One year ago: traumatic experiences linked to disease

One year ago I wrote about a study that linked trauma during childhood to increased risk for certain diseases later in life. The study in question was done in humans and I compared that research paradigm with the cruel experiments done on animals to imitate child abuse and neglect.

By comparison, other perhaps less creative and certainly less compassionate people try to create animal "models" of child abuse and neglect by subjecting baby animals to maternal deprivation or by purposefully taking healthy babies and putting them with aggressive adults. If the baby animals used in these terrible experiments survive, they suffer from a range of physical and psychological pathologies, conditions that are rarely acknowledged or treated. The outcome has many similarities to post-traumatic stress disorder.

Studies that explicitly examine post-traumatic symptoms in elephants, chimpanzees and other animals only serve to bolster this claim.

Revisit the original story to read more about the trauma-disease link.

Trauma in early life, disease in later life

The long history of primate vivisection

Primate experimentation has a long and ugly history. An interesting short essay in this week's BMJ reminds us of these ancient roots.

Writer Wendy Moore gives us a history lesson in quackery featuring Claudius Galen, a Roman doctor who insisted that bloodletting restored internal balance and health. Moore writes:

"Letting blood at specific points was his favourite remedy for restoring balance; he once denounced a quack for letting blood from the “wrong arm.”

His daily dissections of apes, pigs, and sheep led him to numerous mistaken conclusions on the human body, which remained unchallenged until the 16th century."

And yet science and society remain chained and shackled by the fallacious conclusions of vivisection even today. This despite the fact glaring evidence of its failures:

• 99% of drug candidates fail without making it to human clinical trials


• Of those drugs "proven" safe and effective in animals, 92% (more for cancer meds) fail in human trials.


• Of those drugs that make it through human clinical trials and end up on the market, approximately 40% undergo major relabeling or are eventually withdrawn. This despite the fact that relatively few drugs undergo rigorous post-marketing evaluation.

Industry-funded "marketing material" passed off as scientific articles

PLoS Medicine has just published a study which found that essentially ALL reports from clinical trials in one European survey (40 over one year) were written by industry ghost-writers rather than clinicians (all if we use the most liberal definition of ghost-writer, nearly all if a strict definition is used.) Conflict of interest and financial disclosure policies should preclude such nonsense, or perhaps such reports should be marked as advertisement. (Or, for the sake of public health, tossed.)

This is deeply disconcerting:

This study is the first that has systematically examined the prevalence of ghost authorship using a cohort of protocols and corresponding publications. The authors conclude that "ghost authorship in industry-initiated randomised trials is very common, and we believe that this practice serves commercial purposes". They go on to urge that in order to reduce the prevalence of ghost authorship, existing guidelines such as those drawn up by the International Committee on Medical Journal Editors, World Association of Medical Editors and European Medical Writers Association, are followed. This action could increase the chance that publications accurately, fairly, and comprehensively reflect the data collected from trials

A related perspective by Liz Wager, an independent editorial consultant, who has been involved in drawing up guidelines for medical writers, discusses the implication of these findings further.

Full article available online, here, at PLoS Medicine: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040019

Viet Nam News

Viet Nam News

Revenge of the cloned monkeys

JAMA article cautions on reliability and utility of animal testing

The predictive value of animal studies has been questioned yet again by a new, independent study that found only one in ten successful animal trials might lead to an approved drug for humans.

Researchers from the University of Toronto reviewed 76 prestigious animal studies, each originally published in such journals as Science and cited by at least 500 other papers, to see if any had resulted in a human trial of the treatment in question. Despite all the animal studies being positive (that is, the treatment was effective) only 8 of the studies resulted in approved drugs for humans – that’s a mere 11%.

Despite the prestigious journals in which they originally appeared, more than half of the 76 highly-cited animal studies used methods and design that rated poor or low. Quality of the design, however, didn't appear to affect the main outcome: studies with "good" methods were no more likely to be replicated in human studies.

The authors of the new study warned that even the very limited success rate of 11% was likely to be an overestimate because they examined only highly-cited studies featured in very prominent journals. They went on to conclude that,

“...patients and physicians should remain cautious about extrapolating the findings of prominent animal research to the care of human disease”.

The reference for the study is: Hackman, D.G. and Redelmeier, D.A. 2006. Translation of research evidence from animals to humans. Journal of the American Medical Association 296, 1731-2.

From ECEAE newsletter "Testing Times" November issue

The eyes have it: Part II

Recently, I mentioned some vision experiments that I dubbed "Life through a keyhole," and "The eyes have it: Part 1." Here is another example of a vision experiment performed on monkeys.

Citation: L Kiorpes, C Tang, and JA Movshon (2006) Sensitivity to visual motion in amblyopic macaque monkeys. Vis Neurosci 23(2): 247-56.

Summary of experiment: Nine young male rhesus macaques were used in the experiment. In addition, data from nine others used in an earlier study served as normal controls. For four of the experimental monkeys, a “lazy eye” was induced surgically at ~4 weeks of age. Judging from the detail in the methods section, surgery was performed under ketamine sedation rather than anesthesia and no analgesia was mentioned. The other five monkeys were raised wearing a single defocus lens beginning from ~4 weeks of age and ending before 8 months of age. Operant conditioning for visual tasks was used to measure the perception of motion ranging from very small to larger movements. Tests were done for motion at different speeds, visual distances and levels of contrast. General vision tests (like the ones humans get for glasses) were also performed.

Results: Under some conditions the lazy eye performed better than the “fellow” eye and under other conditions worse. In some cases, performance was roughly equal.

My notes:

• The first author has been publishing articles on monkey vision since at least 1984.


• Many of the papers cited in this article pertain to “lazy eye” and vision in humans. Why bother with a model?


• They mention providing visual and tactile enrichment for the monkeys who they are blinding. Infants and blind animals satisfy the requirements for special consideration under Section 3.81 of the AWA regarding psychological well-being.



• Infants were "obtained" from WaNPRC and hand-reared in the NYU visual neuroscience laboratory.


• Approved by UAWC and conformed to “the Guide.”


• Given the many test conditions in this experiment, and changes that take place as the animal ages and becomes more experienced (with the testing), the lack of independence between each eye in a pair belonging to a single monkey, the statistical analysis is suspect.

Affiliations: New York University Center for Neural Science

Funding Acknowledged: National Eye Institutes EY05864 and EY02017. Additional support was provided by an investigatorship from the Howard Hughes Medical Institute. Also acknowledged RR00166 to the Washington National Primate Research Center.

The Scientist : PETA asks journal to retract paper

The Scientist : PETA asks journal to retract paper

Pretty self explanatory.

The eyes have it - Part I

Phototherapy is a common, successful treatment for age-related macular degeneration and other retinal disorders among people. Laser treatment of the affected eye can help patients with such conditions, and the power of the laser treatment and lens employed are calibrated to the unique qualities of each patient’s eye – including axial length. Monkeys naturally have axial lengths shorter than those of people. Despite this, and the fact that there are already human data on this treatment, some still choose to experiment on animals.


Citation: Effect of axial length on laser spot size during photodynamic therapy: an experimental study in monkeys. M Kondo, Y Ito, K Miyata, N Kondo, K Ishikawa, and H Terasaki. Am J Ophthalmol, January 1, 2006; 141(1): 214-5.

Summary of experiment: Authors used some pediatric equipment because of the size of the monkeys' eyes. The authors indicate that they have not treated any patient with an axial length in the range of these monkeys.

“Although we have not performed PDT on patients with very short axial lengths, a reduction of the spot diameter should be considered for such cases.” P. 215

Three monkeys with healthy eyes received the laser treatment. After one week there was an unusually powerful response to the laser, so they cut the eyes out to examine them. Once they figured out how their equations for laser calibration had to be adjusted, they performed the experiment on one additional monkey, cut his eyes out and got the results they expected.

My Notes:

• Procedure tested on these monkeys has already been vetted through a variety of clinical trials in humans.
• Despite existing data on humans treated with phototherapy and their natural variation in axial length, AND the fact that experiments with a model eye have shown that there is an important relationship between axial length and how the eye responds to this specific form of phototherapy, investigators decided to conduct an experiment in monkeys.
• The authors did not indicate whether the animals were killed in addition to having their eyes removed.
• There was very little detail about the methods, as this was a short communication.

Author affiliation:
Department of Ophthalmology, Nagoya University School of Medicine, Nagoya, Japan

Funding acknowledged: Supported by a Grant-in Aid 16591747 (M.K.) and 16390497 (H.T.) from the Ministry of Education, Science, Sports and Culture, Japan

Bored to distraction

The barren environment of the laboratory is associated with a number of physical and psychological pathologies among animals used in laboratory experiments. New Scientist recently reported on a lethal experiment ("Bored monkeys make for stupid monkeys" 11/19/05) demonstrated how "standard" and "enriched" environments affected adult monkeys' brains. I think that "bored" is, at best, an understatement for what these animals experienced, but I suppose word choice is the sort of thing that comes with editorial power.

I simply had to respond to the fact that the ethical implications of such experiments were sidestepped in an opinion piece printed in the most recent issue: Bored to distraction.

Sad Simians (Depressed to Death)

We've all heard the cliche about dying from a broken heart. For some monkeys, it's not a cliche at all. It's the result of a lifetime of suffering in captivity - isolated from friends and family and surrounded by individuals who are enemies who cause fear, pain distress and suffering. Others don't appear to care one way or the other. Some of those individuals are other monkeys - and some of them are the humans involved in the experiments.


Citation:
Shively, C. A., Register, T. C., Friedman, D. P., Morgan,T. M., Thompson,J., and Lanier, T. (2005). Social stress-associated depression in adult female cynomolgus monkeys (Macaca fascicularis). Biol Psychol 69:67-84.

Summary of experiment:
Female monkeys were put into unnatural social groups intended to induce extreme depression in some animals. The social stress was devastating.

"Over the course of the experiment, 56% of the monkeys in the highest quartile of depression died (5/9), whereas there were only one (11%) or two (22%) deaths in each of the other quartiles. Thus, behavioral depression was associated with increased mortality..."

*Only one or two deaths*? In a setting where proper nutrition is supposedly provided, there are no predators or natural disasters, and veterinary care is readily available, what could the mortality rate be? Apparently there are some very serious risks for morbidity and mortality in this lab.


Institutional affiliations:
Wake Forest University School of Medicine

Funded by:
National Institute of Mental Health
National Institute of General Medical Sciences
John D. and Catherine T. MacArthur Foundation

Speed kills (brain cells and monkeys)

Maryland, USA

People take prescription stimulants for ADHD. This article reported results from experiments on monkeys to see if normal clinical doses of a prescription stimulant caused brain damage in NHPs after 4 weeks of use. The authors write about two baboon experiments and one experiment on wild caught squirrel monkeys.

Citation: Ricaurte, G. A., Mechan, A. O., Yuan, J., Hatzidimitriou, G., Xie, T., Mayne, A. H., and McCann, U. D. (2005). Amphetamine treatment similar to that used in the treatment of adult attention-deficit/hyperactivity disorder damages dopaminergic nerve endings in the striatum of adult nonhuman primates. J Pharmacol Exp Ther 315:91-8.

Summary of Experiment:
These authors don’t report the number of monkeys clearly in their methods section. My best effort to understand how many animals were used from the captions to their figures are that there were 9 baboons and 9 squirrel monkeys…but the ambiguity means this is a minimum # of animals and there may have been more.

All animals were killed after about 4 weeks of drug administration. The brains of amphetamine-treated animals differed from controls. Based on the damage done to the brains of animals given the drug, the authors concluded that clinical doses of stimulants were neurotoxic and they called for more controlled studies.

Author affiliation: Department of Neurology, Johns Hopkins Medical Institutions, 5501 Hopkins Bayview Circle, Rm. 5B.71E, Baltimore, MD 21224, USA.

Funding acknowledged: United States Public Health Service Grants DA13946, DA017964, and HD050202