Joshua D. Milner, MD - Chief, Genetics and Pathogenesis of Allergy Section - NIAID, NIH
What was your path to getting into Immunology?
As an 18 year old high schooler, I got into a program that placed summer students in labs at the NIH (since I had enough of being a camp counselor). Randomly, I was placed in Mike Lenardo’s lab, where it felt like important discoveries were being made on a daily basis, even though I couldn’t understand any of what was going on at the time. However, despite having been in other types of labs over the next few years while in college, my interest in immunology remained ever present. In medical school I did a year of research in David Hafler’s lab at Harvard, and eventually came back to the NIH for my Allergy/Immunology fellowship, where I was in the lab of the great Bill Paul, of blessed memory. The basic immunology I had learned formed the foundation for the translation to the clinic that is ever evolving—I get to see my patients not as simple clinic visitors, but as possessors of pathway disruptions that I need to find, which to me is a tremendous opportunity. My mentors, who made it seem like the sky was the limit when it came to discovery in immunology, are to thank for it. My lab is now around the corner from where I summered 18 years ago.
What do you think is important in immunology and/or medicine in the near future?
Of course the genomic revolution is happening faster than the medical field can keep up. We will have masses of critical genomic data with no questions even having been asked yet, as opposed to what we are used to, which is scientific questions awaiting data to answer them. Furthermore, the clinical relevance of the patient’s genomes on a thumb drive will be far greater than what scientists are used to when it comes to a new molecular finding. The translation will need to happen rapidly, and given that much of our organ of interest is easily available by phlebotomy, we should help lead the way to bridge the clinical management with novel genomic findings as patients come through.
Do you have any inspiring patient stories you would like to share?
Sometimes, particularly when it comes to certain types of chronic allergic conditions, patients and/or parents can become very difficult to manage. The impact on their lives and the lives of their family is immense. So when patients can keep a sense of humor when dealing with their malady, when they can be persistent in trying to find answers without ruining the partnership we are trying to forge in working them up, it is always inspiring. One such patient once attended a lecture I gave. His social skills and capacity to communicate were very limited, and his disease burden, shared by his father and grandfather, was intense. But when I mentioned that allergies may be due to the effects of moving from farming in the country to toiling in the big city, and analogized it to Taylor Swift’s transition from country to pop music, his doubled-over belly laugh might have been one of my favorite moments as a clinician.
Joao Bosco Oliveira, MD - Instituto De Medicina Integral Prof. Fernando Figueira
What was your path to getting into Immunology?
I started to love immunology during my internal medicine rotation. I had this wonderful mentor named Francisco Barretto, who would talk about foreign concepts such as CD4 cells and molecular pathways. Up to that point I wanted to be a cardiac surgeon, but after this experience I never stopped thinking about immunology. I then decided to study abroad after completing my Internal Medicine Residency, and went on to take USMLE steps. Following that I had the fortune of being accepted for a fellowship by Dr. Thomas Fleisher, at the NIH, and the additional luck of having the chance to do my research project with Dr. Mike Lenardo, also at the NIH. This was really a transformative experience. I was so fascinated and challenged as I never thought I could be. Today I cannot imagine myself being anything else but an immunologist.
What do you think is important in immunology and/or medicine in the near future?
The specialty is growing in importance over the years, as the immunological and genetic basis of many disorders are being unraveled. Immunologists need to be fluent in basic mechanistic concepts, genetics, and also in diagnostic laboratory techniques, to properly handle the current influx of data. Training programs should adjust accordingly, to provide the necessary skills to our future colleagues. Lastly, I’d like to say that Immunology will dominate the world!
Do you have any inspiring patient stories you would like to share?
Patients are the real drivers of my research. It is very gratifying to go from a clinical diagnosis all the way to the discovery of a novel (or known) genetic defect. One recent case that was really touching was when we found the genetic cause of SCID in a child who died post-transplant. They are now planning to have a new baby through pre-implantation diagnosis, and we know we changed that family’s life.
Kathleen E. Sullivan, MD PhD - Children's Hospital of Philadelphia
What was your path getting into immunology?
I started off my thesis training in neuroscience and I loved the developmental aspects of it. I was attracted to the idea of how cells defined themselves in development. Where I was training, there weren't any neuroscience labs doing molecular biology and (eons ago) that was all the rage and I knew I wanted to be a part of molecular biology so I switched to biochemistry /immunology. I ended up in an adult rheumatology lab and always thought I would become an adult rheumatologist like all my role models. I still love hematology and my bench research is on lupus but along the way, the genetics of primary immune deficiencies called to me and I started seeing patients with primary immune deficiencies. I continue to be involved in rheumatology but over the years, I had to refine my clinical practice and I stopped seeing rheumatology patients about 6-7 years ago.
What do you think is important in immunology and/or medicine in the near future?
I think the next generation of immunologists will need to be fluent in the language of genetics and know how to interpret whole exome sequencing results but I think the research will be all cell biology and new therapeutics. In my mind new therapeutics is really the piece that needs a leg up in our specialty.
Do you have any inspiring patient stories you would like to share?
I've learned so much from my patients over the years. A current patient that I diagnosed with IPEX-like symptoms nearly ten years ago now is quite plainly a different beast and I am glad to have the opportunity to re-think about him and perhaps offer a better treatment option. Patients like him have kept me humble over the years. In immunology, things are not always as they seem.
Kimberly Risma, MD PhD - Cincinnati Children’s Hospital
What was your path getting into immunology?
When I was a graduate student I wanted to learn immunology so I could study asthma, but I didn’t find an immunology mentor during my research rotations. For my thesis project I put this desire on hold and focused on acquiring skills that would serve me well in the lab over the years- pharmacodynamics, molecular biology, cell biology, and animal models. As a pediatric resident I was once again moved to learn about asthma. When I realized that I could learn basic immunology as an Allergy/Immunology Fellow, I knew just what to do. Although I thought for sure I would become an asthma researcher, it was the immunodeficiency clinic and the diagnostic immunology lab that really energized me as a fellow. It seemed this was an ideal field for a physician scientist- there were endless mysteries to unravel! After spending a long weekend at Primary immune deficiency summer school, I realized I could make a career out of being an immunologist. I have been fortunate to be surrounded by like-minded colleagues in the lab and the clinic who are also passionate about immunodeficiency. This has kept the fire burning!
What do you think is important in immunology and/or medicine in the near future?
A major challenge is having a huge repertoire of new diagnostic tools available to us, forcing us to consider the meaning of an abnormal test—whether it be an abnormal newborn screen; a PCR-diagnosed, persistent viremia; or an exome sequence analysis. It is difficult to discern what is benign versus pathogenic. I am concerned patients will be “over-diagnosed” with primary immunodeficiency and other genetic disorders. A tincture of time to observe the natural history of the patient’s disease is critical for evaluation, but patients have very high expectations for immediate “answers” in our informatics-based culture.
Do you have any inspiring patient stories you’d like to share?
This year was a highlight in my career—I met a baby boy whose T cells recovered following gene therapy for X-linked SCID. We held our breath week by week until the first cells appeared. Awesome!
Thomas Fleisher, MD - NIH Clinical Center
What was your path getting into immunology?
My interest started with my pediatric residency which was at the U of Minnesota while Robert Good was still there, we had a large number of primary immunodeficiency patients who were intriguing (also at times management nightmares for the house staff). After my training I stayed on at the U of M to do bone marrow transplants followed by fulfilling an obligation to the military (linked to the Vietnam war) that brought me to Bethesda where I continued doing BMT at the Naval Medical Research Institute. Upon completion of that two year commitment, I was offered the opportunity to come over to the NIH as a Clinical Associate in the lab of Dr. Thomas Waldmann and in my mind that really set the course for my career.
As I reflect back, what I think really kept me in the field was the extraordinary pace of new developments that could always be linked back to human disease, a series of terrific mentors and a medical/scientific community that was overall very welcoming. I do not want to under estimate the importance of serendipity in my career as at many juncture points, an opportunity presented that I had not envisioned and by very good fortune these generally worked out extremely well. In addition, I also do not want undervalue the environment in which you train and work. Having terrific colleagues who are fun to work with and provide an environment where success is readily possible has definitely benefited me, the NIH definitely provided this for me. I also should note that my non-NIH colleagues throughout the US and world are great to work with and have made my career choice not only satisfying but also fun.
What do you think is important in immunology and/or medicine in the near future?
Taken together, it is my view that the community of clinician investigators in the field of primary immunodeficiencies works in a field that is ever more exciting and as a group, we are committed to attracting and supporting the next generation to keep this momentum going.
Alexandra Filipovich, MD - Cincinnati Children's Hospital
What was your path to getting into Immunology?
As a medical student at the University of Minnesota (trying to make some money during the summer), I had the privilege to work in an Immunology lab directed by Edmond Yunis. Peter Nowell had just published a method to identify human T cells due to their property to bind sheep red blood cells to their surface, the so-called E rosette formation (1976), and I was charged with re-creating this phenomenon. At the time, I didn’t fully appreciate the fact that I had been imprinted. My first rotation as a pediatric intern was on the Heme Onc ward which had just been fitted with a laminar flow “tent” where I participated in the first two bone marrow transplants performed at the U of M. Tom Fleischer was my supervising fellow. After residency I elected to pursue research into preventing GvHD by T cell depletion ( my “personal Immunology fellowship”) under the tutelage of John Kersey, at a time when T and B cells were still being identified and sorted as T and B cell rosettes.
What do you think is important in immunology and/or medicine in the near future?
At a time when inflammation is widely recognized as the underpinning of a vast number of inherited and “acquired” disorders and conditions, immunology (and the genetics regulating immune responses) are proving key to improving human health .
Do you have any inspiring patient stories you would like to share?
Nine months ago I had the privilege of supervising the gene therapy of an 8 month old boy with X SCID (who is currently at home doing well). What was very inspiring about this experience was the privilege to work with very thoughtful, brave parents who are full partners in this effort, and to experience personal growth through the interaction with more than fifty colleagues in the gene therapy group at Cincinnati Children’s as well as an international consortium of investigators.