Monthly Archives: October 2010

Defending Against the Inaccurate (and sometimes downright false)

Each year, as the rainy season returns to Oregon, so too does another all-too-predictable event: new claims of abuse leveled against my employer the Oregon National Primate Research Center. Nearly every fall, a small animal rights organization called Stop Animal Exploitation Now (SAEN) fuels their yearly “National Primate Liberation Week” with alarming press releases accusing my institution and others of abuse.

This of course would be understandable and acceptable if the facts were indeed true. However, in my decade of working at one the country’s eight national primate centers, I’ve learned that most SAEN claims are based on misunderstandings or misstatements. Their goal: to cause anger and hatred of scientists attempting to end suffering for both humans and animals.

SAEN’s most memorable headlines over the past few years include:

In 2010: “Group Names OHSU 6th Worst U.S. Primate Lab; Government Records Document Federally Sanctioned Animal Cruelty”

In 2003: “Research Labs Under Reported Primate Use, Broke Law, Says National Watchdog Group”

and perhaps the most alarming:

In 2004: “’Epidemic’ Sweeping Oregon Primate Center, Hundreds of Infant Monkeys Dead, Charges Watchdog Group”

Any person with a pulse will certainly react to such news with anger and disgust. The problem however, is that none of these claims are true.

Just last week, SAEN accused Oregon’s primate center of depriving monkeys of food and water, allowing animals to live in uncleaned cages and forcing animals to live in housing that was too small. Here’s the release: Group Names OHSU 6th Worst U.S. Primate Lab; Government Records Document Federally Sanctioned Animal Cruelty. (SAEN release Oct 19)

SAEN said that federal documents prove their case. So do they? We’ve posted them online and as you can see for yourself…the allegations and the truth hold little resemblance:

SAEN Claim: Animals were deprived of food

What the records show: In one study animals would not receive fruit or vegetables for a short period because they were receiving these vitamins in another form. In another health diet study, animals were given a smaller portion of food. In a third case, animals underwent temporary change in feeding schedules so animals could be trained.  Food was provided after daily training. Clearly SAEN’s claims of starving animals are inaccurate.

SAEN Claim: Animals were forced to live in dirty cages

What the records show: Cage washing was delayed for one day because it would have interfered with the research study. In another case, the cage washing was delayed briefly to limit stress for the animals.

SAEN Claim: Animals were forced to live in housing that was too small.

What the records show: Monkeys were temporarily placed in a slightly smaller group housing to better encourage socialization.

While reasonable people can debate what is truth and what is a lie, few can deny that at best, SAEN’s allegations are a gross exaggeration of the facts.

As for our previous experiences in responding to SAEN’s inaccurate claims:

In 2003, SAEN claimed that the Oregon primate center was lying about the number of animals in its care. Read the claims for yourself.

Again, not true.

SAEN leveled this claim by juxtaposing two reports to two separate federal agencies. One report contained in the NIH Annual Report lists all animals at the Oregon primate center. The other report, the USDA Annual Report of Research Facility lists all animals involved in research. Because a large number of our animals live outdoors in one-acre breeding habitats (meaning they are not used in research), these two reports clearly measure two entirely different things.

Of course SAEN’s allegation of fraud is very serious, but in this case it was based on either a complete misunderstanding, or a deliberate misrepresentation of the facts

In 2004 SAEN leveled its most incredible charge. That year, SAEN reported that an epidemic had killed almost 400 monkeys at the Oregon primate center.

How did this happen?

The simple answer: It didn’t.

SAEN based this claim on an annual census report provided to the National Institutes of Health annually.

Here’s the report belowIn making it’s claim, SAEN pointed to column 5 of the report – a reduction of 394 infants that year. So where did these animals go? See the additions just two columns to the left. 304 of these animals became adults. The rest were temporary transfers to other locations in and outside of the center and as for SAEN’s epidemic, it never occurred.

So when SAEN is made aware of their errors are they quick to set the record straight? Based on the fact that all of this information remains posted on their Web site – clearly not.

Of Course Oregon’s primate center is not alone in combating SAEN’s frequently inaccurate claims.

Speaking of Research has written about this issue on many previous occasions.

So why are these many untrue allegations such a serious issue for health research institutions such as ours? Because, many times these unverified claims are reported as fact meaning that those who wish to mislead the public are often quite successful. We should all be disturbed when the media reports only one side of the issue and places the burden of proof solely on health researchers.  The validity of claims made by organizations such as SAEN deserves the same sort of skepticism and study as our responses.

So, who will pay the ultimate price for all of this inaccuracy? Everyone.  Every single person on the earth has benefited from animal studies. Thanks to animal-based research, we have vaccines, medications and new surgical approaches. But despite these successes, SAEN and others want us to reject this important method for treating disease by repeatedly bombarding the public with inaccurate claims of abuse.

Hopefully Speaking of Research and can continue to shed light on the matter and convince Americans to wait for both sides of the story before making judgment. In the meantime, we’ll start preparing for SAEN’s next press release.

Jim Newman

The First Decade of the Human Genome: What’s on the Horizon?

To mark the 10th anniversary of the sequencing of the human genome the BBC aired a documentary yesterday evening entitled “Miracle cure: a decade of the human genome” that can be viewed on the BBC iPlayer.  It was an enjoyable look at what has been accomplished since the famous announcement at the White House in June 2000, and while I think the program could have done with exploring some of the science in more depth, it gave a good overview and didn’t shrink from the sheer complexity of many of the questions that face scientists who are now attempting to understand the genome.

Sophie Longton holds a vial containing a gene therapy treatment that may one day cure her of cystic fibrosis. Image Courtesy of the BBC.

The program followed three individuals as they sought to understand what impact the knowledge gained from studying the genome could have on illnesses that have affected them, breast cancer, cystic fibrosis, and alcoholism, and what basic, applied, and clinical research is currently underway. The case of a woman whose breast cancer is linked to a defective BRCA1 gene turned to discussion of the potential for the development of personalized medicine – treatments that are tailored to the genetic makeup of an individual patient’s cancer cells. Animal research plays a very important role in the development of targeted therapies that can be used in personalized medicine, and an early example of this is the drug Herceptin, which is used to treat cancers that express the HER2 gene.

The cystic fibrosis thread focussed on the development of gene therapy and clinical trials now underway under the direction of Professor Eric Alton of the UK Cystic Fibrosis Gene Therapy Consortium. These gene therapy trials use lipid spheres to transport working copies of the CFTR gene – defective in cystic fibrosis – to the lungs of patients, and the particular lipid formulation used in these trials, known as  GL67A was selected after careful evaluation against other candidates, first in CF mice and then in sheep (1).  Mice models of cystic fibrosis have helped researchers to understand more about the disease and to assess therapies, but until very recently research has been hampered by the lack of a large animal model of cystic fibrosis that models the lung pathology of cystic fibrosis.  This situation finally changed in 2008 when scientists at the Universities of Iowa and Missouri produced genetically modified pigs that lack the CFTR gene and develop all the pathologies that are characteristic of cystic fibrosis in humans. This new animal model for cystic fibrosis will be very useful for evaluating the safety and efficiency of new gene therapy techniques as the science advances.

Finally the thread on the influence on genetics on alcoholism was a reminder of just how complex the interaction between an array of genetic variations and the environment can be, and that while it may be possible to identify factors that predispose an individual towards a particular condition it is often difficult, if not impossible, to identify a single cause that tips the balance. Considering the enormous damage caused to society by addiction, and the high failure rate of addiction treatment programs, there is no doubt that addiction research is a neglected area within biomedical science.  This is sad because research into the physiological underpinnings of addiction can aid the development of more effective treatment programs. Hopefully the identification of genes that predispose certain individuals to addiction will help society to realise that science can make an important contribution to solving this medical and social problem.

Paul Browne

1)       Griesenbach U, Alton EW; UK Cystic Fibrosis Gene Therapy Consortium. “Gene transfer to the lung: lessons learned from more than 2 decades of CF gene therapy.” Adv Drug Deliv. Rev. Volume 61(2), Pages 128-39 (2009) DOI: 10.1016/j.addr.2008.09.010.

Writing About Medical Research – Top Marks!

It’s been a while since I’ve posted anything, nonetheless a little while ago I was sent a research paper that a student submitted on animal research. It was so good that I asked her if I could reproduce it on SR (she said yes!).

Meredith Milligan’s paper “The Medical Necessity of Animal Research” is a shining example of a well thought out research paper on the animal testing issue. The full document can be downloaded below. In it you can find out how she comes to the following conclusion:

In the end, we will always be forced to pick between the lives of animals and the lives of humans. Vaccines, treatments, and procedures developed through animal testing continue to save thousands of lives every year, yet their production also costs animal lives. Because animal testing is essential to the acquisition of new medical knowledge and because there are no absolute alternatives to it, to save the lives of these animals, we would have to abandon all animal research.  We would have to abandon our search for treatments, and eventually cures, for AIDS, cancer, cystic fibrosis, and other deadly human diseases. Yet we must make a choice. Though steps have been taken, and should continue to be taken, to reduce the number of animals used in research, to refine experiments to minimize the discomfort of animals involved, and to replace animal testing when possible, animal testing cannot be eliminated from the scientific process. The cost, thousands of human lives that could be otherwise improved or potentially saved, would be far too great.

The full paper can be downloaded here (pdf document).

Hopefully papers such as these can support and inspire others to write similarly well researched, and well written articles for schools, news and elsewhere.

Regards

Tom Holder

“The biggest achievement of veterinary history”

That was how John Anderson, the head of the United Nations Food and Agriculture Organisation, described yesterday’s announcement by the Global Rinderpest Eradication Programme (GREP) that the dreaded cattle disease Rinderpest has been eradicated.  For over a millennium Rinderpest has stalked cattle herds around the world, often leaving famine in its wake, and in the past century it has had a particularly devastating effect on both domestic cattle and wild animals in Africa.

 

Rinderpest, which once devestated cattle herds around the world, has become the second deadly virus to be eliminated.

 

Eradicating Rinderpest was a huge undertaking, requiring the co-operation of international bodies, national governments, and non-governmental organizations, and on the ground thousands of scientists, veterinarians, and farmers made sure that outbreaks were detected, contained and eradicated. A key part of both the GREP campaign that finally eliminated Rinderpest, and of the national and regional programs that preceded it, is vaccination.

The first attempts to develop a vaccine for Rinderpest took place at the end of the 19th century, including a vaccine derived from the bile of an infected ox by the famous Robert Koch. A more effective vaccine developed by Arnold Theiler and Herbert Watkins-Pitchford which involved simultaneously injecting the animal with blood from an infected animal that contains the virus  (at that time not yet identified) and antiserum from an infected animal that protects the animal for long enough to allow the animals own immune system to respond to the virus.  While these methods were effective they were also risky, a small minority of cattle would often succumb to the disease following vaccination, so these vaccines were usually only used during Rinderpest outbreaks. They did however allow outbreaks to be controlled in a number of countries including India, Egypt and Russia during the first three decades of the 20th century.

An important breakthrough was in the 1920’s when J. T. Edwards of the Imperial Bacteriological Laboratory at Izatnagar (now the Indian Veterinary Research Institute) modified Rinderpest by growing it serially in goats, and after 600 serial passages, and many tests of the virus in cattle along the way, the virus was sufficiently attenuated so that it did not cause the disease but rather conferred lifelong immunity to rinderpest. This live–attenuated vaccine could be freeze-dried for storage and was easier to, but the vaccine still had the drawback that it could cause disease in cattle with a weakened immune system.

The next great advance was in 1962 when Walter Plowright and R.D. Ferris applied the methods used by Albert Sabin to develop the oral Polio vaccine to produce tissue culture rinderpest vaccine (TCRV), a live-attenuated vaccine grown in vitro in calf kidney cells.  To produce the TCRV required many passages of the virus in cell culture, accompanied by frequent and thorough assessment of the virus in cattle. A virus produced by the 90th passage was found to confer immunity while being stable, not spreading between animals, and not causing disease even in cattle with weakened immune systems. Due to its safety the vaccine developed by Plowright could be used to immunize cattle even when there was no immediate threat from Rinderpest, and it vaccines developed from Plowright’s vaccine were key to the final push to eliminate Rinderpest. Walter Plowright did not confine his work to the laboratory, he also worked to improve production of the vaccine and its use in the field, including a program to immunize wildebeest (an important wild reservoir for the virus); small wonder that he was awarded the World Food Prize in 1999.

 

Walter Plowright, who developed the tissue culture rinderpest vaccine. Image courtesy of the World Veterinary Association.

 

The eradication of Rinderpest is a timely reminder that while we may often focus on the contribution animal research makes to human medicine, we should also remember that it is also key to many advances in veterinary medicine.

 

Addendum: Veterinary blogger The Dog Zombie notes that the eradication of Rinderpest, which involved decades of interplay between human medical research and veterinary research, is a good illustration of One Health in action.

 

Paul Browne

Reference:  “Rinderpest and Peste des Petits Ruminants: Virus Plagues of Large and Small Ruminants” Edited by: Thomas Barrett, Paul-Pierre Pastoret and William P. Taylor, Academic Press Inc. (2005) ISBN: 978-0-12-088385-1

USDA gives Primate Products, Inc. the all clear

Last week Allyson Bennet wrote about how animal rights groups often misrepresent the facts in order to further their agenda of ending the use of animals in medical research, citing the example of a campaign against Primate Products, Inc.

The USDA inspection report has now been published and confirms that no non-compliant items were identified during the inspection at Primate Products Inc. on September 20 2010. This was the inspection carried out in response to the allegations made by PeTA and other animal rights groups.

In addition Ed Silverman of the Pharmalot blog quotes USDA Spokesman Dave Sacks as saying:

It was a clean inspection report…there was nothing found that was against animal welfare regulations…Group housing of primates is allowed in the animal welfare regulations…with the mindset that’s more closely adapted to how they live in the wild. These animals do various fighting among themselves for hierarchy…so that will carry through to how they are housed…But if in those housing situations, if there is a monkey that gets injured, we require the facility to provide adequate care.”

We are glad to see that the USDA understands rhesus macaque behavior, unlike the animal rights activists who have made unfounded allegations against PPI.

Mice help identify promising prostate cancer treatment

Prostate cancer is responsible for hundreds of thousands of deaths each year, so the news today that in a clinical trial of more than 1,000 men a new drug named abiraterone acetate prolonged the lives of patients with advanced prostate cancer in a by an average of four months has been greeted with considerable excitement.

Prostate cancer is currently treated by surgery, radiation, ultrasound, and hormonal therapy which blocks the secretion of testosterone and other androgens (hormones that control the development and maintenance of male characteristics) by the testes. Unfortunately in most cases after a remission of two to three years most patients on hormonal therapy progress to terminal cancer, a progression that is believed to be due at least in part to the production of androgens by tissues outside of the testes.  Abiraterone acetate works by blocking the enzyme cytochrome p45017alpha that is involved in the production of androgens, including those produced by tissues outside the testes.

Abiraterone acetate was initially developed by Cancer Research UK-funded scientists working at the Institute of Cancer research, who screened a series of potential cytochrome p45017alpha blockers in mice, before selecting abiraterone acetate (then known as CB7630) due to its ability to suppress circulating testosterone to undetectable levels and markedly decreased the weights of androgen-sensitive organs without affecting organs that are not sensitive to androgens (1).

New trials are now planned to determine if abiraterone acetate can help men with less advanced prostate cancer, if it can then it may be able to offer prostate cancer patients extra years, rather than months, of life.

Paul Browne

1)      Barrie S.E. et al. “Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase).” J Steroid Biochem Mol Biol. Volume50(5-6), Pages 267-273 (1994) PubMed:7918112.

Barrie SE, Potter GA, Goddard PM, Haynes BP, Dowsett M, & Jarman M (1994). Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). The Journal of steroid biochemistry and molecular biology, 50 (5-6), 267-73 PMID: 7918112

Mice, Nanotechnology, and Inflammatory Bowel Disease

Back in March I discussed a new therapy that combines nanotechnology and RNA interference (RNAi) to treat metastatic melanoma, and how basic and applied animal research has contributed to its’ development.  Now researchers at the Georgia Institute of Technology and Emory University have reported the development of another nanotechnology and RNAi approach to treating inflammatory bowel disease (IBD), and the report published in Georgia Tech Research News highlights the importance of research in a mouse model of ulcerative colitis to the development and evaluation of their novel nanoparticle drug.

Nanoparticles remain intact in healthy tissue (upper panel). In inflamed tissue reactive oxygen species break down the nanoparticle shell to release siRNA and lower TNF-alpha levels through RNAi (lower panel). Image courtesy of Scott Wilson.

 

 

 

 

 

 

IBD is a term that covers a range of conditions where a dysfunctional immune system causes inflammation in the intestine, and includes disorders such as Crohn’s disease and ulcerative colitis which can be very debilitating to sufferers, and ultimately very damaging to their health. While treatments are available they do not work well in all cases, and often have serious side effects, so new treatments that target the inflamed tissue while sparing healthy tissues are highly desirable.

The way this new nanoparticle developed by Georgia Tech and Emory targets inflamed tissue differs from that used by scientists at Caltech to target melanoma cells. The latter employs nanoparticles coated with a protein called transferrin that is preferentially absorbed by cancer cells, while the former relies on reactive oxygen molecules produced by the inflamed tissue to break down the thioketal polymer shell of the nanoparticles, releasing the siRNA payload that triggers RNAi.

What the two approaches share is that they demonstrate the vital role played by animal research in advancing the use of nanotechnology in 21st century medicine.

Paul Browne