Harbor-UCLA Pediatrics

Dr. Emil Kakkis is world renown for his work over the last 18 years developing novel treatments for neglected rare disorders. Three of these treatments are now FDA-approved and in clinical use, helping patients live longer, better lives.

Dr. Kakkis received his bachelor’s degree in Biology from Pomona College, and his medical degree and Ph.D. at UCLA (Biological Chemistry). He completed his pediatric residency at Harbor-UCLA in 1991, followed by a fellowship in medical genetics at Harbor-UCLA and was on the faculty here until 1998.

Dr. Kakkis was Vice President and Chief Medical Officer at BioMarin Pharmaceutical Inc. (Novato, CA) prior to founding the Kakkis EveryLife Foundation, which is dedicated to improving the diagnosis and treatment of rare disorders. His work will be honored at this year’s LA BioMed Discovery Gala on November 6, 2009.

How did you decide to go into research?
During my college years, I was given an opportunity to do a research project using a method I had learned in a biology lab. I decided to do the work and discovered that I really liked finding out new things that had not been known and that gathering new data and analyzing it was exciting and challenging. I found myself spending the hours on it and did not tire doing it. And so a small college project let me discover my desire to discover.

How did you get interested in medical genetics?
During my MD/PhD training, I had already a focus on developing treatments but was learning molecular biology. Combining the power of molecular biology with treating human disease naturally led to genetic diseases as an important area of great promise but now a new opportunity. Although gene therapy was the first attraction, the disease states were compelling and interesting and offered the possibility of treating something that had never been treated before.

What made you select Harbor for your training?
I decide to rotate at Harbor because at one point my father had been doing some attending there in Neurology but I quickly found an affinity for the concept of dedicated highly skilled people treating the underserved and also doing research. The Pediatrics program was also a great draw as it offered intensive clinical training, with a strong requirement for independent thinking and excellent judgment that would make my purely clinical years the most effective for training given my research direction. The residents and camaraderie were great and the way everyone pitched in to help whoever was getting slammed, really felt right.

Of people who have helped or mentored you, what made them good mentors?
From the clinical side at Harbor, there was a consistent combination of excellent practical clinical judgment/experience combined with high academic standards, for all the fields, whether it is in medical genetics, ambulatory pediatrics, neonatology, heme-onc, cardiology or whomever.

Any especially memorable stories from your time at Harbor?
On the clinical side, there are always some great saves for patients and also a few losses that you never forget. As an intern, I was already interested in biochemical genetics and on my first rotation in PICU my very first month, a 2 week old baby showed up in coma, with acidosis, hyperammonemia and bone marrow suppression. Having just studied this on a genetics sub-I, I knew it had to be an organic acidemia that night on call (which seemed like a zebra-like choice of a beginning intern), and started treatment. The kid later turned out to have propionic acidemia. That was the only one I diagnosed myself through residency and fellowship. I had a night in the nursery as an R2 that had 15 admissions to NICU and Level 2, with ( and this is the unbelievable part) 2 pairs of twins with Rh or ABO incompatibility needing double volume exchange transfusions in the same night. One night in the PACC, we had two kids we diagnosed with bleeding cerebral AVM’s on CT, one with a non-focal neuro exam who the mom thought was not right, and the second a transfer with pneumonia and “diabetes” that were both wrong diagnoses. Of all the clinical stories, there is nothing quite as satisfying as treating a nurse-maid’s elbow in a child, when the parent thinks they have seriously damaged their child’s arm, and with a simple maneuver, you can fix them miraculously and send them home.

On the research side, we had many good days in C3 working to get things done, with some very sharp and dedicated people that also ignored the appearance of the space. One of the key moments for the MPS (mucopolysaccharidosis) research was when I figured out that the enzyme we were synthesizing in the cells was “high uptake”. I was running the fluorometer late at night completing an all-day assay, and saw the numbers come up and knew that the affinity must be very high, solving a great point of concern for Liz Neufeld and me. I had to call someone, so I called Adam Jonas at night to tell him the big result. At that moment, the probability of succeeding seemed likely on the MPS I project.

Among your many discoveries, which are you most proud of?
When I started doing research I was focused on making discoveries but in fact, the most important result of my research was less about discovery and more about fighting through the system and making the enzyme for the first study. It seemed impossible to do, but knowing that if I did not do it, it would never happen, transformed my thinking of research as sometimes less about discovery, and more about getting the treatment to patients.

What was the hardest part of your work?
There were some days where the combination of an ongoing research experiment and Pediatric ward work combined with genetics consultations, that would just exceed even the most enthusiastic physician’s capacity to work and succeed, leading to the feeling that none of it was being done well enough.

Any comments on health policy, as applied to genetic disorders?
The latest idea permeating single payer health care systems is “health care equity”. This means we all get a slice of the pie at most, and not more, because as we all know, there is only so much pie. This is the easy, non-thinking way out for a bureaucrat with a budget. Just make a list, and when someone comes in the door that is really sick, tell him, “You ain’t on the list”.

The problem here is that someone struck by genetic lightning, life destroyed, with little help or opportunity is now being told, that “I am sorry, you are too expensive, and so no more pie for you!” Health care planned by economically-driven policy wonks will destroy the solemn commitment of caring and treatment between doctors and patients that says we will treat what needs to be treated. An aggressively applied health equity approach is simply a new form of eugenics. Rather than actually kill the defective patient, we simply let them die without care. That is not the medicine we want for anyone, including genetic patients.

What advice would you give a new pediatric resident about how to get the most out of their training?
Learn to love it all, the hours, the call, the staff and the hospital. Be happy as the time goes by fast, and you will never be back here again. The faster you learn to love it just as it is, the faster you will be seeing the great opportunities to treat and learn that residency is. I struggled too much with the system but in retrospect, there was never a better moment to learn and treat people in often the biggest crisis of their lives, and see the good in one’s work and of those around you.

For more information on Dr. Kakkis’ foundation to improve rare disease treatments, visit http://curetheprocess.org.