Monthly Archives: June 2014

How you can support understanding of animal research in thirty seconds

In February 2013 we wrote a post called “The Science of Linking”, which looked at how other organisations’ website linking to pages like Speaking of Research could have an impact on its ranking in Google searches.

The efforts of our followers paid up, with Speaking of Research’s PageRank (a key factor in Google search result order) rising from 6 to 7. This puts us equal to HSUS, and above both PETA (who dropped from 7 to 6 last year) and PCRM.

This video may help explain how some of these factors, including PageRank, influence search results.

Despite early success, we can continue to improve. Ideally, we need to be a first page search result for terms such as “animal research” and “animal testing”, and you can help us do that. Google considers links from .edu and .gov websites to be of greater value than those from less established websites (thus why SR outranks PETA despite having far few incoming links). So what could you do in thirty seconds?

We need you to send an email to your department website editor (and convince friends in other life science departments to do likewise) to ask them to add links to pro-research organisations on an appropriate page. Many of you will have direct control over sections of your department’s page, so please take a few seconds to add the middle section of the letter below.

Dear Webmaster

Please can you add the following paragraph to our departmental website, on our page about animal research here: <insert url>

For more information about the role of animals in research we recommend the following resources:
http://www.speakingofresearch.com – Speaking of Research
http://www.amprogress.org – Americans for Medical Progress
http://www.fbresearch.org – Foundation for Biomedical Research
http://www.animalresearch.info – Animal Research Information

Kind Regards

<insert name>

You may also wish to link to specific resources, for example our briefing notes on animal research in the US or Canada:

So you’re now twenty-five seconds down and still have a spare 5 seconds to help research just a little bit more. Well, at the bottom of this post, like every post there is a box that looks like this:

sharing speaking of research

This one comes from our successful post about misused pictures of cats

So please share this post, and others on this website, on Facebook, Twitter, Google+, WordPress, Reddit, Digg, StumbleUpon and tumblr. Your efforts can make all the difference in our efforts to improve and widen our communication about animals in research.

Speaking of Research

Addendum:

We’d like to thank all of the organizations which do link to Speaking of Research. To name a few of them, The Wake Forest School of Medicine, The University of British Colombia and The Californian National Primate Research Centre at UC Davis.

 

“Animal Rights …Or Wrongs?” – July 1, 2014

Next Tuesday, July 1st. at 8:00pm ET, Nickelodeon’s “Nick News with Linda Ellerbee” will air a program titled “Animal Rights…Or Wrongs?” It promises to be a balanced look at both sides of the use of animals in research. “Nick News” has been on the air for 22 years and is recognized for discussing social, political, and economic issues important to children, teenagers, and adults.

On the “pro” side of the discussion will be Dr. Cindy Buckmaster, Director for the Center for Comparative Medicine at Baylor College of Medicine and AALAS Vice President. Dr. Buckmaster has been a longtime advocate for the responsible use of animals in research and has frequently spoken about the need for those in laboratory animal science community to speak out about what we do and why we do it. She has frequently given her talk, “Stop Hiding…and Change the World” at various meetings and conferences. In addition to Dr. Buckmaster, “Nick News” will be presenting the story of Liviya Anderson  whose life was saved by animal research when she developed aplastic anemia.

animal rights or wrongs

On the “con” side will be Dr. Aysha Akhtar, a board certified neurologist currently working for the Office of Counterterrorism and Emerging Threats with the FDA and is a Fellow of the Oxford Centre for Animal Ethics (unaffiliated with Oxford University). She is also a frequent contributor to The Huffington Post arguing against the use of animals in research. Dr. Akhtar has been covered by Speaking of Research in the past here and here. At this time there is no further information available regarding who else may be a part of the “con” side.

“Nick News” states its aim is to explore both sides of the story. They will talk to children who have opinions on both sides from those actively working to end all animal research to those like Liviya who are alive today because of it.

In addition to the interviews with experts and children, Baylor College of Medicine allowed the “Nick News” crew to film animal in the vivarium including an experiment with a mouse model for Alzheimer’s disease performing a memory task in the lab.

Assuming that this segment will indeed be an unbiased look at both sides of the story, it will be interesting to see how children respond to the same tough question we all grapple with routinely: If we stop using animal models in research, then what?

We hope this program indeed provides an unbiased look at the issues surrounding the use of animals in research. It’s one thing to argue in the abstract about what, in a perfect world, should or shouldn’t happen. It’s another thing altogether to look a patient like Liviya, or any number of others suffering from debilitating diseases, and essentially say they aren’t worth saving. Although those participating in the program will not likely come face-to-face with real patients or their families in this segment, hopefully those watching will see there are potentially real consequences for real people should animal research be discontinued. Additionally we hope the program doesn’t allow any misrepresentations of the science to go unchallenged or the use of images which don’t accurately represent current research.

Undermining a cornerstone of medical research – examining a biased commentary on animal studies

Medical sociologist, Pandora Pound, and epidemiologist, Michael Bracken, recently wrote an opinion piece entitled “Is animal research sufficiently evidence based to be a cornerstone of biomedical research?” for the British Medical Journal. The article was chosen as the editor’s choice, leading to an editorial by the editor in chief, Fiona Godlee.

BMJ Pound and Bracken

Pound and Bracken criticise the poor quality and reporting of many animal studies, asserting that this is leading to ineffective drugs going on to clinical trials before failing.

Pound and Bracken make some suggestions for improvement, concluding:

In addition to intensifying the systematic review effort, providing training in experimental design and adhering to higher standards of research conduct and reporting, prospective registration of preclinical studies, and the public deposition of (both positive and negative) findings would be steps in the right direction. Greater public accountability might be provided by including lay people in some of the processes of preclinical research such as ethical review bodies and setting research priorities. However, if animal researchers continue to fail to conduct rigorous studies and synthesise and report them accurately, and if research conducted on animals continues to be unable to reasonably predict what can be expected in humans, the public’s continuing endorsement and funding of preclinical animal research seems misplaced.”

While some aspects of the article are reasonable, the overall impression the reader is left with is that animal research doesn’t work and can’t work in its current form. Their bias is obvious to those who are familiar with the arguments of those who argue against animal research. When they’re not incorrectly conflating basic science* with animal research (most basic biomedical research does not involve animals, e.g. human genetic research), Pound and Bracken argue that “lack of translation” is (apparently) not just from poor research practises, but also due to fundamental differences between humans and other animals, writing:

Even if the research was conducted faultlessly, animal models might still have limited success in predicting human responses to drugs and disease because of inherent inter-species differences in molecular and metabolic pathways.”

However, the bulk of the supporting literature they present to support this statement is – unlike most of the claims made in their commentary – not in the form of peer reviewed scientific research papers or meta-analyses but rather commentaries and books written by (other) opponents of animal research, including a certain Dr Greek whose misleading claims we have discussed several times on this blog (most recently here). For a commentary that sets great store by its evidence-based credentials this is, to say the least, disappointing.

Indeed, in their 2004 publication on whose anniversary this commentary was published, Pound, Bracken and their co-authors found that in all 5 cases where a therapy appeared to be successful in pre-clinical animal studies but later failed in human studies, more rigorous meta-analysis of the pooled pre-clinical animal studies showed that the treatment was not in fact successful in them, and that for one therapy (thrombolysis for stroke) such rigorous analysis would have enabled a serious side effect observed in clinical trials to be identified in the pre-clinical animal studies. In short, their own work shows that animal studies can predict the human outcome when their results are analyzed properly..

Other investigators who have examined failed therapies in cancer, ALS and stroke, have come to the same conclusion that too many therapies in some areas of research have failed in clinical trials not because of species differences, but because they never actually succeeded in animal studies, with most of the apparent successes being false-positive results due to flaws in experimental design and biases in reporting and publication. The authors all agree on a number of steps that need to be taken to avoid false-positive results being taken through to clinical trials, including better study design, requirement for independent replication of results in several animal models of the condition in question, publication of negative results (where the candidate therapy doesn’t work), meta-analyses of animal studies before beginning human trials.

An excellent analysis of animal models of stroke by van der Worp et al (2010) covers many of these issues, but also advises that to avoid false negative results in the clinical trials – where poor trial design leads to the erroneous conclusion that a therapy doesn’t work when in fact it does – human trials should match as closely as possible the conditions e.g. time to drug administration, dose, type of injury) of the successful animal studies.

The “rapid responses” to Pound and Bracken’s piece shows that many scientists who specialize in translating research from bench to bedside are alert to the flaws in their analysis.

To quote the response by Andrew Whitelaw and Marianne Thoresen, Professors of Neonatal Neuroscience at the University of Bristol:

The reader was left with impression that there were no examples in recent years of animal research leading directly to major advances in human health.

Three life-saving treatments in neonatal medicine would never have been given ethical approval for clinical trial if there had not been high quality animal models showing efficacy.

Rather than unselectively condemning the whole of biomedical animal research, we suggest that a more critical approach by funding bodies and journal editors could reduce bad research while supporting the good.

They ought to know, as basic and applied research in animals was crucial to the development of techniques that use cooling and xenon gas to protect babies from brain damage following oxygen starvation during birth.

Dr Thomas Wood, is more succinct:

[T]he overriding message of the article is somewhat confusing – demanding that we optimise and streamline animal research is very different from suggesting that it is useless, but both of these ideas are presented side-by-side.”

Prof Malcolm Macleod, a neurologist at the University of Edinburgh, and a frequent critic of poor design in some animal studies, agrees with many of Pound and Bracken’s criticisms, but in a more balanced manner, noting:

When conducted to the highest standards, animal research can indeed inform the development of human medicines. Given that there are many diseases for which we do now have treatments, it is perhaps self evident that the diseases which remain are more challenging, probably requiring research that is done to a higher standard – there is less signal, and more noise.”

Professor Macleod is one of Europe’s leading experts on the development of therapies for stroke, and is one of the leaders of the EuroHYP-1 trial of therapeutic hypothermia in adult patients with acute ischaemic stroke, a trial he advocated after undertaking a rigorous meta-analysis of studies on this therapy in animal models of ischaemic stroke.

Dr Charles M Pearman discussed how basic science makes up the building blocks that lead to human medicine:

Much clinical research is performed by standing on the shoulders of giants. A phase III drug trial comparing two antihypertensives will have much greater direct impact on clinical decision making than any individual animal model based basic science study. However, hundreds or thousands of such “low impact” works are needed to develop the drugs in questions. The authors reference Wooding et al. who themselves acknowledge this and conclude that clinically motivated basic biomedical research should be encouraged.

Basic biomedical research may try and may fail. Without it, however, there will be no successes to base clinical triumphs upon.

There have been many other comments, Prof Fernando Martins do Vale discusses why some of Pound and Bracken’s criticisms may not have much of an impact on results. Prof Robert Perlman argues that evolutionary differences between species can inform animal research. And Dr Vanitha A J explains that much cancer research has been effectively translated from animals to humans, noting in particular recent progress in cancer immunotherapy.

Another, separate, but strong response to Pound and Bracken’s paper was from Dr Liz Harley at Understanding Animal Research. Harley notes that many of the criticisms made in the original opinion piece are already being addressed by the industry. The UK Government’s delivery plan, “Working to Reduce the Use of Animals in Scientific Research”, explicitly mentioned the problems of poor experimental design and outlined several initiatives aimed to improve current practices. While Pound and Bracken call for a lay person to sit on ethical review bodies, they fail to note this is standard practice in the UK, while US regulations demand a lay person unaffiliated with the university stand on their Institutional Animal Care and Use Committees. Clearly Pound and Bracket do not do their homework sufficiently.

We finish with a quote from Prof Martins do Vale:

But the existence of bias and errors does not invalidate Science; on the contrary, as Karl Popper said, the awareness of errors is the first step for their correction and scientific progress.”

Pound and Bracken’s article opens up some important questions, but their biased interpretation risks throwing out the baby with the bathwater as they use flaws in experimental design to try and argue for a fundamental flaw in animal research. Their attempts to use legitimate concerns over experimental design to attack animal research are in fact a dangerous distraction from ongoing efforts to address problems that affect all areas of biomedical research (and indeed any areas of research where scientists have looked for them) from the most fundamental in vitro molecular biology studies right through to clinical trails.

Speaking of Research

* Confusion over what is meant by basic research is a theme throughout Pound and Bracken’s piece, it’s notable that many of the examples of “basic” research they mention are in fact applied or translational research, and that they focus on a paper on translation of basic research published by Contopoulos-Ioannidis et al. in 2003, a paper whose serious flaws in both design and conclusion we have discussed previously.

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.

Unpleasant Truths vs Comforting Lies

Scientists use animals  in research to elucidate basic questions about biological function in health and disease.  Such basic research in the life sciences, like parallel studies in other fields of science, yields knowledge about nature.  Such knowledge, in turn, can be applied to a myriad of problems to alleviate suffering, improve our well-being, and make this a better world.  Our students at UCSF provide this wonderful example of how our work leads to progress and make a solid case for why the public and our government should support basic research:

In contrast, those that oppose the use of animals in medical research find comfort in lies. They deride the work as being “curiosity-driven research” that merely results in “knowledge for knowledge sake”.  They believe basic research is without any value at best, and fraudulent at worst.  In doing so, such activists highlight their lack of knowledge about science in general and about who scientists are as individuals.

Sadly, such grotesque views on basic research is just one of the many comforting lies that form a part of the animal-rights belief system which can be readily summarized in the following form:

comforting lies

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.

Index of animal rights groups/activists

Ever needed more information about an animal rights groups or individual? Well we’ve produced a page specifically to index some of the more influential or extreme individuals and groups in the US and UK (hopefully we can expand this to other countries too).

Speaking of Research has written an awful lot of information about animal rights groups over the past 6 years, so this index should help you find some of the main posts we have about some of the main groups involved. For each group/individual we have strived to choose 2-3 SR posts which best describe some of their activities. See below for an extract.

animal rights groups

Click this image to go to see more

In order to help people navigate the hundreds and hundreds of posts on Speaking of Research, we will be creating more indexes like this to help people find older posts animal disease models and philosophical discussion.

Pro-Test Italia Marching for Science

On June 14, 2014, Pro-Test Italia will hold a second rally in Milan to support the use of animals in medical research. See our event on Facebook.

Everyday, Italy continues down a psuedoscientific path. Stamina method, vaccines-causing-autism and exotic diet cures against cancer, are all promoted by national media and TV programmes like “Le lene”. This anti-scientific agenda has resulted in stringent rules placed on animal research by the Government.

What is at stake is the safety of a country that allows people to use dangerous and non-scientific methods in our hospitals, with our money. What is at stake is the future of research because more and more young people, who specialise in biomedicine will be forced to emmigrate if they wish to further their career. What is at stake is also the economy of a country, because research produces patents and jobs.Italy has to decide if it wants to compete with Germany, United Kingdom and USA on the field of innovation, or to compete with less developed countries for low quality products, adapting itself to their work standard.

We risk losing an important parts of Italian economy like the biomedical and pharmaceutical sectors, that possess a high level of innovation, if politicians persist in writing a long term scientific strategy based on the whims of small groups of fanatics.

Pro-Test Italia rally success

Pro-Test Italia held a successful rally in Milan in June 2013

Pro-Test Italia organized this rally to demand that the Italian government listen to the scientific community when creating laws that will affect heir research. We demand they reconsider restrictions added by Italy to the EU legislation 2010/63; restrictions that the EU itself says are illegal and will result in massive fines. We demand the government increase funding for research, because only by investing in our future can we save Italy from its dire economic crisis. We demand better protection from the growing threat posed by animal rights extremism.

Students, researchers and veterinaries should being their white coat, there will be stands for fund raising and for distributing informative leaflets.
For more information, please contact by e-mail: info@pro-test.it
If you’re concerned about research in Italy, please join us on 14 June at 15.30 in via Mercanti, in Milan.

Animal Research saves millions of lifes every year, including of those who would see such scientific endeavours end.

Marco Delli Zotti

Kicking off a new era for neuroprosthetics, or just the warm-up?

Tonight, if everything goes according to plan, a young person will stand up in front of a global audience numbering in the hundreds of millions, walk a few paces, and kick a football.  This by itself may not seem remarkable, after all this is the opening ceremony of the World Cup, but for the Miguel Nicolelis and the more than 100 scientists on the Walk Again project – and the millions watching from around the world – this will mark the triumph of hope and dedication against adversity, for the young person in question is paraplegic.

Image: Miguel Nicolelis

Image: Miguel Nicolelis

The exoskeleton that is being used in this demonstration is a formidable technological achievement, collecting nerve signals from non-invasive EEG electrodes placed on the scalp of the operator, and converts these into commands for the exoskeleton, while sensors on the operators feet detect when they make contact with the ground and send a signal to a vibrating device sewn into the forearm of the wearer’s shirt. This feedback, which has never been incorporated into an exoskeleton before, allows the operator to control the motion of the exoskeleton more precisely. While this is not the first EEG controlled exoskeleton to be tested by paraplegic individuals, videos released by the Walk Again suggest that it has allows for far quicker and more fluent movement than existing models.

 

A late substitution

What many viewers may not know is that the use of EEG (Electroencephalography) was not part of Miguel Nicolelis’ original plan, as late as spring 2013 he was planning to use an alternative technology, implanted microelectrode grids within the cerebral cortex of the operator. Unfortunately about a year ago it became clear that the implant technology he was developing would not be ready for use in humans in time to meet the deadline of the opening ceremony of the 2014 FIFA World Cup, so the team had to fall back on the more established technique of EEG.

Is this an issue? Well, to understand this you first have to know a little about the two approaches.

EEG is a very mature technology. Its development dates back to 1875 when Richard Caton observed electrical impulses on the surface of the brains of rabbits and monkeys. In 1912 Vladimir Pravdich-Neminsky published the first EEG in dogs, and in 1924 the first EEG in human subjects was recorded by Hans Berger. It has the advantage that it doesn’t require surgery, but also serious disadvantages. The main disadvantage is that it records the combined signals from millions of neurons across wide areas of the cortex simultaneously, and this makes it difficult to separate out the signal from the noise. By contrast microclectrode implants record the individual signals from just a few neurons.

A common analogy is that EEG records the sound made by the whole orchestra, whereas microelectrode implants record individual instruments.  The result is that EEG can only be used to give relatively simple commands “move leg forward” “back” “stop” “kick” and requires a great deal of concentration by the operator. It is unlikely that the performance cam be improved upon very much. By contrast the microelectrode implants, while requiring invasive surgery, have the potential to enable much finer control over movement.

A pioneer of brain implant technology

There is no doubt that for over a decade Miguel Nicolelis and his colleagues at the Duke University Center for Neuroengineering have been among a very select group of scientists at the forefront of brain implant research, demonstrating that implanted electrodes could be used to control a simple robotic arm in rats in 1999 and in monkeys in 2000 (1). In 2012 Nicolelis highlighted the importance of animal studies to progress in the field in an article for Scientific American:

The project builds on nearly two decades of pioneering work on brain-machine interfaces at Duke—research that itself grew out of studies dating back to the 1960s, when scientists first attempted to tap into animal brains to see if a neural signal could be fed into a computer and thereby prompt a command to initiate motion in a mechanical device. Back in 1990 and throughout the first decade of this century, my Duke colleagues and I pioneered a method through which the brains of both rats and monkeys could be implanted with hundreds of hair-thin and flexible sensors, known as microwires. Over the past two decades we have shown that, once implanted, the flexible electrical prongs can detect minute electrical signals, or action potentials, generated by hundreds of individual neurons distributed throughout the animals’ frontal and parietal cortices—the regions that define a vast brain circuit responsible for the generation of voluntary movements.”

In 2008 the Duke University team showed that microelectrode arrays implanted in the cortex could be used record the neuron activity that controls the actions of leg muscles (2), and that this could be used to control the movements of robotic legs.

It was this that spurred Nicolelis to try to develop a mind-controlled exoskeleton that would be demonstrated at the World Cup opening ceremony.

Brain Machine Interfaces – from monkeys to humans.

So, if brain implant technology to control an exoskeleton wasn’t ready for 2014, when will it be ready?

The answer is probably very soon, as this approach has already been demonstrated successfully in humans.

In 2008 we discussed how Andy Schwartz and colleagues at the University of Pittsburgh had succeeded in developing a brain-machine interface system where microelectrode arrays implanted in the motor cortex of macaque monkeys allowed them to control the movement of a robotic arm with a degree of dexterity that surprised even the scientists conducting the study.

Then in 2012 we reported that Jan Scheuermann, quadraplegic for over a decade due to a spinal  degenerative disease, was able to feed herself with the help of two intracortical microelectrode arrays developed by the University of Pittsburgh team.

 

What happens now?

Tonight’s demonstration will mark the culmination of an extraordinary year-long effort by scientists and patients, but it also marks the public debut of a revolution in brain machine interface technology that has been gathering pace over the past decade, largely unnoticed by the mass media.

Miguel Nicolelis has come in for some heavy criticism for the cost of the Walk Again project, and for raising hopes too high, but the criticism is largely unfair. His team set themselves an extraordinarily ambitions target, and that they have fallen a little short is understandable. Once they have recovered from their exertions they will no doubt set to integrating the exoskeleton technology that they have developed with the implant technology that they are developing back in the lab at Duke University.

And that technology is increasingly impressive, more advanced implant systems that allow monkeys to simultaneously control two virtual arms, microelectrode arrays that allow signals from almost 2,000 individual neurons to be recorded simultaneously (3) (in contrast the already very capable BrainGate implant system used by the University of Pittsburgh team records from less than 100 individual neurons) potentially allowing for much more subtle and delicate control, and interfaces that will allow sensory information from prosthetics to be transmitted directly into the brain. We will certainly be hearing from Miguel Nicolelis and his colleagues at Duke – and their colleagues and competitors around the world – again very soon.

So tonight, as you watch the opening ceremony, remember this; for Brain Machine Interface technology as much as for the World Cup itself, this is just the warm up!

Paul Browne

p.s. And of course BMI controlled robotic exoskeletons are just one promising technology under development to help paralysed people, stem cell therapy, epidural stimulation and intraspinal microstimulation have all delivered impressive results in recent studies.

1) Wessberg J, Stambaugh CR, Kralik JD, Beck PD, Laubach M, Chapin JK, Kim J, Biggs SJ, Srinivasan MA, Nicolelis MA. “Real-time prediction of hand trajectory by ensembles of cortical neurons in primates.” Nature. 2000 Nov 16;408(6810):361-5.

2) Fitzsimmons NA, Lebedev MA, Peikon ID, Nicolelis MA. “Extracting kinematic parameters for monkey bipedal walking from cortical neuronal ensemble activity.” Front Integr Neurosci. 2009 Mar 9;3:3. doi: 10.3389/neuro.07.003.2009. eCollection 2009.

3) Schwarz DA, Lebedev MA, Hanson TL, Dimitrov DF, Lehew G, Meloy J, Rajangam S, Subramanian V, Ifft PJ, Li Z, Ramakrishnan A, Tate A, Zhuang KZ, Nicolelis MA.”Chronic, wireless recordings of large-scale brain activity in freely moving rhesus monkeys.” Nat Methods. 2014 Jun;11(6):670-6. doi: 10.1038/nmeth.2936.

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.