Today I'd like to tell you how I became a scientist.
I decided I wanted to be a scientist when I was 9 years old.
Actually, I think that I didn't decide that I wanted to be a scientist.
I decided that I wanted to continue to explore things,
take them apart, see if I could put them back together.
Part of the reason I became a scientist was because of something that my uncle said to me.
He had a Master's degree in Chemistry, and he showed me one day
a paper that he had written that had just appeared in the Journal of Chemistry.
It had some title that made absolutely no sense to me.
It was long, and it had these figures in it, and he took the paper, and he said to me,
"This was easier to write than an English paper."
That made a big impression on me, because papers were not easy to write.
So, that was intriguing. I think the other thing that got me started
was that my mother had told me that she wanted to be a botanist.
She was very interested in plants and how they worked.
But, as a child, she had gotten rheumatic fever,
missed a year of class, was promoted an extra year ahead,
and she kind of never caught up with arithmetic and mathematics.
To her credit, when I was 13, my mother went back to school, took a class in statistics,
which was very difficult, but she did pass the course, and that taught me something about the
importance of persistence and of not being afraid to do the things that you want to do.
When I got to college... Actually, it was when I was in junior high school,
I went to a program that the National Science Foundation had.
It was called Summer Science Training Program.
And kids in junior high school got together at a college campus,
and we got to do experiments and listen to lectures. It was a wonderful summer.
It was in a small campus in Tyler, Texas,
The campus organizers bought me the book, Calciphylaxis.
I had read a Reader's Digest article about Hans Selya,
and was interested in the stress response in animals and humans.
So, I bought his textbook, which I mostly did not understand.
I don't remember much about the experiments,
except that I did take out adrenal glands and followed the rats.
I took the rats home with me, by the way.
Many of them got away and there were...
For many years, you could find black and white rats in the neighborhood now and then.
So, that kind of solidified my interest in what a wonderful thing science might be.
It was really fun. It was a group effort that we had in Texas.
I made very good friends there, and I felt very satisfied that I was doing something
with both my brains and my hands.
That was very satisfying.
So, when I went to college, I wrote to someone at the University of Washington,
where I was thinking of going and asked, "How do you become a physiologist?"
which is what Hans Selya was.
And he told me that as an undergraduate, I should go take... I should major in chemistry.
I went off to the University of Washington. It's the only school I applied to,
and I applied there because I had an uncle in Seattle.
Well, chemistry was pretty hard. And, although I'd been a very good student in high school,
I found myself struggling, and so about mid-way through the year,
I went to my advisor, whose name I can't remember for the life of me.
I'd like to remember it, because I'd like to embarrass him.
And I told him I was having difficult in introductory chemistry,
and he said, "Well, of course you're having trouble. Chemistry's not for girls."
Being a freshman, and not knowing any better, I said,
"Oh, ok." And I went and changed my major.
I went through 5 majors in my first 2 years as an undergraduate.
I went from chemistry, I went completely outside of science into history.
Didn't like that because the first class was really big and pretty boring, actually.
Then I went and found the history of medicine, which was extremely interesting.
And I found then, there, that library work -- looking into magazines and history --
could be another exciting way of exploring things.
And I almost did that, but there was really only one person
who was doing that at the University of Washington.
And, you know, you're really sitting by yourself in the library most of the time.
I then went back to biology, and had the very good fortune to take a class
that was given by Robert Kohn.
It was the only time the class was given because
it was very expensive and unwieldy to give for undergraduates.
In the class, we used radioisotopes, we were in the lab 24 hours a day, taking turns in sleeping bags.
Following experiments as we went.
We also had visitors -- visiting scientists -- who came in
and treated us as serious people who wanted to listen to their results.
One of them was John Gurdon. That was a surprise to me, because we had read Gurdon's papers,
and they were very important papers in the field.
Though I had envisioned him as an older man with grey hair and glasses
because that's what a scientist looks like, right?
Of course, I was wrong. I was impressed with how young he was, this red-headed man
full of energy and fun who obviously delighted in telling us about the experiments he had done
and the way in which he had come to his conclusions.
That kind of solidified my interest in developmental biology.
That question of how, from a single cell, you end up nine months later with a human being,
who grows up. Truly, a remarkable, miraculous series of events.
And how that exactly happens is, of course, one of the most interesting questions
that still stands before us.
We've learned a lot, but we don't really have the whole picture yet.
So, I decided to do developmental biology,
I asked my professors how I should go about this, and they told me I had to go to graduate school.
So, I said, "Ok." Now, there was one small problem
During those years when I was having trouble with chemistry,
I was also discovering the joys of a social life, and I was going out with a lot of people,
and I was skipping classes
and so forth. So, my grades were, shall we say, a little erratic.
Well, about that time, I met a medical student,
or really what happened was he tripped me in the cafeteria in Seattle.
We went out -- he had to make up for tripping me, after all.
And, we got together and it looked like that was something that might last.
But then, he was going to go off to do his residency on the East Coast.
So, I asked my advisors about schools on the East Coast, where he would be,
and since he was going to be in Bethesda, they said why don't you go to Johns Hopkins?
I couldn't go to Johns Hopkins because that was an all-men's school at the time.
Dates me a bit.
So, I ended up at Goucher college, which was close by and the sister college - an all woman's college.
A very good college for me because it was very small,
very different from the University of Washington, and I got a lot of attention from the professors,
including one of them found me a job for the summer at NIH in the laboratory of Loretta Levi,
who was a microbiologist and who introduced me to the concept of molecular biology.
She pretty much taught me everything from how to hold the pipette to the fact that
you really, really have to have small stretches of dialysis membrane
if you don't want them to get all tangled up in the stir bar in the flask.
She was the person who would be writing references for me when I was applying to graduate school.
I applied in Boston because that's where my then-husband was going to be as a doctor.
Well, I applied to every school in Boston except MIT.
Loretta asked me why I hadn't applied to MIT, and I said,
"I hadn't applied to MIT because my vision of MIT was a bunch of guys
"running around with slide-rules doing math."
And I was not fond of math, and I wasn't very good at it either.
So, she looked at me, and she said,
"You have told me that you want to do developmental biology and molecular biology.
"If you want to do that, you have to apply to MIT,
"because that's the best program in the country right now."
So, I applied to MIT.
And, it's a good thing that I did, because MIT is the only school in the Boston area that accepted me.
That was an important lesson. You will not get anything that you do not ask for.
You will not get anything that you don't apply for.
So, do it. Just apply for it.
Getting into MIT was one of the best things that ever happened to me.
It was an extremely exciting place to be a graduate student or a scientist.
MIT is really graduate-student heaven.
The science that was going on was remarkable.
The faculty considered us their junior partners.
We were talking all the time about something interesting going on and learning all the time.
I worked there with David Baltimore and Harvey Lodish
who had very different, but complementary approaches to science and who taught me a lot.
Developmental biology wasn't... there wasn't somebody in that department
that I wanted to work with who was doing developmental biology.
So, instead, I did a joint project with David Baltimore and Harvey Lodish
that used virology that David was doing and protein synthesis
-- cell-free protein synthesis -- that Harvey was doing,
and I put them together. I was the first student at MIT to have joint PhD advisors,
and it was an interesting way to do it and very useful.
Except for the part when I started writing papers.
For a while, I would take my paper to one of them and they would make suggestions on it,
and then I would take it to the other, and they would reverse the suggestions.
So, I finally took to just going directly between the two of them before we got the first paper out.
David and Harvey were extremely good mentors for me for different reasons.
They expected a lot of their students. It was there that I learned that hard work can be extremely fun,
especially if you're working with a group of other people.
We worked hard and we played hard.
And, we learned a lot.
And those people are still very good friends and close colleagues today.
After graduate school, the question was, "What do you do next?"
And I wanted to go back to developmental biology.
So, I began with listening to seminars.
I heard Fotis Kafatos give a talk on the silk moth as a model system
for studying protein synthesis in a developing system.
So, I went to talk to him, arranged a post-doc,
and I went back and told David and Harvey that I had my post-doc all set up.
To my surprise, they were both very offended.
And it turned out that they were offended because each of them thought
that I had gone to the other for advice and help in setting up the post-doc.
And I learned then that part of the job of a good scientist is
to mentor the scientists that come after them, the people they are training.
And they took that very seriously.
I also found out later, as I interacted with other people,
that often the busiest scientists are the best mentors.
They're the ones that are working the hardest, they're the ones that have the most connections,
and they're the ones that it is worthwhile being persistent
about getting to, and talking to, and learning from.
I learned a lot in Fotis's lab, including the power and the value and the pain of failure.
Things had worked very well as a graduate student.
I got 6 papers out, had a lot of experiments, did a lot of collaborations
with people not only at MIT, but around the world.
So, when I got to Fotis's lab, and things didn't work, that was pretty tough to take.
In addition, that was the time when the recombinant DNA controversy was all in full bloom.
And for those of you who might not know,
that was the time at which there was a fear that if you took DNA from one source
and connected it to DNA from another source,
and then put it into a bacterium or a yeast or anything like that,
you might create a new creature that would be a super dangerous germ or somesuch.
Never very credible scientifically, but it had a lot of force socially.
And what that meant for me in particular was that I could not do the science
that I wanted to do in Boston.
It was banned in Boston and Cambridge.
And so, I went to Cold Spring Harbor with Tom Maniatis,
and with a couple of his graduate students and post-docs,
and I spent the summer in Cold Spring Harbor, trying to do something,
which in retrospect was not possible,
which is to clone a very large genome into a plasmid, which is a small piece of DNA.
I like to think that maybe that failure encouraged Maniatis
to think about the phage packaging system, which he developed shortly thereafter.
I returned to Harvard with no positive results from a year at Cold Spring Harbor.
That was very discouraging. At that point, a friend of mine, Argiris Efstratiadis who was in
Fotis's lab came to me and said, I'd like you to work on this project with me and Wally Gilbert.
We're trying to clone insulin.
Actually, what he said is, "We're trying to clone insulin."
Arg was quite a character. He had been a Shakesperean actor in Greece,
had a medical degree from Greece, but when he came to the US,
he decided that his, as he said, "MD from Greece is useless."
So, he entered the PhD program and was working on his graduate degree with Fotis.
That project led to probably the most interesting project of my scientific career.
First of all, everything worked. That practically never happens in science.
It was six months from the beginning of the project until the publication of that paper.
That paper and many others that were published during that time,
led to a new direction for many biologists.
It led biologists from the bench directly into the real world
of business and applications of their science -- something which had not happened before.
But that's another story that perhaps we'll approach another time.