Thanks a lot for all of your feedback on the past issues and I highly appreciate that! We are exploring a new format in which each issue focuses on original and in-depth discussions on one topic and will contain references and links for follow-up reading.
Besides, the focus of this newsletter is always quality rather than quantity, and I hope every issue will be useful for you. As a result, I will decrease the email frequency to bi-monthly to give myself more time to research topics and to prepare high-quality essays (I will add one-off issues if bandwidth allows).
Please see below the first issue of the new format. Thanks again for your readership and please feel free to let me know if you have any suggestions or feedback. :-)
In Search of Memory
Eric Kandel won the Nobel prize in 2000 for his contribution to the understanding of memory at the molecular level. His autobiography, In Search of Memory, describes both his experience of escaping from Austria to America and his inquiry into the science behind our memory throughout his career. This essay is created based on the autobiography and extensive researches on the web.
Escape from Holocaust
Eric was born in a Jewish family in Vienna. As a Jew, Eric's childhood was dominated by the Nazi's growing influence in Austria. From its very beginning of the 1920s, the Nazi party aimed to merge all German-speaking people into a Greater Germany. In 1937, Hilter forced the Austrian chancellor Schuschnigg to resign and sent his troops to occupy the country, which was the largest German-speaking state outside Germany. The event, known as Anschluss, was welcomed by the Austrian Germans because a lot of them felt Austria was not fairly treated in the Treaty of Saint-Germain signed after WWI. After the Nazis took the power in Austria, a lot of Austrian Jews were forced to leave the country due to the violence targeting them (e.g., Kristallnacht). Thanks to the help of a local Jewish organization Kultusgemeinde, Eric's family was able to emigrate to the United States of America in 1939. The young Eric was only Nine by then.
Most of the Jews who didn't escape Nazi Austria became the victims of the Holocaust. The experience of escaping the Holocaust greatly influenced Eric throughout his whole life. Later after Eric won the Nobel prize in 2000, he used his influence to press the Austrian government to recognize the misfortune of the Jew community during Anschluss, which was largely ignored post-WWII, and to advocate the rights of Jews community in the country.
After emigrating to the US, Eric finished his education first in a Jewish school and then attended Harvard College. There Eric was attracted to psychoanalysis because it was imaginative, comprehensive, and empirically grounded. His attraction to psychoanalysis was further enhanced by the fact that its founder Freud was Viennese and Jewish and had been forced to leave Vienna. He later enrolled in New York University and aspired to become a psychoanalyst. In the fall of 1955, Eric decided to take an elective at Columbia University with the neurophysiologist Harry Grundfest. Since then, Eric's research career gradually shifted to find the biological basis of mental function.
Eric is particularly interested in the formation of memory. In 1890, William James concluded that memory must have at least two different processes: a short-term process and a long-term process. The basic units of the brain are the neurons, which are connected through synapses. Signals of one neuron are passed to the next neuron through chemical neurotransmitters that are available in synapse. One common hypothesis is that short-term memory is stored as the distribution of neurotransmitters across different synapses. A stimulus would activate a spatial pattern of activity across neurons in a brain region, which will deplete the neurotransmitters. The distribution of neurotransmitters will form a trace of the stimuli, which is the short-term memory.
The short-term memory trace decays over time as neurotransmitters are re-generated. As a result, short-term memories need to be consolidated to long-term storage. Behavioral experiments suggest it happens through repetition --- what is well known as "Practice makes perfect".
Scientists also realized the importance of the hippocampus in turning short-term memory into long-term memory thanks to the extensive research on Henry Molaison (H.M.), who is probably the most famous patient in the history of memory research. After a treatment operation in which his hippocampus was removed, H.M.'s intelligence was intact, yet he lost the ability to form new memories. Other than this vague picture, Scientists had very little knowledge of the exact biochemical process of memory. It was under such a background that Eric entered the domain of memory research.
The first question Eric needs to answer is how neurons could adjust their connections based on environmental stimuli. Unfortunately, Human brains are too complex for any thorough analysis, each human brain has about 100 billion neurons. As a result, Eric experimented on Aplysia instead, whose brain has only about 20,000 cells, making it a perfect model animal to analyze how neurons work. In 1962, Eric joined the lab of a French scientist Ladislav Tauc, one of the few scientists who worked on Aplysia then, as a post-doc to learn about this interesting sea slug. Eric's work on Aplysia has laid the foundation for understanding the mechanism of memory -- so much so that Eric presented a picture of Aplysia wearing a Nobel medal during his Nobel prize ceremony,
In Search of Memory
Eric and his team realized that long-term memories are formed as anatomical changes of the neurons. A single neuron has approximately 1300 presynaptic terminals (only 40% of which are active) with which it contacts about 25 different target cells. Through the consolidation process, the creates long-term memory, both the percentage of active presynaptic terminals and their total number. The number of synapses changes during learning. Memory is recalled when a certain sensory stimulus triggers the "reads out" of the new state of the synapse, which has been altered by learning.
In 1953, Waston and Crick proposed the famous Double Helix model of DNA, which opened the new world of molecular biology. In the memory-research field, Louis Flexner from the University of Pennsylvania discovered that applying a drug that inhibits the synthesis of proteins would disrupt long-term memory. Eric realized that the same process also applies to Aplysia and that long-term memory storage requires the synthesis of new proteins.
One revolutionary breakthrough in molecular biology was the realization that gene function can be regulated up and down in response to environmental signals. Inspired by this breakthrough, Eric continued to investigate genes' role in learning and memory formation. Through researching Aplysia, Eric and his team realized that long-term memory is formed through switching on and off certain genes that increase or inhibit the growth of certain synapses.
For decades, Kandel has been studying how we create short-term and long-term memories at the molecular level. His work helps reveal the full picture of the memory-forming mechanism:
The memory storage takes place in at least two stages: A short-term memory lasting minutes is converted -- by a process of consolidation that requires the synthesis of new protein -- into stable, long-term memory lasting days, weeks, or even longer.
A single stimulus strengthens the synapse through the depletion of neurotransmitters, which form the short-term memory.
Repeated stimulation causes certain genes to be switched on and the growth of new synapses, which creates long-term memory.
Eric's journey from a refugee from Austria to a Nobel Laureate is a great example of how the tolerant and open environment of America could release boundless energy from immigrants like Eric and inspire them to think in new ways. In contrast, the city of Vienna, once a center of art and science, lost its glory under the suppressive occupation by the Nazis. His experience is still important for us after a hundred years.