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.
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?
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.
What types of factors go into the immune system’s decision to respond or not?
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.
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.
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
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.
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?
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!
Rich O’Brien, MD, PhD, the Disque D. Deane University Professor of Neurology and chair of the Department of Neurology, is an expert in memory disorders. He discusses why a person might be able to recall a retirement party they attended thirty years ago, but not what they had for lunch that day.
Welcome to head scratchers, a mini cast from the Duke University School of Medicine. We asked Duke experts to help us understand the questions in science that have us scratching our heads. Today we're speaking with Dr. Rich O'Brien, an expert in memory disorders. We asked Dr. O’Brien, my mother has dementia. She can remember her retirement party 30 years ago, but now what she had for lunch today. Why is that?
Dr. Richard O'Brien
What you're essentially asking me is the difference between short term and long term memories. Short and long term memories are stored in different parts of the brain. Short term memories are dependent on the hippocampus. For a short term memory to become consolidated takes about a week. Once that week has passed, you can remove the hippocampus and the memory will stay there forever.
What memory is, is a reenactment of the actual event by the parts of the brain that processed it initially. So when you recall a memory you essentially re-process and go through the event again, just like you initially experienced it. Your mother's retirement party 30 years ago is a series of sounds that she remembers, visions that she remembers, and emotions. Because it was a highly emotional event she is far more likely to retain that memory, just like most of us have very strong memories of September 11th. What she had for lunch today might have been incredibly dull, something she has quite frequently, and she might have been distracted while she was eating it. And for all those reasons, she might not remember what she had for lunch and have absolutely nothing wrong with her.
However, if her husband is concerned that she can't remember what she had for lunch or dinner, can't remember her keys, seems to get lost when she's out of the house, and keeps asking the same question over and over, like, “When is it time for lunch?” even though she's just eaten lunch, then it could be because she has a memory disorder. The rule we use in clinic is that if you're worried about your memory, there's nothing wrong. If someone else is worried about your memory, that's a big problem.
Thanks for listening. This podcast was produced by the Duke University School of Medicine. Visit us online at headscratcherspodcast.duke.edu
Sana Mustapha Al-Khatib, MD, is an expert in sudden cardiac death. She discusses how – and why—an otherwise healthy young person can die suddenly of sudden cardiac death and the difference between the terms “sudden cardiac death” and “heart attack.” Dr. Al-Khatib is a professor of medicine in the Duke University School of Medicine.
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 scratching our heads. Today we're speaking with Dr. Sana Al-Khatib, an expert in sudden cardiac death. Dr. Al-Khatib, occasionally we hear reports on the news about a young, otherwise healthy person dying of sudden cardiac death. How and why does that happen?
So why would someone in their 20’s die suddenly? There are different heart conditions that could lead to that outcome, the most common of which is hypertrophic cardiomyopathy. Hypertrophic means enlarged; cardiomyopathy is an abnormal cardiac condition. With hypertrophic cardiomyopathy, the heart muscle itself is thicker than normal, and the tissue itself is not normal, meaning the muscle fibers are not sitting in an organized manner. They actually are in complete disarray. They have a scar tissue. And once you have scar tissue in the heart, that certainly increases someone's risk of going into a life threatening abnormal rhythm that is really fast in the bottom chamber -- and when the bottom chambers go really fast -- we're talking 200, 250, 300 beats per minute -- that can actually stop the heart.
Hypertrophic cardiomyopathy itself, it's an inherited condition. People have an abnormal gene, and that's what leads to hypertrophic cardiomyopathy. But it is important to keep in mind that there are other conditions that can lead to thickening of the heart muscle in this age group. We call them cardiac channelopathies. That's when they have abnormal genes, where because of the abnormal channels, their heart goes into life threatening arrhythmias that could go really fast that could stop the heart as well.
An important thing to note is that sudden cardiac death is different from a heart attack. From talking to a lot of my patients, they seem to confuse the two. A heart attack is when you don't have blood flow, either adequate blood flow or no blood flow at all, to a certain area in the heart, because of a blockage in one of the arteries to the heart muscle. Now, of course, that can also lead to a life threatening rhythm that can lead to sudden cardiac death, but not every sudden cardiac death is due to a heart attack.
So in this younger age group, people may wonder how can they prevent the risk of sudden cardiac death? How can they be aware that they are at an increased risk to start with. And that's where people really have to pay attention to two main things. Number one is family history of sudden cardiac death. The other thing is symptoms, you know, we talked about sudden cardiac death, that it is a condition that occurs in people who don't have symptoms. We actually have numerous studies now showing that actually some of these people have symptoms, but they just ignore these symptoms.
I don't want to scare people because you know, some of these symptoms can be pretty broad. But, if people are having passing out spells or feeling like they're going to pass out or, you know, palpitations leading to dizziness, lightheadedness, things like that, I think it is important to, to seek medical attention and get that worked up, just to make sure that they're okay. Most patients are going to check out fine, they're going to be reassured that their, their heart is normal. But if people don't do that, then we miss the few people who are at an increased risk for sudden cardiac death.
Thanks for listening. This podcast was produced by the Duke University School of Medicine.
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Vaccine development expert Dr. Tony Moody explains why creating a universal flu vaccine—which protects against all strains of the virus—is so difficult, and how researchers at Duke are addressing this challenge. Dr. Moody is an associate professor in the Department of Pediatrics, Division of Infectious Diseases, and the Department of Immunology at Duke University School of Medicine. He is director of the Laboratory of B cell Immunotechnology at the Duke Human Vaccine Institute.
Music: HipJazz by Bensound
Welcome to Head Scratchers, 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. Tony Moody, an expert in vaccine development.
Dr. Moody, I get a flu vaccine every year, but I hear it only protects me from certain strains of the flu. Why is that? Why isn't there a vaccine that can protect me from all of the strains?
To make a flu vaccine, it really means you're trying to predict the future. The flu vaccine that's currently given has three or four strains. We're having to make a guess as to whether or not those strains are going to be the ones that are circulating at the time when winter comes around and people start to get sick. Given that it takes six months or more to make the vaccine,
t’s actually being done constantly, because there's a vaccine made for the Northern Hemisphere, and for the Southern Hemisphere. We have to make a new vaccine essentially every six months because of the way flu changes.
Over time, it mutates slowly. And so you actually wind up with viruses that are resistant to the immune response that already is present in the population.
So one of the things that people would like to be able to do is to make what's called a universal flu vaccine, that is, a single vaccination that would protect you against all of the various strains of influenza. The problem is that influenza is quite variable. And to make a universal vaccine, you either have to have a vaccine that will attack each strain, or something that will attack all the strains at the same time. The diversity of the virus makes it really hard to get one thing that will cover all of the different strains. Even if we get something today, it may very well turn out that tomorrow it's no longer effective, because the virus has learned how to get around it.
And then there's also the problem of not knowing which new strains might jump into the population. And we want to try to protect against those as well. So some of what we're trying to do is to break the problem down. I mean, the truth is if we could make a vaccine that actually cuts down on symptoms, or cuts down on people shedding the virus and giving it to other people, that's still a big win for influenza vaccines, because it would cut down on the number of people who get sick.
So yes, the perfect goal would be a universal vaccine that would prevent all disease in all people. But even if we can't get that, we can do better hopefully than, than what we've got now. And we could still have an impact on public health.
Thanks for listening. This podcast was produced by the Duke University School of Medicine. Music by Ben sound.
Visit us online at headscratcherspodcast.duke.edu