Tuesday, March 10, 2020

From Chiang Mai with Stem Cells - Sean Legler


If one wants hope for humanity, one must look no further than the authors’ names in a medical journal. The day before I left for my international medical experience in Thailand, I led a journal club session on an article in the Lancet that had contributors from 41 different countries. You won’t see a headline on the 5 o’clock news that exclaims, “Humans from Around the World Work Cooperatively Together to Try to Reduce Suffering with Science and Diligence,” yet this happens everyday in medical research. As I finish my second week of hematology here in Chiang Mai, I continue to be amazed by this reality as I see it. But first, let’s go back in time and back to my hometown of Minneapolis...

In 1968, the University of Minnesota physician Dr. Robert Good and his team performed a bit of a miracle: they gave a 5 month old boy with a severe immune deficiency the first successful stem cell transplantation from a non-identical sibling. They inserted the bone marrow harvested from his sister through his stomach, which remarkably worked after a second try. The sister’s stem cells took to their new home as they eventually made their way into his little bones, and would serve as the immune cells to defend him from deadly infections. While the infants’ family had been plagued by early deaths from infections at a young age, he was the first in the world to get a cure for what we now call X-Linked SCID

This little miracle was not a lucky accident though, and Dr. Good’s success was preceded by many failures and the slow accumulation of knowledge around the world regarding how the immune system interacts with the blood and bone marrow.  Indeed, leading up to this, Minnesota’s success where others had failed was only made possible by the first descriptions of HLA immune antigens in humans by a Dr. Dausset in France, a Dr. van Rood in Holland, a Dr. Payne in the United States, and a Dr. Ceppellini in Italy, and countless others. Like most great science, it was an international affair from the beginning.

Dr. Good himself had a unique story: he had been the first medical student at the University of Minnesota to ever complete a combined MD and PhD degree, graduating in 1947. He had been wheelchair-bound for much of his education due to polio. Only in 1950 did a Polish doctor who had fled the Nazis, Hilary Koprowski, develop a live attenuated polio virus and only in 1955 did the American doctor Jonas Salk build on his work to develop the more widely used inactivated virus for immunization. As he was unfortunately just a few years away from benefiting from this humanity-changing medical innovation, Dr. Good was paralyzed by polio for a time and wheeled in a wheelchair by his mother to many of his classes as an undergraduate student in Minneapolis. He eventually regained the ability to walk, but for the rest of his life he would walk with a limp. However, being a few years behind the medical science that could have kept him walking without a limp did not stop him from planting seeds for medical innovation in the next generation.

Fast forward to 2011: I find myself as an undergraduate researcher at the University of Minnesota, at a stem cell transplantation lab under the guidance of Dr. Jakub Tolar, a combined MD PhD himself who came to Minnesota from the Czech Republic. In his lab, the seeds from Dr. Good have firmly taken root. Since that first successful transplant, the University of Minnesota has become a center for a number of incredible achievements in stem cell research and treatment. In 1975, there was the first successful transplant in a patient with lymphoma. In the 1980s, the development of the autologous marrow transplantation—using the patient’s own stem cells harvested earlier in time—was performed for the first time in a patient with CML. Then in 1982, there was the first transplant for an inherited metabolic disease. By 2007, over five thousand stem cell transplants had been performed for a multitude of fatal diseases at the good old “U of M.”

My mentor Dr. Tolar had made his own mark in 2010, when he published in the New England Journal of Medicine how he had used a stem cell transplantation (first in mice, and then in children) to cure a deadly skin-blistering disease called recessive dystrophic epidermolysis bullosa. I loved Dr. Tolar. He had a serious intensity coupled with a quiet joy for the science of medicine that inspired me. While in the lab, he and his colleagues taught me how to pipette samples, splice genes, make fluorescent proteins, and explore how gene-editing and other methods might give these children an even better chance for a cure. In the clinic, we would see his patients, which some called “butterfly children” (named for the fragility of their skin), along with their families who had come to Minnesota from around the world for a chance to save their children from early death. We would walk from the clinic then over to the hospital, where we donned protective coats to limit infections and visit with the children who had recently undergone transplants.

Fast forward to 2020: I stand today in the stem cell transplant unit at Chiang Mai University hospital in Thailand. We take off our shoes to enter the unit and put on special green flip flops for sanitation, which denotes one of the few noticeable differences from a stem cell transplant unit back home (we tend to keep our shoes on!). Here in their stem cell transplant unit we see patients from all around Thailand who are undergoing transplantation for cancer. To say the least, the doctors I work with, such as Dr. Lalita Norasetthada and Dr. Adisak Tantiworawit, are tremendously intelligent. I am humbled as I listen to them describe the results from the latest oncology clinical trials in the past couple months, trials that I--as a mere second year internal medicine resident--often know little about beforehand. In the clinic, I also realize that many groundbreaking drugs are being tested here in Chiang Mai in close coordination with other doctors, universities, and pharmaceuticals around the world. I am cognizant of the fact that the results of these trials will help inform the treatment of the patients I see back home in Minneapolis. There is a two-way street to global health; once a torch is lit, it reflects light back. 

Later, I sit in journal club with the Thai hematology residents and fellows, who carefully further dissect the latest trial results with their faculty, debating the internal and external validity of the authors’ trial design, and the applicability of their results to a resource-limited universal healthcare system like Thailand’s. “If you had a patient with multiple myeloma, and you could only test four genetic markers with FISH analysis because they cost about 2,000 Thai Baht each...” Dr. Norasetthada asks, “which ones would you choose?” My head swirls with thoughts, first of incompetence for not knowing the third and fourth translocations associated with the highest relapse risk for multiple myeloma, and second, with inspiration from knowing that the Thai residents sitting beside me do know.

As the journal club goes on, one name pops up on the screen as they are reviewing the latest results from the 2019 OPTIMISM-M trial out of Boston, Massachusetts: the author was Dr. Paul Richardson, a brief mentor of mine while in medical school. He leads many of the groundbreaking studies in cancer research, and I vividly remember being with him at his VIP clinic six years ago. CEOs and the well-connected would find their way across the world to see what he might be able to offer them. Yet here I am now in Thailand, and I see that the Thai electrician that grew up here in Chiang Mai with the very same cancer might be getting the very same experimental drug.  Dr. Tantiworawit here tells me he is involved in 10 active trials, and he is the lead on two of these trials. It seems as if every other patient in clinic is getting registered in a clinical trial with a novel pharmaceutical agent. 

I walk home after journal club, like many of the locals, with my PM2.5 facemask on. The facemask limits exposure to the air pollution coming from burning forests hundreds of miles from the city.  Thailand has been hit hard by overdevelopment and human-induced climate change. The air pollution worsens each year. Things aren’t perfect here, certainly, and there are problems to solve. 

On the healthcare side, certain treatments, including types of stem cell transplants, simply cannot be afforded in a universal healthcare system with only modest means (though many of the most effective treatments are still covered). Back home in Minneapolis, I indulge in non-essential extra tests and treatments, while the Thai doctors here carefully weigh the economic, physical and emotional costs of everything they do. 

Medicine and humanity advance slowly, imperfectly, non-linearly. But what I see here brings me hope. Dr. Good, Dr. Salk, Dr. Tolar and countless others around the world in a way are all connected to and interwoven with Dr. Norasetthada and Dr. Tantiworawit and the thousands of others working here in Thailand to make the world a better place. 

So now in 2020, as the Earth warms, I sit here at my desk in Chiang Mai, with the ruby red sun cascading over the mountains, filtered by the gray smoke, all making for an unnaturally beautiful sunset… and my heart warms too.

Friday, December 6, 2019

Blair's Week 6 and 7 Update


Week 6 & 7 Update





My second and third week of endocrine has gone well. In clinic, I've seen a smorgasbord of diabetes, thyrotoxicosis, papillary thyroid cancer, acromegaly, congenital adrenal hyperplasia (21-hydroxylase deficiency), agranulocytosis 2/2 PTU, and a patient following up after recent thyrotoxicosis periodic paralysis (which is much more common in Asians). For patients with hyperthyroidism requiring radioactive iodine (RAI) ablation, the goal in much of Thailand (with some exceptions) is to make the patient euthyroid rather than hypothyroid. As I understand it, this is because many rural Thai patients object to the prospect of daily levothyroxine. The drawback to this approach is that a certain percentage of patients are still hyperthyroid after RAI and require a second ablation. On rounds, we’ve had several interesting cases, the most recent being a patient with limited access to healthcare who presented with paroxysmal palpitations, diaphoresis, and according to family had a cardiac arrest the prior year. His workup revealed dilated cardiomyopathy and abdominal mass concerning for a paraganglioma.




Over the weekend I made a trip to Chiang Rai Province where I visited the Mae Fa Luang district (Doi Tung and Tham Luang cave), and Golden Triangle (Mae Sai, a brief crossing into Myanmar, and Opium Museum). Doi Tung represents a successful development project by the royal family (particularly the mother of Rama IX) to encourage alternatives to growing opium – primarily coffee and macadamia. The Mae Fah Luang gardens are especially gorgeous.




In Mae Sai, I briefly crossed into Tachileik, Myanmar; a peculiar crossing that required I forfeit my passport to immigration authorities to ensure I wouldn’t venture any further. While there I visited some temples and a highly regarded meditation center (Ngwe Taung Oo) where many monks and nuns from various countries train in Vipassana.




Prior to returning to Chiang Mai, I stopped at the Opium Museum which is ambitiously curated to cover the opium trade since ancient Egyptian times but primarily focuses on the colonial opium wars and the introduction of opium to Siam.



From Chiang Mai with Stem Cells - Sean Legler

If one wants hope for humanity, one must look no further than the authors’ names in a medical journal. The day before I left for my intern...