carolina Garcia de Alba
Andrea Devigili
Erin Severs
Patricia Foley
Mary Zelinski
Alison Weiss
Savanna Chesworth
Christy Carter
Joel Ortiz
William Levick
Lauren Renner
David Andrade Carbajal
Federico Simonetti
Daniele Melani
Dwayne Godwin
Howard Winet
Jeremy Bailoo
Stephan Roeskam
Mary-Ann Griffiths
Carolyn Pelham
Francesca Digiesi
Nicola Bordin
Dianna Laurent
Joe Erwin
Jennifer Picard
Vicki Campbell
Erin Vogelsong
Bob Schrock
Silvia Armuzzi
Elizabeth Harley
Wendy Jarrett
Barbara Rechman
Daria Giovannoni
Patricia Atkins
Scott Hall
Vickie Risbrough
Liam Messin
Brian McMillen
John Meredith
Aleksandra Gondek
Tehya Johnson
Nancy Marks
Leonardo Murgiano
David Markshak
William Horn
John J Eppig
Mila Marvizon
David Robinson
Steven Lloyd
Shari Birnbaum
Matthew Jorgensen
Karen Maegley
Barry Bradford
Corinna Ross
Stephen Harvey
Deborah Otteson
Bette Cessna
Steven Wise
Michael Conn
Gregory Cote
James MacMillan
Suzanne Lavalla
Lisa Peterson
Jennifer Perkins
Richard Nyhof
Beth Laurent
Gabriele Lubach
Michele A. Basso
Cindy Chrisler
Jian Wu
Mahmoud Loghman-Adham
Claire Edwards
Daniel T. Cannon
Emil Venz
Hyeyoung Kim
Jon E. Levine
Ken Linder
Kathy Linder
Matt Thornton
Margaret Maloney
Regina Correa-Murphy
Kristine Wadosky
Victor Lavis
David Fulford
Josiane Broussard
Fabio De Maio
Rachel J. Smith, PhD
Trinka Adamson
Cobie Brinkman
Emily Slocum
Michael J. Garrison
Tom Greene
Jenny Kalishman
Marcia Putnam

Join Pro-Test for Science to End the Age of Terror!

We will be counter-demonstrating:

When: February 15, 10:15am sharp!
Where: Franz Hall Lobby @ UCLA (near Hilgard and Westholme)  http://maps.ucla.edu/campus/


Somewhere in the United States, there is a scientist reporting data that says that humans are causing the world to warm at an alarming rate. In return, he receives email death threats.

In another case, a pediatrician is harassed and shouted at because, in her expert view, vaccinations are necessary and safe for children and prevent a whole range of childhood diseases.

And then there is the medical researcher who is threatened because he has been responsible for generating embryonic stem cells and suggesting they might be a cure for Alzheimer’s disease.

Finally, there is the law professor who is nearly killed by a bullet because of his views on Middle East politics.

These are not hypothetical situations. This is the real work of a growing number of fanatics living on the fringe of society.  The anger generated by their failure to make a persuasive argument to the public, amplified by their sense of self-righteousness, is sufficient to convince them they are entitled to use violence to achieve their goals.

One of the most salient examples of this type of fanaticism is exhibited by animal rights extremists.

Researchers, professors and students at UCLA have been the targets of terror tactics for so long that it’s easy to forget the history or to ignore the fact that it continues today. The present wave of criminal attacks goes back more than a decade.

Here is a very short summary:

Back in 2003, Neurobiology Professors John and Madeleine Schlag saw their property vandalized at a home demonstration. “The way it proceeded … we felt that the door was going to be kicked in,” they commented in an interview.

In 2006, Professor Lynn Fairbanks was targeted with an incendiary device. It turned out animal extremists got the wrong address and planted the firebomb at the doorstep of an elderly neighbor.

In June 2007 another firebomb was placed under the vehicle of Professor Arthur Rosenbaum, who dedicated his life to pediatric ophthalmology by helping children with strabismus. His wife later received a threatening note which told her to persuade her husband to stop his research or “…we will do exactly what he does to monkeys to you.”

In 2007, Professor Edythe London finds her home flooded by animal rights extremists, and received the threat, “water was our second choice, fire was our first.”  She decided to reply by explaining, in a thoughtful OpEd in the LA Times, the reasons for her work.

In 2008, the UCLA community saw once again an incendiary device char the front door of a home owned by a Professor, the vandalism of three vehicles parked outside the home of a postdoctoral student, and the firebombing of a university commuter van.

Then, in 2009, the car of Professor David Jentsch, parked in his driveway, is set on fire while he was sleeping at home.  He subsequently received a letter containing razor blades and a threatening note that fantasized about sneaking up behind him and cutting his throat. He replied with an open letter to these coward terrorists.

Animal rights extremists torched my car in 2009

Car arson at Professor Jentsch’s house. The Animal Liberation Brigade would claim responsibility for the attack 2 days later.

Though these events are graphic, frightening and chilling, they were neither the beginning, nor the end of the violence propagated against us. These criminal vandalistic acts have been accompanied by monthly “home demonstrations,” conducted by screaming mobs who shout obscenities and taunt researchers from the street.  These assaults on our residences are the essence of violence, aiming to turn safety and security into fear and panic.

These groups (which have organized under a range of monikers: “See You in the Streets”, “FUCKHLS” and [now, quite ironically] “Progress for Science”) claim that their demos are educational, a form of genuine activism or simply “prayer vigils” that honor the lives of animals involved in research. No one should be deceived. They are little more than liars and thugs whose goal is to inflict fear in researchers and our neighbors, and their own words show this to be true.

Over the years, these demonstrations have typically been followed up by “wrap-ups” written by the protesters, right alongside the publication of “anonymous communiques” that include direct threats and patent lies about our research. Their words show them for who they really are.

On Feb 19 2011, this group (including members who still protest to this day), marched out front of the home of Dr. London. Knowing that she is the daughter of Holocaust survivors, they cut right to the chase:

“… Edythe London – aka “Hitler with a cunt”. She does things to primates that even Dr. Mengele didn’t do to Jews, gays, gypsies and other disenfranchised people in Europe. Though she claims to be Jewish, she must be somehow related to Hitler, since she uses the same methods of hideous deprivation, abuse and killing of our closest living relatives, non-human primates.” (WARNING: the following link takes you to an AR website: Click here for the full post).

On another occasion, this group marches in front of Professor Jentsch’s home, with a reporter from Los Angeles Magazine in tow. The reporter is writing a feature on the struggle between researchers and activists. Even with the scrutiny of the press, they can’t help themselves:

“David Jentsch—you cocksucking bastard!”
“David Jentsch—you sick pervert, I hope you 

And later, the leader of the group whispers to the reporter:

“Wasn’t Jentsch’s car burned or something?” Then, above the din of chants, she adds, “I don’t know how to put this—I only wish he were in it.”      

That kind of language is hardly surprising when you see the general pattern of behavior during these aggressive and hateful demonstrations. An April 2010 demonstration is summarized here:

When we attempted to open up dialogue on the science and ethics of animal research, including the points of view of animal rights activists, by organizing a discussion panel at UCLA, the only thing we got in return from these activists was more threats:

Activists protested him [Dario Ringach] and will continue to protest him because he has become a defacto leader of the pro-vivisection group ‘PRO-TEST‘ where he now speaks out to anyone who will listen regarding the need to torture and kill animals, especially primates. In fact, he is one of the speakers who will be at the “discussion” panel February 16th at UCLA’s Covel Commons. 

All the neighbors came out to see what was going on and activists filled them in on Dario’s long, atrocious history of abusing, torturing and killing primates and now his NEW job of going around PROMOTING it! The neighbors were actually very supportive of the activists and in fact, one neighbor told an activist and we quote, “I’ll be watching that asshole; I don’t want that piece of garbage and his family living in this neighborhood. He ought to be experimented on.” 

They went as far as targeting his children because of his pro-research stance (here and here).

So do not believe a single word when extremists argue that what they want is dialogue.  Here is their rephrasing of the truth:

When attempts at dialogue and peaceful attempts to make change and alleviate suffering are frustrated, some activists are willing to use more forceful means to help animals. North American Animal Liberation Press correspondent Camille Marino makes an apt comparison: “LA citizen Richard Ramirez, known as the “Nightstalker”, was a cold, sadistic and violent serial murderer — his behavior was eerily similar to that of any vivisector. While he was actively inciting an atmosphere of terror, the media relentlessly covered the newsworthy developments. While vivisectors like J. David Jenstch and Dario Ringach are active, the animal liberation networks are committed to relentlessly cover their sociopathic reign of terror. When average citizens finally apprehended Ramirez, they beat him mercilessly for his crimes. Jentsch and Ringach have earned the right to fear retaliation for their crimes. … They each make a potent case for individuals who need to be stopped by any means necessary.”

How have scientists reacted?  In a couple of occasions the UCLA community conducted campus rallies in support of our faculty and the fantastic work done at our university.  The message was that we are not going to tolerate such attacks any more.

So it should not come as a surprise to anyone that after a decade of harassment, intimidation and threats,  we have decided to mount counter-demonstrations when these animal right terrorists show up at our homes.

These activists now have the shameless audacity to play the victim of this encounter. Incapable of understanding the message, they are now recruiting more misguided individuals to join them in their fanatical crusade and come back to harass us at our homes on February 15th.

We will be there to meet them once more and convey one simple message,

We are not going to take it anymore!

Please join us to defend UCLA, our science, and the hope for medical advances and new cures.

When: February 15, 10:15am sharp!
Where: Franz Hall Lobby @ UCLA (near Hilgard and Westholme)  http://maps.ucla.edu/campus/

Join us to end the decade-long age of terror at UCLA!

David Jentsch and Dario Ringach

Reflections of an Animal Rights Arsonist

A sympathetic judge sentenced confessed arsonist Rebecca Rubin to 5 years in prison for her role in four fire bombings in the name of the Animal Liberation Front and the Earth Liberation Front.  The judge also ordered Rubin to make monthly restitution payments totaling $13 million. Rubin was on the run for 6 years before turning herself in.

Convicted animal rights arsonist, Rebecca Rubin

Convicted animal rights arsonist, Rebecca Rubin

Seeking clemency in a letter to the judge, Rubin offered enligthened reflections about her past behavior:

“The years I spent leafleting, trail building, working in animal sanctuaries, peacefully protesting, blockading, hunger striking, canvassing, and letter writing, all seemed to have accomplished nothing.  I let my frustration and desperation override my ability to make well-reasoned decisions; to maintain the calm and patience required of slow, sustained struggle; and I failed to seriously consider the negative consequences of my actions in both the short and long term.” 

“Although at the time I believed my only motivation was my deep love for the earth, I now understand that impatience, anger, egotism and self-righteousness were also involved”

“In retrospect, I recognize how immature my actions were. I am now forty years old and have had much time to reflect on and consider the consequences of my choices, and my thinking has become much more coherent. I know now that my actions were not merely destructive of inanimate objects but were also harmful to other, feeling human beings. […] I chose to disconnect from them emotionally and was thus able to dehumanize and vilify them.  In doing so, I thoughtlessly disregarded the adverse emotional and psychological impact that would result from my actions.”

“I would never have forgiven myself had anyone been injured, or worse, in the fires, and l am disappointed in myself that I took such a risk. I realize that instead of causing damage and destruction, I could have been advocating for, or nursing, or otherwise helping animals, while at the same time retaining my compassion for people”

Indeed, damaging decades of scientific research, firebombing homes, blowing up cars, and straightforward threats and harassment are not truly directed at inanimate objects, they are attacks that have the specific goal to harm people to advance a political cause. The judge had simply words for Rubin on this issue:

“That kind of damage is not how democracy works or how true change is accomplished.”

Rubin’s self-revelation and the judge’s lesson stand in sharp contrast with the words of other animal rights extremists, such as Carol Glasser, of the mis-named group “Progress for Science”, who apparently holds the view that an activist’s frustration is good reason to justify criminal behavior when she says:

Whatever we are doing as a movement is not working, it is not saving animal lives. I think it is a waste of our time to demonize people who put their own life, their own  safety, their own health, and their own freedom at risk, because they can’t imagine another way to help the animals.  It is total bullshit of us, to point a finger and demonize them.

Carol Glasser of "Progress for Science"

Carol Glasser of “Progress for Science”

That is, of course, exactly how Rubin felt.  And today, even Rubin would disagree with these awful words.  One can only hope the impatient, angry, egotist and self-righteous animal rights extremists of today will learn something from those of yesterday.  Harassment, intimidation and violence are not the way to advance a political cause.  They would be wise to learn from the mistakes of others before they make their own and are admonished with the same words — that is not how democracy works.

We will be counter-demonstrasting!

When: February 15, 10:15am sharp!
Where: Franz Hall Lobby @ UCLA (near Hilgard and Westholme)  http://maps.ucla.edu/campus/


Guest Post: Characterising high fructose corn syrup self-administration in laboratory rats

It’s January, and across the country millions of people have promised themselves that they will eat less, loose weight and become healthier. But why do some people eat more than others? No matter what they try there seems to be no way to stop their overeating. Public education is a powerful tool to combat some of these issues but what happens when it turns into an addiction? It is challenging to provide accurate information when food addiction is a little studied field. In an effort to answer these questions scientists can use laboratory rodents to explore neurobiological mechanisms involved in relapse to drug-seeking behavior, comorbid mood and substance dependence disorders, as well as perseverative reward seeking. These complex answers cannot be solely obtained though human patients because the physiological and psychological mechanisms that influence food addiction are not fully understood.

AnneMare Levy is a PhD student and Francesco Leri is an Associate Professor of Neuroscience and Applied Cognitive Science in the Department of Psychology at the University of Guelph. In the article below these scientists explain how and why the development of a new animal model to understand the addictive properties of some foods is necessary and how its use can begin to answer some of these questions. They believe that through studying rats their findings could lead to novel pharmacological interventions for obese individuals that could help them selectively reduce intake of unhealthy foods.

The views expressed below are that of the authors alone and do not necessarily reflect the views of her employer or institution.

Overconsumption of foods high in sugars and saturated fats is an important contributing factor to the modern epidemic of overweight and obesity1, which are leading causes of metabolic disorders and cardiovascular diseases2. It is therefore important to understand why patterns of excessive food intake develop and persist despite the negative health consequences. Considerable evidence supports the hypothesis that, for some people, addiction to food may motivate these behaviours3-4. In fact, behavioural and neurobiological similarities between obesity and drug dependence support the “food addiction” hypothesis5-8 and studies in both humans and laboratory animals have identified a variety of biological and behavioural indicators of “food addiction”9-12.

The food addiction hypothesis suggests that similar to drugs of abuse, particular foods should reinforce behaviours that lead to their consumption. Therefore, to assess the addictive potential of such foods, we adapted procedures commonly used for studying the reinforcing properties of drugs of abuse (i.e. operant intravenous drug self-administration) to the investigation of operant self-administration of sweet solutions delivered directly into the mouth of rats. To this end, an intraoral cannula was surgically implanted13 into the cheek of rats and the animals were subsequently trained to press a lever to voluntarily receive a test solution directly into their mouth; hence the term intraoral self-administration. The sweet solution selected for testing was high fructose corn syrup (HFCS) because, although controversial14, there is evidence that HFCS may be linked to the modern epidemic of obesity15.


The disadvantage of requiring minor surgery to employ this procedure is offset by several advantages that make intraoral self-administration in rats optimal for studying the reinforcing properties of sweet solutions. First, an operant response (i.e., pressing a lever) is required to obtain an infusion and therefore it is possible to modify the schedule regulating the relationship between response requirement and delivery of intraoral infusions. Hence, by employing a progressive ratio (PR) schedule16, whereby more lever presses are required to get more sweet solution, it is possible to assess how much an animal “wants”17 the next infusion and by employing a continuous schedule of reinforcement, whereby each lever response is reinforced, it is possible to measure total intake, escalation of intake, and the development of bingeing behaviour.  Second, intraoral self-administration allows testing of any concentration and any volume of any water-soluble food additive. The importance of controlling and manipulating concentration/volume ratios is mandatory in experiments where intake can be modulated both by the caloric value of a solution (i.e., nutrient-specific satiety) and by how much of that solution can be consumed within a given period of time (i.e., fullness)18. Third, intraoral self-administration shortens the delay between the operant response and the delivery of the primary reinforcer, a factor that plays an important role in the acquisition and maintenance of operant behaviour19-21. Finally, this procedure allows for the delivery of passive intraoral infusions of controlled quantities of the test solution.  This makes it possible to measure orofacial responses of “liking” (objective hedonic reaction such as tongue protrusions)22 as well as administer priming infusions23 of the test solution prior to tests of reinstatement of sweet-seeking behaviour.

The objective of this study was to characterize HFCS self-administration behaviour in laboratory rats. It was important to establish a reliable animal model of self-administration because it will allow future studies to identify and manipulate the neurobiological substrates that are responsible for the escalation and maintenance of excessive food intake. Moreover, using this animal model, the rats will be able to self-administer solutions for extended periods of time (i.e. months) to establish how sweeteners, such as HFCS, may contribute to the development of metabolic disorders.  For all experiments, rats were surgically implanted with an intraoral cannula while under an anaesthetic. Post-operative care included administering analgesic, daily flushing of the cannula with an anti-bacterial solution as well as closely monitoring weight gain and food intake. Following recovery, rats received one 3-hour self administration session per day, whereby, rats were placed into a standard operant chamber and trained to lever press to receive intraoral infusions of different concentrations of HFCS (8%, 25%, and 50%) on either continuous or PR schedules of reinforcement, as previously described.

It was found that the behavioural profile of rats responding for HFCS is similar to the pattern of intake observed when rats self-administer drugs of abuse24-25. Using intraoral self-administration, it was established that on a continuous schedule of reinforcement, rats acquire and maintain intraoral self-administration of a wide range of HFCS concentrations (8%, 25% or 50%), and that rats adjust their self-administration behaviour according to the different concentrations (i.e., rats self-administer twice as much a 25% solution than a 50% solution)13.  Furthermore, higher concentrations of HFCS engender higher responding on the PR schedule of reinforcement, suggesting that increasing the HFCS content likewise increases the reinforcing value of the solution. The relationship between operant responding and HFCS concentration on continuous and progressive ratio schedules is similar to the dose-response relationships observed when rats self-administer drugs of abuse24.

It was further noted that total intake of 25% HFCS escalated over three weeks of testing, possibly reflecting the development of “bingeing” behaviour9,13. In fact, after a week of self-administration, rats displayed a clear period of elevated intake during the initial 90 minutes of each self-administration session and this “loading” increased in magnitude over the weeks of training. This effect is reminiscent of escalation of drug intake and increased loading that are observed when rats have prolonged and/or repeated access to drugs of abuse26.

The results of these experiments also indicated that HFCS is reinforcing because of its caloric content. Even though 0.1% saccharin (a non-caloric sweetener)27 and 25% HFCS produce similar hedonic reactions (i.e. the perceived palatability of the two solutions is similar in tests of taste reactivity17), 0.1% saccharin could not maintain self-administration at the same level that 25% HFCS. Moreover, when substituted for HFCS, a wide range of saccharin concentrations (0.01%, 1.0%, and 10%) significantly reduced self-administration behaviour, indicating that HFCS reinforcement is largely determined by its caloric content rather than its palatability.

Taken together, these experiments indicate that intraoral infusion of HFCS reinforces lever-pressing in rats, and this behaviour was maintained primarily by the caloric content and not the palatability of the solution made available for self-administration.  In these rats, stable self-administration was maintained for up to three weeks, it was concentration-dependent, and rats developed a tendency to “binge” on HFCS at the start of sessions. Using intraoral self-administration, future studies should investigate the possibility that HFCS engenders other “addictive-like” behaviors, and whether escalation of HFCS self-administration can be causally linked to the development of metabolic changes (i.e., weight gain, insulin resistance) associated with obesity and type-2 diabetes.

AnneMarie Levy & Francesco Leri

University of Guelph

University of Guelph

Department of Psychology, NACS


1. Barry D, Clarke M, Petry NM (2009) Obesity and Its Relationship to Addictions: Is Overeating a Form of Addictive Behavior? Am J Addict 18: 439-451.

2. World Health Organization (2013) Obesity and overweight Fact sheet N°311. Available: http://www.who.int/mediacentre/factsheets/fs311/en/index.html#. Accessed 20 June 2013.

3. Davis C, Carter JC (2009) Compulsive overeating as an addiction disorder: a review of theory and evidence. Appetite 53: 1-8.

4. Ifland JR, Preuss HG, Marcus MT, Rourke KM, Taylor WC, Burau K, Jacobs WS, Kadish W, Manso G (2009) Refined food addiction: a classic substance use disorder. Med Hypotheses 72: 518-526.

5. Avena NM, Bocarsly ME, Hoebel BG, Gold MS (2011) Overlaps in the nosology of substance abuse and overeating: the translational implications of “food addiction”. Curr Drug Abuse Rev 4: 133-139.

6. Volkow N, Wise RA (2005) How can drug addiction help us understand obesity? Nat Neurosci 8: 555-560.

7. Fortuna J (2012) The Obesity Epidemic and Food Addiction: Clinical Similarities to Drug Dependence. J Psychoactive Drugs 44: 56.

8. Levy AM, Salamon A, Tucci M, Limebeer CL, Parker LA, Leri F (2012) Co-sensitivity to the incentive properties of palatable food and cocaine in rats; implications for co-morbid addictions. Addict Biol:  doi: 10.1111/j.1369-1600.2011.00433.

9. Avena NM, Rada P, Hoebel BG (2008) Evidence for sugar addiction: behavioural and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32, 20-39.

10. Gearhardt AN, Davis C, Kuschner R, Brownell KD (2011) The addiction potential of hyperpalatable foods. Curr Drug Abuse Rev 4: 140-145.

12. Johnson PM, Kenny PJ (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci 13:  635-644.

13. Levy AM, Limebeer CL, Ferdinand J, Shillingford U, Parker LA, et al. (2014) A novel procedure for evaluating the reinforcing properties of tastants in laboratory rats: operant intraoral self-administration. JoVE: in press.

14. White JS (2008) Straight talk about high-fructose corn syrup: what it is and what it ain’t. Am J Clin Nutr. 88: 1716S-1721S.

15. Bray GA, Nielsen SJ, Popkin BM (2004) Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity, Am J Clin Nutr 79: 537-543.

16. Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66: 1-11.

17. Berridge, K. C., & Robinson, T. E., Parsing reward. Trends in Neuroscience 26 (11), 507-501(2003).

18. Houpt, K. A. Gastrointestinal factors in hunger and satiety. Neuroscience and Biobehavioural Reviews 6 (2), 145-164 (1982).

19. Panksepp, J. & Trowill, J. A. Intraoral self injection: I. Effects of delay of reinforcement on resistance to extinction and implications for self-stimulation. Psychonomic Sciences 9 (7), 405-406 (1967)

20. Mazur, J. E. Effects of rate of reinforcement and rate of change on choice behaviour in transition. Journal of Experimental Psychology 50 (2), 111-128 (1997).

21. Samaha, A. N., & Robinson, T. E. Why does the rapid delivery of drugs to the brain promote addiction? Trends in Pharmacological Sciences 26 (2), 82-87 (2005).

22. Berridge, K. C., & Kringelbach, M. L. Affective neuroscience of pleasure: reward in humans and animals. Psychopharmacology (Berl) 199 (3), 457-480 (2008)

23. Shaham, Y., Shalev, U., Lu, L., De Wit, H., & Stewart, J. The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168 (1-2), 3-20 (2003).

24. Deroche-Gamonet V, Belin B, Piazza PV (2004) Evidence for addiction-like behaviour in the rat. Science 305: 1014-1017.

25. Carroll ME, Lac ST (1997) Acquisition of IV amphetamine and cocaine self-administration in rats as a function of dose.  Psychopharmacology 129: 206-214.

26. Ahmed SH, Koob GF (1998) Transition from moderate to excessive drug intake: change in hedonic set point. Science 282: 298-300.

27. Miller SA, Frattali VP (1989) Saccharin. Diabetes Care 12: 74-80.

Visionary Science: Gene therapy saves sight thanks to animal research

Yesterday the BBC News and Guardian Newspaper reported that a team led by surgeon Professor Robert Maclaren at the Oxford Eye Hospital had succeeded in using gene therapy to halt the decline in vision in six patients with the progressive eye disorder choroideremia.

All six patients were taking part in a clinical trial, and what was especially exciting was the sustained improvement in vision in the two patients whose vision had deteriorated the most. This is great news for the patients themselves, and as the technique is likely to be applicable to many different genetic eye disorders it is also good news for many millions of people who may benefit in future. It is also an excellent example of how years of research in mice, dogs and monkeys can lead to an important clinical advance.

Choroideremia is caused by a defect in the CHM gene, which encodes the Rab escort protein 1 (REP1), and lack of this protein leads to gradual degeneration of the retinal epithelium layer  (RPE) and rod photoreceptor cells in the eye, causing a progressive decline in vision that usually starts with night blindness and loss of peripheral vision, and eventually leads to total blindness.

To halt this decline Professor Maclean’s team used a vector  based on a modified adeno-associated virus serotype 2 (AAV2) which could express the healthy CHM gene in the eye and produce REP1.  Why did they choose AAV2 out of all the potential virus vectors available? The Lancet paper reporting on this trial cites a key study published in the Journal of Molecular Medicine in  2013* by Professor Maclaren and colleagues, which describes the development and evaluation of the vector used in the trial. In their introduction and discussion they discuss the rational for choosing the AAV2 vector:

With a functional fovea, safety with regard to avoiding a vector-related inflammatory reaction is of paramount importance. Two recent clinical trials had demonstrated that serotype 2 adeno-associated viral (AAV2) vectors have no long-term retinal toxicity when administered at the dose range 1010–1011 genome particles [12, 13]. Importantly, in addition to transducing the RPE, AAV2 is also known to target rod photoreceptors efficiently in the non-human primate [14], providing the ideal tropism for a CHM gene therapy strategy.

… Although one might argue that other serotypes such as AAV8 may be more efficient in targeting photoreceptors, AAV2 with the CBA promoter remains the gold standard for retinal transduction as evidenced by the sustained vision in Briard dogs treated with AAV2 vector over a decade ago [35].

12. Cideciyan AV, Aleman TS, Boye SL, Schwartz SB, Kaushal S, Roman AJ, Pang JJ, Sumaroka A, Windsor EA, Wilson JM, et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci U S A. 2008;105:15112–15117. doi: 10.1073/pnas.0807027105.  13. Jacobson SG, Cideciyan AV, Ratnakaram R, Heon E, Schwartz SB, Roman AJ, Peden MC, Aleman TS, Boye SL, Sumaroka A, et al. Gene therapy for Leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Arch Ophthalmol. 2011;130:9–24. doi: 10.1001/archophthalmol.2011.298.  35. Bennicelli J, Wright JF, Komaromy A, Jacobs JB, Hauck B, Zelenaia O, Mingozzi F, Hui D, Chung D, Rex TS, et al. Reversal of blindness in animal models of Leber congenital amaurosis using optimized AAV2-mediated gene transfer. Mol Ther. 2008;16:458–465. doi: 10.1038/sj.mt.6300389.

So which two clinical trials are they referring to? Well, as you can see from the references they are referring to the successful trials of gene therapy for Leber Congenital Amaurosis (LCA)whose development we discussed on this blog back in 2009. As McLaren and colleagues point out, the sustained expression of RPE65 and long-term recovery of vision in the Briard dog model of LCA was a key factor in their decision.  The observation that AAV2 could be used to drive gene expression in rod photoreceptors was also important, as Maclaren and colleagues had previously generated a genetically modified mouse model of Choroideremia by knocking out CHM expression in the eye, and established that in Choroideremia the degeneration of rod photoreceptors is independent of the degeneration of the RPE, so it is crucial that the vector can drive healthy gene expressed in both the rods and RPE.

To develop the vector Maclaren and colleagues first compared the efficiency of 3 different promoters (promoters are sections of DNA that promote gene expression) -AAV2/2-EFS, AAV2/5-EFS and AAV2/2-CBA  - in driving expression of the CHM gene when added in vitro in a variety of dog and human fibroblast (connective tissue cell)  lines in an AAV2 vector, and then when injected in vivo in the retinas of healthy mice. These studies demonstrated that the most efficient AAV2 vector – named AAV2/2-CBA-REP1 – could drive expression of high levels of REP1 in both the RPE and rod photoreceptors of mice. After identifying the most effective AAV2 vector for expressing REP1  they assessed whether it was capable of expressing REP1 in isolated human retina’s obtained post-mortem from human donors, which it did. They then evaluated whether there as any toxicity associated with expressing REP1 in vivo in the retina of healthy mice, finding that AAV2/2-CBA-REP1 was non-toxic even when injected into the retina at high doses, and that it did not adversely affect vision.

Following these studies the question remained; would injection of AAV2/2-CBA-REP1 stop deterioration of vision in choroideremia?

To address this Maclaren and colleagues turned again to the genetically modified mouse model of choroideremia thay they had created earlier. Injection of the vector into the retinas of these CHM mice:

Subretinal injections of AAV2/2-CBA-REP1 into CHM mouse retinas led to a significant increase in a- and b-wave of ERG responses in comparison to sham injected eyes confirming that AAV2/2-CBA-REP1 is a promising  vector suitable for choroideremia gene therapy in human clinical trials.”

In other words the therapy worked in the mouse model of choroideremia, paving the way for the successful clinical trial reported this week.

This new therapy is another example of the importance of animal studies to the development of new clinical techniques and therapies, but also highlights the fact that medical science is a long game, with basic and applied research conducted more than a decade, even two decades,  ago being crucial to this week’s exciting announcement. This is something policy makers would do well to remember!

Paul Browne

* While this paper was published in 2013, the work it reports was completed several years earlier, before the clinical trial was launched in 2011.

1) Tanya Tolmachova, Oleg E. Tolmachov, Alun R. Barnard, Samantha R. de Silva, Daniel M. Lipinski, Nathan J. Walker, Robert E. MacLaren,corresponding author and Miguel C. Seabra “Functional expression of Rab escort protein 1 following AAV2-mediated gene delivery in the retina of choroideremia mice and human cells ex vivo”  J Mol Med (Berl). 2013 July; 91(7): 825–837. PMCID: PMC3695676

Speaking of 2013: A year in summary

As another year for Speaking of Research has passed it seems only appropriate to spend a moment looking back.

Animal research is important because of its contributions to human and animal health. In 2013 we saw a promising clinical trial for epidermolysis bullosa (EB), the development of pluripotent human stem cells from cloned human skin  cells, a new diabetes treatment developed from the Gila Monster, the first transplanted liver that had been preserved at room temperature, and a gene therapy for hemophilia A in dogs. Then, of course, the Nobel Prizes reminded us of the value of animal research once again. No doubt 2014 will continue to push the limits of medical science, with animal research continuing to play a vital role.

Sadly, despite the many successes of animal research, animal rights extremism was in the rise in Europe in 2013, particularly in Italy. In response to an attack on the University of Milan, over 5,000 people signed the Basel Declaration’s call for solidarity. There was hope, with the rise of Pro-Test Italia, who held their first rally in June 2013. Sadly, in August 2013, the Italian Chamber of Deputies passed amendments which would limit some aspects of research in Italy. Just before the New Year, Caterina Simonsen, an Italian veterinary student, received a string of abuse for posting a message on Facebook about animal research is keeping her alive (expect us to write more on this in the coming days). See her message below:

Translation: ""I am 25 thanks to genuine research that includes experiments on animals. Without research, I would have been dead at nine""

Translation: “I am 25 thanks to genuine research that includes experiments on animals. Without research, I would have been dead at nine”

In our blog, we spent a fair bit of time looking at the process of drug development and the regulations involved. In 2013, the UK transposed EU Directive 2010/63/EU, updating and harmonising animal research regulation in the EU, into UK law. The EU released its 2012 statistics on animal research. We wrote about how research progresses from an idea to a study and clarified differences between “animal testing” and “animal research”. Expect us to continue such posts.

Animal rights activism also persisted through 2013. PETA’s ongoing campaign against UW Madison involved celebrities crashing meetings (among other celebrity shenanigans), creating video games where characters must beat up scientists (also see PETA’s pathetic defence), putting out expensive bus adverts condemning UW Madison, and generally ignoring all inspections that found no wrongdoing by the University of Wisconsin Madison. We have discussed PETA in other contexts, such as the hypocrisy of one of scientific consultants, Dr Laurence A. Hansen. Activity by groups like PETA made us look long and hard about what makes a good response to animal rights allegations.

As usual there was much debunking of animal rights misinformation. Prof Robin Lovell-Badge provided us with two posts which dealt with statistics which are misused by members of the animal rights community – one on the FDA’s drug failure rates, and a second on the success rate of animal research. Mark Wanner of Jackson Labs explained why failures in some animal models do not mean failures in others. We spent time debunking the Huffington Post diatribes of Aysha Akhtar, twice, as well as putting the story straight on the history of diabetes, and debunking the myths of a new UK activist group, For Life on Earth.

We had a variety of guest posters this year which included Kelly Walton explaining why she became a laboratory animal veterinarianPeter Wright discussing UK regulations, and Brian Anderson explaining how animal research was saving the life of his daughter Liviya, who suffers from aplastic anemia. We will be hoping for many more guest posts in 2014, and encourage people to write about their research in the Speaking of Your Research series.

Thank you to all who have followed us this year. Please continue to help us, reading and sharing our writings, in the hope we can make 2014 the best year for animal research outreach yet.

Speaking of Research

Cancer Immunotherapy: A breakthrough made through animal research

The prestigious journal Science has published its top 10 Breakthroughs of the Year 2013, and top of the list is a development that promises to have a huge impact on the lives of millions of people in the coming decades – Cancer Immunotherapy.

The article focuses on three particular therapies that have recently shown great
promise in clinical trials – chimeric antigen receptors, anti-CTLA4 therapy, and anti-PD1 therapy – all of which highlight the fact that his is a field
where animal research is making an absolutely critical contribution.

Regular readers will remember that we discussed how studies in mouse xenograft models of acute lymphoblastic leukaemia (ALL) contributed to the development of chimeric antigen receptor (CAR) therapy that has now shown very promising results in clinical trials against ALL and Chronic Lymphocytic Leukemia, and as Science reports is now being evaluated against many other cancers.

The Science news article on cancer immunotherapy notes that a mouse study published in Science provided key evidence that antibodies that target the protein CTLA-4 – a receptor that acts to suppress the activate the T cells of the immune system – can increase the effectiveness of the immune system in eliminating tumor cells.

Similarly – as discussed in this open access review – the development of anti-PD1 immunotherapy started when was found that PD-1 knockout mice developed autoimmmune disorders, indicating that PD-1 played a role in regulating the immune response. Subsequent preclinical studies in a variety of mouse cancer models demonstrated that administration of antibodies against PD-1 greatly increased the ability of the immune system to attack the tumors, even well established and metastatic tumors.

Laboratory Mice are the most common species used in research

Cancer Immunotherapy – adding even more accomplishments to an already impressive CV!

The examples of CAR, Anti-CTLA4 and anti-PD1 therapies highlight how the field of cancer immunotherapy is maturing, but it is a field which has already delivered some important therapies.  For, example back in 2009 Emma Stokes wrote an article for this blog on the discovery and development of Rituximab, a chimeric antibody therapy that has revolutionized the treatment of B-cell cancers such as Non-Hodgkin’s lymphoma. This work has not stood still either, last week the BBC reported on the successful trial of a new chimeric antibody therapy named GA101 in patients with chronic lymphocytic leukaemia (CLL) and other B-cell conditions. GA101 targets the same protein – CD20 – as Rituximab, but was designed to induce a more powerful anti-cancer activity with fewer adverse effects. The abstract of the 2010 paper reporting on the preclinical research leading to the development of GA101 highlights the role played by studies in mouse models of cancer and in monkeys.

CD20 is an important target for the treatment of B-cell malignancies, including non-Hodgkin lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall survival in patients. Here, we report the development of GA101 as the first Fc-engineered, type II humanized IgG1 antibody against CD20. Relative to rituximab, GA101 has increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity in cellular assays and whole blood B-cell depletion assays. In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival. In nonhuman primates, GA101 demonstrates superior B cell–depleting activity in lymphoid tissue, including in lymph nodes and spleen. Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders.”

Of course there are another 9 breakthroughs on Science’s list, and it’s notable that several others involve animal research. One of these is CRISPR, a technique that allows scientists to modify the genes of organisms in vivo or cells in vitro with unprecedented precision, and more recently showed potential in mouse studies as a therapy for genetic disorders. Another is CLARITY, a technique that renders brain tissue transparent so that it can be studied in more detail than has previously been possible, and which joins a range of new techniques that are part of a revolution in neuroscience. Of course there was also the news of the first human stem cells created through cloning by Professor Mitalipov at Oregon Health and Science University, a pioneering scientist whose work we have discussed on several occasions.

The choice of cancer immunotherapy, and indeed of this list as a whole, is a reminder at the end of what has been a very difficult year for science in several countries across the world of the extraordinary progress that is being made, and why it is vital to support the scientists who make it happen. As we bid farewell to 2013 and greet 2014 we can only guess at what new discoveries and breakthroughs the year will bring, but we also know that now – perhaps more than any time in recent history – we need to join together across the world to stand up for science!

Paul Browne

Should chimps have rights?

Steven M. Wise and the Nonhuman Rights Project think so.  In Wise’s own words, chimpanzees are complex, autonomous beings that should have the basic right “to be left alone.”

Seeking a court’s support for their position, the organization petitioned New York courts for writs of habeas corpus on behalf of several chimpanzees they view as being held unlawfully.  Habeas corpus petitions have been used to seek freedom from unlawful detention of human beings.  The Nonhuman Rights Project believes the statute should also apply to non-human animals as well.

In part, the New York statue states that the petition may be brought by:

“A person illegally imprisoned or otherwise restrained in his liberty within the state, or one acting on his behalf […] A judge authorized to issue writs of habeas corpus having evidence, in a judicial proceeding before him, that any person is so detained shall, on his own initiative, issue a writ of habeas corpus for the relief of that person.”

Is it really surprising that this week three different judges denied habeas corpus petitions requested by Wise acting on behalf of these chimpanzees? The courts seem to have interpreted the word “person” as referring to a “human being” and not any other non-human animal.  Wise plans to take the case to appeal.

Steven Wise

This recent attempt by Wise and colleagues to have a non-human animal declared a person ended in a similar way to a PeTA’s suit that argued orcas held at SeaWorld are slaves who should be freed under the 13th Amendment of the Constitution.  In that case, U.S. District Judge Jeffrey Miller dismissed the lawsuit explaining the 13th Amendment pertains to human beings, not animals. Some even found comic relief in PeTA’s approach, asking if the whole thing was nothing more than a publicity stunt.

Wise and other animal rights activists appear obsessed with the goal of seeking rights for non-human animals. Unfortunately, this is not a very effective way to advocate for animal welfare. At the end of the day, and after all the philosophical debate of what basic rights mean and who are legitimate holders, the only question that can be meaningfully answered is the following — How is that we, humans, think we should treat other living beings?

The substantial resources and funds devoted in pursuit of the fixation of animal rights could have had a more real impact if devoted to improve animal welfare directly. In the specific case of chimps, for example, a legal push to outlaw individual, private ownership for non-scientific, non-education purposes would make more sense and be more effective to the animals than publicity-seeking lawsuits.

How we treat animals is a legitimate public debate to be had.  But, as correctly pointed out by Richard Cupp in a rather interesting exchange with Steven Wise this week, the proper object of concern should not be animal rights, but human responsibility.  Accepting that evolution has put humans in a place to be the stewards of our planet, its environment and all living creatures within it, carries a  responsibility that we must accept and face. Understanding this to be the outcome of evolution is not speciesist. In contrast, denying relevant differences between living beings is what leads to the idea that animals should have the right to be “left alone.”  If successful, such move may actually free humans of responsibility and let the animals fend for themselves in an environment increasingly shaped by human activity.