Speaker 1: Hey, this is Leon Napok. I'm the host of Fiasco,
Speaker 1: but you may also know me from the podcasts Slowburn,
Speaker 1: Think Twice, Michael Jackson, and Backfired the Vaping Wars. I'm
Speaker 1: excited to be sharing with you the next season of Backfired,
Speaker 1: titled Attention Deficit, which is now available exclusively on Audible.
Speaker 1: Backfired is a podcast about the business of unintended consequences.
Speaker 1: In the first season, my co host ri L Pardess
Speaker 1: and I dove deep into the world of vaping and
Speaker 1: how the well intentioned quest for a safer cigarette went awry.
Speaker 1: Now we're tackling ADHD and how the push to destigmatize
Speaker 1: this hard to define childhood diagnosis has led to an
Speaker 1: explosion of stimulant use in kids as well as adults.
Speaker 1: It's a story about the promise of psychiatry to fix
Speaker 1: our brains and the power of the pharmaceutical industry to
Speaker 1: shape how we and our doctors think about what's wrong
Speaker 1: with us. To hear both seasons of Backfired, go to
Speaker 1: audible dot com slash Backfired and start a free trial
Speaker 1: that's audible dot com slash backfired. Previously on Fiasco.
Speaker 2: My main job was to try and develop drugs that
Speaker 2: could treat this devastating disease.
Speaker 3: The FDA announced today it would formerly streamline it's drug
Speaker 3: approval process.
Speaker 4: This thing of hoping for like a magic bullet, that
Speaker 4: you know, we would all be activists for two or
Speaker 4: three years, and then the cure would come, the vaccine
Speaker 4: would come, and we would all go back to our
Speaker 4: lives wasn't going to happen.
Speaker 5: People need medication now, ten years from now, they'll be dead.
Speaker 1: When the virus that causes AIDS was isolated in nineteen
Speaker 1: eighty three, it looked kind of like a time bomb.
Speaker 1: HIV could eat away at someone's immune system for months
Speaker 1: or years before they experienced any serious symptoms. Then one day,
Speaker 1: pretty much any infection could become fatal. In nineteen eighty seven,
Speaker 1: a young chemist at the pharmaceutical company Murk came up
Speaker 1: with an idea for how to disable the bomb. His
Speaker 1: name was Irving Siegel.
Speaker 6: What Siegel took on was really an impossible task. No
Speaker 6: pharmaceutical scientist had ever really taken on such a challenge
Speaker 6: as this.
Speaker 1: David France is the author of the book How to
Speaker 1: Survive a Plague and the director of the documentary film
Speaker 1: by the same name. During the height of the epidemic
Speaker 1: France was an activist and a journalist who covered the
Speaker 1: search for AIDS treatments. He says that after the release
Speaker 1: of the first AIDS drug, AZT, many drug companies scrambled
Speaker 1: to produce knockoffs.
Speaker 6: When AZT had come out in eighty seven, it immediately
Speaker 6: proved that there was a massive and very of financially
Speaker 6: rewarding market for drug companies to exploit.
Speaker 1: But as you've heard, AZT was not a miracle drug.
Speaker 1: Even when AZT seemed to make someone better at first,
Speaker 1: the virus rapidly mutated inside their body, which meant that
Speaker 1: eventually almost everyone who took it still developed AIDS. Irving Seagull,
Speaker 1: the scientist at MERK, was convinced he could build something
Speaker 1: better than AZT, a new class of drug that would
Speaker 1: attack HIV in a totally different way.
Speaker 6: Irving Siegel, he was young, he was charismatic. He pulled
Speaker 6: together a team of very excited researchers, and the very
Speaker 6: first thing that he focused on was a very novel approach.
Speaker 6: No one else was taking it, and that was an
Speaker 6: approach to look at protease inhibitors.
Speaker 1: Maybe you've heard that phrase before protease inhibitors. I definitely had,
Speaker 1: but I also did not know what a protease was
Speaker 1: or what it meant to inhibit it. So as I've learned,
Speaker 1: the HIV one protease is an enzyme that plays a
Speaker 1: critical role in allowing the virus to replicate in the body.
Speaker 1: Siegel believed that the key to treating HIV was stopping
Speaker 1: the protease from doing its job. After getting some initial
Speaker 1: buy in from the higher ups at MERK, Siegel and
Speaker 1: his colleague Nancy Cole started working on it, and just
Speaker 1: a few months later they completed a paper reporting a
Speaker 1: promising result. By inhibiting the HIV protease, it was possible
Speaker 1: to stop the virus from replicating, at least in the
Speaker 1: confines of a lab experiment. The quick turnaround was typical
Speaker 1: of Siegel. His wife Catherine told me he was someone
Speaker 1: who took the stairs two steps at a time when
Speaker 1: he came into work, and was often moving so fast
Speaker 1: that he would forget to button his shirts all the way.
Speaker 2: Can remember very clearly saying to myself, I have to
Speaker 2: keep up with this guy, because he's just he did.
Speaker 2: That's how rapidly he moved, That's how rapidly his brain
Speaker 2: worked too.
Speaker 1: Emilio Emini is a virologist who worked with Siegel as
Speaker 1: the head of Murk's efforts on HIV. He was a
Speaker 1: co author on that first paper about the HIV protease.
Speaker 2: So you can imagine, you know, a very you know,
Speaker 2: thin individual who is constantly moving and whose brain is
Speaker 2: constantly functioning, absolutely extraordinary.
Speaker 1: By December of nineteen eighty eight, Siegel and his team
Speaker 1: were on the cusp of a major advance, producing the
Speaker 1: first three D image of the protease. After more than
Speaker 1: a year of intensive work, they finally had a clear
Speaker 1: understanding of its unique cellular structure. Emilio Emini sometimes compares
Speaker 1: the HIV protease to a pac man, introducing it has
Speaker 1: a wedge like mouth which it uses to chomp down
Speaker 1: on HIV proteins and slice them into smaller pieces. These
Speaker 1: smaller pieces then spawn new HIV proteins throughout the body. Siegel, Emini,
Speaker 1: and their colleagues at MURK wanted to jam the pac
Speaker 1: man's mouth and render it incapable of doing any chomping
Speaker 1: or slicing. They believed that once this happened, the virus
Speaker 1: would stop replicating.
Speaker 2: So if the protease is not functional, or if it's
Speaker 2: rendered non functional and cannot perform this cutting activity, then
Speaker 2: the viral proteins that are produced won't be assembled into
Speaker 2: new viral particles right, and therefore the viral infection cycle
Speaker 2: is terminated.
Speaker 1: The three D image of the protease gave Segel and
Speaker 1: his colleagues a precise map of the enzyme, showing them
Speaker 1: where exactly they had to jam it. Now they could
Speaker 1: move on to the next step developing a drug, a
Speaker 1: protease inhibitor that could be digested by human beings. Siegel
Speaker 1: was confident that it could be done, but then shortly
Speaker 1: before Christmas, Siegel had to travel to London to deliver
Speaker 1: a long scheduled lecture. After three days away from his lab,
Speaker 1: he was eager to get back, so at the last
Speaker 1: minute he decided to change his flight to a red eye.
Speaker 1: Pan Am flight one oh three left London on the
Speaker 1: night of December twenty first, nineteen eighty eight. Less than
Speaker 1: an hour after takeoff, the plane exploded over Lockerby, Scotland,
Speaker 1: killing everyone on board.
Speaker 7: Just after seven this evening, a jumbo jet crashed onto
Speaker 7: the town of locker Bit in the Scottish borders. It
Speaker 7: was a Pan American Boeing seven four seventh.
Speaker 2: I remember very clearly where I was when I got
Speaker 2: the news. I was at home. Actually it was right
Speaker 2: before Christmas. It was right before Christmas in nineteen eighty eight.
Speaker 7: We now know there were two hundred and forty four
Speaker 7: people on board, including three children.
Speaker 1: Irving Seagull was just thirty five years old when he
Speaker 1: died in the locker be bombing.
Speaker 2: It was absolutely devastating, as you can imagine. It was
Speaker 2: devastating for what we were doing collectively, was devastating for
Speaker 2: the science. It was devastating for the whole field. But
Speaker 2: more importantly, it was devastating personally for Irving and for
Speaker 2: his family.
Speaker 1: Seagull's vision of a protease inhibitor would eventually lead to
Speaker 1: a massive paradigm shift in AIDS treatment as part of
Speaker 1: the so called triple cocktail. It would unlock the first
Speaker 1: effective therapy for HIV and AIDS, and it would finally
Speaker 1: make it possible for people who had the disease to survive.
Speaker 1: But none of that would happen until nineteen ninety six,
Speaker 1: nine years after Segel first saw promise in the HIV protease,
Speaker 1: and fifteen years after the first cases of AIDS were
Speaker 1: observed in America. It's impossible to say whether an effective
Speaker 1: treatment might have come sooner if Irving Siegel hadn't changed
Speaker 1: his flight from London. What's clear enough is that his
Speaker 1: death was a major setback, one of many in science's
Speaker 1: long and grueling campaign against AIDS. I'm Leon Napak from
Speaker 1: Audible Originals and Prologue projects. This is fiasco.
Speaker 3: Typically, the stronger the drug, the faster HIV adapts to
Speaker 3: resist it.
Speaker 4: It seemed that everything we had done up to that
Speaker 4: point hadn't been enough.
Speaker 8: Researchers say a new class of drugs are working.
Speaker 9: Where once there was only desperation, there is now genuine hope.
Speaker 10: I'm looking falling through a future, the Lazarus effect that
Speaker 10: people described it felt like a miracle.
Speaker 1: In this episode, the darkest days of the AIDS crisis
Speaker 1: in America followed at long last by a glimpse of light.
Speaker 1: By the nineteen nineties, HIV had spread all over the globe.
Speaker 11: Fourteen million people in the world are now HIV positive.
Speaker 11: The number grows dramatically every year.
Speaker 1: And affected just about every demographic.
Speaker 11: Still, no cure still no vaccine to prevent it.
Speaker 1: In the US, cases among women and people of color
Speaker 1: were climbing at a particularly alarming rate, and as the
Speaker 1: time bomb went off and more and more people, the
Speaker 1: death totals were rising.
Speaker 3: Every year in this country, four hundred thousand have gotten AIDS,
Speaker 3: two hundred and forty thousand have died.
Speaker 2: Whatever we've been doing has not been enough.
Speaker 6: It wasn't until we hit nineteen ninety three and nineteen
Speaker 6: ninety four and nineteen ninety five that the body counts
Speaker 6: became extreme.
Speaker 1: David France again, these were.
Speaker 6: Mass dying events each year. Forty three thousand Americans died
Speaker 6: in nineteen ninety three, fifty thousand Americans in nineteen ninety four.
Speaker 6: So we entered a period of real despair.
Speaker 1: For many AIDS activists, the tragedy wasn't just about how
Speaker 1: many people were dying during this period. It was also
Speaker 1: that many of the dead had been leaders in the movement.
Speaker 6: Nineteen ninety three opened with the death of Bob Ravski,
Speaker 6: who was a key member of Act UP, one of
Speaker 6: its kind of poet warriors.
Speaker 12: Questions, what does a decent society do with people who
Speaker 12: hurt themselves because they're human? Who smoke too much, we
Speaker 12: too much, you drive carelessly, who don't have safe sex?
Speaker 12: And the answer, I think the answer is at a
Speaker 12: decent society does not put people out to pastor and
Speaker 12: let them die because they've done a human thing.
Speaker 6: His death was a trauma for the movement and the community,
Speaker 6: and then by the end of the year, Michael Callen died.
Speaker 1: You met Michael Callen in our second episode. He was
Speaker 1: the singer, an early AIDS activist who spearheaded a safe
Speaker 1: sex campaign in New York and helped create a Bill
Speaker 1: of Rights for people with AIDS.
Speaker 13: It's hard to believe Michael Callen is no longer with us.
Speaker 13: For more than a decade, he made beautiful music and
Speaker 13: worked tirelessly to improve the quality of life for people
Speaker 13: with AIDS, all the while fighting the disease himself.
Speaker 10: We won.
Speaker 6: Michael Callen was the author of a book on surviving
Speaker 6: HIV and if the guy who was a self proclaimed
Speaker 6: long term survivor couldn't survive, then it seemed we were
Speaker 6: all lost.
Speaker 14: I realized that some people could look at my life
Speaker 14: and say, oh, it was so sad when he died
Speaker 14: of AIDS, And isn't that tragic? But what I want
Speaker 14: to come through is that even after all the pain
Speaker 14: and all the torture, and even having AIDS, I can
Speaker 14: honestly say being gay is the greatest gift I was
Speaker 14: ever given. I wouldn't change it.
Speaker 2: For the worlds.
Speaker 1: Amid all of this death, more and more activists started
Speaker 1: to burn out Garantz. Frankie Ruda, who had joined Act
Speaker 1: Up as a teenager in the late eighties, was one
Speaker 1: of them.
Speaker 10: I think people have just had a lot of unprocessed
Speaker 10: grief and we're just really like unraveling.
Speaker 1: Honestly, Like many in the movement, Frankie Ruda was exhausted
Speaker 1: by the lack of progress on medical treatment and by
Speaker 1: infighting among her fellow activists.
Speaker 10: All activist organizations have kind of a half life. They
Speaker 10: burst onto the scene, they're incredibly viral, and then they
Speaker 10: start to sort of change.
Speaker 1: The changes Act UP was going through might have been
Speaker 1: easier to take if Frankie Ruda wasn't also losing friends
Speaker 1: to AIDS on a routine basis.
Speaker 10: A lot of people had been infected around the same
Speaker 10: period of time, and there was a sense amongst a
Speaker 10: lot of people that they were not getting out of
Speaker 10: this alive. Some people were very pessimistic about whether or
Speaker 10: not they were going to see the end of the pandemic.
Speaker 1: The sense of despair deepened in June of nineteen ninety
Speaker 1: three when scientists made a crushing announcement about AZT at
Speaker 1: the International AIDS Conference in Berlin.
Speaker 11: Discouraging news Today about the effectiveness in some cases of AZT.
Speaker 1: French and British researchers had conducted the largest study ever
Speaker 1: on AZT. Their conclusion was that in the long term
Speaker 1: the drug simply did not work well.
Speaker 4: The T yes it was, there no significant benefit in
Speaker 4: terms of survival or profession to AIDS.
Speaker 3: Reading from slides on a big overhead screen, the head
Speaker 3: of the European study told the delegates patients inspected with
Speaker 3: HIV who take AZT before they develop symptoms of AIDS
Speaker 3: are no better off than patients who take it after
Speaker 3: they come down with the disease.
Speaker 1: The limits of AZT were already well known, but according
Speaker 1: to the new study, the drug didn't extend life for
Speaker 1: people with AIDS by a single day. In fact, patients
Speaker 1: in the placebo group actually lived a little longer. After
Speaker 1: the conference, the Washington Post described it as the most
Speaker 1: depressing moment in aid's treatment history. Mark Harrington, the act
Speaker 1: UP member you first met in our previous episode, was
Speaker 1: in Berlin at the time of the AZT announcement.
Speaker 4: I think at that point it was pretty universally felt
Speaker 4: that we were all doomed and anybody that had HIV
Speaker 4: was going to die. We're not going to be changing
Speaker 4: the field fast enough to to save our lives or
Speaker 4: the lives of most of our friends that had HIV
Speaker 4: and most of the other millions and millions of people
Speaker 4: that had HIV. So it seemed that everything we had
Speaker 4: done up to that point hadn't been enough.
Speaker 1: Three weeks after the conference in Berlin, a group of
Speaker 1: AIDS activists channeled their sorrow into a protest in Washington, Free.
Speaker 3: The deaths of years we are taking any harm.
Speaker 1: It was a new kind of protest known as a
Speaker 1: political funeral.
Speaker 6: It got to the point where the community started this
Speaker 6: campaign to show our deaths, to show what AIDS looked like,
Speaker 6: and the most dramatic way that that happened was through
Speaker 6: political funerals, in which the corpses of the fallen comrades
Speaker 6: were taken out into the streets and displayed in these
Speaker 6: these really heartbreaking expressions of anger and rage.
Speaker 1: The point of political funerals was to force an awareness
Speaker 1: of the death toll from AIDS onto those who might
Speaker 1: otherwise find it easy to look away. Mark Harrington says
Speaker 1: that activists didn't want AIDS to be a private epidemic.
Speaker 4: We wanted the American people to see the cost, to
Speaker 4: see the lives that were being lost, and to be
Speaker 4: made aware by us putting it into their faces that
Speaker 4: the people that were dying were loved and were valued
Speaker 4: members of our society. And so this was a sign
Speaker 4: of desperation, of despair, but also a beautiful sign of solidarity.
Speaker 1: It was the summer of nineteen ninety three when an
Speaker 1: act UP member with AIDS named Tim Bailey took a
Speaker 1: turn for the worse. As he lay dying, Bailey told
Speaker 1: his friends that he wanted his body thrown over the
Speaker 1: White House gate. It would be a nod to an
Speaker 1: act UP protest held the previous year when more than
Speaker 1: a dozen activists poured out the ashes of their loved
Speaker 1: ones onto the White House lawn.
Speaker 5: And we're here today to bring home to George Brush
Speaker 5: the results of this murders in action.
Speaker 1: Tim Bailey's idea to have people throw his actual body
Speaker 1: onto the lawn was a little more extreme, and his
Speaker 1: friends demurred, but they promised him they would do something
Speaker 1: in front of the White House.
Speaker 5: True Love.
Speaker 1: On July first, nineteen ninety three, a few days after
Speaker 1: Bailey died, his friends drove his body from a funeral
Speaker 1: home in New Jersey to Washington, d C.
Speaker 6: This was carried out like a military operation. They rented
Speaker 6: a van and they called upon Act Up members around
Speaker 6: the country to meet them in Washington.
Speaker 1: The plan was to meet up at the Capital reflecting pool,
Speaker 1: then marched down Pennsylvania Avenue in a procession, But by
Speaker 1: the time the activist van pulled into a parking lot
Speaker 1: near the Capitol, the authorities were already there. Some were
Speaker 1: wearing riot gear.
Speaker 10: This is this is the last whistles, It's in the will.
Speaker 2: There are legal permits, there are family members here.
Speaker 5: You're going to You're going to interfere with a funeral
Speaker 5: procession in front of.
Speaker 15: All this press.
Speaker 6: It was a showdown of remarkable tension and anger. There
Speaker 6: was rage and tears coming from the protesters, who felt
Speaker 6: that they owed it to Tim Bailey to be able
Speaker 6: to accomplish what he had asked for and yet they
Speaker 6: were being blocked.
Speaker 1: According to one witness, a federal agent at one point
Speaker 1: reached into the van holding Bailey's casket and snatched the
Speaker 1: keys from the driver. Activists surrounded van and sat down
Speaker 1: so it couldn't be driven away. After a tense standoff
Speaker 1: that lasted several hours, they flung open the back doors
Speaker 1: and forced the casket.
Speaker 6: Out, But the pushback from this phalanx of police officers
Speaker 6: was such that the whole casket nearly fell over and
Speaker 6: nearly emptied itself in the parking lot. Everything you wanted
Speaker 6: to do, and now you're fucking hell.
Speaker 1: You have to god damn more. Eventually, the activists regained
Speaker 1: control of Bailey's casket and managed to get it back
Speaker 1: into the van. The police then surrounded the van and
Speaker 1: escorted it onto the highway back towards New Jersey.
Speaker 6: The escort lasted into Maryland to Baltimore, and Tim's body
Speaker 6: was returned ultimately to the funeral home and he was
Speaker 6: given a regular burial after that.
Speaker 1: By nineteen ninety three, activists weren't the only ones losing hope.
Speaker 1: Scientists were also beginning to doubt whether an effective treatment
Speaker 1: for HIV was possible AZT like drugs had proven ineffective,
Speaker 1: and while MIRK was putting its energy behind protease inhibitors,
Speaker 1: there was no guarantee that those would work either. Here
Speaker 1: again is Emilio Emini, the virologist who ran Merk's HIV efforts.
Speaker 2: What was in everyone's back of everyone's mind was, well,
Speaker 2: maybe every single drug we develop against this virus, or
Speaker 2: even an inhibit of the protease, maybe the virus can
Speaker 2: very quickly defeat it by simply becoming resistant quickly.
Speaker 1: Thanks to Irving Siegel and his colleagues, MIRK had been
Speaker 1: early on protease research, but in the years after Siegel's death,
Speaker 1: progress had been slow. It wasn't just because Siegel wasn't
Speaker 1: there to help. Everyone I spoke to said his team
Speaker 1: continued working on protease inhibitors with the same urgency as before.
Speaker 1: It was just that making a functional drug out of
Speaker 1: Siegel's idea was extremely hard. Here's David Franz again.
Speaker 6: It was the most complex pharmaceutical production ever undertaken. To
Speaker 6: create this molecule took fourteen painstaking steps, each one very
Speaker 6: time consuming. Each one depended on the one before it.
Speaker 6: The idea that this would work was certainly far from
Speaker 6: but reliable.
Speaker 1: The drug that Merk was working on would eventually be
Speaker 1: called krick Savan. The scientist in charge of producing it
Speaker 1: happened to also be a chef, and in an interview
Speaker 1: with the Philadelphia Inquirer, he explained that making krick savan
Speaker 1: was like cooking an intricate, multi course meal for a
Speaker 1: thousand people. If you wrote the recipe for krick savan,
Speaker 1: he said, each of the fourteen steps would cover sixty pages.
Speaker 1: The effort seemed to be paying off. Kricks Evan worked
Speaker 1: extremely well in lab trials, so well that, according to
Speaker 1: David France, the team at Merk did something pretty unusual.
Speaker 6: As Merk and the HIV team were getting more and
Speaker 6: more excited about kricks evan from what they saw in laboratories,
Speaker 6: they wanted to push the thing into human trials very quickly,
Speaker 6: and they had such faith that it would work that
Speaker 6: they did something that is not done in pharmaceutical research.
Speaker 1: Typically, after successful lab trials, pharma companies test their drugs
Speaker 1: on healthy animals to make sure the drugs aren't toxic
Speaker 1: and can be absorbed into the bloodstream. According to France's reporting,
Speaker 1: Merk skipped the animal trial.
Speaker 6: Sort of What they did instead was they tested it
Speaker 6: among the scientists. They took it themselves, and so they
Speaker 6: knew that it was safe because they all survived the
Speaker 6: exposure to it. And it's something that has often joked
Speaker 6: about in the pharmaceutical world as a big chimp study,
Speaker 6: in which the big chimp is the scientist himself.
Speaker 1: We asked Emilio Amini about the big chimp trial. He
Speaker 1: declined to comment. I told you a bit ago about
Speaker 1: the devastating AZT announcement in Berlin. It was about six
Speaker 1: months later that Merk ran a trial of krick Savan
Speaker 1: and a group of people who were all HIV positive.
Speaker 1: A week into the study, each patient's viral load fell dramatically.
Speaker 1: Krick Savan appeared to work, at least in the short run.
Speaker 2: What we initially saw was that there was in fact,
Speaker 2: very clear and rapid decline a virus load in those individuals.
Speaker 2: And this was the first time that was seen with
Speaker 2: any drug, you know, for HIV. So it gave us
Speaker 2: a sort of a glimmer of hope that you know,
Speaker 2: we have, you know, something potentially useful here, right, you know,
Speaker 2: we felt, well, maybe there's something special about the proteuse.
Speaker 2: Maybe there's something special that the virus cannot rapidly become
Speaker 2: resistant to this class of drugs, and so we were encouraged.
Speaker 1: The question was would the virus find a way to
Speaker 1: mutate around the drug like it had with AZT. The
Speaker 1: researchers at MERK were optimistic enough that they had shared
Speaker 1: their preliminary results with other AIDS researchers, but soon their
Speaker 1: hopes were dashed. Once again, HIV had mutated and effectively
Speaker 1: become resistant to the new drug.
Speaker 2: So if if we go back to the pac man analogy,
Speaker 2: and you consider the protease inhibitor has been a something
Speaker 2: a ball of rock, whatever you want to call it,
Speaker 2: that gets in the mouth of the pac mand so
Speaker 2: that the pac man can no longer, you know, close
Speaker 2: its mouth and chump up the viral proteins. What the
Speaker 2: mutation does is that the mutation alters the structure of
Speaker 2: the pac man mouth just ever so slightly, but ald
Speaker 2: is it enough so that the inhibitor can't bind into
Speaker 2: that mouth anymore.
Speaker 12: The one.
Speaker 1: Just to make sure you got that, the mutation occurred
Speaker 1: right in the pac man's mouth. Now, the protease inhibitor
Speaker 1: that Murk had spent years developing and fine tuning didn't
Speaker 1: fit properly, and so the pac man the protease went
Speaker 1: right back to chomping and slicing HIV proteins and enabling
Speaker 1: them to replicate in patient's bodies. HIV was rebounding in
Speaker 1: Murk's study participants, and it was happening extremely fast. By
Speaker 1: that time, we had a good feel for this.
Speaker 2: We already knew that what we were looking at here
Speaker 2: was resistant selection.
Speaker 1: It was harder.
Speaker 2: It was harder for the virus to become resistant against
Speaker 2: the protease inhibitor, but it wasn't that hard.
Speaker 1: HIV was the ultimate Darwinian nightmare. It seemed to evolve
Speaker 1: around every obstacle put in its path. After years of
Speaker 1: effort and hundreds of millions of dollars spent, Merk's new
Speaker 1: drug appeared to be meeting the fate of every other
Speaker 1: HIV treatment. The disappointment of krick Savan didn't mean that
Speaker 1: protease inhibitors in general would never work, or that a
Speaker 1: different drug based on the same idea wouldn't produce different results.
Speaker 1: In fact, in the early nineties, several pharmaceutical companies other
Speaker 1: than Merk were attempting to develop their own protease inhibitors.
Speaker 1: In May of nineteen ninety four, a company called Hoffman
Speaker 1: Laroche became the first of Mrk's rivals to put a
Speaker 1: protease inhibitor in front of the FDA.
Speaker 11: But new drug called the most important advance since AZT.
Speaker 1: The drug was called sequineverr.
Speaker 11: Sha quivnaire, the first of a new generation of AIDS
Speaker 11: fighting drugs.
Speaker 1: Hoffman Laroche was asking the FDA for accelerated approval, which
Speaker 1: was exciting news for AIDS activists patients across the country.
Speaker 1: Merk's protease inhibitor hadn't panned out, but maybe Hoffman the
Speaker 1: Rosch's version would turn out to be the real deal.
Speaker 3: Researchers caution against too much optimism, but it is the
Speaker 3: most powerful weapon yet developed against the AIDS virus.
Speaker 1: There was, however, a surprising hitch in the company's plan
Speaker 1: to get sequinevere to market quickly. A small but influential
Speaker 1: group of former act UP members was standing in the way.
Speaker 1: They called themselves the Treatment Action Group or TAG for short.
Speaker 1: TAG included many of the science oriented activists from act UP,
Speaker 1: including Mark Harrington. As you heard in our previous episode,
Speaker 1: Harrington and some of his colleagues had split off from
Speaker 1: act UP, in part because they wanted to work with
Speaker 1: government officials, not just antagonize them. By nineteen ninety four,
Speaker 1: TAG was in regular contact with the FDA, and one
Speaker 1: of its members served on the Agencies of FI Advisory Board.
Speaker 1: As the FDA considered the possibility of early approval for sequinivere,
Speaker 1: the activists in TAG made it known that they were
Speaker 1: against it. I asked Harrington to explain their thinking. So
Speaker 1: TAG opposed fast tracking the drug, and I think as
Speaker 1: we tell our listeners about that, that their first instinct
Speaker 1: will be to say, wait a second. I thought these
Speaker 1: guys wanted to fast trike the drugs.
Speaker 4: What happened Berlin happened.
Speaker 1: After the conference in Berlin, where it was revealed just
Speaker 1: how much of a failure AZT was. Harrington had come
Speaker 1: to view the drug as a cautionary tale. Years earlier,
Speaker 1: AZT had been fast tracked and given the benefit of
Speaker 1: the doubt. Now the pitfalls of moving too fast were
Speaker 1: all too clear.
Speaker 4: We recognized that some of the things that we'd done
Speaker 4: to change clinical trials had led to false answers that
Speaker 4: weren't accurate. We found out that the fast tracking for
Speaker 4: drugs resulted in some drugs that didn't work being released
Speaker 4: onto the market.
Speaker 1: Harrington felt that he and his fellow activists had been
Speaker 1: naive for years. They had agitated for drugs to be
Speaker 1: released as quickly as possible to people with AIDS on
Speaker 1: the theory that anything was better than nothing, and.
Speaker 4: We had gotten a scientist in the regulators to also
Speaker 4: be naive. But everyone was tired of all the deaths
Speaker 4: and all the sick people and the lack of hope.
Speaker 4: Everyone wanted these drugs to work, but just wishing.
Speaker 1: Doesn't make it so sequinevere. The protease inhibitor developed by
Speaker 1: Merk's rival Hoff and Laroche struck the members of TAG
Speaker 1: as yet another source of false hope. Among other things,
Speaker 1: Harrington was alarmed by the way Hoff and Laroche had
Speaker 1: conducted its trials.
Speaker 4: They did a little study in fewer than three hundred people,
Speaker 4: and in summer of ninety four they wanted to FDA
Speaker 4: to give it accelerated approval, and we said, no, this
Speaker 4: is three hundred people. You want to do the first
Speaker 4: of a new generation of AIDS drugs with a shitty
Speaker 4: inadequate sample size. That's far too load to tell us
Speaker 4: even if there's a side effects, let alone whether the
Speaker 4: drug works, and you need to redraw your whole clinical
Speaker 4: development plan from scratch.
Speaker 1: From tag's perspective, if sequinavere were approved hastily, it had
Speaker 1: a good chance of dominating the market for protease inhibitors.
Speaker 1: That was what had happened with AZT after the FDA
Speaker 1: fast tracked approval of that drug back in nineteen eighty seven.
Speaker 1: David Franz explains.
Speaker 6: They did not want an AZT like scenario to take place.
Speaker 6: If sequinavere was probably the least promising of the protease inhibitors,
Speaker 6: and yet if it had gotten to market before anybody else,
Speaker 6: they worried that it would you take all the oxygen
Speaker 6: out of the air for the other developed compounds.
Speaker 1: TAG demanded that Hoffman Laroche go back to the drawing
Speaker 1: board and dramatically expand the trial size for sequinavier. They
Speaker 1: proposed eighteen thousand participants, a sixtyfold increase from the original study.
Speaker 1: Hoffman Laroche executives weren't exactly pleased to hear this, and
Speaker 1: to gin up support for their fast track application, they
Speaker 1: faxed tag's proposal to a bunch of other AIDS activist
Speaker 1: groups across the country. When those activists learned about tag's opposition,
Speaker 1: many of them were outraged.
Speaker 6: When TAG went their own way, they stepped on a
Speaker 6: lot of feet. In fact, they stepped on just about
Speaker 6: every foot in the movement. AIDS activists had never before
Speaker 6: this point tried to slow down a drug to market,
Speaker 6: and it created an amazing shit storm in the activist community.
Speaker 1: Dozens of AIDS groups signed a statement registering their disagreement
Speaker 1: with TAG over sequinivir, but TAG by this point had
Speaker 1: built up a lot of sway with the FDA, and
Speaker 1: Hoffman Laroche's application was rejected.
Speaker 4: The controversy was fast and furious between libertarian activists who
Speaker 4: really thought people should just take anything they want, and
Speaker 4: then kind of more rigorous activists who thought we needed
Speaker 4: better data before approving drugs that were going to be
Speaker 4: taken by hundreds of thousands of Americans and millions of
Speaker 4: people around the world. People from the community were yelling
Speaker 4: at each other and calling each other killers and murderers
Speaker 4: and so on.
Speaker 1: TAG made it clear that they were not just singling
Speaker 1: out Hoffman Laroche. They wanted every drug company working on
Speaker 1: protease inhibitors to take their time to run large, rigorous
Speaker 1: trials that would yield rich, clean data. Other activists stuck
Speaker 1: with what they had been saying for years, and people
Speaker 1: with AIDS didn't have time to wait. Back at Murk,
Speaker 1: Emilio Emini and his colleagues were continuing to track the
Speaker 1: participants of their protease inhibitor trial. Remember, they had seen
Speaker 1: their virus levels plummet in the first week of using
Speaker 1: crick savan, and then like clockwork, the numbers had shot
Speaker 1: back up in all of them, all of them except
Speaker 1: one patient, number one hundred and forty two. For some reason,
Speaker 1: that patient's viral load remained nearly undetectable, not just at
Speaker 1: first but for months afterwards.
Speaker 2: And that one patient, for reasons that to this day
Speaker 2: are never never been really understood, that one patient, the
Speaker 2: virus level came down but never came back up again.
Speaker 3: And this was.
Speaker 2: The first time any patient, as far as we knew,
Speaker 2: that had been treated with an HIV inhibitor, had actually
Speaker 2: demonstrated the ability for prolonged virus suppression. And we kept
Speaker 2: following that patient and never came back up, and just
Speaker 2: stayed down.
Speaker 1: Amini and his colleagues didn't just write this off as
Speaker 1: an anomaly. The data was real, and patient one hundred
Speaker 1: and forty two wasn't some kind of superhuman And.
Speaker 2: What we said to ourselves was, well, the fact that
Speaker 2: it happened in one patient doesn't tell us that, you know,
Speaker 2: we have a high probability that we're going to be
Speaker 2: able to do this, you know and everybody. But you
Speaker 2: know what it does tell us. It tells us for
Speaker 2: the first time that it's actually possible to do it.
Speaker 1: Patient one hundred and forty two became Mrk's north star.
Speaker 2: In fact, various members of the team had mouse pads
Speaker 2: actually made up that actually showed the virus load in
Speaker 2: this one individual. It was a way of saying to ourselves, look,
Speaker 2: we actually did it. Now what we now need to
Speaker 2: figure out is how do we do it in everybody.
Speaker 1: Emini and his colleagues followed their small phase one study
Speaker 1: with a much bigger Phase two trial that would track
Speaker 1: thousands of subjects over many months. Even just producing enough
Speaker 1: drugs for a study that big was a challenge.
Speaker 2: The process of making the drug was not trivial. It
Speaker 2: would require the establishment of literally a brand new chemical
Speaker 2: manufacturing facility. One of the steps was an extreme exotherm,
Speaker 2: which is a way of saying that it was an
Speaker 2: explosive step that if you didn't do it carefully, it
Speaker 2: would blow up your factory literally.
Speaker 1: While the trial got underway, Amini and his colleagues began
Speaker 1: testing out different doses of cricksivan on patients. They also
Speaker 1: tested the drug in combination with other kinds of drugs,
Speaker 1: including AZT. That was a relatively new idea meant to
Speaker 1: address HIV's ability to rapidly mutate around pretty much every
Speaker 1: drug researchers had thrown at it.
Speaker 6: A thought occurred to scientists, and it was simultaneously in
Speaker 6: multiple labs that it's simply a matter of math that
Speaker 6: two drugs is better at preventing the virus from mutating
Speaker 6: in ways that will escape the drug treatment.
Speaker 1: Emilio Emini was one of the scientists who'd helped make
Speaker 1: this discovery. It's so called combination therapy was more effective
Speaker 1: than using a single drug. Before protease inhibitors were developed,
Speaker 1: there had only been in two classes of drugs to
Speaker 1: try in combination with each other, AZT and one other.
Speaker 1: Now there were three each one would attack HIV in
Speaker 1: its own way and essentially back the virus into a
Speaker 1: corner until it could no longer mutate its way out.
Speaker 6: People wanted to try a third drug and to see
Speaker 6: if attacking the HIV virus in three different ways would
Speaker 6: indeed flummix the HIV to the point of being able
Speaker 6: to actually produce lasting results.
Speaker 1: A group of patients were given cricksavan along with AZT
Speaker 1: and the other drug. The early results were remarkable, and
Speaker 1: by the end of nineteen ninety five, Amini and his
Speaker 1: colleagues at MURK were ready to tell the world about
Speaker 1: what they were seeing.
Speaker 8: There's a major new reason for hope in the fight
Speaker 8: against age. Tonight, researchers at an age conference in Washington
Speaker 8: say a new class of drugs were working.
Speaker 1: On January thirtieth, nineteen ninety six, Amini was in Washington,
Speaker 1: d c. To address the annual Conference on Retroviruses and
Speaker 1: Opportunistic Infections. There, he delivered some major news.
Speaker 9: Studies presented at the conference show that over a six
Speaker 9: month period, the drug sharply reduced the level of virus
Speaker 9: in the body. Also, over a six month period, people
Speaker 9: taking the drugs died at half the rate of people
Speaker 9: not taking the drugs.
Speaker 1: Crick Savan, combined with the two other drugs, had made
Speaker 1: HIV undetectable in most patients, and the effect didn't appear
Speaker 1: to be temporary. At the time of the conference, it
Speaker 1: had persisted for six whole months. Audience members gasped at
Speaker 1: the data. For the first time since the AIDS epidemic began,
Speaker 1: a treatment was having a lasting impact. The three drug
Speaker 1: combination was working. After all those years of disappointment. AZT
Speaker 1: did end up being part of an effective therapy, but
Speaker 1: the development of proteus inhibitors had made the crucial difference.
Speaker 1: By March, crick Savan and two other protease inhibitors have
Speaker 1: been approved by the FDA. They were the fastest approved
Speaker 1: drugs in the agency's history.
Speaker 2: I'd be lying if I didn't say it wasn't emotionally
Speaker 2: and personally very satisfying. And what was most gratifying was
Speaker 2: not just looking at the virus load. But it was
Speaker 2: clear that as soon as the drugs became available and
Speaker 2: started to be used appropriately as a combination from the
Speaker 2: very beginning, that the impact it was having on progression
Speaker 2: to as was us extraordinary.
Speaker 1: The three drug combination became known as the Triple Cocktail.
Speaker 1: It came with difficult side effects at a huge price
Speaker 1: tag upwards of fifteen thousand dollars a year. Still, many
Speaker 1: people were able to obtain it through their health insurance
Speaker 1: or through the federally funded AIDS Drug Assistance program. That summer,
Speaker 1: Mark Harrington began taking the Triple Cocktail and experienced an
Speaker 1: almost immediate change.
Speaker 4: My fire load went from over two hundred thousand to
Speaker 4: nothing over the next three months, and it's been either
Speaker 4: very low or undetectable in the twenty five years since.
Speaker 4: And none of us could really believe it at first.
Speaker 4: It was too good to be true, But the truth
Speaker 4: was that these drugs really did stop the progression of HIV.
Speaker 9: Nobody is proclaiming a cure for AIDS yet, but based
Speaker 9: on the results with a new drug combination, many people
Speaker 9: are starting to believe it may soon be a possibility.
Speaker 1: Harrington's friend and fellow activist Garantz. Frankie Ruda had joined
Speaker 1: the movement at the tail end of the Reagan administration.
Speaker 1: By nineteen ninety six, she had scaled back her involvement
Speaker 1: and had enrolled in college hoping to become a doctor.
Speaker 1: She still remembers where she was when she heard the
Speaker 1: triple cocktail was working.
Speaker 10: I was in New York that summer, and I remember
Speaker 10: talking to folks and sort of getting the news and
Speaker 10: just like being in this elevator to this crappy little
Speaker 10: apartment I was sharing with some friends in college.
Speaker 2: Like.
Speaker 10: Feeling like, even though I knew it was the work
Speaker 10: of men and science, it felt like some grand act
Speaker 10: of mercy made manifest. And I think the Lazarus effect
Speaker 10: that people described for these medications on people sort of
Speaker 10: coming off their deathbeds and coming back to life gives
Speaker 10: you a sense also that even the scientists and the
Speaker 10: doctors had to take a recourse in biblical and religious
Speaker 10: language to describe what happened, because it felt like a miracle.
Speaker 9: Where once there was only desperation, there is now genuine hope.
Speaker 13: Started getting weight, and little lakers and pains and problems
Speaker 13: that I had in my body started resolving, and sort
Speaker 13: of like everything went back to normal.
Speaker 15: And now I feel that I have a great potential
Speaker 15: to live a much longer lifespan than was originally fought
Speaker 15: when I was diagnosed in nineteen eighty seven, and I
Speaker 15: look forward.
Speaker 3: To being here for my daughter's graduation next year from college.
Speaker 1: I have a fourteen month old grand.
Speaker 2: Baby that I you know, so I'm looking forward to
Speaker 2: a future.
Speaker 1: The opportunistic infections disappeared, a ma seated people began gaining
Speaker 1: weight again. The so called AIDS wards in America's hospitals
Speaker 1: emptied out and closed down.
Speaker 9: In New York City, which has the most AIDS cases
Speaker 9: in the country, the death rate from AIDS dropped almost
Speaker 9: half from nineteen to day last January to eleven a
Speaker 9: day in July. Across the country, hospitals are seeing fewer
Speaker 9: AIDS patients and fewer deaths.
Speaker 4: When I found out that they were working for me,
Speaker 4: and they were also working for other people that had
Speaker 4: started them, I could exhale, you know, I could say, okay, okay,
Speaker 4: we can move on now. We have got to this point.
Speaker 9: Nineteen ninety six was a watershed year in AIDS.
Speaker 13: It was the first year, the first time that treatment
Speaker 13: actually outpaced the virus.
Speaker 4: And the first time in fifteen years of the pandemic,
Speaker 4: we had something that we could offer to anybody with
Speaker 4: HIV or AIDS that could keep them healthy if they
Speaker 4: had HIV OR, that could reverse their AIDS and save
Speaker 4: their life if they had AIDS, and that was truly unbelievable,
Speaker 4: and yet it was true.
Speaker 1: With that, a new era in the history of AIDS began.
Speaker 1: But the nightmare wasn't over yet, not even close. On
Speaker 1: next week's season finale, why the HIV AIDS epidemic persists
Speaker 1: after the development of the Triple Cocktail, and why it
Speaker 1: continues to this day.
Speaker 13: Anytime you're talking about sex and drugs, it's a moral
Speaker 13: issue rather than a public health issue.
Speaker 1: Fiasco is presented by Audible Originals and Prologue Projects. The
Speaker 1: show is produced by Andrew Parsons, Sam Graham Felsen, Madelin
Speaker 1: kaplan Ula Cualpa, and me Leon Nafock. Our researcher is
Speaker 1: Francis Carr. Editorial support from Jessica Miller and Norah waswas
Speaker 1: archival research by Michelle Sullivan. This season's music is composed
Speaker 1: by Edith Mudge. Additional music by Nick Silvester of God Mode,
Speaker 1: Joel Saint, Julian and Dan English, Noah Hect and Joe Valley.
Speaker 1: Our theme song is by Spatial Relations. Our credits song
Speaker 1: this week is Philosophers by Peter Sandberg. Music licensing courtesy
Speaker 1: of Anthony Roman audio mixed by Erica Wong with additional
Speaker 1: support from Selina Rabbe. Our artwork is designed by Teddy
Speaker 1: Blanks at Chips and Y. David Blum is the editor
Speaker 1: in chief of Audible Originals. Mike Charzak is the vice
Speaker 1: president of Audible Studios. Zach Ross is head of acquisition
Speaker 1: and development for Audible. Thanks to Peter Yasse, Nancy Cole,
Speaker 1: Elliott Siegel, and Catherine Siegel. Thanks to you for listening.
Speaker 1: Come back next week for the final episode of our season.