Dr. Ann Marie Schmidt devoted decades of her life to research that could change the lives of people living with diabetes. Then, in one night, it was all destroyed. Hear how - despite this devastating loss - she and her team found their way back.
Dr. Ann Marie Schmidt devoted decades of her life to research that could change the lives of people living with diabetes. Then, in one night, it was all destroyed. Hear how - despite this devastating loss - she and her team found their way back.
Vital Signs - Season 2: Dr. Anne Marie Schmidt
Sirius XM - NYU Langone Health
Title: Are They All Gone?
Description: "Dr. Ann Marie Schmidt devoted decades of her life to research that could change the lives of people living with diabetes. Then, in one night, it was all destroyed. Hear how - despite this devastating loss - she and her team found their way back"
Participants:
Ann Marie Schmidt, MD
Rose Reid, Narrator
Dr. Schmidt: A few days before the forecast for hurricane Sandy approaching was really becoming more and more dismal. So most of the day was okay, but then toward the early evening, the Smilow building lost electricity, I think it was around 7:00 PM. After that point, most of us safely tucked away in our homes, we lost contact. No one could have anticipated - I don't think I anticipated truthfully - that they all could have been pretty much destroyed.
Dr. Schmidt: My name is Ann Marie Schmidt. I'm the Iven Young Professor of Endocrinology here at NYU Langone. And essentially I am a full-time researcher.
Narrator: When Hurricane Sandy slammed into the New York City region on October 29th, 2012, it was technically no longer a hurricane. It was a large, powerful, and unusually dangerous post-tropical cyclone. Maximum sustained winds topped out at 80 miles per hour, and these strong winds extended for a thousand miles from the storm’s center.
Sandy’s arrival coincided with high tide, and sent a 15-foot high storm surge rushing into the streets of New York City. Perched on the east side of Manhattan, just steps away from the East River, NYU Langone Medical Center was in a very precarious position.
News clips: Hurricane Sandy is more than 200 miles off the coast and is about to crash into two other systems when it makes landfall. FEMA personnel are working closely with state and local governments. The highest storm surge ever for New York City going all the way back to the nineteenth century. If you have not evacuated to a safer location and out of the zone, it’s crucial that you do so as soon as possible. Time is running out.
Narrator: When power went out that night and backup generators failed, the staff of NYU Langone Health evacuated 322 patients to safety. This careful, determined heroism saved lives. But, they couldn’t save everything.
Dr. Schmidt: I remember I asked her, I said, Jennifer, are they all gone? And she just turned around and she didn't say a word.
Narrator: From SiriusXM and NYU Langone Health, this is Vital Signs, where medicine is made personal. I’m your host, Rose Reid.
Narrator: It takes a lot of people to make medicine happen, and to push it forward. Clinicians who work directly with patients are obviously important, but another critical component takes place entirely behind the scenes: research. That’s where Doctor Ann Marie Schmidt thrives.
Dr. Schmidt: As I was doing the doctor of medicine, basically medical training, I started to become more curious about why some of these things were actually happening. I had a lot of patients with diabetes, even back then, actually I graduated medical school in 1983. And when I started my internship and residency, it was pretty clear that diabetes was already on the rise. And I started to realize that there were basic questions about why people with diabetes were so vulnerable to all these complications that I was taking care of in the clinic. And that's when my interests really started to move a little bit toward more of the underpinnings of the disease and not solely the treatment.
Narrator: Understanding the origin of a disease is often crucial to figuring out why it acts in certain ways. The same might be said of doctors. While the lab is now Dr. Schmidt’s home, it wasn’t always.
Dr. Schmidt: I was the chief resident actually here at NYU and then did a fellowship. All during that time I was taking care of patients. And I remember how well the senior residents had taught us about, you know, what we used to call the checklist. Go down that checklist, you know, start with the eyes, go down to the feet and make sure that, you know, you take care of all of these things. I remember during one point in my training I was in the Bellevue hospital clinic and just took care of this lovely woman who was starting to develop very substantial complications. She had type two diabetes. It was pretty clear that even over the four years that I took care of her, she was developing more eye disease and also more evidence of kidney disease.
Dr. Schmidt: When I had to tell her that I was leaving the clinic. Oh my goodness. She got so upset and started crying because I had a good bond with her. And that was Particularly difficult because even though I had filled a void for her, there came a point that I had to stop. I had given her my phone number. So I was able to make sure she was OK. There were a few patients that reacted that way, but this one particular woman, it, it really remains with me.
Dr. Schmidt: It's not that I don't miss patient care. It's just that I have reorganized the way I feel that I'm best effective. I've always acknowledged how consuming patient care is, how much responsibility you have, not just for the 30 minutes when the patient is sitting with you, but for all of the time afterward. And for me to be able to execute the research mission to the best of my ability, the patient care component truthfully is best left to others who can really dedicate that level of time and follow up time that’s really, in my opinion, required for optimal patient care.
Dr. Schmidt: I felt that the work that I had done with the patients really helped me in a very substantial way to understand these things and believe it or not, it kind of made it easier, especially in the first years, to figure out how to design experiments in cells and in diabetic animals.
Dr Schmidt: In my fellowship, it was 2 years clinical, and then 1 year research. I wouldn’t have thought of the research component as being something that could be life changing. I guess I would have thought of it, truthfully, as something that would have enriched my understanding, but not necessarily be transformative. So, that’s a pretty amazing gift.
Narrator: The frustrating - and amazing - thing about medicine is just how much we still don’t know. The key for any researcher at the start of their career is to ask new questions, or try to answer old, elusive ones. They search for uncharted territory like an explorer in pursuit of new land. Dr. Schmidt’s research focuses on diabetes, a disease that occurs when a blood sugar called glucose is too high. A hormone you’ve probably heard of - insulin - is produced in the pancreas, and helps transfer glucose from our blood into our body’s cells. Sometimes, the body doesn’t make enough, or any, insulin, which means the sugar stays in the blood for too long, and never reaches the cells.
Narrator: When blood sugar is elevated for too long, it is known as hyperglycemia. This is the hallmark of diabetes. Prolonged, excess blood sugar can damage large and small blood vessels throughout the body. This damage, in turn, increases a person’s risk for stroke, heart attack, blindness, and kidney disease. There are a few types of diabetes, but the vast majority of people have either type 1 or type 2. People with type 1 diabetes don’t make any insulin at all. For these patients, insulin is life-saving, and must be taken daily.
Much more common is Type 2 diabetes. According to the CDC, of the 34 million Americans who live with diabetes, 90 to 95 percent have type 2. In this case, the body typically doesn’t make or use insulin efficiently, causing blood sugar to rise. These patients sometimes need insulin but not always, and can also take medications or make lifestyle changes to try to manage their condition. Regardless of which type of diabetes someone has - it’s bad news.
Dr. Schmidt:
I always say diabetes is a head to toe disorder because it just affects so much of the person's body. You know, it's one thing to control the glucose, but the real problems with diabetes, especially in type two, is that you're trying to maximize, optimize and prevent blindness, premature strokes and heart attacks, kidney failure. All of these things are very devastating and then they feed into each other. So once people have kidney failure with diabetes, then cardiovascular disease accelerates probably because of all of these toxins, you know, that are normally daily removed in us by our kidneys. But when they don't work and you have to go to dialysis, you have to be very vigilant. It's a very difficult life, I think, to be a diabetic person, particularly, those that have had it for many, many years.
Narrator: Dr. Schmidt moved on from NYU Langone, where she had done the bulk of her training, to Columbia University. It was at Columbia that she realized exactly what she did want to dedicate her time to: a minuscule molecule now known as RAGE, which stands for receptor for advanced glycation end products.
Narrator: Basically, the RAGE molecule is involved in promoting inflammation in the body. Inflammation can be beneficial - it helps the body fight against harm from injuries, infections, and toxins. But when inflammation is sustained over a long period of time, it can be a problem. The RAGE molecule, and the inflammation it causes, have been linked to obesity, heart disease and - most important to Dr. Schmidt - diabetes. Knowing this molecule exists and how it functions in the body can help researchers develop drugs to treat these common, and often devastating, conditions.
Narrator: The RAGE molecule is a big deal, and Dr. Anne Marie Schmidt discovered it. Not long after, she and her team of researchers returned to NYU Langone Health to further their work. And a lot of that work depended on mice.
Dr. Schmidt: Yea, so the mice are special. I remember that I asked a number of people did you ever work with diabetic mice? No, no, no. So went to the literature and found a very tried and true way to induce diabetes in mice.
Narrator: More than 98 percent of mouse DNA is exactly the same as human DNA. They have shorter life spans, which makes it easier to study the effects of certain diseases or treatments on individual mice, and across several generations. They’re also susceptible to many of the same health problems we are, including diabetes.
Dr. Schmidt: For all practical purposes, just like people do they have an increased urination, they have increased thirst because they're hyperglycemic. They have high levels of blood sugar. And so those first endeavors into inducing diabetes and working with diabetic animals was really very humbling for many reasons just to be able to work with live creatures and test ideas. But also to learn which we do to this day, we write in the protocols and reinforce with the young people how important it is to monitor them. And I'm very happy, proud to say really that the people in our laboratory are very careful with the animals.
Narrator: For Dr. Schmidt and her team, inducing diabetes in these specially bred mice was crucial, because it would help them try to understand more about the RAGE molecule.
Dr. Schmidt: Obviously we're just enamored with trying to understand what's going on. Why did nature make this molecule, what is its purpose? Did you miss anything in the animals that might have suggested a beneficial effect of the molecule?
Narrator: This last question was particularly important. Before researchers start to develop and test a therapy targeting a molecule like RAGE, they have to make sure the body definitely does not need it.
Dr. Schmidt: Nothing nature made is ever totally there for bad things. That's impossible. And so understanding of this rage molecule and that seesaw of good versus the bad is really very important. So those mouse models, you know, certainly have tremendous importance to us in that regard.
Narrator: Dr. Schmidt and her team at NYU Langone Health began this work with diabetic mice in 2010. They were carefully curating these very special mice to research the RAGE molecule. The goal was to discover how and why it works in the body, and to use this information to find new treatments for diabetes, and possibly other health problems. It could be incredibly meaningful for the millions of people living with these conditions. Initially, her lab was housed in the basement of the Smilow Research Center at NYU Langone Medical Center. And that’s where she was at the end of October 2012, when the weather reports began rolling in.
News report: This storm is one of the largest we’ve ever seen in the Atlantic basin. So big, in fact, that it’s almost a third the size of the entire United States.
Dr. Schmidt: A few days before, you know the forecast for hurricane Sandy approaching was really becoming more and more dismal.
News report: Even the moon was on Sandy’s side, with an astronomical high tide delivering higher water levels than normal. This storm is going to be destructive, historic, and unfortunately life threatening. During its life cycle, it can unleash and release the same amount of energy as ten thousand nuclear bombs. This storm is monster sized - three elements, colliding over the country’s most populated area.
Dr. Schmidt: The full moon and all of these other factors. We understood that there was an increasing risk that flooding, which is very uncommon, of course, in, you know, Midtown Manhattan was starting to become more of a reality.
News Report: That's my biggest concern for New York City - the storm surge. The rain has really picked up. The beach used to be about 150 yards that way. But we’re on the bad side of the storm, there will be a domino effect of different things that will happen - then you start taking transformers out, then you have power outages.
Dr. Schmidt: And we all were advised to go into a mode of thinking about saving computers, research materials, making sure that everything was as organized as possible. And NYU and their typical rigor of all the things, the way they do things, the animal care, the veterinarians, the, the head of science here, all of these people were thinking about all of the components of the research infrastructure. And of course the animals were very important in that. Particularly I would think in the Smilow research building, because that, to my knowledge, was the only research building where the animals were actually housed technically below the ground.
We knew when we left the lab on Friday that we had everything as well put together as possible.
Narrator: Hurricane Sandy began as a tropical wave off the coast of Nicaragua, and eventually grew into a category 3 hurricane as it meandered around the Caribbean Sea. Over the next few days, Sandy weakened slightly in the Atlantic Ocean, touching The Bahamas before targeting the Northeast coast of the United States. The storm made landfall in Southern New Jersey around 8 PM on Monday, October 29. Hurricane Sandy was a monster - the largest storm by diameter that has ever been measured in the Atlantic Ocean. People in the area did their best to prepare, including Dr Schmidt’s team and others with labs in the basement of NYU. They tried to ensure the mice had enough food and supplies, and moved cages to higher shelves. And then, like everyone else in the city, they waited.
Dr. Schmidt: Most of the day was okay, but then toward the early evening, an email had come, that the Smilow building lost power. After that point, most of us even safely tucked away in our homes, we lost contact. The internet went out, the cell phones were no longer working. And so the last thing that we knew, was that the power was out in the Smilow research building. And after that, it, it took a while, you know, for communication to come back. Actually, our emails were, were destroyed. So we were literally relying on texting each other in the aftermath, hoping that, you know, some form of communication would start to trickle through.
Narrator: The United States incurred an estimated 50 Billion dollars in damage. Sandy flooded 51 square miles of New York City, including large swaths of the subway system, three vehicular tunnels in and out of Manhattan, and one very large, very busy hospital. The storm’s 15-foot surge overwhelmed the banks of the East River, and more than 15 million gallons of water burst into the basement of NYU Langone Medical Center. Across portions of the city, electricity was knocked out for days, including along First Avenue, where NYU is located. Backup generators failed, and 322 patients - including 20 infants - were safely evacuated to nearby hospitals. As for the inhabitants below ground, Dr. Schmidt didn’t know what to expect.
Dr. Schmidt: The worst of it was trying to anticipate, how bad could this be? I thought maybe what the worst case scenario was is that they would have had to have moved them. And in that situation, they would do what we would have to call, break the barrier, which means they live in a very, very controlled environment where there's very little outside pathogens that can affect them and hurt them. And that would have been, even in itself would have been a challenge, but it would have been surmountable. But I think all of us thought that that might have been the most likely thing that could have happened was simply that they would have had to have moved them.
Dr. Schmidt: And essentially, you know, they live in these little racks, right? So they're stacked up. And most of the racks have seven to eight rack components where they can live and then move up vertically. Actually, our mouse manager, she didn't tell me she did this, but she put the most precious one on the top shelf. It took a number of days to get to them. The way they reached them was through the ceiling because I think it was still flooded in the room. So we didn't know really what had happened. And it took a few days for more transparency about what actually had transpired as people were able to physically come back here and then be able to start to communicate. They started to learn really, you know, the depth of everything that had happened. And I can't honestly say I remember the day of the week, but it was later in that week when we were finally allowed to come across the bridge from New Jersey where I live into New York. And basically people were just, there were pre-set meetings where everyone was organizing. They were so wonderful. You know, how are we going to get dry ice? How are we going to clean out the Smilow building because every single floor was permeated with that diesel fume. And all of these things, we would go almost every single day after that and just wait for these meetings. And it was that, that first meeting that I had attended that I um, I um, I met Jennifer Pulliam.
Narrator: Dr. Jennifer Pulliam was, and still is, the veterinarian overseeing care of the laboratory animals at NYU Langone Health.
Dr. Schmidt: I just saw Jennifer, she turned around, I said, Jennifer, are they all gone? And then Jennifer didn't say a word. She just hugged me. And you know, you didn't need words, her, her whole demeanor and everything. You know, truthfully at that point I had been warned, I'd been warned. I think our mouse manager had some information that this didn't look good, but she, she probably just couldn't bring herself to tell me this so directly. You know, it was very, very traumatic because all I could picture was just this massive destruction of everything that we had built.
Dr. Schmidt: I don't think I anticipated truthfully. I think I had, you know, just, just blocked that out of my mind, that that was even a possibility that they all could have been destroyed.
Narrator: Figuring out what actually DID happen in the basement of the Smilow Research Building was an essential part of making sure it would never happen again. The area that housed the mice was thought to be impenetrable.
Dr. Schmidt: What we were told is that it was a weakness in one of the, uh, wall structures in the adjacent building - the medical science building. When that water came, it was the path of least resistance to be able to break that down. And then it went thoroughly through the Smilow vivarium. It was a beautiful, beautiful structure and there were no rooms that were spared; it just flooded the entire thing. And luckily there were outflows for the people who were, who were in there watching our mice to be able to get out of there, you know, and, and get out of there safely.
Narrator: In the immediate aftermath of Hurricane Sandy, many NYU Langone physicians and researchers were scattered around the city, practicing their medicine and their science at neighboring institutions. Dr. Schmidt and her colleagues found themselves 30 blocks north of NYU, at another hospital - Memorial Sloan Kettering. Their mice were gone. Years of meticulous work wiped out by a once-in-a-lifetime weather event. Getting back on track would not be quick, or easy, but it was essential.
Dr. Schmidt: We didn't even make those mice ourselves. Those mice were made by experts in a company in France called genOway. And genOway was still in the process of trying to cryopreserve those animals. And they didn't even have that process completed. So that when we lost the initial ones that they had sent us in the Sandy, we had to reach out to them. And that process took almost a year to get those mice back.
Narrator: Research animals are bred to have very specific genetic traits. Starting from scratch is an elaborate process. It involves sperm, and stem cells, and time. In Dr. Schmidt’s case, it had taken about a year and a half to produce the mice they needed to study the RAGE molecule. They had just started to get into the swing of experiments when Sandy stole it all away.
Dr. Schmidt: I just saw before me, like, this is not survivable. And then of course the idea of what happened to the animals, and there were just so many layers. All the young postdocs, the students, all of the implications for their futures, for their research. There were no limits to the potential complications and it took every bit of resourcefulness and resilience to like, not give up, not give up, but to say, you know, we just have to move on. And I tried very, very hard to always be a voice of survive, thrive. We'll all be okay. And to make sure that all of those young people that were affected had futures and next steps. But there's no question that there were many, many layers of challenges for the lab, for the young people, for the loss of the mice. It really was quite, quite an experience and understanding what your commitment is and how resilient. you can be, even though you never thought you'd ever have to do that, but, anything can happen as they say.
Narrator: It took a while, but Dr. Schmidt and her team were able to start over again. They obtained the mice they needed from commercial vendors and colleagues, and worked diligently to expand and recharacterize the mice for their research. It was never immediately clear if or when they would succeed. It turns out that even the biggest, darkest, and most destructive storm clouds can have a silver lining.
Dr. Schmidt: I would say, you know, 2015, 2016, I think we're, we're pretty confident that we had made it. There actually was a bright side to Sandy. So what was the bright side? We didn't need mice. We didn't need anything that was frozen that was a loss. All we needed was NYU's robots. We needed our cell culture hood. And we needed to be able to do the bench experiments to advance the compounds. That work was accelerated because of Sandy. So, um, I'm grateful even though I didn't realize it at the time I had the ability, unbeknownst to me to understand that there's always a way out and there's always a way forward.
Narrator: Tragedy often begets innovation. As a result of Hurricane Sandy’s destruction, NYU Langone Health rebuilt its research labs, and took extra steps to ensure that an entire line of specifically bred research mice would never be lost again.
Dr. Schmidt: So what NYU did in terms of, you know, basically ensuring perpetuity for these animal strains is that there were no shortcuts taken.They added in the idea that for certain strains, they needed to make copious amounts of animals to cryopreserve, freeze embryos, or in other types of strains, they cryo-preserved sperm from the mice. So you can imagine that that takes a lot of time, enormous amount of resources. When they completed the process for all of the researchers, they included that cryopreservation so that there never would be this type of, you know, panic and catastrophe of, you know, generating a new line like that. That process took years. That process only finished relatively recently
Narrator: The research that Dr. Schmidt restarted in the wake of Hurricane Sandy has been incredibly valuable. In 2019, her lab published a surprising study. They discovered that the RAGE molecule has a strong link to obesity, and in certain mice, If you take away RAGE, you eliminate obesity and diabetes, two diseases that often go hand-in-hand. This work earned Dr. Schmidt attention, and accolades.
Dr. Schmidt: I was very fortunate in, in 2020 to receive the basic science research award of the American Heart Association. And this particular award recognized the discovery of RAGE and all the work that our team had done to understand RAGE, discover RAGE, and, and be part of the expansive breadth of this molecule and its potential. I'm just, so humbled by these sorts of things, I'm kind of like always embarrassed by them because I just don't see myself, like as, as anything other than, you know, part of like a bigger team, but that was really pretty amazing.
Narrator: As Dr. Schmidt’s work with the RAGE molecule continues, its implications are becoming only more apparent. Her team is now looking at whether RAGE might also be linked to more severe COVID, and possibly Alzheimer’s disease. The discovery of this tiny molecule has changed medicine. Dr. Schmidt knows that as a researcher this research has defined her career. She left direct patient care behind long ago, but those early experiences at Bellevue Hospital have never left her mind, or her motivations.
Dr. Schmidt: I am so fortunate that for a very small sphere of my life, I was a doctor. I took care of people. I looked at feet, I looked in my eyes and I understood the challenges of being ill and having a chronic illness that was never going to go away. So I was very fortunate to see that and then to be on the other side of it and everything that I've learned from what I've seen is it's just so worth it, It has to be worth it. That's our duty. And, um, it's, it's just an incredible, incredible path to take. And it's worth it.
Narrator: Vital Signs is a co-production of NYU Langone Health and SiriusXM. The podcast is produced by Jim Bilodeau, Julie Kanfer, and Keith King, with sound design by Jim Bilodeau and writing from Julie Kanfer. SiriusXM’s executive producer is Beth Ameen, in partnership with Allison Clair and Jim Mandler of NYU Langone Health. Don’t miss a single episode of Vital Signs and subscribe for free wherever you listen to podcasts. To hear more from the world-renowned doctors at NYU Langone Health, tune into Doctor Radio on SiriusXM channel 110. Or listen anytime on the SXM app. To get in touch with our production team, email VitalSigns@siriusxm.com. For the Vital Signs podcast, I’m Rose Reid. Join us next time as we bring you stories of medicine made personal.