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What are the prospects for halting or curing the deadliest epidemic ever to challenge modern medicine? NOVA finds cause for both hope and alarm in the battle against AIDS.

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00:00Tonight on NOVA, Bruce and Bobby, a young married couple at the beginning of their life
00:10together. There's only one problem. Bobby has AIDS. She is only one of over 11,000 Americans
00:17with the disease. Another 15,000 have already died. In the face of this new and deadly epidemic,
00:25Bruce is engaged in a desperate fight to understand and overcome the AIDS virus. What we're finding
00:30is truly astounding. It's as if this virus comes from the depths of the sea, encrusted
00:35with new biological organisms that we've never seen before at all in all of biology. The
00:41scientists, society, and the victims are drawn together by a single haunting question. Can
00:47AIDS be stopped? Major funding for NOVA is provided by this station and other public
00:58television stations nationwide. Additional funding was provided by the Johnson & Johnson
01:05family of companies, supplying health care products worldwide. And by Allied Signal,
01:13a technology leader in aerospace, electronics, automotive products, and engineered materials.
01:43The following film contains graphic illustrations of human anatomy and sexual behavior. Viewer
01:48discretion is advised.
02:06U.S. Army Fort Detrick, Maryland, once renowned for its biological warfare experiments.
02:13More AIDS virus is produced here than anywhere else in the world, but it's being grown for an entirely peaceful purpose.
02:27It's part of a race to make a vaccine against one of the most deadly and perplexing infections
02:35ever to challenge modern medicine. Around the world, there's an intense scientific effort
02:43to unravel the complexities of this strange and deadly virus. Its prime target is a human
02:55white blood cell. Usually the linchpin of the body's immune defense system, this cell
03:01is crippled and on the verge of destruction. Littering its surface, hundreds of virus particles
03:07are budding forth, ready to spread the disease. This is how AIDS begins.
03:22Over the last three or four years, we have seen every one of our worst predictions confirmed.
03:28I believe many of us felt like Cassandra, who could see the future, could speak the
03:32future, would be listened to, but would not be believed. I think from now on, the facts
03:37will speak for themselves. We are seeing the mounting number of AIDS cases in this country
03:41and around the world that we anticipated two or three years ago. We are seeing the devastating
03:46health effects, the health effects, the impact on our healthcare delivery system. Those facts
03:51will speak for themselves.
03:54AIDS was first observed in 1981, when it affected only a small group of male homosexuals and
04:00intravenous drug users. At the time, it was just a medical curiosity. But medical science
04:08was unable to stop the disease. And today, AIDS threatens millions of lives.
04:17The disease is caused by this virus, called HTLV-3.
04:29It belongs to an unusual family, known as retroviruses, one of the simplest life forms
04:35on Earth. Scientists have only recently discovered how retroviruses do their damage.
04:46Within the spiky outer shell is a protein core that protects the virus' genetic heart,
04:52the key to its deadly behavior.
04:56The viral genes are permanently inserted into the normal cellular DNA of the infected cell
05:03of the particular person that got infected. So that infection of that cell is forever,
05:08because the viral genes are now part of the cellular genes, integrated right in.
05:14This integration occurs when the short chain of viral genes invades the DNA of the human cell.
05:25The human cell is now taken over, and infection has begun.
05:32Not only is that cell infected for a lifetime, when that cell divides, the daughter cells
05:37will also have not only the cell genes, but also the viral genes. So infection of the
05:42person is forever.
05:49And infection by the AIDS virus can spell disaster.
05:56Bobbie and Bruce had been married for less than a year when she developed acute pneumonia.
06:00Her lung infection was the first indication there was a problem.
06:04I was so sick. I had high temperatures. I had immediately lost 15 pounds.
06:10I had gone from 105 down to 90 right away.
06:14I had difficulty breathing. I'd spend most of my day just in bed.
06:20Three years earlier, Bobbie had required a blood transfusion.
06:24At that time, there was no accurate test for the AIDS virus in blood.
06:28One of the units Bobbie received was contaminated.
06:31In the summer of 1985, she was diagnosed with AIDS.
06:34I was scared. I immediately thought back to the blood transfusions and knew that's exactly where it came from.
06:44And I was, first of all, very scared of dying. I mean, I've done a lot of reading on AIDS, being a nurse.
06:51And I know that the outlook was supposedly very bad, that people don't survive over three years.
06:59And the patients that I've seen who've had the AIDS, they were all very, very sick people, you know, just dying people.
07:09Well, it was just unbelievable sadness that this would happen to her.
07:13You know, that we were basically just starting out on our lives.
07:17And to think that instead of all the good things that you try to expect, at least at the beginning,
07:24that immediately it's going to be just sickness and pain.
07:28And it's very unfair.
07:32The AIDS virus targets the body's immune system, causing it to break down.
07:36Its victims succumb to infections that they can no longer fight off.
07:44The process begins in the blood.
07:50It's the body's white blood cells that are responsible for the immune defense system.
07:54There are many different varieties of white blood cell which act together to protect the body from infection.
08:00The AIDS virus attacks and kills a specific cell called the T4 helper lymphocyte.
08:08Without the T4 cells, the immune system plunges into chaos.
08:12The virus fuses with the T4 cell's outer membrane, injects its genetic blueprint into the cell,
08:24and begins the insidious process of taking control.
08:31The results can be devastating.
08:35It's devastating because, first of all, it can attack the critical cell of the immune system,
08:39the cell we call the T helper or T4 cell, which regulates much of the function of our whole immune mechanisms,
08:44and therefore you get a lot of other infections, what we call opportunistic infections.
08:48Opportunistic infections means you have an infection by an organism which normally doesn't hurt you,
08:52but in this case it'll hurt you because you don't have proper functioning of your immune system.
08:57Things that we normally live with can kill, in other words, because your immune mechanisms are so altered.
09:03The AIDS virus doesn't attack just the immune system.
09:07Scientists now know it can also infect the brain.
09:10In infecting the brain, it can cause dementia and it can cause death directly.
09:14These are cases that often go unreported because they're not showing up as AIDS but as brain disease.
09:19People don't often know the virus is there.
09:21Can you see these numbers here?
09:23Yeah.
09:24There are numbers like 1, 2, 3, and 4.
09:25Right.
09:26Also letters like A, B, C, and D.
09:28Right.
09:29I want you to take this pen and connect these circles, but in a special way.
09:32I want you to alternate number, letter, number, letter.
09:35Scientists are trying to learn just how AIDS can affect the brain.
09:38They want to find out how many people infected with the virus show signs of mental problems
09:43and to determine the severity of their symptoms.
09:46Okay, excellent.
09:47Number, letter, number, letter, number, letter, number, letter.
09:50Researchers Mark Greenberg and Alexandra Beckett have begun a long-term psychological study
09:55of 150 people who have been infected by the AIDS virus.
09:59Ready?
10:01Go.
10:03Some people infected with the virus can experience mental problems
10:06long before they show serious symptoms of disease.
10:10This volunteer, for example, has only a mildly damaged immune system.
10:14Aha.
10:15Okay.
10:16I used to have a real good memory.
10:18You'd give me a list of 100 items in the store and I could read them back to you,
10:23frontwards, backwards, what sequence they were in, all that stuff.
10:28Now it's like I go to the store for five items and I forget three of them, you know.
10:34Brain scans reveal the damage that can be done by the virus.
10:38The brain literally shrinks and fluid, shown here in black, fills the space.
10:43Over 50% of AIDS patients may ultimately suffer from dementia.
10:47The complaints that we've most often heard are that people are having difficulty concentrating.
10:53We've commonly had people describe episodes during which they have a sudden strong emotion,
10:59un-precipitated by anything that they can point to,
11:05and that they feel they're performing less well than they used to at tasks that they are quite familiar with.
11:13Go.
11:15By repeating the testing at regular intervals, the researchers can monitor the course of the disease.
11:22Stop.
11:25And the indications are that brain damage is something many people infected with the virus will increasingly have to face.
11:32I'm less upset by it. I say, well, you know, that's just what's happening, that's what it's doing.
11:37And I live with it, you know.
11:40I mean, diabetics live with the fact that they have to take insulin and they have problems with that.
11:44And, you know, I have this virus and I live with the problems that it brings.
11:50So AIDS poses a double threat in attacking the immune system and the brain.
11:56How many people are at risk?
12:00It's a characteristic of this disease that many people infected with the AIDS virus do not have AIDS.
12:06But out of 100 infected individuals, about a dozen each year develop early symptoms called ARC, AIDS-related complex.
12:15With each additional year, a proportion of those with ARC will develop full-blown AIDS.
12:22Will any of those infected fight off the disease or will everyone eventually succumb?
12:28It's a crucial question because the numbers could be enormous.
12:35We have no good answer to what the percentage of people who get truly infected are
12:41who will develop fatal disease of one form or another.
12:44We can only say what a minimum is at any period of time, at least for another few years.
12:49So, you know, I think the minimum is going to be 10% or so.
12:53Probably going to be significantly more.
12:55At the moment, new cases of full-blown AIDS are being diagnosed at the rate of 1,000 a month.
13:01In five years, it is estimated that 270,000 Americans will have full-blown AIDS
13:07and millions more will be infected with the virus.
13:10And everywhere around the world, the disease is on the increase.
13:17In the last few years, a lethal form of the AIDS virus has become widespread in several Central African countries.
13:25Political conditions make research difficult,
13:28but Western specialists believe that across the continent, millions are infected and tens of thousands are dying.
13:36In Europe, numbers are more certain.
13:39The three most affected countries are France, West Germany and the United Kingdom.
13:46At the latest count, there were almost 3,000 in Europe as a whole.
13:55In the United States, 26,000 cases of AIDS have been reported
13:59and well over a million people carry the virus without yet showing any symptoms.
14:05The disease is concentrated in San Francisco, Los Angeles, New York and Miami,
14:11cities with large populations of homosexuals and IV drug users.
14:16The same major risk groups are affected in Canada and Haiti, both with around 600 cases.
14:25And in South America, Brazil now has 800 cases in the cosmopolitan cities of Rio de Janeiro and Sao Paulo.
14:36As for the rest of the world, only Australia is significantly affected, with about 200 cases there.
14:44But it's in Africa that AIDS is at its most acute.
14:47With millions infected, the question has become how to account for the wide and rapid spread of the disease.
14:55At the end of 1985, an international conference was held in Brussels, focusing on AIDS in Africa.
15:01Some African governments are reluctant to acknowledge an epidemic
15:04that's associated primarily with homosexuality and drug abuse.
15:10If there is AIDS in their countries, they say,
15:12it must have been brought in by Western tourists purchasing homosexual favors.
15:18It is a taboo, you know, homosexuality is culturally a taboo in our environment.
15:22And with urbanization, poverty, it is easy for these young men who lost their identity
15:32from the rural setting into the urban areas, you know, to fall prey to these practices.
15:41But the weight of evidence doesn't support the argument for homosexual spread alone.
15:46For the disease in Africa affects almost equal numbers of males and females.
15:50And this suggests that AIDS may also be spread heterosexually between men and women,
15:55thus enlarging the group of people at risk.
15:59I have become more convinced than I was before that AIDS in Africa
16:04is transmitted principally by sexual contact, and principally by heterosexual contact.
16:12There may be other factors, such as the reutilization of hypodermic needles
16:18that haven't been properly sterilized.
16:21And some people have said perhaps insect-biting insects like mosquitoes might spread the virus.
16:26But the one thing that's come through loud and clear is that AIDS is spreading
16:30in the most sexually active people in a community, and particularly amongst the promiscuous.
16:38Mosquitoes and needles do not select between those people so very much.
16:44So I think it still comes down to saying, if you want to avoid AIDS,
16:49avoid having too many sexual partners.
16:56Project Aware, Suzanne speaking.
17:00Yes, I'd like to ask you some questions to see if you meet the criteria for this study.
17:05Does the devastation in Africa portend the future for the rest of the world?
17:10One group in San Francisco, Project Aware, is trying to find out
17:13how much the virus is spreading heterosexually there.
17:17So they're looking at rates of infection in women in the Bay Area.
17:20So you're afraid that you may have been exposed to the virus.
17:23Let me ask you a few questions.
17:25How long ago was that relationship?
17:29And was your past boyfriend sleeping with other men during that time?
17:37We have three rather different risk groups.
17:39We have women who have put themselves at risk through a particular relationship with a man we know is at high risk.
17:45We may even know that he has AIDS or ARC or is antibody positive,
17:49or just is a member of a group with a very high rate, so he's presumed to be at high risk.
17:54Then we have a group of women who are sexually quite active
17:57and may not know enough about all of their sexual partners
18:01to know whether they are high-risk people or not,
18:03because a casual encounter doesn't necessarily produce that kind of information.
18:08Finally, we have a group of women who are sexually quite active
18:11and expect to be paid for it, that is, women in the sex industry
18:14who have a number of partners because that is what they do for a living
18:18and they expect payment of some kind for it.
18:21So we have those three different groups at risk.
18:24The Project's field workers go into the streets,
18:27recruiting from these three groups of women.
18:30The job requires patience and a diplomatic approach.
18:42It's a difficult thing to get people to enroll in a study like this.
18:45There are no lists.
18:46You can't look up a list of prostitutes and call them on the phone and say,
18:48will you come in?
18:49Even if there were such a list, they wouldn't come in.
18:51So we have a very skilled field staff who walk these areas
18:56and our reputation in the community is of people who can be trusted.
19:02Women who volunteer are given a blood test for the virus
19:05and questioned about aspects of their sexual behavior that may have put them at risk.
19:10How many men have you had sexual contact with during the last six months?
19:16I don't exactly know how I'm supposed to answer that question.
19:21Just tell me approximately how many men you think you've had in the last six months.
19:25How many do you have per day?
19:27On the average, in the last six months, about three a day.
19:32About three a day.
19:33Okay, do you work every day?
19:36I work about six days a week, yeah.
19:38Okay, so let's see, six times three is 18.
19:42Okay.
19:43Eighteen a week.
19:44Yeah, so 18 a week.
19:46The arithmetic works out at about a thousand partners a year.
19:51We have now enrolled and tested over 300 women.
19:55The study is not complete, but among those early participants,
19:59we have found that about 4% of them are in fact seropositive for the virus at this point.
20:05Some people might regard that as very good news,
20:07given that these are high-risk women by definition.
20:10Only 4% are seropositive.
20:12On the other hand, that's a lot of women who have something to worry about.
20:16It's not just prostitutes who are contracting the virus.
20:19The AWARE study shows that sexually active women with far fewer sexual contacts
20:24are equally at risk for AIDS.
20:26Armed with this information,
20:28the field staff also works to alert women to the dangers from the virus.
20:33So you're taking extra precautions as compared to maybe a year or so ago,
20:37as far as safe sex goes.
20:39Yeah, pretty much, and I believe in birth control.
20:42I'm a strong believer in birth control.
20:44You're being fairly picky and choosy about who you're going out with anymore?
20:48I always pretty much have been.
20:51So people of both sexes can be at risk for AIDS,
20:54here as well as in Africa.
20:57Many people ask us about how much it's reasonable to extrapolate
21:01from the African information to information in countries like the United States.
21:06And it's a very difficult question to discuss,
21:09because on the one hand, we believe that we know of no virus that has a sexual preference,
21:15that it does, in fact, attack lymphocytes from both males and females, this virus.
21:20Can it be a heterosexual disease? Clearly it can be.
21:24Everything we know about this virus suggests to us that there is no reason
21:28that it can't be transmitted from a man to a woman,
21:31and possibly from women to men.
21:33In fact, if you look at the epidemiological evidence,
21:36it looks as if that happens.
21:38The frequencies, nobody knows what the real frequencies are.
21:41I think the major uncertainty at this point is not can it and will it, but how fast will it,
21:46and how big the infection will be in the heterosexual population.
21:51In the United States, I think that the problem is going to be an increasing one and a subtle one,
21:57because the women and some of the straight men who are infected
22:02may truly have no knowledge that they had been involved in behavior
22:07that would get them infected,
22:10and therefore may truly not know that they're at risk or risking others.
22:16One message is clear for both men and women.
22:20Preventing AIDS will mean safe sex, avoiding physical contact with other people's bodily fluids.
22:29There's definite proof that a woman can be infected via her vagina.
22:33This happened to four women in Australia following artificial insemination with contaminated semen.
22:39The virus may not penetrate the thick walls of the vagina itself,
22:43but it can probably enter a woman's bloodstream via the uterus with its rich supply of surface vessels.
22:49When a woman is infected, the virus becomes present in vaginal secretions,
22:54presenting in turn a danger to males.
22:59There's no evidence to say exactly how the AIDS virus infects men.
23:03Promiscuous men sometimes have an inflamed urethra due to other sexually transmitted diseases.
23:09Possibly a small sore just inside the penis may offer a route of entry.
23:13Condoms are definitely a sensible precaution.
23:19Homosexual anal intercourse has frequently been blamed for spreading the disease.
23:24Unlike the vagina, the lining of the rectum is thin and bleeds easily.
23:29One theory is that infected semen might cross into the passive partner's bloodstream,
23:34or because the lower intestine swarms with the same T-cells the AIDS virus targets,
23:39a direct cell-to-cell infection route might be possible.
23:46And there is yet another group at risk for AIDS in Western countries, intravenous drug users.
23:52The habit of sharing needles means that withdrawn blood is often left behind in the syringe between fixes.
23:58It's a perfect way to spread a blood-borne virus.
24:04The link with sex and drugs, behavior considered illicit or taboo, is another deadly aspect of AIDS.
24:11It makes public education controversial, and it exposes victims of the disease to prejudice and fears.
24:18Well, that's what hurt me the most, the fact that I was a nurse in the hospital.
24:22They all knew I was a nurse in the hospital, and I was right, my room was right outside the nurses' station,
24:29so I could always hear them talking about me.
24:32There was one nurse who actually refused to take care of me, which that hurt.
24:36I was, I wasn't referred to as Bobby. They referred to me as the nurse with AIDS.
24:42And, I mean, I just kept thinking that if this is how they treat a fellow nurse, what do they do to the other patients there?
24:50But the AIDS virus is fragile and is not casually transmitted.
24:54Bruce no longer fears catching AIDS from Bobby.
24:57We take some precautions with ourselves.
25:00It's not like we have different kinds of laundry or different sets of sheets or different glassware or anything like that.
25:09You know, we live together, we sleep together, we're man and wife.
25:14The AIDS virus is not easy to catch.
25:17It requires direct and intimate contact with blood or bodily fluids in order to spread.
25:22So AIDS can be prevented.
25:24But for those already infected, the question remains, can AIDS be treated?
25:30An effective treatment will have to find a way to disrupt the viral life cycle within a human cell.
25:38When the AIDS virus binds to the T cell's outer membrane, it injects its genetic core inside the cell.
25:46As a retrovirus, its genes are stored in an unusual form on a chemical variant of DNA called RNA.
25:56A special enzyme, reverse transcriptase, is needed before the virus can translate the RNA into normal DNA and replicate.
26:09Researchers at the National Cancer Institute in Washington have been leading the hunt for a drug that might block the reverse transcription process.
26:18They've tested hundreds of such drugs.
26:22They've tested hundreds of substances and narrowed the search to the contents of what is known as the magic box.
26:29All of these compounds show some promise against the AIDS virus, and most of them work in a similar way.
26:36They're all chemical modifications of the natural building blocks used by the virus to make the DNA copy of its genes.
26:46A small molecular change can transform a building block into a chemical stop sign.
26:55No further building blocks can be added, and replication of the viral genes grinds to a halt.
27:04To determine which chemicals work best, scientists have developed a simple comparative test.
27:11Both tubes contain cultures of human T cells, the cells the AIDS virus attacks.
27:17But the cells on the left have been infected by the virus, and the colony at the bottom of the test tube is smaller.
27:24The virus is killing those cells.
27:29To find out if a chemical can stop the virus, a sample of the drug is added to a newly infected tube.
27:36This time, the two colonies stay the same size, so this drug is protecting the T cells from the virus.
27:43But will it work in humans?
27:45I think one always has to bear in mind that a tissue culture technique may not predict for what happens in a person.
27:53There are many other factors in a person.
27:55There is toxicity of the drug against various organs.
27:58There's how a given drug can be handled by various parts of the body.
28:02There may be inherent sites in a person that are essentially immune, so to speak, from the effects of a drug,
28:09where a drug cannot reach or cannot be metabolized actively enough to bring about an effect.
28:15So I think that it is a leap of faith to assume that because one has an agent that works in a test tube,
28:24that one will have an agent that will work in human beings.
28:29One of the most promising of the chemicals is called AZT.
28:35Testing of AZT began in July 1985 on a small group of AIDS patients.
28:40Bobbie was one of them.
28:42I was scared about going down to Washington.
28:45I looked terrible at the time.
28:47I could just tell by how the people were looking at me that, you know, they might not have wanted me, you know.
28:53And I tried to look good that day because I wanted so desperately to be in the program.
28:57You know, I made my face up.
28:59But I was just so darn weak at the time.
29:01But they accepted me in.
29:03The first day that we were there, they gave me the drug, but they just did it a one-day thing.
29:09Test dose.
29:10Yeah, I guess to see if I wasn't allergic to it and that it was getting into my system.
29:14And they brought me to my room.
29:17It was a lovely room.
29:18I had a lovely view.
29:20I met all the nurses who were really friendly to me.
29:22And I was thinking, what's going on here?
29:25He's being so friendly and nice to me.
29:27You know, why is this going on?
29:29Don't they know what disease I have?
29:31Hello.
29:32How are you today?
29:34Every two weeks, Bobbie flies down from New York at government expense
29:38for a careful evaluation of how well the drug is suppressing the virus in her body.
29:42How was the flight?
29:43Not bad.
29:44You know, 45 minutes, but it was on time and everything, so it ended up being okay.
29:48Very good.
29:49Step up on the scales, please.
29:52I'm going to get your weight.
29:5450.3.
29:55Oh, good.
29:56I was 49 last time, so another kilo.
29:58Very good.
29:59You're gaining.
30:00Mm-hmm.
30:01Objective signs of how well Bobbie is responding to the treatment are essential.
30:06Dr. Sam Broder must decide how much Bobbie's well-being is due to the drug
30:10and how much to her remarkable determination to overcome the virus.
30:15Tell me a little bit about what's been happening since we saw you last.
30:17Well, the first thing is, look here.
30:20There was a bud in there, and today I sat down and it snapped.
30:23I've put on quite a bit of weight.
30:25How much have you gained?
30:26I've gained, well, today I'm 50.3 kilograms, which I've never weighed that in my life before.
30:32What about your fevers?
30:33I haven't had any fevers at all.
30:36My temperature's usually 37 exactly.
30:39Okay.
30:40So, no, things are going really well.
30:41Well, I'm very pleased.
30:43In all fairness, I cannot.
30:45Yeah, I mean, you don't know how pleased we are.
30:48I mean, we are so happy right now.
30:50But you have to understand that although I'm extremely gratified about your response,
30:53I can't be sure that the drug that we gave you did this.
30:57I mean, it's way too soon to make that conclusion.
31:00I attribute it to the drug, though.
31:02I do.
31:03I don't care what anybody else says.
31:04It's the drug.
31:06Despite Broder's professional caution,
31:08Bobbie's positive response to AZT was shared by other AIDS victims early in the clinical trials.
31:15In September 1986, AZT was made available to many AIDS patients on a much wider basis.
31:21It is the first true ray of hope in the long battle against the disease.
31:25Your dose is 12 ml every four hours.
31:28For patients, it's a lifeline to clutch on to,
31:31although it must be taken every four hours, night and day.
31:34How much of a supply is this?
31:36This is a week's supply.
31:37Okay.
31:40You know, I'm convinced that perhaps I'll have to be on this drug the rest of my life,
31:43but, you know, it's not that bad.
31:45Okay, thank you.
31:46You're welcome.
31:47Bye-bye.
31:48Bye now.
31:49I just feel that the drug is making me better.
31:53The researchers stress that there are still many uncertainties about AZT.
31:57It stops the virus from multiplying but can't undo the damage already done to the immune system.
32:03So it's considered a treatment, not a cure, for AIDS.
32:06And its potential for dangerous side effects is still unknown.
32:12But it offers Bobby and many others the precious gift of time.
32:18Obviously, she's doing very well,
32:21and I think that her immune system is not getting any worse
32:27so that even if she were to get another infection, it could be treated and she'd get better.
32:32And we have a lot of time, I think, now,
32:36and I'm sure that certainly in the time that we have, a cure will be found.
32:42I'm confident of that.
32:45If a cure can be found, it will probably be based on recent breakthroughs in understanding the virus,
32:51particularly the workings of its genes.
32:55Like all retroviruses, the AIDS virus has three standard genes.
33:01The first makes the core proteins that protect the virus's genetic material.
33:06The second makes the reverse transcriptase enzyme, already the target of several experimental drugs.
33:13The third makes the spiky outer shell.
33:16But the AIDS virus has extra genes that scientists have never seen before.
33:23One of them, called the transactivator, controls the way the whole virus reproduces.
33:32The transactivator comes into play long after the initial infection by the AIDS virus.
33:42The virus can remain dormant for years,
33:45but when the immune system is activated to fight off another infection,
33:49the virus within the critical T cells begins to multiply.
33:54The transactivator gene plays a crucial role in this process.
34:00Without that transactivator, the virus is completely dead, just can't grow.
34:05That was not predicted from anything we knew about other viruses.
34:09We had predicted that it would just replicate slowly, like most other viruses, without its transactivator.
34:15However, we find, without its transactivator, no growth at all.
34:19That has an important implication for therapeutic intervention, for making new drugs for AIDS viruses.
34:26What we are always looking for are things that a virus does that a cell doesn't do.
34:31And this particular positive feedback loop is unique to this virus.
34:35Cells don't do it. It's a viral gene product.
34:38And what's very important is that it's a viral gene product without which the virus cannot grow.
34:43And therefore, we have a new target for anti-AIDS drugs.
34:48So the search for treatments will not stop with AZT.
34:52Right now, four other experimental anti-AIDS compounds are undergoing preliminary testing in humans.
34:58One of the drugs, like AZT, is designed to interfere with the virus life cycle,
35:03two others to destroy infected cells, and one to bolster the body's immune system.
35:09The drugs which show promise will be further tested, both alone and in combination.
35:14Initial results of these trials will be known in early 1987,
35:18and it is possible that additional treatment could be made available to AIDS victims within five years.
35:25But what about a vaccine that would prevent infection in the first place?
35:32If an AIDS vaccine is ever made, it will be traced back to this house in Scotland.
35:37More than a hundred cats lived here with their eccentric owner.
35:41In the early 1960s, a number became ill with an infectious form of leukemia.
35:46The mini epidemic was brought to the attention of Bill Jarrett at Glasgow University.
35:51The culprit turned out to be a retrovirus,
35:54and Jarrett was eventually able to develop a vaccine to protect cats from the disease.
36:00Jarrett was the first and only vaccine against a retrovirus,
36:04and it provides a model for AIDS vaccine research.
36:09Well, the basic principle is the same in them all.
36:12You're trying to preserve a certain set of molecules which are on the surface of the virus,
36:18and the virus uses these molecules, they stick out from the surface,
36:22and it uses them to penetrate the cells of the body.
36:25Like the common cold going into your nose, these prongs on the virus, so to speak, stick into the cell,
36:31and that's the way the virus gets into the cell.
36:33And when you become immune to a disease like the common cold,
36:38your body has generated molecules which attach onto these spikes on the virus
36:45and stop it getting into the cells.
36:47Now, the idea of every vaccine, and there are many different ways of making vaccines,
36:52is to preserve these molecules and present them to the body in such a way
36:57that the body thinks that it's the virus and responds to it.
37:02So a vaccine looks like a virus to the body, but contains no harmful materials.
37:07It's made up of molecules with spiky outer shells, similar in shape to the virus,
37:12which alert the immune system, tricking it into manufacturing protective antibodies.
37:18These antibodies then stand guard to recognize and repel any later attempt at infection by a real virus.
37:27But traditional approaches to making vaccines don't work against the AIDS retrovirus.
37:32To give you an example, we would rule out immediately using a live virus.
37:39I have mutants in the laboratory that have been developed here about a year ago
37:43that do not kill the T cell they infect.
37:46They infect, but they seem to do nothing harmful.
37:49One might say, gee, that's a vaccine.
37:51I would think that would be crazy because they probably would cause leukemia after a while
37:54because, remember, these are retroviruses, and the other name for retroviruses are leukemia viruses.
37:58So if you don't die of AIDS, you might die of a malignancy, a cancer,
38:02especially a leukemia or a lymphoma.
38:05Okay, so we dismiss mutant viruses.
38:08The next thing you might say is, what about an inactive virus, a whole virus inactivated?
38:13We would rule that out too because, at least for the time being,
38:18you have nucleic acid in this virus that would be very hard to prove would not be damaging to someone.
38:27So at centers around the country, scores of scientists have had to develop new techniques in their search for an AIDS vaccine.
38:35The key to a vaccine, they believe, lies in using only one part of the virus,
38:39its spiky outer shell, known as the envelope.
38:42By itself, it can't harm the body, but might be able to induce an immune response.
38:50One approach to manufacturing this empty envelope for experiments begins with growing the virus itself.
38:57Here at Frederick, we produce a virus under highly contained conditions called P3 conditions for protection of the investigators.
39:05Individuals have to enter through a limited access doorway.
39:09They dress in protective clothing.
39:11The air balance is set such that the air is negative to all of the rest of the building.
39:16The virus is propagated inside of cells that we keep in a large wall.
39:21The virus is propagated inside of cells that we keep in a large walk-in incubator.
39:27We produce somewhere around 250 liters a week.
39:30Since we've been in operation, we've produced somewhere in the range of 12,000 liters of virus.
39:35That's 3,000 gallons.
39:37It should total up to be somewhere around 1,000 trillion virus particles.
39:42The virus is harvested twice a week.
39:45It's separated from the cells in which it grows and purified to extract the critical spiky outer shell.
39:54To elicit the strongest possible immune response, a few drops of an experimental enzyme are added to the virus shells, which are made of pure protein.
40:03The mixture is then placed in a dialysis bag, where the two substances slowly react with one another.
40:21If conditions are just right, the enzyme causes the viral proteins to clump together,
40:28forming miniature particles called immune-stimulating complexes, or ISCOMs.
40:34The hope is that these ISCOMs will be highly visible to the immune system
40:38and induce the body to mount an effective defense against the real AIDS virus.
40:45Another promising approach to making a vaccine comes from recombinant DNA technology.
40:50These genetic engineering techniques do not use the virus itself,
40:54Instead, they begin by extracting the gene that makes the viral envelope.
40:58Then they put the gene into another living cell, which acts like a tiny factory, producing pure envelope protein.
41:05Like ISCOMs, these proteins should fortify the immune system against the virus.
41:14But manufacturing a prototype vaccine is only the beginning.
41:19The first step in the vaccine is to see whether you can make it.
41:22And the second step is to put it into animals.
41:24There is no way of testing a vaccine apart from doing animal experiments.
41:27So that's in the monkeys.
41:29And the first thing we measure then, as I said, was whether the monkeys managed to produce antibodies against that.
41:35We have tried different doses of the vaccine.
41:38We had to start with very small doses to make sure it was safe and didn't harm the monkeys.
41:42It didn't.
41:45So we've stepped up the dose now.
41:48And this has produced a very good antibody response.
41:51That's stage two.
41:53Lab animals have produced strong antibodies in response to experimental vaccines.
41:58But scientists have been unable to tell if these antibodies can protect against AIDS.
42:03To find out if the vaccine does provide protection from the virus,
42:08it must be tested in the only animal vulnerable to the AIDS virus other than man.
42:13Chimpanzees.
42:15Results from the first set of experiments with chimps will be known by midwinter 1987.
42:21By then, the incubation period of the virus will be over.
42:24If the chimps continue to be healthy, the vaccine is protecting them from the disease.
42:31Our primate relatives may offer another ray of hope.
42:35One species of monkey, the African green, naturally carries a virus very similar to the AIDS virus.
42:41This may be how AIDS began.
42:43A chance scratch or bite may have caused this virus to jump from monkey to man,
42:48where it later mutated into the deadly form we know as AIDS today.
42:53But the African green monkey never becomes ill.
42:56This fact sparked an entirely new line of inquiry
42:59by researchers Myron Essex and Phyllis Kahnke of the Harvard School of Public Health.
43:04They wondered if a benign form of the AIDS virus could exist in people,
43:08like the harmless one that infects monkeys.
43:13They began their search in West Africa.
43:16There, they took blood samples from prostitutes,
43:19a population they suspected would likely have been exposed to the AIDS virus.
43:24When they examined the blood, they found that their hunch had been correct.
43:28They had discovered a new virus, a close relative of the AIDS virus called HTLV-4.
43:35Like the green monkey virus, it infects T-cells, but it doesn't kill them.
43:39People carrying this new virus are healthy,
43:42and perhaps it's even protecting them against AIDS.
43:46And I think probably the most important thing is that these people are apparently healthy.
43:51There hasn't been AIDS or other related clinical syndromes like AIDS in this region of Africa.
43:58So it could be, it's at least a possibility,
44:02that the virus does not cause disease as readily as the prototype AIDS virus does.
44:10Researchers are just beginning to experiment with this new virus
44:13and to compare it to the deadly AIDS virus.
44:16The differences between the viruses in both structure and behavior
44:19may give them valuable insight into strategies for both treatment and vaccine development.
44:26But despite these advances, the task will continue to be difficult.
44:31The AIDS virus mutates and can thus evade the body's defenses.
44:37The protein spikes are what count in the immune response.
44:43Key points on the surface of these proteins are recognized by the antibodies.
44:48So an extremely small mutation in the virus can defeat antibodies produced both naturally and by a vaccine.
44:58Antibodies made to the old configuration will no longer bind,
45:01and the virus can stay one jump ahead of the immune system.
45:06The major headache, I think, would be that the virus may have different types.
45:14You may have one type in New York and another type in San Francisco.
45:18And it's already known that there are genetic differences in the structure of these viruses.
45:23But we don't know whether that means that the antigens of the virus,
45:29the molecules that produce the immunity,
45:32we don't know whether they're different or not.
45:34This is still to be found.
45:37Generally, they are the same.
45:39They're the same structure and the same size.
45:41But small differences might make a difference.
45:44And this does happen in viruses.
45:46Some have many different types.
45:49You see, there are so many common cold viruses,
45:51dozens of them, that it's not possible to make a vaccine here.
45:55With rabies, there is only one type, so it's easy to make a vaccine.
45:59We don't know just where AIDS lies here.
46:06And there's yet another obstacle.
46:09The AIDS virus might evade a vaccine entirely
46:12by entering the body already encapsulated in a cell.
46:16This foreign cell would then be engulfed by the immune system,
46:19allowing the AIDS virus to pass directly from one cell to another,
46:23undetected by any protective antibodies in the blood.
46:28Well, these are hypothetical questions.
46:30And we don't know the answer to them.
46:32I mean, the only way you can do it is to try it, to suck it and see it.
46:36I mean, we've got to make the vaccine.
46:38It was thought to be a daunting prospect,
46:40and kept looking, for example, where there are several forms of the virus.
46:43But in fact, one vaccine protects against all the different types.
46:48So we've just got to go ahead, as usual in science, and do the experiments.
46:52Progress in understanding the AIDS virus and its fundamental mechanisms
46:55has gone extremely rapidly.
46:57We've built upon a very large body of knowledge
47:00that we had accumulated from other studies of retroviruses
47:03and used all of that knowledge.
47:05We now are up to the point we are with any retrovirus, and beyond that.
47:10This virus is doing truly new things that have never been seen in biology.
47:14It's as if something had come up out of the depths of the sea,
47:17encrusted with new biological organisms that we had never seen before.
47:22And I think that what we will learn from this virus will help not only AIDS,
47:26but many other diseases, leukemia and other chronic human diseases.
47:31If AIDS were almost any other disease,
47:34the level of scientific understanding achieved so far
47:37would be considered remarkable.
47:39But with a number of new cases doubling every eight months,
47:42and extending beyond the initial risk groups,
47:45there's a heightened sense of urgency.
47:47And efforts to overcome the virus are intensifying.
47:51Yet the scientists are painfully aware of their limits.
47:55We're usually confident of our ability,
47:59our technological ability to solve problems.
48:02And I think that's given us a great sense of comfort in this disease,
48:06and I think it's a false sense of comfort.
48:08We, that is, we who work with the fundamental aspects of this virus,
48:11know how far away we are from even understanding its workings,
48:15understanding how it causes the diseases it causes,
48:18and even some aspects of how it's transmitted.
48:21We have many areas of uncertainty.
48:23Not the least of our uncertainties are how to stop it.
48:26Although there is some hope now for drugs,
48:29and some hope for vaccines,
48:31we can't, and nobody with reliability,
48:33can predict when and if we can slow down the spread of the disease,
48:37or even stop what appears now to be an inevitable decline
48:40once the disease begins.
48:42So we are a long way from being able to control it.
48:46So in the absence of a medical solution,
48:48the only certain way to halt the spread of AIDS
48:51is to discourage the behaviors that place people at risk.
48:55This will require public education on a large scale.
49:03A model for the effectiveness of public education is San Francisco,
49:07where the AIDS epidemic was first seen among homosexual men.
49:11Here, a determined effort has been made
49:13to teach people about the danger from the virus.
49:18San Francisco is also where they've been charting the progress
49:21of the disease for the longest time.
49:24One of the studies is being run by epidemiologist Andrew Moss.
49:29When we began working on AIDS in 1982,
49:33the first thing we did was a study in this neighborhood.
49:38And we found out that about 1 in 300 gay men living in a mile of here had AIDS.
49:48And now it's about 1 in 30.
49:52In this area of San Francisco,
49:54well over half of the gay men are now infected with the AIDS virus.
49:58And this has made them especially cooperative.
50:02The participation rate was amazing.
50:05It's because the gay men who lived here wanted the disease to be solved.
50:09They wanted it to be understood and cured and so forth.
50:12Their determination to fight AIDS led to a massive educational campaign.
50:17The people of San Francisco were bombarded with AIDS information.
50:23They were informed of how AIDS is spread and how to avoid getting it.
50:27The message? Prevent AIDS by changing sexual behavior.
50:37The entire city was put on alert, and the effort continues today.
50:43This man's lover died of AIDS four years ago.
50:47Since that time, he's been participating in one of the studies,
50:51part of an ongoing survey to monitor the disease.
50:54The scientists are trying to chart its course,
50:57and they're looking for clues that will tell them if education has made a difference.
51:01When all this first started, there was no information whatsoever on AIDS.
51:05And when he was dying from AIDS, he had asked me to get involved in this program.
51:13Every year, a few days before Christmas, he arrives at Ward 86, the AIDS clinic,
51:18to become a vital statistic in the survey.
51:31The medical examination is only the beginning.
51:35Volunteers are also asked to reveal the history of their sex life,
51:39what they did, with whom, how often, and with what protection.
51:46Your sexual habits changed since you were last here?
51:49Well, I used to go, a few years ago, I used to go to the baths.
51:53I used to meet men on the buses and on the street and stuff.
51:57And ever since the information on AIDS came out,
52:00and I've had a few friends who have died from AIDS,
52:03ever since then, I've really stopped doing all that stuff.
52:10What about safe sex practices?
52:17Pretty much I don't have intercourse with anyone,
52:21because I figure that's the biggest risk that you can be taking right now.
52:26I'll loosen the tourniquet in just a moment.
52:29Does such sexual restraint actually make a difference?
52:32The answer can be found in the blood of Andrew Moss' subjects.
52:37And there are signs that education has slowed the spread of the virus.
52:42What we see is a flattening out.
52:44After four years in which numbers went like this,
52:47numbers that are going like this,
52:49we see about 60 cases of AIDS a month in San Francisco,
52:52and have done for the last year.
52:54Now, what does this mean?
52:56I think it reflects a major change in sexual behavior
52:59amongst gay men in San Francisco, beginning three or four years ago.
53:03We're finally beginning to see the results of that in the incidence data.
53:07But I want to make a caveat.
53:10What we see, what we measure, what we count,
53:13is just AIDS as it has been defined for the last four years.
53:17And the AIDS virus is a retrovirus,
53:19and we know that retroviruses can have lifelong manifestations.
53:23And it's possible that what's flattening out and maybe going away
53:26is just the early manifestations of the virus,
53:29and that we'll see new manifestations later on in its course.
53:33It's been suggested that primary neurological AIDS,
53:36or perhaps a kind of lymphomas, a subgroup of lymphomas,
53:39may be diagnoses that we'll see more of.
53:41So we want to be cautious and watch it carefully
53:44before we say it's going away.
53:49Scientists will continue their search for a vaccine and a cure for AIDS.
53:54But for now, the answer lies in prevention.
53:57For some individuals, that will mean changes in behavior.
54:01For society, it will mean guaranteeing that educational efforts take place.
54:06Then, just possibly, AIDS can be stopped.
54:18Mass education has to happen.
54:21More importantly, people have to hear it,
54:24realize that the problem is a small one, probably with few people,
54:31but that that small problem with small numbers
54:35affects directly or indirectly almost everyone.
54:45For more information on AIDS, call toll-free 800-342-AIDS.
54:52AZT Information Hotline 800-843-9388.
55:22For more information on AIDS, call toll-free 800-342-AIDS.
55:52For a transcript of this program, send $4 to NOVA, Box 322, Boston, Massachusetts, 02134.
56:17Please be sure to include the show title.
56:20To purchase film or video copies of this program for educational use,
56:24call toll-free 1-800-621-2131.
56:28In Illinois or Alaska, call Collect 312-940-1260.
56:38Major funding for NOVA is provided by this station
56:41and other public television stations nationwide.
56:45And by Allied Signal, a technology leader in aerospace,
56:49electronics, automotive products, and engineered materials.
56:57And the Johnson & Johnson family of companies, supplying health care products worldwide.
57:14Next on NOVA.
57:15For centuries, people have wondered, could there be intelligent life beyond Earth?
57:20Finally, science has developed the means to find the answer.
57:23The methods include sophisticated computers,
57:26some unusual ideas of how a message might be sent,
57:29and an assist from science fiction.
57:32Their goal? To answer one of humanity's oldest questions.
57:36Is anybody out there?
57:38With host Lily Tomlin, that's next time on NOVA.
57:45NOVA is a production of Iowa Public Television

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