When researchers Arvid Carlsson, Paul Greengard, and Eric Kandel shared the Nobel Prize in Physiology or Medicine in 2000, we commissioned memory researcher John H. Byrne to write an essay on what their achievements meant to the field. In his 2001 essay, “How Neuroscience Captured the Twenty-First Century’s First Nobel Prize,” Byrne starts with a good chunk of Kandel’s acceptance speech; gives a cogent review of each scientist’s separate path and how their discoveries eventually entwined; describes how this changed the field; and considers what it might mean for the future. As you might suspect, it’s a long essay, but full of gems.
Whether overdue or just in the nick of time (as the Decade of the Brain closes), this Nobel Prize celebrates an achievement different in kind from previous observation, speculation, and investigation of the brain. For the ﬁrst time, an unambiguously mental phenomenon—memory—has been explained in wholly material, mechanical terms. The hypothesis of a separate, nonmaterial, otherworldly realm has become superﬂuous. A banquet is not the place to spin out these disturbing implications, but Kandel does acknowledge them, for those who will hear, by returning to where his story began—“Know thyself.”
From Kandel, who spoke for all three that night:
“The three of us whom you honor here tonight, and our generation of scientists, have attempted to translate abstract philosophical questions about the mind into the empirical language of biology… We three have taken the first steps in linking mind to molecules by determining how the biochemistry of signaling within and between nerve cells is related to mental processes and mental disorders. We have found that the neural networks of the brain are not fixed, but that communication between nerve cells can be regulated by neurotransmitter molecules.”
In reviewing the history of neuroscience and research, Byrne describes “gaps in the foundation” in understanding how the brain works at mid-century:
Although the task was daunting, the next step in understanding the hardware of the brain was to explore its wiring to see how billions of similar neurons might be connected to process information. Some nagging questions, and the implications of certain new discoveries, however, also began to suggest gaps in our knowledge. The computer analogy was already looking inadequate. First, two neurotransmitters seemed sufﬁcient (one to excite and another to inhibit); but more were known to exist, and perhaps there were still more to be discovered. Was more than simple excitation and inhibition going on? Or did some circuits in the brain have speciﬁc neurotransmitters dedicated to their exclusive use?
Nor did this brain model, as it stood, go very far to solve the mystery of learning and memory. How could richly interconnected but stable neurons store a memory? Perhaps memories were stored in reverberating loops of electrical activity in interconnected neural networks. Or perhaps synapses might themselves be plastic and growing. If so, exactly how did they change? Finally, and, perhaps most important, what were the underlying mechanisms of various brain diseases? Despite progress at the level of basic understanding, by the 1950s not a single neurological or psychiatric disorder was understood at a mechanistic level. There were precious few treatments, few drugs available, and no understanding of why the drugs worked.
While the history section is clearly written and fascinating, the most telling part for me was toward the end. In the past decades, have we moved any farther along this path?
Carlsson’s work led directly to a rational treatment for Parkinson’s disease; it seems likely that the discoveries of Kandel and Greengard will benefit the treatment of other diseases such as age-related memory loss, mental retardation, and Alzheimer’s disease. But much remains to be done. There is a treatment for Parkinson’s disease, but not a cure. What are the mechanisms that lead to the degeneration of the dopamine neurons, and how can we prevent this process? Similarly, there are treatments for schizophrenia and depression, but the underlying mechanisms are unknown.