Wednesday, March 13, 2013

More discussion about Kalin's goals and methods

These are observations from "The Ethics of Animal Experimentation: A conversation between bioethicist Rob Streiffer and research critic Rick Marolt" that was held on March 11, 2013, sponsored by the UW Animal Rights Society and recorded in the video at the end of this post. I've written here in regard only to the part of the conversation that specifically addressed the details of Ned Kalin's project.

Both Rick Marolt and Rob Streiffer are familiar with the details of the procedures; they both had access to the protocol for months, and in Streiffer's case, many months. In Streiffer's case, this has to have included significant focused discussion about those details with people who were also familiar with the protocol.

Their difficulty with these details underscores just how devilishly hard it is to talk with people about these matters. I don't understand why it is so hard to understand what is in store for these baby monkeys, but quite clearly, even people familiar with the protocol and who have had ample opportunity to think about it still find it difficult to understand.

(Times here are fairly accurate but could be off by a few seconds.)

24:10 Marolt: My understanding is that the researchers are interested in developing an anxious personality.

This is sort of right, but it misses Kalin's main point. A significant part of Kalin's decades of experiments on monkeys has been based on his ability to identify monkeys with the trait-like characteristic of being highly anxious. (They use the term "trait-like" and phenotype, because the genetics underlying this characteristic is not understood.)

See my post from July 8, 2008: "Trait-like anxious temperament in primates." And see too the the papers: Lateralized effects of diazepam on frontal brain electrical asymmetries in rhesus monkeys. Davidson RJ, Kalin NH, Shelton SE. Biol Psychiatry. 1992. And, "Lateralized response to diazepam predicts temperamental style in rhesus monkeys. Davidson RJ, Kalin NH, Shelton SE. Behav Neurosci. 1993.

Since learning that he could identify monkeys with an anxious temperament, Kalin's experiments have used such monkeys almost exclusively.

His point in this case is to record brain development over time in an effort to identify the molecular differences between the brains of monkeys who were raised under adverse conditions and those who were raised under less adverse conditions.

At about 26:00 Streiffer explains that the surrogate the infant will be kept with during the first three to four weeks of his life will have the ability to "rock back and forth, which past research has shown, helps infants develop [more normally, he seems to imply.] Kalin's protocol says: "While in the incubator, an upright surrogate covered with a soft material that is able to move back and forth at the infant's discretion will be provided for the animal."

Streiffer's comment regarding past research is correct. But from the very limited description offered in the protocol, it isn't completely clear what the surrogate will actually be. There is research showing that the "standard" moveable surrogate that seems to be referred to in the protocol, isn't the best choice if one wants the infants to develop normally, which of course, in this particular case, they don't. See: Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta). Dettmer AM, Ruggiero AM, Novak MA, Meyer JS, Suomi SJ. Dev Psychobiol. 2008.

At about 26:48, they try to explain the changes in housing over the course of the babies' lives. When they are removed from the surrogates, Marolt thought they would be placed in a colony situation at some point, but Streiffer corrected him and said that they would remain with a peer throughout their life. Marolt was sort of right when he says that they will be re-caged with a different peer later on, but he mistakenly thought it was to facilitate the study of the formation of a new social relationship. This is understandable because Kalin does make this claim, but it appears to be a second thought.

In fact, the babies will be placed with a new peer at six months of age because that is the age at which the 20 control monkeys will be taken from their mothers and placed with a peer, a common husbandry method used in the labs. (In the wild, infants remain with their mothers for a year, and can remain in the same troop as their mother throughout their life.) The change in peers of the peer-reared monkeys is intended to mimic -- at the same developmental time point -- the social upheaval that will be experienced by the mother-reared monkeys when they are removed from their mothers.

The idea in and of itself seems to make some sense in an experimental design sort of way, but a moment's thought suggests that it's pretty silly; it flies in the face of the fundamental design claim. The whole idea of maternally depriving the infants and subjecting them to other various stressors is to alter their brain development. It makes sense that it will, but at six months, many, research suggests most, of these changes are likely to have already occurred. So, the brains of the monkeys in the two groups, the deprived-adversely-effected group, and the control group, will already be too dissimilar to think that the removal from their peer, and the removal from their mother, will have similar neurodevelopmental effects, yet that is the reason given by Kalin.

At about 28:25, Streiffer says that the surrogate-reared babies have to be placed with other surrogate-reared babies rather than mother-reared babies because the peer-reared monkeys "don't know how to behave in a normal social environment."

It's not clear to me how he came to this conclusion. I cannot find such a claim in the protocol, but maybe I keep missing it. In any case, if this is what he was told, or what Kalin has claimed, it seems unlikely.

The infants are placed with a peer sometime between their third and fourth week of life. Kalin says that they cannot be placed with a peer earlier on because there isn't room in the incubator for two infants, and that they cannot be taken from the incubator until they are able to self-thermo-regulate, or control their own body temperature.

At three to four weeks of age, a macaque's social environment has been nothing other than close physical contact with his or her mother. "Social behavior" in a monkey of this early age is simply clinging and some exploration of the mother's body. The immediate reaction by a "normally socialized" four week-old infant to being taken from his mother is unlikely to be any different than the reaction of a surrogate-reared monkey taken from his "mother." They would both suffer profound emotional distress.

There actually isn't a reason not to pair the maternally deprived infant with a mother-reared infant (if you could even call being with one's mother for three to four weeks rearing); the actual reason is that they have the orphans on-hand because they created them. There isn't a need to look for some other rationale, and Kalin does not appear to offer one, but again, maybe I missed it.

Beginning at about 30:10, Streiffer explains Kalin's goals. He begins with Kalin's claim that he will discover changes in gene function and the genes involved in the development of an anxious phenotype. (Phenotype is the word used in biology to say observable or observed characteristics, like hair color, behavior, etc. It is commonly used to mean the characteristics that result from an organism's genotype, or genetic make-up.) I've recently written about this line of study here, and about Kalin's methods regarding the genetics underlying depression here.

At about 30:43 Streiffer quotes Kalin's protocol and says that the research has the "potential" to identify new targets for the treatment of the effects of early adversity.

But in correspondence with others, Kalin hasn't been so guarded. He has said that "Using primate models allows us to be certain that the knowledge we acquire is directly relevant to understanding the causes of human suffering." But even using humans hasn't meant any certainty about the knowledge gained being relevant to the understanding of the causes of human suffering. See: Molecular Neurobiology of Depression: PET Findings on the Elusive Correlation with Symptom Severity. Smith DF, Jakobsen S. Front Psychiatry. 2013.

It you have an interest in the philosophical framework of ethics, you may find the discussion of interest in spite of the occasional misunderstanding of Kalin's methods and goals.

The Ethics of Animal Experimentation from luciano M on Vimeo.

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