Welcome to Influencers!

Today, we have with us Martin. For those of you who were listening last episode, there were several hints to suggest who Martin is. He grew up around Chicago. He is a Biologist but he has a very nice award in Chemistry. And as a hint, there is a surprisingly similar reference to aspects of his life in a book by the Brazilian author, Jorge Amado, called Tent of Miracles.

Then, the second interview is anonymous. If you can figure out who it is before we reveal it in the following podcast, you could win a coveted invitation to the Influencer Salon.

Listen To The Podcast Here:

Advice For Scientists From Nobel Prize Winner Martin Chalfie

I am so excited many of you have already figured out that our guest today is the legendary Martin Chalfie. Martin, thank you so much for joining us. I am in awe of the work that you’ve done. Martin, what year did you win the Nobel Prize?

2008.

There’s this famous thing that they call you in the middle of the night. Is that right?

Yes, but I missed that. I slept right through it. This has to do with my wife. One of the things when you have done science that other people appreciate, and the work I did has been appreciated by quite a number of people, some of your friends come up to you and they tell you a horrible thing. They’ll say, “You might get the Nobel Prize, if they call you in the middle of the night, give me a call. I’ll come right over, we’ll celebrate.” While this is very nice and it’s very good that your friends tell you this, the problem is that sometimes you believe them. This means that every once in a while you might wait up for that phone call, which of course doesn’t come. I had had a couple of friends that had told me this. I had had a couple of sleepless night in the years before my prize was actually announced. That was a little bit silly, so I stopped doing that.

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I went and looked online to see who had won. It’s very, very strange to see your name listed at the Nobel Prize website.

The night before the prize was announced I got an email from a student about the upcoming Chemistry Nobel Prize. I showed the email to my wife, who looking at it and remembering the sleepless nights before, said “Don’t be an idiot. I think GFP is the most wonderful thing in the world. Everybody uses it. I have to tell you the truth, it is never going to get a Nobel Prize. Just go to sleep and don’t think about it.” I listened. I went to sleep and woke up at about 6:10, something like that, in the morning. The Nobel Prize, you’re living in New York, it’s usually announced at 10:00 or 5:00 in the morning, New York time. I knew that they had made the announcement. Since I hadn’t been woken up by the phone, clearly, somebody else must have won it. I went and looked online to see who had won. I can tell you it’s very, very strange to see your name listed at the Nobel Prize website. Actually, I went back several times over the following months just to make sure they haven’t erased the name from the site. It was quite a surprise.

What did you win it for?

It was the Prize in Chemistry. I shared it with Osamu Shimomura and Roger Tsien. Osamu Shimomura had discovered a very interesting protein in 1962. That protein is called the Green Fluorescent Protein or GFP. It’s a protein that, by its name, is fluorescent. It means that light comes in, in this case blue light, activates the molecule and green light is emitted. You can see wherever it is by shining blue light on it. In 1989, I heard about this. Finally in 1992, 30 years after the discovery, we were able to show that if you put this protein, had it made by a bacterium or a worm or subsequently many, many other organisms, then you could see where that protein was in the organism simply by shining blue light on it and seeing which parts of the animal or plant or bacterium were green.

This meant that people could label parts of organisms and look at them in living organisms in real time so we could follow biological processes. That’s what really took off. The third person, Roger Chen, greatly improved the original molecule, made it brighter and had different colors and came up with several clever tricks about it. The three of us were honored with the chemistry prize. I’ve always thought it was actually a prize to the molecule and the three of us came along for the ride.

You literally can see life as it occurs. When people discover this incredible accomplishment, and since then you’ve done research and you continue to do research and so on, what’s their most common question?

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Nobel Prize: “How did you come up with the idea?” I was fortunately in the right place at the right time.

Usually it’s, “How did you come up with the idea?” is the usual question. For that, I was fortunately in the right place at the right time. To explain what I mean by that, when I first heard about GFP, which was in 1989, I had been doing work for quite a while, for about twelve years, on a small roundworm, scientific name Caenorhabditis elegans, for which we know an enormous amount. It’s a very well-studied organism and it has certain advantages for scientific study. One of these advantages is that it’s very small. The adult is only a millimeter long and you have to do everything under a microscope. The animal is transparent. That is a wonderful thing because under appropriate conditions, you can see every single cell in this tiny animal. They all basically look the same.

We were studying a set of cells, nerve cells, that were sensing touch in the animal and we were starting to clone genes that were needed for that cell to function. We wanted to know, were those genes needed in the cell or maybe in some other cells? There were lots of techniques that would allow us to see what cells were active, which cells turned on the gene. All of those procedures meant that you had to prepare the samples, which usually meant fixing them, making sure nothing moves around and then permeabilizing them, allowing things to get in. Once you did that, you could say, “Yes, this thing is made in these particular cells, or no, it’s not made in those cells.” Once you made the prep that was it because it was already fixed and prepared. Those are the two things. We were looking at where genes were being turned on and I worked in a transparent animal.

I go to a seminar and I sit down listening to the introduction and in the introduction the speaker mentioned the Green Fluorescent Protein and that all you have to do to see the green light is to shine blue light on it. It wasn’t a great feat of genius to come up with the idea of, “Wait, I work on a transparent animal. I want to know where these genes are turned on. What if the genes made this protein? Then I could see it being turned on simply by shining blue light on the animals. Wherever the animal was green, that’s where the gene was active and the protein was being made.” That was the idea. I spent the entire rest of that seminar not listening to the seminar but thinking about all the experiments I would like to do if this worked out. Fortunately, it did.

Now, for example, to give you some ideas, we study the development of nerve cells. Nerve cells start off as a cell body and they send out processes, long neurites that connect up to other nerve cells to make the nervous system. We would very much like to know what governs, how many cells are made, where the cells are made, how many processes they extend, all of these questions, how they migrate perhaps throughout the organism. By labeling the cells with GFP, we can follow their entire development. More than that, since this is an organism where genetics is very easy to do, we can find mutants, variants in which the cells are missing or there are more cells or the cells are in the wrong place or they have fewer outgrowths or more outgrowth. We can then study the genes that caused those defects. Being able to see something allows you to study it. That’s what GFP and then subsequently other fluorescent proteins have allowed people to do.

What always seems to strike me is that there seems to be this random element at play. When you speak to the people, anyone from Nobel laureates to successful business entrepreneurs or executives, it seems that the question of where the idea came from was almost unpredictable. A certain confluence of elements came together and then the individual grabbed hold of it, got obsessed with it and that eventually led to their success. In light of that, for people who want to go into the sciences, do you have any suggestions or tips?

There are a couple of things. I want to talk about this aspect of something new and unusual happening. It is a wonderful aspect about the Nobel Prizes that they acknowledge or recognize individuals that have done something that has changed science. Not the smartest people, not the people with the most grant money or the best publication records or anything, but people who have done things that have changed the way people do or see science. At least when I go in and read the various Nobel Prize lectures, it’s surprising how many of them remark about the chance observation they’ve made or that they were actually working on something else.

It was John O’Keefe who won the Medicine Physiology Prize in 2014, who starts out his lecture saying something to the effect of, “I was doing electrical recordings in the thalamus when I suddenly made a mistake and was recording from the hypothalamus.” That’s really led to all the work that he did that he got recognized for. Or you look at Penzias and Wilson who discovered the background radiation of the universe but were not looking for it, but discovered that because there was a background in their recording that they had been making of the night sky that they couldn’t explain that eventually led them to realize that they had found this ancient signature of the Big Bang.

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Nobel Prize: These accidental experiments come about all the time because we don’t control everything in our experiments.

These accidental experiments are things that are quite wonderful. They come about all the time because we don’t control everything in what we’re doing in our experiments. It’s fortunate that people sometimes look at them and say, “I have an idea about that. I should look at that.” They go down that pathway of the unexpected and see things. In terms of advice, I would say don’t be afraid to follow up unusual things. That doesn’t always work. This is not the world’s best advice. Not to ignore them would take away a lot of the excitement.

One other story about this I should say is that the original discovery of GFP was a complete accident as well. Osamu Shimomura, who was a terrific biochemist, and I urge your listeners to go to the Nobel Prize website and look up his essay and read up about his life, which has been quite remarkable. He was studying a very interesting biological problem and that is, how do different organisms that can produce light do that biochemically? People, when he started his work, had known how fireflies produced light, but there are lots of other organisms that produce light. Earlier he had deduced how a small crustacean called sipra dina produced its light. This time he was studying a jellyfish that produced a beautiful green light. He went about studying this. As I said, he’s a spectacular biochemist. He used all the tricks he knew of but no matter what he did, the experiments fail completely. He spent the whole summer getting jellyfish, trying to isolate the chemicals, the proteins that were needed to generate light and nothing produced light.

One night, he was working late in the lab, his preparation had once again failed and he decided, “That’s it for the evening. I want to go home and have dinner.” He cleans up after himself and he throws all the samples he had been working on into the sink, which had overflow from some seawater tanks that were in his lab. He turns off the light and he’s about to leave for home when all of a sudden, he turns back and sees the sink is glowing brightly. This is a big surprise. He goes back to the sink, thinks about it for a little bit and realizes that the seawater that was in the sink contain something he had never tried in his sample. That was calcium ions. After that, sewing days when he made other preps, every time he added a solution with calcium in it, he got this burst of light. That’s a wonderful but accidental discovery. Sometimes I advocate the students they should throw things on the floor, the lab bench or the sink to see what happens. But it’s not a really tried and true method.

In any case, he had a problem. He had answered his question. His question was: What is the molecule that produces light? Now, he had a way of detecting it by adding calcium, he could easily purify that protein, which he did. He named it after the jellyfish. It was called the Corin. There was only one problem with what he had discovered. The jellyfish produces a wonderful green light but the protein he found the Corin produces a beautiful blue light. He didn’t really answer the question he wanted to, but realized at the last minute, “Wait a minute, there must be something else that makes green light.” He found the second protein that didn’t create light but converted blue light to green. That’s Green Fluorescent Protein. Two accidents led him to this wonderful discovery.

What are the pitfalls of going into the sciences? There’s this romanticized notion of discovery and exploration. What is it that people don’t really talk about or that they should watch out for if they want to get into the industry?

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Nobel Prize: You have to deal with failure in almost every walk of life. The experiments don’t always work.

One of the main things as I’ve referred to before is that you really have to deal with failure. You have to deal with failure in almost every walk of life. The experiments don’t always work. You sometimes have to put ideas aside and go to other ones and then come back to think. Sometimes you come back many times over the years to address a problem that you’re interested in. It takes some time and it’s hard work. Beginning people often also don’t realize that doing one experiment doesn’t make a paper or a finding that there’s lots more to do and much more to learn about. There are some more general problems that we have right now and that is that we are probably at the most exciting time for doing science ever. Probably every year of my life I could have said that sentence but it’s really true. Every year new discoveries along new possibilities and it’s a very exciting time to do science.

Science costs money and we need to have support for that. People have to be able to articulate why they’re doing their science and why it is important. To convince not themselves so much but the whole world around them that especially, what I would call fundamental science, some people call it basic science, is absolutely crucial. None of the wonderful things we have and enjoy in our world would be possible except from basic research that’s led to them. This is certainly the case of all computers, cellphones, but also laser surgery. Everything else that’s done with lasers just started as a basic physics investigation. Basic research is critical for any application. People often get hung-up in the application. “I want a cure for X. I want to be able to do something.” We all want those but building the foundation is absolutely critical.

I remember that the amount of research and discovery that required us to go to the moon, there’s this very rough estimate that it essentially catapulted the entire communications and telecom industry and had such huge impact on our society that it would have never looked the same if we didn’t go for that endeavor. It sure costs a lot of money. Being on the moon doesn’t provide any specific value to anyone of us as an individual, but the fact that that research and that creativity and that investment took place, pushed us forward as a culture and as a global economy.

Also understanding basic biological principles gives people new insights at which to address disease problems that people usually face. Over the years, this tiny worm that I work on and thousands of other people worked on has been the vehicle whereby we’ve learned some astonishing biology that has implications for human health, not directly but maybe in terms of, “If you can manipulate this, you can change that. Maybe this is a new approach to disease.” This has come up repeatedly as people have found new techniques to manipulate the genomes of organisms or ways that cells develop that we would never have learned by studying people but have a great insight by studying other organisms. Some people call these model organisms but I don’t like that term. I don’t like the idea that we’re modeling anything. These are organisms that we use for discovery. I prefer to use the term pioneering organisms because they lead us into whole new areas.

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Nobel Prize: I prefer to use the term pioneering organisms because they lead us into whole new areas.

What’s something completely unexpected about reaching this level of success or notoriety within your field?

I get invited to a lot of things that for some reasons having the stamp of approval on Stockholm means that I get invited to meet many more people than I would have ever imagined, go places I always wanted to go but never had the opportunity. It’s a key that opens up many doors. It’s quite nice and gives me a chance to do things that I normally would have liked to have done but never had the time or the opportunity. I talk a lot with students. I am on advisory boards now of some other scientific endeavors. I have taken on a second job as the Chairman of the Committee on Human Rights of The National Academies. That’s becoming an almost full-time job and one that I appreciate very much being able to be part of.

Let’s talk about the things that have influenced you. Who is your hero?

I have several heroes. I was very fortunate in college to have met a wonderful professor in the Biology department named Woody Hastings. It was nothing that he taught that impressed me as much as the fact that one day, I was on the swimming team, I couldn’t come in the afternoon to the library to read and the library was locked in the evenings. I went to his office and I said, “I’d like to be able to read the articles for your class but I can’t get to the library. I need a key. Could you help me get a key?” This man just got up from his desk and said, “Come with me” and walked four flights of stairs down to the administrator’s office in the department and said, “Give this guy a key. He needs it.” The fact that somebody would get up and walk four flights of stairs for me, I thought was astonishing. I had a great PhD advisor, Bob Pelman, who let me ask any questions I wanted. He was always kinds and considerate of me and really made my life wonderful.

Then when I was a post-doc, I worked with probably one of the most amazing scientists I ever worked with or known and that’s John Sulston, a deeply moral person, won his Nobel Prize in 2002 and really set the tone on how to be a scientist.

Are there certain books that have really influenced you or specific lessons that you learned?

There are books that I like quite a lot. When I was growing up in high school, the book my friends and I read, reread and reread again was Catch-22 by Joseph Heller. To me they’re all classics. The other book which was an assigned book in school but I’ve always loved was Alan Paton’s Cry, the Beloved Country. It was an absolutely wonderful book. The other books that I’ve enjoyed are quite a number of them that are wonderful books. Julie Schumacher’s Dear Committee Members that I think any academic would absolutely adore or should adore. It’s written all in letters of recommendation. It’s a wonderful novel. I’d have to say my favorite book is a book by the Brazilian author, Jorge Amado, called Tent of Miracles, which has many, many different layers to it and talks about mixing of the races and why that has strengthened Brazil. It also has a very funny start to it or near the start of it. It has a Colombia University professor who has won a Nobel Prize coming down to Salvador in Bahia in Brazil to give a lecture. I was fortunate enough to follow that fictional laureate’s footsteps by being able to give a talk at the university in Salvador. I like that quite a lot. The book itself is just magnificent.

What would have you accept an invitation from a stranger for a meeting? Let’s say you get a voicemail or an email, what’s in that email or message?

I have to say I’ve been quite busy so if it just came out of the blue and it wasn’t something I could check with friends or colleagues to know about, I might not be as open to that. For the most part, I look at these invitations. I think that the thing that I look for is something with students. Is this something that will help them in some way? Then I’m much more inclined to do that. Although, I do not do that if the thing in question is actually a for-profit organization. I want this to be something that the students are not charged for. There have been some incidents in the past where people have wanted me to help them make money in a sense by being part of the group. I tried to look into things so that I don’t do that.

As far as from a personal perspective, is there some organization, non-profit or cause that you’re really connected to?

As I said, I’m the Chair of the Committee on Human Rights of The National Academies of Science, Engineering and Medicine. That’s the organization that I do most of my work for, to help them. Any human rights organization is probably looking for funds to help its work, to aid in what it is doing. We work on behalf of colleagues, that is any natural or social scientist or health professional or engineer anywhere in the world that would be at risk because of expressing their human rights that are embodied in the universal declaration of human rights.

What’s a very human secret you would feel comfortable sharing on the podcast? There’s this image of people who have achieved their level of success as just being brilliant minds who have all their stuff together.

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Nobel Prize: I’m constantly surprised of how many mistakes I make and how many misconceptions I have.

That’s pretty simple. That would just be wrong. I’m constantly surprised of how many mistakes I make and how many misconceptions I have. I certainly don’t feel that I have any superior knowledge of the world or how things happen. I certainly have made my share and probably will continue to make many more mistakes in the future.

Last question, if you could meet any three people who are currently living and eat dinner with them, who would they be? It’s people you don’t know personally.

One of them would be Barack Obama. That’s a person who I would very much like to talk with. I’ve had such an opportunity to meet people outside of my field that I can’t think of additional people outside the field that immediately spring to mind.

If people want to learn more about your work or find anything you’ve written and so on, where can they check you out?

The first thing that gives people plenty of background about me and about GFP and our work with that is to go to NobelPrize.org, which is the Nobel Prize website. They can look up the 2008 Chemistry Prize and there they’ll find me. I have my lecture that I gave there is listed there. They also had me write an autobiographical essay. A lot of my longwinded stories wound up in that autobiographical essay. That’s probably the best way of finding out about it. For those that know about the website PubMed, which is a governmental site that has all published papers on it. They can certainly look up Chalfie and see the scientific papers. For a general thing about me, the NobelPrize.org website is the best.

Martin, thank you so much for joining us today and for taking the time. I know you’re incredibly busy and there’s plenty of research to be done in the world. Thanks for taking a break and sharing your stories and insights. It’s been a real pleasure.

Pleasure for me too, Jon. Take care.

Listeners, stay tuned for the anonymous interview.

 

About Martin Chalfie

TIP 015 | Nobel PrizeMartin Chalfie was born in Chicago. His parents worked in the garment industry, but they encouraged their three sons to pursue academic careers. Chalfie took an interest in the natural sciences, especially chemistry, and received a doctorate in biochemistry at Harvard. He did various short-term jobs before continuing studies for his doctorate. Later he conducted research in Cambridge, England, where he did his Nobel Prize-awarded work. Since 1982 he has served at Columbia University. He married Tulle Hazelrigg, and they have one daughter, Sarah.

Anonymous Guest Interview

I’m so excited to be hosting Bill today. I actually used to work in the same building as Bill for several years. He was one of the few people that I’d go and visit his office and we’d talk and chat about the future of our industry and how we could revolutionize it. What I love about Bill is that he was such a visionary. He really got it. He was so open to any type of concept that had the potential of growth. Bill, thanks for coming on.

Jon, it’s great to be here.

Let’s give the listeners a few hints about who you are. Let’s start off with the basics. Where did you grow up?

I grew up in Western Pennsylvania, in a small town about 90 miles east of Pittsburgh.

I couldn’t even point that out on a map, but I’m sure it was a lovely place to grow up and a great childhood.

It was. It was a very small town area, a town of 4,000. The fact is few people actually leave that town. The fact that I escaped was a wonderful thing. My parents always encouraged me to get the hell out and enjoy the world, see the world. After I did that, they said, “How come you never come back?” They were a big influence in terms of getting me out of that town, which again, most people don’t leave.

Was there an incident or a teacher or experience that inspired you to go in the direction that you went?

I wasn’t the most focused student growing up. The influence was actually a negative influence, in that my parents owned a general store in this town. This was a store that sold penny candy, bread, milk, and newspapers and had a laundry machine, that type of stuff. I saw my parents working twelve, sixteen hours a day. When I reached probably age ten or eleven, I started working a lot there. Every evening, every weekend, I was working. I just didn’t want that life. I wanted to go off to college and pursue some dream. I didn’t know what that dream might be. My parents really encouraged it.

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Nobel Prize: it really became clear to me that I had to figure out what I wanted to do with my life.

It’s funny, I remember, I went out to breakfast one morning with my dad. We used to go to the business very early on Sundays to put the newspapers together. They were so big at the time. They came in three different parts and you had to put them together, Sunday papers. We’d have to go to the business by 4 AM to start putting these papers together. One day, he wanted to go out for breakfast first, which we did. He said to me in the middle of breakfast, “Billy, I’ve decided I’m not going to give you the family business.” I was like, “Great, because I didn’t want it anyway.” He said, “You’re going to college.” I was like, “Okay, I’m going to college.” I was probably fifteen, sixteen at the time and that’s when it really became clear to me that I had to figure out what I wanted to do with my life.

Was there an accomplishment in your career that you’re most proud of?

Winning the National Magazine Award for General Excellence in 2015. It’s the Oscar of the magazine industry, so absolutely, that accomplishment.

If there was ever a movie about your life, for whatever reason, who do you think would play you and why?

There’s this great actor named Jon Levy, I could see him doing it. He’d have to shave the beard though.

If it’s something I’m good at, it’s definitely not acting. There are a lot of other Jon Levys, so you might be talking about one of them.

Sure, we’ll pick any of those.

There are always these stories about people taking on absurd dares or stunts that caused their success. Is there anything that you’ve done throughout your career that really just stands out as, “That was completely insane. I can’t believe it worked out.”

It wasn’t so much a dare or a stunt. I was at a major magazine in New York and the magazine that I spent the following thirteen years at including the Forbes’ Editor-in-Chief, they called it. They were based not in New York. My girlfriend at the time, who’s now my wife, she said, “Play this. Play this for a raise at your current job.” She had no interest in leaving New York. I went on the interview just to get some leverage with my current employer. Then I got really interested in the job. Before you knew it, we were moving out of the city. Even then, my wife was like, “You only get two years.” Literally, for the first seventeen, eighteen months, she was like, “We’re moving back. We’re moving back. We’re moving back.” Then, at the two-year mark, we’ve fallen in love with the area. I’d fallen in love with the job. I was seeing it as a stepping stone to something better, but the reality was it was a stepping stone for a better me. That’s a case where it wasn’t so much a dare but it was something I did on a whim with no intentionality at all and it turned out to change my life.

Was there a certain moment or experience that you felt that you had arrived to some degree like you’re now playing with the big boys or girls?

Yeah, I wrote a story in 2005. It was an investigation into my father’s death. I recorded it out throughout 2005. It ran in a fall 2005 issue. My dad passed away at the age of 59, nobody understood why he had something going on in his brain. The story was an investigation into this potential genetic disorder that might be in the family and what that would mean to me if in fact that’s what killed him. The story got tremendous praise just among my peers, among the company and then was nominated for National Magazine Award itself. That was like, “I can write with anyone.” That was probably the moment and that was 2005.

Congratulations on that. That’s quite an achievement. Last question, what hint or riddle would you give to people to figure out who you are?

You know my name is Bill. I would say that my last name rhymes with a brand of light bulb.

Listeners, you have a ton of information to go on. Let’s see who figures this out between now and the next episode.