Bringing CNS Members Together to Make Children’s Lives Better


By Daniel J. Bonthius, MD, PhD | CNS Connections Editor | Spring 2017

Dr. Huda Zoghbi
Dr. Huda Zoghbi

QUESTION| What is the most important quality that a physician-scientist can have?

Curiosity. Especially, the ability to question assumptions and to dig deep for answers.

QUESTION| What is the most important thing that a mentor can teach his or her student?

To strive for the best quality in everything they do – details matter, and so do aesthetics, whether you’re cutting brain slices, performing a western blot, or creating a table for a manuscript. If we had ignored a tiny speck of blue (LacZ staining) that appeared in a mouse embryo, we would never have discovered the role of mouse atonal homolog 1 (Atoh1) informing inner ear hair cells or secretory cells of the intestine.

QUESTION| You’re had a remarkable career. Are there any moments that stand out more than any others?

Two moments stand out: the first (chronologically),when Harry Orr and I exchanged faxes on the same day revealing the discovery of the genetic mutation causing SCA1. Second, returning from vacation and meeting my post-doc at the time, Ruthi Amir, in my house, and realizing that she had identified the genetic basis of Rett Syndrome,after my lab had been pursuing the gene for 16 years.

QUESTION| What was the most discouraging moment in your research career, and what kept you going?

Many moments during the search for the genetic basis of Rett Syndrome! Early on, many physicians didn’t even believe it was a distinct disease entity, and for a long time, because the disease is usually sporadic, scientists thought that looking for the gene was a lost cause. I learned to stop talking about that project (because I didn’t want to be discouraged) and just kept plugging away, because I had seen the patients, and the consistency of their clinical phenotype (including their all being female) convinced me that there has to be a gene choreographing this very striking disease. This comes back to what I said before, about the importance of being observant.

QUESTION| What is your proudest professional achievement so far?

Mentoring young scientists and physician-scientists who go onto be successful in their own labs.

QUESTION| What advice would you give to a college student who is contemplating a career in science?

Don’t focus too narrowly; use your university education to learn as much as you can, as broadly as you can. The time to focus is in grad school. Nobel laureates and other successful scientists are much more likely than less-successful scientists and the general public to be polymaths,and to have developed their skills in another area, such as art, music,or photography. The key is really to develop the skill and knowledge in another field, not to just be a dilettante, so that those new skills and perspectives can inform your scientific pursuits (and vice versa).

QUESTION| What obstacles should a physician-scientist,who is beginning his or her career, anticipate and avoid?

There is a risk of letting clinical duties take too much time away from dedicated research. Lack of focus is another major problem, especially for the physician-scientist, who tends to be curious and wants to pursue all sorts of interesting questions. People have to learn to build their research program one step at a time. Early on, depth is more important than breadth.

QUESTION| What areas of neuroscience do you foresee as the most promising for advancement in the next 20 years?

I think our molecular genetic understanding of disease is already leading to treatments, and the pace of translational research will accelerate. For example, the amazing success in translating our understanding of the basis of spinal muscular atrophy to a targeted therapy (antisense oligonucleotide) is changing the course of the disease in infants and children. I can also envision a better articulation of the circuits underlying various neurological functions serving as a framework for applying neuromoduIation (e.g., deep brain stimulation)to reverse circuit pathology in various disorders. But the beauty of science is that when curiosity leads a group of talented people to pursue good questions, you never know what will come of it – except you know it will be exciting!