Can AIDS Be Stopped?
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.
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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