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2008-05-11T15:45:34-05:00

Associated Press May 11, 2008 WASHINGTON - Families claiming that a mercury-based preservative in vaccines triggers autism will challenge mainstream medicine Monday as they take their case to a federal court. 


The Role of Pheromones in Sex and Aggression


Image: Dr. Catherine Dulac and AAAS
This activity includes:
- Introduction
- Video
- Discussion Questions

Living organisms use a variety of means to communicate with one another. The bared teeth of a growling dog, the cry of a startled bird, and the wail of an infant all send clear messages, such as "back off," "danger," or "help me!" Likewise, many organisms use pheromones to signal sexual receptivity or territoriality. For example, when a female cat is in estrus, tomcats can smell the pheromones that signal a readiness to mate; similarly, dogs micturate along fences, trees, and other objects in their territory to mark the area as "occupied."

How such signals are perceived is an area of active research among psychological scientists, who have studied the effects of pheromones on behavior through the use of "knockout mice"-laboratory animals specially bred to eliminate a specific gene or genes deleted from their DNA. Scientists have designed all manner of knockouts; some have a predisposition to alcohol while others an aversion; some are prone to kidney or skin diseases. Knockout mice provide an important tool for investigating diseases in humans.

Dr. Catherine Dulac at Harvard has used knockout mice to study how a specific brain center called the vomeronasal organ (VNO) controls rodent sexual behavior. Dulac and her colleagues found that they could create a knockout mouse that was missing an important functional pathway in the VNO known as the TRP2 ion channel. Her knockout mice were therefore normal except for a dysfunctional VNO. How would these knockout females react to a normal, sexually-mature male?

As it happens, gender recognition is largely based upon olfactory cues that are present in the urine of adult males and females. These pheromones are detected through the VNO. Under normal conditions, a male mouse will react aggressively when a second male is introduced into its established territory. An attack by the aggressor is typically preceded by rigorous tail rattling. Thereafter, the aggressor typically lunges toward the other male, biting the victim's flanks and/or hindquarters. By contrast, a male mouse will not attack a female that is introduced into its territory, but will instead attempt to mate with her.

Dr. Dulac's findings are demonstrated in a series of short video clips, presented here. In the first research condition a normal male (left) is paired with a castrated male that produces no pheromones.

>>Watch the Video
[this movie requires the Flash 6 plug-in ]
Video reproduced with permission of Dr. Catherine Dulac and AAAS.

>>Watch the Video
[this movie requires the Flash 6 plug-in ]
Video reproduced with permission of Dr. Catherine Dulac and AAAS.

The castrated mouse shown in the first condition provokes no response from the resident male, suggesting that something other than the mere presence of the mouse signals a territorial threat to the intact mouse. However, in the second condition, the resident male attacks the castrated intruder carrying intact male urine. While the mice are the same in both trials, trial 2 differs in that the castrated male intruder is carrying normal male pheromone. These two experiments suggest that sexual identity is signaled not by vocalizations, behavior, or appearance in male mice, but by pheromones instead. In the absence of the male pheromone, the resident feels no need to defend his territory.

In the third research condition, a TRP2 knockout resident male mouse is introduced to a castrated intruder that has been swabbed with urine from an intact male mouse. Will the knockout mouse defend its territory? In fact, a knockout mouse may react to a male intruder in a fashion not typically shown by intact males.

>>Watch the Video
[this movie requires the Flash 6 plug-in ]
Video reproduced with permission of Dr. Catherine Dulac and AAAS.

Rather than attacking the intruder, the TRP2 knockout attempts to mount the other male. Moreover, the knockout mice also emitted ultrasonic courtship vocalizations toward male intruders. Males typically make such vocalizations only during encounters with females. Dulac and her colleagues interpret these findings to mean that without the TRP2 ion channel, the VNO of the knockouts was unresponsive to pheromonal cues; thus, the knockouts were unable to discriminate male from female intruders. This interpretation was supported by the observation that neuronal activity in the VNO that is triggered in response to male or female urine was not observed in the VNO of knockouts. Furthermore, the investigators suggest that the most adaptive strategy for the knockouts to adopt during encounters with a strange mouse of indeterminate gender was to initially treat all intruders as females.

Discussion Questions:

  1. The article available online from the Harvard Gazette indicates that we all have a VNO early in utero, but that it shrinks as we develop. What does this suggest about the role of the VNO in humans?


  2. Do humans communicate via pheromones? Behavioral neuroendocrinologist Martha McClintock was an early investigator into human pheromones. McClintock found that undergraduate women who were close friends or roommates averaged 9 days apart for the onset of their menstrual cycles. One member of the pair then wore an armpit pad that was swabbed across the upper lip of the other member of the pair. Over the course of the experiment, the woman's cycles converged. Do McClintock's findings support or refute the suggestion that there is a human analog of the VNO?


  3. Assume for a moment that in the near future, medical researchers will learn to selectively turn specific genes in humans on and off. If Dulac can "disable" the VNO with a knockout procedure, should scientists try to "knock out" schizophrenia, depression, or violent tendencies?


  4. Brain architecture also plays a part in sending chemical messages. Given the differences in brain structure between a mouse and a person, do you think that discovering a way to stimulate any VNO-like structure in humans will lead to the ability to easily turn human sexuality on and off?

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Web Links:

To read the original article in Science Daily on Dulac and the TRP2 gene, visit www.sciencedaily.com/releases/2002/02/020201074842.htm.

Two brief summaries of the work of Catherine Dulac are available online:

The Howard Hughes Medical Foundation: www.hhmi.org/news/dulac.html.
The Harvard Gazette online: www.news.harvard.edu/gazette/2002/02.07/01-mice.html

Primary References:

To read more about pheromones and menstrual synchronicity, see K. Stern and M. McClintock, "Regulation of ovulation by human pheromones," Nature 392 (1998): 177-79.

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