Nobel Laureate Thomas R. Cech on why Ribonucleic Acid rocks

hello and welcome to the point blank show my name is abhishek i'm honored to be joined by

dr thomas keck who shared the nobel prize in chemistry with sydney altman back in 1989 for

the discovery of the catalytic properties of rna their work demonstrated that rna is not only a

molecule that carries genetic information but can also act as a catalyst in biochemical reactions

that was a role that was previously thought to be exclusive to proteins this has helped us

understand a range of subjects like the mysteries of the origin of life mrna vaccines among many

other things tom's book titled the catalyst rna and the quest to unlock life's deepest secrets

was released recently and is a fascinating read thank you so much tom for doing this

i'm glad to be here

thank you and and first of all uh full disclosure i'm not even going to pretend uh that i'm remotely

qualified to speak about this subject with you and uh the irony is not lost on me this is a

commerce graduate with a background in management talking chemistry to a nobel laureate so the only

thing connecting me to science is my mom who recently retired as a you know science teacher

school science teacher she would teach chemistry there but much to her chagrin i didn't take up

that subject what was what are your first thoughts about the subject of chemistry and how did you

first react you know recollections of science as a kid what introduced you to this world

abhishek i i knew that i wanted to be a scientist from the time i was perhaps five years old my

earliest memories i was always intrigued about how nature worked i was very interested in rocks

and minerals and fossils and i would collect them i would hit

them with a hammer to see what was inside and i had a physician father who was sort of driven into

medicine by his family for financial reasons but always really wanted to be a physicist and so

he would talk on any family excursion he would always talk about nature from a very scientific

viewpoint and this resonated with me and so i always

knew i wanted to be a scientist and i've read somewhere that you were also a fan of sitting

outside and looking at meteor showers and trace the parts of meteors in the sky somewhere in

middle school perhaps is that what it was yes i would set up my old camera and i would you know

on a time exposure so that i could capture the meteorites blazing across the sky astronomy was

exciting to me when i was in middle school and then later i turned more to physics and then to

chemistry very last to biology and how did your professors back in the day react how do they react

to curious students i'm imagining that you were terribly curious back in the day as well knocking

on professors doors to know about things that other students may not ask yes i lived in a

university town

called iowa city iowa and that's where the university of iowa was located and i had no

even though i am a rather shy person i was so excited about the science that i would knock on

the doors of the geology professors and quite remarkably they were very kind to me and they

would call me into their office and tell me about some things that they were doing and i hope

that i have that much patience with young students today and talking about patience

you've confessed in the past that you are not a patient doesn't come very naturally to you or

didn't when you were in your 20s and lab work which is pretty much where all the discoveries

take place require a lot of patience how did how do you square with that or have you changed over

time yes of that impatience as you called it can be a useful quality

but it drove me out of chemistry where the experiments tended to be very long take a long

time to do and i much preferred applying my chemical knowledge to biological systems where

you can often do an experiment each day and already the next day you get an answer sometimes

the answer is that you made a mistake and it didn't work but there's constant feedback between

experiments and experiments and experiments and experiments and experiments and experiments and

experiment and idea and for me that was very attractive and then came a day when you called

yourself a dna guy in slang tell us about it how did you get attracted towards the field itself and

you decided to dedicate your life to it yes when i became disillusioned with chemistry i was in the

uncomfortable position of being a chemistry graduate student

at the university of california in berkeley and knowing that i really didn't want to do chemistry

and so i was fortunate to find a professor his name was john hurst who had been trained as as a

physical chemist at caltech but now was working on chromosomes and dna and i didn't really know

what this was but i knew that it was very different i mean i knew a little bit but i knew that it was

very different from studying small molecules hitting into each other in the gas phase and so

maybe this would be something that would be of more interest to me and as soon as i joined his

laboratory and started doing the experiments i found that this was really what i love to do

and dna of course being the master molecule responsible for

all of life the storehouse of genetic information who could possibly want to study anything more

important than dna right and i think for non-science background folks like me the word dna

i mean it's a verb we've used it let's say the brand should have a particular dna the organization's

dna is this so something that is very fundamental and hardwired into the individual or the company

is supposedly that and do you see

rna becoming a whoop someday i i really was not very interested in rna when i was a student i

thought it was just the product of the dna and you know the dna was the mastermind and the rna

was just a servant working for the dna so it took some time for me to wake up to the fact that rna

had many wondrous qualities actually

much more than dna in one podcast i remember you talked about you compared rna you said it it's

more it was more like a chorus or a background singer to the pop diva that dna was and and it's

like for me it's a stuntman versus the main actor is how people perceived it so very briefly

what does rna do which you realize later as you suggest should get the necessary spotlight what

are some of the functions of rna which

do your mind back in the day so at the time we really didn't know about most of these functions

we knew that rna could store information and in fact many viruses such as the sars cov2

but also ebola virus the influenza virus these don't even have dna they just use rna as their

genetic information and we knew that rna could be a messenger

and that role has been turned into vaccines with the mrna vaccines but the really wonders of rna to

me are all of the things that it can do beyond being a coding molecule or a message and these

include being able to make cells immortal being able to drive crisper genome editing which i think

many people have heard about and to

have a lot of research on is that rna is a natural source of DNA and it's a very interesting

technology and we've been able to do this for over a decade now and i'm in the process of

researching this and i'm really excited to be able to show you what this can do and i'm

very excited to be able to tell you where these things go and how they're going to affect our

lives so for example if you are doing a biocatalysis or something like that what you get is a

biocatalysis and what it does is it will act as a biocatalyst and perhaps provide the secret of how

cameras or anything remotely as close to that. So how do you even go about approaching such

problems, Tom? You are absolutely right, Abhishek. Anyone who says that they have proven how life

started on the planet or that they know how life started, they are exaggerating. We can come up

with laboratory experiments that tell us what is plausible, what might be realistic, but it is

difficult to know exactly what happened. But here's the story. So for many years, scientists

were puzzling over how the first self-reproducing system, very primitive life, could have gotten

started on the planet Earth. Now, if you think about what you need for life, you need to have

an informational molecule, right? You need to have some information that you

pass down to the next generation. Well, we know now, for us, that is DNA. And also for all the

plants and all of the bacteria and every life form on this planet, it is DNA. But DNA doesn't

do anything by itself. It just sits there. It needs to have an enzyme, a protein catalyst,

to make one mother copy into two daughter copies, right? So you need some machinery to

reproduce it. So how could this possibly get started then? If you need, in the same little

place at the same time, both the informational molecule and a catalyst to copy it by some random

chemical processes, seems very difficult. So now, following on from the discovery of RNA catalysis,

we know that RNA, in addition to being an informational molecule,

can be a copying machine. Think about a photocopier in your office, right? The RNA can both be the

thing that is being copied, but it can also, at the same time, be the machine that is doing the

copying. So this is a potentially shortcut to understanding how life could have gotten started.

We call this the RNA World Hypothesis. That at the beginning, there was RNA,

RNA replicating itself, and that the proteins and the DNA came later.

And if you can replicate this in the lab, then the odds are that that may have happened back in the

day. Yeah, that's, you know, some people think that it's, that they just understand that that

must have been what happened, that RNA must have been there at the beginning. I'm a little bit more

cautious. And I say, it's an extremely exciting,

exciting idea. It's a scientifically reasonable idea. But again, the experiments that are done

under controlled conditions in the laboratory are rather artificial. We buy the reagents that we use

from a chemical company, and they come by mail. Well, at the origin of life, you're not allowed

to send out for, you know, people to ship your reagents. It has to all happen spontaneously.

On the other hand, to argue the other direction, you do have a huge amount of time,

perhaps 100 million years, that to do these random experiments on the primitive Earth,

and you can do them in a million locations at the same time. So now something that is perhaps seems

rather unlikely, you multiply by a million times a million, and you can see how maybe it could have

gotten started.

Recently, RNA was right in the news everywhere was when the pandemic struck, because we had mRNA

vaccines, Moderna, BioNTech, everywhere. In India, we were the generic manufacturers once we got the

chemical composition in place and millions of doses were produced. One common, you know,

news everywhere was, it appeared that it happened pretty much overnight. So how do you react to

that? And people were, you know, skeptical that no, it's not going to happen. And so, you know,

I don't think enough research has gone in, etc., which probably wasn't the case, but you are in a

better position to help us understand what exactly happened there.

Yes, Abhishek, I did think a lot of the concern and reluctance to get the vaccine, at least in our

country, was fueled by the fact that it all happened so quickly. In fact, it all happened

within one year, if you will recall, within the year 2020. At the beginning of the pandemic, we

had a lot of people who were, you know, we had a lot of people who were, you know, we had a lot of

people who were, you know, we had a lot of people who were, you know, we had a lot of people who were

of the year, both BioNTech and Moderna started their projects. And by the end of the year,

we had approved vaccines. And so how could this happen so quickly? Well, it was, I'd like to

think about this as a jigsaw puzzle that you have to put together, right? And so all of the pieces

of the puzzle had already been discovered in the last decades before,

2020. So we knew how messenger RNA worked. We knew how to make RNA in large quantities by copying

DNA in the laboratory. We knew how to stabilize the mRNA so that it would not cause bad reactions

in the human body. And all of these ideas were already there. And they were like the puzzle

pieces laying out on the table. And what the vaccine did was, it was able to stabilize the

RNA. And so what the vaccine makers needed to do was just fit them together. And that was

important. And it was creative. And I'm not belittling what they did. But they never would

have been able to do this if it hadn't been for the decades of research preceding 2020.

I think the economists had mentioned that the RNA vaccines are a testament to the insight of

Eddie Cantor, a comedian, that it takes 20 years to become an overnight success.

So it's possibly that then. It was all put together. And then it came to the fore when we

all needed it. And yes, there was open source, all researchers who would not show their notes,

like you were in school, right? Kids would not show their notes to each other. That all went away.

People, you know, researchers, scientists got together, shared each other's observations so

that we could get there faster. How, you know, the science community, Tom, could you just help

me understand? It's very competitive, because, you know, not everybody,

may want to show what's going on without making too much noise, because it's your discovery. How

does it work? And during such crisis, is it the human primal nature to collectively take on a

force like the pandemic caused us to do that? Or is that very natural in the community?

Well, you know, so you're absolutely right that the pandemic was a special situation. And everyone

just naturally thought the right thing to do was to cooperate, to share, to help, to

collaborate, to help everyone out. And there was really very little discussion about that. But

otherwise, scientists are quite competitive. And they do sometimes, they're sometimes careful about

revealing everything that they know. I always encourage, you know, whenever my students ask me

if they're going to an international conference, they say, is it okay for me to talk about my

experiment?

I'm worried that someone might steal my ideas. And what I tell them is that if you are open

about communicating your ideas, two things could happen. One is someone could steal your idea,

and that's not good. The other thing is someone will help you go to the next step. And also,

they will remember the conversation, they will give you credit for the idea. And since you don't

know which of these ideas is right, you can't tell them. And so, I'm worried that someone might steal

your idea. But if you know that one of these things has a greater weight to it, then do the right

thing for science, which is to be open about your ideas and realize that occasionally you're going to

be unhappy with what happens. But overall, that's the right thing to do.

I think, sorry, please go ahead.

I was just going to say, I think also the competition drives us to be better,

right? Just as it does in the Olympics, just as it does in

business in your field, you know, in commerce. If it weren't for competition, things would

sink down to sort of a very low level of quality and creativity. And it's when you have to

compete against other really smart, energetic people that you bring out the best in people.

So competition overall is a good thing. And this part about letting go and trusting

science or trusting the other person to do the right thing, is that something you,

for example, when you moved from, quote unquote, the DNA guy to RNA, that itself must have been a

big change. How did you decide that? All right, I've got to be open enough. Let's see what RNA

has in store for me. And maybe you work all your life to do one thing and realize that the data is

pointing you in another direction. How did you manage to let go? You would have learned new

things there. But from I'm talking about now a little philosophically,

in terms of life as well, it needed you to shed something that unlearn something and

try to figure out what's happening on the other side. I wonder how you manage that.

Well, I have two comments. Thank you for that excellent question. First of all, the

system we were trying to understand was so intriguing that we were so curious about how

it could be working that it just sort of sucked us in. And I think that's one of the things that

we had to understand. And the answer had to be in the RNA molecule, not in the parent of the DNA.

It was the RNA that was doing these gymnastics, as we sometimes call them. And so that drew us

into the RNA. And then the other thing I will say is that this was a small scientific discipline at

the time. There were not...

There were enormous numbers of people working on RNA, but there were some leaders in this young

field. And they took me in and were very supportive of me. And if we were doing something that wasn't

quite up to the standards, they would say, well, you're doing a good job, but you really should

consider learning this new technology. And then that was very helpful. So having the support

of some of these people, I think, was a very helpful thing. And I think that's one of the

key people in the community was also critical at that time.

And when you were on the path, you discovered something big in an experiment that you

conducted yourself. If you could explain a bit about the Tetrahymena experiment is what I read.

And to quote you, and I find this funny, there is a video on YouTube posted around 13 years ago,

where you talk about your experience. And I quote you, you say, I did this experiment rather

quietly. I didn't tell any of the graduate students what I was doing. I didn't want to

look foolish if this reaction failed as it was probably destined to. Well, so yes, I was also

teaching very heavily at the time. And so I had to only do experiments for myself at night. And

often there was not very many people around. Yes. The Tetrahymena, this is a pond animal.

It is single-celled organism.

Which like a human cell has the DNA in the nucleus. And so the RNA is made in the cell

nucleus and then shipped out into the cytoplasm of the cell. So it has some features of higher

organisms, but it is as easy to grow and as cheap to grow as bacteria. So I thought that was an

attractive system. So when I moved from MIT in

Cambridge to Boulder, Colorado, I decided to set up my own laboratory studying this pond animal,

Tetrahymena. But there was another reason for being interested in it. And that is it had 10,000

identical copies of a particular gene. And that's a large number. Most of,

Abhishek, most of your genes, you have two copies of. One from your mom,

and one from your dad. So 10,000 is a big deal. And I was a chemist by training. And so having

a lot of stuff to work with was attractive. And it turned out that the RNA made from these 10,000

genes was the one that had this catalytic activity, which we called then eventually when we

figured it out, we called it ribozyme for ribonucleic acid with enzymatic activity.

And it wasn't just me in the lab. Yes, I did this experiment late at night when nobody was watching,

but I had some excellent people in my small laboratory, particularly Art Zogg and Paula

Grabowski, who I talk about in my book, who made key contributions as well.

Right. And how do you react when you discover something?

Something that isn't written in any textbook. None of the scientists are talking. Something

that is bizarre, first of its kind. How do you even process that? If you could flash back into,

I think this was, were you in your late 30s back in the day or early 40s?

No, I was just barely 30.

Wow. Amazing. Right. Okay.

I had just started out as an assistant professor. The first thought is that a mistake was that

it's wrong, that there's just a mistake in the experiment. And then when, so you repeat it a

number of times, and it seems, and when it's very robust, when it is reproducible, then you say,

okay, it's not due to a mistake. But then we thought that it was due to a contamination,

that there must be, because everyone knew, all of the textbooks said all enzymes are proteins.

Right.

And so clearly there was some enzymatic process taking place with this RNA. So we said, okay,

it has to be a protein. There must be a protein contaminating our RNA. So that was the first

thought, is that we needed to work harder to get rid of this protein contamination.

Right. And I think one of your colleagues, when you guys were still figuring this out,

gifted you a plastic daisy flower, didn't she? And I found that funny, where

one of the petals said, it's a protein. It's not, if I remember that correctly.

Right, yes. And fortunately, we were able to think of something more scientific

than picking the petals off the daisy flower to resolve this problem. And it turned out,

it's not, there was not a protein involved. And this was the first

example where RNA had been found to act as a catalyst in the absence of protein.

And there is this line by Isaac Asimov. He says that the most exciting phrase to hear in science,

one that heralds new discoveries, is not Eureka, but, hmm, that's funny. Is that something you

agree with? Yeah, yeah. Well, I think you get both of those happening. The first, it's always the,

the first one is always, that's strange. You know, that's funny. That's the early one. And then the

Eureka comes when you figure out how the funny thing was happening.

And your case, it's in the family. You said your dad was a physician. Also, you've written about

your wife. You're married to a fellow biochemist. Does that also help? And she had a little hand

in the experiment as well, is what you're right. Yes, she did. She gave us a key reagent

at one point that she had in her laboratory. And I also have two daughters who both became scientists.

And I always wished that they would go into something else like fashion or something like

that so that I wouldn't, so that they wouldn't require advice from me. Sometimes the apple

doesn't fall far from the tree. And so I am proud that the whole family has this scientific bent

to it. Lovely. And did you ever feel like screaming outside your balcony back in the day when you said,

RNA does far more things than you think?

It can, because I found something here and it took the world a while to realize that

when you, among your colleagues at the time, were the first ones to get there. And after having

reproduced those results, how did you, you know, try and deal with that bit? Did you ever feel

like screaming into the pillow, for example? Well, you know, what was very important was that

other people rather quickly found additional examples, right? And this is key in science,

that, that, you know, if only one laboratory can get an experiment to work, you really worry that

it's, that there's a problem there, right? But if other laboratories, including your competitors,

perhaps, get your experiment to work, this is a glorious day. And the next example was with

Sidney Altman at Yale University, working on a completely unrelated system to what we were

working on. This was a bacterial,

enzyme that had both an RNA and a protein part. And he found that the RNA part by itself

could be catalytic. And this was then a huge extension of our original finding

and led to Altman sharing the Nobel Prize with me. And it did not take very long, Abhishek. It was

just seven years after our publication, six years after Altman's publication, that we shared the

Nobel Prize. So that's, that's, that's, that's, that's, that's, that's, that's, that's, that's, that's,

that's pretty quick.

Take me inside your lab, Tom. Back in the day, you have to do this

cutting edge research. The first lab, you were the assistant professor is when you got keys to it.

It must have been a big day. How did the lab look like for, if you could describe that, please?

It looked like something out of the 19th century. It had soapstone lab benches,

which had,

which had been used for many decades and were quite worn. It had oak wooden drawers. I think

it had been used as a teaching laboratory. I think when we opened one of the drawers,

we found the remains of a rat that had been dissected by a student. It did not have very

good ventilation, but it was mine, right? It was my own place. It was a place where I could do,

my students and I could do, I could do anything. I could do anything. I could do anything. I could do

what we wanted to do. And so to me, it was beautiful.

So there's a lesson in there. You don't have to wait for things to be perfect. Then

you just try and do what, what you're given. And hopefully you develop something at the end

of the day, which is beautiful. Make the best of what you've, what you've got. And now that we have

beautiful modern facilities, I don't think the experiments we do are any better than what we did

back then.

The importance of repetition that you touched upon a minute ago,

how, you know, we say even whether it's learning a musical instrument or trying to learn a new

language or whatever, you make mistakes, you repeat, you repeat, and hopefully you get there

in the kind of work that you do and your colleagues do. Is that the key? And, and hoping

that you don't lose your mind because you may not get what you're looking for, but you keep

repeating it. Is that how it works then? Yeah, I, I think that, you know, repetition

by repetition is the key. And I think that's the key. And I think that's the key. And I think that's

by itself would not, does not get you very far, right? I mean, it might be a, it's a good

ingredient, but I think that having a passion for your project is, is critical because science,

if you're working on the cutting edge of science, it's always sort of two steps forward and one

step back, or some weeks it's two steps back and no step forward. And so you have to be

the committed to wanting to understand the answer to something. And one thing I have found

is that instead of telling a student what they should do in the laboratory, you want them to

have some ownership of their own project. So you talk to them and you say, well, you know,

what would you like to do? You could work on this, or you could work on this, or you could

work on this third thing. They're all of interest to me. You tell me what,

what you want to do. And then if they choose what they want to do, and of course it has to

be something that has to do with what we know about. It can't be astrophysics, you know,

that wouldn't make any sense. But as long as it has something to do with RNA and they articulate

a reasonable project, I will say, good, that sounds good. Let's work on that. Let's see why

you can make some progress on that. And for those who are listening and including me when I,

until I read the book,

this is painstaking work to give an example from your book itself. One of your colleagues was

transferring worms that were transparent from one petri dish to another, I guess, that were

transparent and thinner than a human eyelash. And then the person was injecting tiny volumes of

dissolved RNA in it. And you really need to have good eyesight and precision. I think threading

the needle is easier than doing these things and hope. And that is only the start of the project.

You don't know what's at the end of it. So it's hard work.

It is hard work.

And this, again, just like tetrahymena has taught us much about what ended up being relevant to

human biology. This transparent worm, round worm, that is so tiny, has led to many discoveries that,

again, turned out to be relevant to humans, but it was much easier to figure it out in this worm

and then apply it to humans later.

And do you still get butterflies in your stomach when you do some experiments,

if you still continue doing them? Or are you now a pro and it doesn't really happen that way?

I am now stuck in my office working on my computer, and I only get the joy of experimental

discovery by talking to my students and my postdoctoral fellows. And they're the ones who

are doing the actual laboratory work. And what advice would you give them in terms of dealing

with failure in the lab? Because young blood, 20s, 30s, and 40s, you might do something for years

together, and failure is more like a cousin, perhaps, for lack of a better word. It's like

Edison had said that I did not fail. What was it? A thousand times, I just was experimenting,

and then I got the light bulb out. So what is your advice to them when you talk to your students?

So first of all, we try to, we have this word called troubleshooting. It's a very long word,

but it's a very long word. And it's a very long word. And it's a very long word. And it's a very

trying to figure out why the experiment didn't work. And then asking the student, well, that's

the way science goes, making them feel better about it. Everybody has problems. Of course,

that's too bad that you lost a whole week there, but that's the way it goes. Maybe it'll be better

this week. But then also trying to look at it and say, is there something we can learn from what you

did? Even though it looks,

it doesn't look very promising. Did we learn anything? And then sometimes you say, oh, yeah,

it looks like, you know, maybe this part of the experiment might have worked. And then I say,

well, okay, we can't believe that yet, but maybe it did. So why don't you now do a new experiment

focused on that part that you think worked and see if it really is working, right? So I don't know.

It's just like all human endeavors, right? You have to learn to deal,

with failure and to celebrate success.

Right. And can a student who's got lower grades in a classroom still ace it in the lab or does,

is there a correlation there?

Very little correlation. And I was always very good in the classroom, always getting the A,

the top grades. And I'd say my laboratory skills were rather average, but I had a student who was

very poor in the classroom, had to take exams.

Over and over again, and was so creative in the laboratory. And he's now, he's had a wonderful

scientific career, is quite famous and has been elected to the U.S. National Academy of Sciences.

And so clearly the correlation between success in the classroom and success in research is

fairly random. Right. And what is not random is the folks who, you know,

go to Stockholm and are fitted with the highest prize in science. Tell me, Tom,

where were you when you got that phone call that you have been elected to receive the Nobel?

Well, I had, I was in, I was at Harvard getting an award and I was sharing this award with a good

friend, Joan Stites, who is an RNA scientist at Yale and was one of the ones who was helpful to

me when I was starting out.

And so Joan Stites and I had just received the Warren Triennial Prize given every three years

at Harvard. And during the dinner, they said that many of their recipients got the Nobel Prize

within 10 years. Well, about seven hours later in my hotel room, the telephone rang and it was

Stockholm. And they told me that,

um, uh,

that Sydney Altman and I were sharing the Nobel Prize in chemistry in that day in 1989. So I was

completely unexpecting this. I was very shocked. I was very nervous. And I put down the phone

and it rang again and it was David Baltimore, a Nobel laureate from MIT. And he said,

I just heard the news, Tom. He said, come on over to the Whitehead Institute and we will,

we're going to take care of all of the press, all the questions and everything. And you can have a good time with your friends here at MIT. So, so that was a wonderful day that I had because I had been a student at MIT. And so it was great to be at MIT and Harvard when I got the prize. And then I flew back that night and had more celebrations back in Colorado.

Until you got that second phone call, did you suspect that the first one was a crank call at all?

Did you?

The first call, they put on a friend of mine from Stockholm and and just to tell me in person that that this was not a crank call.

But the truth is that that because the phone was ringing with all kinds of reporters from all the newspapers, it would have had to have been quite an elaborate joke.

Yeah. Yeah. And what was it to accept that prize on the day?

If I were the audience, what would I be watching and how did you do on the day?

Well, it's not a day, it's a week.

They organize dinners and and concerts and you go to the American embassy and you go to the various lectures.

And it's really quite a an elaborate week.

And my family and I also invited the people from my laboratory and their families joined me.

They're in Stockholm. And for many of them, it was the, you know, the greatest week of their life.

For me, I think I was a little too much in the spotlight to really feel very relaxed about it.

But it was certainly the most memorable week of my life.

And oops, I think a few books have acknowledged that just fell down from the library up there.

You write somewhere that you forgot you forgot to take a bow.

Was it in front of one or two bows is what you forgot in front of the king and the queen and then to the Royal Academy and then to the audience or some such.

Perhaps the spotlight caused you to do that.

Yes, they they had given us a dress rehearsal on the stage where we practice bowing and the order of the bows to the king, to the Royal Academy and to the audience.

And I screwed it up during there.

I did OK during the practice.

I only screwed it up for the real.

The real time.

But it didn't matter.

Right.

Absolutely not.

Gave me the medal even.

Yes.

And did that change your life in the weeks leading after the big day?

It must have been quite a buzz as a young, you know, you're barely 41 or 42 at the time, weren't you?

If I got my calculation right.

So I am going to turn 42 next year.

So I can only imagine what it might be for someone that age to get there.

How was it?

How did the how did your neighbors, your family, your parents, you know?

Colleagues, et cetera, treat you after that?

So, you know, I think that in the scientific community, I already had a good reputation and so not much changed.

But in the but what changed was in the city, in the when I would go into the grocery store or to the school.

And, you know, previously it had a wonderful anonymity.

And now all of a sudden I was.

I was known and I was recognized.

And this took place.

This continued for quite a few years.

And then fortunately, about a decade later, some more Nobel Prizes came to our university in the physics department.

And then the pressure was off of me.

Right.

This Robin Williams, once upon.

I'm not comparing the Oscars and Nobel at all, but he'd been asked, you know, how did it feel to win the Oscar for Good Will Hunting?

He'd done a brilliant job that he said in the first week.

There's a congratulations.

Great stuff.

A second week.

Yeah.

Way to go.

Good Will Hunting.

Third week.

Hi, Mark.

Because he was there as the Mark and Mindy, one of those sitcoms back in the day when I wasn't even born.

But people, you know, slowly got got to their usual lives.

Obviously, for you, it wasn't that you still had to wait for a little longer.

And by the way, that Mark and Mindy show was took place in Boulder, Colorado.

Oh, really?

What are the odds?

Brilliant.

How?

How is it still here?

Lovely.

And one last one is this bit of a cliched question, Tom.

But with the benefit of the wisdom that you've amassed over the years, what advice might you give yourself who was 21?

If you were to tell something to your 21 year old self or 25 year old self with the benefit of hindsight.

So my 21.

Year old self.

So this was when I was still in college and or maybe about ready to graduate from college.

You know, I think I probably this may sound strange, but I probably studied too hard.

I was in the library doing, you know, homework all of the time and and reading books.

And.

That's important, but I think it's also important to talk to people, to learn from other people.

I was rather shy.

I did not have a lot of friends.

I was fortunate to have a girlfriend and that was very important who became my wife and is still my wife.

But I think that I would encourage people to have a full life and to work hard, but also to play hard.

Lovely.

And this is the book that I'm holding up for those who are not listening on on Spotify or elsewhere, but on YouTube.

And one thing that reached out to me, Tom, is that it speaks to the common man and it must have been a bit of a challenge for you to leave out.

How did you decide how much to leave out?

That must have been quite difficult, I'd imagine.

Abhishek, I'm so excited that you found it readable because that was my goal.

And I will tell you that.

Every time I wrote a chapter and sent it to my editor, she would say, it's too technical.

You need to make it simpler.

And I would work harder on it and send it back.

And eventually it got to a point where she thought it was OK.

But it was it is difficult for a practicing scientist to leave aside the jargon that we use in the laboratory.

Every field.

Every field has jargon, right?

It's a good thing in the laboratory, it makes it easy to have a conversation very quickly.

But when you're trying to extend your reach to the non-scientific public, it's a challenge.

And I did work very hard at it, and I thank you for saying that I was at least partially successful.

Absolutely, Tom.

Thank you very much for the book as well as for your gracious time on this podcast.

Thank you so much.

I really had fun talking to you.

at home. Likewise. Take care. Thank you.