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Welcome to the Microscopists,

a bite-sized bio podcast hosted by Peter Oto,

sponsored by Zeiss Microscopy. Today on the Microscopists.

Today on the Microscopists,

I'm joined by Ron Germaine for the National Institute of Health,

and he discusses why you need to think like a surfer.

There's a certain amount of thinking about being a surfer when you're doing

science. There's little ripples in the ocean if you're paying attention.

And if you are a really good surfer,

you can pick out the ones that are going to be the waves that you want to surf,

but then you have to paddle at the right rate so that that doesn't pass you,

if it goes past you, you're too slow. If you go way too fast,

it's gonna hit you in the head. But if you do it just right,

you're on that crest and you're going ahead.

How we learned to let go and give up, being a control freak.

And I've always remembered, you know,

sitting there and hearing that from him and deciding that there was, uh,

a sort of compromise to be made between what I might consider to the utmost

efficiency,

sort of controlling everything where I thought maybe what I knew better,

and allowing people to sort of grow themselves

And what he does to entertain himself when he gets bored in meetings,

If I really got bored and, you know, you can get bored, even in good meetings,

sometimes I would begin to pull up some of my photographs and let them

cycle on my screen. 'cause I wasn't, I wasn't taking notes anymore,

knowing that everybody behind me in the audience could see my computer. Um,

and that made me sort of well known to my colleagues as a photographer,

All in this episode of The Microscopists.

Hi, I'm Peter Oto from the University of York, and today on the Microscopist,

I'm joined by Ron Germaine from the N I H V.

It is an absolute pleasure and an honor to meet you today.

Very nice to meet you and have a chance to do this. I look forward to it.

I, I've gotta say your, your name in the,

even the logical world is huge. It, it, it's, you know,

I'm not a hardcore immunologist,

but everyone knows you and, and

yeah. You know, it's not often on semi starstruck, but,

Well, I couldn't all start off with a little story about that.

Go on.

So there is a Norwegian, uh,

immunologist who decided to write a book about immunologists,

both the deceased and living.

And I was chosen as one of the living immunologists. And we did a walking,

um, recorded discussion of this type.

And then she sent me the transcript for this. And I looked at it,

and I was very upset because there were a few ums and uhs here and there.

And I said, uh, that's very embarrassing. And I,

I edited it lightly and sent it back. And she said, no, you don't understand.

I've never had anybody do an interview like that with me,

including the Prime Minister of Norway that wound up

getting published in Norwegian. And, uh,

a few years later, I visited her and she said, an interesting thing happened.

My book was pirated off of Amazon.

And then I got an email from this young lady who said,

I saw my father's name in your book in the chapter by Ron Germaine.

And it turns out this was the daughter of a veterinarian who gave me my

first set of inbred mice to do experiments in my basement when I was 15.

Oh, wow.

And so I got, uh,

her email and contacted her to ask if her father was still

alive, and if I could get his email, which I did.

And we wound up corresponding, he had moved from, uh,

Sloan Kettering to being the head veterinarian at Rockefeller University,

but had retired. And of all things,

his hobby was the same as mine photography.

So we wound up exchanging photographs. Now, this person,

I'll stop in a second here, but this person has an interesting last, uh,

interesting name. It's Ozzy Bag Jr.

It turns out that b c,

the mouse strain stands for bag albino.

That's what B means.

And it was his father who created those inbred mice.

So everything goes around and comes around. Ah,

Wow. It small, big, small world, isn't it? Yes. So, I'm, I'm gonna take you.

So you were 15 Yes. When you started. Explain.

So I, I'm gonna, okay, so I'm gonna take you back even Yeah.

I usually come up with this late, this question slightly later on.

What was the first career that you ever thought you might want to be as a

youngest child?

What was your first thought of job that you thought you'd want to be? And

I only can remember back exactly to the moment I became an immunologist.

Actually, I may have wanted to be a lawyer before that, before that. Uh,

and there's stories that go with that.

But I know where I was sitting and what I was doing.

The moment I became an immunologist at 15

Nickel,

I had to do a science project, uh, for my, um,

school science class.

And I went to the library and started reading the Time Life,

big Book of Science. And I said, well,

I'm not gonna build a rocket ship or do a volcano.

And then I got to a page that had a picture of a white mouse with a brown patch

of fur. And that was the, uh,

prototypic output of a classic experiment from Billingham,

Brent and Metar of in Ute in utero Tolerization.

And I said, that's what I'm going to do.

You're great.

Why? I wound up getting the inbred mice. My father ran a, a garage,

but one of his customers was Ozzy Bag Jr. And my father asked him,

can you help my son? He can't use these pinto mice from the pet store.

And I wound up going to a branch of Sloan Kettering and getting mice out the

back door. I'm a little manual about their anatomy,

so I could harvest spleens and lymph nodes and built cages and put them on my

ping pong table in my basement,

and bred F one mice and gave them parental cells.

So they had G V H and then tried to cure them with a thymus graft. And remember,

I'm doing this in 65, which are four and five,

which is about a year after Jacques Miller starts publishing on the thymus,

which I had read about already. And I even wrote him and it said,

uh, I don't understand how to do aseptic th grafting. Can you help me?

And the letter followed him, uh,

to the Chester Beatie and then to a sabbatical he was doing at N I H.

And he wrote back, uh, and it was terrific.

And 30 years later, I get an email from Jacque Miller, Ron,

you're one of the world's experts on antigen processing and presentation.

How does cross presentation work? And I wrote him back and said, Jacques,

you don't remember, but 30 years ago as a high school student,

I wrote you asking for advice.

And I find it rather cool that 30 years later you write me asking

for advice. And I actually had a copy of our, you know, exchange.

Some of the slides, have that information and send him a copy.

And that's now a story they use at Wehi to introduce me when I give a

talk, because it's, it's spread throughout the institution.

I, I'm gonna, I'm gonna throw it out. I, I, I can,

I cannot believe that has happened today. Well, I, I don't,

we'd never get the mice out to, to start with, so that, that couldn't happen.

But if a 15 year old was to write you a, a letter saying,

I'm really interested in this, can you help me? Could you,

could you even let them into start helping in the lab and welcome them as a

placement to a summer student? You know, how much could they do now?

Uh, I didn't quite get down to 15,

but a high school student who was I guess 17 at the time,

wrote me saying he had just read a paper that we had published in immunity on,

uh, thymic development and selection. And he had a number of questions,

and I said, oh, that sounds familiar. And I got in touch with him,

uh, and, uh, he had a lot of interesting questions, clearly very smart.

And I actually invited him to spend time at N I H, which he did.

He wound up going to Harvard, uh, and m i t for his PhD,

and has started biotech company since then.

Wow. And and you, you did, so those listening won't be able to see the pictures,

obviously. So we'll, we'll describe the picture. So this,

this looks like you at a, uh, possibly at the age of 15.

Yes.

It's probably the only picture anybody has available to them without a beard.

And, and this is, uh, is this your school project?

Yes. The,

the on the behind you to your left shoulder is one of the homemade

cages that, that I prepared for doing this. And, uh,

and it describes the, um, runting disease,

the G V H that I was trying to, uh, cure.

So, so that's

There at that time. Yeah.

So you knew where you were going at the age of 15. Yeah.

You knew what you wanted to do. So, so where I where did you go to study?

So, uh, initially I, I was in my home,

then I did some work at my high school.

And my high school biology teacher stayed after school late every day except

Friday when he had bowling night. Um,

I then, uh, was accepted to,

we didn't have AP bio in one of these advanced placement courses in my high

school,

and I applied to the National Science Foundation to take an a p e biology

course, which I did at Syracuse University. Uh,

and that was meant just to be a class.

But I had already been doing this research,

and I didn't wanna spend the summer not engaged. And I said,

are there any immunologists here? And they said, yes,

there's this woman birdie Arris in the basement of the building where the course

was.

And so I wandered on down and knocked on her door just like I wrote the Jacque

Miller. And I said, I want to do research with you this summer. And,

um, she was obviously a bit nonplused about this,

and there was sort of pimply 15 year old saying they wanna do

sophisticated immunological research.

So she figured she'd get rid of me by sending me off to read three or four j e m

papers and come back, uh, and report on them to her.

And I'm supposed to be three o'clock,

and I remember it was a Monday or a Tuesday. And again,

I had this written recount from her, so I know this is all, you know,

not my imagination. She said, at precisely 3:00 PM on the anointed day,

I knocked on her door and proceeded to explain to her all the details and all of

these JM papers. And so I wound up doing research with her in the summers, uh,

through most of college.

Right. You,

you must've been almost frightening for them to come across someone who's,

who's so dedicated and picks it up. So picks it up so fast, so naturally,

you know, it, it's not a natural thing to just to instinctively pick up.

And you obviously have a gift, uh, in that, on that side of things.

So that was when you were 15 moving through into college.

So usually I'd say, you know, when you were at university, did, was there,

has there been any moment in your career where you wish you'd done something

different?

Um, not really. I mean,

there are individual specific sub choices,

but not different from the main thing that I've done. No,

I think it was the right choice.

Is there any path that you followed that you regret going down a, a specific,

a specific project or something else that was just destined to fail or anything

else in hindsight? Well,

Well, there is an older field of immunology,

uh, that's been renamed actually. So now we call them regulatory T cells,

but back in the day they were called suppressor cells.

And I did quite a bit of work on suppressor cells. Now,

I don't regret the work I, I did,

and I think I did it as well as it could be done at that time.

Uh,

but there were many immunological careers that founded on the shores of

suppress neurology,

whereas a few of us have managed to sort of resurrect ourselves.

So Doug Green was in that category when he was with Dick Gershon,

uh, Harvey Canter, obviously, who was doing all the work with, with, with Dick,

uh, myself.

But there are others who have not fared so well in,

in the new world of, of immunology, so not regret. But, uh,

there are many interesting stories about, uh, folks in,

in the field. Um,

teasing would be the polite way of pointing out how they

remind people of my involvement, uh, in, in those studies.

I, but, but as you say, at the time, it's the best technology. It's the, it, it,

it's, it's what makes sense. It's what the evidence is showing at the time.

It's only until other technologies come through.

And I'm looking at your background now,

and you've got lots of very colorful light microscopy,

confocal fluorescence images, how much I,

I I know you're moving into spatial omics type technologies now as well.

How much do you think technology drives the science?

And how much does the science drive the technology, or,

or is it truly hand to hand in hand?

I had a discussion when I was trying to help, um,

some other folks at N I H set up an n i H wide systems biology program.

And one of the scientific directors, obviously,

the people who control the budget for the intramural research at N I H and

individual institutes said to the group, um,

tell us what you're going to do. And I said,

we're going to learn how to do system biology. And he,

he repeated his question saying, I guess he didn't hear me. Um,

what are you going to do? And I said,

we're going to learn how to do systems biology. And he said,

I just, I'm not getting through. And I said, no, you have to understand,

do you think Sanger cared about F i x 1 74 or how to sequence D N A?

I said, we are trying to learn how to sequence V N A. And he said, no,

but you have to tell me what you're going to do. He just never, he never got it.

Um, so,

but that's related to your question, which was you need,

if you can develop a new technology,

or you can take one from a totally different field and apply it in a new way,

you get to ask questions and get answers that are new

and that other people would have trouble getting.

And as general principal, I've actually given talks to,

to trainees about the fact that there's a certain amount of

thinking about being a surfer when you're doing science,

there's little ripples in the ocean if you're paying attention.

And if you are a really good surfer,

you can pick out the ones that are going to be the waves that you want to surf,

but then you have to paddle at the right rate so that it doesn't pass you,

if it goes past you, you're too slow. If you go way too fast,

it's gonna hit you in the head, but if you do it just right,

you're on that crest and you're going ahead.

And so I've changed my career multiple times. So I, as we discussed,

I was a cellular immunologist in my, you know, let's call it my youth,

but in the late seventies, very early eighties,

so I'll date myself a bit, uh,

I became aware of something called recombinant.

D n a wasn't making much of an impact at any in immunology at the time,

but I said, for biology, this is going to be a big deal.

I don't know anything about it.

I couldn't really staff my lab with people who knew it.

And so I took an illegal sabbatical from N I H to learn molecular

biology. In fact, I took a course on recombinant d n A at Harvard,

where I outranked the person teaching the course.

And he asked me during the course, why was I doing the homework? And I said,

because I wanna learn the subject. And that wound up, uh,

leading me to N I H and working with John Seman and Cloney, uh, mouse,

m a c class two molecules. And then,

because I was both a cellular immunologist who was already known to the people

at the laboratory of immunology, but now had become a molecular immunologist,

I got a tenured position. And that's where I stayed ever since. But I then,

after a a period of time, uh, using that approach,

switched to doing cell biology in terms of the biochemistry of t-cell

receptor signaling, or the movement of molecules, uh, in the,

the processing pathways, and then switched again, uh,

to use imaging as a primary tool. Because at the time,

you know,

we really didn't have much in the way of an understanding of exactly what's

happening at people. You have gallons, which tells you the stuff, you know,

small insights are circulating around and cannulating people, cannulating sheep.

But if you wanted to understand how all the things that I and others had worked

on in antigen processing and presentation and t-cell recognition were actually

happening in secondary lymphoid tissues, we had to look at 'em.

So we got into imaging, you know, right at the

crest of the wave. So I think it, it is completely joined at the hip.

Uh, I couldn't build a microscope,

but I could work out technology for using the microscope.

And those I think, are very important. People forget that most Nobel Prizes,

good fraction of them, are given for technology,

not for the biological or chemical or physical discoveries,

because it's recognized that that's how science really advances,

you know, p c R two for sequencing, take a look. Uh,

so I think people who don't think about technology and how to import it or

develop it, um, are taking short shrift in,

in what they can really do in terms of,

Yeah, that's a, it's a really excellent point.

You think super resolution microscopy for the Nobel Prize,

you think the cryo-electron microscopy solving a completely,

it's the technology G F P Yeah, yeah, absolutely. Tool.

Uh, they weren't that interested in G F P per se, and understanding the phrase,

understanding the manipulation, how to use it as a tool, right.

That got that prize. So certainly the microscopy.

Do you remember the first microscope we used?

I had a, I don't remember whether it was a tasco, but you know,

one of the kinds of microscopes you would buy as a kid. And I used it, uh,

when I was young, back in, in the day that we're talking about to, to look at,

um, I tried to be luen ho and look at, at things in drops of water, you know,

and esia, uh, but also insect wings and various things.

I actually gifted that microscope to my niece when she, uh,

was young with the view that she might follow in that path.

But she became an investment analyst, so it didn't,

didn't work out.

But the interesting thing about microscopes is I have no background in optical

physics. I have no real background or training in microscopy.

When we started doing the imaging that my lab has done for the past 20 years,

the only thing we used a microscope for was to count cells.

So we really developed all of these tools, uh,

sort of by the seat of our pants.

But that was the thrill, wasn't it?

Yeah, that was terrific.

It's, um, we

Also had some help, and I do, I want to have, make a call out because it's,

it's important for thinking about the collegiality versus the competition in

science. When we got our first two photon instrument, I actually went, sat down,

you know, turned it on, tried to look at things, and it was black.

We didn't see anything. And I said, this doesn't make any sense.

And luon Adrian had, you know, been, uh,

doing work in this area.

He's been doing microscopy for a lot longer than many people actually

recognized. And so I called him up, or I wrote him, I forget.

I emailed him and said, did you have any suggestions? And said,

which objective are you using? Take a look at the back aperture.

And we looked at it, it's this little tiny thing. And he said, oh, no,

you need this Olympus lens with this big fat back aperture.

And we managed to get the Olympus rep in and, and borrow one of those lenses,

screwed them into the scope, turned it on, and all of a sudden,

now we can see things. Now, you know,

ULI was basically a principal competitor at that point.

We were working on almost exactly the same thing, but he was

without any hesitation, willing to share that information.

And then later on,

he hosted two of the postdocs from my lab to learn the

inal method that he and his, uh,

brother-in-law th thorston ple had developed.

So I think that's a very important aspect.

You know, not everybody behaves that way.

Yeah, no, uh, I think it was a very good example of how to work. Uh,

everyone's competing against everyone,

but we should collaborate and support as well, uh,

because that's because science goes faster, I guess.

You mentioned your microscope, you handed to your niece, um, you became a,

an analyst.

Have any of your family moved into the science world?

So, a little bit of background. Um, neither of my parents completed college.

They both were of an age where, uh,

the depression required them to go to work for their family. They,

my mother was finished high school at 16, you know, at the top of her class.

My father had done very well. Uh, my father started college, but again,

they had to go to work. Uh, in the end, my mother was a part-time bookkeeper.

My father had a, a lamp business that didn't succeed as the,

the newer large scale things like the covax kinds of companies came up.

And he worked with my uncle to run the garage that connected me eventually to

Aussie Bag jr. Um, so no professional really in, in the family,

uh, at that point, but that's changed a bit.

So we now have three MD PhDs in my immediate family,

myself, my son, and my daughter-in-law. Oh, wow. Uh,

my son is now, uh, just about to start on the faculty at Wash View,

uh, as a A M o, uh, specialist, uh, with laboratory.

So sort of the double or triple threat that's, um,

always a pro a problem these days. And, uh,

as I actually talked to you briefly about before, uh,

I did science projects with my son, uh, all through his elementary school,

middle school, and high school. And that tradition continues in the family. Our,

uh, my grandson, who's now six, uh, was gifted with, uh,

a molecular modeling kit.

He got very interested in gems and crystals and did his first science project on

the bonding in diamonds and rubies.

How long did you say?

Six.

Oh, good golly. You sent me this. So would you like to describe what this,

this, this picture is? Right.

So on the top is, um,

are some notes I took attending Zan Cohen's

seminar series at Rockefeller University. So as a high school student,

I couldn't drive in New York City,

but my mother would drive me into New York to attend those seminars at

Rockefeller. And I'm drawing macrophages and lymphocytes in this note. Well,

many years later, I volunteered to give, uh,

a talk about the immune system to my son's first grade class, uh,

which is what you see, uh, drawn in that little diagram.

That's me standing there with the projector. This is before PowerPoint.

These are real slides. And all the class wrote me, um,

these thank you notes, uh,

and my son was required to write it as dear Dr. Jermaine,

not dear dad to be the equivalent of all the other students in the lab.

So, uh, what goes around comes around.

And, uh, I How important is that engagement with school children?

Because obviously you are inspired as a school child.

Do you still get to go into schools or do you,

do you change any of your team into schools to help try and inspire that younger

generation?

Um, I did have what's called a post-baccalaureate student recently who did an

outreach project, uh, with students, uh, about vaccines. Um,

in Baltimore,

I used to volunteer when my institute had a special program of outreach with

high schools in the community.

And I ran the science fair in my son's elementary school for many years.

And I would go in right before the, the science fair season,

and I had developed, um, a very, um,

simple way of sort of showing them things they could think about doing.

So if you took a water soluble, um,

green ink and you put it on a coffee filter and dipped it in water,

you'd separate it into blue and yellow in real time.

I could do that right in front of the class. And even my son's quote,

jock friends would be running home saying, mom,

do you have any Mr coffee filters in the house?

I gotta do this really cool experiment. Um,

but eventually the lawyers in the community complained that they

couldn't help their children do their science fair projects at home in the way

that I could, and it all ought to be done in school.

And they canceled the science fairs other than what was done in the class. So,

oh, wow. Yeah. Even in a, in a wealthy, uh,

well-educated community, they're still resistance to,

to science in a certain level. They're very disappointing. That's

Competitive parents that Oh, wow.

But yes, I, I have done it, and I do think it's important. And I think, I,

I always think that the meetings with the,

the graduate students and fellows when I give lectures at universities,

is one of the more important things of the day, um,

and look forward to that.

But thinking about, so you've got your lecturing, you've got the outreach side,

you've got, obviously you get to conferences, you've got your research side,

the panels that you sit on, committees that you sit on. It's an intense job.

You've got children, they're growing up, they've moved out.

But how did you find time with the children?

How did you balance that work versus life? And, you know,

how, how did you inspire them as children?

So, I, I was incredibly fortunate. My wife was a research psychologist and,

uh, children's, um, psychologist.

And she decided that it was important for at least one parent

to spend a lot of time at home with, uh,

a very young child. And so she moved to halftime work. So she was home,

uh, a lot of the time. And,

and that relieved me of some responsibility.

On the other hand, one of the nice things about doing research,

and especially if you are not actually there running the flow cytometer

or collecting the images where you've gotta do that on a time schedule,

your time is your own. I can decide to cut out a time from say,

you know, five in,

in the afternoon to eight at evening when a young child would,

you would be going to sleep and then work after that, which, you know,

was mostly, you know, you know, reading literature or writing papers.

And so I went to many of my son's soccer practices to as many of the

ga gains as possible. But the other thing,

as I said that I did from the very earliest days when he was in

elementary school, is work with him on projects. Uh,

and there are always discussions about, well,

you did some of the work on the poster board that he, you know, turned in.

Isn't that wrong? I said, no,

because he's going to learn what this,

how to really do this and how to do presentations.

By the time my son was in high school,

he was the go-to person for all people doing project,

uh, presentations in the school.

And same thing's happened at Wash U that he is the person,

everybody asked about how to clean up their PowerPoints and do the

presentations. So, uh, a lot of it was, you know,

father to, to to child handed down, um,

through those interactions in addition to the ones that would've been banned

performances or soccer games or anything else.

Think thinking of a, you say you used to play soccer. What is your sport? What,

what's your favorite sport? Oh,

Well, I didn't play soccer. My son played soccer. Um, I went to his, his, um,

practices and his games. I was not

a sports person per se. I ran cross country for a while.

I used to consider myself rather fast,

even though I wasn't long and lanky until I got to high school.

And it turns out that my high school track team

set the national records for things like the four 40 and the four, you know,

400 meter and relays.

And one of my classmates won a bronze medal at the Olympics.

And I realized that I was not fast and should not continue to do that. That's

Not fair. That's just not fair though, is it?

And, uh, I also was a wrestler in high school and,

and did fine in my weight class,

but I never found it all particularly enjoyable to, to do that.

And so I started a hobby when I was in college,

and, uh, you're gonna find this interesting. It's actually photography.

So I did imaging in the lab and photography when I'm out of the lab.

And, um,

I, I was going to ask you, what, what is your photographic subject?

What sort of photography do you like? They, they're,

They're very diverse. I do landscapes, cityscapes, um,

street photography portraits. Um,

I'm learning how to do bird photography right now, which is a challenge.

It's, it's not so, so easy to do it really well. Uh,

the problem has been I've become the go-to photographer,

so I am almost never in any of the pictures.

I have tons and tons of family pictures at Thanksgiving.

Everybody's there, all the food is there, but I don't, I'm not there.

Is is that not outta choice? I, I, I look,

No, I don't. I just,

I'll take the picture.

No, I, I occasionally I'll turn the camera around and sort of do a selfie,

but I'm talking about a real camera, not a, not a, you know,

not an iPhone in doing this.

And there was a period of time where I would go to meetings

and if I really got bored and, you know, you can get bored,

even at good meetings,

sometimes I would begin to pull up some of my photographs and let them cycle

on my screen. 'cause I wasn't,

I wasn't taking notes anymore knowing that everybody behind me in the audience

could see my computer. Um,

and that made me sort of well-known to my colleagues as a photographer,

and actually with no multiple invitations to create books, uh,

for, for them or, you know, they, they encouraged me to,

to start it as a business, which even that I'm an n I h that's even,

even that's a problem. So, no, I didn't do that.

Yeah, that bird photography, I'm with you. So actually,

I, I was one of the very first digi scopes, if you've heard of Digi scoping. Uh,

so you take photographs of who, your telescope of birds. Uh, so I, you

Need long lens. You need a long lens to do it really well. Yeah,

That's what a telescope is. It's a big lens, super portable. Uh,

so it's very early days of digital photography, full stop. And, uh,

hence I was one of the first digi scopes.

Now everyone does it and they've got the big cameras and everything else,

but he'd mean,

I've got published in a lot of the birding magazines for picking up the rare

birds when they're landed in the country. But that's a sad hobby.

That was from a long time ago.

That work took over my life and the family took over my life.

There's just no time for that at the moment, or very little time anyway. Uh,

so that's your comedy. If, so, we talked about being 15.

We talk about where you are now in your, your hobby with photography as well.

If you could do any job in the world for a day or a week,

what would you like to try and sample?

Hmm.

I'm gonna give you a slightly strange answer because I certainly don't wanna

sample it in one day. Would never be useful, potentially.

But I will tell you that I, um,

often work on my lectures, you know,

mentally I run through them as if I'm rehearsing a script.

So I know what I'm going to say while I do the same thing in

lectures as if I was a major politician.

What would I say to get people to understand they should get vaccinated or

they should worry about the climate. And I, I write all these speeches out,

but I'm not sure I'd want to be the politician for a day,

because usually one day doesn't get you anywhere. Uh,

and in the current environment, I think it would be somewhat unpleasant,

but the notion of being able to rationally influence

a larger audience for, for the better, you know,

for good would be, would be very interesting.

So would you want to be the politician or would you want to be the script writer

that is writing the script for the politician?

Uh, I prefer to write my own speeches so

I can both, I'm not sure how many politicians do write all their own speeches.

Yeah. Uh, because as you say,

actually getting the message across succinctly and,

and inspiring and to get people on side, it is a gift. It's a, it's a,

it's an art. Uh, so I'll,

I'll have you down as a politician then at that point. Mm-hmm.

I'm sure I could think of other things, but that is, that's sort of a

No, I, that's a good answer. No, I think that's a really good answer. I,

I, I have a question, which is usually who inspired you? And actually,

I think you've inspired yourself and your science teacher help develop that. Uh,

is there anyone in the community that you, you actually look up to? I, I, I,

I'm sure there's plenty that you've looked across to and looked up to,

but is there one or one person who stood out as being an inspiration, uh,

that you admired particularly? I'm sure there's plenty of you admire, but,

you know, just it's a one standout person.

I, I don't think I could give you that, that answer. I, because in part,

if you go back to what I said before,

I've always looked beyond the narrow area that I'm working

in. And so there are people in,

in different fields who make different contributions that I've always, um,

admired for what, for what they've done. But there's no one that has,

you know, changed the,

the direction of my work or in influenced me in a way beyond, um,

the personal mentor. So, as I said, I had the high school teacher.

I then worked with Bernie arduous for, for many years. Um,

and, you know, I think she was a very strong influence.

She used to Dutch in a very rigorous, you know, in a sort of Dutch way. Um,

and a lot of my time spent in the lab was washing pipettes. You know,

you had to learn how to do science at one level and then go

do things like cleaning the pipettes and making sure all the, you know,

al CanOx is rigged out of them, and you could use them again.

So that a certain sort of compulsive level of, uh, being careful about your,

your, uh, experimental work that, that came. And then I, you know, I did my,

uh, PhD with Baruch and he has a, a very,

uh, many different sort of, uh, reputations, if you will,

at a certain level. But if you knew him very well,

and he wasn't the most open person to everybody, but I knew him very well,

actually shared a birthday, not by year, but by date. Um,

he was incredibly insightful a about,

um, the way things worked. And he could,

he could look at data and, and pull out an,

an interesting, um,

story about what it was telling us. And I think you say, who would I admire?

People who can do that,

who can look at the data and tell you something that's not obvious in it

attracted me. And it's, it's sort of now in a way,

what I'm known for, whether it's in asking questions at meetings,

or whether it's, it's looking at data and,

and putting a very different spin on it.

So this, I, I'm gonna pull up some pictures in a minute from your,

from your past. Uh, so I'm not sure who they are,

so you can tell me who they are in a moment.

But you mentioned that the importance of data and pulling out information from

the data or being able to see things in the data that isn't instinctively there.

How much of a role do you see ai, uh,

coming into this now and playing your role and

speeding up science using machine learning through to the AI to identify?

We can't see.

We use machine learning and neural networks,

which is a form of AI in, uh,

interpreting our very complex imaging data. Now,

it's just not possible to do it by just looking at it. I mean,

pictures are pretty, but if you've got 80 parameters, you're,

you can't just look at it and,

and figure out what's really happening and extract all the relevant information.

Uh, and I get a weekly mathematical seminar from one of my current fellows,

uh,

who's developed software tools to take the process data that we use machine

learning to create from our images and turn it into spatial

understanding. What are the relationships that exist in the tissue, uh,

that are not, you just look at it now, of course, that's what's going on.

The T-cells are outside the tumor, they're inside the tumor.

And I have to learn about generalized mutual information and bits of,

of, of mutual information, data. And, you know, it's really, you know,

very interesting. So I think in the general sense,

I think there are enormous roles for it.

I think we should be using it more correctly.

Um, it has to limitation because it can find things,

it can tell you certain things,

but often there's a kind of black box that goes from the primary data to that

interpretation where you don't know how that can connection was made.

And sometimes knowing the connections,

what the steps are between things is actually important.

It's a level of understanding rather than just an answer that's going to be

important.

So I would like to see it evolve in a way in which there's a certain

level of an ability to deconstruct what comes out at the end

to understand how that, uh, feature space arose.

But I do think it's gonna be incredibly important as we do more and more high

content work.

Yeah. And, and as we started, I think a little while back, spatial OMI is,

is really having to push our abilities in that side and actually connecting all

the dataset is not that easy. And you mentioned your fellows and your team,

so I presume this is your current team.

Uh, it's about a year old, but many of the people are, are still in the group.

That's still a big group.

So this is not just my lab. This includes people who are,

so for example, the, the woman just to the right in the green, uh, shirt.

So she was an independent research scholar.

So that's a transitional appointment between postdoc and faculty

and two of the, uh, individuals, the two, uh, on the, the far,

uh, your left hand side over there are,

were part of her group, so that those are not, um,

my fellows, the gentleman in the yellow T-shirt actually has a,

a junior faculty appointment in the cancer institute. And two of the people are,

um, postdocs with him. So this is, uh,

let's let's say an extended family. Yeah.

Still 50. I I think I counted about 15, 15, 6, 6 around that. So it's,

it's an, it's an impressive array o of, uh, students,

postdocs, fellows, and, and yeah, extended team. You, now you sent me this,

'cause this, this is looking like a very young of yourself. You say,

now you've got a beard.

I I've had the beard a long time, but then I used to have hair, and

That's

Clearly changed. But as I said, uh, Ben Asel,

who's the other person in the I r Jean T-shirt, uh, was my mentor.

And we both had the same birthday, October 29th. Um,

and I was not allowed to give him a present. He often gave me some presents.

Mostly what I did is I resurrected old,

older photographs of him or photographs I had taken and, uh, framed them up and,

and gave them, and that I was allowed to do. But anyway, just to go back,

if you, if you still have it, the IR gene, that's immune response genes,

which is the original name for M H D molecules,

which is what he won the Nobel Prize for in 1980. Uh,

and so this was a dual gift from the laboratory to us sort of

matching t-shirts.

And so this, uh,

That's the Nobel Prize celebration, so that's the day that it was announced.

Oh, so, so that was in, in the office at the time. That's,

That's in his office at the time.

And if you look at me looking a little bleary eyed, holding a,

a glass of champagne, I have a camera.

I was the semi-official photographer for that as well.

Of course. Yeah. And then,

So this

Obviously a few years afterwards, right?

So three generations. So, um, bill Paul,

who's the other individual in this picture, was a, uh,

fellow with Benoff,

and he became the head of the laboratory of immunology when Ben Assef moved from

n I h to Harvard to become the chair of pathology. And Bill, of course,

was my, um,

lab chief for, uh, let's see,

how many years would it have been?

33 years when I was at N I H.

So not my official mentor, but a mentor of sorts. Um,

and so there was a lot of, um, lineal connection here.

That's wonderful. Now going back, you sent me some,

uh, near, well, not far side, near side pictures in this instance. Mm-hmm.

Uh, all, all featuring yourself. So who drew these?

They, one was the near side was drawn by a, um,

physician who worked in the lab briefly, and the far sides were,

or the, um,

Calvin and Hobbes were annotated by members of the,

the laboratory, um,

as illustrations of what it was like to be in the lab. So I'm,

I'm well known to operate in fire hose mode. So when, uh,

the person raises their hand and says, Dr. Jermaine, may I be excused?

My brain is full. That's a, uh,

a comment many people would be, uh, familiar with

control freak is, uh, that's actually quite interesting.

So when I started the lab, I,

I was pretty controlling about how experiments were done.

And I had a, a fellow who I now have to call Sir Robert.

I don't know if you know who I'm talking about, Robert Lechler.

Okay.

Um, who was, uh,

became a sir during the Jubilee celebration.

And he was also the recent head of the equivalent of the Academy of Medicine in

the US in, in the UK from Hammersmith.

But then he was at King's for a long time.

He wanted an exit interview as a postdoc. And I,

what is an exit interview? He said, well, I want to discuss, you know,

what it was like to be here, you know, how things worked. And he said,

um, it was terrific, really enjoyed it, but

I would have data that I might even have for a week or so before we have our

meeting,

and I'd show it to you and in 30 seconds you would tell me exactly what the

next experiment should be,

exactly what the controls and the experiment should be. And you were right,

essentially every time you would do that.

But that was not so helpful for my career development.

Um, and I've always remembered, you know,

sitting there and hearing that from him and deciding that there was, uh,

a sort of compromise to be made between what I might consider the

utmost efficiency of sort of controlling everything where I,

or maybe quote I knew better and allowing people to sort of grow

themselves. And that's evolved into a,

a style in the lab where I expect the fellows to take ownership

of their project to a level where they know more about that topic than I do.

And I'm really a colleague and consultant based on my

experience of how to be sure we're choosing the right question, uh, to look at,

uh, the data and, and how to tell a story about it,

but not to control, you know, what they do.

And the best thing is when they come in and they show me something and I say,

well, it would be really nice if,

and then they turn on the next slide and the PowerPoint and they say, yeah,

I've already done that experiment here. Here's the results. And they're,

they're ahead of me. And I think that's terrific. So I'm not,

not the control freak in that, in that anymore.

I, I think that's amazing advice, but I do wonder if,

so Robert actually thought that, uh,

came up with the ideas himself before he walked into your office so he could

develop those skills. Obviously it's doing no harm whatsoever. Uh,

but you do want No, I,

Yeah,

He must have tested himself. He must have thought. Right? What's wrong?

Gonna say, let me predict. Ready

For Yes, absolutely. So I,

I'll tell you that this actually is something interesting because it's goes back

to rif.

So I was the equivalent of PubMed at,

at Harvard for immunology.

When I was a student and an early faculty member.

There were only a couple of journals you really had to know. I'd read,

I'd read all of 'em as soon as they came in. They're all in print,

obviously at the time. And somebody could come and ask me, do you know if,

and I'd say, yeah, in the middle of the march jm,

there's a paper by so-and-so that that has that information.

And so the discussions with Ben Asra would go as follows.

The JM would come in in the morning,

and I know I'd get a call from him at night and he would say, Ron,

have you read? And I'd say, yes, I've read the,

the article by Zinc Nagel in the JM today. And he says,

and do you realize that? And I said, yes, I understand that it means this, that,

and the other thing. And he said, well, then we, and I said,

I've already set up the experiment that that's the conversation I had to know

what he was going to ask me about and which journal by what person in which

article with what interpretation and what experiment needed to be set up in,

in real time.

And the best of my fellows do exactly that as well.

Yeah. I, I quite difficult to comprehend the matter of reading.

That must have gone on. I'm doing research as well. Well,

I'm gonna switch tack a bit and I'm gonna ask some quick fire questions.

So the first question is, are you an early bird or a night owl?

Both.

Both. Okay.

Right. Reasonably early. And I keep working reasonably awake. Well,

What, what time, what time do you typically wake up?

What typ time do you typically go to bed then

By, by 6:00 AM Yep. And

these days, you know, I go to bed a little earlier than I used to. 11

Still, that, that's burning both ends. When's your most productive time of day?

Uh, different strokes for different times.

There's certain things that work well, uh, in a quiet evening,

you know, when you're want really com com you know,

contemplate things and they're,

they're not other zooms or meetings coming up or other, other events.

And there are other things that sort of do well in real time.

Okay. PC or Mac?

Mac,

McDonald's or Burger King?

Equal,

Equally good or equally bad?

They're useful for what they're useful for. Not a frequent meal. Okay.

That's okay. Coffee or tea?

Coffee.

Short or long? Espressos or Americanos?

I make my own lattes.

That's, uh, grind your own beans as well.

No. Espresso

Beer or wine?

Neither. Very rarely drink

Chocolate or cheese.

Hmm. There were moments where the chocolate is really important,

but I have, uh, I eat much more cheese.

Okay. So if you were to eat, go to a conference, take it back,

what would be your,

the best food that someone could actually serve in front of you?

Before I became allergic to it,

it would've been probably really good sushi,

but unfortunately that's limited now pretty much to tuna.

'cause everything else is a white fleshed fish. And I now have an allergy. Ugh.

So outside. So, okay. We, what would be the worst?

So then it would be Chinese food,

Excluding allergic sushi.

What would be the worst thing that someone could put in front of you?

Incredibly spicy garlic filled Tex-Mex.

You know, there's not many people that give a straight answer that I'm,

I'm impressed. I can, I can understand why. That's good answer for it.

You cook at home or do you wash up at home?

I cook and wash up.

You must have a dishwasher though.

Yes. Yeah,

TV or, oh, what is your signature dish?

Uh, I wanted chef's competition for vinegar, slithered pork.

Uh, so Jacques tro competed in in that there was a,

a meeting, uh,

in Dallas where everybody had to bring a recipe and did a kind of, um,

chef's competition. And, uh,

everybody thought Jacques would win for this very, you know,

lobster sauce scallops. But I won with the vinegar,

flittered, pork and vegetables.

Congratulations, sir. I've never had that.

So now I'm gonna have to look that up. TV or book.

I think I know the answer to this, but TV or book?

Uh, these days it's actually tv.

And is it serious TV or do you watch any,

watch any mindless TV to shut off at the end of the day?

Mindless TV at times. And, uh, I love action movies.

Uh, okay, so my next film, my next question is, what is your favorite film? I

Don't have a favorite film, but I have to admit that,

um, I've watched Hero, I don't know if you know that movie

N Not Seen it. So Hero. So

It is gorgeous. This is by the, uh,

director who name I would tor, you know,

completely ruin if I try to pronounce it,

who did the opening of the Beijing Olympics.

And the photography, uh,

the colors, everything is just amazing.

And at the same time, the ending is actually a surprise.

And

there's a dub version and a subtitle version.

And I don't like the dub version at all because you lose the

impact of the,

the statement that the person who becomes the first emperor,

who is the first emperor of China makes, even though you can't,

I can't understand what he's saying without the subtitles.

The way it is said is incredibly moving.

So this is quite a combination of, of, of, of sort of history,

um,

this visually stunning Do you,

but there are other movies that are sort of close to that category that are

completely different. So eclectic taste,

Oh, star Wars or Star Trek. Then,

Uh, I was always more of a Star Wars person, but when I go back and look,

I find them incredibly hokey in most of the most cases

That taste good. I, that's, that's understandable. Uh,

what about your favorite Christmas movie?

Don't have one.

Okay. And what sort of music do you like listening to?

Uh, it alternates between classical and blues.

Okay. And one final quick fire question. What's your favorite color?

Probably red.

No one to date that said rho domine or fluorescein? They always go

Tomato.

Uh, we are nearly up to the hour, so I'd like to ask one more question actually,

or maybe two if we can squeak it in. Uh, everything.

Your career sounds serene, you know,

wonderfully sailing from a young 15 year old all the way through to where you

are today, but there must have been some hard times in your career.

What was the most difficult time that you've encountered throughout your career?

Um, since this is relatively well known, I'm not disclosing anything.

I had Hodgkin's disease in 1989,

sort of right at the peak of early, you know, career success.

And I had to go through six months of, uh, chemotherapy and radiation.

And so that was not a very productive period in the lab,

both because I was basically out of it,

but I couldn't direct any of the other folks in the group.

And I had to stop going to meetings. And a lot of people were sort of,

of the mind and I might not be around very long, so I wasn't on lists for,

for future invitations. And when the treatment worked,

I decided I had to resurrect my career

and I was sure,

I did not think any of the fellows or other people in lab were gonna do it for

me. I had to do it. And it had to be something, uh,

fairly quick and fairly dramatic under these circumstances.

And I had had, uh, a postdoc, Andrea San,

who had trained a technician to do, um,

metabolic labeling gels to look at immuno precipitated M H C

molecules. And Allen Townsend had just, uh,

published the paper on R M A S cells about peptide being important for the

stability of class one molecules. And based on what I knew, I said,

I think that's going to be true of class two as well.

And I know just how to do that experiment because there's an old study from Jack

Trogers group that showed that, um,

mature M h c class two molecules did not fall apart in S d Ss,

unveiled ss d s gels. And so I went to Laura, the technician, I said,

this is what I want you to do.

I want you to take these B cells and put a bucket of h e l in,

in with some of them,

and then I want you to do a pulse chase and I want you to do a boiled un boiled

gel, and we're gonna know in two weeks if I'm back. And she did the experiment,

you know, opened the gels up, looked at 'em, and said, yep.

Then turned into a nature article, uh,

that was accompanied by a nature letter with the messer who did

the in vitro equivalent of showing that peptide stabilized class two molecules

I, and

Very difficult period. And it was a lesson, you know,

that I try to talk to other people 'cause you have these ups and downs in your

career. And I said at, at the end of the day,

when you wanna get out of a valley, you have to get out of the valley.

You can't get your fellows or your students, you know, other people to do it. I,

I, I did have one more.

I'm not gonna ask the last question 'cause I think that's a perfect moment

to end on actually. 'cause I think that advice is Yeah.

Inspirational in itself. And Ron, you've been a pleasure to talk to. Uh,

you know, you are a benchmark as well as an inspiration for, for knowledge

Was even more fun and enjoyable than I anticipated that it was going to be,

which I had high hopes for to begin it. So I,

I really enjoyed that tremendously. And uh,

hopefully it will turn into the final product. You hope it will be.

Yeah. Ron,

thank you very much and just keep on going 'cause it's amazing work and everyone

who's listened, watched, please subscribe to the channels.

But go and read tomorrow, Ron's work if you don't know it personally. Uh,

and if you are a, you've got a young family,

get to listen to how Ron developed his career. 'cause you know,

it could trigger the next Ron domain. Ron, thank you very much.

Thank you so much, Peter. Take care. Bye.

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