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Measles: The Cancer Killer?... from Incubation · What's Your Problem?

0:15
Speaker 1: Pushkin. Hey, it's Jacob. There's another podcast that I host
0:23
Speaker 1: called Incubation. It's a show about viruses, and recently we
0:28
Speaker 1: did an episode that I thought would be particularly interesting
0:31
Speaker 1: to you, to people who listen to What's Your Problem,
0:36
Speaker 1: it's about measles. Measles turns out to be way more
0:39
Speaker 1: interesting and way more insidious than we thought, but also
0:44
Speaker 1: measles may be a new way to fight cancer. I
0:49
Speaker 1: hope you liked the episode. I really found it interesting.
0:51
Speaker 1: One last thing, we won't be publishing episodes of What's
0:54
Speaker 1: Your Problem over the next few weeks. We'll start up
0:57
Speaker 1: again in January. I thought I knew what I needed
1:02
Speaker 1: to know about what happens when you get measles. You
1:05
Speaker 1: get a fever and a rash. Maybe you get very sick.
1:10
Speaker 1: If you're really unlucky, you die. But chances are you
1:14
Speaker 1: get measles, you get better, and that's the end of
1:17
Speaker 1: it as it happens. I was wrong. I did not
1:21
Speaker 1: know what I needed to know about measles. Because a
1:24
Speaker 1: recent discovery has blown open our whole idea of what
1:27
Speaker 1: the measles virus does to our bodies.
1:30
Speaker 2: The world thought that measles was done being discovered and
1:34
Speaker 2: then boom, all of a sudden, there's this new idea
1:39
Speaker 2: of something that really had massive, massive consequences on humans
1:43
Speaker 2: that we didn't even realize.
1:45
Speaker 1: I'm Jacob Goldstein and this is Incubation, a show about viruses.
1:50
Speaker 1: Today on the show how measles attacks your immune system
1:54
Speaker 1: and how researchers are trying to use measles to cure cancer.
2:07
Speaker 1: My guest for the first half of today show is
2:10
Speaker 1: Michael Minna. He's an epidemiologist slash immunologist, slash physician, and
2:15
Speaker 1: he's kind of a measles superfan. He did a lot
2:18
Speaker 1: of work we'll talk about today while he was a
2:20
Speaker 1: professor at Harvard. He's now chief scientific officer at a
2:24
Speaker 1: company called emed. We started by talking about a surprising
2:28
Speaker 1: thing that happened after the measles vaccine was introduced in
2:31
Speaker 1: the nineteen sixties. As more and more kids were vaccinated
2:35
Speaker 1: against measles, the rate at which kids were dying of
2:38
Speaker 1: infectious disease went down way more than anybody expected. It
2:43
Speaker 1: went down so much that it couldn't be explained by
2:45
Speaker 1: measles alone.
2:47
Speaker 2: After the vaccine was introduced, we saw market reductions in
2:53
Speaker 2: childhood mortality overall following the vaccine, which drove a lot
2:58
Speaker 2: of questions, why did that happen? Is it the vaccine
3:03
Speaker 2: actually acting directly to somehow prevent other infections, or is
3:07
Speaker 2: there something else at play?
3:09
Speaker 1: Even if zero people died of measles, even if zero
3:12
Speaker 1: children died of measles, you wouldn't get that large of
3:16
Speaker 1: a reduction immortality. Right, some weird thing is going.
3:19
Speaker 2: On, that's exactly right.
3:21
Speaker 1: Weird good thing, weird usually.
3:23
Speaker 2: That's right, A very weird good thing was going on.
3:26
Speaker 1: So now we have this interesting kind of happy mystery
3:30
Speaker 1: in a way. Why are so few children dying of
3:33
Speaker 1: infectious disease after the rollout of the measles vaccine? What
3:37
Speaker 1: do you do to try and figure out what's going on?
3:40
Speaker 2: We said, well, maybe it's because measles had detrimental effects
3:45
Speaker 2: on somebody's immune memory that might be putting them at
3:50
Speaker 2: risk for other stuff, other infections. And so what we
3:53
Speaker 2: did was we said, well, if that's the case, then
3:55
Speaker 2: if we look at a lot of data, could we
3:58
Speaker 2: map the numbers of cases of measles to the numbers
4:02
Speaker 2: of deaths from other things besides measles from year to year?
4:07
Speaker 2: And what we found was prof boundly predictive. Is if
4:12
Speaker 2: you asked what were the number of measles cases in
4:14
Speaker 2: nineteen forty nine and what were the numbers of deaths
4:18
Speaker 2: from non measles infections from nineteen forty nine, nineteen fifty
4:24
Speaker 2: and nineteen fifty one. When you accrued all three years,
4:28
Speaker 2: it became extraordinarily predictive of how many children would die
4:33
Speaker 2: over the next three years of non measles infectious related deaths.
4:38
Speaker 1: So, just to be clear, what you found is that
4:40
Speaker 1: when there's a measle's outbreak in one year, the rate
4:43
Speaker 1: at which kids died from other infectious diseases went up
4:46
Speaker 1: in the next few years.
4:48
Speaker 2: That's exactly right.
4:49
Speaker 1: So you used in your answer just there this phrase
4:52
Speaker 1: that I just want to spend a moment on immune memory.
4:56
Speaker 1: What is immune memory?
4:58
Speaker 2: Immune memory is very similar to our regular memory. All
5:04
Speaker 2: of our body's memories, whether it be muscle memory, brain memory,
5:08
Speaker 2: or immune memory, is stored in cells. The way that
5:12
Speaker 2: immune memory works is when you bump up against a
5:17
Speaker 2: pathogen as let's say, a virus like measles or coronavirus,
5:21
Speaker 2: whatever it might be, your body actually sees it, it
5:25
Speaker 2: recognizes that virus. It learns from it, and it actually
5:29
Speaker 2: remembers it in B cells and T cells and plasma cells.
5:34
Speaker 2: And that's how our immune system works in terms of
5:38
Speaker 2: developing immune memory and utilizing it to combat infections that
5:42
Speaker 2: we see in the future.
5:44
Speaker 1: Is what you're finding that in some way measles is
5:46
Speaker 1: attacking the kid's immune memory. Is that the hypothesis that follows.
5:52
Speaker 2: That's exactly the hypothesis that follows. For example, if a
5:56
Speaker 2: six year old got measles, then maybe that measles infection
6:02
Speaker 2: could destroy some of the immune memory the defenses that
6:06
Speaker 2: that child gained over the last six years, and therefore
6:10
Speaker 2: when they are seven or eight years old, are actually
6:13
Speaker 2: more vulnerable than they otherwise would have been to those
6:18
Speaker 2: infections that they gained the immunity to when they were
6:20
Speaker 2: two or three.
6:21
Speaker 1: So, okay, you have this hypothesis, how do you test it?
6:25
Speaker 1: How do you investigate what's really going on?
6:28
Speaker 2: There's a long, rich history of how to predict where
6:33
Speaker 2: measles is going to go next. It's actually famous for
6:36
Speaker 2: how predictive it is because it is so infectious that
6:40
Speaker 2: you just need to know how many people are vaccinated
6:43
Speaker 2: in a community, and if there's any measles anywhere in
6:45
Speaker 2: the region, you can expect that pretty soon at below
6:49
Speaker 2: certain levels, there's going to be an.
6:51
Speaker 1: Outbreak below certain levels of vaccination.
6:53
Speaker 2: That's right, and that's why measles is considered the canary
6:56
Speaker 2: and the coal mine for vaccine rates. It's literally the
7:00
Speaker 2: thing that pops up on the radar when you say
7:03
Speaker 2: who's what communities are having trouble vaccinating their population, and boom,
7:06
Speaker 2: if you see measles, you know they're having trouble vaccinating
7:08
Speaker 2: their populations. And so what we can do is we
7:12
Speaker 2: can leverage everything we know about measles epidemiology to help
7:18
Speaker 2: identify where might outbreaks happen. And that's exactly what Rick
7:23
Speaker 2: de Swart and his team did. They are in the Netherlands.
7:27
Speaker 2: He's at Erasmus, which is in Rotterdam, and so he
7:30
Speaker 2: was able to say, hey, right in our backyard, there's
7:33
Speaker 2: a community that, for religious reasons, they chose not to
7:37
Speaker 2: vaccinate their children against measles. So they said, well, if
7:41
Speaker 2: you're not going to get a vaccine, would you be
7:42
Speaker 2: interested or willing to have us just draw a little
7:46
Speaker 2: sample of blood from your kids today and should measles
7:50
Speaker 2: catch up to them in the future. Could we come
7:52
Speaker 2: back and draw another sample of blood.
7:55
Speaker 1: You have the before measles blood samples, and you have
7:58
Speaker 1: from the same children the after measles blood samples. We
8:02
Speaker 1: have everything ready to go. What happens.
8:06
Speaker 2: There was a big outbreak, and almost immediately we aren't
8:09
Speaker 2: seeing that we can measure all of these antibodies in
8:13
Speaker 2: the blood samples. And then when we actually look at
8:16
Speaker 2: the blood samples from right before the kids got measles
8:19
Speaker 2: to those same kids blood samples that they collected after,
8:23
Speaker 2: we saw marked reductions. Not just in a couple antibodies,
8:28
Speaker 2: but some kids lost eighty percent of all of the
8:31
Speaker 2: diversity of their antibodies that existed in that blood sample
8:36
Speaker 2: before they got measles. And we compared it, we said, well,
8:40
Speaker 2: maybe that's normal. So we looked at kids who had
8:42
Speaker 2: gotten vaccinated for measles. We like the kids who just
8:45
Speaker 2: had no infections, And what we saw was the average
8:48
Speaker 2: person from any two time points, there'd be like five
8:52
Speaker 2: percent difference in their overall antibody repertoire. But the measles kids,
8:57
Speaker 2: the kids who got measles lost anywhere from twenty percent
9:00
Speaker 2: to eighty percent of their whole immunological memory pool. This
9:05
Speaker 2: is the whole lifetime of immune memory that they've spent
9:10
Speaker 2: years building up and building up, just poof wiped away
9:15
Speaker 2: because of this measles infection and these kids. What that
9:18
Speaker 2: means is now, across millions and millions of kids who
9:21
Speaker 2: were before the vaccines, almost every child got measles. And
9:25
Speaker 2: so at that scale, when you have so many people
9:29
Speaker 2: getting measles and this effect happening, which we call immunological amnesia,
9:35
Speaker 2: essentially they forgot their body, forgot because of the infection
9:40
Speaker 2: the immune memories that they formed before the infection. What
9:43
Speaker 2: that means is that you have all of these kids
9:46
Speaker 2: that are more susceptible to other infectious diseases. So most
9:50
Speaker 2: most kids would survive, but it turned out that of
9:54
Speaker 2: those kids who did die from other things, about half
9:59
Speaker 2: of those deaths could be attributed to the immune amnesia
10:04
Speaker 2: associated with measles.
10:07
Speaker 1: Is there something particularly insane if that happens at a
10:10
Speaker 1: population level. If you imagine a group of people in
10:13
Speaker 1: the absence of a vaccine entirely, where it's like, not
10:16
Speaker 1: only is each kid more vulnerable, but because all the
10:20
Speaker 1: other kids are more vulnerable, everybody is more vulnerable. Is
10:23
Speaker 1: there something like that that happens.
10:25
Speaker 2: I am so happy you asked that question.
10:28
Speaker 1: You're welcome.
10:29
Speaker 2: So, yes, it is. It's a much much harder thing
10:34
Speaker 2: to measure.
10:35
Speaker 1: I mean, it's sort of like the reverse of herd
10:37
Speaker 1: immunity in some weird broad spectrum way, right.
10:41
Speaker 2: So what's so interesting that you bring that up? Because
10:44
Speaker 2: before my musle's work, I was working on influenza and
10:47
Speaker 2: its impacts on other bacterial infections. And during my PhD,
10:51
Speaker 2: I coined a term called generalized herd effects, and I
10:57
Speaker 2: explicitly didn't call it herd immunity because maybe it's not
11:00
Speaker 2: going to reduce things, but maybe you could exacerbate things.
11:03
Speaker 1: Yeah, how about herd vulnerability. I want the opposite. What's
11:07
Speaker 1: the opposite of herd.
11:08
Speaker 2: Immunity, that's herd vulnerability is a great term, and so
11:11
Speaker 2: the idea there as well. If you have a pathogen
11:14
Speaker 2: that's impacting your susceptibility to a lot of other pathogens,
11:18
Speaker 2: you could, you know, create a herd vulnerability because of
11:22
Speaker 2: infections of that initial pathogen. And on the contrary, if
11:27
Speaker 2: you figure out a vaccine against that initial pathogen, like
11:30
Speaker 2: the measles vaccine, you create massive benefits in getting rid
11:36
Speaker 2: of that herd vulnerability.
11:38
Speaker 1: So what's going on on a cellular level.
11:42
Speaker 2: As far as we know, measles is unique in its class.
11:47
Speaker 2: It's actually it's an amazing story. So if you give
11:49
Speaker 2: me forty seconds to describe it.
11:52
Speaker 1: I will, oh go, you got a minute if you
11:55
Speaker 1: need it.
11:56
Speaker 2: So, every virus has a receptor that it binds to
11:59
Speaker 2: and needs to latch onto on a cell. For measles,
12:02
Speaker 2: it's this molecule that's called CD one fifty or it's
12:06
Speaker 2: called SLAM. SLAM stands for a signaling of Lymphocyte Activation molecule,
12:12
Speaker 2: and it's when somebody gets a measles infection. The virus
12:18
Speaker 2: comes into somebody's lungs and we have these cool dendritic cells.
12:21
Speaker 2: And dendritic cells are like these cells of big arms,
12:23
Speaker 2: and they go out and reach pathogens that they that
12:25
Speaker 2: they know shouldn't be there, and they capture them and
12:28
Speaker 2: bring them in and then they shuttle them into the
12:31
Speaker 2: lymphoid system, which is where all of our immune cells are.
12:34
Speaker 2: And so normally what would happen is the dendritic cells
12:37
Speaker 2: would say, hey, immune system, you know here's a pathogen,
12:42
Speaker 2: take it and develop immune memory against it. And so
12:45
Speaker 2: it literally hands it off to B cells and T cells.
12:48
Speaker 2: In this case, when the dendritic cell does exactly that
12:52
Speaker 2: same process, it hands off Measles virus to B cells
12:56
Speaker 2: and T cells. And this is a big mistake because
12:59
Speaker 2: now you have a virus that, instead of being handed
13:02
Speaker 2: off to a B and T cell and having that
13:03
Speaker 2: B and T cell you know ingest it and learn
13:07
Speaker 2: from it. The Measles flips on it receptor utilization and
13:10
Speaker 2: grabs city one point fifty or slam these molecules on
13:14
Speaker 2: the outside of the B cells and the T cells
13:17
Speaker 2: and it actually invades them like a trojan horse.
13:21
Speaker 1: Aha. So it's like a like a trick, right, Like
13:25
Speaker 1: Measles is there acting like a normal virus until it
13:29
Speaker 1: gets to the B cells in the T cells in
13:31
Speaker 1: the immune system. And normally the B cells in the
13:34
Speaker 1: T cells would destroy Measles, would destroy the virus. But
13:37
Speaker 1: in that case this doesn't happen, right, So what does happen?
13:41
Speaker 2: Now It's in the cushy lymphoid system and it's just
13:45
Speaker 2: full of food and it just replicates like crazy inside
13:49
Speaker 2: the immune system all the while cell by cell destroying
13:54
Speaker 2: the valuable immune memory is stored inside each of those
13:58
Speaker 2: cells that it's destroying.
14:00
Speaker 1: That is very compelling. That it's like a viralogical horror
14:04
Speaker 1: movie inside your body.
14:06
Speaker 2: It absolutely is. And what we see when we see
14:10
Speaker 2: the prototypic measles rash, which is like dots all over
14:14
Speaker 2: a child's body, red dots, it is truly the tip
14:18
Speaker 2: of the iceberg in terms of where the damage is
14:21
Speaker 2: being done. The real damage inside a child is much
14:25
Speaker 2: much deeper and much much more profound in terms of
14:29
Speaker 2: destroying a huge, huge population of very important cells inside
14:34
Speaker 2: of our body.
14:35
Speaker 1: So if you sort of step back and think about
14:39
Speaker 1: this idea that measles not only gives you measles but
14:43
Speaker 1: makes you vulnerable to lots of other infectious diseases, does
14:48
Speaker 1: it make you think differently about viruses, about the immune system,
14:51
Speaker 1: Like where do you land?
14:53
Speaker 2: Measles brings together for me mathematics, biology, ecology and evolution
15:01
Speaker 2: and vaccinology, And I love bringing those pieces together. It
15:09
Speaker 2: gives you a very deep appreciation for the delicate balance
15:13
Speaker 2: we have between infectious diseases, immunity, cancer, and autoimmune disease,
15:19
Speaker 2: and how those all interplay with each other. You know,
15:23
Speaker 2: the world thought that measles was done being discovered and
15:26
Speaker 2: then boom, all of a sudden, there's this new idea
15:32
Speaker 2: of something that really had massive, massive consequences on humans
15:37
Speaker 2: that we didn't even realize, and so it drives this
15:41
Speaker 2: renewed excitement around measles vaccination and the importance of it.
15:45
Speaker 2: It's not just a cool finding. It hopefully helps us
15:48
Speaker 2: move further and further towards eradication of the virus altogether.
15:55
Speaker 1: It was great to talk with you. Thank you so
15:57
Speaker 1: much for your time.
15:58
Speaker 2: Well, thank you so much. It was a lot of fun.
16:01
Speaker 1: Michael Minna is Chief science Officer at EMED Digital Healthcare.
16:05
Speaker 1: He was previously a professor at the Harvard School of
16:08
Speaker 1: Public Health. When we come back using measles to fight cancer,
16:23
Speaker 1: going back all the way to the eighteen hundreds, which
16:26
Speaker 1: was before anybody even knew what a virus really was,
16:30
Speaker 1: there have been occasional reports of cancer patients who get
16:34
Speaker 1: some kind of viral infection and then go into remission
16:38
Speaker 1: from cancer. And at a certain level, this makes sense.
16:42
Speaker 1: Viruses are highly evolved to enter and destroy cells. Normally
16:47
Speaker 1: we think of this as a bad thing, but if
16:49
Speaker 1: a virus is entering and destroying cancer cells, this ter
16:53
Speaker 1: a cell and destroy it property might be a very
16:56
Speaker 1: good thing. By the nineteen fifties, researchers were actively trying
17:00
Speaker 1: to figure out how to use viruses to treat cancer.
17:04
Speaker 1: But then new kinds of cancer drugs were discovered, basically chemotherapy,
17:09
Speaker 1: and researchers got less interested in that virus cancer link.
17:14
Speaker 1: My guest for this half of the show is Stephen Russell.
17:17
Speaker 1: Stephen has spent his career trying to use viruses to
17:21
Speaker 1: cure cancer, and as you'll hear, he and other researchers
17:24
Speaker 1: in the field have made real progress. When Stephen was
17:28
Speaker 1: starting his career in the nineteen eighties, he was interested
17:31
Speaker 1: in using retroviruses as possible cancer treatments. Then he told
17:35
Speaker 1: me he turned his attention to measles.
17:38
Speaker 3: Yeah, well, measles became the next love.
17:40
Speaker 1: You fell in love with measles? Yeah, of course, why
17:44
Speaker 1: do you fall in love with measles? Well?
17:46
Speaker 3: All viruses are quite beautiful, I have to say, and
17:49
Speaker 3: the life cycles are extraordinarily elegant. But measles I could
17:55
Speaker 3: do things with. I knew that there was a very
17:58
Speaker 3: remarkable case of a boy with a retro orbital Burkitt lymphoma,
18:04
Speaker 3: a very aggressive lymphoma that was sort of bulging his
18:08
Speaker 3: eye out, and he went to a clinic and was told, well,
18:11
Speaker 3: come back in a couple of weeks and we'll start
18:13
Speaker 3: the therapy. And he came back in a couple of
18:16
Speaker 3: weeks and the tumor had just resolved. But in the
18:20
Speaker 3: meantime he'd had a severe measles infection. Huh, And so
18:24
Speaker 3: it looked like it was pretty certain that the measles
18:27
Speaker 3: infection had driven this response that he had.
18:31
Speaker 1: Burko lymphoma also caused by a virus, right, the first
18:35
Speaker 1: tumor we knew was caused by a virus.
18:37
Speaker 3: Epstein By Yeah, so go on, I apologize. So anyway,
18:42
Speaker 3: I looking at measles, it seemed to tick a lot
18:45
Speaker 3: of boxes. But there was this whole history of the
18:48
Speaker 3: development of a vaccine strain of measles, and measles had
18:52
Speaker 3: been the vaccine had been created by taking a virus
18:56
Speaker 3: from the throat of a patient with measles. He was
19:01
Speaker 3: an eleven year old boy at the time, David Edmonstone
19:04
Speaker 3: in nineteen fifty four, and then growing that virus on
19:08
Speaker 3: cancer cells in tissue culture, and the virus had required
19:12
Speaker 3: the ability to propagate efficiently in cancer cells, but it
19:17
Speaker 3: lost the ability to cause measles.
19:20
Speaker 1: And wait, I just just to be clear, this was
19:23
Speaker 1: just they weren't trying when they were doing this to
19:25
Speaker 1: fight cancer. They were just trying to develop a measles vaccine.
19:30
Speaker 1: They were just saying, we're going to grow this measles
19:33
Speaker 1: in culture over time and make it be attenuator, make
19:36
Speaker 1: it be weaker. And it adapted in such a way
19:39
Speaker 1: that it preferred to infect tumor cells and not to
19:42
Speaker 1: infect non tumor.
19:43
Speaker 3: Cells because of the way they adapted it. Because remember
19:46
Speaker 3: that the cells that they were growing in the lab
19:50
Speaker 3: that they could put the measles virus on were basically
19:53
Speaker 3: cancer cells.
19:54
Speaker 1: And is that just because those are easy cells to
19:56
Speaker 1: grow because they liked to propagate.
19:58
Speaker 4: Yeah.
19:58
Speaker 3: Yeah, It's very, very difficult to grow non cancerous sects.
20:02
Speaker 1: Yeah, it's like the problem with cancer, right, it just
20:04
Speaker 1: loves to divide.
20:06
Speaker 3: Yeah. Yeah. So they put this virus on on the
20:10
Speaker 3: cells in culture, and the virus had actually adapted and
20:14
Speaker 3: it had learned to use a receptor that is more
20:19
Speaker 3: abundant on cancer cells than on normal cells, and it
20:23
Speaker 3: was losing all sorts of things that it needed in
20:27
Speaker 3: order to cause disease because it didn't need them to
20:30
Speaker 3: be able to propagate the cancer cells. So it spontaneously
20:34
Speaker 3: attenuated through a lot of mutations that arose in the
20:38
Speaker 3: viral genome. And so there it was and had been
20:42
Speaker 3: given to billions of people, and it looked like it
20:45
Speaker 3: was fairly well adapted to test in human studies against cancer.
20:54
Speaker 1: The measles virus used in the vaccine didn't make people sick,
20:57
Speaker 1: and it tended to attack cancer cells. So Stephen started
21:01
Speaker 1: using that form of the virus in studies to see
21:04
Speaker 1: if measles could treat cancer. Eventually he landed on a
21:08
Speaker 1: kind of cancer called multiple myeloma that can take hold
21:12
Speaker 1: in the bone marrow and suppress the immune system. And
21:15
Speaker 1: there was one multiple myeloma patient in particular who had
21:19
Speaker 1: a huge effect on how Stephen thought about using measles
21:23
Speaker 1: to fight cancer. The patient's name was Stacy.
21:26
Speaker 3: Erholtz, so Stacy. She had multiple myeloma. She had been
21:32
Speaker 3: on treatment for ten years, on and off, but probably
21:37
Speaker 3: more on than off treatment for the first ten years
21:40
Speaker 3: of her diagnosis, because every time she stopped the treatment,
21:45
Speaker 3: or even if she continued on it, the disease would
21:48
Speaker 3: come back and then she needs switch to something else.
21:52
Speaker 3: She had a large tumor on her forehead that was
21:54
Speaker 3: destroying the underlying bone and compressing her brain. She had
21:59
Speaker 3: four other solid tumors, and then her bone marrow was
22:03
Speaker 3: diffusely infiltrated with myeloma and it was moving fast, and
22:08
Speaker 3: she was out of treatment and options at the time.
22:10
Speaker 3: I mean, there was nothing.
22:11
Speaker 1: She was going to die soon.
22:13
Speaker 3: She was going to die, yeah, and she had three
22:17
Speaker 3: children still at school and everything to play for. She
22:21
Speaker 3: was fifty years old at the time. We'd moved up
22:24
Speaker 3: through every dose level that FDA had negotiated with us.
22:28
Speaker 3: Based on a starting dose level of a million, we'd
22:32
Speaker 3: gone up to just tenfold short of a billion.
22:36
Speaker 1: Like, how much did she get compared to how much
22:38
Speaker 1: somebody gets when they get the measles vaxing.
22:40
Speaker 3: It's about ten million doses of vaccine, okay.
22:43
Speaker 1: For this one person, So she's getting quite a lot.
22:47
Speaker 1: And what happens.
22:48
Speaker 3: Well as with other patients, she had a reaction to
22:54
Speaker 3: the infusion of virus. So she got the virus infused.
22:58
Speaker 3: She felt fine for a couple of hours, and then
23:02
Speaker 3: she started shivering and shaking, and her temperature rose and
23:06
Speaker 3: she felt pretty unwell overnight, but by the following morning
23:10
Speaker 3: it had settled down.
23:11
Speaker 1: And is that essentially like a response to a massive infection.
23:15
Speaker 1: She's essentially has this massive infection.
23:17
Speaker 3: Yes, it's similar to that, although it wasn't causing measles
23:23
Speaker 3: in her so it was it was more the body
23:26
Speaker 3: reacting to the foreign stuff in the blood and a
23:30
Speaker 3: very kind of rapid reaction. That settled down, and then
23:34
Speaker 3: she left hospital, went home and after a few days
23:40
Speaker 3: she started noticing that the tumor on her forehead she
23:44
Speaker 3: and her family had named it Evan, and this tumor Evan,
23:50
Speaker 3: started to shrink and actually melted away. And you know,
23:54
Speaker 3: we conducted thorough evaluations on her intervals thereafter, and we
24:02
Speaker 3: were staggered to see that she went into a complete
24:05
Speaker 3: disease remission. She felt fantastic. You know. We thought at
24:10
Speaker 3: the time, Okay, we've got it. This is the way
24:13
Speaker 3: to cure multiple myeloma, and so we gave it to
24:18
Speaker 3: a lot of other multiple myeloma patients and it didn't
24:22
Speaker 3: work nearly so well. There was some partial responses, but
24:26
Speaker 3: there was really nothing as dramatic as Stacy. So we
24:30
Speaker 3: studied Stacy pretty intensively. To try and understand what was
24:34
Speaker 3: special about her, because that would be the key to
24:39
Speaker 3: the success of virotherapy. I mean, what we knew from
24:42
Speaker 3: Stacy as wow, this can actually happen. You can give
24:45
Speaker 3: a virus systemically nothing else, and you can get a
24:50
Speaker 3: dramatic resolution of tumor at all sites. So the studies
24:56
Speaker 3: that we did on Stacy showed that number one, she
24:58
Speaker 3: had no anti measles antibody detectable. She had, however, been
25:04
Speaker 3: vaccinated as a child, and then she had lost her
25:08
Speaker 3: immune and she'd been revaccinated after her first stem cell transplant,
25:14
Speaker 3: the immunity had come back, and she'd lost it again
25:18
Speaker 3: after the second stem cell transplant. Huh, So she had
25:22
Speaker 3: no antibodies to block the virus from getting to the target.
25:26
Speaker 1: So basically, her immune system was the same as the
25:30
Speaker 1: immune system of a person who has never had measles
25:32
Speaker 1: and not been vaccinated for measles.
25:34
Speaker 3: Not quite, because we looked at her T cells, the
25:39
Speaker 3: cells that come into the tumor and attack the virus
25:42
Speaker 3: infected cells, and she had a very high level of
25:47
Speaker 3: anti measles T cells.
25:50
Speaker 1: As it turned out, this was a perfect combination. Stacy
25:54
Speaker 1: didn't have any antibodies, so the measles virus was free
25:58
Speaker 1: to go into her body and infect her tumor cells.
26:01
Speaker 1: But she did have anti measles T cells, so once
26:05
Speaker 1: the measles infected the tumor cells, those T cells could
26:08
Speaker 1: attack hack her tumor cells. So now she had both
26:12
Speaker 1: the measles virus and her own T cells attacking and
26:16
Speaker 1: destroying the tumor. Stephen told me he learned a lot
26:21
Speaker 1: from Stacy's case and it helped him figure out how
26:23
Speaker 1: to move forward with his research.
26:26
Speaker 3: Yeah, so there are two pathways that we took. One
26:29
Speaker 3: was to switch to a different virus that people do
26:33
Speaker 3: not have prior exposure to, and so we started working
26:37
Speaker 3: with the sicular stomatitis virus VSV, which causes naturally a
26:43
Speaker 3: blistering illness in cattle.
26:45
Speaker 1: Uh huh. So that's that's one way to get around
26:49
Speaker 1: the immunity to measles problem. Right, You're you're using a
26:53
Speaker 1: virus that most people don't get and are therefore not
26:56
Speaker 1: immune to. How is that going?
26:59
Speaker 3: It's going. It's going well. Where you know, it's not
27:03
Speaker 3: in every cancer that we see anything, but the results
27:07
Speaker 3: that we have at the moment are looking very promising
27:11
Speaker 3: in certain indications. The other approach we took was to
27:17
Speaker 3: stealth measles virus so that it would still be measles virus.
27:23
Speaker 3: It would still be that vaccine strain, but it would
27:26
Speaker 3: have a new coat, huh, that was no longer recognizable
27:31
Speaker 3: by circulating antibodies, And so we would in that situation,
27:36
Speaker 3: we would have a virus we could give systemically that
27:39
Speaker 3: would penetrate the tumor, and that would then be subject
27:44
Speaker 3: to attack by these t cells that exist in people
27:48
Speaker 3: who've been measles immunized.
27:51
Speaker 1: Well, does it work in mice? Okay, it's a start.
27:56
Speaker 3: We haven't taken that one into human clinical tests yet.
28:00
Speaker 1: Let's talk for a minute about using viruses to treat
28:04
Speaker 1: cancer more broadly. Right, people have been trying other viruses
28:10
Speaker 1: to treat other cancers. What's the state of the field
28:13
Speaker 1: more generally?
28:15
Speaker 3: There has been incremental progress, and there are viruses that
28:18
Speaker 3: are looking very promising in brain cancer injected into the
28:23
Speaker 3: brain tumor, in bladder cancer instilled into the bladder, and
28:29
Speaker 3: I think many ongoing programs which show great promise. So
28:36
Speaker 3: I'm still a complete believer in the capability of viruses
28:41
Speaker 3: to really bring a transformation in the approach to cancer therapy.
28:47
Speaker 3: I feel like it's coming soon, but not everybody agrees
28:53
Speaker 3: with me.
28:56
Speaker 1: I appreciate your time so much. It was great to
28:58
Speaker 1: talk with you.
28:59
Speaker 3: Great talking with you too. Thank you very much.
29:02
Speaker 1: Stephen Russell founded the Department of Molecular Medicine at the
29:06
Speaker 1: Mayo Clinic. He is currently the CEO of Viria, a
29:09
Speaker 1: company that is trying to use viruses to treat cancer.
29:13
Speaker 1: One last thing, Stephen told me that he's still in
29:16
Speaker 1: touch with Stacy Airholtz, the patient who had multiple myeloma
29:20
Speaker 1: and went into complete remission after being treated with measles.
29:23
Speaker 3: Stacy Holtz is, you know, a guiding light for me.
29:28
Speaker 3: I'm friends with her, I'm in contact with her on
29:31
Speaker 3: a regular basis, and she's got grandkids. She's having a
29:35
Speaker 3: happy life. She's a very positive woman.
29:38
Speaker 1: Thanks to both of our guests today, Michael Minna and
29:41
Speaker 1: Stephen Russell. Next week on the show, I talked to
29:44
Speaker 1: a scientist who discovered an entirely new kind of virus,
29:48
Speaker 1: and it turns out this virus is everywhere.
29:51
Speaker 4: Boiling Springs Lake, deep Sea Sediment's Korean air sample, monkey feces,
29:56
Speaker 4: dragonfly guts, soil just outside the lab at Portland State University.
30:00
Speaker 4: Basically anywhere that we have looked, we found these cruci viruses.
30:07
Speaker 1: Incubation is a co production of Pushkin Industries and Ruby
30:11
Speaker 1: Studio at iHeartMedia. It's produced by Kate Furby and Brittany Cronin.
30:15
Speaker 1: The show is edited by Lacey Roberts. It's mastered by
30:18
Speaker 1: Sarah Bruguer, fact checking by Joseph Friedman. Our executive producers
30:23
Speaker 1: are Lacey Roberts and Matt Romano. I'm Jacob Goldstein. Thanks
30:27
Speaker 1: for listening.