102 | December 2021 www.facs.website EN: Yes, grounding sounds like a perfect analogy. Only now, 15 years after our initial discovery, have we come to understand our system and can answer many of the questions raised by the referees of our 2007 Science paper. The carbon nanotube is an active participant rather than an inert bystander. EK: It would be great if more people could join this line of research, which still depends on a $4 million EM machine. What can attract more chemists to join the club? EN: I have a question for you. Why don’t you study individual molecules like biologists studying individual animals and flowers? Chemists may be too accustomed to discuss their business using structural formulae and spectroscopic data. Why shouldn’t they be proud of discussing and teaching chemistry using the movies of molecules in action? Chemistry has been so successfully built on the images of molecules that chemists have probably lost their naive interest in molecular reality. Abstraction is the power of science, but I sense that there is still a lot to learn from molecular reality. Please remember the enthusiasm shown by people worldwide for the NaCl movie. The movie has successfully visualized the chemical reaction that everyone has known since their primary school period. Chemists should share this naive feeling of people because “Scientific breakthroughs often build upon the successful visualization of objects invisible to the human eye”–– citation of the 2017 Nobel Prize for cryo-EM technology. As to the instrument, most research universities already possess the necessary instrumentation in their analytical center. I know that you have excellent EMs at the Technion, so your colleagues can do similar experiments. It is up to you to approach electron microscopists and discuss your chemistry. Many people are already working in this field. The EM technology and infrastructure are rapidly becoming democratic, as once expensive NMR machines have become commonplace. EK: From my perspective as an organic chemist, the turning point will be when the video analysis of single-molecule atomic resolution time-resolved EM (SMART-EM) crosses the barrier between organic chemistry and physical chemistry. Many will join once this technology becomes relevant to organic chemistry rather than just physical chemistry. I am sure this will happen one day, but how can you accelerate the process? Your work on the crystallization of sodium chloride inside a nanotube renders the technology highly attractive to experimental inorganic chemistry. But the key is the relevance to organic chemists. You know that organic chemists believe that they can do everything. If you show them something valuable that they cannot do, they will become highly interested. EN: Indeed, things are moving fast in that direction. With Dom Lungerich of Yonsei, we have already reported a time-resolved evolution of the conversion of a flat C60H30 molecule to a spherical C60 molecule, where we identified several transient intermediates that other methods could have never identified. We are now finishing work on the aggregation behavior of daptomycin, a cyclic peptide that is effective against many drug-resistant bacteria. Using our SMART-EM, we could determine the structure of the products of their calcium-mediated aggregates at atomic resolution. We installed a fishhook using Jeff Bode’s KAT ligation method. Our approach is the only way to obtain atomistic structural information on small and medium-size peptides or their aggregates, none of which is crystallize. Other people do in-silico studies of daptomycin aggregation, and we can provide them with the actual structure as a realistic reference point for their computations. We provide themwith the reality for their molecular dynamics study. Altogether, we are getting closer to organic chemistry. We have started a collaboration project with Yoram Cohen of Tel Aviv University, studying the supramolecular chemistry of pillararenes. Another study focuses on the aggregation of amyloid-beta model compounds together with James Nowick of UC Irvine. With Tobin Marks of Nortwestern, we are uncovering new reaction intermediates in heterogeneous Mo catalysis, and, with Toray people, intermediates in the formation on carbon fibers. And for inorganic chemistry, we see various polymorphs of inorganic solids at a nanometer scale. We can see them as crystal nuclei and how they go from one polymorph to another. We can even study the relative stability of the polymorphs. Polymorphism has always been a fundamental phenomenon in science, but people could only study big crystals, averaged over many atoms. We can now see atom by atom in the initial stages of crystallization and start understanding polymorphs formation. EK: The new applications of the EM technology are indeed mind boggling, and I am sure we’ll see many people joining this technology soon. I wish to conclude our conversation by going back to the movie “A Scientist and A Musician.” In one episode, you offer advice to the young generation: “Doing just what you like is wrong. It would be best if you did what you could. Find something that you like and can do and do it thoroughly.” Would you please explain what did you mean? EN: In the Japanese culture these days, and probably everywhere, most parents encourage their kids to do whatever they enjoy, and I find it wrong. I would better advise kids to find out what they can do best and then go for it. Kids may be very interested in something but cannot meet the requirements. For example, I may like baseball very much, but my body is too fragile to make a good baseball player. I wish I were Shohei Otani. EK: In many cases, kids like what works for them at best, so the two issues eventually merge. If kids do something right and gain much satisfaction and external appreciation, they ultimately like what they do. So, being driven by what one wants and can do becomes the same thing. EN: This is correct, and happy people succeed in doing what they like. But you need a certain level of human competence. Problems arise when people are interested in things they cannot accomplish. A temporary attraction to something unrealistic provides some short-living indulgence and transient satisfaction. But the following day, the kid may want something else. In contrast, if they try to find out what they can do best, they can develop a successful, enduring career. I like music, but I know my limitations and abilities. However, my music progresses still at this age, as chemistry does the same. ◆ Nakamura and Keinan floating on the Dead Sea together, October 2007. Opposite Page: 1. “The whale club” welcomed Ehud Keinan, March 26, 2004. From front left: Toshikazu Hirao, Masaaki Suzuki, Ehud Keinan, Tsutomu Katsuki, Koichiro Oshima. From back left: Eiichi Nakamura, Hisao Nishiyama, Ilhyong Ryu, Tamio Hayashi, Takao Ikariya. 2. In the TEM room in December 2020. ©MONTAGE. INC. 2021 3. Eiichi and Yoko Nakamura with the Keinan family, Bethlehem of Galilee, Israel, January 4, 2003. 4. Watching a quantum dot. ©MONTAGE. INC. 2021 5. Playing the baroque flute in Keinan’s home, Timrat, Israel, January 2003. 6. Nakamura with Gilbert Stork, Tateshina Meeting, November 2003, 7. Nakamura with Keinan, Jiro Tsuji, Henry Kagan, and Keiji Yamamoto at the front gate of Tokyo Institute of Technology, July 1985. 8. Nakamura with John D. Roberts at the Tateshina Meeting, November 2003.
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