The root of all evil

Remember the horrendous bilateral leg fracture experiment from last week? The senior author on that study is featured again this week! I think we should name this guy the Marquee du Sade of primate experimentation. This week he’s published an article about the interactive effects of tooth infection, root canal, bone healing and an experimental bone growth support treatment. They subjected 6 crab-eating macaques to dental hell for approximately one year.

Citation: Bergenholtz G, Wikesjo UM, Sorensen RG, Xiropaidis AV, Wozney JM. Observations on healing following endodontic surgery in nonhuman primates (Macaca fascicularis): effects of rhBMP-2. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Jan; 101(1):116-25.

Summary of experiment: All monkeys were given tooth infections in their upper (4) and lower (4) incisors using a gruesome technique developed 25 years ago:

“The pulp tissue in each tooth included in the study was accessed, lacerated with endodontic files, and exposed to the oral environment for 1 week to induce a pulpal infection.”

A temporary filling was put in each tooth for 4 (upper teeth) or 7 (lower teeth) months. Bone lesions developed in 37/48 teeth. Several months after the temporary fillings were put in, they performed root canals for the infected teeth. Teeth on one side of the mouth were treated with the experimental agent. Dental exams and photos were taken pre- and post-surgery and at 1, 3 and 4.5 months post-surgery. Animals were euthanized for histopath.

There was some degree of healing over time – seen as early as one month after surgery.

“The findings corroborate previous observations on bone healing and cementum regeneration following endodontic surgery including a human biopsy material and experimental lesions in laboratory animals.”

However, there were complications. At 4.5 months post surgery, all animals had completely or partially necrotic pulp in the infected teeth. There were complications in 3 surgeries – which authors attributed to the difficulty of there being two root canals so close together on roots that were narrow and curved (not really very much like human teeth). At 1 month, x-rays revealed that 4 of the canals had been over-filled with root filling material – something that hadn’t been noticed in the post-surgery x-rays.

My Notes:

• Animals were anesthetized with telazol for X-rays and exams
• A prophylactic antibiotic injection was given within one hour of each surgery + 5 day treatment with broad spectrum antibiotics. (Given the necrosis and lesions, not enough to control infection.)
• Long-acting opiate pain killer (buprenorphine) was given for TWO DAYS after each surgery for pain control. AFTER you have holes drilled in 8 teeth with pulp laid bare? Or after 4 simultaneous root canals????? 2 days of pain medicine?
• Euthanasia by Phenobarbital overdose

The experimental agent didn’t have any effect on outcome, but they didn’t say it that way:

“In conclusion, from a clinical perspective this study does not generate support for the use of powerful biologic agents to enhance bone healing following endodontic surgery.”

Um, if there was no difference, the substance didn’t enhance healing and apparently wasn’t powerful.

Author affiliations:
Göteborg University, Göteborg, Sweden
Temple University School of Dentistry, Philadelphia, PaWyeth Research, Cambridge, Mass

No funding acknowledged

3 Rs: reduction and replacement

The FDA announced new guidelines for drug testing today.

"Concerned about a system in which more than nine out of 10 experimental drugs fail when tested in humans, the Food and Drug Administration issued suggestions Thursday on how researchers can more efficiently evaluate the promise of new laboratory discoveries.

The vast majority of drug candidates fail once they're tested on humans, invariably for safety or efficacy reasons difficult to predict based on initial experiments done in test tubes and on animals. That can waste significant amounts of time and money, slowing the process of developing new drugs."

There are provisions for reducing the amount of animal testing done before human testing can begin and for an expanded roll for earlier invetigational trials in small groups of human subjects. One such approach is microdosing, where people are given very small doeses of a drug to study how the human body deals with the chemicals.

OT: I hate mornings

Waking up is horrible, and it takes hours for me to even feel like a human being. And no wonder. A study released earlier this week suggests that we are half-witted when we first wake. The effects on cognition are more severe than either sleep deprivation or being legally drunk.

Morning grogginess more debilitating than drunkeness or sleep deprivation, according to CU-Boulder study

Since another study found that 7% of workers drink on the job and 9% go to work despite nursing serious hangovers, I suppose that the grogginess and hangovers would be worst in the morning, then the on-the-job drinking kicks in at lunch time. Maybe the lesson is to call customer service in the evening if you really need something done.

Monkeys have it, we don't

Just think of all the monkeys that have been infected with SIV and S/HIV in the last 10 years in the effort (wholly unproductive) to find medicines for people with HIV and vaccines against the disease. Turns out that most people lack some genetic machinery (TRIM5 gene) that macaques have for fighting retriviruses like HIV.

A clue from macaques yields evidence for impaired retroviral defense genes in humans

Help! Our empathy is missing!

After reading the article Cells That Read Minds (New York Times), I was struck by the fact that there wasn't a single mention of the human ability to "feel" for the monkeys in these experiments.

They mentioned the electrodes, but not the restraint chair or the crainotomy needed to bolt a steel chamber to her head to hold those electrodes. They didn't mention that she was alone in a cage, rather than with other monkeys with whom she could use her mirror neurons.

So, I wrote a little letter to the NY Times...since they never seem to publish what I send them, I'm posting it here for good measure.
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To the Editor,

Your story on mirror neurons and the biology of empathy (Cells that read minds, 1/10) overlooked something conspicuous – our society’s lack of empathy for the monkey strapped into a chair with electrodes stuck in her brain. Despite their bright minds and unique personalities, many primates languish in small laboratory cages where they endure pain, fear, boredom and distress. Mirror neurons also provide vicarious terror when they see other monkeys wrestled from their cages, or injected with drugs, or maybe even killed at the end of an experiment. To see an example of what monkeys in laboratories commonly see, your readers can visit www.covancecruelty.com.

Given all we know about primates, it’s clear that how we keep and use them in labs is replete with ethical problems. If we take a long, hard look at the suffering of laboratory primates, our mirror neurons will tell us it’s time put an end to the cruelty.