Headscratchers Podcast Duke University School of Medicine

Immunology expert Allan Kirk, MD, PhD, discusses what compels the immune system to respond to danger, and how our immune systems change over time. Dr. Kirk is a transplant surgeon and the chair of the Department of Surgery. He is also professor in the Departments of Immunology and Pediatrics at Duke.
Transcript:
LK
Welcome to HeadScratchers, a mini-cast from the Duke University School of Medicine. We ask Duke experts to help us understand the questions in science that have us scratching our heads. Today, we're speaking with Dr. Allan Kirk, a transplant surgeon and the chair of the Department of Surgery here at Duke.
Dr. Kirk, what causes a person's immune system to weaken?
AK
The immune system is best envisioned as a way of sensing your environment, just like your nerve system. As it senses what's around you, it's continuously making decisions about what's important to respond to. And, if it's gonna respond, whether it's gonna be aggressive and try to attack it, or whether it's going to be passive and allow it. Each time it makes one of those decisions, it changes a little bit and becomes better. It develops memory. So nobody's immune system is the same. And in fact, a person's immune system is not the same day to day. Even identical twins have completely different immune systems by the time they're just a few weeks old, based on what they've been exposed to.
But in general, time and exposure eventually leads to immune exhaustion. So the natural history of an immune cell as it responds, is to eventually become exhausted, meaning it can't respond anymore, so that you're not continuously having an immune response to something. Fortunately, you can make more of your immune system. But as you grow older, the things that help you make your immune system, like your thymus and your bone marrow, become less good at it, and you slowly run out of immune cells.
The most common cause for your immune system weakening is just, then, living a long time -- which is a good thing.
LK
What types of factors go into the immune system’s decision to respond or not?
AK
Really, the immune system works hard to stay off unless something dangerous impels it to go on. When you're considering a context, you're looking for something called danger. That's actually an immunological term. And there are molecules that are associated with danger, with inflammation, with pain. And those things drive an immune system to assume that it's a dangerous context and make an aggressive immune response. Whereas, if those signals are not there, the assumption is that things are fine and there's no need to have an immune response. So something that's harming you, you should respond to, and something that's not, you should accept. In fact, if we would act more like our immune system, we might get along better.
LK
Thanks for listening. This podcast was produced by the Duke University School of Medicine, music by Blue Dot Sessions. Visit us online at headscratcherspodcast.duke.edu. You can also find us on all your favorite podcast players. Don't forget to hit the subscribe button -- and if you like us, leave us a review.
Medical Disclaimer & Terms of use at https://bit.ly/2LrjWdh

Cancer expert Kelly Marcom, MD, discusses the role that genetics and environmental exposure play in the role of understanding why a person develops cancer.

Dr. Marcom is a professor of medicine and member of the Duke Cancer Institute (DCI). He is part of a team of experts at DCI that offers genetic testing and counseling to people diagnosed with cancer, as well as people at risk of developing cancer.
Transcript Lindsay Key: Welcome to HeadScratchers, a mini-cast from the Duke University School of Medicine. We ask Duke experts to help us understand the questions in science that have us scratching our heads. Today we're speaking with Dr. Kelly Marcom, an expert in genetics and cancer. Dr. Marcom, what are the factors that contribute to someone getting cancer? Dr. Kelly Marcom: Well, it's a very complex question, and one that we continue to work on very hard. Cancer is not a very intuitive disease process. Unlike a lot of things that affect our bodies, you know, you get a heart attack, you block a blood vessel -- those things are fairly straightforward. But cancer -- cancer is something that we don't naturally have a good intuitive understanding for. And it always then, consequently, is a bit of a mystery to many people why they got it. Fundamentally, cancer is a genetic disorder, by which I mean that the underlying cause of the problem is damage to the genes in the cells. But that understanding of cancer is really something that's still relatively recent. Watson and Crick identified DNA in the 50s, and so that began the whole process of understanding DNA and what it does. And, while people had always made observations about inherited patterns of cancer within families, it wasn't necessarily evident what the basis of that was. Now, prior to that time, there was a great deal of emphasis on the infectious nature of cancer, as caused by viruses. You can imagine, if you see cancer being transmitted through a family from one generation to the next, you might naturally assume that it's an infection. And there was a good scientific rationale for that: clearly it had been shown that certain viruses were responsible for certain types of cancer -- the most classic and probably one of the most important being cervical cancer, caused by papillomavirus. And so that whole story really came together with understanding that cancer is developed because you get damage to the DNA that perpetuates the additional damage to the DNA, and propagates itself through the cancer cells, and leads then to unregulated growth. And figuring out how those viruses cause cancer was in damaging DNA, and damaging things in the cells in the cervix in the course of the virus growing. So if genetics are the basis of the cancer, what is the influence of environmental exposures? Most of the things that contribute from a lifestyle have to do with exposing your body to things that damage your DNA. Smoking is the biggest culprit. Too much sun -- that's going to cause DNA damage. All those lifestyle factors, they all have some exposure that increases that risk for DNA damage. Ultimately, when we understand why cancers develop, it first helps us understand how to treat it, but then also we use it to help us understand how to screen people for cancer, and then ultimately -- hopefully -- a better understanding about how to prevent it. LK: Thanks for listening. This podcast was produced by the Duke University School of Medicine. Music by Blue Dot Sessions. Visit us online at headscratcherspodcast.duke.edu. You can also find us on all your favorite podcast players. Don't forget to hit the subscribe button! And if you like us, leave us a review
Medical Disclaimer & Terms of use at https://bit.ly/2LrjWdh

Addiction expert Nicole Schramm-Sapyta, PhD, discusses signs of addiction, who is most vulnerable, and the best antidote. Dr. Schramm-Sapyta is an associate professor of the practice in the Duke Institute for Brain Sciences and the Department of Psychiatry and Behavioral Science.
Transcript:
Lindsay Key: Welcome to HeadScratchers, a mini-cast from the Duke University School of Medicine. We ask Duke experts to help us understand the questions in science that have us scratching our heads. Today we're speaking with Dr. Nicole Schramm-Sapyta, an expert in addiction.
Dr. Schramm-Sapyta, I'm curious. Coffee, cigarettes, opioids, alcohol, sugar: these are all substances that people consume and struggle with how much to consume. What is the difference between habit and addiction?
Nicole Schramm-Sapyta: A habit is something we do out of convenience. We do it without thinking, and it makes things easier for us, or else we enjoy it. An addiction is something that we do over and over again, despite causing harm to our lives. And that's easy to see with drugs and alcohol; a little bit harder to see with cigarettes although we know the health risks; even harder to see with caffeine and sugar. But the main definition of addiction is that it's causing harm and yet the person is still doing it.
LK: Is it possible for a person to become addicted to a drug after trying it one time?
NS: The short answer to that question is no. Changes in the brain occur with every use of an addictive substance. And those changes in the brain take time to build up to the point of causing an addiction.
So the things that might happen after the first time someone takes a drug are: they have a great time, they might feel better than they've ever felt before -- might feel what other people would call normal for the first time, and really want to keep taking it. But they have to keep taking it before true addiction emerges -- for those changes in the brain to occur that lead to compulsively take the drug over and over despite negative consequences.
What really causes addiction is the combination of repeated taking of the drug with a brain that is otherwise vulnerable to those changes that form the really bad patterns of taking the drug despite negative consequences. People who have psychopathology, particularly depression and anxiety, are much more vulnerable to what we call self-medication. Another vulnerability comes from socio-economic factors, social factors: abuse, trauma in the home, other negative social circumstances that one might want to escape and use the drug to escape from.
The most hopeful thing that I have learned in all of my years of research and getting to know people in recovery is that recovery is absolutely possible. But since it's a bio-psychosocial problem, we have to bring biological and psychological and sociological solutions to the problem.
What has most inspired me about meeting people who are in recovery is the perspective that they have. They've been to the depths, done things that they absolutely regret, you know, stolen from family members just to buy drugs, lied to their family members, and yet they've managed to recover and figure out what really matters to them in life. The main antidote for addiction is a life filled with meaning and purpose. So if I have wonderful family, wonderful job, good friends, good reasons to get up out of bed and not get high every day, I've got an amazing life. And so people in recovery, they know what gives them meaning, and I find that incredibly inspiring.
LK: Thanks for listening. This podcast was produced by the Duke University School of Medicine. Music by Blue Dot Sessions. Visit us online at headscratcherspodcast.duke.edu. You can also find us on all your favorite podcast players. Don't forget to hit the subscribe button -- and if you like us, leave us a review.
Medical Disclaimer & Terms of use at https://bit.ly/2LrjWdh

Infectious disease expert Greg Gray, MD, PhD, FIDSA, discusses why COVID-19 spread so quickly, why it’s so deadly compared to other viruses, and what we should be doing to prevent another pandemic.
Dr. Gray Is an infectious disease epidemiologist, professor of medicine in the Division of Infectious Diseases, and member of the Duke Global Health Institute.
Transcript: Lindsay Key: Welcome to HeadScratchers, a minicast from the Duke University School of Medicine. We ask Duke experts to help us understand the questions in science that have us scratching our heads. Today we're speaking with Dr. Greg Gray, an expert in infectious disease. Dr. Gray, the coronavirus has spread quickly around the globe. What makes this virus so special? Why did it catch us so off guard?
Dr. Gray: Well, this virus is unique in that 100% of people, essentially, are susceptible to infection. And it is highly infectious. And it has a long incubation period. It's a real super challenge, if you will. It's difficult to control. LK: As an infectious disease researcher, is this epidemic that we're experiencing? Is it something that you thought might happen one day or were you really surprised by it? GG: Yeah, I think those of us in infectious disease epidemiology recognize that in the last 25 years, we've had seven or so of these events. This is not the first one. And it's a repetitive issue: we see the emergence of a virus that causes an epidemic in man, we try to understand it, we mitigate it. And we do the best that we can to put out the fire. So what can we do when the next virus surfaces? We need to do a better job. What we need to really be doing is looking at the human-animal interface and monitoring for novel viruses that might emerge from that interface. Looking at people who have close contact with animals and seeing when they have evidence in their respiratory tract of a new virus that's emerged from the animals, and then making preparations way before the virus cycles over and over and becomes highly infectious to man. And we can do that -- and the way to do it is through something called One Health. Working together with human health, veterinary health, environmental health on specific problem areas like these, to get ahead of this, so we're not always responding to the latest threat. Often we've been to that in partnership with the animal industries, animal production industries. You might not know it, but there have been three emerging coronaviruses that really had a big negative impact on the swine industry, they've not affected humans. But we could help, and at the same time we're looking for novel viruses that would have an impact on humans, we could help them get a handle on the viruses that are going to only cause deaths in their animals. We talk about zoonosis as a pathogen that causes disease. And usually we talk about a pathogen that moves from animals to man. But we can also see zoonosis, sometimes called reverse zoonosis, where a pathogen that is normally affecting man moves to the animals. And that's another reason to do One Health -- because understanding zoonosis, we can help not only human health, but animal health and the animal industries. So, Duke has been a great place to do the research we do, because Duke is very forward thinking and we're very connected to the Global Health Institute. And we have studies right now in about 14 countries and many of these studies are looking for zoonosis. Right now we're doing big studies and northern Vietnam. We just wrapped up a study in Yangon, Myanmar. We're wrapping up a study that was conducted in South Africa. And over the last several years, we've done studies in many different places. Yeah, we’ve found some pretty unusual things right now that we're still working them up -- some viruses that shouldn't be in humans, and unless you look for them, you can't easily find them. But we're able with some of the technologies that we've adapted or developed here

Dr. Jeffrey Crawford, MD, George Barth Geller Distinguished Professor and Professor of Medicine, explains the relationship between smoking and lung cancer.
Transcript:
Host: Lindsay Key
Welcome to Headscratchers, a mini-cast from the Duke University School of Medicine. We ask Duke experts to help us understand the questions in science that have us scratching our heads. Today we're speaking with Dr. Jeffrey Crawford, an expert in lung cancer. Dr. Crawford, my aunt lived her entire life without smoking but developed lung cancer. My uncle smoked his whole life and never developed lung cancer. How can that be?
Dr. Crawford
Well, I think in that question is the question is smoking always related to lung cancer, and do all patients who smoke get lung cancer? And the answer to that is no, they don't. But what's important from the uncle's perspective is that smoking is associated with 480,000 deaths per year in the United States, of which about 150,000 are due to lung cancer. So the other major causes of death from smoking, are heart disease. plus a host of other cancers, head and neck cancer, pancreatic cancer, kidney cancer, cervical cancer, colon cancer all have some relationship to smoking, as well as some others. So the point is that if you're an active smoker, you're likely to live 10 years less than if you never smoked. So for the uncle who may not have developed lung cancer, he certainly suffered in some way from his lifelong smoking.
Now, the aunt, on the other hand, falls into a group of never smokers who developed lung cancer. As many as 20% of patients who develop lung cancer never smoked, or had very minimal smoking exposure. And that's probably because there are other causes. We think radon is a cause we think chemical exposure in the workplace, air pollution, all can contribute to lung cancer risk. Second hand smoking is a significant risk. Perhaps 7 or 8,000 people a year die from lung cancer due to secondhand smoke. More than 30,000 people secondhand smoke die from heart disease. So secondhand smoke is a big deal.
Now, the other thing that we've learned from the never smoker population is that they harbor a significant number of genetic mutations that occur in the tumors that may be driving the cancer. That can happen in smokers but more common in the never smoker. We don't know why that occurs. But that's leading us to develop new techniques and new treatments just for those never smokers, we have these we call targetable mutations. That mutation, we can sometimes target with a specific drug that blocks the effect of that mutation on the cancer cell and ultimately destroys the cancer. The smoking/never smoking relationship has helped us really understand that lung cancer comes in many different varieties. There's not one lung cancer, there's one lung cancer for every patient that has it. And personalized medicine is the way to approach that.
Now returning to the uncle one more time, it's never too late to quit smoking. So you never want to start smoking, but it's never too late to quit. If you are under the age of 40, and you quit smoking, you can reduce your risk of dying by 90% from smoking related causes. And that'll decrease over time, but even in people over 70, quitting smoking can reduce the risk of some of these other causes. So if you smoke, stop.
Host: Lindsay Key
Thanks for listening. This podcast was produced by the Duke University School of Medicine. Music by Blue Dot Sessions. Visit us online at headscratcherspodcast.duke.edu, or subscribe on iTunes or SoundCloud. If you like us, leave us a review!
Medical Disclaimer & Terms of use at https://bit.ly/2LrjWdh

Ken Poss, PhD, James B. Duke Distinguished Professor of Cell Biology and Director of the Regeneration Next Initiative, explains how salamanders can regenerate limbs and discusses what implications that has for the future of human limb regeneration.
Transcript

Lindsay Key
Welcome to Headscratchers, a mini-cast from the Duke University School of Medicine. We ask Duke experts to help us understand the questions in science that have us scratching our heads. Today we're speaking with Dr. Ken Poss, an expert in human regeneration. We asked him: Dr. Poss, I've heard about how a salamanders’ limbs can regrow after being amputated. How do they do that? And why can't human limbs do the same thing?
Dr. Poss
When a mammalian species loses an arm? Well, first, there's a lot of bleeding. There's clotting, there's inflammation. And ultimately what happens is, it forms a scar to limit the damage and that limb will form a stump that can be adequate for the rest of that animal's life. Now, salamanders, it's different. After an amputation, there's bleeding. There's clots. There's inflammation -- those first things happen.
But then something special happens, something that's really important for regeneration. And that is the formation of a structure called the blastema. And a blastema is a unique structure in biology, even kind of hard to describe. Many have considered this similar to a tumor. It's a mass of cells that continues to grow, and it forms kind of a ball of proliferative, or dividing, cells. But in many other ways, it's nothing like a tumor, because that blastema has all of the information needed to recreate that limb. A new limb essentially sprouts from the blastema; really fascinating.
We are on our way to understanding how to stimulate something similar in, say, an injured human limb. I think something people may not realize is that we humans are actually really good at regenerating certain things. So while we can't regenerate something like an amputated limb, we can regenerate our blood, our liver; our intestinal lining is continually regenerating. I think humans have the general machinery where it's possible, with the right manipulations -- we will be able to make human limbs regenerate at some point in the next decade, two decades, 50 years. It's going to be very exciting. We really might be able to change things.
Lindsay Key:
Thanks for listening. This podcast was produced by the Duke University School of Medicine music by Blue Dot Sessions. Visit us online at headscratcherspodcast.duke.edu, or subscribe on iTunes or SoundCloud. If you like us, leave us a review.
Medical Disclaimer & Terms of use at https://bit.ly/2LrjWdh