A common adage in medical training goes, “When you hear hoofbeats, think horses (not zebras).” For most doctors in conventional practice, that means that exotic explanations are rarely right. The most prosaic diagnosis for a patient’s symptoms is usually the correct one.
Elaine Zackai, MD, surrounds herself with zebras. In medical practice, Dr. Zackai routinely discovers zebras when treating patients with the rarest and most complex, and often unknown, genetic disorders, as director of Clinical Genetics at the Children’s Hospital of Philadelphia. In her office, she is surrounded with the motif of zebras, from plush toys and figurines to picture frames and the pictures within them — tchotchkes of every stripe, all zebra-striped.
“Think zebras” is a mantra that Dr. Zackai learned from a fellow who trained with her some years ago, and one that she continues to impart to trainees to this day. It’s clear that they appreciate the insight as one of many other aspects of Dr. Zackai’s mentorship. A group of 38 of her former trainees submitted testimonials endorsing her in a nomination for the first-ever Mentorship Award from the American Society of Human Genetics (ASHG). A presentation at the ASHG Annual Meeting Oct. 21 honored Dr. Zackai as the winner.
On the occasion of this honor, Cornerstone recently sat down with Dr. Zackai, who is also a professor of Pediatrics and Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania. We discussed mentorship and what she has learned and hopes her trainees will continue to learn about the treatment and study of rare genetic disorders. The edited conversation follows below.
Is mentoring a skill you deliberately sought to cultivate?
That’s a very hard question because I treat the fellows like they are peers. We are all there to solve problems together, so I will share ideas back and forth with them as if I’m talking to a peer. And then the further along they are in their career, the more they are able to dialogue back with me. Every case is a brand new situation that we’re in this together to solve.
That’s not exactly deliberate mentoring, but it’s mentoring just the same.
That is an admirable approach: Treating people as equals is a way of seeing and cultivating their full potential.
Yes, and you bring out the full potential and you learn from them. If they’re in the lab and I don’t know a certain technique, they teach me about it. And if no one knows about a certain syndrome, we see if we can’t get it together.
And I love my work. Even though these difficult diseases are not themselves “fun,” in the course of figuring them out, the fellows and I have fun. If it’s not fun, you can’t do the job. I think that is very infectious. You take that enthusiasm, and you put it to the person who’s right next to you. To me, that’s mentorship.
Are there any secrets of success you share with trainees?
Never drop a case. Never. If you don’t solve it today, you may solve it later. If it’s a big problem, it always comes back. That’s one secret.
One piece of advice, period, to anybody, anywhere, is never burn a bridge. You never know when you’re going to find that person again in another context.
I encourage everyone to develop perseverance and to pay attention to detail.
When all else fails, the most rare finding in the child will open up the case. If you look behind you, there’s a lot of zebras. A fellow gave me this saying, “When you hear hoofbeats, don’t think horses, think zebras.” That’s a mantra.
The right motivation is a major secret of success. In this work, everything is challenging, everything is new, and you’re learning something every single minute. And the purpose of it is to help people. In the back and forth between you, the patient, and the parent, the most important thing is that it is tremendously gratifying to help make things clear for the parent. Even if the child has a very difficult problem that is not going to be remediated, you and the family can get a lot of satisfaction out of knowing the cause, and for parents to understand it as much as you do in a language that they’re able to deal with.
Can you give an example of a difficult “zebra” case that you figured out with your fellows?
Everything starts with a patient and then goes further. We had a very interesting case where the parents were second cousins, and the child had different abnormalities in different systems and had terrible vertebral anomalies. No matter what we did, we couldn’t solve it. The chromosomes were OK. We noticed that there were areas on the chromosomes where the two parents matched each other, being second cousins, so we looked at genes in those areas, and we still didn’t find it.
Then we ordered whole exome sequencing, where you can look at the message from every gene, and it came up with a mutated gene that had only been seen once before in another family whose condition was not exactly the same. Then we really branched out when we realized that that gene was abnormal in Holstein calves that die at birth. In the Holsteins, everything started with a single bull that was bred to produce daughters with a lot of milk production. Descendants of that bull were sent to Japan and Denmark and the USA. When those descendants were bred with others descended from the original bull, all of a sudden some of the offspring started to die at birth because they inherited a double dose of this gene.
Sure enough, we found that those calves have the same vertebral anomalies, the same kind of contractures of the digits, as the child we were treating. Now we can go back to the parents and understand the inheritance pattern for this genetic anomaly and counsel them on their risk of future children having this condition. The fellow who was with me working on the case is now in the lab to understand more how it works. D
o you have any advice to other clinicians and investigators for working with trainees?
Don’t treat them like trainees. That’s the advice. You stay young like that, by the way. Sure, the classes are younger every year, and even though you’re older each year, you’re just one of them. It’s been that way for 45 years. It’s good. I’m still in my first job. They seem to keep me, so I’m happy. Everybody should feel as happy in their job as me and should be as enthusiastic in their job. That’s what I wish for everybody. And if they’re not, they’ve got to get a different job.
I‘m in a fabulous environment at CHOP, and that is very important. Everybody here has the same attitude, which is, “How can we help people?” It’s a fabulous esprit d’coeur. What can we do for the child, what can we learn from the case, and how can we go further?