WEBVTT 00:00:00.000 --> 00:00:01.766 [Slate] 00:00:01.766 --> 00:00:09.066 [Program Number: 9017 Title: AIDS: Acquired Immunodeficiency Syndrome 00:00:09.066 --> 00:00:18.099 Record Date: 4 November 1984 Length: 58:30 Production Company: Arna Vodenos Productions Inc. 00:00:18.100 --> 00:00:28.133 Producer: Arna Vodenos Director: John Niehaus Producer's Video 3700 Malden Avenue] 00:00:28.133 --> 00:00:34.399 [Narrator:] Today AIDS, acquired immunodeficiency syndrome, is the number one priority of U.S. Public Health Service. 00:00:34.400 --> 00:00:42.000 Since AIDS was first reported in the United States, the Public Health Service has received reports of almost 6,000 cases of the disease. 00:00:42.000 --> 00:00:45.733 In our program, "AIDS: Acquired Immunodeficiency Syndrome," 00:00:45.733 --> 00:00:49.933 a part of the Medicine for the Layman Series at the National Institutes of Health, 00:00:49.933 --> 00:00:53.666 we'll take a closer look at the latest information on this new disease. 00:00:53.666 --> 00:01:03.199 [ Music ] 00:01:03.200 --> 00:01:06.066 In our program, "AIDS: Acquired Immunodeficiency Syndrome," 00:01:06.066 --> 00:01:09.899 a part of the Medicine for the Layman Series at the National Institutes of Health, 00:01:09.900 --> 00:01:13.766 we'll take a closer look at the latest information on this new disease. 00:01:13.766 --> 00:01:28.466 [ Music ] 00:01:28.466 --> 00:01:33.232 In the public interest Primark presents the following special program 00:01:33.233 --> 00:01:37.866 as part of its ongoing dedication to enhancing healthcare education and delivery through its subsidiary, 00:01:37.866 --> 00:01:41.732 the Hospital Satellite Network. 00:01:41.733 --> 00:01:58.433 [ Music ] 00:01:58.433 --> 00:02:12.866 [Medicine for the Layman] 00:02:12.866 --> 00:02:16.899 [AIDS: Acquired Immunodeficiency Syndrome] 00:02:16.900 --> 00:02:18.766 [Doctor Linda Reid:] Hello, I'm Doctor Linda Reid. 00:02:18.766 --> 00:02:22.532 Welcome to the Medicine for the Layman Series at the National Institutes of Health. 00:02:22.533 --> 00:02:26.166 Today we're going to be listening to Doctor Anthony Fauci. 00:02:26.166 --> 00:02:30.532 He's going to be talking about AIDS, the Acquired Immunodeficiency Syndrome. 00:02:30.533 --> 00:02:34.799 Doctor Fauci is with the National Institute of Infectious Diseases and Allergy. 00:02:34.800 --> 00:02:38.766 Let's find out why some people came to the lecture. 00:02:38.766 --> 00:02:40.866 [What do you want to learn about AIDS?] 00:02:40.866 --> 00:02:43.999 [Student:] I came because I'm a nursing student at George Mason University 00:02:44.000 --> 00:02:49.766 and I'm co-facilitating a seminar on AIDS with a friend of mine. We came together. 00:02:49.766 --> 00:02:52.399 [Dr. Reid:] Have you found that you've been a victim of discrimination? 00:02:52.400 --> 00:02:56.700 [AIDS Patient:] [laughs] Definitely. I have definitely been a victim of discrimination. 00:02:56.700 --> 00:03:03.166 I was fired from my job. I have been refused housing. 00:03:03.166 --> 00:03:06.966 Some medical care has been refused, but not here at the National Institutes. 00:03:06.966 --> 00:03:10.732 [Dr. Reid:] Are you worried about the future? 00:03:10.733 --> 00:03:14.033 [AIDS Patient:] [laughs] Definitely. Definitely. Right now I'm... 00:03:14.033 --> 00:03:22.033 while I'm on a research protocol at the National Institutes of Health, the government is paying for me to live in a hotel 00:03:22.033 --> 00:03:24.599 and my medical costs are covered. 00:03:24.600 --> 00:03:29.900 However, as soon as my protocol runs out I have no apartment to go back to, 00:03:29.900 --> 00:03:34.966 I have no job to go back to, and I am very scared about what's going to happen to me. 00:03:34.966 --> 00:03:41.232 [Dr. Reid:] We've seen how AIDS can gravely affect those who have it and those who are at risk for it. 00:03:41.233 --> 00:03:44.866 Now, let's take a look at another aspect of AIDS, research. 00:03:44.866 --> 00:03:51.999 In our cover story tonight we'll talk with a leading scientist about his work in AIDS research. 00:03:52.000 --> 00:03:56.300 [Narrator:] In this lab at the National Institutes of Health, the new illness that has attracted much media 00:03:56.300 --> 00:04:01.766 attention called Acquired Immune Deficiency Syndrome, or AIDS, is being carefully studied. 00:04:01.766 --> 00:04:06.432 Since the disease was first reported in the United States in mid-1981, 00:04:06.433 --> 00:04:11.933 scientists have been able to make some important breakthroughs in the discovery of what causes the disease. 00:04:11.933 --> 00:04:18.133 [Dr. Anthony Fauci:] Well, the most exciting breakthrough is unquestionably the fact that in just a few short years 00:04:18.133 --> 00:04:26.833 from the recognition that this disease exists, scientists have been able to identify and isolate the underlying cause, 00:04:26.833 --> 00:04:32.733 or etiologic agent. And AIDS is caused by HTLV3. 00:04:32.733 --> 00:04:39.433 [Narrator:] The Public Health Service has received reports of about 5,800 cases of AIDS with a case fatality ratio of 45 percent. 00:04:39.433 --> 00:04:44.999 Doctor Anthony Fauci is hopeful that the answer to this dreaded disease may be in sight. 00:04:45.000 --> 00:04:53.100 [Dr. Fauci:] I believe now that we have the agent in hand that the amount of effort and energy that's being put into it by biomedical sciences, 00:04:53.100 --> 00:04:57.433 that within a reasonable period of time we'll have a lot of these answers. 00:04:57.433 --> 00:05:01.666 [Dr. Reid:] Well, it's certainly nice to know that the future looks brighter. 00:05:01.666 --> 00:05:05.366 Now, let's go to the lecture and join Doctor Anthony Fauci as he talks about AIDS. 00:05:05.366 --> 00:05:15.366 [Dr. Fauci:] This evening what I'd like to do is discuss with you a topic which I'm sure all of you to a greater or lesser degree are aware of. 00:05:15.366 --> 00:05:25.366 It's a topic that has occupied the interest and energy of a substantial proportion of the biomedical research community 00:05:25.366 --> 00:05:33.799 here at the NIH and throughout the country and the world, most recently, and that is the subject of the Acquired Immunodeficiency Syndrome. 00:05:33.800 --> 00:05:39.966 I'm working directly on AIDS, both clinically and from a basic science standpoint, 00:05:39.966 --> 00:05:45.199 but it gives me a great deal of pleasure and excitement to talk about AIDS, 00:05:45.200 --> 00:05:50.166 because it really is one of the few, or actually one of the only subjects, 00:05:50.166 --> 00:05:58.466 of all of the subjects that we tackle throughout the years, where you really have to change your lecture every month 00:05:58.466 --> 00:06:04.432 because of the extraordinary advances and evolution of this syndrome. 00:06:04.433 --> 00:06:11.533 That has provided a great challenge for the scientists involved in this and has provided, in many respects, 00:06:11.533 --> 00:06:16.666 hope for the individuals who are afflicted with this terrible syndrome. 00:06:16.666 --> 00:06:24.466 What I'd like to do this evening is to review for you some of the most recent advances in AIDS 00:06:24.466 --> 00:06:33.466 as well as provide for you a background for understanding how we got to where we are today in our understanding of AIDS. 00:06:33.466 --> 00:06:41.932 So what I'll be discussing is some historical aspects of AIDS, the epidemiology, or as we say, the profile of the syndrome, 00:06:41.933 --> 00:06:44.733 how it came about, the populations that it afflicts. 00:06:44.733 --> 00:06:49.633 We'll talk about some of the clinical manifestations, or how the disease 00:06:49.633 --> 00:06:52.799 expresses itself in the patient population. 00:06:52.800 --> 00:06:58.266 We can now talk about something that I couldn't talk about just a few months ago, 00:06:58.266 --> 00:07:05.632 and that is the etiology of AIDS and how an understanding of the etiology has allowed us to make great advances, 00:07:05.633 --> 00:07:12.099 not only within the syndrome of AIDS, but also in a number of other diseases that have immunological components to them. 00:07:12.100 --> 00:07:18.466 And then finally we'll talk some about the treatment and prevention of this syndrome. 00:07:18.466 --> 00:07:22.499 Now, first of all we must have a definition of AIDS. 00:07:22.500 --> 00:07:28.600 And I will tell you right off that the definition that is given, although it is a good definition, 00:07:28.600 --> 00:07:33.000 in fact it's an excellent definition, it has some serious flaws. 00:07:33.000 --> 00:07:43.000 And the reason for the flaws are that it's an empiric definition that is based on the secondary complications that someone will get, 00:07:43.000 --> 00:07:47.733 who has AIDS, and let me explain what I mean. First we'll go through the definition. 00:07:47.733 --> 00:07:55.099 It's the presence of pneumocystis carinii pneumonia, or other opportunistic infections, or Kaposi's sarcoma. 00:07:55.100 --> 00:07:58.033 Now for those of you who aren't used to hearing that terminology, 00:07:58.033 --> 00:08:06.399 what it is is the presence of the disease in an individual that you would not expect to see in someone 00:08:06.400 --> 00:08:09.700 who is otherwise normal immunologically. 00:08:09.700 --> 00:08:18.600 For example, if I said, "influenza" or "the common cold" or some other disease, you'd expect to see that in a normal population. 00:08:18.600 --> 00:08:22.533 In a population that does not have an immunological defect. 00:08:22.533 --> 00:08:29.266 But these diseases are present in individuals with AIDS but the most important component of this definition 00:08:29.266 --> 00:08:34.932 is that there's an absence of a known cause of this underlying immune deficiency. 00:08:34.933 --> 00:08:43.599 In other words, they have a very severe defect in the mechanisms that protect them against these strange infections 00:08:43.600 --> 00:08:48.466 and against these tumors, which, one of which we'll call Kaposi's sarcoma. 00:08:48.466 --> 00:08:56.332 But we can't figure out a reason why they have that defect. In other words, we didn't give them any medications to get this defect. 00:08:56.333 --> 00:09:00.899 They don't have any underlying tumors that might cause an immune defect. 00:09:00.900 --> 00:09:09.933 Now, for sure, this definition is going to change in the next several months or thereabouts, 00:09:09.933 --> 00:09:20.799 and the reason is that this definition does not account for the large number of individuals who have the immune defect, 00:09:20.800 --> 00:09:28.800 but have not yet gotten what we call the secondary complications; namely those infections or those tumors. 00:09:28.800 --> 00:09:39.700 For example, if I had AIDS...if I had the infection with the virus that causes AIDS, which we'll talk about in a moment, 00:09:39.700 --> 00:09:46.500 but I hadn't yet gotten an infection, by strict definition, from the Centers for Disease Control, 00:09:46.500 --> 00:09:51.533 I could not be classified as having AIDS. 00:09:51.533 --> 00:09:56.199 There are a lot of individuals that are out there that have the defect. 00:09:56.200 --> 00:10:00.500 The reason it's important to recognize that is because the statistics 00:10:00.500 --> 00:10:07.433 that one sees regarding AIDS are based only on what I will call full-blown AIDS, 00:10:07.433 --> 00:10:14.299 and do not take into account the large number of individuals who have the defect already. 00:10:14.300 --> 00:10:19.766 Another very important aspect of this is that the transmissibility of the disease, 00:10:19.766 --> 00:10:26.099 you usually think of someone having AIDS transmitting the disease to someone else, when in fact, 00:10:26.100 --> 00:10:28.833 as I'll discuss with you in a bit, 00:10:28.833 --> 00:10:35.833 the transmissibility might occur prior to the time that an individual develops one of these infections 00:10:35.833 --> 00:10:40.099 and is thereby classified as having AIDS. 00:10:40.100 --> 00:10:44.366 Now, now that we understand and appreciate and recognize the etiologic agent, 00:10:44.366 --> 00:10:53.166 and we'll be developing tests for this, we might be able to better get a handle on the profile of this group of patients. 00:10:53.166 --> 00:11:04.966 [Did you know? AIDS is a serious condition characterized by a specific defect in natural immunity against disease.] 00:11:04.966 --> 00:11:08.766 [Next...Historical Perspective] 00:11:08.766 --> 00:11:16.632 Historically, we first recognized this disease actually as a new disease in 1981. 00:11:16.633 --> 00:11:23.533 The cases were first brought to the attention of the Centers for Disease Control, or the CDC, in 1979. 00:11:23.533 --> 00:11:32.766 In the summer of 1981 there were reports of unusual infections and/or tumors in otherwise healthy homosexual men. 00:11:32.766 --> 00:11:38.532 Now again, if I were giving you this lecture when we started working on AIDS a few years ago, 00:11:38.533 --> 00:11:46.566 I would be spending the first 10 minutes or so trying to convince the audience that we were dealing with a new disease. 00:11:46.566 --> 00:11:50.766 In fact, we don't need to waste any time on that. 00:11:50.766 --> 00:11:55.099 This is a new disease, at least in the United States. 00:11:55.100 --> 00:11:58.966 Where it came from, we'll discuss in a short while. 00:11:58.966 --> 00:12:01.466 But in the United States it's new. 00:12:01.466 --> 00:12:08.366 And it's very interesting and somewhat perplexing to have gone through, as an investigator, 00:12:08.366 --> 00:12:14.532 those early years in AIDS because when you're dealing with a new syndrome like that and you don't really understand it, 00:12:14.533 --> 00:12:23.999 anyone's hypothesis about what this might be is held in equal respect to a well-thought out hypothesis. 00:12:24.000 --> 00:12:30.233 And I think that led to a lot of the misunderstanding, not only regarding AIDS in general, 00:12:30.233 --> 00:12:40.033 but regarding the entire homosexual population and how they may have been the early victims of this particular disease. 00:12:40.033 --> 00:12:46.199 And as I'm sure you're all well-aware, there was an extraordinary amount of difficulty in that regard, 00:12:46.200 --> 00:12:55.400 particularly with the intensification of the already existing unfortunate discrimination against these individuals. 00:12:55.400 --> 00:13:07.133 I can remember in early, in the summer of 1981 when I first read in the report from the CDC of these cases of strange infections 00:13:07.133 --> 00:13:15.299 and tumors in patient, in male homosexuals in New York City area and in California, LA and San Francisco. 00:13:15.300 --> 00:13:22.333 I had thought initially that this might be a transmissible agent, but maybe it was some toxic substance, 00:13:22.333 --> 00:13:24.299 some drug or what have you, that they had ingested, 00:13:24.300 --> 00:13:32.966 but then when it became clear that such a large number of individuals, on both coasts, were getting it, we became rather suspicious 00:13:32.966 --> 00:13:34.899 that we were dealing with an infectious agent. 00:13:34.900 --> 00:13:42.133 And then as soon as the IV drug users became infected, and then hemophiliacs, 00:13:42.133 --> 00:13:49.299 with the common denominator of the possibility of blood-borne transmission in addition to sexual transmission, 00:13:49.300 --> 00:13:59.566 then it became clear that we were dealing with a very special, unprecedented situation, which we'll have the opportunity to go through with you. 00:13:59.566 --> 00:14:06.066 [Did you know? No cases have been found where AIDS has been transmitted 00:14:06.066 --> 00:14:09.899 by casual contact with AIDS patients or persons in high risk groups.] 00:14:09.900 --> 00:14:13.300 [Next...Epidemiology] 00:14:13.300 --> 00:14:15.566 What do we mean by risk groups? 00:14:15.566 --> 00:14:22.632 The risk groups are those individuals who, because of the epidemiology or the profile of the disease, 00:14:22.633 --> 00:14:26.933 appear to be at a particular risk of getting the disease. 00:14:26.933 --> 00:14:36.433 Now, if one looks at the profile in the United States, 71 or more percent of the individuals with this full-blown AIDS now 00:14:36.433 --> 00:14:39.666 are homosexual or bisexual men. 00:14:39.666 --> 00:14:43.832 Seventeen and a half percent of them are intravenous drug users. 00:14:43.833 --> 00:14:45.766 Four percent are Haitian. 00:14:45.766 --> 00:14:48.232 A little less than one percent are hemophiliacs, 00:14:48.233 --> 00:14:55.233 and about six percent of them don't fall into any of the known above risk groups. 00:14:55.233 --> 00:15:03.866 This number is much less now because there's been an expansion of the risk groups, which are related to now our understanding 00:15:03.866 --> 00:15:08.266 of the etiology and transmissibility of this disease. 00:15:08.266 --> 00:15:19.232 I'll get to in some of the later slides how this disease, which we surmised early on, started off in the male homosexual population 00:15:19.233 --> 00:15:27.099 in this country, not that there was anything intrinsically different or wrong or what have you about homosexuality, 00:15:27.100 --> 00:15:30.766 it was very simple; it's straightforward epidemiology. 00:15:30.766 --> 00:15:38.266 You take an infectious agent and you introduce it into a population in which the spread among those individuals, 00:15:38.266 --> 00:15:43.199 if it's sexual-contact spread, it's a perfect setup to spread. 00:15:43.200 --> 00:15:49.800 In any event, what we had was a concentration of cases, as you'll see here, 00:15:49.800 --> 00:15:54.400 in the New York Metropolitan Area, New York City and New Jersey, 00:15:54.400 --> 00:15:58.366 and in Los Angeles and San Francisco in California. 00:15:58.366 --> 00:16:06.232 Some of the data that I'll be showing you now is based on the first 4,000 cases of AIDS in this country. 00:16:06.233 --> 00:16:17.733 Right now, in October of 1984, there are greater than 6,000 documented cases of full-blown AIDS in the United States. 00:16:17.733 --> 00:16:28.033 Now, this color diagram, with the darker areas being the most intense areas with regard to the populations involved, as you can see, 00:16:28.033 --> 00:16:32.099 now it's spread into most of the states in the United States. 00:16:32.100 --> 00:16:35.400 As a matter of fact, it has spread throughout the world. 00:16:35.400 --> 00:16:44.200 But the earlier concentration in New York and California again merely reflected that since the majority of the patients 00:16:44.200 --> 00:16:52.966 at that time were male homosexuals, there is a great concentration of what has been called "fast-lane" homosexuals, 00:16:52.966 --> 00:16:59.199 and I'll explain what I mean by that in a moment, here in New York City and in the two cities in California. 00:16:59.200 --> 00:17:07.000 "Fast-lane" is an unfortunate term that's used to designate a large amount, or a great degree, 00:17:07.000 --> 00:17:15.066 of sexual contact, meaning large numbers of sexual partners, in many cases anonymous sexual partners. 00:17:15.066 --> 00:17:20.932 Now, people kind of get hung up on that with regard to the concept of homosexuality. 00:17:20.933 --> 00:17:28.099 And that's unfortunate because all that is telling us is that if someone has multiple sexual contacts, 00:17:28.100 --> 00:17:35.266 and has a sexually-transmitted disease, that disease will spread within that population, 00:17:35.266 --> 00:17:38.032 and that's exactly what we were seeing. 00:17:38.033 --> 00:17:46.633 And as you can see the breakdown of New York, San Francisco, Miami, etc. is right there. 00:17:46.633 --> 00:17:56.366 At the time that the disease was first recognized, we had no idea that this was a viral agent that was introduced into the population. 00:17:56.366 --> 00:18:08.099 So investigators, particularly the Centers for Disease Control, the CDC, tried to collect a wide range of epidemiologic data, namely, 00:18:08.100 --> 00:18:13.133 what is the profile of these patients? 00:18:13.133 --> 00:18:19.266 And the information merely bounced back as telling us what the profile of the risk groups were. 00:18:19.266 --> 00:18:26.432 For example, at the time this data was collected, we knew that the majority were male homosexuals, 00:18:26.433 --> 00:18:31.666 but there was a rather substantial group that were IV drug users. 00:18:31.666 --> 00:18:36.266 And if one looks at race/ethnicity, the reason we broke it down into race/ethnicity, 00:18:36.266 --> 00:18:42.732 we wanted to determine if there was any factor, genetic or otherwise, which would predispose someone to AIDS. 00:18:42.733 --> 00:18:47.599 As you can see, about 58 percent of the individuals were white, non-Hispanic. 00:18:47.600 --> 00:18:55.233 If you did a profile of the male homosexuals in New York and California, the majority of them would be white, non-Hispanics. 00:18:55.233 --> 00:19:00.033 There was a lesser group that were black, non-Hispanics and others were Hispanics. 00:19:00.033 --> 00:19:07.833 If you look at the IV drug users in those major cities, the majority of them would be blacks and Hispanics. 00:19:07.833 --> 00:19:11.399 So all we were seeing were profiles of the risk groups. 00:19:11.400 --> 00:19:15.000 The same held true if we tried to break them down by age. 00:19:15.000 --> 00:19:20.966 Most of the individuals were seen between the 20 and 49 year age group. 00:19:20.966 --> 00:19:30.699 All that told us is that is exactly the age group where most of the actively practicing male homosexual population in this country is. 00:19:30.700 --> 00:19:39.066 Again, merely a reflection of the epidemiology of the risk group, and didn't really tell us much about the disease. 00:19:39.066 --> 00:19:42.499 Now, what about transmissibility of AIDS? 00:19:42.500 --> 00:19:52.666 Again, I need not go into the data explaining why we know now for sure that a) this is a new agent, 00:19:52.666 --> 00:20:02.632 and b) this agent is transmitted by sexual contact and by blood or blood products. 00:20:02.633 --> 00:20:14.899 Now, I suggested the hypothesis to you a few minutes ago that the disease started off in this country within the male homosexual population, 00:20:14.900 --> 00:20:17.200 and that's exactly what happened. 00:20:17.200 --> 00:20:22.433 There are some theories of how it got introduced into the male homosexual population. 00:20:22.433 --> 00:20:34.599 If that is the case, which indeed it is, then the transmissibility will relate to the contacts within the male homosexual population 00:20:34.600 --> 00:20:43.300 as well as the overlap between the male homosexual population and other populations that became risk groups. 00:20:43.300 --> 00:20:45.566 And now that's very clearly seen. 00:20:45.566 --> 00:20:50.666 Now, you keep getting asked, why the male homosexual population? 00:20:50.666 --> 00:20:58.866 Well, as I mentioned, for reasons that will become clear shortly, the virus was introduced into the population, 00:20:58.866 --> 00:21:02.466 and it's a sexually transmitted disease. 00:21:02.466 --> 00:21:06.432 Therefore sexual contact spreads the disease. 00:21:06.433 --> 00:21:12.966 Since male homosexual individuals almost invariably, not always, 00:21:12.966 --> 00:21:17.199 confine their homosexual activities, or their sexual activities, 00:21:17.200 --> 00:21:24.300 to other male homosexuals, what you are going to have is a compounding and a spread within that group. 00:21:24.300 --> 00:21:30.000 There's nothing intrinsic about homosexuality that would make them susceptible to the disease. 00:21:30.000 --> 00:21:40.833 If you want to create an analogy, let us say that this disease was transmitted by sneezing, which it is not, 00:21:40.833 --> 00:21:49.833 it is clearly not transmitted that way, then if you had the disease introduced into schoolchildren, 00:21:49.833 --> 00:21:54.366 schoolchildren would have it in a rampant form because they sneeze all over each other. 00:21:54.366 --> 00:21:58.666 Not to mention, people who ride the subways and elevators and things like that. 00:21:58.666 --> 00:22:00.999 That's not the way this disease is spread. 00:22:01.000 --> 00:22:06.466 It is spread by sexual transmission and it was introduced into a population 00:22:06.466 --> 00:22:13.399 in which sexual contact is rather substantial with regard to numbers. 00:22:13.400 --> 00:22:19.800 The same thing holds true for blood or blood product, it can be transmitted by blood or blood products. 00:22:19.800 --> 00:22:27.800 So what is the link then with how the disease got out of the homosexual population into other risk groups? 00:22:27.800 --> 00:22:34.900 This is diagramed here on this slide because if you look at the male homosexual population, 00:22:34.900 --> 00:22:40.266 a proportion of them, a small proportion, but nonetheless a proportion of them, 00:22:40.266 --> 00:22:44.066 overlap with intravenous drug users. 00:22:44.066 --> 00:22:52.199 Since this is a virus, and the virus can go by bloodborne transmission now from the homosexual group 00:22:52.200 --> 00:22:55.300 to the needles of IV drug users. 00:22:55.300 --> 00:23:04.533 Hence you now have it in IV drug users who spread it among themselves by sharing the needle, which is contaminated by this virus. 00:23:04.533 --> 00:23:10.933 We know that individuals can be walking around carrying the virus and not know it. 00:23:10.933 --> 00:23:13.499 They give blood transfusions. 00:23:13.500 --> 00:23:21.766 They give blood products that will ultimately be, later they are transformed into plasma products 00:23:21.766 --> 00:23:28.466 to be given to the hemophiliacs, who need those clotting factors to reconstitute their deficient clotting. 00:23:28.466 --> 00:23:33.999 Hence the disease can then overlap into the hemophiliac population. 00:23:34.000 --> 00:23:42.866 And as I'm going to show you in a moment, that risk group, of the four major risk groups, has expanded some for the reasons 00:23:42.866 --> 00:23:50.032 which I have just explained, namely contact between the original risk groups and other risk groups, 00:23:50.033 --> 00:23:51.666 which have now accumulated. 00:23:51.666 --> 00:23:57.332 And on this slide what we have is what we'll call the expanded risk groups. 00:23:57.333 --> 00:24:02.599 We've spoken about the first, the second, the third, and the fourth. 00:24:02.600 --> 00:24:14.333 Now, the Haitian situation has created some controversy in this country, and the reason is that we have, public health officials 00:24:14.333 --> 00:24:18.199 have designated the Haitians as a separate risk group. 00:24:18.200 --> 00:24:23.700 Now, the objection to that and it's a reasonable objection is that discriminates against Haitians. 00:24:23.700 --> 00:24:27.066 Why should you call the Haitians a separate risk group? 00:24:27.066 --> 00:24:33.666 We call them a separate risk group because only a very small percentage of the Haitian population, 00:24:33.666 --> 00:24:38.399 their AIDS can be explained by homosexual activity or IV drug use. 00:24:38.400 --> 00:24:45.166 So there's something else going on there and we'll get to that when we talk about what we're calling now, the African connection. 00:24:45.166 --> 00:24:52.366 Transfusion related; again the disease is clearly transmitted from transfusions. 00:24:52.366 --> 00:24:56.966 Does that mean you should feel unsafe about getting a transfusion? No. 00:24:56.966 --> 00:25:05.132 Because the risk is so small that the chances of getting AIDS from a transfusion are less than the chances of somebody mixing up the blood 00:25:05.133 --> 00:25:10.666 and giving you the wrong blood and you're winding up with a transfusion reaction and dying from it. 00:25:10.666 --> 00:25:16.766 So, the fact is, from an epidemiological standpoint we must be aware of that, but the risk is not great. 00:25:16.766 --> 00:25:21.132 So the fear of getting a blood transfusion is unwarranted. 00:25:21.133 --> 00:25:25.666 Female sexual partners of AIDS patients, or persons at risk for AIDS; 00:25:25.666 --> 00:25:36.366 a very important clue of the profile of that disease in this country, because the female sexual partners of bisexual males 00:25:36.366 --> 00:25:40.266 or of IV drug users have gotten the disease. 00:25:40.266 --> 00:25:49.332 What we haven't seen, and it is probably the reason why this disease has not spread rampantly into other risk groups, 00:25:49.333 --> 00:25:56.966 is that we're not seeing what we call back-transmission, or transmission from a woman back to a man, 00:25:56.966 --> 00:26:05.732 and that has an important implication that is different from what we're seeing, as I'll mention shortly in the African connection. 00:26:05.733 --> 00:26:10.599 Now, children in households of AIDS patients, we'll get back to that in a moment. 00:26:10.600 --> 00:26:16.033 Certain black Africans, such as those in Chad, Zaire, etc. and persons in none of the above risk groups; 00:26:16.033 --> 00:26:18.799 this number nine is really rather small. 00:26:18.800 --> 00:26:22.066 Let's take a look at some of these risk groups. 00:26:22.066 --> 00:26:25.266 Can it be transmitted by blood transfusions? 00:26:25.266 --> 00:26:33.699 Clearly we have documented a significant number of cases of transfusion-related AIDS. 00:26:33.700 --> 00:26:41.333 In other words, someone who was carrying the virus donated blood and that whole blood or blood products 00:26:41.333 --> 00:26:46.466 were then transfused into an individual who was not in any of the other risk groups. 00:26:46.466 --> 00:26:53.199 That individual two years, three years, and even as late as four or five years, comes down with AIDS. 00:26:53.200 --> 00:27:00.133 The question, that's very interesting and important, is that blood was given to a large number of individuals. 00:27:00.133 --> 00:27:04.166 Why does only maybe one or two come down with AIDS? 00:27:04.166 --> 00:27:08.332 And the reason for that is probably related to what we call co-factors, 00:27:08.333 --> 00:27:14.799 or there are intrinsic or innate susceptibility to getting AIDS, which if you don't have that, 00:27:14.800 --> 00:27:18.966 even if you're exposed to the agent, you won't get it. 00:27:18.966 --> 00:27:22.832 In essence, AIDS is a difficult disease to catch. 00:27:22.833 --> 00:27:25.699 It definitely is a difficult disease to catch. 00:27:25.700 --> 00:27:33.166 We know how it's transmitted, but you can be exposed to that agent and not at all get the disease. 00:27:33.166 --> 00:27:38.466 Moving on then to other possibilities: what about heterosexual contact? 00:27:38.466 --> 00:27:45.166 I gave you the example of the heterosexual female partner of a male with AIDS. 00:27:45.166 --> 00:27:54.066 Heterosexual contact indeed is one of the major modes of transmission, for example in Africa. 00:27:54.066 --> 00:27:56.632 That's different than in the United States. 00:27:56.633 --> 00:28:04.999 We don't know why if a woman has AIDS in the U.S. population she will, at least by the data so far, 00:28:05.000 --> 00:28:10.666 not transmit the disease back to her male heterosexual partner. 00:28:10.666 --> 00:28:14.466 Now, there is a lot of hypothesis of why that is so, 00:28:14.466 --> 00:28:16.866 and again, we don't know for sure. 00:28:16.866 --> 00:28:26.232 But one of the possibilities is that the disease, although it's sexually transmitted, needs to enter into the bloodstream. 00:28:26.233 --> 00:28:36.166 Now, from heterosexual contact, from vaginal intercourse, it is unlikely that the agent can break through the vaginal mucosa. 00:28:36.166 --> 00:28:44.432 But that is not the case if one thinks for example of the anal intercourse that is the common practice in the homosexual population, 00:28:44.433 --> 00:28:54.866 which may be one of the reasons why those, that the small rents or tears in rectal mucosa may be a perfect entry site for the virus. 00:28:54.866 --> 00:29:02.999 Again, these are things that you'll read about and that you'll hear about. The proof of that is not really well-established. 00:29:03.000 --> 00:29:04.766 AIDS in infants. 00:29:04.766 --> 00:29:12.366 Now, you might remember some time ago when the newspapers broke that AIDS was seen in infants 00:29:12.366 --> 00:29:18.932 in households of an individual at risk for AIDS or who had AIDS. 00:29:18.933 --> 00:29:27.166 It was that which brought to focus the possibility and the conjecture on the part of the lay-press 00:29:27.166 --> 00:29:34.366 that perhaps AIDS could be spread by casual contact, namely by having an infant or a child in a home 00:29:34.366 --> 00:29:41.566 being rocked or put on the knee of an uncle who was an IV drug user and in fact was harboring the virus. 00:29:41.566 --> 00:29:53.532 That was very unfortunate because what that led to was a fear that maybe it was transmitted by casual contact. 00:29:53.533 --> 00:30:00.433 We know now, from the work of Bob Gallo and his colleagues, that if you examine the infants with AIDS, 00:30:00.433 --> 00:30:08.666 and their mothers, the mother in three out of four cases has the virus in an asymptomatic way. 00:30:08.666 --> 00:30:17.166 In other words, the child did not get it from casual contact or even close, intimate contact that you would give to a baby. 00:30:17.166 --> 00:30:24.732 The child got it either intrauterinely or perinatally because the mother had the virus. 00:30:24.733 --> 00:30:35.233 So that brings us then to a question that is very important and that is asked constantly of me and my colleagues in this area. 00:30:35.233 --> 00:30:39.233 Can AIDS be transmitted by casual contact? 00:30:39.233 --> 00:30:43.133 And we've learned to never say never and never say always in medicine, 00:30:43.133 --> 00:30:51.433 but we've also learned to look at the scientific data and the scientific data is overwhelming 00:30:51.433 --> 00:30:57.266 that in fact AIDS cannot be transmitted by casual contact. 00:30:57.266 --> 00:31:03.099 In other words, a waiter, someone in the elevator, someone sneezing on you, 00:31:03.100 --> 00:31:10.566 or even someone embracing you or hugging you or holding your hand is not going to transmit AIDS. 00:31:10.566 --> 00:31:22.132 So the fear of individuals who either have AIDS or are at risk group for AIDS transmitting AIDS is an understandable fear, 00:31:22.133 --> 00:31:31.199 but really might translate into uncalled-for discrimination, which unfortunately has been the case. 00:31:31.200 --> 00:31:39.466 And that's an issue that I really must emphasize over and over again; that there is no scientific evidence at all 00:31:39.466 --> 00:31:41.966 that it can be transmitted by casual contact. 00:31:41.966 --> 00:31:45.666 Now, what about the geographic origin of AIDS? 00:31:45.666 --> 00:31:52.832 What I'm going to tell you in the next couple of minutes and in this next two slides is scientific data, 00:31:52.833 --> 00:31:56.866 and I'll tell you with the data, and then some speculation. 00:31:56.866 --> 00:32:03.866 The scientific data is that AIDS exists in Africa, in central Africa, particularly in Zaire. 00:32:03.866 --> 00:32:08.566 It exists in a rather substantial way. 00:32:08.566 --> 00:32:14.632 The incidence of AIDS in Zaire is as great as it is, per 100,0000 population, 00:32:14.633 --> 00:32:16.399 as it is in San Francisco. 00:32:16.400 --> 00:32:23.566 If one does epidemiologic study by examining the sera of individuals in Africa, 00:32:23.566 --> 00:32:31.466 we know that the disease existed there in the early 70s, before it existed in the United States. 00:32:31.466 --> 00:32:38.132 Is then central Africa the source or the origin of AIDS in the United States? 00:32:38.133 --> 00:32:39.933 I don't know that. 00:32:39.933 --> 00:32:43.299 Now we're talking about hypothesis. Let me tell you another fact. 00:32:43.300 --> 00:32:53.533 In the late '60s and early '70s, thousands, not a few, but thousands, of Haitians came to Zaire, particularly in Kinshasa, 00:32:53.533 --> 00:32:59.799 the capital, to work as technical advisers for the Zairian government. 00:32:59.800 --> 00:33:05.000 After several years there, because of the nationalization of much of the industry, 00:33:05.000 --> 00:33:12.200 they were essentially kicked out of Zaire and came back to Haiti, to the United States, and to Canada. 00:33:12.200 --> 00:33:14.400 Is that a possible connection? 00:33:14.400 --> 00:33:21.566 The answer is yes, because it is very likely that the male homosexuals in New York City, 00:33:21.566 --> 00:33:27.699 who frequently travel to Port au Prince in Haiti for vacations and for sexual contacts down there, 00:33:27.700 --> 00:33:35.400 picked up the virus in Haiti and then, because of the mobility of the population between New York and the West Coast, 00:33:35.400 --> 00:33:38.133 there was spread back and forth from the West Coast. 00:33:38.133 --> 00:33:46.366 In addition, the early cases in Europe, in France, the early cases in England and in Germany, can be clearly traced 00:33:46.366 --> 00:33:51.332 to homosexual contacts from individuals who resided in New York. 00:33:51.333 --> 00:33:56.266 But there's also a very important clue there because most of the cases in Belgium 00:33:56.266 --> 00:34:05.032 in fact were among black Africans who had come from Zaire and had gone to Belgium for medical assistance. 00:34:05.033 --> 00:34:09.333 As you probably know, Zaire was formerly the Belgian Congo. 00:34:09.333 --> 00:34:12.933 So there's a great deal of link between Belgium and Zaire. 00:34:12.933 --> 00:34:18.333 That was the first clue that perhaps the disease might have originated there. 00:34:18.333 --> 00:34:27.299 So we don't know really scientifically where it originated, but a series of circumstantial happenings strongly suggest 00:34:27.300 --> 00:34:36.100 that this may have been the original focus and how it happened to get introduced into the male homosexual population. 00:34:36.100 --> 00:34:40.366 [Did you know? Many AIDS patients do recall having symptoms before being diagnosed. 00:34:40.366 --> 00:34:45.899 They include fever, night sweats, swollen glands, weight loss, yeast infections.] 00:34:45.900 --> 00:34:51.133 [Next...Clinical Manifestations] 00:34:51.133 --> 00:34:53.233 What about the clinical manifestations of AIDS? 00:34:53.233 --> 00:34:58.066 In other words, what happens to individuals who get full-blown AIDS? 00:34:58.066 --> 00:35:05.632 Well, first of all there are what we call opportunistic infections, and I'll explain that in a moment. 00:35:05.633 --> 00:35:10.733 Then there is tumors called Kaposi's sarcoma, which we'll explain. 00:35:10.733 --> 00:35:13.866 There's an interesting syndrome called chronic lymphadenopathy. 00:35:13.866 --> 00:35:18.232 There are certain other tumors and there are what we call autoimmune phenomenon, 00:35:18.233 --> 00:35:23.199 which merely reflect an aberrancy of the body's immune system. 00:35:23.200 --> 00:35:26.133 What do we mean when we say opportunistic infection? 00:35:26.133 --> 00:35:33.799 An opportunistic infection is an infection which occurs in a person whose defense mechanisms are impaired, 00:35:33.800 --> 00:35:41.666 hence the microorganism uses the opportunity to invade the person because of the weakened defenses. 00:35:41.666 --> 00:35:47.066 In other words, it takes the opportunity, hence it is an opportunistic infection. 00:35:47.066 --> 00:35:52.399 You wouldn't expect to see that infection in individuals who have normal immunity. 00:35:52.400 --> 00:35:56.200 And here are some of these opportunistic infections. 00:35:56.200 --> 00:36:02.000 They have very strange names that I'm not going to run through, but I'm going to give you some examples of them. 00:36:02.000 --> 00:36:09.366 It's important to realize that these were big, red flags for us early on in our study of AIDS, 00:36:09.366 --> 00:36:15.899 because you would not expect an otherwise healthy individual, like a healthy young homosexual man, 00:36:15.900 --> 00:36:23.866 to get any of these things unless something was very, very wrong with his immune system. 00:36:23.866 --> 00:36:32.699 The first is a particular type of pneumonia, which is called pneumocystis carinii pneumonia, which is caused by a protozoa organism 00:36:32.700 --> 00:36:36.433 that is ubiquitous, it is all over, it's in my lung. 00:36:36.433 --> 00:36:44.433 The reason I don't have pneumocystis carinii pneumonia, because my defense mechanisms are keeping that organism in check. 00:36:44.433 --> 00:36:49.466 If I were to take drugs that would markedly immunosuppress me, 00:36:49.466 --> 00:36:53.666 there would be a reasonably good chance that I would get that pneumonia. 00:36:53.666 --> 00:36:58.232 That's what happens to the AIDS individuals, as I'll show you when we talk about immunology. 00:36:58.233 --> 00:37:00.533 They're substantially immunosuppressed. 00:37:00.533 --> 00:37:04.166 What about this microorganism? 00:37:04.166 --> 00:37:08.966 It's called mycobacterium avium intracellulare, again a bizarre illness. 00:37:08.966 --> 00:37:14.666 I have been doing infectious disease consults in this building for the last 16 and a half years 00:37:14.666 --> 00:37:23.299 and I have seen one case of mycobacterium avium intracellulare in cancer patients who we immunosuppressed with chemotherapy. 00:37:23.300 --> 00:37:27.466 We see it all the time now in our patients with AIDS. 00:37:27.466 --> 00:37:36.532 Here's an individual who has oral thrush, or candida, in the mucosal membrane of their mouth. 00:37:36.533 --> 00:37:40.166 It can also affect the esophagus. 00:37:40.166 --> 00:37:44.632 This is an x-ray of an esophagus in which we poured dye down the esophagus, 00:37:44.633 --> 00:37:52.333 and what you see, it's difficult if you haven't read these before, but this should be a very smooth surface because your esophagus 00:37:52.333 --> 00:37:58.899 is very smooth, which allows the food to go down there in an almost imperceptible way. 00:37:58.900 --> 00:38:03.600 Here are what we call scalloping of the esophagus. 00:38:03.600 --> 00:38:10.033 That's due to the invasion of the mucosa by the candida microorganism. 00:38:10.033 --> 00:38:17.133 And also there's a disease called cytomegalovirus, which is a virus that isn't the cause of AIDS, 00:38:17.133 --> 00:38:22.566 but it's one of those opportunistic infections that comes in and attacks an individual. 00:38:22.566 --> 00:38:30.299 And here is a photograph of the eye of a patient of mine with AIDS, which as you can see is what we call chewed up. 00:38:30.300 --> 00:38:35.566 And I'll show you what we mean by that when one compares it with a normal retina. 00:38:35.566 --> 00:38:40.199 See the smoothness and the easy ability to look at the blood vessel. 00:38:40.200 --> 00:38:43.033 This is what it looks like in an AIDS patient. 00:38:43.033 --> 00:38:47.599 The virus has infiltrated the cells of the retina. 00:38:47.600 --> 00:38:50.300 What about tumors in AIDS? 00:38:50.300 --> 00:38:56.433 Well, Kaposi's sarcoma we'll explain in a moment, and diffuse undifferentiated Hodgkin's lymphoma. 00:38:56.433 --> 00:38:57.333 Now what do I mean by that? 00:38:57.333 --> 00:39:06.833 All that means is that there's a particular type of a tumor of a particular type of a cell that is seen in these individuals with AIDS. 00:39:06.833 --> 00:39:12.233 These are the typical skin lesions of Kaposi's sarcoma. 00:39:12.233 --> 00:39:14.033 Now, what is Kaposi's sarcoma? 00:39:14.033 --> 00:39:18.699 It's a tumor of those cells which make up blood vessels. 00:39:18.700 --> 00:39:20.733 What we call them, endothelial cells. 00:39:20.733 --> 00:39:27.499 The disease is usually confined to the skin, but in AIDS patients it spreads to all organs of the body. 00:39:27.500 --> 00:39:33.633 Ten percent of Kaposi's sarcoma in non-AIDS patients spreads elsewhere. 00:39:33.633 --> 00:39:40.466 75 percent of AIDS patients who have Kaposi's will have spread if you do not check the disease, 00:39:40.466 --> 00:39:44.099 and this, Kaposi's can really come in very strange places. 00:39:44.100 --> 00:39:47.466 Here it is in the eyelid of an individual. 00:39:47.466 --> 00:39:52.332 There is a syndrome that's related to AIDS called chronic lymphadenopathy. 00:39:52.333 --> 00:39:59.566 And all that is is swelling of the lymph glands, either in the groin, in the axilla, in the neck or cervical area. 00:39:59.566 --> 00:40:06.299 If I were giving this lecture eight months ago I would have a slide that had a question: 00:40:06.300 --> 00:40:09.800 what is the relationship of chronic lymphadenopathy to AIDS? 00:40:09.800 --> 00:40:11.066 Is it related? 00:40:11.066 --> 00:40:20.332 Well, we now know from virus isolation that greater than 85 percent of individuals with this syndrome have the virus in them. 00:40:20.333 --> 00:40:24.966 The real question that we don't know the answer to now, in October of 1984, 00:40:24.966 --> 00:40:30.599 is what proportion of those individuals will ultimately go on to develop AIDS. 00:40:30.600 --> 00:40:39.033 The key, or the secret, to protection against full-blown AIDS may be in these chronic lymphadenopathy patients. 00:40:39.033 --> 00:40:42.733 In other words, why aren't they all getting AIDS? 00:40:42.733 --> 00:40:52.466 We're studying these individuals to try and determine what component of their immune response is keeping the AIDS virus in check. 00:40:52.466 --> 00:40:58.932 We do know, with regard to my question of the relationship of persistent lymphadenopathy to AIDS, 00:40:58.933 --> 00:41:08.199 that from 2.5 to 17 to 19 percent of those individuals, over a two to three year period, will develop AIDS. 00:41:08.200 --> 00:41:12.300 We don't know what the five and ten year figure will be. 00:41:12.300 --> 00:41:19.466 Now, what about the fatality of this disease, before we get onto the etiology and immunology. 00:41:19.466 --> 00:41:28.366 The number that is given by the Centers for Disease Control, is approximately 43 percent of all the patients. 00:41:28.366 --> 00:41:35.932 But if you break them down from individuals who were diagnosed in 1979 and look up to the point of individuals 00:41:35.933 --> 00:41:42.066 who were diagnosed this year, one can see that there are very few, if any, individuals still alive 00:41:42.066 --> 00:41:44.666 who had the disease back in 1979. 00:41:44.666 --> 00:41:50.332 Obviously there are a large number here, 80 percent of them are alive, who were diagnosed in 1984. 00:41:50.333 --> 00:41:59.433 Right now, the ultimate mortality of someone who has full-blown AIDS, namely already has the secondary complications, 00:41:59.433 --> 00:42:02.099 might approach 100 percent. 00:42:02.100 --> 00:42:06.933 Now, when you say that, you go now, "Wait a minute, there are a lot of people out there who have AIDS. 00:42:06.933 --> 00:42:09.233 Are they all going to die?" 00:42:09.233 --> 00:42:11.599 The answer to that is we don't know. 00:42:11.600 --> 00:42:14.466 But that's the way the research is going now. 00:42:14.466 --> 00:42:22.366 That is the reason why we are furiously looking at means, be them direct attack on the virus itself, 00:42:22.366 --> 00:42:32.432 or attempt to reconstitute the immune response with various factors, such that we can curb this very high fatality rate 00:42:32.433 --> 00:42:37.966 and we won't have 100 percent mortality, and we have a lot of hope that in fact, given the work that's going on now, 00:42:37.966 --> 00:42:44.032 we might see a realization of that hope in some time, hopefully very soon. 00:42:44.033 --> 00:42:48.433 [Did you know? Since the disease was reported, the Public Health Service has received reports 00:42:48.433 --> 00:42:54.699 of about 5800 cases with a case fatality ratio of 45 percent.] 00:42:54.700 --> 00:43:00.200 [Next...Etiology] 00:43:00.200 --> 00:43:01.833 What about the etiology of AIDS? 00:43:01.833 --> 00:43:06.699 I've been alluding throughout this entire discussion to this virus that causes AIDS. 00:43:06.700 --> 00:43:09.033 What about this virus? What is it? 00:43:09.033 --> 00:43:11.233 I'm sure you've heard about it in the paper. 00:43:11.233 --> 00:43:18.266 We call it the human T-cell leukemia lymphoma virus, or HTLV3. 00:43:18.266 --> 00:43:27.099 And the reason we call it that was that a few years ago Bob Gallo, from the Cancer Institute here at the NIH, had discovered that a virus, 00:43:27.100 --> 00:43:34.333 a retrovirus, as we call it, and that's what it is, a retrovirus because it has a particular type of an enzyme in it, 00:43:34.333 --> 00:43:40.933 which gives you a reversal of the usual genetic process of propagating itself, was causing 00:43:40.933 --> 00:43:47.433 this HTLV1, was causing adult t-cell lymphomas and leukemias that were endemic in Japan, in the Caribbean, 00:43:47.433 --> 00:43:50.499 and in certain southeastern states of the United States. 00:43:50.500 --> 00:43:59.900 In fact, a variant of this HTLV1, which we've been calling HTLV3, is in fact the etiologic agent of AIDS. 00:43:59.900 --> 00:44:05.833 An agent was discovered in France, which the French call lymphadenopathy-associated virus, or LAV. 00:44:05.833 --> 00:44:08.399 It's the same thing as HTLV3. 00:44:08.400 --> 00:44:13.466 So the virus in Europe, in Africa, in the United States is the same. 00:44:13.466 --> 00:44:22.199 Here is a schematic diagram showing you that this virus has a propensity to attack a particular type of cell. 00:44:22.200 --> 00:44:30.033 That's a really, truly critical point because before we knew what the virus was, 00:44:30.033 --> 00:44:36.133 the only thing we knew was that our patients had a selected defect of a particular type of a cell. 00:44:36.133 --> 00:44:38.699 And it was a T-helper cell. 00:44:38.700 --> 00:44:40.533 I'm going to explain what I mean by that in a moment. 00:44:40.533 --> 00:44:51.299 That was the clue for the individuals who were doing the virology to look for a virus that infected T4 cells, or helper cells. 00:44:51.300 --> 00:44:58.600 Now, we already knew from Gallo's work that lymphoproliferative, or adult t-cell leukemia, was caused by this virus, 00:44:58.600 --> 00:45:08.533 so therefore a major effort was directed at determining if a variant of this virus could actually cause depletion of lymphocytes, 00:45:08.533 --> 00:45:11.466 or acquired immunodeficiency syndrome. 00:45:11.466 --> 00:45:17.032 And as it turned out, a variant of that virus, in fact, caused the syndrome. 00:45:17.033 --> 00:45:20.366 We have to understand some basic fundamentals about the immune system. 00:45:20.366 --> 00:45:22.966 There are major components of the immune system. 00:45:22.966 --> 00:45:24.932 There are cells called B cells. 00:45:24.933 --> 00:45:31.299 We call it B because it's bone marrow derived, or bursa-equivalent. It's a technical term 00:45:31.300 --> 00:45:38.566 that merely connotes that this cell has a certain derivation, but its function is what's important. 00:45:38.566 --> 00:45:43.332 It makes the antibodies, those proteins that attack microorganisms. 00:45:43.333 --> 00:45:45.866 B cells produce antibodies. 00:45:45.866 --> 00:45:48.366 We need them for our defenses. 00:45:48.366 --> 00:45:54.099 In addition to B cells there's a very interesting kind of cell called a helper cell. 00:45:54.100 --> 00:46:04.400 The reason we call it a helper cell, it is because it is responsible for helping, not only this B cell but all other cells, perform their function. 00:46:04.400 --> 00:46:07.833 It's the catalyst that makes the immune system go. 00:46:07.833 --> 00:46:13.266 It's the focal cell that orchestrates the immune system, this T-cell. 00:46:13.266 --> 00:46:16.499 It's called T because it's derived from the thymus gland. 00:46:16.500 --> 00:46:25.500 And it is a T4 cell because it has a designation of a monoclonal antibody that can recognize it, or some technique that we use to identify it, 00:46:25.500 --> 00:46:29.433 and it has inducer or helper function. 00:46:29.433 --> 00:46:38.099 In addition to balancing immune response, we have suppressor cells, which can actually dampen down the immune system. 00:46:38.100 --> 00:46:45.666 So we have B cells making the antibodies, T-cell doing the orchestration, suppressor cells keeping the lid on things 00:46:45.666 --> 00:46:49.332 so that the immune system doesn't run away with itself. 00:46:49.333 --> 00:46:52.933 When it does, as a matter of fact, that's how you get autoimmune disease, 00:46:52.933 --> 00:46:56.766 which is a different topic that we don't have time to discuss this evening. 00:46:56.766 --> 00:47:05.132 With that as a very basic background of the immune system, how does HTLV3 affect these human t-cells? 00:47:05.133 --> 00:47:08.633 Well, it selectively infects the t-cell. 00:47:08.633 --> 00:47:11.066 It has what we call a tropism for it. 00:47:11.066 --> 00:47:18.366 If you put a lot of cells in the tube and you throw in HTLV3 it'll go right for that T4 cell and infect it. 00:47:18.366 --> 00:47:21.466 It has an affinity for the helper cell. 00:47:21.466 --> 00:47:30.066 It seems to leave the suppressor cell alone and it damages, but does not immediately kill the cell, but ultimately depletes the cell. 00:47:30.066 --> 00:47:34.899 This T4 cell, as I alluded to earlier, is the critical cell. 00:47:34.900 --> 00:47:43.233 What it does is that it's responsible in a direct or indirect way for virtually everything the immune system does. 00:47:43.233 --> 00:47:46.099 It induces suppressor cells. It induces killer cells. 00:47:46.100 --> 00:47:53.300 You don't have to remember all this, just merely get the concept that if, teleologically, I wanted 00:47:53.300 --> 00:48:00.400 to pick out the one cell that if I damaged that cell I would do the most damage to the immune system 00:48:00.400 --> 00:48:04.433 I, as an immunologist, would pick out the T4 cell. 00:48:04.433 --> 00:48:07.566 That's exactly what this virus did. 00:48:07.566 --> 00:48:14.632 It picked out the T4 cell and it created a tremendous amount of damage in the immune system. 00:48:14.633 --> 00:48:23.699 Now, in the peripheral blood of man, about 60 percent of the cells are helper cells and about 30 percent of them are suppressor cells. 00:48:23.700 --> 00:48:28.166 What happens in AIDS is that we start losing these helper cells. 00:48:28.166 --> 00:48:33.999 And if you look at the profile immunologically of any of my AIDS patients, what you'll see is that 00:48:34.000 --> 00:48:39.233 they're markedly deficient in their T4 or helper cells. 00:48:39.233 --> 00:48:42.599 Now, the immunological abnormalities in AIDS. 00:48:42.600 --> 00:48:47.066 First of all, as I mentioned just now, there's a quantitative t-cell defect. 00:48:47.066 --> 00:48:54.032 Now, I can't expect anybody except an immunologist in the audience to be able to understand what this profile is, 00:48:54.033 --> 00:48:59.266 but there's something in it that I chose to show you, even if you don't understand immunology. 00:48:59.266 --> 00:49:07.532 This is a computerized technique of writing out the amount of cells that an individual has in their blood. 00:49:07.533 --> 00:49:10.266 This is the background, as you can see there's nothing there. 00:49:10.266 --> 00:49:17.432 This is the T4 blip on the computer of the helper cells in the normal, healthy individual, 00:49:17.433 --> 00:49:20.866 who is the identical twin, by the way, of this patient with AIDS. 00:49:20.866 --> 00:49:25.666 If you look at the AIDS patient, this individual has virtually no helper cells. 00:49:25.666 --> 00:49:31.232 The suppressor cells are normal, normal blip in each individual, 00:49:31.233 --> 00:49:34.699 the normal individual and the individual with AIDS. 00:49:34.700 --> 00:49:38.166 There's a functional t-cell defect. 00:49:38.166 --> 00:49:47.499 In other words, this helper cell here, which I've schematically diagrammed as being infected with this HTLV3, 00:49:47.500 --> 00:49:55.433 generally tells this B cell what to do, tells some of the other cells what to do, usually there are about two of these to every one of these. 00:49:55.433 --> 00:49:56.866 What happens in AIDS? 00:49:56.866 --> 00:50:00.399 These get depleted and these fellows take over. 00:50:00.400 --> 00:50:02.266 What else do we see in AIDS? 00:50:02.266 --> 00:50:04.632 There's a B cell hyperactivity. 00:50:04.633 --> 00:50:12.399 In other words, there's factors likely that are released by this infected t-cell, which trigger that B cell. 00:50:12.400 --> 00:50:23.266 In addition, the B cell itself, we know now, might be susceptible under certain circumstances to infection with this HTLV3. 00:50:23.266 --> 00:50:28.499 What does that mean with regard to the patient's ability to respond to a particular stimulus? 00:50:28.500 --> 00:50:35.166 That is suppressed because the B cell, which is supposed to recognize these foreign antigens, 00:50:35.166 --> 00:50:44.099 doesn't do it anymore because it's remarkably weakened because it has been, one, either infected with the virus, 00:50:44.100 --> 00:50:51.700 or, as I mentioned earlier, it requires a good healthy t-cell to kind of push it to do what it wants to do. 00:50:51.700 --> 00:50:55.166 What it needs is help from the t-cell. 00:50:55.166 --> 00:50:57.099 That's why we call it a helper t-cell. 00:50:57.100 --> 00:51:00.266 But the helper t-cells are gone in this patient. 00:51:00.266 --> 00:51:06.699 So the B cell cannot respond well, another insult to the immune system. 00:51:06.700 --> 00:51:13.333 Also the monocyte, which is a cell that's responsible for killing a lot of infections. 00:51:13.333 --> 00:51:16.199 This is blocked in AIDS patients. 00:51:16.200 --> 00:51:17.400 How can that be? 00:51:17.400 --> 00:51:19.600 Well, by a number of mechanisms. 00:51:19.600 --> 00:51:27.633 This T-helper cell--here he comes again--that cell is responsible for telling the monocyte what to do. 00:51:27.633 --> 00:51:34.699 If I get infected; for example I made the analogy of the pneumocystis carinii pneumonia in my lung. 00:51:34.700 --> 00:51:37.633 Why aren't I getting pneumocystis pneumonia? 00:51:37.633 --> 00:51:45.133 Because my T-cells are telling my monocyte to make sure that those pneumocysts don't grow very much. 00:51:45.133 --> 00:51:51.866 Now, if I don't have those t-cells, the monocyte's not gonna know that and I'm gonna get pneumocystis carinii pneumonia. 00:51:51.866 --> 00:51:54.466 That's exactly what's happening in AIDS. 00:51:54.466 --> 00:52:01.066 In addition, in our body, there are a number of cells, which we call killer cells, 00:52:01.066 --> 00:52:07.032 that are responsible for killing either virus-infected targets or tumor cells. 00:52:07.033 --> 00:52:09.199 They're our way of surveilling. 00:52:09.200 --> 00:52:10.633 They look around. 00:52:10.633 --> 00:52:12.666 They want to see if there's a virus around. 00:52:12.666 --> 00:52:14.132 If there is, they attack it. 00:52:14.133 --> 00:52:16.633 They look around to see if there's a tumor around. 00:52:16.633 --> 00:52:18.099 They attack it. 00:52:18.100 --> 00:52:20.033 The same problem exists. 00:52:20.033 --> 00:52:27.966 These cells don't do very well unless that T4 helper cell is prodding them on. 00:52:27.966 --> 00:52:32.899 So although we have normal numbers of these cells, they're not hearing any information. 00:52:32.900 --> 00:52:36.266 They're not getting marching orders from the T4 cell. 00:52:36.266 --> 00:52:46.932 So what this slide here does is that it essentially summarizes how this focal cell here, which is infected with the deadly virus, 00:52:46.933 --> 00:52:55.899 is responsible for the activity of almost all of the other cells that have something to do with immunity in our body. 00:52:55.900 --> 00:53:03.766 For example, the B cell, as I mentioned, just to review for you, the B cell cannot do any of the things it's supposed to do. 00:53:03.766 --> 00:53:09.332 The monocyte macrophage can't kill because it's not getting the signal. 00:53:09.333 --> 00:53:16.433 The T4 induction of other cells, such as the natural killer cell, they don't work right. 00:53:16.433 --> 00:53:21.466 Other T4 cells, which are supposed to do other things immunologically, don't work right. 00:53:21.466 --> 00:53:24.166 Other cell types such as suppressor cells, 00:53:24.166 --> 00:53:34.366 in other words, this hypothetical scheme, which is no more hypothesis, explains the apparent paradox of the immune defect. 00:53:34.366 --> 00:53:35.799 What is that paradox? 00:53:35.800 --> 00:53:44.066 You have one cell that's infected specifically with a virus that has a given function. 00:53:44.066 --> 00:53:49.066 And yet, when you look at the immune system it is globally wiped out. 00:53:49.066 --> 00:53:55.566 So how can one cell cause a global wipeout of a system that's made up of so many different cells? 00:53:55.566 --> 00:54:05.232 And the reason is that those different cells are critically dependent upon that one cell that's the victim of the virus. 00:54:05.233 --> 00:54:09.799 Now, what about the treatment and prevention of AIDS? 00:54:09.800 --> 00:54:12.466 That is a very difficult problem. 00:54:12.466 --> 00:54:19.932 Prevention by public health awareness of contact; the male homosexual community has responded 00:54:19.933 --> 00:54:27.333 in a most encouraging and extraordinary way of educating themselves and their brethren 00:54:27.333 --> 00:54:35.166 about the dangers of certain types of contacts, of anonymous contacts, and preventing the spread among themselves. 00:54:35.166 --> 00:54:36.866 That is an important point. 00:54:36.866 --> 00:54:45.566 We'll get to in a moment vaccination, which is a potential, a real potential, for prevention of this disease. 00:54:45.566 --> 00:54:50.932 What have we been doing and what have been some of the very discouraging results, 00:54:50.933 --> 00:54:54.399 which although they are in and of themselves discouraging, 00:54:54.400 --> 00:55:01.433 have nonetheless provided information which we feel will be the foundation for investigation, 00:55:01.433 --> 00:55:08.966 which we hope and believe deep down will not be as discouraging as we have experienced in the past. 00:55:08.966 --> 00:55:15.932 First of all what you have to do is you have to treat the opportunistic infections and/or Kaposi's sarcoma. 00:55:15.933 --> 00:55:16.999 We're doing that. 00:55:17.000 --> 00:55:22.966 We tried immunological reconstitution with bone marrow transplants and lymphocyte transfusion. 00:55:22.966 --> 00:55:24.666 It did not work. 00:55:24.666 --> 00:55:26.032 Why didn't it work? 00:55:26.033 --> 00:55:29.766 It did not work because the virus was still in the individual. 00:55:29.766 --> 00:55:32.166 Immunological enhancement. 00:55:32.166 --> 00:55:35.899 We're now trying factors that are made by the lymphocytes, 00:55:35.900 --> 00:55:41.800 giving them to individuals for a number of reasons to try and boost up their immune response 00:55:41.800 --> 00:55:48.766 to perhaps curtail the virus in a way that we don't think will completely eliminate it, 00:55:48.766 --> 00:55:56.432 but curtail it enough so that when we develop an agent that has specific activity against the virus, 00:55:56.433 --> 00:56:05.966 namely something that can kill the HTLV3, then we can combine that with these reconstitution experiments, 00:56:05.966 --> 00:56:10.199 which will hopefully no longer be experiments, but will be common practice. 00:56:10.200 --> 00:56:16.800 And those two things together might then rid individuals who are already infected with the virus 00:56:16.800 --> 00:56:22.766 by a combination of killing the virus and reconstituting the immune response. 00:56:22.766 --> 00:56:29.599 And finally, as you I'm sure have read in the papers, given the fact that we now have the virus in our hands, 00:56:29.600 --> 00:56:36.866 it is quite possible, in fact it's invariable, that we will develop a vaccine for AIDS. 00:56:36.866 --> 00:56:47.066 The question that remains to be answered is will that vaccine be effective in protecting individuals against infection with the virus? 00:56:47.066 --> 00:56:53.299 And we don't know that, but that's exactly where much of the research is going on at the present time. 00:56:53.300 --> 00:57:03.733 In summary then, we have discussed the broad implications, clinically and otherwise, of the Acquired Immunodeficiency Syndrome, AIDS. 00:57:03.733 --> 00:57:10.033 We know now that it is caused by an infectious agent, that it's a transmissible disease, 00:57:10.033 --> 00:57:19.966 and that it works its damaging effects by specifically modulating in a negative way the immune system. 00:57:19.966 --> 00:57:29.466 We don't know a lot about AIDS but we also know an incredible amount about it from our experience over the past three or four years, 00:57:29.466 --> 00:57:37.699 and hopefully our recent advances of being able to isolate, identify, and characterize the agent, 00:57:37.700 --> 00:57:43.633 together with the advances in understanding the natural history and pathophysiology of this disease, 00:57:43.633 --> 00:57:51.666 will allow us over the next year to come back to you and tell you that we now not only have hope and hypothesis, 00:57:51.666 --> 00:57:56.032 but that we have a real prevention and indeed a real cure. 00:57:56.033 --> 00:57:59.366 Thank you. [ Applause ] 00:57:59.366 --> 00:58:03.899 [Dr. Reid:] Let's recap the most important points from the lecture. 00:58:03.900 --> 00:58:08.100 AIDS is a new disease that first appeared in the United States in 1979. 00:58:08.100 --> 00:58:14.633 There are two major groups at risk for AIDS: homosexuals and IV drug users in this country. 00:58:14.633 --> 00:58:18.199 Also there are other multiple risk groups. 00:58:18.200 --> 00:58:23.300 AIDS can be transmitted sexually or through blood or blood products. 00:58:23.300 --> 00:58:30.800 The clinical manifestations of AIDS are multiple opportunistic infections and unusual neoplasms. 00:58:30.800 --> 00:58:37.833 The cause of AIDS is HTLV3, a virus which selectively affects a subset of lymphocytes. 00:58:37.833 --> 00:58:43.799 Multiple approaches to prevention and treatment are mostly in the experimental stages. 00:58:43.800 --> 00:58:55.000 These include: vaccine development, antiviral chemotherapy directed against HTLV3, and immunological reconstitution. 00:58:55.000 --> 00:58:56.200 Thank you for joining us. 00:58:56.200 --> 00:59:00.266 I'm Doctor Linda Reid for the Hospital Satellite Network. 00:59:00.266 --> 00:59:02.432 [Producer Arna Vodenos] 00:59:02.433 --> 00:59:04.599 [Director John Niehaus] 00:59:04.600 --> 00:59:06.933 [Production Associate Debbie Brown] 00:59:06.933 --> 00:59:10.133 [Cameras Rip Lambert, Ross Jones] 00:59:10.133 --> 00:59:12.933 [Editor Dave Mills] 00:59:12.933 --> 00:59:15.766 [Engineer Paul Wilkinson] 00:59:15.766 --> 00:59:18.799 [Lighting Director Lou Karp] 00:59:18.800 --> 00:59:21.366 [Production Assistant Terese Winslow] 00:59:21.366 --> 00:59:24.332 [Presented by The Warren Magnuson Clinical Center, National Institutes of Health] 00:59:24.333 --> 00:59:27.266 [Presented by Office of Clinical Reports & Inquiries. CC] 00:59:27.266 --> 00:59:29.999 [Marian Segal, OCR & I Lecture Coordinator] 00:59:30.000 --> 00:59:31.733 [Medical Arts and Photography Branch, NIH] 00:59:31.733 --> 00:59:33.899 [Audiovisual Section NIH Technical Support] 00:59:33.900 --> 00:59:36.666 [Production Support Domus Design Studio] 00:59:36.666 --> 00:59:42.499 [Upcoming Lectures: Parkinson's Disease: Natural and Drug-Induced Causes Sleep and Its Disorders] 00:59:42.500 --> 00:59:49.433 [Copyright 1984 Hospital Satellite Network All Rights Reserved] 00:59:49.433 --> 00:59:55.566 [Narrator:] The preceding program has been a presentation of the Hospital Satellite Network. 00:59:55.566 --> 01:00:04.966 [ Music ]