Tomorrow, I’m teaching my first graduate-level class as an invited guest lecturer for Harvard’s Cellular Metabolism and Human Disease course. I plan to go over the story of how fetal hemoglobin was first observed to influence clinical outcomes in sickle cell disease and thalassemia, then discuss fetal globin regulation, and look forward to emerging gene therapies for monogenic disease. Along the way, we’ll have a discussion about iron metabolism in human health, and talk about the state of iron research. And to provide clinical context, I suspect we will spend a substantial amount of time diving into my story with thalassemia.

In preparing for this lecture, I am reminded of the serendipitously fortuitous timing of various medical advancements in my own life. For instance, consider a patient with thalassemia born in 1980, just a little over a decade before I was born. In this period of time, HIV screening had not yet been implemented for the blood supply (and hepatitis testing, while in place, had not been optimized). Patients receiving chronic transfusion therapy were at a huge risk of contracting HIV. Indeed, I have personally met several patients who were the unlucky victims of contaminated blood transfusions and have had to live thereafter with not one, not two, but three separate chronic diseases (thalassemia, HIV/AIDS, and hepatitis). Only in the mid-1980s did stringent HIV screening come into being, resulting in the near-complete cessation of transfusion-transmitted infections. And only several years later was I born.

In the late 1980s/early 1990s, given poor iron control and still-maturing standards of care, thalassemia brochures still cited 40-50 as the life expectancy for patients with transfusion-dependent thalassemia. I remember as a kid reading one of these pamphlets and, terrified, asking my parents whether I would really only live until 40. (Spoiler alert: a doctor recently told me he expects me to into my 80s or older. And, he added, I’d better not have retired by then. I’m hopeful about that first statement, though practicing medicine into my 80s is a more tenuous goal.) The overwhelming majority of thalassemia patients succumbed to complications of iron chelation or iron overload. When I was a child, Desferal (deferoxamine) was the only available chelator, and its half life was so short that I needed a subcutaneous pump for 8 hours a day. The pump dictated my sleep schedule.

One of my main concerns as a schoolkid was what I would do when I started college. Would I need to carry a pump with me all the time? How would that affect my friendships and relationships? Would I need to start giving myself subcutaneous injections? All these questions were at the forefront of my mind for much of my life growing up.

Then in middle school came another stroke of good luck. A groundbreaking new medication called Deferasirox had been developed and was now available for patients with transfusional hemochromatosis. Deferasirox was a tremendous blessing, as it was a daily medication and could be taken orally! The day my mom packed up my infusion pump and all the needles and put them into storage is a leading contender for the best day of my life. The advent of Deferasirox turned out to be one of the most important contributions to thalassemia care, since adolescent patients no longer had to self-administer their Desferal shots and could drink their medications instead. Up until now, patient non-adherence was one of the biggest obstacles in achieving optimal iron control, and I suspect was one of the biggest indirect causes of morbidity in the thalassemia patient population.

It was due to these biomedical advancements that thalassemia has more or less been an illness of inconvenience. Several of my patient peers have mentioned to me that none of their friends or colleagues even know about their disease.

Fast forward to present-day. Thanks to the in-depth study of hematopoiesis and its derangements in red cell disorders like sickle cell disease and thalassemia, we now have a solid understanding of disease modifiers in hemoglobinopathies. The past two decades have also brought fruitful research in the fields of gene-editing and gene-addition therapies, to the point where we are now seeing very real applications of gene-editing cures in the hospital. The 2010s have seen an uptick in the number of clinical trials for gene therapy as applied to hemoglobin disorders, and very recently have seen curative results in a set of patients with sickle cell disease and thalassemia (though data should – as always – be interpreted very cautiously). And it may not be too premature to predict that in the mid- to late-2020s, gene therapy will become added to the standard-of-care repertoire for patients with hemoglobin disease.

Take a step back and admire all of these achievements. In the span of 26 years (the number of years I have been alive) we have seen a very serious disease go from deadly at age 40 to nearly cured with gene therapy.

Medicine often gets a bad rap for its reluctance to embrace innovation. Indeed, in many areas (think EMRs, for instance) progress moves like molasses. But here is a very real case of a disease which has seen tremendous progress in the span of a patient’s lifetime. I’ve briefly touched upon iron chelation and gene therapy, but I haven’t even mentioned other innovations that have made a direct impact on my life, such as improvements in imaging technology (in the form of MRIs supplanting liver biopsies for iron measurements).

It’s easy to dismiss bench-to-bedside progress as a very slow-moving process. But if you know where to look, you’ll see progress being made all the time.

I tell these stories for several important reasons (not the least of which is simply a brain-dump to organize my thoughts for tomorrow’s lecture):

  1. Science works. And science saves lives. It is an utter shame that science as a whole has become largely politicized, and that funding for important research and education is suffering because of it.

  2. We often get lost in the weeds of life and find ourselves placing great emotional weight on minor day-to-day details that end up lost in the sands of time. It is a good exercise to overlook these weeds sometimes and take appreciation in the things we take for granted, like our health. There are times when I find myself complaining about thalassemia and – in reminding myself of all the ways my care and quality of life have improved over time – later realize that things could be much, much worse.

  3. These stories serve as an important reminder not to over-credit ourselves where credit is not due. As a successful student at a top school, I have often been praised over and over again for my achievements. Praise feels good, and it is easy to fall prey to self-worship when praise is received often enough. But I hope that it’s clear that my own academic achievements are not the results of my own efforts, but a testament to the efforts of all the scientists and physicians (and of course family) involved in getting the disease course of thalassemia to the point where I could even begin to focus my effort on school. Had I been born just two decades too early, my life would have looked far different: I would most likely be considerably less healthy, and otherwise wholly unremarkable.

There’s a quote I heard from my first year of medical school which has stuck with me ever since:

“There’s nothing that makes you more in tune with your health than living with a chronic disease. And nothing that makes you more appreciative of what you’ve got than to be at risk of losing it all.”