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Legionellosis is a text in two volumes that presents the modern viewpoint of the agent and the disease. It also chronicles the history of the discovery of Legionella pneumophila. Volume 1 discusses current aspects of the microbe including taxonomy, morphology, biochemistry, and physiology. It also discusses the illness including clinical features, pathology, and therapy. Volume II details the laboratory diagnosis, epidemiology, and pathology. The contributors are amongst the most eminent scientists in their respective fields.
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Part I: History of Legionellosis
Chapter 1
Isolation of A New Microbe
An interview conducted with Dr. Joseph McDade, the scientist who isolated Legionella pneumophilla, by Dr. Sheila Moriber Katz January 25, 1983
Dr. Katz: Why did you become a scientist?
Dr. McDade: Because my uncle was paying for my college education and he wouldnât pay for it if I became an English teacher.
Dr. K: Are you pleased about the choice?
Dr. M: Reasonably so. I donât have any basis for comparison. I donât know what it would have been like if I had become an English teacher. Suffice it to say that I have enjoyed what I have done to this point. I have no regrets.
Dr. K: What is your academic background?
Dr. M: I have a Bachelorâs Degree in biology from Western Maryland College and a Masterâs Degree and Ph.D. degree in microbiology at the University of Delaware. I spent a couple of years after graduate school with the Army, assigned to the U.S. Biological Labs at Fort Detrick. Then I spent another year or so working with Microbiological Associates in Bethesda. After that I got back into the general area of research when I took an assignment with the University of Maryland School of Medicine in 1971. As part of that program I spent 4 years out of the country working on a project in the rickettsial field â first in Cairo. Egypt for 2 1/2 years and then for a year and a half in Addis Ababa, Ethiopia. I came to the CDC in 1975, and Iâve been here since.
Dr. K: A versatile background.
Dr. M: Thatâs one of the reasons I havenât regretted being in the field of biology. I canât imagine many English teachers being able to spend 2 years in the Middle East.
Dr. K: How old are you?
Dr. M: Iâll be 43 next month.
Dr. K: Do you have family?
Dr. M: I have a wife and two children. My son, Michael, was bom in Maryland in 1968 and my daughter, Karen, was born in Cairo in 1971.
Dr. K: Would you like your children to become scientists?
Dr. M: I really have no strong feeling one way or the other, as long as they do what they enjoy.
Dr. K: Along those lines, how do you assess the future of medical research is in this country?
Dr. M: Well, itâs directly related to funding, of course. We go through cycles, a sort of sine curve related to the budget. Generally speaking, I think the prognosis will be good. The question is which particular areas will be emphasized as time goes on.
Dr. K: Do you see any particular direction in medical research?
Dr. M: Obviously, genetic engineering is the most prominent wave of the future. I also look for an amalgamation of immunology, embryology, neurology, and endocrinology. All of them are currently dealing with receptors, and 1 would expect that these four areas would come together rather nicely in in the next 20 years.
Dr. K: Currently, what are your own scientific interests?
Dr. M: I have always maintained an interest in the Rickettsiae and in applied applications pertinent to public health. Annually, we have tens or perhaps even hundreds of thousands of undiagnosed cases of rickettsial illness throughout the world, all of which could be treated effectively with antibiotics were there good and reliable techniques for early diagnosis. I think that if I did nothing more in my entire time here than to develop a reliable method for early diagnosis of these diseases, then I will have made a contribution. This is where I intend to put most of my effort.
Dr. K: What exactly are you working on now?
Dr. M: Weâre developing monoclonal antibodies for various spotted fever group Rickettsiae. Our overall game plan is to try to see whether or not we can develop a serologic reagent which will detect antigens in infected animals, either in body excretions, urine for example, or in other body fluids, early enough on to allow for early diagnosis. This is one area of our research. Other people in our laboratory are interested in doing restriction endonuclease analyses of various Rickettsia for a variety of reasons. Understanding some of the differences between the virulent and avirulent forms of the organisms is one possible application of the DNA work. Of course there are other applications, epidemiologic and so on.
Dr. K: What are your hobbies?
Dr. M: I donât have time for hobbies. At least I donât seem to. I shouldnât get into my family situation, but with childrensâ activities and a working wife thereâs really not a whole lot of time left over for much else other than simple things like jogging or working out on the NautilusTM or puttering around the house.
Dr. K: Letâs go back in time. Do you remember what you were doing on July 4, 1976?
Dr. M: Not specifically, but if the Braves were in town I was probably at the baseball game, which is a hobby of sorts.
Dr.K: Where were you and what were you doing when you first read about Legionnairesâ disease?
Dr. M: I donât know that I ever really much read about it. I had only been back in the country for about 9 months and I was still out of the habit of watching television and reading newspapers, so most of what I heard about Legionnairesâ disease was at work.
Dr. K: What were your initial thoughts, though, when your first heard about it from your colleagues?
Dr. M: I assumed it was a viral infection of one sort or another. Flu came first to mind. Seemed a little severe for flu, but it was probably the first thing that I was thinking of.
Dr. K: What else?
Dr. M: You know, I really didnât think about it much beyond that. Iâm not a physician, so my expertise outside of the rickettsial field is really kind of limited. Other than influenza or psitticosis nothing else really came to my mind.
Dr. K: Did you think youâd be investigating it?
Dr. M: I didnât think Iâd be involved at all.
Dr. K: When did you first start investigating?
Dr. M: I canât remember exactly, but I think it was the early or middle part of August of 1976, which was probably the first or second week after the outbreak was finally reported. Having only been here about 8 or 9 months, I really wasnât aware of how the CDC, as an organization, dealt with an epidemic investigation. I had no idea how many people or which people would be selectively pressed into service. But it didnât take very long to figure out that since the disease was a pneumonia, one of the things that had to be ruled out was Q fever. I didnât think it was Q fever, though. I thought it was psitticosis or flu.
Dr. K: Why did you think it couldnât be Q fever?
Dr. M: Fatality rate for one. It seemed to me to be a bit severe for Q fever, although certainly this was within the realm of possibilities.
Dr. K: What approaches did you initially take to investigate it?
Dr. M: Well, we looked at it from two points of view. What they had asked me to do was look for serologic evidence of rickettsial antibodies in convalescent sera and to try to isolate any rickettsial agents. We did this simultaneously. We took lung tissue from three patients and inoculated them into guinea pigs in an attempt to try to isolate any Rickettsia that were present. It became a bit complicated after that.
Dr. K: Did the guinea pigs initially become ill?
Dr. M: Yes. There was no question about it. The problem was that they developed fevers 2 or 3 days after we inoculated them. I concluded, of course, that it wasnât Q fever because Q fever has a much longer incubation period. So we did a number of things from there to try to sort out what was causing the fevers. My first guess was that it was bacterial contamination, although guinea pigs ususally donât respond too much to bacterial insult. So we werenât quite sure what it was. We did a number of things. We passaged the spleens of some of the guinea pigs into other guinea pigs to see if we could find some sort of continuing fever pattern, but it didnât really develop in the second set of animals. A couple of them developed transient fevers but none of them became as ill as the original set. And when we subcultured from the second set of guinea pigs, none of the next group developed fevers at all. Of course we saved serum specimens from all of the guinea pigs to see if we could find antibodies to any rickettsial agents in the guinea pigs that were inoculated. We also took some of the guinea pig tissues and made smears of them and stained them by a variety of techniques to look for organisms. We also looked at a lot of different smears, as I recollect, but the only thing we consistently saw were Gram-positive cocci in the lungs. We also saw rare rod-shaped organisms in the liver and the spleen. We attempted to culture organisms from the ill guinea pigs by inoculating their tissues onto a variety of bacteriologic media. Nothing grew except some strep, which we considered contaminants. Then the last thing that we did was inoculate the guinea pig tissue into embryonated eggs containing penicillin streptomicin mixture to try to isolate Rickettsiae. Those attempts turned out to be negative; in retrospect of course, pen-strep knocked out what was there, I mean the Legionella. At that point, I didnât know what to make of it. At that time there was the theory that a toxic substance, nickel carbonyl or something like that, was present in the animals. My results were not inconsistent with a toxic substance. I was certainly willing to accept that theory: I surmised that what we were seeing in the guinea pigs was an initial toxic reaction to the lung tissue that couldnât be passed from animal to animal. I was satisfied with that.
Dr. K: How long did you work on the project?
Dr. M: Roughly, the first part of August through the middle of September. But some serums didnât filter in until a month later, and we did most of the virologic testing in one fell swoop. Probably in late September or the first part of October.
Dr. K: And then you went back to it in November?
Dr. M: No, not until December. It was after Christmas, probably the Monday after Christmas. There had been a couple of things that nagged me over a period of time. Many people have asked me, âWhy do you go back and look at it again when you had left it alone?â I donât know that there is any real answer to that â probably two things, one is that the toxic theory had gone down the tube by that time. The second thing was that even though I had only seen a rare rod in the tissue specimens I was surprised that the rod didnât show up on bacteriologic media. I didnât think too much about it at first. But as time passed I was determined to be able to get that rod to grow up so I could show what it was and rule it out as a possible cause.
Dr. K: In December, what did you do that was different?
Dr. M: Only one thing. The second time I used eggs without antibiotics, because at this point I was no longer interested in trying to cultivate only Rickettsia. I wanted to see everything that was there. I was looking for my so-called âcontaminantââ. Actually, that âcontaminantâ turned out to be very nearly a pure culture. Virtually all we got out of the tissues were Legionella. By eliminating the penicillin and streptomicin from the mixture we were not just looking for Rickettsiae, we were looking for anything, including bacteria, and thatâs just what we got.
Dr. K: At first, did you doubt your findings?
Dr. M: Oh sure. No question about it. By this point, I was certainly aware of the notoriety that it was getting. I was very reluctant to accept any of my own data. As a matter of fact, when we started doing serologies with patientâ sera, I made sure they were tested in a double- blinded manner. We had independent readers look at the serologies to make sure that we were in no way being biased, and then we decoded everything at the end. In fact, those of us in the lab would have liked many more weeks to work to verify our preliminary findings. But the disease of course, was of public health significance. At that point, we also didnât have the slightest idea how dangerous it was or what its potential was for spread, and so as soon as it became reasonably clear that we had a potential agent, we announced our findings. Obviously, a person is very conservative about these things and would like as much time as he can to be absolutely 100% sure. As time went on our confidence level increased and we became certain that we did, in fact, have the agent.
Dr. K: How did it feel to discover the new microbe? A rather trite question.
Dr. M: Well, I donât know that it is. Iâve only appreciated it in retrospect and my retrospect keeps changing. At the time we were so busy and so caught up in it. We had no time to see the impact. We had no idea whatsoever how important it was: whether or not it was the cause of hundreds of cases, thousands, tens of thousands, whether or not there were other species, and so on. Now...
Table of contents
- Cover
- Title Page
- Copyright Page
- Preface
- The Editor
- Contributors
- Acknowledgement
- Contents
- Part I. History of Legionellosis
- Part II: The Microbe
- Part III: The Illness
- Index