Monthly Archives: June 2008

Three Challenges for the coming months

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

Want information on animal research? animalresearch.info!

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

How mice helped develop a new drug for MS

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

)60918-6

2) Jönsson S. et al. “Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3 -quinolinecarboxamides for treatment of autoimmune disorders: structure-activity relationship.” J. Med. Chem., Volume 47(8), Pages 2075-2088 (2004). PubMed 15056005

3) Brunmark G. et al. “The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis.” J Neuroimmunol., Volume130(1-2), Pages 163-172 (2002). PubMed 12225898

AR groups winning hollow PR victories

Animal Rights groups like PETA and HSUS have been trumpeting the latest PR victories by animal rights campaigners – but what’s behind these “success stories”?

The first “victory” for AR groups, recently touted by PeTA, was a ban on animal testing put in place by the small country of San Marino. However, let us put this in perspective. San Marino is a country smaller (in size) than Manhattan (New York City), and with a population of just 30,000 (comparable to a medium sized American University). So what impact has the ban had on the world’s oldest republic? None! Not one iota of difference has been made. Not a single animal will be saved in this hollow stunt. San Marino’s biotech industry is non-existent, and its borders contain just one University – The Advanced School of Historical Studies (Scuola Superiore di Studi Storici), unsurprisingly not a university reknowned for undertaking biomedical research.

Spurred on by this victory can we expect animal rights groups to attempt a similar ban in Monaco? Or perhaps the Vatican City? Why stop there – perhaps we’ll start hearing about people banning animal research in their own homes.

The second triumph was HSUS convincing 13 educational institutions to ban “severe and unrelieved pain and/or distress” in research, despite the fact that such experiments account for only 7% of the total. It was interesting that most of the institutions, such as Amherst, are liberal-arts colleges and do not carry out any pain-causing research (for example many used animals for just behavioral studies), and, unsurprisingly, none of these institutions are well known for their animal experiments.

It has been a common tactic by animal rights groups in need of a “victory”, to ban animal research where it doesn’t exist. In 1986 the British Union for the Abolition of Vivisection (BUAV) passed a law in parliament banning Great Ape Research. The result? A waste of public money – scientists in Britain had already stopped using great apes by choice long before the ban, preferring to use lower primates which provided similar quality results without the very high upkeep costs required for great apes.

All for now!

Tom

Animal research and the Millennium Technology Prize

Yesterday in Helsinki Professor Robert Langer was awarded the 2008 Millennium Technology Prize for his work on intelligent drug delivery. The Millennium Technology Prize is the world’s largest award for technological innovation and is considered by some to be the unofficial Nobel Prize for technology*.  Prof. Langer was up against some very strong competition for the prize,  including Sir Alec Jefferys whose invention of DNA fingerprinting helps to solve thousands of crimes every year.

http://www.msnbc.msn.com/id/25095043/
http://www.millenniumprize.fi/news/89/66/d,news/
http://web.mit.edu/newsoffice/2008/langer-millennium-0611.html

For more than thirty years Prof. Langer has pushed the boundaries of biomaterials research; his work on controlled drug release has benefited millions of people worldwide, but his more recent work on areas as diverse as  tissue engineering and ultrasound drug delivery (think Dr. McCoy in Star Trek) is also acknowledged to be world-leading.  His research group at MIT includes over 100 scientists, making it the largest biomaterials laboratory in the world.

http://web.mit.edu/langerlab/

Obviously such research draws on a huge range of scientific disciplines, but in a review published a few years ago (1) Prof. Langer makes clear the important role played by animal experiments in the development and evaluation of  technologies such as polymer microspheres used to deliver drugs to treat prostate cancer and polymer scaffolds used to engineer tissues such as cartilage.  Animals are not only vital to the research process, but can also inspire new developments.  In a recent publication by Prof. Langer and a team lead by his colleague Dr. Jeff Karp describes a  waterproof adhesive bandage inspired by the sticky feet of the gecko lizard (2) and discusses the tests in rats that evaluated the adhesive properties and safety of different tissue adhesive designs. The bandage can hold together tissues but dissolves over time after the wound heals, which should make it ideal for the treatment of internal injuries and a safer alternative to stitches that are usually used today.

http://www.msnbc.msn.com/id/23189028/

Yesterday’s award is further evidence of the enormous contribution made by animal experiments to exciting and innovative medical research. We congratulate Professor Langer and his colleagues on winning this award, and wish them well in their ongoing research.

* There are other awards that compete for this title, notably the Charles Stark Draper Prize awarded every year by the National Academy of Engineering which Prof. Langer won in 2002. http://en.wikipedia.org/wiki/Charles_Stark_Draper_Prize

Cheers

Paul Browne

1) Langer R. “Biomaterials in drug delivery and tissue engineering: one laboratory’s experience.” Acc Chem Res.  Volume 33(2), pages 94-101 (2000) PubMed:10673317.

2) Mahdavi A. et al. “A biodegradable and biocompatible gecko-inspired tissue adhesive.” Proc Natl Acad Sci U S A. Volume 105(7), pages 2307-2312 (2008). PubMed: 18287082.

Americans Living Longer Thanks to Animal Research

Americans are living longer, healthier lives and we owe much of that success to biomedical research,” said Robert Palazzo, Ph.D, President of the Federation of American Societies for Experimental Biology (FASEB). This comes after the CDC announcement that US life expectancy has surpassed 78 years for the first time.

Declines in death rates for heart disease, cancer and diabetes, can be attributed to leaps made in the treatment of such conditions, much of which is funded by the NIH (National Institute of Health). Palazzo continued:

It is so easy to take for granted the amazing medical advances that NIH has afforded us, but many of the terminal illnesses that haunted previous generations are now treatable, and sometimes curable, conditions. When you take a moment to reflect, the life-saving discoveries funded by NIH are truly extraordinary.

Cheers

Tom

Animal Rights extemism reaches #2 in UCLA “worst moments!”

A recent editorial in the popular UCLA (University of California, Los Angeles) campus newspaper, The Daily Bruin, decided to consider the best and worst moments of the recent academic year. Narrowly beaten by hikes in student fees (but beating UCLA’s loss at basketball in the Final Four of March Madness) was the Animal Rights extremism which has plagued the University.

The Animal Liberation Front continued to terrorize professors, including an attack on a UCLA researcher’s home.

Clearly students are not getting onside with the sadly violent campaign which some animal rights groups have waged against many universities in the UC (University of California) system. Now hopefully students will begin to go further in the other direction to stand up and defend the need for lifesaving medical research to continue unhindered by half-truths, lies, harassment and violence.

Cheers

Tom

Calming the storm…while killing the virus

A couple of months ago Pro-Test blogged about some interesting research that may lead to new drugs that to prevent the lethal “cytokine storm” that was responsible for most deaths in the SARS outbreak.

However SARS is not the only virus that kills by inducing an excessive immune response; the threat posed by the  H5N1 strain of bird flu is of grave concern to many public health officials http://www.cdc.gov/flu/avian/. With an observed mortality rate of between 45% and 80% in infected humans here is little doubt that if it was to mutate into a form that was highly contagious in humans it could pose a great risk to the population, and possibly cause a pandemic on the scale of the 1918 Spanish flu. During outbreaks it has been observed that although some anti-viral medicines can kill the virus they did not reduce mortality rates, probably because they were administered too late to stop the virus from provoking the cytokine storm.

A study published online in Proceedings of the National Academy of Sciences of the United States of America (PNAS) this week (1) by Prof. Kwok-Yung Yuen and colleagues at the University of Hong Kong shows that it should be possible to both kill the virus and prevent the cytokine storm.  Working with mice infected with the H5N1 virus compared administering the anti-viral drug zanamivir alone or in combination with anti-inflammatory drugs. A key element in their study was a decision to delay treatment for 48 hours after infection in order to mimic the real world clinical situation where the illness may not be diagnosed until some time after infection.  Their results confirmed that zanamivir alone did not reduce mortality when compared to an untreated control group, and even though viral levels were a lot lower than in the control group only 13% of mice survived.  In contrast when zanamivir was combined with the anti-inflammatory drugs celecoxib and mesalazine 53% of the mice survived, a very significant improvement, without compromising the ability of zanamivir to kill the virus.
Since all the drugs this study are already approved for human use this result should make a real difference to how we respond to any future H5N1 outbreaks, and indeed to outbreaks of other viruses that kill in the same way.  It is sobering to reflect that even with this improved treatment the mortality rate was still frighteningly high, more research is clearly needed to help develop better drugs for the treatment of virus induced cytokine storms.

Cheers

Paul Browne

1) Zheng B.-J. et al. “Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus” Proc. Natl. Acad. Sci. USA, Published online on June 3, 2008 DOI:10.1073/pnas.0711942105