Popular Press vs. Scientific View of Gene Discovery
Is There a Gene for
Information about the NMDA receptor
SUMMARY OF SCIENTIFIC PAPER
"Genetic Enhancement of Learning and Memory
in Mice" by Ya-Ping Tang, Joe Tsien, et. al.
Nature, Vol 401, September 2, 1999
In this paper, the researchers attempt to prove that overexpression of NMDA (N-methyl-D-aspartate) receptor 2B (NR2B) in transgenic mice leads to increased activation of NMDA receptors and enhanced learning and memory.
In the abstract, Hebb's rule is mentioned, which states that "learning and memory are based on modifications of synaptic strength among neurons that are simultaneously active." Therefore, since NMDA receptors are "synaptic coincidence detectors", overexpression of subunit NR2B which regulates channel gating and Mg2+ dependency, should increase plasticity and thus increase learning and memory. The reason the researchers went after the NR2B subunit is because the NR1-NR2B complex in vitro showed "longer excitatory postsynaptic potentials" (EPSPs) compared to other subunits. Therefore, this should allow NMDA receptors to have more time to detect synaptic coincidence. Another reason they chose the 2B subunit is because NR2B expression is "downregulated during the transition from juvenile to adult" which corresponds to decreased memory during this time period.
Before showing results of behavioral learning and memory tests with the transgenic mice, the researchers first show that the NR2B transgenic mouse does indeed have an increased expression of NR2B mRNA and protein when compared to wild type mice. Then they attempt to prove that the transgene is located in the same brain location as the normal gene and that the transgenic mice had functional synaptic sites. They provide the necessary data to verify their methodology. They also continuously mention that no structural, functional, or behavioral problems have been observed in the transgenic mice. In addition to gathering evidence to support their hypothesis, the researchers also want to show that overexpressing the NR2B gene doesn't cause any problems in the mice. If their results are validated and trials are conducted on primates and eventually humans, they want to be sure that unexpected side effects won't result from overexpression of NR2B.
The next section of the paper is dedicated to showing that overexpression of NR2B indeed causes improvements in synaptic function and behaviors that test learning and memory. Again, they provide sufficient data to support their hypothesis. They successfully demonstrated that overexpression of NR2B results in prolonged opening of NMDA receptors, enhanced NMDA activation , and enhanced EPSPs. They also demonstrated that these results were do specifically to the increase in NMDA receptors and that AMPA receptors and GABA mechanisms were not having an impact on the data. The researchers performed many electrical tests both inhibiting and stimulating various pathways related to NMDA activation and found that the NR2B receptor was functioning as predicted. By testing the mice performing different learning tasks, the researchers determined that enhancement of synaptic responses from 10-100 Hz represents an "optimal plasticity curve." They also found differences, not in the ability of mice to retain information for short time periods, but rather the transgenic mice excelled when long term memory, associative and dissaciative emotional memory, and spatial memory were tested.
In conclusion, these researchers successfully identified NR2B as a "molecular switch" in the memory process and hope to target this gene for treatment of learning and memory disorders. The researchers state that their results suggest that "genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible." I guess since it is a broad statement, they are correct in saying it, but I believe that much research remains to be done before scientists will be able to alter intelligence in humans. The aim of authors of scientific papers is to convince the reader that their interpretation of the data is correct. They also hope to persuade the reader that the issue they are investigating is important and research in the area should continue. Authors of popular press articles have different goals as will be discussed in the next section.
SUMMARY OF POPULAR PRESS ARTICLE
"Smart Genes?" by Michael Lemonick
TIME, September 13, 1999
Although the opening picture of this TIME article is a brainy looking little girl, the inset title is "IQ Gene," and the first two paragraphs introduce the reader to "supermouse," I was impressed by the coverage of this scientific story in a popular press magazine. The article was published in response to the above scientific article in Nature reporting the collaboration of scientists at Princeton, MIT, and Washington University to overexpress the NMDA receptor subunit 2B gene in mice which resulted in enhanced learning and memory abilities.
Although the author quotes the most optimistic sentence from the scientific paper where the scientists write that their "results suggest that the genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible," he states in the following sentence that many "colleagues called the researcher's conclusions unwarranted and farfetched." The author continues to mention possible difficulties with the research throughout the article which I commend. He even brings up the idea that the mice may not be "supermice," because the researchers interpreted the data they received. They couldn't assess the intelligence of the mice by having conversations with them :-) The research indisputably brings hope and may possible future experiments to the world of neuroscience and understanding how learning and memory function, but scientists are still a very long way from designing intelligent babies. The author conveys this idea to the readers when he states that although this discovery makes scientists hopeful that they will one day be able to treat human learning and memory disorders such as Alzheimer's, he states that the "major impact of this work at the current time is to give neurobiologists further evidence about what memory is and how is works."
Another idea that the author touches on that shows the complexity of the issue is discussing the definition of intelligence itself. How does a scientists define or measure intelligence? Especially, how is this done is mice? Intelligence can be defined as possessing various qualities such as creativity, problem-solving, wrote memory, the ability to understand people, etc.,etc.,etc.--the list can go on forever. Also, although the researchers did show data supporting their claim that when the NMDA receptor was overexpressed, the mice learned various tasks more quickly and remembered them longer, changing this one component in animals or humans might not make them that much more 'intelligent.' The basis for intelligence, whether it is inherited or environmentally shaped is another issue that has been argued for centuries. What impact do experiences have on the brain?
Here, the author discusses the complex working of learning and memory. He touches on the issue of plasticity and states that it is not located in a single area of the brain. He says that "although memory plays a central role in our mental lives, we do not have a memory system in the brain. We have memory systems that interact together to create what we call, memories." He brings in a famous psychological case to demonstrate his point. I thought this was a good way to both expose people to the complex fragmentary nature of memory and the field of psychology and neuroscience. He also briefly touches on the different types of memory, associative and explicit. When H.M., the individual in the story had his hippocampus removed, he lost the ability to form new memories (long term memory), but retained his short term memory. He also discusses briefly how the brain changes as people learn new things. Connections are made between cells and the strength of these connections is altered by experience. Again, the author brings in a famous psychologist to support his point; Hebb and his coincidence detector theory.
From all of the basic information provided, the reader should be able to follow
why scientists hypothesize that the medial temporal lobe and hippocampus are
key in transforming short term memories into permanent ones and that permanent
memories are stored elsewhere. The small diagrams depicting the NMDA receptor
are helpful in understanding the effect the scientists manipulation of the NMDA
gene had on the functioning of the mice brains.
In conclusion, I felt that although the TIME article did exaggerate the research at times, the author did a good job providing basic terminology and scientific information while presenting various sides to the story. Eye catching pictures, titles, and the mention of hot diseases like Alzheimer's are necessary to peak the public's interest in the article and once they start reading they should realize that although this was a great discovery, it's not a miracle cure and people won't be altering people's intelligence overnight. The article presents both the pros and cons of the science and the dreams and actual uses for the technology. Although the animals haven't experienced any adverse reactions as far as I know, the drugs that might be produced from this study to boost the action of the NR2B molecule may cause problems, especially if trials are attempted in humans. The transition from humans to mice is the big jump, so it will be interesting to see the results when the research reaches that point. The interpretation of intelligent mouse behavior may have no correlation to human behavior.
The main difference between the two articles stems from the audience they are trying to reach. The scientists are writing their paper for their peers who already know most of the neuroscience information and they are just trying to convince their peers of their methodology and data interpretation. The popular press author on the other hand, must grab the attention of the reader who might have no background in the sciences and help him or her understand the procedure the scientists performed, the data the obtained, and the future implications of the research. I did find many other popular press articles that really exaggerated the findings of this study, but I thought TIME did an excellent job. Hopefully after reading this article, the public won't be going to their doctor asking for them to make their next child more intelligent.
*All quotes taken from the paper discussed in the section.
Lemonick, Michael D. September 13, 1999. "Smart Genes?"Time. 54-58.
Tang, Ya Ping; E. Shimizu, G. Dube, C. Rampon, G. Kerchner, M. Zhuo, L. Guosong, J. Tsien. September 1999. "Genetic Enhancement of Learning and Memory in Mice." Nature. 401: 63-69.
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