A long life entirely devoted to science
Susumu Tonegawa, sole recipient of the 1987 Nobel Prize for Medicine, recently revisited Basel—after a decades-long absence from the city where he had accomplished all the work that was eventually crowned with the highest honor in the field.
Every single seat in the large auditorium in Building 71 was occupied at 10.30 a.m. on 22 January, as Nobel laureate Susumu Tonegawa took the podium to give a lecture on the “Neuroscience of Memory.
Visibly moved, Susumu (74) started off by saying how pleased he was to be “back home.” By “home” he was, of course, referring to his ten years residence in Basel, from 1970 to 1980, working at the Basel Institute of Immunology, the basic research institute founded and sponsored by Roche. “This was really a great time for me in my career,” added Susumu. “We had complete freedom. Niels Kaj Jerne, the first director, put together the most amazing immunology science institute in the world.”
I want to understand memory by investigating the physical brain
Three Nobel Prize winners emerged from the institute, and they did all their important work at this now legendary place in Basel: Niels Kaj Jerne, Georges Köhler, and Susumu Tonegawa. Susumu discovered and elucidated the genetic origin of antibody production, the mechanisms by which the almost endless diversity of these immune defence molecules is generated. He made the outstanding discovery that genes can be rearranged in specific ways to produce this diversity. He was able to reveal the basic structure of antibody genes as well as the mechanisms by which they are expressed. This great discovery was to become the indispensable prerequisite of recombinant antibody technology.
Physical underpinnings of memory
Since 1981, Susumu Tonegawa has been a Professor at the Massachusetts Institute of Technology (MIT) in Boston, where he still heads a research lab. Around about the year 1990, he gradually transitioned from immunology to the neurosciences.
He says, “I wanted to understand what we traditionally call ‘mind phenomena’, such as memory and learning, by investigating the physical brain.” Thus, Susumu has been keen on investigating the molecular, cellular and neural circuit mechanisms underlying learning and memory. In this wider context, Susumu likes quoting DNA co-discoverer Francis Crick, who in his book The Astonishing Hypothesis wrote: “Your joys and sorrows, memories and ambitions...are no more than the behavior of a vast assembly of nerve cells and their associated molecules.”
By using genetically engineered mice and subjecting them to a set rigorously designed studies, Susumu has been able to catch glimpses of the physical, or material, underpinnings of “mind phenomena” such as memory.
Creating a “false memory”
For instance, in experiments Susumu calls “the rodent version of Pavlov’s classical conditioning,” he placed mice in two different chambers, and elicited context-dependent fear conditioning in mice in chamber 1. He did this by delivering a short electrical foot shock to them. The next time these mice were again put in chamber 1, although no foot shock was delivered, they instantly “froze” (typical self-protection reaction out of fear). This is ample proof that they instantly “memorized” or rather associated this chamber with danger, namely the foot shock. In chamber 2, where the mice had never been delivered any foot shock, they moved freely about, also during their subsequent visits, not showing any fear whatsoever.
Now what Susumu and his team succeeded in was to create a “false memory” in the mice by manipulating those brain cells in the rodent’s hippocampus that are known to carry traces of memory (so-called memory engram-bearing cells). That is, by optically reactivating the right neurons during fear conditioning in a different context, the mice showed a classical “freezing” reaction also in a context where they had never experienced any foot shock. These experimental data demonstrate, in essence, that it is possible to generate a behaviorally expressed “fear memory” by purely artificial means.
At the forefront of basic research
Toward the end of his talk, Susumu Tonegawa emphasized the importance of doing basic research. He contended that most of the really important applications in medicine had their roots in basic research. Then Susumu commended Roche for its far-sighted vision in establishing the Basel Institute of Immunology, and he concluded: “It is wonderful that a company like Roche has been at the forefront of basic research as well as at the interface between basic and applied research.”