Opening Doors: Joan Steitz and Jennifer Doudna, Two Women of the RNA World

OPENING DOORS: JOAN STEITZ AND JENNIFER DOUDNA, TWO WOMEN OF THE RNA WORLD

By Laura L. Mays Hoopes

Introduction

In my life in science, there have been a few impressive women whose life-pathways I’ve wanted to follow.  While I was growing up in North Carolina, I had women teachers for both biology and chemistry. I thought science was for women.  In a bigger pond, I found it wasn’t necessarily so. At a National Science Foundation high school summer honors class at Appalachian State Teachers’ College in Boone, NC, I learned ecology research methods, but all my professors were men. Back home again, I treated gladiolus with gibberellic acid, trying to make them giants for the Science Fair. I went to the first ever National Science Fair in Indianapolis with my biology teacher, receiving honorable mention. But it didn’t bring me into contact with any scientific women among the speakers or the judges. 

Goucher College offered me a chance to meet women science researchers, especially my advisor Ann M. Lacy.  She was a role model for me, but like the other women professors there, she remained single. I longed for a role model who had a research career along with marriage and children.  In graduate school at Yale, there were no women professors in my field. It was up to me and my generation of women in graduate school to forge ahead without exact path-breakers to follow. 

Decades later, teaching Biographies of Biologists as a writing seminar for first year students at Pomona College, I resonated with my female students who burned to read a biography of a married woman with children who had a solid current career in biology.

I couldn’t find one. 

The women in that class asked and begged me to put my own life on paper until I wrote my memoir, Breaking Through the Spiral Ceiling.  I’m a married liberal arts college professor with children.  I carried out funded research throughout my career, but I wasn’t a major research university professor who could contend for the Nobel Prize. 

My students wanted to read how such a woman combined biology and family.  Jennifer Doudna is a married woman with a child, a professor at University of California, Berkeley who had conducted outstanding research, received the Waterman Award for outstanding young scientists from the NSF, and is often mentioned as a strong contender for Nobel laureate. She visited Pomona College to deliver the week-long Robbins Lectures.  I told her I’d like to write a dual biography of her along with Joan Steitz because there was no such biographical material for young women considering careers.  She agreed. Doudna helped me to recruit Joan Steitz.  This book is the result.  My hope is that this book opens a window into the lives of women who balanced top-flight careers in science with family.

Joan Steitz and Jennifer Doudna took the road less traveled, choosing a career in science—a courageous choice because of the dismal record of those women who had tried it.  During their times, women began to major in science, progress into assistant professor positions at major research universities, and move up through ranks from associate professor to full professor. It was fearfully demanding academically and personally.

Women dropped out at every step. 

Even today, only about 15% of full professors in STEM (science, technology, engineering, and mathematics) fields are women, even though half the PhDs in STEM fields are women. The National Science Foundation reports that this disparity has lasted for over twenty years. At entry level, among assistant professors, there is a higher proportion of women. But as a mature woman scientist, I still feel pessimistic that women of science will reach gender parity in the top ranks of academia any time soon. Why not?  That’s one of the things we’ll discover in this book.

Joan Steitz and Jennifer Doudna are women of the RNA World (RiboNucleic Acid World), supporters of the theory that the first molecules leading towards living cells were made of RNA, not its close relative DNA (DeoxyriboNucleic Acid).  They entered the field of molecular biology twenty years apart. Joan began ten years after the birth of molecular biology with Watson and Crick’s model of DNA in 1953, just as the field of molecular biology gained steam in the US, about the time Jennifer was born. Jennifer started twenty years later. Both began their study of molecular biology before anyone imagined the RNA World.  Each woman committed herself to understanding RNA, married another molecular biologist, and raised a son while she unveiled RNA’s secrets. They pushed past barriers, ignored slights, braved rejections, chose hard but promising scientific problems, and blossomed into outstanding scientists and people.

Family relationships? 

The desire for family seems normal for women, but once women in science stayed single. For example, Barbara McClintock and others of her generation chose science alone. McClintock received the Nobel Prize in 1983, years after she discovered mobile genes. She appeared married to her science in the same way sailors are married to the sea. Marie Curie and some other early women in science married their collaborators. 

But most STEM women remained single.   

Joan Steitz, Jennifer Doudna, and I didn’t believe that we had to choose science over relationships. My generation (the same as Joan Steitz’s) said we wanted to have it all; cutting-edge science plus family.  Back in the 1960s and 70s, balancing career and family was difficult. It’s still challenging.  But as you will see in comparing these two women’s lives, as time passed, men began to accept women in joint roles as scientist and mother. 

This book covers a spectacular time for American science.  Chronos is one Greek work for time, similar to time in English. Kairos is another.  Kairos means momentous time, time of great change.  The time after the Soviets fired the first satellite, Sputnik, into space on October 7, 1957 proved to be a time of kairos. Americans feared the Soviet threat.  School children practiced hiding under their desks in case of nuclear attack. Congress blamed outdated American science education. The result? New government science education programs were developed overnight. 

Women weren’t excluded.

Girls entered science fields in unprecedented numbers, although the science establishment struggled to assimilate us.

Joan Steitz and I both belonged to this post-Sputnik wave of scientists.  Steitz (then Argetsinger) didn’t have women professors to serve as role models in Chemistry at Antioch College. In 1963, she planned to go to Harvard Medical School because she knew women were doctors but not scientists. Twenty years later, when Jennifer Doudna studied at Pomona College, she actually did undergraduate research with Sharon Panasenko, a female Chemistry professor. There were many more women graduate students at Harvard during Jennifer’s period of graduate study than in Joan Steitz’s day and some became research university professors.  But still, fewer women than men in her graduate school cohort went into academic positions at top-flight universities.  That was also true of my own graduate school cohort from Yale. There, the average man took a faculty position while the average woman became a permanent postdoctoral fellow with a male professor.  

Women who succeed in science today often point to the importance of their mentors and friends among top scientists.  Steitz and Doudna each found an influential mentor in her Harvard PhD advisor.  In Steitz’s case, it was James Watson, one of the team of 1953 Nobel laureates who published a structure for DNA, the chemical form of most genes.  Jack Szostak became Doudna’s mentor. Szostak received the Nobel Prize in 2009, in combination with Carol Grieder and Elizabeth Blackburn. Their award recognized their work on telomerase, an RNA-protein complex which maintains chromosome ends.  Both Steitz and Doudna bonded right away with powerful, brilliant scientists.

The relationship of these two women with each other also contributed to their success, especially to that of Jennifer Doudna. Joan Steitz’s academic career began and grew strong at Yale University. Jennifer joined Joan’s department at Yale after she concluded her postdoctoral training.  Joan Steitz was helpful to Doudna in many ways, including friendship during a difficult time for her personally as her first marriage disintegrated.  As her department chair, Steitz nominated Doudna for the Waterman Award, a major prize given by the National Science Foundation to an outstanding young scientist conducting breakthrough research.  Jennifer was inspired by a photograph of Joan’s enjoyment of her newborn son when she was thinking seriously about having children after her second marriage.  It was very difficult for Doudna to leave Yale to join her new husband at University of California, Berkeley because of her friendship with Joan and Tom Steitz.

Joan Steitz and Jennifer Doudna chose and established careers at the top ranks of American science.  Their scientific thinking led them to insights about their chosen molecular subject of study, RNA. More roles for RNA are being discovered daily, as RNA proves important in gene regulation, telomerase action, messenger RNA assembly, the assembly of proteins, protein transfer across membranes, and other cellular processes.

Why are these discoveries important? RNA is beginning to supplant DNA as the most important member of the triumvirate of informational macromolecules, DNA, RNA, and protein. 

In Crick’s Central Dogma of molecular biology, the path of information flow is DNA to RNA to protein. The classic role assigned to RNA is messenger RNA: copying the code for a protein out of the DNA and delivering the instructions to the protein factory called the ribosome.  New RNAs with completely different roles became non-coding RNA, a category of immense importance to the cell. In contrast, DNA only knows how to save information and with help from proteins and RNAs, pass it on to offspring.  RNA can do that and also catalyzes chemical reactions.

RNA runs and regulates most cellular processes.

Those who find these scientific relationships difficult to understand may want to read the pretend interview with JoJo, a schoolgirl reporter, that concludes this book.

In the early days, when Crick first put forward his Central Dogma, DNA was considered the most important biomolecule. The most glamorous RNA used to be messenger RNA, the coding member of the RNA family. As mentioned, it carries the genetic code allowing a protein to be translated.  During her dissertation research, Joan Steitz was the first to reveal important structural features of virus messenger RNA. Then she went on to show that messenger RNA contained its own start and stop signals during her postdoctoral fellowship with Francis Crick, the other Nobel laureate for DNA, in Cambridge, England.  When she took up her position as assistant professor at Yale, Steitz discovered a major group of non-coding RNAs, those involved in splicing together segments of messenger RNA in higher organisms.  It was the first known group of RNAs that wasn’t a direct part of Crick’s Central Dogma; thus, it opened people’s minds to more roles for non-coding RNA. Though she didn’t find self-splicing, the first RNA catalytic reaction discovered by others, she did discover non-coding RNAs that she later found were catalytic.

During her PhD research, Jennifer Doudna showed how an RNA can increase its efficiency in catalyzing its own synthesis.  Later, as a young faculty member at Yale University, she worked with Cech, one of the men who won the Nobel Prize for discovering catalytic RNA, to obtain the first x-ray crystallography-based structure of a ribozyme, an RNA that can speed up or catalyze chemical reactions.  She was thrilled to see how its structure explained its unexpected abilities.

Here’s an interesting analogy. I think of Joan Steitz’ era, the late 1960s, as a time when the unit of academic science began with a male scientist, complete with the beard, glasses, and lab coat that young children automatically supply when asked to draw a scientist.  He sat in his office, protected by file cabinets of papers and huge collections of books, isolated from the hurly-burly of the laboratory, calling friends in other laboratories to find out their new findings, going on tours to speak about his laboratory’s findings.  Next in line, organizationally speaking, was a long-time postdoctoral associate, also male, perhaps shyer than the professor, not interested in speaking in front of others or competing for grants, but happy to organize the laboratory and keep everything running smoothly.  Then there were several more postdoctoral fellows and graduate students, a white male cohort of admirers of the science of the laboratory leader, amplifying his paradigm as Thomas Kuhn, author of The Structure of Scientific Revolutions, might put it. 

I think this lab-group-of-the-past aligns precisely to the Central Dogma.  The scientist is like DNA. Let me give you a mental image of the role of DNA in the cell. I used to teach my beginning students how to act out the synthesis of the protein insulin, with each student taking the role of one of the molecules.  In the post-activity discussion, nobody was glad to have enacted the DNA.  It had been, every time, a popular choice before we embodied the events.  DNA is very inactive, staying safely in the nucleus, protected from chemicals and radiations, while the messenger RNA is copied from the DNA in the nucleus and moves out to the cytoplasm.  The messenger RNA binds to the ribosome, a protein synthesis factory, and directs protein assembly stepwise.  The head postdoctoral associate is like the messenger RNA; he knows everything and makes all the infrastructure function.  But, he gets no particular credit.  The gene is DNA and the messenger RNA is only a throwaway copy, but useful at the time as one of my students said.  Other participants portray building blocks of protein, amino acids attached to transfer RNAs, active, moving and working, but according to a script they did not write.  In my class simulation, they form a protein, insulin, that is secreted and has an anti-diabetic role practically every student is familiar with, regulating sugar uptake.  In retrospect, every student wishes to have been a part of the messenger RNA or the protein rather than the protected, inactive DNA.  The students enacting DNA often say they can’t even see what’s going on.  The amino acids and the transfer RNAs are like the graduate students and postdoctoral fellows passing through the lab for their training.

In the history of science, place of privilege for publication and awards is automatically granted to the inactive thinker, planner, and grant proposal writer in his office rather than those carrying out the experiments and observations, sometimes referred to as just hands. Even today when teams do so much of science and single-author papers are rare, the individuals in charge of laboratories receive the Nobel Prize and other recognitions.  The DNA equivalent in academic science is the part that is prized. 

However, in the decades since the Central Dogma was promulgated, several things have happened to the model laboratory I evoked.  Some of the scientists are now women.  Many of the postdoctoral associates are women. When the early women PhDs in science couldn’t get academic positions, they often became career-long postdoctoral associates with male faculty members. In life sciences, proportions of women graduate students slowly increased to approximate parity between the sexes.  Postdoctoral fellows and graduate students in a particular laboratory in today’s world are a mixture of males and females. 

During the time when women came into prominence, the role of the scientist as the sole source of ideas began to be disrupted.  Both men and women moved to increase the autonomy of their junior associates.  It became more common for graduate students and postdoctoral fellows to think of their own projects, although it is still not universal.  Ironically, that system had been in effect for Joan Steitz at Harvard and Cambridge earlier. However, the award and recognition structure still emphasized the role of the laboratory director.  Most junior scientists can cite several examples of senior scientists who provided a laboratory and some financial support but who later reaped all the recognition for the breakthrough ideas and experiments of their postdoctoral fellow or graduate student. 

Both Joan Steitz and Jennifer Doudna have continued to push the boundaries of our knowledge of RNA structure and function.  RNA World, the theory that RNA was the first biomolecule on earth, and once carried out all the roles that now are performed by DNA, RNA, and protein, was based upon the wide range of RNA abilities, discovered in part by Steitz and Doudna. Thus I’ve entitled this biography Women of the RNA World, to salute their major contributions to that theory.

Chapter 1.  Sailing Day

Joan Steitz and Jennifer Doudna crossed paths at Yale University when Joan was well established and Jennifer was a new faculty member.  They sailed from time to time on the boat belonging to Joan and Tom Steitz, out of the coastal property they own in Stony Creek section of Branford, north of New Haven, with a view of the Thimble Islands.  Tom Steitz planted flowers in a small area at their house, emulating the tiny bright gardens of England.  He told a reporter, Steve Courtney, that "The field I’m in is so slow I want to do something in my life that moves at some reasonable pace.  Flowers come up, bloom,