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(1 of 4) Our introductory conversation with Dr. Steve Kornguth, biochemist and translational medical researcher who teaches in the Department of Kinesiology and Health Education. He shares an insider’s view into the sense-making process through which physicians categorize, diagnose and treat illness. Using autoimmune disorders as a special focus, Dr. Kornguth presents a perspective of disease as a compromise in function due to an interaction between external threats and internal vulnerability factors. Like the students in his small format undergraduate course, listeners will enjoy learning from Dr. Kornguth’s sixty years of experience.

Learn more

Professor Kornguth's KHE faculty page
More about Paul de Kruif
More about Ignaz Semmelweis
Daily Texan article on Dr. Kornguth's CTE research


Transcript

KAREN FRENCH: Welcome to Learning from Texas Education Innovators, a podcast series hosted by the Office of Instructional Innovation in the College of Education at The University of Texas at Austin. Our group supports faculty and student instructors in the College, particularly through the use of technology enhanced teaching. I’m Dr. Karen French, the Associate Director of OII. My role in these discussions is to ask the questions from our professor-colleagues that may uncover a bit more about what they have to teach us through their research and classroom teaching. The folks here have fascinating stories to tell. Each time I visit with them, I learn something new. I hope you will join us and do the same.

We plan for our discussions to last twenty to twenty-five minutes - about as long as it takes to walk across the forty acres of the UT campus at a brisk walk. When there is more to say, we have tried to divide the topics into chunks. Our first guest, whose distinguished career as a medical researcher and teacher spans more than half a century had a great deal to share. I have to admit I also enjoy visiting with him - he tells a great story. So, our series begins with four chats Dr. Steven Kornguth, Senior Research Fellow in the Department of Kinesiology and Health Education who teaches a wonderful undergraduate course that uses autoimmune diseases as a window for understanding medicine. In addition to his role in the college of education, Steve is a Professor of Neurology in the Dell Medical School. Before coming to UT Austin, he was a professor of Neurology and Biomolecular Chemistry at the University of Wisconsin from 1962 to 1998. There, he researched neural development, autoimmune diseases and the development of binding agents for MRI contrast materials. When he came to UT Austin, he led federally funded research in biological defense and explored the impacts of sleep deprivation on decision making in soldiers and athletes. His current research focuses chronic traumatic encephalopathy - also known as CTE - degenerative brain disease found in athletes, veterans, and others with a history of repetitive brain trauma.

In our first podcast, Steve and I talk about his sixty year career in translational research and his novel - or at least new to me - conceptualization of wellness based on a deep understanding of medicine and autoimmune disease. In later podcasts, we explore some of the specific topics in his research expertise: including paraneoplastic syndromes, CTE, and multiple sclerosis. But for now, let’s begin with my good friend, Dr. Steven Kornguth

The topic of today's discussion is: “Turning the biological system of defense (the immune system) into an attack system: how disequilibrium creates illness”. Why would you choose a title like that?

Steven Kornguth: Yes, because it describes, essentially, the basic principles of autoimmune disease. The immune system, as you know, we think is a protective system evolved in animals to protect us against bacteria, fungi, things of this sort, autoimmune disease is essentially the turning of this intrinsic defense system into an attack system that can cause illness in the patient as well as protect us against these external agents be they trauma or infection or cancer even.

Karen: Do you want to talk about the central themes of the course?

Steve: The major discussion elements today, they'll be four of them. The first of these is sense-making, and we'll talk about what that means in a minute. The second is disease because we're talking about clinical issues, the third is disease emergence and the fourth is autoimmune disease. So what do we mean by sensemaking in a clinical sense?

Autoimmune disease so what do we mean by sense making in a clinical sense as the patient walks into the physician is typically not one very specific problem that the patient is facing; there a different difficulties aches pains difficulties in body function that the patient is going to describe the position. That physician has to then aggregate those different signs and symptoms reported by the patient into a common theme with a diagnosed illness. So what do we mean by illness? The second point of the discussion.. and so an illness is a compromised function of the patient in the patient's mind as well as in a management mind -the boss of the patient - what is expected of that patient of that individual in his or her work and what is she or he expect themselves and how does clinical state with very specific signs and symptoms compromise the function that is expected of them. The third is what is disease emergence due to? It is due to the the interaction between an individual and the vulnerability of that individual to external stressors in the environment so the external stressors in the environment can be a bang on the head it can be an infection infectious agent virus bacteria fungus it can be cancer and internal cell which is replicating rapidly and taking advantage of the body system to finally compromise that patient’s wellness and it can include various drug abuse or drug overdoses and fatigue all of these interacting together are external stressors on the ability of the body to function. There are external factors and internal factors. The internal factors are the vulnerability factors of the patient. These include genetic vulnerability factors of the patient these include genetics of the person’s prior medical history, infections and the nutritional state of that person. The interaction between these vulnerabilities inherent in the person and the external stressors are what gives us the disease emergence. And finally then what is autoimmune disease? Autoimmune disease is disease which is caused by the immune system. This protective system which is intrinsic to the patient and the molecules involved in initiating the autoimmune disease are typically proteins in the body, carbohydrates in the body, fats - that is, lipids, and nucleic acids so these are the four topics that we’ll be considering: sensemaking, disease emergence (from disease), and autoimmune diseases.

Karen: With these themes in mind, when we first met I learned that you were teaching an undergraduate signature course at UT Austin the name of the course was Autoimmune Disease as a Window into Medical Principles. Why did you choose to teach this as an undergraduate signature course?

Steve: Fascinating. So, as you probably know, these diseases typically affect people between the age of 15 and 40 they are very heavily are biased most of the time to occur in women with a ratio of 2 to 1 women to men all the way to 9 or 10 to 1 in favor of women to men so the age group of the population is the age group of our students we have half of the school or women and the other half depends upon interacting with women to generate knowledge learning family structures and everything of this sort so this is exactly a wonderful window and wonderful topic that should be of concern to students as well as the faculty who are involved in the course.

Is there something specific about it being a signature course that attracted you…?

Steve: Yes it is. So a signature course is comprised of one of two kinds of structures, typically a small group of 18 to 20 students from all colleges on the University of Texas campus or two hundred or so students. The thing that interested me is we can bring together students from engineering from Liberal Arts from education from the physical sciences and biological sciences all of whom should have an interest in their own wellness and health and how does the world around them impact that wellness so for an introductory course to the University of Texas Austin this is an ideal sort of subject wellness, health, external stressors, and so forth.

Karen: So you have been in the field of medicine for…

Steve: Sixty years.

Karen: What got you here?

Steve: How did I get interested in...

Karen: How’d ya get here?

Steve: ok…

How did I get interested in medicine? So when I was 12 there was this fascinating book that I loved. Was called Microbe Hunters by Paul de Kruif I think that was written in the thirties a lot of my colleagues and cohorts of my age became interested in medicine because of this book. It gave stories on such notables as Semmelweis, a Hungarian physician who understood the role of infectious disease in caring for patients and his discovery or insight had to do with puerile fever, an infectious disorder which affected pregnant women. And there were women in one wing or one corridor and these groups were separated by a hall, and the women in the first corridor were adjacent to the post mortem room; the women opposite were not. The women who had just given birth or were in the process of birth and were adjacent to the post-mortem room came down with high mortality rate and the women in the distant ward or corridor had exceedingly low mortality, and Semmelweis concluded that the physicians who were examining the cadavers from the post-mortem room were transmitting the disease to the women adjacent to that room and that became the issue of washing of the hands extensively. He was a young professor and the pattern of behavior of the more senior people was to discount the younger professors’ recommendation to wash their hands extensively. Led to disaster in Semmelweis’s life, but it was catastrophic for the women who were affected. His recommendations and almost demands of washing the hands led to his non continuance for a while in the school. But as we know now we go through this same need to wash hands. Of very great attention to sanitary procedures not only for physicians working with cadavers, but if you're going from one patient to another as a means of controlling nosocomial infections - infections acquired in the hospital - and that came out of Semmelweis’s work and that was magnificent stimulation to me as a young kid to do something in medicine that will benefit patients’ lives.

Other little stories in that book included the the story of Pasteur and a variety of other scientists and I thought, “What a great thing to look forward to in the future.” That’s how l I got interested in medicine.

Karen: When you were 12.

Steve: 12, yes.

Karen: So, from 12 where did you go?

Steve: Well, I got older. And… as I got older, I went to a wonderful high school, which was very heavily oriented toward sciences, it was called Stuyvesant High School in New York. I was son of immigrants so the going to a good school that gave you possibilities of an education was of a very high priority to both myself and my parents. Then I went to college at Columbia University and studied chemistry and biology and philosophy. Finishing Columbia, I asked my professor, “Well do you know where I should go for doing research - I wanted to get a PhD biochemistry world-” and he said, “well, yeah, how about University of Wisconsin?” And there was a fellow there called Mark Stahmann and Mark was a very excellent mentor to me, and he was working on the question of how would you take a protein that normally occurs in a person and make that generate antibodies against itself when injected into the same animal that that protein came from. And that was the beginning - in my mind - of how does autoimmune disease occur.

Karen: So that’s where you started with autoimmune disease, what kept you with autoimmune disease? It’s been, what, 50 years. {Sixty} Sixty years.

Steve: Yes, so. So what kept me in autoimmune disease there is such a variety of topics that accompanies autoimmune disease. So you have got multiple sclerosis - and we'll discuss that in a bit - you have got systemic lupus erythematosus. Both of these disorders affect the central nervous system, and what got me interested in the topic in the first place other than the challenge how could you take a protein in an animal and make the animal itself believe it's a foreign protein - that would initiate the production of antibodies to this protein. Well, in order for that to make any sense, there has to be a memory element involved. That is, a body has to recognize meaning… know self from non-self or have have a way of coding for that system. At that time the whole question of how does memory occur was explained by Leo Szilard. He was a Hungarian scientist, again a refugee, came to the United States around the second World War, and his notion was one nerve cell recognizes another nerve cell in the body to make a synapse (this is the communication system of the brain) in the same way an antibody recognizes an antigen. So when we were looking at how could you make a self protein initiate an antibody against itself, this would be an analogous potentially - this goes back to the 1950s - how does one nerve cell recognize another by an immune system? So classifying and clarifying that process of immune specificity, I thought at the time would give us insight into memory coding. We don't have that insight yet but that was the direction that kept me excited about the field.

Karen: So thinking this and the work that you have done, it's translational medicine is it not? {It is, totally} How do we translate this course, this work, into the things that people can use for everyday life?

The goal that you had for this course was things that the students could use for their lives... how do we use this in everyday life? how do we translate this?

Steve: So if you think of autoimmune disease… Typically, the disease has two phases. One is a worsening of signs or symptoms called exacerbation and the other is the lessening of the compromised function called remission, and the disease indicates this waving or oscillatory pattern. How then, does the patient accommodate these changes in wellness - and this is true not only for autoimmune disease - but we all go through phases where we are more able to deal with the stresses of the environment externally, and less able to deal with that. In terms of the interaction between the patient and the doctor... the doctor is looking to get all of the symptoms that make sense to him to classify what works for that patient which drugs are useful; which treatments are useful; but the patient is not only a patient interacting with a doctor ; the patient is in fact interacting with different communities around them, and as they are learning to accommodate their function to the needs of the community around in the family the employer and so on... The knowledge that the physician is going to communicate to them, enabling function is one element.

The second is that you have got treatments today based totally on immune protection... so we've been talking about the immune system to help protect from viruses and bacteria and fungi. There is a new emerging technology for cancer treatment where the cancer cell comes from the self - from the individual - and in the same way as you can make a self protein initiate antibodies in a host against itself, the hope is we can make the cancer cell that's in the body initiate high production of antibodies to that cancer cell so that the patient is protected from the malignancy and from the further development of the tumor. That technology is called checkpoint inhibition. We have excellent capabilities at The University of Texas in many people, but particularly, two: George Giorgiou in Engineering, and Brent Iverson, in the Natural Sciences, who have developed technologies to increase the affinity of binding of antibodies to targets, and with these high bindings they proved you can protect people against anthrax.

Is this relevant at all to cancer treatment? Absolutely! In the same way that they selected for the antibodies that could wipe out the anthrax threat, the same kinds of antibodies can be used to attack cancer cells, and this is now being explored in various laboratories around the world. So this is how knowledge of the autoimmune system as a window into medical principles is translatable in social interaction and in medical treatments of individuals as well.

Karen: Can you help me understand how you... understand... wellness?

Steve: So if you take a young person who has no clinical signs or symptoms that is compromising their function, we all know that you can have a range of functional capabilities which depending upon how much sleep you're getting, how much exercise you've done, what you're eating habits are, you're either at a very high state of readiness, or a lower state of readiness. When challenged, if you are within a boundary that you are meeting your expectations of what you can do and you're not exceeding that stress beyond it, we call that healthy. Why? Because you are perceiving yourself as completely well, you're invulnerable. You're doing everything you’re expecting to do, you are doing everything your parents and your classmates, and your physician and your community employer expect you to do. You all well. There's no challenge to that. At some point this stress, or when combined with other stresses, fatigue with now a viral attack will compromise that function, and you are not able to do the activities you believe you could do and you've been trained to do. As you cannot do that, that now is going to be called a problem... a dysfunction, and if there are a set of symptoms associated with that inability to perform what you believe you should, do we call that a disease. And so the disease is not an absolute; it's an inability to function within a band of expected functions the tasks you believe you have to do and everybody around you depends you to do. So this is a range of functions but it's not an inability to perform as you believe you have to. If… does that make sense?

Karen: It does. It makes good sense, and I think that’s a good understanding of the concept. {Good} I think that’s a different one than I had before.