Featured Article March 17, 2021

Five questions with Nadia Rosenthal

JAX Scientific Director Nadia Rosenthal in an image collage header

An interview with Scientific Director Nadia Rosenthal

What sparked your initial interest in science?

Though it hits everyone differently, the feeling of infectious curiosity is unmistakable. My own obsession with science sprang, unexpectedly, out of an early passion for art. I began drawing as soon as I could hold a pencil. I’d draw anything I could. I wanted to see if I could get it just “right”—by high school I had gone to the extremes of hyper-realistic painting.

My epiphany at 15 was sparked as much by the recurring themes in nature that I had been trying to capture in paint as by the phylogeny, evolutionary biology and biochemical pathways of metabolism I was gobbling up at school. The spirals in seashells and sunflower heads and the shifting symmetries of embryonic body plans raised persistent questions about general form and the forces that shape them, and convinced me that the biology of pattern formation would satisfy my curiosity more than painting ever could.

How did your undergraduate studies shape your approach to science?

Entering college, in my ignorance, I was sure that the processes of developmental biology had been worked out to the same degree of mechanistic detail as on my intermediary metabolic charts, and that at university, Nature would reveal her morphological secrets to me.

I never found those morphogenetic charts at university, nor anywhere else for that matter. It wasn’t until I came across a popular science magazine in my university library that I realized how limited the collective knowledge was at that time. A picture of a child’s outstretched hand was on the cover. The caption read: “How Does a Hand Know to Become a Hand?,” but the article didn’t shed much light on the actual process of limb patterning, and instead posited the presence of hypothetical morphogen gradients and reviewed current concepts of positional information. I was fascinated, and rushed off to do more reading, but emerged disappointed by the lack of mechanistic detail in the articles I found. My professors only affirmed what I suspected: The field was awaiting the molecular revolution that would take another two decades to unfold.

In the interim, I found other satisfactions: first in the revelation of evolution at work as we caught our first glimpses of mammalian gene structure, then in the pursuit of elusive molecular interactions underlying the new genetic code of eukaryotic gene regulation, and later in the excitement of testing our hypotheses of transcriptional control in living animals through transgenic and gene knockout technologies. It has been a capricious path, but peopled with marvelous colleagues, and the synthesis of collective discovery is a joy for which nothing I learned from my textbooks could have prepared me.

Did you have women role models on our way to becoming a scientist?

My childhood in a family of artists had prepared me for a different trajectory, but the new world of science, opened up by an inspiring high school teacher, was even more compelling. She showed us how awesome nature was in its detail, beautiful and unpredictable. That was what gave me strength during the times when the going got rough later on. The promise of a truth that would stand up to nature’s scrutiny made the hard work and endless obstacles of no particular consequence to me.

Decades later, I still feel this way, and I do whatever I can to foster the same excitement in my own students. Many are women, I am glad to say, and to date, very few of these wonderful scientists have been lost to the profession. There is safety in numbers, and the numbers are growing. When I was awarded a Ph.D., I was the only female student left from my entering class. We had started out well—an equally balanced group—but the intervening years had taken their toll; although it was a personal triumph to have survived the process, it also reinforced my fear of future failure. One more casualty that year, and there would not have been a single woman on the podium at graduation. A few years later I was fortunate enough to visit my teacher at my old high school and give a special class to the students from her podium on advances in molecular biology. That was my best gift back to her.

 

What advice would you give to a female college student considering science as a major and career?

As scientists, we are all bitten by the same bug of universal curiosity and have the same dread of personal failure, but women have the additional burden of discrimination. Society is now generally comfortable with the abstract notion that a woman is equally entitled to satisfy her scientific curiosity. Female life scientists abound in academic institutions, at least until the positions and money and space become limited (usually at the associate professorship level), then the attrition rate is embarrassingly high.

And it’s not just about children. There are plenty of childless women on the dropout list, and those who have attained positions of power in their profession are just as likely to have children as not. There are a thousand subtle and not-so-subtle ways to discourage a young researcher, to distract her from the joys of discovery and dissuade her from demanding more space or more support when she clearly needs and deserves it.

It’s important to identify our own impediments. We are not all well enough equipped to deal with competition—for positions, promotions or papers—and competition is a constant in research. Above all, we need to recognize the power imparted by external research funding. I once sat on a committee to analyze the plight of women (or lack thereof) in senior research positions at Harvard, and was mortified to discover that female laboratory heads were receiving, on average, 40 percent less funding from the National Institutes of Health (NIH) than their male counterparts. For years I had served on NIH grant review panels; how could I have missed this blatant discrimination on the part of my colleagues? The real horror struck when we examined the data in detail: The women had asked for 40 percent less money on their applications. I repeat this tale to every young postdoctoral fellow leaving my laboratory. They understand the message: “Male or female, you won’t get what you do not ask for in this world.”

Despite the practical difficulties and psychic pitfalls, I have maintained a sense of freedom to pursue my curiosity—not only because of some lucky breaks along the way, but because I found I just couldn’t put up with anything less. I tell my students to do the same when they enter the laboratory, and it has paid off over and again.

Please describe your current work.

I floated into the regeneration field about 25 years ago because of an absolutely serendipitous event, where I ended up submitting a grant proposal to the National Institute on Aging rather than my usual funder. Of course once you’re interested in aging, you get interested in why it is that some organisms seem to do a much better job at it than others by regenerating. It also became clear that the same problems that we are continuously faced with in understanding how organisms develop are recapitulated when you’re trying to regenerate a tissue or organ. 

Regenerative medicine is a relatively new way of looking at health. It's not waiting for the problem to happen the way one has to treat a cancer or other unpredictable diseases. It’s trying to diagnose the underlying issue—why is it that we do not regenerate?—and to see if there's any way to intervene or counteract that seemingly inevitable fact that parts of our body don't do very well when they get injured or old.

For the last couple of decades my group has been trying to unlock the reasons why creatures like salamanders and zebrafish regenerate limbs, fins and even hearts, yet heart attacks and heart disease are major killers because the human heart can’t regenerate. Imagine if we could tweak our evolutionary playing card and make a shift in the regenerative capacity of a patient’s heart so they could heal from a heart attack, rather than progress to heart failure.

We are currently focusing on tweaking the immune system, by studying differences in some strains of mice that are much less susceptible to heart damage after injury.  We’ve also been studying the sex differences in heart disease prevalence. Heart disease in younger women is lower than in men but after menopause the incidence is similar, indicating that hormonal signals may contribute to differences we see in cellular composition present in the heart tissue of females, and suggesting new approaches to improve our clinical treatments.

Recently I’ve initiated a new program at JAX, working with my faculty to develop animal models of COVID-19 by humanizing our genetically diverse mouse strains to better reflect the dramatic differences in patient responses to the virus. It’s a team effort that has kept us together during these strange, dissociated times.

How would you describe the culture for women scientists at JAX?

At JAX, I continuously ask myself these questions: How do we promote a sense of entitlement amongst women in science? How can we protect the original obsession that drives us into the field in the first instance, and fires the necessary engines to steer one’s personal path through the obstacle course of today’s competitive research environment? It’s a multifaceted problem that affects both women and men, and requires much more attention than it has received.

As I reflect on the characteristics that help scientists to realize their dreams, I am impressed by the resilience we need to withstand the tribulations of the profession to keep focused on discovery and on the promise of epiphany that originally drew us into the field. Any strategies we develop or employ to survive and flourish must begin with seizing the moment as it unfolds and using it to our best advantage. Patience is not the virtue I would espouse here, but rather a stubborn intolerance of personal compromise when it comes to pursuing your ideas and that is what I try to foster in our scientists at JAX.

The safety nets and opportunities JAX has built for its researchers are highly unusual and encourage risky scientific exploration, but man or woman, it takes clever strategizing to keep doing what you’re interested in doing, in the face of shifting fashions and inconsistent funding. The politics and practicalities of research are necessary parts of the game, and can work just as well in your favor as against it. But the centerpiece has to be the science. If you are truly obsessed with a magnificent question, Nature never lets you forget it. At JAX, my aim is to support and encourage that sense of obsession in all our scientists, so that the question of gender becomes irrelevant to the quest.

If you weren’t a scientist, what would you be doing instead?

My parents expected me to gravitate towards art, which is something I have always kept up, but it doesn’t feel like time off from science. I started both when I was very young—I drew before I talked, and I became interested in scientific research when I was a teenager. The two never seemed to be at odds with each other.

I never thought of myself as a scientist, at least not in the way scientists are conventionally portrayed to the public: solitary, disheveled figures working late, bending over bubbling beakers, with leaky pens in the pockets of their lab coats, oblivious to their surroundings. Of course that probably is exactly what I looked like as a molecular biology graduate student at Harvard in the 1970s, but inside my head I was exploring a world most people never have a chance to see. I was a naturalist of the nucleus, on a trail of detection that was as exciting as anything I had ever encountered.

My fascination with nature has always infused my art.  Art and science share certain qualities: They both offer the satisfaction of accomplishment, and they’re both hard work. Both take a lot of very close observation. I find art a great way to focus on nature, as is science. It’s just that with art, the endpoint is less easy to find.  Scientists are always looking for an approximation of reality, and we’re just as subjective about our way of going about science as artists are in their work. The difference is that we have nature to bring us up short and keep us on course. Artists have art critics. I think nature is a more interesting challenge than an art critic, so I guess that’s why I’m a scientist!

What brought you to JAX? What surprised you most after getting here?

I've been in and out of JAX my whole life. My family spent summers on the Cranberry Islands where we still have a house, and I made my first transgenic mice at JAX with Peter Hoppe back in the 1980s, picked them up from the loading dock in a box and drove them back to my Boston lab in my old Saab. I had close friends on the JAX Board of Trustees back in the ‘80s. Shirley Tilghman and I would sit on the dock and fantasize about making JAX less of a genetics bunker and more of a Cold Spring Harbor environment, teaming with visiting scientists. Win Knowlton [Winthrop Knowlton, Chair Emeritus of the JAX Board of Trustees] asked me to teach him molecular biology, and every week we would have a session at his Cambridge house about the weekly reading material (The Molecular Biology of the Gene), then later he hired me as his consultant for his biotech venture capital company.

I worked with many JAX scientists during my years in Boston, visiting them in the winter, which made me very popular as all the summer visitors had long fled and people were getting cabin fever. I knew and admired Ed Liu from my years in Australia when he was in Singapore, and I knew how he would internationalize the institution. So there were very few surprises by the time he approached me about taking on the Scientific Directorship.