Monthly Archives: August 2009

Mending a Broken Heart

An interesting item in the news today about research on repairing the damage to the heart caused by a heart attack. The report in PNAS can be read by those with a subscription at:

While there have been several attempts to bioengineer cardiac tissue for transplant  in vitro using starting from cells seeded onto a scaffold, so far these efforts have been hampered by difficulties in getting the capillaries necessary to supply blood to enable the muscles in the tissue patch to grow properly.  Due to these difficulties engrafted heart patches have until now had limited benefits on heart function in animal models of heart attack, and consequently this approach has not yet been assessed in human clinical trials.

A cross-section of the new tissue with functional blood vessels (the hollow ovals) containing red blood cells

A cross-section of the new tissue with functional blood vessels (the hollow ovals) containing red blood cells

In this project the scientists at Ben-Gurion University started with  a similar approach to that used previously by other scientists. They grew the patch of tissue from neonatal rat heart cells which were seeded in scaffolds designed to allow cardiac cell organization and blood vessel penetration after transplantation, and supplemented them with a mixture of growth factors that encourage cell survival and blood vessel growth. After the cells had been cultured in vitro for 24 hours to allow initial organization of the cells within the scaffold  they introduced a new step, implanting the patch into the rat omentum, an abdominal tissue that is particularly rich in blood vessels, in the hope that the interaction with the blood vessels of the omentum would encourage the development of mature blood vessels in the heart patch.

They observed that the blood vessels of the omentum connected with those developing in the heart patch, encouraging blood vessel development and growth of cardiac muscle. The real test came when they compared the ability of omentum-grown heart patches to repair tissue damage in rats which had undergone experimentally incuced heart attacks 7 days earlier, with that of heart patches that had been grown in vitro.  The result was clear, the omentum-grown heart patches had better blood vessel and muscle quality than the in-vitro grown patches and integrated more strongly into the heart.  When they examined several parameters of heart  function they found that the hearts of those rats which had received omentum-grown patches worked better than those of control rats and those which had received in-vitro grown patches.

So what does this mean for the treatment of heart attacks? The authors point out this is a relatively straightforward procedure that could be assessed in human trials, but also caution that the extra surgery required to grow the heart patch on the omentum would be to risky for many elderly or ill patients so it is a procedure suitable for only a minority of heart attack patients.  What the authors suggest is the development of in vitro bioengineering techniques that mimic the influence of the omentum on the growth of blood vessels and muscle within the heart patch, and with this study they have begun to determine what the requirements of such in vitro systems are.

Needless to say as such in vitro techniques for stimulating heart tissue growth are developed they will need to be assessed in animal models of heart injury before they can enter clinical trials in human patients.

Regards

Dr. Paul Browne

Just when you thought they couldn’t sink any lower…

… it seems we should never underestimate the depths to which the Animal Liberation Front (ALF) are prepared to lower themselves to..

A few weeks ago we covered the arson attack and graverobbing aimed at Novartis CEO, Daniel Vasella, where a family urn was stolen by animal rights extremists (see our new AR: Extremism section) who wanted to try and sever Novartis’s links to the research facility Huntingdon Life Sciences (HLS).

The ALF desecrated the graves of Daniel Vasella's family, leaving a chilling warning

The ALF desecrated the graves of Daniel Vasella's family, leaving a chilling warning

Recently on the ALF website, Bite Back (Warning: AR Website), the following message was left for Mr. Vasella:

Daniel Vasella,
Because of you there are thousands of animals dying unnamed in mass graves, but yours was all too easy to find. If you wish the urn that was taken from the grave to be returned then you need to publically finish with Huntingon [sic] Life Sciences immediately.
You have 2 choices Mr Vasella: lose HLS or LOSE THE URN

As if this wasn’t enough they went on to threaten further desecrate the remains:

This time you’ve got the chance to receive back your family’s urn in exchange for dropping HLS for now and for ever, Daniel, and if you don’t act fast enough we can just empty the urn in the closest TOILET…

One hopes that the police on the case have breakthroughs soon in finding those responsible, bringing them to justice, and returning the urn to Mr. Vasella.

Regards

Tom Holder

Open Letter to Dr. Greek

This is a copy of a letter written to Dr. Greek long ago (July 2003) in response to his request for a written contribution from me.  Everything I say in this letter is the honest truth of what I think now, as I did then, with regard to cognitive neuroscience in the non-human primate.  At the foot of the letter I add a glossary of terms unfamiliar to other readers.

Dear Dr. Greek,

Thank you for your letter of July 8 inviting me to contribute a chapter to your new book on the scientific evaluation of the animal model in science and medicine.  It seems a highly worthwhile and timely project.  Unfortunately, because of my–deserved or undeserved–reputation, to which you kindly refer, I am unable to contribute the chapter that you solicit.  I have a very active research program, a splendid group of graduate and undergraduate students to teach, and an apparently never-ending list of meetings and writing commitments.  In a word, I’m swamped.

However, because I think the issue is legitimate and important, and you are interested in hearing both sides of the controversy, I cannot refrain from addressing it here with a few words, although only sketchily.  Of course, I presume you see me, correctly, on the side of those who believe that the animal model is extremely useful, at least for some aspects of neuroscience.  Indeed, I firmly believe that, with regard to the cerebral cortex, there is no adequate substitute for the non-human primate model (no set of algorithms, no computer simulations, no inferences from human imaging or scalp electrophysiology).  The value of the primate model, in what pertains to cognitive functions and the role of the cortex in the human, rests in the homology between the cortex of the non-human primate and that of the human.

That homology is structural as well as functional.  As you probably know, the cytoarchitectonic structures of the two cortices are very similar, almost indistinguishable from each other.  Functionally, the homology is just as striking.  Here I am referring to the physiological mechanisms and principles of operation of the principal cognitive functions (perception, attention, memory, intelligence); not language, of course, which is exclusive patrimony of our species.  Certainly, human cognition is immensely richer than monkey cognition, but the same essential network structure and dynamics can be recognized in the cortex of the two species.  I do not need to explain to you the implications of the similarities in cortical structure and function for the pathogenesis, etiology, diagnosis, and treatment of certain nervous and mental disorders, even though some of those implications may not be direct or immediate (“lifesaving”).

To be sure, we have to be aware of the limits of the homology and of the important and undeniable inter-species differences.   We have to also avoid the simplistic, indeed silly, assumption that homology is reducible to genetic identity.  In the cortex, as in genetics, relationship is what really matters.  Relationship–between cortical cell assemblies or between genes–is what ultimately defines the cognitive structure (percept, memory, etc.) or the phenotype.  In the 21st century, as I see it, both cognitive neuroscience and genetics will finally make the much-needed Copernican shift from the sterile down-spiral of reductionism into molecules to the more holistic view of how biological systems operate  (I recommend to you Hayek’s Sensory Order, U. Chicago, 1952 and my Cortex and Mind, Oxford, 2003, sorry I have no extra copy at hand to give you).  For that crucial shift, the primate cortical network model is going to be pivotal.

For many years, in my laboratory, we have been working on the neuronal foundation of memory and the role of the cortex, especially the prefrontal cortex, in it.  It is difficult research, with its problems and limitations, like any research in complex systems.  It is also quite rewarding and productive.  Again, to a person like you I do not have to explain, because you will readily understand, that we study neural activity at the cellular level because we are interested in cortical systems and networks and in the functional relationships between neurons and between cortical areas.  Much of the knowledge we acquire in the monkey is undoubtedly transferable to the human.  Some of it is not.  On the whole, our work is not only consistent with, but also supports, the network model of cortical function.  Nowadays it gives me considerable satisfaction to see that model slowly but surely penetrating current thinking in cognitive neuroscience.

However, precisely because of the homology, indeed the unquestionable similarities, between human and monkey in cortex and cognition, we face some special problems.  In your letter you state that you are not interested in ethical or philosophical questions.  Yet, in our field, some of these questions are inextricable from scientific questions.  In the first place, on scientific grounds alone, we cannot tolerate that our monkeys experience stress or pain.  You know how detrimental both stress and pain can be for cognitive functions.  Stress and pain, even minimal, can be serious obstacles to the attainment of our scientific aims, especially when we have to use behavioral tests for cognitive assessment.  We have to avoid them in our monkeys at all costs. This is something that people in the animal rights movement do not seem–or want–to understand, even though I have no trouble understanding some of their ethical concerns.  (In fact, years ago, when we had a miserable regulatory climate, I was gladly one of their best allies.)

Then, of course, there are the very legitimate ethical and philosophical questions of experimenting on animals that are very much like us but lack one of our cognitive functions, namely (no pun intended), language; they cannot tell us what pleases or displeases them, even though they are fully sentient.  Fortunately, of course, they have emotional “language.” (I am sure you know it but, in case you don’t, I highly recommend to you Darwin’s wonderful book on emotional expression in man and animals, reedited by Eckman).  Thus, by vocal, facial and bodily signs, monkeys can indeed tell us how they feel.  (After almost half a century of working with macaques, I think I can proudly add “monkey language” to the list of the other six that I can understand reasonably well!)

So, the challenge in the study of primate cognitive neuroscience is to apply a judicious combination of scientific, ethical, and philosophical precepts.  The ideal balance is difficult to achieve, but the basic principles are simple enough:  (1) Impeccable scientific rationale toward practical and meaningful goals;  (2) Minimum number of animals to attain those goals;  (3) Exquisite care of the animals; and (4) Exhaustive analysis of the data to obtain maximum yield of information and to avoid duplication.

I’ll finish by going back to the scientific aspects, which are those that interest you.  Right now, we are investigating the coupling, in higher cognitive functions, between neural activity–as reflected by neuronal discharge and local field potentials–and hemodynamic change, something that cannot be done in the human.  The results of this exciting research, in my view, may have enormous implications for our understanding of the biophysics of functional imaging methods in the human and the dynamics of cortical networks.

Although I cannot write the article that you graciously invited me to write (it almost seems that this long letter ought to do!), you are naturally welcome to visit my website, where you can find the details of my use of the monkey model in cognitive neuroscience.  That would undoubtedly give you a better perspective of my views on the issue than I have been able to convey in these lines.

I wish you success with your book, which I look forward to reading after it appears in print.  I hope you will, indeed, cover both sides of a very important controversy.

Yours sincerely,
Joaquín M. Fuster, M.D., Ph.D.
Professor, UCLA School of Medicine

Glossary

Cognitive Neuroscience.  The neuroscience of knowledge and memory, that is, of what we know and remember (more).

Cytoarchitecture. Structural geometry of cells and fibers in the brain.

Etiology
.  The cause(s) of disease (more).

Genes
. Chemical substances inside cells that encode the hereditary characters of the organism (more).

Hemodynamic change
.  Change in blood flow in nerve tissue as a result of its nervous activation.  It is an indirect measure of brain activity currently used in hospitals, clinics, and laboratories.  Extremely useful in cognitive neuroscience to assess the cerebral foundation of higher cognitive functions, such as memory.

Homology
.  Equivalence of anatomical and physiological brain features across animal species.

Neural networks
.   Assemblies of interlinked cortical neurons (brain cells) that by their patterns of connectivity encode memories and actions.

Pathogenesis.  The anatomical and physiological foundations of disease.

Phenotype.  The physical manifestation of the developed hereditary traits (more).

Prefrontal cortex
.  The anterior cortex of the frontal lobe, essential for organizing behavior.  It plays a vital role in all the executive functions (working memory, decision-making, planning, etc.) that serve behavior organization (more).

Reductionism
.  The scientific search of ever-smaller physical elements (down to particular chemical molecules) in attempts to understand cause and effect in higher functions (for example, cognitive functions).

Animal Care Technicians

Many misconceptions exist about exactly how animal research is conducted in laboratories.  Some of the misconceptions come from a lack of awareness whereas others come in the form of intentional misinformation on the part of animal rights groups.  Successful research relies on the dedication of many individuals with a variety of roles, from primary investigators doing the research to the veterinary staff providing medical care to the animals.  One group that is often overlooked, but is vital to the success, is the animal care staff.

Most animal research facilities have a dedicated staff of people whose job is to provide daily care for the animals in their charge.  The animals are dependent upon these individuals to provide food, water, clean living environments, and environmental enrichment.  Research animals must be cared for 7 days a week, 365 days a year regardless of weather, holidays or personnel shortages. The job requires the caretakers to stand for long periods, move heavy bags of feed and manoeuvre caging and equipment around to be cleaned.  The animal care staff also must be well versed in caring for many different species of animals.  An animal facility can have many species such as rodents, rabbits, dogs and swine all located within the same facility.  All require different types of care

Laboratory Dogs

CC Image from Understanding Animal Research//Wellcome Trust

Equally important to the task of keeping caging, equipment and facilities clean is the responsibility of the animal care staff to act as the first line of medical care for the animals.   While different facilities have different ways of performing the task of medical care, the animal care staff is typically the first to notice problems with animal health due to their daily contact with the animals.  By bringing problems to the attention of the veterinary staff, the animal care staff help ensure that the animals are provided with timely treatment.  In order to reliably report an animal that is in distress the care staff must know what “normal” is.  Therefore, most animal care programs include extensive training regimes designed not only to provide initial training, but also to provide refresher course that keep individuals up to date on new care standards.  Many institutions also require the animal care staff to obtain certification from the American Association for Laboratory Animal Science (AALAS) or its equivalent internationally.

The certification process shows a commitment by the research institutions to provide superior care and a commitment on the part of the individuals obtaining certification to performing their jobs to exacting standards.  At the technician level there are three certification classifications; the Assistant Laboratory Animal Technician (ALAT), the Laboratory Animal Technician (LAT), and the Laboratory Animal Technologist (LATG). Each level focuses on a different set of skills.  The ALAT focuses on animal husbandry and welfare along with facility operations.  The LAT focuses more on procedural techniques, a more in depth look at animal husbandry and touches on animal facility management.  An LAT candidate is also expected to be able to retain information learned at the ALAT level and questions on the test could come from either level.  The third level is the LATG which splits its focus between higher level animal husbandry needs and facilities management.  It’s not uncommon for research facilities to require at least the first level of certification while strongly encouraging the obtaining of the other two.  For those individuals wishing to move into management positions a certification process is available as well.

Without animal care staff at various research institutes, the important research being conducted would be difficult to complete.  Although this group is not often mentioned in final research papers, these individuals are critical to the success of any research project.

Regards

Dave Bienus

Animal Rights Extremism – Explained!

Given the recent rises in animal rights extremism both in the US and elsewhere, SR has decided to dedicate a page to animal rights extremism and how we can tackle it (AR Extremism) – so have a read and tell us what you think.

This new page deals with four important questions:

  • What is animal rights extremism?
  • How can we tackle animal rights extremism?
  • What should you do if you have been targeted?
  • What you can do to protect yourself?

Go to AR Extremism

At the heart of our argument lies the values of Speaking of Research – that speaking up is better than ducking down when it comes to dealing with the animal research issue.

A Novartis executive has his house burned down by the Animal Liberation Front in August 2009

A Novartis executive has his house burned down by the Animal Liberation Front in August 2009

Cheers

Tom

Federal Agencies rebut Michael Budkie’s misrepresentation of scientific research

On June 1st, Michael Budkie, Executive Director of Stop Animal Exploitation Now! (Warning: AR Website) (SAEN), issued a press release that was picked up by some media outlets, including United Press International (UPI) and USA Today.

The press release read in part:

The next industry meltdown may be in the nation’s research laboratories, an independent research watchdog said today after it field a wide-ranging complaint against 26 laboratories, including those at Harvard, MIT, John Hopkins and the University of California, for fraud.

The formal complaint (Warning: AR Website) alleged that over 20 faculty members at these top academic institutions in the US, such as MIT, Harvard, John Hopkins and the University of California, are defrauding the government  by unnecessarily duplicating experiments in animals.  The complaint came accompanied with a table and an “index” developed by Mr. Budkie to support his conclusions.

On July 28th, Speaking of Research sent an open letter to Mr. Budkie, addressing his concerns and explaining the flaws in his analysis.  In an nutshell, Mr. Budkie’s argument is that because researchers use similar tools and animal species, they must be doing the same work.   He could as well argue that a computer technician and an auto mechanic do the same work because they both use screwdrivers.   His characterization reflects, at best, a gross misunderstanding of scientific research.

Mr. Budkie

Mr. Budkie

Mr Budkie has not replied to our open letter.

Perhaps, not surprisingly, his failure to respond might be due to the fact that his complaint was already investigated and rebutted by both USDA and NIH — an inconvenient document missing from his web site, which still contains the original complaint letter.  His recent newsletter (Warning: AR Website), also contains the same accusations, even though the reply from NIH and USDA must surely be in his hands.  Put simply, Michael Budkie has chosen to ignore the information that clears the investigators of his claims, leaving readers of his website without the vital facts of the matter.

The letter from NIH, obtained by SR through a FOIA request,  essentially parallels the same response we offered in our rebuttal.

Speaking of Research firmly believe that the Freedom of Information Act is an essential part of maintaining transparency and openness between the government and citizens,  however, in our opinion, over the years Michael Budkie has done little more than abuse of the regulatory system, requesting documents through FOIA from NIH and USDA, and filing trivial complaints.  Since 2007 he has filed a USDA complaints at a rate of seven per year (Warning: AR Website), all of which must be investigated at the expense of the taxpayer dollars.  When the resulting investigations fail to substantiate his claims, he argues USDA is failing to do its job.

Mr. Budkie represents himself as a “an independent research watchdog” group, but he is neither independent (he is a well known animal rights campaigner), and his “research” is limited to grotesque misrepresentations of important scientific work.

Mr. Budkie misleads the public and the media into thinking that his organization is concerned about failures of the animal research compliance system and that he supports alternatives to animal research.  Yet, his web-site provides negligible information on this topic, making it difficult to accept SAEN as an organization that has a stated goal of supporting alternatives to animal research.

This one-man “organization”, SAEN, is supported by the Mary T. and Frank L. Hoffman Foundation, which has the stated goal to “restore God’s original creation intent of a plant based diet” and to to promote “the elimination of the use of animals in biomedical research and testing, their use as food, or their use for any and all commercial purposes“.

Hopefully, this information will serve to clarify the only goal of Mr. Budkie’s “organization”: the abolition of the use of animals for medical research.

Regards

Speaking of Research

Animal Liberation Front Strike in the US

It is not just Europe that has been struck by the recent spate of animal rights extremism (to which the North American Animal Liberation Press Officer responded, “We personally can only regret that Mr. Vasella was not present in the home when it burned“). The US has seen a number of attacks which have taken place, rather unsurprisingly, in California. Despite the success of the UCLA Pro-Test back in April, the Californian government has failed to crack down effectively on extremists.

On July 10th 2009 (sorry, I’m a little late) Michael Selsted, an award-winning Warren L. Bostick Professor and Chair of Pathology in the UCI School of Medicine, had two of his cars covered in red paint and a third covered in paint stripper by members of the Animal Liberation Front (ALF). A message was then left for him threatening further actions if he did not quit his work. Let us be clear – when researchers quit their jobs we all lose. Their research is lost, and any potential benefits to humans and animals with it. A more comprehensive report on this attack can be found here.

On 16th July 2009, an ALF cell in Los Angeles visited a firm they believed to be doing business with Huntingdon Life Sciences (HLS), a contract research facility which contributes to medical developments for humans and animals.

ALF attack on Phenomenex, Los Angeles, CA

ALF attack on Phenomenex, Los Angeles, CA

Fliers were taped to the windows and their flowerbeds were trashed and their lawn signs bent up and ripped from the ground

Despite this being clearly unacceptable behavior, I can’t help feeling that it was more pathetic than anything else – saying this, we should probably be thankful it was nothing more violent.

Cheers

Tom Holder

p.s. Remember to follow Speaking of Research’s blog on Twitter – @SpeakofResearch