Partial Transcript: Could you start off maybe by telling us a little bit about where you grew up and your early family life?
Segment Synopsis: Ms. Kennedy shares her education and background that led her to her first laboratory job, and how she became a guest researcher in Steve McDougal’s laboratory.
Keywords: A. Ragab; activist; B. Jones; City Commission; D. Gordon; J. S. McDougal; Rome, Georgia; science teacher; women
Subjects: Arthritis Foundation; CDC; Centers for Disease Control and Prevention; Egleston Children’s Hospital; Eli Lilly and Company; Grady Memorial Hospital; leukemia; Medical College of Georgia; Oxford College of Emory University
Partial Transcript: Tell us a little bit, expand little bit; you said you were a guest researcher working for the Arthritis Foundation. If you could expand a little bit about that, and maybe tell us a little bit how that fit into Steve McDougal’s lab.
Segment Synopsis: Ms. Kennedy explains her position as a guest researcher in the lab at CDC and the antibody testing standardization McDougal’s lab created. Kennedy describes what it was like to work in the laboratories 30 years ago.
Keywords: antibody testing; B. Evatt; commercial tests; D. Gordon; Division of Host Factors; DOS [Microsoft Disk Operating System]; E. Tan; ELISA [enzyme-linked immunosorbent assay] assays; F. McDuffie; Immunology Branch; mainframe computer; rheumatologist; S. Isoke; standardized reference sera
Subjects: Arthritis Foundation; CDC
Partial Transcript: You’re arriving three months before the first MMWR and just beginning to do this work on developing standards for rheumatological disease testing. It’s not soon after that, that things start to percolate in terms of these unusual cases popping up.
Segment Synopsis: Ms. Kennedy describes how the lab at CDC used state of the art technology to do antibody testing on some of the earliest cases of AIDS and how they were able to see these cases had very low numbers of T-helper cells.
Keywords: animals; antibodies; B. Jones; blocking; C. Dawson; CD4 cell; CD8 cell; D. Cross; FACS; first samples; flow cytometer; fluorescent-activated cell sorter; immune system; J. Carter; J. McDougal; J. Nicholson; Los Angeles; lymphocytes; New York City; reporters; S. Orloff; susceptible; T-helper cells
Subjects: AJC; anti-HIV antibody; Atlanta Journal Constitution; CDC; glycoprotein; gp120; HIV; human immunodeficiency virus; immunoprecipitation; leukemia; Science; Western blot
Partial Transcript: What I’d like to talk a little bit about what you said was your particular area of specialty expertise, the Western blot.
Segment Synopsis: Ms. Kennedy provides details regarding the evolution of testing for AIDS, beginning with the subjectivity of the Western blot.
Keywords: 1978; accuracy; B. Evatt; C. Schable; CDC employee; coagulation disorders; commercial blot; death sentence; diagnosis; disrupted virus; E. M. Southern; electrophoresis technique; ELISA assay; end-stage AIDS; epidemiological study; first positive; French isolate; G. Schochetman; hemophiliac samples; immunology group; J. McDougal; LAV; Lymphadenopathy virus; proteins; R. George; rapid tests; RNA; S. Browning; serial samples; state health departments; T cells; trans-blot; V. Tsang; virologist; Western blot
Subjects: CDC; Institut Pasteur; National Institutes of Health; NIH
Partial Transcript: Speaking of state health departments, your work examining hundreds, thousands of these specimens and figuring out ultimately through diagnostic criteria to call a blot positive or not, then wasn’t it the next step to push out this testing to state public health laboratories?
Segment Synopsis: Ms. Kennedy explains how she along with the help of CDC’s Division of Training taught classes on confirmation tests to state health departments, and some of the challenges to that training.
Keywords: 1985; 1987; classes; commercial kits; Division of Training; ELISA; K. Handcock; M. Wilson; S. Whaley; training lab; V. Tsang
Partial Transcript: I think you mentioned an astounding observation that the vast majority of these persons with hemophilia ended up acquiring HIV infection. That was because—
Segment Synopsis: Ms. Kennedy explains how AIDS could spread so quickly to hemophiliac patients who used concentrated cryoprecipitate and how Steve McDougal figured out a way to make the concentrate safer.
Keywords: AIDS epidemic; B. Evatt; clotting factor; concentrate; cryoprecipitate; exposure; Factor VIII; hemophiliacs; J. S. McDougal; Seattle, Washington
Subjects: Alpha Therapeutic Corporation; Canada; Cutter Laboratories; Puget Sound Blood Center
Partial Transcript: You did some of the work that looked at ways to inactivate the virus with household bleach?
Segment Synopsis: Ms. Kennedy shares how her lab was able to inactivate the virus by using bleach and explains "The Killer Tomato Project".
Keywords: 10% bleach; alcohol; bleach; blood; capture assay; dilutions; disinfecting; fruits and vegetables; H. Jaffe; infect; inject; J. McDougal; kill; L. Martin; log reduction; no-win situation; pH study; quantitate virus; S. Isoke; S. Orloff; T. Spira; tomatoes; unexplained lymphadenopathy patients; W. Roper
Subjects: CDC; FDA; Food and Drug Administration
Partial Transcript: It strikes me now that this must have just been a tremendous volume of work for a relatively small number of people.
Segment Synopsis: Ms. Kennedy shares her experiences and stories of the camaraderie in Steve McDougal’s lab.
Keywords: 70%; A. Mawle; aerosol; airborne; all women; antiretroviral; busy; camaraderie; cell cultures; controlled environment; D. Cross; every six months; exposure; fun; growth; iceberg; in-house; infected; J. Jason; J. McDougal; J. Nicholson; L. Martin; live virus; medical technologist; nickname; positive; pregnant; samples; self-monitoring; Serum Bank; T. Spira; testing; three-times-a-day gatherings; urgent; virology; weekend work; worry
Partial Transcript: Just a few questions in closing, before we wrap this up.
Segment Synopsis: Ms. Kennedy expresses her desire to have seen more awareness or education of the epidemic earlier but believes in general, all of CDC was doing what it could..
Keywords: administration; awareness; biological safety cabinets; education; gay men; hybridoma lab; laboratory; M. Bird; M. Hubbard; moving fast; retired; S. Isoke; S. McDougal; small group; stopped
Subjects: AIDS; CDC; The Arthritis Foundation
CHAMBERLAND: This is Dr. Mary Chamberland, and I am here with [M.] Susan Kennedyat the Centers for Disease Control and Prevention [CDC] in Atlanta, Georgia. Today is Monday, July 10, 2017. I'm interviewing Ms. Kennedy as part of the oral history project, The Early Years of AIDS [acquired immunodeficiency syndrome]: CDC's Response to a Historic Epidemic. Susan, welcome to the project. Do I have your permission to interview you and to record this interview?
KENNEDY: Yes, you do.
CHAMBERLAND: Susan, your career as a CDC laboratorian spans some three decades.It began only three months before the June 1981 publication of the first MMWR [Morbidity and Mortality Weekly Report] report on Pneumocystis carinii pneumonia among homosexual men. Your work, and that of your colleagues under the leadership of the late Dr. [J.] Steven McDougal, resulted in some of the early seminal discoveries and publications about the human immunodeficiency virus or HIV. However, before we talk about your CDC work, let's talk a little bit about 1:00your background. Could you start off maybe by telling us a little bit about where you grew up and your early family life?
KENNEDY: I grew up in Rome, Georgia, which is about 70 miles northwest ofAtlanta. I have two older brothers and a younger sister. My father worked in a hardware store, and my mother had various part-time jobs when we were little. She later ran for the school board in Rome and then decided to run for the City Commission. She was the first and the only woman during her time to be elected to the City Commission in Rome.
CHAMBERLAND: A real pioneer.
KENNEDY: Yes. She was a real activist.
CHAMBERLAND: Interesting. With all of that influence, in terms of decisionsabout going on for college education and all of that, where did you go? Where 2:00did you study?
KENNEDY: My science teacher, I think when I was a senior, showed us a movie, andit was about various professions in health, and some of the allied health professions were highlighted in this. One of the things that was in the movie was medical technology. I just got really interested in that, and I decided that's what I was going to do. I started at Oxford College, which is part of Emory [University], with the intention of going on to Emory. My father had gone to Oxford and Emory. I had a partial scholarship at Oxford, but I was not going to have that at Emory, and so I was borrowing money to pay for school. Emory's med tech program was a five-year program, so I looked around. I ended up at the Medical College of Georgia, which had a four-year program, so I could finish a 3:00year earlier with a lot less expense. So that's where I finished, at the Medical College.
CHAMBERLAND: It sounds like your early years were influenced by some very strong women.
KENNEDY: Yes, I guess so. I hadn't thought about that.
CHAMBERLAND: They were ahead of their times, actually, when you think about it,with now the emphasis on STEM [science, technology, engineering and mathematics] type studies and encouraging women to do that.
KENNEDY: My mother had been a science major in college.
CHAMBERLAND: Oh, had she? In microbiology?
KENNEDY: We used to joke that it was just called science back then. She said itwas mostly chemistry. My older brother ended up being a chemist. He worked for Eli Lilly [Eli Lilly and Company] and retired from there.
CHAMBERLAND: What got you to CDC? How did you end up getting to CDC after yougraduated from the program?
KENNEDY: My first job out of school was the only job I ever looked for in my4:00whole career. All the other jobs just were presented to me. I started at Egleston Children's Hospital. After I'd been there about two years, I got a job offer from the hematology oncologist at Emory, Dr. [Abdelsalam Hassan] Ragab, who wanted somebody to work in his research lab. He had approached the lab director and had asked for a recommendation. She had given him my name, so I was never sure if she really thought I was the best person or this was her chance to get rid of me. Anyway, he offered me the job and I took it. I worked in a lab across the street from Grady [Memorial] Hospital, where the lab was.
After I had been there about five years, Bonnie [M.] Jones, who started atEgleston the same time that I did, left about the same time I did and came to CDC. Over the years she would call me when there was a job opening that she 5:00thought I might be interested in. A couple of the times that she called, the job was going to involve animal work, mostly mice. I was very clear [that] I did not want to do any animal work, even mice. She called me about this job, and she said, you know you really need to come and see about this one. You'd be a guest researcher paid by the Arthritis Foundation, but you'd be working for [Dr. J. Steven] Steve McDougal, who is this really great guy. You really should talk to him. So, I talked to Steve, and he offered me the job just because Bonnie had recommended me. We had been operating at Dr. Ragab's on a five-year grant. The grant was about up, and I wasn't sure it was going to get renewed, and there were two of us that worked in the lab. We were also about to move to Emory into 6:00a trailer and that didn't sound very good to me.
So I decided--by then I knew a lot more about CDC, and in fact I had been toBonnie's lab because [Dr. David] Dave Gordon was their branch chief at the time. They were doing this big study on adult leukemias, and they were doing some of the same tests with the adult leukemia cells that I was doing with the pediatric leukemia. I had come to CDC to learn how to do some things in that lab. I decided that would be a good move. I would at least get to CDC and then if there was a federal job that opened up, I'd be around to hear about it and maybe switch again.
CHAMBERLAND: Gosh, it sounds like it was very well timed, the various eventsthat were happening that coalesced perfectly. The stars aligned, as they say. Tell us a little bit, expand a little bit-- you said you were a guest researcher 7:00working for the Arthritis Foundation. If you could expand a little bit about that, and maybe tell us a little bit how that fit into Steve McDougal's lab.
KENNEDY: Steve McDougal was by training a rheumatologist. [Dr. Frederic C.] FredMcDuffie, who was the Medical Director of the Arthritis Foundation at that time, he and Steve and another rheumatologist, [Dr.] Eng Tan, who was I think at Colorado, got together and formed a committee with some other rheumatologists to address the need for standardized reference sera for antinuclear antibody testing. These tests are used to distinguish people who have various rheumatic diseases like [systemic lupus erythematosus] lupus, Sjogren's [syndrome], and mixed connective tissue disease. They have these antibodies to the nuclear 8:00proteins. People were testing for the antibodies, but no one was sure they were testing the same thing because there weren't a lot of commercial tests. They decided there was a real need to have well-characterized standards that people could order free of charge. Then they could make their own in-house standard that would replicate the standard that we sent them. It really started from scratch. We didn't have the equipment that I needed, and the techniques were not set up, so it was a matter really of setting the lab up. One of the things that we needed to do the fluorescent testing was frozen sections of mouse kidney or liver.
CHAMBERLAND: Oh, the animals.
KENNEDY: Yes, here we go to the animals again. I made clear to Steve I was not9:00working with animals. Anyway, we needed a microtome, a cryostat microtome to make these frozen sections, and I'd never done this before.
CHAMBERLAND: That's a very fine knife, if you will, to cut tissue or tissue blocks.
KENNEDY: Yes. I had never done this, but we found one that pathology hadsurplused out to the warehouse. CDC used to have a warehouse, and if you had lab equipment that you weren't using anymore, you sent it to the warehouse. Then you could go shopping at the warehouse and if you found something that you needed, you'd say "Yes, I want this," and they would transfer it and bring it to your lab. We had found this old cryostat and had it delivered to the lab, and I just read about how you do it. I can't remember if I even talked to the pathology people, because they would have been in our same Division at that time, but I think I just learned just and error. It's just a matter of trying it. I would 10:00get another person that worked in the lab, who worked with mice all the time, Sheila [C.] Isoke, and I'd say, "I need a mouse liver," and she would just go and bring me one. I didn't even have to see the mice. She'd bring me the liver. They had us setting up the other types of tests, and then it was a matter of screening the sera, that these rheumatologists would send us.
CHAMBERLAND: Okay, you would get patient's sera.
KENNEDY: They would send us candidate aliquots, candidate sera. If we pickedone, we'd send it out to all of them [the committee members] and they would all test it, so it was everybody on the committee [who] tested. We'd come to consensus [that] if we had a good candidate, they would get a plasmapheresis from that person, and then we would aliquot it and lyophilize [it]. We did all of that here at CDC. After about two years, we had five standards, the lab was 11:00up and going, and we'd already had like 300 requests. As soon as it was available, people were requesting it.
CHAMBERLAND: These were five standards for five different diseases,rheumatologic diseases?
KENNEDY: Five different antibodies, yes.
CHAMBERLAND: Five different antibodies?
CHAMBERLAND: Gosh, I had no idea that that pioneering work was done at CDC.
KENNEDY: Now, the standards today, at last count in 2013, they'd sent out almost30,000 vials.
CHAMBERLAND: CDC to this day is still doing that.
KENNEDY: Yes, they're still available.
CHAMBERLAND: Gosh, OK, and were these also helpful? A lot of these assays arecommercially available now?
KENNEDY: Yes, yes.
CHAMBERLAND: Was the work you were engaged with really the foundational workthat allowed manufacturers to take this and move to development of commercial assays?
KENNEDY: The commercial assays that we have now weren't in existence when I was12:00doing this. The way they do things now is completely different, but they can still use the standards.
CHAMBERLAND: I see, OK.
KENNEDY: If they're testing for the antibody, they know that this is awell-characterized source of antibody.
CHAMBERLAND: Ah, OK.
KENNEDY: The commercial companies were allowed to get five vials a year, whereasan individual lab, we would only give them one vial. All the commercial companies that made the tests did use our standards.
CHAMBERLAND: We've alluded to this a little bit in some of your comments. I waswondering if you could set the scene for us a little bit in terms of 30 years ago. CDC and your domain, the laboratories, were pretty different kinds of places in terms of the equipment. Things that we now consider to be just very ordinary or basic probably weren't even in existence then. I was just wondering 13:00if you could cast your mind back and think of some examples of things, like in this instance you were building from scratch. What are some of the differences if we walked into a laboratory 30 years ago, how it would be different from one today?
KENNEDY: I think the first thing you would notice is there were no computers.You can't buy a piece of laboratory equipment nowadays that doesn't have a computer that runs the equipment, the instrument. PCs [Personal Computers] weren't even invented. CDC had a huge mainframe computer that was in the sub-basement, or the sub-sub-basement of Building 1. It was huge. It took up the whole room and had all this special cooling and everything. As I recall, we had one dummy workstation in the whole branch, and it used DOS [Microsoft Disk 14:00Operating System]. You would sit there and if you needed a printout, you would enter all your information in this DOS format. Then you'd submit it to the mainframe, and then sometime, days later, they would call you and tell you your printout was ready. You'd go and get these huge big reams.
CHAMBERLAND: Were these the rectangular ones with the green and white stripes?
KENNEDY: Yes, with all the white stripes and all the little holes in the sides.
CHAMBERLAND: Yes, exactly.
KENNEDY: That's what we would get back with our data on it.
CHAMBERLAND: That obviously-- the advent of computers completely revolutionizedlaboratory work, among many other things.
KENNEDY: There was really a lack of any automation. We didn't have simple thingslike a plate washer that washes the 96-well plates that are used in all the ELISA [enzyme-linked immunosorbent assay] assays. The pipettes were single-volume pipettes. Everything was glass. We had glass pipette tips for some of the pipettes. You don't find glass anywhere in a lab now, because of the risk 15:00of breakage and cutting yourself. Everything was glass back then. The plastic industry had not-- there hadn't been a demand for it because we used reusable glass-- it was washed.
CHAMBERLAND: I wonder if you could orient us a little bit before we go intotalking about some of the HIV work, orient us organizationally where you, where Steve McDougal's laboratory branch fit in with CDC at the time, because you were part of a larger division.
KENNEDY: Right. I was paid by the [Arthritis] Foundation, but CDC provided labspace and everything else--
CHAMBERLAND: Right, so all of your work was physically on-site at CDC
KENNEDY: --for my position, so I was in the lab with everybody that was doingthe other things that Steve was doing. He was an immunologist and a rheumatologist, so he was doing research on rheumatic diseases. We were within 16:00what was called the Division of Host Factors. I think CDC had been reorganized just before that, because it used to [be part of] the Bureau of Labs [Laboratories]. All the labs were together, all the epi [epidemiology] people were together, and then they decided that they needed to merge and put the epi people with the lab people for their disease. We were immunology-- there was pathology, immunology, hematology, and I think the drug services might have been with us. We didn't fit with a disease, so they just put us all together, and it was called the Division of Host Factors. [Dr.] Bruce Evatt was the Division Director, and Steve was eventually the Branch Chief. When I first came, Dave Gordon was still here, but he left probably within that first year that I was here. He left and Steve became the Branch Chief.
CHAMBERLAND: Ok, so you were in the Immunology Branch, if that's what it was called?
KENNEDY: Immunology Branch, yes.17:00
CHAMBERLAND: How did Steve McDougal's lab first get involved in anyHIV/AIDS-related work? You're arriving three months before the first MMWR and just beginning to do this work on developing standards for rheumatological disease testing. It's not soon after that, that things start to percolate in terms of these unusual cases popping up. Just curious how Steve's lab first got involved.
KENNEDY: One of the first things that they noticed about people with the diseaseat that time was their immune system was really messed up. That's why they were so susceptible to all this pneumonia and the other diseases that they were getting, other infections. Steve was the de facto immunologist at CDC, and we had a FACS, a fluorescent-activated cell sorter. The only one at CDC was in 18:00Steve's lab, and [Dr. Janet K. A.] Jan Nicholson was in charge of that activity. They had been using the FACS because they had been studying leukemia. They had been looking at subsets of lymphocytes, and so they came to us. The samples just came to Steve's branch, because we had the capability to do that.
CHAMBERLAND: These are samples from AIDS patients that clinicians sent in to CDC?
KENNEDY: Yes, the samples from Los Angeles, those very first samples from LA,and then later the ones from New York came to CDC to be evaluated.
CHAMBERLAND: These blood samples would come in, and you and your colleagues wereto run them through this FACS. Is it the same as a flow cytometer?
CHAMBERLAND: Okay. Can you explain a little bit about what that would do? How aflow cytometer, what it's basically doing. What would you come out with in terms 19:00of a result?
KENNEDY: A flow cytometer is an instrument that uses lasers to numerate andidentify particles or cells that have been tagged with a fluorescent dye. In the case of the lymphocytes, each of the subsets of lymphocytes has unique proteins on their surface, and they are named for those proteins. A CD4 [cluster of differentiation 4] cell has CD4 on its surface, a CD8 has CD8 on its surface. You can buy antibodies that have a fluorescent tag on them, to the specific proteins. You would take the antibodies, and add them to your cells. They're aspirated up into the instrument, and the fluidics of the instrument are such that the cells pass through the laser and the detector in single file, one cell at a time, but thousands of cells per second. It counts millions of cells-- you 20:00get a very accurate count. The one that we had, the first instrument we had, was the cell sorter. In addition to identifying and counting the cells, it would actually sort those cells, cell by cell, and give you all the CD4 cells in one tube, the CD8 cells in another tube.
CHAMBERLAND: It would then be able to also give you a count?
KENNEDY: You got your count, and you got your sample back also. Since it was theonly one at CDC, other lab groups would have need occasionally for a cell sort. They'd contact Jan, and [David] Dave Cross was an operator of the machine and later Carolyn Dawson. They would do the cell sorts for anybody at CDC that needed it.
CHAMBERLAND: Oh, gosh. What were some of the findings from these early samples21:00that came to you when you ran them through the FACS machine and looked at the different subsets, if you will, of T-lymphocytes? What were the findings that were coming out?
KENNEDY: What was astonishing is that they had no CD4 cells.
CHAMBERLAND: Are these the T-helper cells?
KENNEDY: The T-helper cells. They had very, very low numbers.
CHAMBERLAND: Had you seen anything like this before?
KENNEDY: It was very rare. I'm sure there were some immunodeficiency diseases,but this was just so dramatic, and it was the same, it was the common factor.
CHAMBERLAND: Patient after patient.
KENNEDY: Patient after patient, [the common factor] was the lack of the CD4.
CHAMBERLAND: Very few, if any, CD4 or T-helper cells. What about the CD8 cells?
KENNEDY: That ratio would be flipped.
CHAMBERLAND: There would be a lot more of them than the helper cells?
KENNEDY: Right, yes, compared to the CD4 cells.22:00
CHAMBERLAND: In the community, apart from CDC, were there other laboratoriesaround the country that had these cell-sorter machines?
KENNEDY: Yes, there were research facilities that had them. Nowadays, they arevery common. Eventually we had to buy more. We just bought more of the cytometers-- we didn't need another separator.
CHAMBERLAND: I've heard the story that because your laboratory had the only oneat the time at CDC, that it became a bit of a tour highlight for VIPs that came to CDC and got a tour of the laboratory, including former President Jimmy Carter. Is that correct?
KENNEDY: That's correct. It was the only one. It was a very impressive machine.It was huge. It has these lasers in it, and it's also water-cooled, so it had pipes and it had tanks and it had lots of dials, and the screen. It was just a 23:00very impressive machine. Visitors, if they were at all interested in what CDC was doing with this new disease, they'd bring them in to show them the flow cytometer. There was actually a picture in the Atlanta Journal Constitution of Steve, Jan, and former President Carter--
CHAMBERLAND: Gazing in awe of the machine.
KENNEDY: --standing in front of the cell sorter.
CHAMBERLAND: Then taking it a step further here, as long as we're on the subjectof T cells and CD4s, you and your colleagues undertook a series of experiments that provided real insight into how the HIV virus infected these T cells. I was wondering if you could describe that work, because there was a lot of interest 24:00and people had no idea how it was that the virus was attacking. You said there were no CD4 cells or T helper cells, so--
KENNEDY: When you did a culture with these, the CD4 cells died very quickly inculture. It happened within a week or so. If you measured the CD4 on the cells, it went away. You couldn't see it on the cell anymore. We did a paper later, in 1985-86, that actually proved on a molecular level that CD4 was the receptor on the cell and gp120 was the protein on the virus that actually attached. There was other evidence that those were the proteins involved, but the experiments that we did really became the definitive proof that that was what the 25:00interaction was.
CHAMBERLAND: The HIV virus has this glycoprotein--that's what "gp" stands for,glycoprotein--and the 120 is its molecular weight?
KENNEDY: Its molecular weight.
CHAMBERLAND: It's that protein that's specifically is hooking onto, if you will,the CD4 site. That's the docking station, almost.
KENNEDY: Right. Like a lock and key.
CHAMBERLAND: For the many non-laboratorians that will be reading and listeningto this interview, tell us a little bit-- I mean, this is elegant work that you and your colleagues are doing. I'm wondering, how is it that you devised these various experiments? Do you all sit around and talk through ideas, go try something, see if it works? I'm just curious how-- because you're on the cutting 26:00edge-- [here's a] new virus, acting in a very strange way, killing off people's CD4 cells. How did you devise these experimental studies?
KENNEDY: I have to give the credit to Steve McDougal. He was a brilliant man,and he had a way of seeing things that other people did not see. There was evidence that CD4 was involved, there was evidence that gp120 was involved, so Steve just came up with this-- it was really very simple, not that difficult to do.
CHAMBERLAND: Tell us a little bit about it.
KENNEDY: We labeled the surface of a cell line, that had CD4 on it, with aradioactive tag, and then we infected it with virus. Then we did what is called 27:00an immunoprecipitation with an anti-HIV antibody. Then you do a Western blot and develop this on a piece of x-ray film. What that antibody pulled out of that mixture was a 58 KD [kilodalton] protein, which is the molecular weight of CD4. By the molecular weight and the controls that we had, we knew it was CD4, and that was the only thing that was there. Then we did the reverse. We labeled virus with the radioactive material, infected cells, and did the precipitation with an antibody to CD4. The only protein, the only thing that showed up on that x-ray was-- we measured it as 110 [KD]. Later on it was more accurately measured as 120, but with our little ruler and molecular markers, we guessed at the wrong 28:00weight. Nobody else had thought to do it this way, but Steve just would come up with these original--
CHAMBERLAND: Would he talk it through with you?
KENNEDY: Yes, and the other thing is that you read every journal that came out.I mean everything about HIV, we read. The journals would come. Steve subscribed to some of them, but they'd be in the library, so you read everything that was published to figure out what to do. The other thing about Steve was, he had a photographic mind-- he remembered everything he read. He would tell me to go to the library, look up this article in the Journal of Immunology by so and so, and see how they did this. Look at the figure, it's at the top of the right-hand page about halfway through the article. And that's where it would be. You would 29:00see methods of what other people were doing. It was that and then just coming up with-- just improvising. We didn't have the reagents we needed, but we had animals. We could make our own antibodies-- we could conjugate them. Steve never believed in buying anything [if] you could make it yourself. So, there were goats and rabbits and mice.
CHAMBERLAND: These are CDC goats and rabbits?
KENNEDY: Yes, they had them out at the farm. We had mice in Building 6, I thinkit was or whatever. But we just immunized them and collected their blood.
CHAMBERLAND: Collected the antibodies that they produced.
KENNEDY: Yes, I could purify the antibody and tag it with whatever we needed, afluorescent antibody or hydrogen peroxidase or whatever we needed. You made your own reagents, and you just figured out, trial and error, how to do it. 30:00
CHAMBERLAND: Did Steve do benchwork himself?
KENNEDY: He loved to be in the lab. He was always happiest if he was in the labworking. But unfortunately, he became the Branch Chief. He would have been a lot happier if he'd just been left alone. He probably would have been more productive if he hadn't had to take on the administrative duties that he had. He was always happiest in the lab. He avoided his office. He would always be sitting in the lab. He would bring his papers, everything. I mean, you didn't have a computer or anything. You wrote out every article, every journal, manuscript, you wrote it out by hand and had the secretary type it up. But he always found a spot in the lab, usually right across from me, and that's where he would sit.
CHAMBERLAND: As he had to take on more of these administrative duties, youobviously carried out a lot of the ideas that he had-- you actually implemented 31:00or made it happen.
KENNEDY: Yes. I mean he would help if it was something that we needed more thanone hand to do. The way the lab was set up, people had their specialty of what they did. There were people who did flow cytometry-- I myself never did any flow cytometry. If I needed my cells identified or whatever, I would just go to Bonnie Jones or Sherry Orloff, and they would do it for me. Nobody else did Western blots but me, and I did a lot of cell culture. I was sort of Steve's hands, I guess.
CHAMBERLAND: Probably a little bit more than that.
KENNEDY: If he were here, he would be the one to do this interview, because this32:00is all his work.
CHAMBERLAND: I have a strong sense, though, that you were a very good team.
KENNEDY: We were a very good team, and we became very good friends.
CHAMBERLAND: This work that Steve and you did in terms of-- it sounds like itprovided the definitive proof that the virus, via glycoprotein 110 or 120, hooked onto the CD4 cell. This was written up in Science, a major scientific journal. It was, I think, hailed as proof that CD4 was the receptor for HIV, and, as I said, that 120 was the viral protein that bound to CD4. It won CDC's Charles Shepard Award that's presented to the best manuscript on original research published by CDC scientists in a peer-reviewed journal. I also read 33:00that this Science paper was cited in other publications more than 120 times during the first 18 months after its publication. Why was this such an important finding? What were the implications of this work?
KENNEDY: The implications were that if there was some way that you could stopthis, block this binding, that you would prevent the virus from infecting the cell.
CHAMBERLAND: That probably gave people a ray of hope that this was one of maybemultiple approaches to try and stop infection, manage infection. What was your reaction, your and Steve's reaction to all of this?
KENNEDY: Science did a pre-release to the newspapers before the journal actually34:00came out. So, it was already in the press before anybody had even read it. This was not something that Steve was--he was not at all interested in any attention from anybody.
CHAMBERLAND: Steve was not a media hound.
KENNEDY: He was not. He was the most humble person. He didn't want to takecredit for anything. He always said, "The credit always goes to the people who are doing the work. I'm just supervising." It was always "everybody else" that deserved the credit and not him. He was horrified. We had reporters just calling the lab. Back then the switchboard would just pass them through. There wasn't the press office and all that CDC has now. We had reporters calling his office. He wouldn't be there-- he's hiding out in the lab because he knows his office phone is going to be ringing. The secretary is directing them to my phone in the lab, so I'm having to answer the phone calls from the reporters. 35:00
CHAMBERLAND: The trial by fire with the media--
KENNEDY: Steve said, "That's it, I am never sending another paper to Science,because I don't want this much attention. We'll just go to a different journal if we ever have anything like this again." He was on other Science papers [as co-author], but he himself as lead author, he never sent another paper to Science after that.
CHAMBERLAND: Oh, my gosh, true to his word.
KENNEDY: He did not want the attention.
CHAMBERLAND: What I'd like to do is talk a little bit about what you said wasyour particular area of specialty expertise, the Western blot. First of all, you have to tell us: what is a Western blot?
KENNEDY: A Western blot is an electrophoresis technique used to identifyproteins, and in our case antibodies to those proteins. It was called a Western blot because the first method, the first test, that used this methodology was 36:00developed for DNA sequencing, and the man's name was E.M. Southern.
CHAMBERLAND: The opposite of Western -- Southern, or not quite the opposite.
KENNEDY: The next test for RNA was called--it was a play on Southern's lastname, a Northern blot. When the Western blot was developed in, I think 1979, as a continued little lab humor, it was called a Western blot. Later there was an Eastern blot, and that's for lipids and carbohydrates. All the procedures, all these blots, are two-step procedures. They use a gel to separate components, and then they do the trans-blot or transfer, a second electrophoresis, to get those components onto a piece of paper. In our Western blot, we took disrupted virus, 37:00and in this case we used LAV--
CHAMBERLAND: Lymphadenopathy virus.
KENNEDY: Yes, from the French. It was the French isolate from the InstitutPasteur, because the NIH [National Institutes of Health] would never send us any.
CHAMBERLAND: How interesting, because they had the HTLV-III [humanT-lymphotrophic virus, type III] from [Dr. Robert] Gallo.
KENNEDY: Right, they had what they thought was their own virus. It turned outlater they were exactly the same, but the French, Institut Pasteur, did send some. They sent it to the virologist at CDC. They knew that Steve had been saying, "We need some, we need some, we've got this blot." Steve had the blot set up to look at antigens in immune complexes, antigen-antibody complexes, so the technology was there. [Sandra] Sandy Browning had set the equipment up. We 38:00had learned how to do it from [Dr.] Victor Tsang, who was in parasitology at the time. He was already doing Western blots before us. You can use it for anything-- it separates any proteins.
CHAMBERLAND: If I can just interrupt for a second: this is at a time when thereis no diagnostic test for the virus, correct?
KENNEDY: No, there is no test.
CHAMBERLAND: You're culturing. You're counting CD4 cells.
KENNEDY: The virus was discovered in mid-1983 towards the end [of the year]-- Idon't remember if it was the end of '83. By this time I had taken a job. Sandy Browning had left, and I was hired.
CHAMBERLAND: Oh, so you were an FTE [full-time equivalent] at long last, not aguest researcher.
KENNEDY: Now I'm a CDC employee working in HIV. Sandy left, so I learned how todo the Western blot before she left. That helped me get the job because they could say that was a requirement for the job, that somebody knew how to do that. Anyway, I was hired in September. I think it was either December, maybe January 39:00sometime in early '84, that we got the virus from the French through the virologist. I'm not sure we got some of the first vials they sent, but we did get some, and that allowed us to grow it and make our own. As soon as we had the virus, we lysed it with a detergent in heat to disrupt it into the various individual proteins. You take that disrupted virus and you put it on top of a gel. In our case, it was made out of polyacrylamide, and because of the detergent that you add, all of the proteins have a negative charge. You apply an electrical current to this apparatus, and the proteins will migrate towards the positive bottom of the gel. They separate out by molecular weight. The lightest ones go all the way to the bottom, and the heavier ones stay towards the top. 40:00You then take the gel out of that apparatus and you put it next to a piece of specialized paper made out of nitrocellulose-- you put that in a second electrophoresis apparatus and you apply an electrical current, and it pushes the proteins out of the gel onto the piece of paper. So, then you have a piece of paper with all--
CHAMBERLAND: So, you can visualize.
KENNEDY: The proteins are on there, but you can't see them yet. You cut thatpiece of paper up into multiple strips. You take each strip of paper and incubate that with your serum sample from the patient, that has antibodies which will stick to the proteins. You add a secondary antibody that has an enzyme on it. You add a substrate and get a color. You end up with a piece of paper with 41:00multiple bands that are each of the individual proteins. The proteins are named by their molecular weight.
CHAMBERLAND: Hence, we were talking earlier about gp110 or gp120.
KENNEDY: gp110 or 120 and 41, 24, the various proteins. It didn't take us longto get that, because we knew how to do the procedure. It was just a matter of figuring out dilutions and how much virus, and that all went pretty quickly. The problem was, what do we call a positive, because when you develop the first test for something, you don't have anything to compare it to. There were no other tests. How do you decide what's a positive? Do they need to have an antibody to every one of those proteins? If they have antibody to only one protein, what does that mean? Does that mean they're positive or negative? We had to figure that out, and the only way we could figure it out was to just start testing samples, collections of samples that CDC had on people that were assumed to be 42:00positive because they had symptoms.
CHAMBERLAND: Would you start with full-blown AIDS patients?
KENNEDY: Yes, and then compare it to people, normal controls. It was a matter oftesting and evaluating the test. It's pretty difficult to do, because what you want is, for a test like HIV, it needs to be as close to 100% sensitive and 100% specific as you can get it to be. There's not a test that has both, so you have to give up one or the other of those: whether you want to be sure you have no false positives or you want to be sure you have no false negatives. In the case of HIV, either result is equally bad. You don't want to tell somebody they're positive when they're really not. You don't want to tell somebody that they're 43:00negative when they're really positive, because back then if you told somebody they were positive, it was a death sentence. So, you had to be right.
CHAMBERLAND: Can you give us any idea how many samples you tested? How many testruns did it take of testing sera from AIDS patients, where you felt pretty confident that you could see the same pattern of the bands that would pop out?
KENNEDY: This took a while, and what we would report back before we were sure,we would just tell whoever the investigator was [which bands or proteins were present], because all the samples that I tested were done in conjunction with an epidemiological study. We weren't getting samples from the general public. All the samples that we had [were] collections of samples, particularly hemophiliac samples, because Bruce Evatt was the Division Director and coagulation disorders were his specialty. He had these collections of samples from hemophiliacs from 44:00all over the country. He had serial samples from the same person collected over time. Those were some of the first ones that we tested. We actually found our first positive from 1978.
CHAMBERLAND: Oh, one of the hemophilia patients whose sample you had that wasdrawn from '78 was positive, as far as back then. That's three years before the first MMWR comes out, when the disease starts to be recognized clinically.
KENNEDY: I remember that blot, because every year there were more and more[positives]. By '83, '84, they were almost all positive. I think [in] the first large collection of hemophiliacs I tested, over 70% were positive. But we used these samples that they knew something about the person, whether they were asymptomatic-- 45:00
CHAMBERLAND: You had good clinical correlation.
KENNEDY: Had a clinical correlation. Now, the samples when I got them, ofcourse, were completely blinded, because in the end, the reading is subjective. You're sitting there and you're looking, and you're trying to decide if there's a band there, if it's dark enough to call it positive or not. You could have two people look at it, and somebody would see something you don't see. There's not a machine that reads this-- this is just human eyeballs looking at it. I just tested and tested and tested.
CHAMBERLAND: Was CDC the first, or one of the first laboratories to demonstratethe utility of Western blot testing for HIV?
KENNEDY: I don't know. I think other people were using it.
CHAMBERLAND: Other people might have been working on developing the Western blot.
KENNEDY: I think other people were doing it. NIH focused very quickly on tryingto get an ELISA assay.
CHAMBERLAND: Nowadays, we fast forward and it's interesting, because if you're46:00going to test someone for HIV, typically you would test an ELISA antibody and then the Western blot would be used as a confirmatory test.
KENNEDY: Nowadays, they're rapid tests.
CHAMBERLAND: That's true.
KENNEDY: You can do them in 15 minutes, and there are rapid tests that are muchbetter than any ELISA or any Western blot. But the Western blot did become the gold standard test, and the criteria that we started using actually were the criteria that were used for 30 years.
CHAMBERLAND: All of this work that you did on it sounds like hundreds, thousandsof specimens, just looking at the banding patterns and then figuring out what would be the very highly predictive bands to say, yep, if you got this band pattern on the nitrocellulose paper, this is a definite--we're going to call this a positive Western blot. 47:00
KENNEDY: Right, and for a long time we would just tell somebody [the bands thatwere present]. The most frequent result that we didn't know what to do with was, somebody would have a band that would show up at p24. Now, in the virus prep itself, there's more p24 protein than any other protein. If you were going to have any kind of cross reactivity or stickiness from an antibody that somebody had to something else, it's likely where it would stick. That's where you would maybe get a false reaction. We would just tell the investigator, it's p24 positive, but we're not sure what that means.
CHAMBERLAND: No other bands.
KENNEDY: No other bands.
CHAMBERLAND: It could have reflected [something] completely unrelated to HIV orpossibly very early HIV?
KENNEDY: Very early or very late. That's the other thing: when you have AIDS inthe end stages, you have no antibody because you have no T cells. So, an end-stage AIDS patient would look like somebody that was recently infected. 48:00
CHAMBERLAND: Did this work serve as, because now these Western blots arecommercially available--
KENNEDY: Correct. They became commercially available not until 1987.
CHAMBERLAND: Oh, so several years later.
KENNEDY: From 1984. Ours was up and running in '84.
CHAMBERLAND: Would the commercial labs be interacting with you, with CDC, intheir development process?
KENNEDY: Steve was never interested in trying to do anything commercially, butVictor Tsang in parasitology did work with the commercial companies in the development of their blot. Steve said, "Well, Vic should get credit for this because he taught us how to do the blots." He wasn't doing HIV blots, but he taught us the techniques. Victor did it. But Steve was never interested in pursuing anything like that commercially.
CHAMBERLAND: Did you ever use commercial blots, or did you always use your homegrown?
KENNEDY: I never used a commercial blot. Again, I say the studies that I did,49:00the samples were all in conjunction with an epidemiological study. There was another routine serology group under [Dr. Gerald] Gerry Schochetman's group, Charles Schable was the-- first [Dr.] Richard George was head of that and then Charles Schable. They never just got samples from the general public, but if there was a question about a diagnosis, they could request that CDC look at the sample. That still goes on today. There's still the lab group, the immunology group, that will get samples from state health departments who can't figure out a diagnosis.
CHAMBERLAND: Speaking of state health departments, your work examining hundreds,thousands of these specimens and figuring out ultimately through diagnostic 50:00criteria to call a blot positive or not, then wasn't it the next step to push out this testing to state public health laboratories?
KENNEDY: We did do that. The state health departments, I don't know if any ofthem had blots set up. The ELISA came out in 1985, but they need to be confirmed, so people were sending samples to state health departments asking for confirmation tests. They didn't have anything, so we taught classes. Vic Tsang, Marianna Wilson, Kathy Hancock, Steve and I, and mainly Shelba Whaley from the training lab at CDC, we taught classes to state health departments. I think we had somebody from almost every state health department that came. Sometimes they would send the lab director. That wasn't always the best move, because this was 51:00a wet workshop. They had to cast gels, they had to do the electrophoresis, trans-blot it onto the paper, and cut it into strips. I mean, they had to do everything. This was so they could set up this whole procedure in their lab, and some of these lab directors hadn't been doing lab work in a while.
CHAMBERLAND: They're learning these skills under your direction and yourcolleagues' direction. Are they in your laboratory? How many can you fit in at a time?
KENNEDY: Back then there was a lot of training going on at CDC. There were labsin the Training, the Division of Training. They had these labs, and you just used them.
CHAMBERLAND: You stock it up with the particulars that you needed?
KENNEDY: They bought all the little apparatus. I used these large gel formats--they were very big. But we went to a very small gel format for them [the 52:00classes]. They ordered all the equipment. You'd just give them a list of what you needed to teach the classes, and they would get it all in there. They would help make the reagents and whatever you needed. But they had these labs. That's all they were used for, just training.
CHAMBERLAND: What a fantastic resource.
KENNEDY: It's a shame that CDC doesn't do that anymore, but they don't.
CHAMBERLAND: It reminds me of high school chemistry. Did everything go smoothlyin these classes?
KENNEDY: Everything did not go smoothly in these classes. I learned very quicklythat you have to be very clear about instructions. If you can do something wrong, somebody will do it wrong. When you've got 25 people who don't know what they're doing and have never done anything like this before, there are a lot of mistakes made. The nitrocellulose paper, you can't touch it with your fingers. 53:00You have to use gloves because you'd get fingerprints on it. It comes between two sheets of this blue paper. We had people who would throw away the white paper, which was the nitrocellulose paper, and they would be trying to transfer their proteins onto this blue, backing paper that was nothing. The worst thing that happened was we actually had a fire. You're using a lot of current to move these proteins around, and it gets very hot. If you use the large gel format, you have to have a cooling coil to keep it cool. But in the small ones, we'd just run it for a shorter time because the gel is shorter, and you don't have to run it as long. We cautioned everyone, big [letters], underlined in caps, "Be sure you cover those wires with buffer to keep them cool." Somebody didn't cover 54:00theirs with the buffer and that wire just gets red hot, and it actually caught on fire. Fortunately, we were in the classroom at the time, but there was somebody in the training lab. They saw it and started yelling. We went in there and unplugged it so it didn't burn the lab down. It was pretty exciting.
CHAMBERLAND: I would imagine, hair raising. Then when people would go back totheir individual public health laboratories in their state, I'm guessing you all got a lot of follow-up questions too, once they--
KENNEDY: I don't remember getting that many follow-up questions. We taught theclasses in '86, and in '87 the commercial kits came out. The kit comes-- it's just the piece of paper, you just put your sample with the antibody-- incubate it with the piece of paper. It's got everything in there you need, secondary antibody. I have no idea how many state health departments actually set up and 55:00ran blots. I never got any of that feedback. If they'd had a question, they probably would have called Vic Tsang.
CHAMBERLAND: You didn't actually have to go out in the field-- everybody wascoming to you.
KENNEDY: No, everybody came here. We did not go to the field because we had somany people that needed training. There were 50 state health departments. We had two classes of 25 people.
CHAMBERLAND: I wanted to circle back a little bit on some of the studies thatwere done of AIDS in persons with hemophilia. Because as you mentioned, Bruce Evatt, the head of the Division of Host Factors where your Branch was situated, was someone who had worked a lot with the hemophilia community before AIDS. He was very involved in these clotting disorders, blood-clotting disorders. You mentioned that you had access to samples for individuals over a period of time, so you could actually watch these individuals, if you will, become positive-- be 56:00negative, negative, and then turn positive. I think you mentioned an astounding observation that the vast majority of these persons with hemophilia ended up acquiring HIV infection. That was because--
KENNEDY: That is because for their treatment they received one of two things.They had either received a cryoprecipitate, which is made from a single donor.
CHAMBERLAND: It's giving them the clotting factor concentrate that they're missing.
KENNEDY: Yes, the clotting factor-- yes, [that] they're missing. Or they wouldget what is called the concentrated form of that, and the concentrate is made from hundreds of donors. If you got the concentrate, every time you got that, you were exposed to hundreds of people. You'd be exposed to thousands of people. We showed very early on that the rate of positivity was about three times higher 57:00in patients who just received concentrate versus patients who had just received cryo. Those samples came from the Puget Sound [Blood Center] in Seattle [Washington]. They had samples from people who had only received concentrate, had received both, and only received cryo. It was a dramatic difference. The very first paper we published was about hemophiliacs, and it was correlated with the fact that they had received these concentrates and cryo.
CHAMBERLAND: That in turn led to another key piece of research coming out of thelaboratory. I don't think you personally were involved in it, but this was the quest to find some way to inactivate the virus in the Factor VIII concentrates, 58:00these concentrates that were made up of individual donors, hundreds of them, in a bag of concentrate. We needed to figure out a way to inactivate the virus, because it's a life-saving product for these people. They need it. On the other hand, it's killing them at the same time.
KENNEDY: Steve and Bruce Evatt got a couple of the companies, Cutter[Laboratories] and I think Alpha [Therapeutic Corporation] was the other company that was willing to participate in the study. Steve figured out a way to do a heat treatment that would not harm the Factor VIII that they needed, but it was enough to kill the virus. This was published, and all the companies, they immediately adopted this. I think the Canadian companies were a little slower, 59:00because later there were some lawsuits. I remember Steve having to go testify in Canada about it, but they didn't do it right away. But it essentially stopped the AIDS epidemic in hemophiliacs. Steve always said that was his greatest accomplishment.
CHAMBERLAND: With good reason that he would say that.
KENNEDY: I mean, it saved thousands of lives.
CHAMBERLAND: It's interesting, as you say, [that] it was picked up immediatelyand implemented. Oftentimes these things take a lot of time to crank through it. It sounded like this was just taken on board very quickly.
KENNEDY: I think that's because we got the companies involved from thebeginning. I mean, they knew that they had to do something.
CHAMBERLAND: In addition to-- certainly this was a huge victory, if you will, tofind a way to inactivate the virus in a lifesaving product that patients had to 60:00have. There were a lot of qualms in general about HIV in the environment, be it in homes or hospitals, and lots of questions about, "Well, how do we decontaminate a surface, how do we kill the virus if it's on our laboratory countertop or in our kitchen, if we're in a household with people living with HIV?" You did some of the work that looked at ways to inactivate the virus with household bleach?
KENNEDY: Yes. We had come up with what we called a capture assay, but it was away for us to quantitate virus. Some of [Dr. Thomas J.] Tom Spira's lymphadenopathy, unexplained lymphadenopathy patients, agreed to give us large amounts of blood. We could get antibody from their serum. Then we could tag that 61:00antibody with a color-producing agent. We had this capture assay that we developed, and once we had that, we could quantitate virus. Then we could do things to the virus to try and kill it. We could use our capture assay to determine if we had killed it or not. We looked at bleach, we looked at alcohol, we looked at all sorts of things. [Dr.] Linda Martin was in charge of a lot of those studies. Sheila Isoke was doing a lot of those experiments, and I think Sherry Orloff probably did some of those things too. They were able to show that bleach was a good killer, and that's why everybody started disinfecting with 10% bleach. Alcohol's not so good. Alcohol has to dry. You'd have to spray it on and let it dry-- it doesn't kill instantly like the bleach does. 62:00
CHAMBERLAND: But you and your colleagues had to figure out the concentration wasjust at 10%, and so this assay would allow you-- so you would be testing various concentrations of bleach against a known amount of HIV, and then you would start diluting--?
KENNEDY: Yes, you would just expose the virus to the different dilutions, andthen you would measure the amount of virus that was there. What you'd get was how many logs reduction there was in the titer. We knew what the titer was to begin with.
CHAMBERLAND: And 10% was the dilution?
KENNEDY: 10% is the dilution that you needed.
CHAMBERLAND: I remember this coming up as a question. What you want to make sure63:00is that you've killed every last bit of virus, and so how would your capture assay be able to--?
KENNEDY: We couldn't say it killed every bit of it, but you could say it reducedit by ten logs or six logs, or five, or three. You could tell what the log reduction was.
CHAMBERLAND: I know your laboratory was also involved-- this was not early work,but I know your laboratory was also involved in yet another experiment where people were interested in determining infectivity of the virus and its inactivation. It went by a very curious name, the "Killer Tomato Project." I really must ask you about the Killer Tomato Project. How did that come about?
KENNEDY: We got a request from the FDA [Food and Drug Administration], who saidthat they had credible rumors that people with HIV were going to inject their 64:00blood into fruits and vegetables to try and infect other people. They wanted us to tell them if this was possible.
CHAMBERLAND: If the virus would survive the injection of a--
KENNEDY: Right, if someone could get infected by eating this injected fruit orvegetable. I guess tomatoes, because they're red, maybe the blood wouldn't show up. I think this was one reason why the tomatoes came up. The request came through [Dr.] Harold [W.] Jaffe, who was our Division Director-- originally it went through Dr. [William L.] Roper, the CDC Director.
CHAMBERLAND: Very high level.
KENNEDY: Yes, high level, because this was one agency talking to another agency.But it got down to Steve's lab, and Steve came in and told me about this. I just immediately thought of that movie, "The Attack of the Killer Tomatoes," a 65:00B-rated movie or whatever that had been out. We just laughed about it, and we thought, "This is crazy. This is not something that we can prove one way or another. There's no way to practically do this." Steve got back to Harold and said, "We don't want to be involved in this. This is a no-win situation for us because we cannot-- we don't know what to do to determine this." I guess it went back to the FDA, and then they suggested we do some kind of study with pH.
CHAMBERLAND: The pH of tomatoes or other vegetables.
KENNEDY: Right. I had to go try and find out what the pH of a tomato was.There's no Google, you can't just--
CHAMBERLAND: Because this is early '90s.
KENNEDY: Yes, this is mid '90s, there's no way to find out this unless you goread it in some kind of reference book or something. That was the first thing I 66:00had to do. Steve said, "We've got to find out what the pH of a tomato is." We decided to do this pH study. The other thing is this is going to take us a month, and Steve thought this was a waste of time, but it came back through Dr. Roper that we would do something. We were to do this-- we didn't have any choice about it. I did the pH study, which is not really that easy to do. You can't put low pH virus into cell culture, because the low pH will kill the cells. It's got to be back up to neutral. What I did was expose the virus to various pHs. We did it at room temperature and also at four degrees. We thought the produce would be refrigerated, so we did it at two temperatures. You expose it, then you have to raise [the pH] that back up, titrate that back up, to get it to neutral pH. I had to do a lot of preliminary titrations to know exactly how much to add. We 67:00wanted it to go down instantly, and we wanted it to come back to neutral instantly, because we were timing this. Then we did our [infectious dose] ID-50 assay and capture assay, and we determined the effect of pH. Steve sent the results back to Harold--
CHAMBERLAND: What were the findings?
KENNEDY: The findings were really not that encouraging, because if it'srefrigerated, the virus is really not that sensitive to pH. There's a lot of other things that have got to happen. Somebody's got to eat that tomato and get [the virus] through the acid in their stomach. We don't know that anybody's ever been infected from eating something like this. It really didn't answer their question completely, but it's all that we could come up with. Anyway, Steve sent the results back through Harold, who was going to send them through Roper, I 68:00guess, back to the FDA. So, in the letter--
CHAMBERLAND: With the results?
KENNEDY: With the results is my reference in my lab book, SK, whatever the datewas, something '95, "Killer Tomato Project."
CHAMBERLAND: This is how you identified the experiment?
KENNEDY: Yes, this is how we identified these experiments in my notebooks. Wedidn't have computers. Notebooks. Steve just assumed that Harold would leave that out, that all he would do is send the graph, and he would write his own letter. I think Harold forwarded it just the way Steve had it written, with that reference in there. What we heard was they were not amused that we had called this the Killer Tomato Project. They sent this very serious letter back to Dr. Roper, thanking us for our efforts. It said something like, "While we hoped for better news, at least now we can concentrate our efforts on certain foods," or 69:00something like that.
CHAMBERLAND: Did you test more than tomatoes?
KENNEDY: No. We couldn't test tomatoes. All we could do was look at the effectof pH on the virus-- we couldn't actually do any putting it in foods and trying to get it back out.
CHAMBERLAND: Oh, my gosh. Was that the end of your FDA--
KENNEDY: That was the only and last request that we had from the FDA that I know about.
CHAMBERLAND: Susan, in preparing for this interview, I went back and looked atsome of the papers, and whatever that came out of the Immunology Branch. I was really impressed, especially after hearing you talk. This is incredibly tedious, time-consuming, very detail-oriented work that you, and your colleagues were doing. Looking back, you realize that the Immunology Branch cranked out a lot of 70:00work in the early-mid '80s in a relatively short period of time. I was wondering, I wanted to ask you, what was it like to keep pace with that? It strikes me now that this must have just been a tremendous volume of work for a relatively small number of people.
KENNEDY: Yes. I think there were, maybe we might have had 15 people at the most.There was so much to learn. No one knew anything, so it was just wide open. It was so easy to think up things to do. We had the samples, and we had very good principal investigators: early on, Linda Martin and then later [Dr.] Allison Mawle, Jan Nicholson, Tom Spira, and Steve, and even a little later than that, 71:00[Dr.] Janine Jason. We had good people who were just able to find things.
CHAMBERLAND: Was it a very stressful environment?
KENNEDY: I would not say it was stressful. We were busy. There was a lot ofweekend work. If you were doing these cell cultures, you had to come in on the weekends, because you just couldn't do something in five days. It would run over to the weekend. There were a lot of us that worked on the weekends. I don't remember that it was stressful. It was just urgent. I felt it was urgent. I felt this real sense of urgency. We needed to find out as much as we could. Testing these samples, it was sobering to think about how many people were infected. People talk about the "tip of the iceberg." When you test a set of samples and 70% of them are positive, we were really starting to see how big that iceberg was. 72:00
CHAMBERLAND: Were you or your colleagues, were you ever concerned about, througha laboratory accident, acquiring HIV? Was that something that you worried about?
KENNEDY: I myself never worried about it. We were all in our 30's-- people werehaving babies. It seems like I remember somebody got pregnant, and they asked not to do any live virus work while they were pregnant. That was fine-- they did something else. The branch was doing a few other things, but mostly we became focused on HIV. That is basically all we were doing. We did early on agree, as soon as we had that blot, everyone in our group agreed to be tested by me every six months, in case somebody had an exposure that we didn't know about. When 73:00you're in a lab, you're in a controlled environment. It's not like you're out in the field, where you might drop a tube or somebody move their arm when you're trying to draw their blood or whatever. You're pretty controlled. So personally, I never worried about it, but I think other people-- you know, there was concern, you had to be careful.
There was glass everywhere. It took us a while to get away from that. But weagreed to do the testing. Every six months, Steve and I would draw blood from everybody in the branch. He would code, just put a number over the names, and give them to me and I would test them. We continued to do that until what was called the Serum Bank at CDC started offering testing to anybody. There were people working in virology with HIV also. But we had set up our in-house thing, and we did that until it was offered by the Serum Bank. I think everyone signed 74:00up. You got a number, you'd go to the clinic anonymously and give them your number. They drew your blood, and they would test it.
CHAMBERLAND: That was again with a lot of foresight to have a self-monitoringprogram to do that.
KENNEDY: Early on, we really weren't sure. We tried not to do anything where youwould create an aerosol, and we didn't have very many procedures that would do that. It's not airborne. You actually had to somehow inject it in you or swallow it or whatever. But we had the eye washes then. We had hydrogen peroxide by the sink that you could put in your eye. We didn't really know what to do. Steve said, just pour bleach on yourself if you cut yourself. Well, that's not recommended.
CHAMBERLAND: I was going to say, people wouldn't think that was a good thing to do.
KENNEDY: Not a good thing to do, but we didn't know what we should do. We just75:00made up these procedures about, this is what you do if you get it in your eye, if you get it in your mouth, whatever. This is what you should do. Now at CDC, they have the antiretrovirals on site all the time. If you have an accident, you can call 24 hours a day and you can get to those antiretrovirals if there is an accident.
CHAMBERLAND: Obviously you were perfectly positioned, because it was yourlaboratory that developed the Western blot test, to test for the presence of the virus.
KENNEDY: Yes, so we could start in '84.
CHAMBERLAND: You could start doing this on your own. It took a while for therest of CDC to catch up to where you were, in terms of organizing a systematic program for laboratory worker safety. You mentioned that it was a relatively small group, about 15 of you. I couldn't help but notice, looking at the Science 76:00paper that, as I said, won the Shepard Prize, that apart from Steve, it looks like everyone else was a woman.
KENNEDY: That's true. That's true. David Cross worked with us early on, and TomSpira, but yes, we were all women. There were several of us that were trained as medical technologists. There are not that many medical technologists in all of CDC. But there were some people, like Steve, who immediately recognized [that] if you get a medical technologist, they know how to do lab work. Whereas if you get a biology major, yes, they may have done some lab work, but they haven't done clinical lab work. He decided he wanted medical technologists, so there were quite a few of us that were medical technologists in his group.
CHAMBERLAND: Along the way you've mentioned a bit about Steve. Sadly, Steve77:00passed away some three years ago, so we, obviously as you said, can't personally capture his stories for this oral history project. Is there anything else you can tell us about Steve?
KENNEDY: Yes, I would love to tell some Steve stories.
CHAMBERLAND: Tell us some Steve stories.
KENNEDY: I said before [that] he was brilliant. He had this way of seeingthings. But also, he was so much fun. If you were there long enough, he gave you a nickname. Everyone had a nickname, and once you had your nickname, that was it, that's all he called you from then on. Every morning at 8:15, he would come around, try to round everybody up and get them to come to the cafeteria, because he wanted coffee. Then at 11 o'clock sharp, he was back around, trying to get everybody to go to the cafeteria for lunch. Two o'clock every afternoon, he's coming around gathering up everybody to go to what he called "treat" in the 78:00afternoon. You went because these gatherings in the cafeteria were like a lab meeting. Everybody talked about what they were doing. Other people at CDC knew that Steve was going to be in the cafeteria at those times of the day. They might not ever find him in his office. He'd be hiding out in the lab somewhere, but they knew if they went to the cafeteria he'd be there. Back then people didn't have any place else to eat. We couldn't eat in the lab. We didn't have a break room. If you wanted to eat, you had to go to the cafeteria. You could bring your lunch, but you still had to go in there to eat. So everyone went. There were a lot of jokes, I think, about Steve and all of his women. There would be Steve and this table of women sitting there. But they were very important, and you really felt like you missed out if you didn't go to one of 79:00these three-times-a day gatherings.
CHAMBERLAND: That sounds really, very inspiring for really good camaraderie andcross-fertilization of ideas.
KENNEDY: Other people-- you saw everybody else in the cafeteria. The virologypeople would be there. CDC was much smaller, and you knew, the lab people knew each other. Steve just made it fun. He just made it so much fun to go to work.
CHAMBERLAND: There are some trade-offs. Now we have a bigger campus, morelaboratory space, fancy machines that as you said at the beginning didn't exist. You did a lot of it all by hand and making your own reagents and all of that. But along the way, it's hard not to think that some things have been lost. People talk about the silos, that we all form our own silos.
Just a few questions in closing, before we wrap this up. Are there any aspects80:00of CDC's laboratory response that you think CDC could have done a better job of? I'm not necessarily asking you to critique your own work, but a lot of times when people look back, they say, "You know, we could have done this, we should have done this." I'm just curious if you've ever had thoughts about how things could have been improved upon.
KENNEDY: I felt like those early years we were moving so fast. We were doingeverything we could. I don't know if the laboratory, our laboratory, could have really done-- maybe if we'd had another couple of Steves around, we would have come up with some other things. But we were a very small group, and I'm just not sure how much more we could have done. It would have been nice if someone had 81:00discovered the virus a little bit sooner and given it to us a little sooner. I think in general, all of CDC was doing what they could. I don't know whose job it was, but it would have been nice if somebody had gotten more education out there and more awareness that this epidemic was as big as it was. Maybe if we'd had an administration that had shown some interest in this problem-- but it was people that nobody cared about. Basically, gay men were left up to themselves to educate themselves.
CHAMBERLAND: Did the lab continue to do non-HIV work at the same time, or didyou ultimately just become an HIV laboratory?
KENNEDY: The Arthritis Foundation continued. After I left, Martha Bird came andthat activity continued.
CHAMBERLAND: But with different people.82:00
KENNEDY: We did a few other things because of Steve's interest in therheumatology, but no--
CHAMBERLAND: Mostly HIV.
KENNEDY: And the hybridoma lab was under Steve at that time, where we made themonoclonal antibodies. That activity just stopped. We took over that lab because they had biological safety cabinets.
CHAMBERLAND: Hydrodoma? I don't think I've--
KENNEDY: Hybridoma. They make monoclonal antibodies, and they'd make them foranybody at CDC. That activity was in Steve's group, but that just stopped. We just went all out for AIDS.
CHAMBERLAND: Any closing thoughts? Is there anything else you'd like to add thatwe haven't covered?
KENNEDY: I am just trying to think if I gave credit to all the other people inthe labs.
CHAMBERLAND: It's clear that your group operated as a true team.83:00
KENNEDY: We did, and we had parties together, and it was like a family.
CHAMBERLAND: And for 30 years you were in this family.
KENNEDY: When I left, I retired in January of '14, I was the last person fromthat original Immunology Branch that was still in the lab. Marjorie Hubbard and Sheila Isoke were still there, but they were doing administrative things. They had not been in the lab for years. Sheila had left and come back. Marjorie had been there the whole time, but she was not actually doing lab work. I was the last one. There were other people still at CDC, but they'd moved on. They were in a different disease or a different area. I was the last laboratorian from that group.
CHAMBERLAND: Wow. You were a huge asset to have, for CDC to have for 30-plus84:00years. Susan, thank you so much for sharing these stories, particularly behind-the- scene stories that don't often get told. I mean, the papers are out there, but there's a lot behind the papers and the work. It's been a real pleasure hearing some of those stories.
KENNEDY: Thank you for including me in this project, and thanks to the peoplethat are funding this project. I think it's important to hear from people.
CHAMBERLAND: Great, thanks so much. 1