There is a disturbing trend in biological research toward not just correcting disorders, but attempting to enhance certain human characteristics that are perceived as advantageous. Clearly, there are a number of ethical issues involved in such practices, but the feasibility is also questionable. There is a fundamental difference between treating human disease and changing traits to "enhance" human functioning. Enhancing function, if such an end is practical, often requires a complete knowledge of the mechanism involved, whereas treating disease can be as simple as correcting aberrant features.
The paradigm case of biological enhancement through biology is memory. In the wake of Nobel Laureate Eric Kandel's research exists the possibility for improving memory through the cAMP (cyclic adenosine monophosphate) pathway. This pathway facilitates a phenomenon known as long-term potentiation, which is the lasting enhancement of synaptic efficacy resulting from repeated stimulation. This is a particularly good fit for a potential mechanism for memory as repeated stimulation results in long-term changes in synaptic transmission.
The protein, cAMP response element binding protein (CREB), has been the focus of much work in the memory field because of its important role as a mediator of long-term potentiation. From Kandel's early experiments in the sea slug, his work in hippocampal sections of mice, and his work with transgenic mice, CREB's central role in long-term potentiation has been incrementally demonstrated in detail. To increase levels of CREB, one can stimulate the second messenger cAMP which will de-repress protein kinase A(PKA), leading to activation of CREB through phosphorylation. CREB, once activated by phosphorylation then acts to increase gene expression selectively to strengthen the connections between synapses, likely encoding memory.
Kandel has continued his work into a private venture looking to capitalize on his research to provide treatments for diseases related to memory loss, such as Parkinson's and Alzheimer's. Further, it is speculated that this could be extended as a "smart pill," such that taking the pill would help people consolidate memories more efficiently, perhaps granting an advantage on your next organic chemistry examination. This would be a great improvement to drugs used to boost memory performance as it would break from the tradition of stimulants like caffeine and modafinil.
But, the question remains, will this "smart pill" work without other complications given the complexity of the nervous system? A helpful case study is the much celebrated "Doogie" mouse. This mouse expresses the NR2B subunit of the NMDA receptor at a greater level than normal and considering that the NMDA receptor has been implicated in memory through long-term potentiation, one would expect an increase in ability to learn. In fact, Tang et al. found that the Doogie mouse performed significantly better on a variety of learning tasks than a matched control with what appeared to be little side effects in a 1999 Nature article. Yet, in a 2001 Nature article, Wei et al. found that the Doogie mouse also has an increased susceptibility to persistent pain along with its superior cognitive abilities.
What can be gleaned from this example is that the possible mechanisms available for enhancement are currently quite crude. A drug specifically targeted at increasing CREB levels will have many other effects both inside and outside of the nervous system, some of which may be deleterious to the organism. Further, an attempt to improve a system that we do not fully understand is not a feasible option for long-lasting improvement without side effects. It is a much easier conceptual task to fix a problem that exists due to a few contributing factors than to be able to improve a complex system toward a particular end. It is unlikely that these mechanisms will have an impact equal to their hype without a more advanced understanding of integrative neuronal signaling and development and a better method for determining the timing and target location of these drugs.
Michael McDuffie can be reached at mm9kn@virginia.edu.