Speaking of Research

I thought I’d dedicate an entire post to a certain statistic which has been repeatedly misused and misunderstood by animal rights groups.

92% of drugs that test successfully in animals fail during human trials

You will find animal rights organizations, such as PETA and PCRM, all using this statistic. Often claiming that this shows that “animal research doesn’t work”.

The statistic is from the FDA (Food and Drug Administration), used to illustrate inefficiencies in drug development. However the actual statistic is much broader, it should be:

92% of drugs fail during human trials

Now it is true that they have passed animal testing to get to human (clinical) trials, but it also means that they have passed non-animal pre-clinical tests, such as in vitro. Consider:

92% of drugs that have successfully passed in vitro tests, fail during human trials

Misleading? Yes. So the next obvious question:

Why do drugs fail at the clinical stage?

Drugs fail clinical trials for two reasons - they don’t work well (lacking efficacy) or they are potentially dangerous. Drugs may fail at different stages of clinical trials - so sometimes a relatively rare, but potentially dangerous side effect turns up late into human trials when many thousands of humans are being used (late in clinical stages many more humans than other animals may have tested the drug - as more people/animals are tested, more side effects are discovered); equally some drugs may simply be ineffective in humans, or ineffective in enough humans (no one wants to release a drug that only works in, say, 30% of people - unless that 30% is a particular and selectable demographic e.g. children), this is bound to be the case since animals are not perfect models for humans, just as humans are not perfect models for other humans (thus why some people get adverse drug reactions and not others).

According to the FDA report, which suggests various improvements to the drug development process, the top area where improvements could be made is to improve the animal models (not remove, but use and improve - they also accept the good track record of animals for finding dangerous chemicals in toxicology tests), with the increase in genetically modified animals allowing us to create better animal models, hopefully we will see that 92% statistic drop.

It is worth highlighting that the FDA says many drugs are failing clinical trials at late stages, meaning that problems with drugs are not becoming clear until they are tested in many people - so it is a mystery as to why the animal rights groups try and put the blame solely on the shoulders of animal research.

What about the benefits of animal safety tests?

Well why DO we use animal safety tests? The 92% statistic ignores all the benefits of safety tests, so:
You have 1000 drugs entering animal safety tests
900 of them fail, of which, say, 20 might actually be safe in humans (false positive).
Of the remaining 100, 92 fail human tests

[The above stats are made up for illustration purposes. Approx 90% of drugs fail at the animal testing stage, and false positives aren't (cannot legally or safely be) measured]

Therefore:

90.5% of dangerous drugs have been kept out of clinical trials thanks to animal safety tests**

(However 92% of drugs have still failed clinical trials)

**[[Dangerous Drugs removed by animal safety tests]] / [[Total number of dangerous drugs]] = [[880/972]]

We can see that the lower statistic makes no mention of the benefits of animal safety tests made clear by the top statistic.

It is worth noting that around 90% of drugs are removed at every stage of safety tests, i.e. 90% are removed at non-animal pre-clinical safety tests, 90% at animal stages, and 90% during human clinical trials.

Check back on the website for more AR debunking!

Cheers

Tom

Americans for Medical Progress, whom Speaking of Research works side by side with, have just released a fantastic new DVD which looks at the impact of animal research on veterinary medicine.

The DVD follows four veterinarians; Marilyn Brown, Arnold Goldman, Lisa Portnoy and John Young, who lent their thoughts, hearts and voices in order to explore the humane nature and value of animal-based research to animal and human medicine. The DVD also follows the dramatic stories of some animals whose lives have been saved by treatments developed through biomedical research.

A clip from the DVD can be seen below:

Another story on the DVD is that of Duke, the research beagle who contributed to the development of the HPV (Human Papillomavirus) Vaccine through his part in trials for the COPV (Canine Oral Papillomavirus) Vaccine. The HPV vaccine was given FDA approval last year and will soon be available to help many people around the world. Learn more about veterinary medicine.

The DVD is free of charge so order one now.

Tom

Duchenne muscular dystrophy (DMD) is an inherited disease that affects about one in every 4,000 males born in the USA. It is caused by mutations in the DMD gene that lead to the protein dystrophin being either absent or faulty, which leads to muscle cell death, progressive muscle wasting and early death, with few patients surviving beyond their 40th birthday.

In recent years scientists have been investigating the possibility of transplanting healthy stem cells into the muscle of patients in order to replace the lost muscle cells and halt the progression of the disease, but it has proved difficult to identify muscle precursor cells that can both make new muscle cells and persist as a pool of precursor cells in the patient, the latter is an important consideration if repeated transplants are to be avoided since muscle cells wear out and need to be replaced.  A paper published in this weeks issue of the scientific journal Cell by scientists at Harvard University is an important step towards developing a means to screen for the right cells and use them to treat DMD

http://news.bbc.co.uk/1/hi/health/7500523.stm

In their work (1) Dr. Amy Wagers and her coworkers concentrated on a type of cell known as satellite cells that are closely associated with muscle fibers in mice and humans; by studying the proteins found on the surface of these cells they were able to identify a sub-population they termed skeletal-muscle precursor cells (SMPs)  in mice that could produce muscle cells while maintaining a reserve of precursor cells for future rounds of muscle cell production.  They next needed to evaluate these cells for their ability to do this when transplanted into an animal whose muscles were being damaged due to faulty dystrophin, in order to determine whether their ideas were correct.
They chose to use the mdx mouse model, a mouse which has a defect in the dystrophin gene and displays many of the biochemical and physiological characteristics of DMD. The mdx mouse displays less severe symptoms than humans with DMD, but like humans is characterized by progressive muscle wasting and early death and has been crucial to the development of many of the new therapies for DMD, including gene therapy and novel drugs, that are currently entering clinical trials. Dr. Wager’s work found that engraftment of transplanted SMPs into the muscles of  mdx animals lead to the production of new muscle cells to replace lost to DMD, and that the transplants also showed therapeutic value by improving muscle histology and rescuing physiological muscle function i.e. the muscles got stronger.  Analysis of the muscles of mice which received transplanted cells also showed that the second requirement that the transplanted cells should give rise to a pool of cells capable of acting as a source of muscle cells in future was also fulfilled.

This is very promising work, and marks an important milestone in the development of stem cell therapy for DMD.  Before human trials can begin however more work will need to be done to develop methods of isolating and preparing human SMPs for use in clinical trials, and there remains the challenge of how to transplant the cells into all the muscles in the body where they are required.

Cheers

Paul Browne

1) Cerletti M. et al. “Highly Efficient, Functional Engraftment of Skeletal Muscle Stem Cells in Dystrophic Muscles” Cell Vol 134, Pages 37-47 ( 2008)

We are sorry to learn of the death of Dr. Michael DeBakey. DeBakey was a world-renowned heard surgeon who developed the roller pump, an essential component of the life-saving heart lung machine (used during Cardiopulmonary Bypass) which propels the blood through the tubing. His pioneering work in the field of cardiology later led him to perform the first coronary artery heart bypass, and more recently he has been a key figure in the development of ventricular assist devices that keep patients alive while they wait for a suitable transplant organ to become available.

He has won the two highest civillian honors in the United States, the Presidential Medal of Freedom in 1987, and the Congressional Gold Medal in 2007, as well as countless other awards in science. These awards recognized not only his great contributions to science and surgery but also his dedication to improving health policy and practice, from the introduction of M.A.S.H units in the US military, to Medicare for the elderly, to the internationally renowned National Library of Medicine.

We are especially grateful for DeBakey’s determination to improve public understanding of the crucial role of animals in medical research, one that he was particularly familiar with from his own research.  The courage, tenacity and charm he displayed as chairman of the Foundation for Biomedical Research will long continue to serve as an example to advocates of humane and responsible animal research.

Tom

Speaking of Research is going up in the world, having now made its way into the (joint) biggest Science Journal of them all (alongside Nature) - Science Magazine. You can download that SR article here. The article, in the Newsmakers section, puts Holder as this month’s “mover” - reporting on his efforts to bring the Pro-Test style movement to the United States.

At 22, Tom Holder is already a veteran of a U.K. student-led campaign to counter demonstrations and vandalism by animal-rights activists. Now he’s hoping to apply lessons learned from those battles to help scientists speak out about the benefits of animal research in the United States where attacks by animal-rights extremists have been on the rise.

Holder has been working hard with Americans for Medical Progress, who helped bring Tom to the US, to travel to Universities and other institutions around the country. If you would like to hear Speaking of Research at your institution go to our Request a Speaker page.

In other news, the Veterinary Benefits page (formerly Veterinary Treatments) has been updated. A surge of visits to the page caused us to give the page a makeover, and we thank the contribution of Dr. Arnold Goldman, DVM, Director of Canton Animal Hospital, for his help in improving the information available. So check that out and discover how animals used in research benefit not just people, but other animals as well.

Regards

Paul Browne

Peta (People for the Ethical Treatmet of Animals) and HSUS (Humane Society of the United States) are both trying to lay claim to the estate of the late Leona Helmsley, once dubbed the Queen of Mean. Helmsley’s fortune is estimated at $5-8 billion (around 3 times the combined incomes of everyone living in Zimbabwe).  Helmsley ammassed her fortune through shrwed real estate investing and a chain of hotels (apparently taking the Monopoly rulebook as a life guide).  She earned her reputation as a tyrannical employer, once quotes as saying “Only the little people pay taxes.” Upon her death she left $12 million to her dog, Trouble, more than to any of her four grandchildren (two were left out the will completely). She put the lion’s share of her fortune in a trust fund for the care and welfare of dogs - this could provide around $400 million per year for various efforts to improve animal welfare.

So should the money go to Peta? An organisation which killed more than 90% of the adoptable animals that entered its shelters in Virginia? Or perhaps to HSUS, which spent less than 8% (approx $6.5million) of its $91 million donations (2006 Budget on website), to support animal shelters, choosing rather to spend the money fighting for animal rights on the hill.

Hopefully Leona Helmsley’s fortune will instead be divided up between much smaller animal shelters which directly contribute to animal welfare. HSUS have long played the trick of gaining donations by associating their effots with their local animal shelters - in truth HSUS absorb many of the resources that would do much to improve animal welfare in individual animal shelters, and use it to fight for animal rights on the hill.

Regards

Tom

It seems Peta is running out of news lately - so its front page has decided to bring back the story of mistreatment of animals at Oregon National Primate Research Center - a story which turned out to be completely false when the USDA investigated. Want proof? Here’s the USDA report giving ONPRC a clean bill of health.

It seems that Peta forgot to check the newspapers after their infiltration because there were plenty of stories regarding the perfectly acceptable conditions inside ONPRC. So for the benefit of Peta members, here’s some of the news coverage.

Peta’s video accused ONPRC of mistreatment - let’s look at some of their claims:

Claim 1. Employers spray high power hoses to clean cages with monkeys inside - soaking the monkeys and upsetting them.

Truth: The Peta video is filmed so that most of the cage is not visible. You cannot see that the technician is actually cleaning the pans beneath the cages while the monkey is safely perched on a shelf away from the water. This is a regular occurrence and does not distress the monkeys. Here is actual footage showing what happens during pan cleaning (rather than Peta’s video which shows how the ceiling appears during pan cleaning).

Peta’s claim that the noise of the water hitting the cages causes the monkeys distress is unfounded when one considers that the monkeys are not sitting right next to the point of impact, but a few feet above on a shelf.

Claim 2. Technicians chase monkeys around their cages in order to move them. This causes the monkeys great distress.

Truth: Unfortunately if you have a large cage then it will is more difficult to capture the monkeys (but most would agree that the other benefits of a large cage, such as the one seen below, outweigh this minor inconvenience). The large cages allow monkeys to move around and play freely - improving animal welfare and adhering to the principle of Refinement within the 3Rs.

In order to reduce the need to “capture” monkeys, positive reinforcement is used to train monkeys to help researchers. Below we can see a monkey being trained to press a button, and later the monkey will be trained to offer up an arm of leg for blood samples.

Claim 3. Mistreatment has resulted in a rectal prolapses in monkeys within the facility

Truth: Rectal Prolapses are a minor problem for monkeys in captivity, similar to hair loss. These problems come and go without causing the monkey much discomfort (if a monkey does appear to be in pain then a veterinarian will attend to them promptly).

Claim 4. The conditions cause monkeys to go mad - animals can be seen in distress, whirling or pacing inside their cages.

Truth: This is perhaps one of the most insidious claims. Peta try to insinuate that the monkeys seen are acting as they always do - whereas it appears that they are acting alarmed by a presence outside their cage (perhaps one with a camera…) This is most certainly not ordinary behavior, and there is a strong chance that the animals filmed are stress-sensitive monkeys used for certain types of experiments at ONPRC. However the fact remains that the footage was almost certainly taken as soon as the intruder entered the room and before the animals had time to acclimatize themselves to the new presence. See the video below for a comparison of Peta’s footage to film taken by members of ONPRC.

[Please favourite, rate and comment favourably on Youtube to ensure more people see this]

CORRECTION:
The following video was entirely shot by Oregon Primate Center (not PETA) to illustrate how certain stress-sensitive monkeys (used for research into behavior) will act abnormally when in the presence of something new (a camera - that looks like a big eye), but will settle down when they realize it is not a threat. Check the previous video to see how a PETA infiltrator misused this fact.

We look forward to next week when Peta will be reporting on cruelty to animals by the Ancient Egyptians.

Cheers

Tom

I recently gave a speech at the International Conference for Animal Research Policy, in it I laid out three challenges for the upcoming months. We’ve all heard of the 3R’s, so this is the 3ES’s:

Enabling Scientists

Encouraging Students

Educating Schoolchildren

We must enable scientists by providing them with an outlet to talk about their work. In Britain animals used in medical breakthroughs are prominently mentioned in news articles (indeed a frontpage headline “The Mouse than Sniffled” in The Independent (UK National Newspaper) shows how far the UK has come in talking openly about animal research, and its contribution to medical progress). A quick search on the BBC Health or science web pages will often bring up recent medical research, with the animals used mentioned openly in the 3rd or 4th paragraph. However the same is not true in the US, with scientists and institutions often hesitant to mention the use of animals in any press releases. The SR blog is just one small area where scientists can talk about the animals behind the medicine. Any scientists interested in writing a guest entry (or two) on their own research, or the research of others, should e-mail tom [at] speakingofresearch.org.

We must encourage students to speak up about animal research. Students today are the scientists of tomorrow - they are also in an environment which is condusive to academic debate on controversial issues. Students across the UK debated the issue of animal research when it stood in the public eye in 2006, and with students talking among themselves, blogging across the internet, preparing themselevs for careers in medicine, science, journalism and politics, they have the power to change public opinion. With the raw facts so convincingly on the side of animal research we must simply encourage students to talk about it in order to bring them onside.

Finally, we must educate schoolchildren. PeTA are in schools across the length and breadth of the country indoctrinating children into believing that animal testing is unnecessary, or cruel. They give presentations to classes of all ages, and offer teachers with one-stop lesson plans on the use of animals in medicine. Thus we too must be getting into schools, giving talks on the contribution of animals in medical research. If you are a scientist willing to give a talk at a local school then go and offer your services, most teachers would be glad to have a lesson off while someone else educates the kids.  Alternatively contact us and we will contact you at a later date if we are invited to speak at a school but are unable to make it. For you teachers out there, contact us to see if we can provide a speaker at your school, or check out these resources for teachers of elementary, middle and high school kids provided by Massachusetts Society for Medical Research.

So with these challenges in mind SR continues to press on.

Cheers

Tom

A new website created by the RDS has been launched a couple of days ago. Animalresearch.info allows scientists to make their own contributions (subject to moderation) to add to the already vast repository of information on “the contribution of animal research to medical science“.

The website offers in-depth information on Nobel Prize winners, drug developments in the last century, different animal models, the drug development process, and much, much more. There are some great downloadable resources which you can use to help make the case for animal research.

Hopefully websites like this will help fight back against the saturation the internet by misinformation on animal research.

AnimalResearch.info is an international collaboration of scientists and researchers. As expert contributors, we provide and edit the content, making it as accurate and up-to-date as possible.

Science is a process, and sometimes there are competing theories – this is not the place where they do battle. This site gives the consensus opinion. If there is not yet consensus then those mainstream theories with the most supporting evidence are considered, and their flaws noted.

There is a thorough verification process to validate the credentials of our contributors. All content is fully referenced, peer-reviewed, scientific research which registered scientists may edit at any time.

Cheers

Tom

In the news today there have been reports that laquinimod, a new drug developed to treat multiple sclerosis (MS), has performed well in an early (Phase IIb) (1). An MS patient’s immune system attacks their central nervous system, leading to impaired communication in the nervous system and finally to physical and cognitive disability. A key feature of MS are the lesions where the myelin sheath that protects nerve cells is damaged, and in this trial patients who took a 0.6 mg per day dose of laquinimod showed a 40% decrease in the number of lesions. Few patients suffered side effects, and those side effects were relatively mild and disappeared when treatment was stopped.

http://www.washingtonpost.com/wp-dyn/content/article/2008/06/20/AR2008062000981.html
http://www.mssociety.org.uk/research/potential_therapies/laquinimod.html

This is good news since at present there are only a few treatments available to block progression of MS and they have serious drawbacks. Current reatments need to be injected and can have cause serious side effects, and some have a general immunosuppressive effect and can leave the patient more vulnerable to infection or cancer.

The team at Active biotech who developed laquinimod knew that they needed a drug that could be given orally and reduced damage caused by the malfunctioning immune system in MS without suppressing the immune system more generally. Their starting point was a drug called linomide (roquinimex) which had shown promising effects against MS before the clinical trials were halted due to severe side effects in some patients. Subsequent studies in beagle dogs indicated that these side effects were, rather ironically, due to the fact that linomide can cause severe inflammation in some circumstances. By making a series of modifications to the chemical groups at different positions on the molecule the Active Biotech team generated numerous chemical derivatives of linomide (2)*. The next step was to determine structure–activity relationship of these derivatives, in other words to determine the relationship between the different structural changes and the ability of the molecule to inhibit the development of symptoms in an experimental model of MS. Since they needed to determine the effect of the modified compounds on the intact immune system they needed to use a whole animal model, and the model they chose was an acute experimental autoimmune encephalomyelitis (aEAE) mouse that reproduces some of the characteristics on MS but develops much more quickly. The new compounds that showed the greatest activity against aEAE were then tested for proinflammatory responses in beagles. These studies resulted in the identification of laquinimod, which has more potent anti-aEAE activity than linomide but a far lower tendency to induce inflammation.

Laquinimod was then evaluated against chronic relapsing experimental autoimmune encephalomyelitis (crEAE) in mice and rats (3) and found to be effective. This was an important result since crEAE is considered to be a more accurate model of MS than aEAE, though it takes longer to develop and is therefor not as suitable for large scale screening of drug candidates. Furthermore it was observed that unlike some current MS treatments laquinimod does not have a more general immunosuppressive effect.

On the basis of these results in animal studies and additional safety and pharmacokinetic data Laquinimod went into clinical trials in MS patients, the early results of which were announced today. A phase III trial involving over a thousand patients is now underway and will with luck confirm these results and demonstrate an effect on the progression of the disease over a longer time period.

Cheers

Paul Browne

* Although this paper was published in 2004 the work it describes was undertaken several years earlier and predates the work described in the 2002 paper by Brunmark G. et al.

1) Comi G. et al. “Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study” The Lancet, Volume 371, Pages 2085-2092 (2008), DOI:10.1016/S0140-6736(08