November 7, 2024 • 31 mins
For a long time, people could tell that there was some connection between chickenpox and shingles. But exactly how they were related was a mystery. Then, in the 1950s, a family doctor shipped out to a remote Scottish island to investigate an outbreak, and made a discovery that shaped our understanding of shingles. On today's show, Ann Arvin, professor emerita at Stanford Medical School, tells us that detective story. Then Robert Johnson of the University of Bristol explains what he's learned about treating pain in his decades working with shingles patients.
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Speaker 1 (00:02):
Shingles is a disease that has been around for thousands
of years. It affects millions of people every year, but
as recently as the middle of the twentieth century, scientists
didn't really know how the disease worked. It was clear
that shingles and chicken pox were related. People sometimes got
chicken pox from people with shingles, but the clarity ended there.
(00:26):
How were the diseases related. Were they caused by different
viruses or the same virus. Could you get shingles from
someone with chicken pox? Nobody knew. But by the mid
nineteen sixties, scientists had figured out what was going on.
And one of the people who did the most to
figure it out was not some high powered researcher at
a prestigious university. It was a family doctor in a
(00:48):
small British town. His name was Edgar Hope Simpson. I'm
Jacob Goldstein and this is Incubation, a show about viruses.
In the second half of the show, we'll talk about
the most common symptom of shingles, pain and we'll talk
(01:12):
about the surprising methods that some doctors are using to
try and alleviate that pain. In this part of the show.
We're going to talk about Edgar Hope Simpson, that family
doctor who helped solve the mystery of shingles. I talked
about Hope Simpson with Anne Arvin. Anne's retired now, but
she spent decades as a clinician and a microbiologist at Stanford.
(01:33):
She studied the Vericella zoster virus, the virus that causes shingles.
Speaker 2 (01:37):
Edgar Hope Simpson, as you just said, was a GP
who was very interested, as many practitioners are, in trying
to solve unresolved issues in medicine. And his practice was
largely older people, and he was seeing a lot of
shingles relatively speaking, but he was also seeing kids with
(02:02):
chicken pox. It was really easy to see that one
kid with chicken pox would give it to fifteen other kids.
They would get chicken pox. That was easy to observe,
Uh huh. It was a lot more difficult to nail
down the question of what about shingles and does exposure
(02:23):
of a child to shingles really result in chicken pox
or is that just coincidence proximity?
Speaker 1 (02:34):
Huh?
Speaker 2 (02:34):
And so that was his question.
Speaker 1 (02:37):
There's this moment, I guess in the nineteen forties when
Edgar Hope Simpson reads in a British medical journal just
a case report, just a letter from a doctor on
this remote Shetland island called Yell. Tell me about Edgar
Hope Simpson and this island of Yell and this sort
(03:00):
of quest to understand the relationship between chicken pox and shingles.
Speaker 2 (03:07):
Yes, so why did he jump on the boat or
train or boat and train or whatever to go practically
a day and a half to get from where he
was in sort of southern England up to this remote
island in the Shetland Islands in the North Sea. Why
did you do that?
Speaker 1 (03:24):
It was going to go on summer vacation. And he's like, no,
I'm not going to go on summer vacation. I'm going
to go investigate this.
Speaker 2 (03:30):
Outbreak because the letter that he read said there was
a school teacher who had shingles and there was an
outbreak of chicken pox in her class.
Speaker 1 (03:45):
In nineteen forty six, Hope Simpson reads this letter in
the medical journal about the school teacher case in Yell,
and then Hope Simpson reaches out to the local doctor
who wrote about the case and they stay in touch
they're corresponding with each other. Eventually, Hope Simpson learns that
there is another outbreak on the island. There's something like
(04:06):
one hundred chicken pox cases that seem to have come
from a single case of shingles.
Speaker 2 (04:13):
When he heard about this crofter who had shingles and
whose five children then had chicken pox, he thought, this
is an irresistible opportunity. I will go up there and
I will actually see this outbreak unfold in real time
from this shingles case. And so undoubtedly the shingles case
(04:37):
did lead to chicken pox in that family. The question
was could he then trace a further outbreak.
Speaker 1 (04:46):
I mean, I guess there's something about a remote island
that's actually a perfect place to test the hypothesis, right
because unlike in you know, twentieth century England, people are
taking trains, people are coming and going, this was like
truly a remote people are like crofters which I don't
even know they're farmers or they're raising sheep or something.
Right Like, it's it's very out there. So he goes
(05:09):
out there and I mean it's amazing, Like what he's
doing is contact tracing basically. Right, there's here, he wrote
this reminiscence that I just want to read because I
love just a paragraph of it. There's this moment when
like they're trying to track down one case and he says,
(05:29):
the team, which is just like him and two other
people walked from mid Yell to the south shore of
the vau Vae is apparently a Shetland word for a
little cove or something road themselves across. He means ourselves
rode themselves across to north of Vo and walked for
several miles across the heather to the home of K six.
(05:51):
And then he was hoping this one particular connection was
going to answer everything, and he writes, alas no, because
this girl who was going to tie it all together
for it was not in fact at this other place.
So anyways, it's a great story.
Speaker 2 (06:07):
I love that. I love that description too, And I
had to look up what is a voe? So I'm
sad that we now know a voe is a bay,
a small bay. I can tell you that kind of
vs V Barricela's osterro virus research. That is not how
we do it now, but it looked kind of interesting
(06:29):
to be able to do that.
Speaker 1 (06:31):
You never you never wrote, did you? How much rowing
did you do in your research?
Speaker 2 (06:35):
Absolutely not so. Anyway, he was trying to see whether
he could get a second, a reproducible finding, so to speak,
because he heard that the person in the other location
had shingles, and then he thought, well, there's going to
be maybe another traceable cluster of cases. So back to
(07:00):
your question about why islands, islands are really important in
epidemiology of infectious diseases, and so the reason is because
the populations are tiny and in that particular geography, as
you just said, you row your boat, you walk three
miles or ten miles or whatever, there's a lot less
(07:22):
contact in a very rural situation. So you can have
the situation in epidemiologic terms where there's a fair number
of susceptibles and you can actually then take the so
called index case and you can map literally house to
house the cases.
Speaker 1 (07:45):
Yeah, but then I think he sort of dug further
and figured out more connections, right, and it did suggest,
although it wasn't conclusive, well, that it's the same virus
and that you can catch chicken pox from someone with ching.
Speaker 2 (08:00):
Right, he went a great distance, so to speak, towards
actually proving that hypothesis.
Speaker 1 (08:08):
I picture him with like a wall, like a map,
but with like pushpins that maybe like red yarn, you know,
like a like in a detective show or something.
Speaker 2 (08:16):
Sure, well, epidemiology is basically a detective story most of
the time. So yes, I think that's exactly what he did.
They went around house to house, took records and ask people.
Speaker 1 (08:31):
Yeah, so this is like a very colorful and you know,
kind of low key heroic thing he's doing to try
and learn something for the benefit of humanity. But he
is doing this longer term study based on his practice
right where he's closely tracking all of the chicken pox
(08:55):
cases and all of the shingles cases over many, many years,
and he winds up giving a lecture, publishing a paper
that is the summation of that work, and he does
wind up solving this mystery. Tell me about that paper.
Speaker 2 (09:10):
That paper is about his long term study. And he
apparently studied everyone in his practice who got shingles. So
not only did he make the diagnosis, he made a
chart of each person and marked on this chart here's
where this person lesions were, this is where the other
person's lesions were. And so he had an enormous set
(09:33):
of data on where the shingles rash appears on people's bodies,
and he also had all of the chicken pox data.
And what he was able to conclude is it's a
one way traffic. Shingles causes vericella. Vericella does not cause jingles, right,
(09:54):
chicken pox. Yeah, So that was his finding, his fundamental observation.
And it's a one way traffic. So that means where
does the virus come from when you've got shingles?
Speaker 1 (10:08):
Uh huh. It doesn't come from someone with chicken pox,
and it doesn't come from someone with shingles, right.
Speaker 2 (10:13):
That's also what he observed. And so he had all
this massive data sets of people who had shingles and
were in close contact with somebody or several other somebodies
and they didn't get shingles, but if there were kids around,
they got chicken pox, but not vice versa.
Speaker 1 (10:32):
So from that beautiful data set he can show clinically
what's happening. And from this clinical finding, he presents in
this paper a hypothesis of what's going on at the
micro level, at the cellular scale.
Speaker 2 (10:46):
What does he hypothesize the hypothesis is what we now
know to call latency. That is, when you have chicken pox.
In the course of your chicken pox episode, the virus
you can imagine, is in those little boxes all over.
And what is also in the skin Right next to
(11:09):
where those boxes are, which are full of virus, there
are nerve endings. And so the virus has created a
great scheme for persisting by taking not just the opportunity
to form skin lesions, but to go backwards up the
(11:30):
nerve axons to the nerve cell body, which is in
what's called sensory ganglia, all up and down the spinal
cord and cervical spine and face. But developing the hypothesis
of how the virus got to the sensory ganglia, he
outlined what he called suppositions. I like the phrase suppositions.
Speaker 1 (11:56):
There's a nice humility to it, right, I don't know,
but let's suppose.
Speaker 2 (12:01):
Yeah. So he created a set of suppositions that have
subsequently been found right. But also because they were suppositions,
a number of them were not right.
Speaker 1 (12:16):
What did he get wrong?
Speaker 2 (12:18):
Well, for starters, he thought chicken pox was a pox virus,
which it isn't. It's a herpes virus related to herpes
simplex type one and type two.
Speaker 1 (12:29):
Let's talk for a minute about just herpes viruses, and
in particular the persistence, right the fact that they have
this from the point of view of virus clever, from
the point of view of a human host, insidious quality
of hanging around forever. Tell me more about that.
Speaker 2 (12:49):
First of all, these viruses are ancient, and they sort
of evolved into different subgroups over millions of years. And
if you look at every specie, they all have their
herpes viruses too. It's not just us. You have a
guinea pig, that guinea pig has guinea pig herpyes virus.
(13:09):
So it is. It is a story that encompasses the
entire family of viruses. And what we know is that
for the most part. The other thing the virus as
agent has to keep in mind is don't make the
person too sick, right, accommodate if you can, just don't
(13:33):
even cause any symptoms at all. Just arrange to be
periodically showing up at a mucosal surface. In fact, a
few cells, dump a few virus particles into the saliva
or whatever, and so be it.
Speaker 1 (13:50):
Everybody's happy. Everybody's happy, right, problem.
Speaker 2 (13:55):
No problem, so in fact, you know, chicken pox is
a bit unusual in the It does typically cause symptoms,
but very very mild. When it's not mild, it is
potentially lethal. And so that's why all of us in
the field work so hard to develop vaccines, vaccine for
chicken pox and vaccine for shingles.
Speaker 1 (14:17):
So when you look back at Hope Simpson's work, what
do you make of it?
Speaker 2 (14:24):
Well, I think it's pretty straightforward for me to say
why I and my colleagues so much admired the work
that he did and the suppositions that he came up
with because he was looking from an evolutionary perspective. He
was asking why does this happen? And what he proposed,
(14:50):
which is definitely true, is that the virus gives itself
a kind of second chance to spread. So, if you
look at it from an evolutionary perspective, and you're thinking
from the point of view of the virus, how to
sustain your life if you will, your life cycle in
(15:11):
a community is as important as how to sustain it
in one person. And so you have to imagine a
rural community if chicken pox isn't reintroduced as a kid
with chicken pox showing up from somewhere. That is it
for the virus unless unless there's another way for it
(15:36):
to introduce itself again, so to speak. And that is
where the Shingles think. So that is why his work
in Yale was really important. He was actually showing that
life cycle as it rolls out in a community.
Speaker 1 (15:54):
Yeah, like the virus as agent. Right, it's giving the
virus agency.
Speaker 2 (16:00):
Which we know not to do. But it's so.
Speaker 1 (16:03):
Tempting, I mean, whatever that's a word. I mean, I
think there's a non anthropomorphic way, Like, I don't care
what anybody says, it's clever that the virus is doing that.
It's very clever.
Speaker 2 (16:13):
Certainly my point of view. Yeah, So it's an evolutionary
strategy of the virus. That's one reason why this work
is important. And the other reason, I think is back
to the suppositions. He did not assume that the story
was fully understood, and that was that he knew and
(16:36):
identified the gaps. So there's a way in which you
can say we've been filling in the gaps that he
placed out there as suppositions.
Speaker 1 (16:45):
I think there's something also really elegant, maybe even romantic,
if I'm being honest about the family doctor, the general
practitioner as epidemiologist. You know, he's he's there every day
treating patients. And the thing that he did, I mean
besides going to yell, which is very dramatic, but the
(17:06):
less dramatic but maybe ultimately more important thing that he
did is keep this meticulous data as you say, about
where the where the rashes are and what the household
connections are. I mean that transforms his work from you know,
helping individuals to like making this significant breakthrough in human
knowledge exactly.
Speaker 2 (17:28):
And picking picking a question. I mean, there's always a
science of great challenge is pick a question where you
can really gather some data that's going to lead somewhere.
That's as much of a contribution as a researcher as
actually finding answers to some of those questions.
Speaker 1 (17:53):
Thank you for your time. It was great to talk
with you. You too, And Trevin is a retired clinician
and microbiologist at Stanford. In a minute, I'll talk with
a physician and researcher who was a friend of the
late Edgar Hope Simpson and who has spent decades studying
shingles and pain.
Speaker 3 (18:26):
Anyone who has done any work on shingles. Probably the
first name they will come across is Edgar Hope Simpson.
Speaker 1 (18:34):
Is it true that you knew him?
Speaker 3 (18:36):
Oh? Yes, I can't tell you precisely when, but I'll
tell you how.
Speaker 1 (18:41):
Robert Johnson is a physician who spent decades treating shingle's patients.
He no longer has a clinical practice, but he still
does research at the University of Bristol.
Speaker 3 (18:50):
It was about nineteen ninety four. There were a group
of us who were going to be presenting in a
symposium and somebody said, is Simpson still alive? And I said,
I have no idea. Let's have a look and telephone directory.
So we looked up and there was Hope sinstance siahen sister.
So we phoned him. I think it was about eight
(19:11):
o'clock one evening, and there was a fairly brusque answer.
I Hope Simpson here, I said, is that doctor Egger
Hope Simpson? He said yes, And I said, could I
ask you? Are you still interested in shingles?
Speaker 1 (19:25):
Oh?
Speaker 3 (19:25):
Yes, he said, And that was the start of it.
And he was brilliant. He was the most humble man
you can imagine, an enormous breadth of knowledge. Everyone had
stories about him, both from the medical point of view,
as a friend and in particular as a general practitioner.
(19:46):
He was clearly extremely caring, and they told me that
he'd be known to ski in the winter out to
a patient for an emergency call. He was obviously a
very dedicated a character.
Speaker 1 (20:03):
So I want to talk about shingles as a disease
and about your work with shingles. What happens in the
body when you get shingles.
Speaker 3 (20:14):
What happens is that the virus, which has been dormant
in nerve tissue near to the spinal cord and near
to the certain areas of the brain, has found itself
able to reactivate without getting an immune response adequate to
prevent its spread. And then the virus replicates it, It
(20:37):
increases its numbers, it multiplies and spreads along the peripheral
nerve that runs from the area where it was latent
and eventually reaches the skin, where you get the typical
rash of shingles.
Speaker 1 (20:51):
So I had chicken pucks decades ago, and right now
inside my nerve cells inside my body, there is that
virus still just hanging out weeding more or less and
if there is some moment when my immune system is
compromised in some set of factors, a line I will
(21:11):
get shingles.
Speaker 3 (21:12):
Yes, you're absolutely right. In a lifetime, about thirty percent
of us will get shingles, and if one lives into
one's eighties, which these days is very common, it's about
a fifty percent chance of getting shingles.
Speaker 1 (21:25):
Tell me more about the symptoms of having shingles. What
is it like to have shingles?
Speaker 3 (21:29):
Very frequently one has several days of pain or tingling sensation,
maybe feeling a little bit unwell, but then the rash
appears and the diagnosis becomes clear. Almost always, the acute disease,
the first three or four weeks is painful, and it
can be extremely painful. In some people, the lucky ones,
(21:54):
the rash the pain over a period of ten days
to three weeks disappear. There's often a little bit of
scarring and that's the end of it. But in others
that's not the case. The pain persists. It can be intermittent,
but it can go on for weeks, months, or even years,
(22:14):
and when it reaches three months from the rash appearance,
we call it post Pettit euralgia.
Speaker 1 (22:21):
So post herpetic neuralgia is the technical term, the term
of art for basically long term pain after you have shingles.
You can sort of unpack it right, post her petic
after herpes and neuralgia is a pain from from the nerves,
right from the nerve, absolutely, and it seems like that
is I mean, shingles is the thing you don't want.
(22:44):
Post herpetic neuralgia, long term pain from shingles is the
thing you really don't want, right, So let's talk some
more about that. I know you're working on that. What
is the mechanism of post her petic neuralgia. Why is
it that some people get it and some people don't.
Speaker 3 (23:00):
I'd say I don't know, but I will try and
give you a full answer without waffling too much. There
is definite damage to nerve tissue, nerve fibers right from
the skin to the spinal cord and indeed within the
spinal cord. But the problem starts with the clinical side,
(23:24):
because there is no single pain syndrome of post de
pendant euralgia. You can have numbness, or you can have
a severely increased sensitivities to touch. You can have a
reduction in sensitivity to heat and cold, or you can
have an increase. You can have a continuous burning pain,
(23:45):
you can have severe intermittent lancinating, page shooting, electric shock
like pains, And if you take that forward to months
and years, you can see what it can do to
a patient.
Speaker 1 (23:59):
Let's talk about eatment and prevention, right, Okay, what can
you do to avoid getting shingles in.
Speaker 3 (24:05):
The first place? Don't have chicken pox, And the only
way you can be fairly confident in not having chicken
pox is to be vaccinated against it, which in the
States you have done pretty routinely since nineteen ninety five.
But it's going to be some years before we see
any marked effect on that in shingles because those people
(24:28):
are still, relatively speaking young as far as the age
for getting shingles is concerned. So vaccination against chicken pox
is one, the next one is vaccination against shingles.
Speaker 1 (24:42):
If you are not fortunate enough to prevent shingles, what
is the treatment both for the initial disease and for
post herpetic neuroalgia.
Speaker 3 (24:55):
Right, Well, one may have a capacity to actually even
when shingles has started prevent post to pedant euralgea. It's
a bit uncertain. Anti virals we hoped would have a
massive effect on that. And the anti viral drugs are
remarkable for treating the acute symptoms and any serious disease,
(25:18):
But how much they influence development of post to pedant
euralgia's always remained a bit of a gray area. It's
very hard to see why they wouldn't. But if they do,
it hasn't reduced the incidence of post pedant euralgia overall
very much.
Speaker 1 (25:34):
If they work, we can't see it.
Speaker 3 (25:37):
Well, that's sort of how it is. Yes, Having said that,
I wouldn't want to underplay the value of the antiviral drugs.
My personal view is that almost everybody who gets shingles
should receive them.
Speaker 1 (25:50):
I know you're working now on a study looking at
it at another way of treating shingle's patients with lasting pain.
Tell me about that.
Speaker 3 (25:58):
We're now looking. In England, we have a study based
on Bristol looking at amitriptlen that was originally an antidepressant drug,
but in very low doses it has an effect on
europathic pain. And another neurologist called David Bouscher from Liverpool
(26:19):
in England had published a study all three decades ago,
perhaps basically showing that probably low dose ami triptlen given
early in the course of jingles reduced the incidents of
post dependant eualgia dramatically. David Bouscher was a character and
(26:41):
he did push the case of herpes oster extremely well
as far as people getting interested in research in it.
It was a very interesting paper and very indicative that
further research was needed, but it didn't prove the case.
Speaker 1 (27:00):
This is a very odd the decades or antidepressant yes,
or drug that was developed as an antidepressant, yes, why
why might it help reduce postropedic neuralgia.
Speaker 3 (27:14):
Well, again it's not fully understood, but it does have
certain effects which can affect transmission of impulses within nerves
and excitability of damaged nerve tissue, possibly effects within the
spinal cord at inhibition of pain from impulses which traveled
(27:40):
down from the brain out towards the spinal cord and
the peripheral nerves. There are all sorts of possible mechanisms,
but I think it would be wrong with me to
say we know the answer.
Speaker 1 (27:52):
I want to talk about pain a little bit more
more broadly. And you know, when you mentioned an antidepressant
as a treatment for pain, there's one universe where there
is some very direct mechanism in the peripheral nervous system.
I mean, there is also a universe where pain is
related to our psychological state. And as a doctor who
has treated pain a lot, I'm curious about your view
(28:14):
on that. More generally, on pain, you know, as part
of this broader complex of well of a person psychological state. Oh.
Speaker 3 (28:24):
Absolutely, pain is biopsychosocial. There's a pathology, the biobit, there's
the psychology, and there's the social the environment that we
live in, and all these things play a part in
pain and how we respond to it. And you know,
just go back to Hope Simpson for a second. When
(28:45):
Hope Simpson talked about management of patients in general practice
with shingles, he said the main thing was to care
for the patient, to take an interest in the patient,
to follow the patient up, to encourage them. And this
is so true. My wife and I started a herpesoster
(29:06):
clinic here in Bristol or many years ago now, and
we saw mainly post a petit euralgia patients, but we
were very happy to see acute patients that general practitioners
referred us who had unusual features or severe pain, or
were particularly distressed. And it was really the persistence and
(29:28):
the interest shown in the patients which made a huge
difference to their progress. The treatments we had available were
pretty limited, and you just had to persevere. We worked
through the treatments with them, We discussed the treatments with them,
and I think it makes a world of difference how
(29:48):
you treat the patient overall. And one of the things
that is essential is to encourage them to get back
to social interactions, to go out and meet people, not
to hide away nursing the pain.
Speaker 1 (30:05):
Why Why is that so important?
Speaker 3 (30:07):
Because pain is multifactorial, and if you can address one
or more of the bio psychosocial elements, you're going to
get improvement. Well, the bio we weren't so good on,
although we did have drugs and we did have other treatments.
The psycho, I don't know much about that, but the social, yes,
(30:28):
you could definitely influence that. Encouragement and taking a concern
about the patient's problem is essential.
Speaker 1 (30:41):
It was really lovely to talk with you. I thank
you for being so generous with your time. Thank you,
Andrew Knowledge, Thank you very much. Robert Johnson is a
researcher at the University of Bristol. Thanks to both my
guests today, Anne Arvin and Robert Johnson. By the way,
last week's show, in case you missed it was all
so about a herpes virus. That show was about the
(31:03):
epstein bar virus EBV, which also has some very insidious
long term effects. Next week on the show, the HIV
epidemic that changed the world and the scientists who are
racing to understand it. We have something, We have something.
Incubation is a co production of Pushkin Industries and Ruby
(31:26):
Studio at iHeartMedia. It's produced by Kate Ferby and Brittany Cronin.
The show is edited by Lacey Roberts. It's mastered by
Sarah Bruguier, fact checking by Joseph Friedman. Our executive producers
are Lacey Roberts and Matt Romono. I'm Jacob Goldstein. Thanks
for listening.
Shingles is a disease that has been around for thousands
of years. It affects millions of people every year, but
as recently as the middle of the twentieth century, scientists
didn't really know how the disease worked. It was clear
that shingles and chicken pox were related. People sometimes got
chicken pox from people with shingles, but the clarity ended there.
(00:26):
How were the diseases related. Were they caused by different
viruses or the same virus. Could you get shingles from
someone with chicken pox? Nobody knew. But by the mid
nineteen sixties, scientists had figured out what was going on.
And one of the people who did the most to
figure it out was not some high powered researcher at
a prestigious university. It was a family doctor in a
(00:48):
small British town. His name was Edgar Hope Simpson. I'm
Jacob Goldstein and this is Incubation, a show about viruses.
In the second half of the show, we'll talk about
the most common symptom of shingles, pain and we'll talk
(01:12):
about the surprising methods that some doctors are using to
try and alleviate that pain. In this part of the show.
We're going to talk about Edgar Hope Simpson, that family
doctor who helped solve the mystery of shingles. I talked
about Hope Simpson with Anne Arvin. Anne's retired now, but
she spent decades as a clinician and a microbiologist at Stanford.
(01:33):
She studied the Vericella zoster virus, the virus that causes shingles.
Speaker 2 (01:37):
Edgar Hope Simpson, as you just said, was a GP
who was very interested, as many practitioners are, in trying
to solve unresolved issues in medicine. And his practice was
largely older people, and he was seeing a lot of
shingles relatively speaking, but he was also seeing kids with
(02:02):
chicken pox. It was really easy to see that one
kid with chicken pox would give it to fifteen other kids.
They would get chicken pox. That was easy to observe,
Uh huh. It was a lot more difficult to nail
down the question of what about shingles and does exposure
(02:23):
of a child to shingles really result in chicken pox
or is that just coincidence proximity?
Speaker 1 (02:34):
Huh?
Speaker 2 (02:34):
And so that was his question.
Speaker 1 (02:37):
There's this moment, I guess in the nineteen forties when
Edgar Hope Simpson reads in a British medical journal just
a case report, just a letter from a doctor on
this remote Shetland island called Yell. Tell me about Edgar
Hope Simpson and this island of Yell and this sort
(03:00):
of quest to understand the relationship between chicken pox and shingles.
Speaker 2 (03:07):
Yes, so why did he jump on the boat or
train or boat and train or whatever to go practically
a day and a half to get from where he
was in sort of southern England up to this remote
island in the Shetland Islands in the North Sea. Why
did you do that?
Speaker 1 (03:24):
It was going to go on summer vacation. And he's like, no,
I'm not going to go on summer vacation. I'm going
to go investigate this.
Speaker 2 (03:30):
Outbreak because the letter that he read said there was
a school teacher who had shingles and there was an
outbreak of chicken pox in her class.
Speaker 1 (03:45):
In nineteen forty six, Hope Simpson reads this letter in
the medical journal about the school teacher case in Yell,
and then Hope Simpson reaches out to the local doctor
who wrote about the case and they stay in touch
they're corresponding with each other. Eventually, Hope Simpson learns that
there is another outbreak on the island. There's something like
(04:06):
one hundred chicken pox cases that seem to have come
from a single case of shingles.
Speaker 2 (04:13):
When he heard about this crofter who had shingles and
whose five children then had chicken pox, he thought, this
is an irresistible opportunity. I will go up there and
I will actually see this outbreak unfold in real time
from this shingles case. And so undoubtedly the shingles case
(04:37):
did lead to chicken pox in that family. The question
was could he then trace a further outbreak.
Speaker 1 (04:46):
I mean, I guess there's something about a remote island
that's actually a perfect place to test the hypothesis, right
because unlike in you know, twentieth century England, people are
taking trains, people are coming and going, this was like
truly a remote people are like crofters which I don't
even know they're farmers or they're raising sheep or something.
Right Like, it's it's very out there. So he goes
(05:09):
out there and I mean it's amazing, Like what he's
doing is contact tracing basically. Right, there's here, he wrote
this reminiscence that I just want to read because I
love just a paragraph of it. There's this moment when
like they're trying to track down one case and he says,
(05:29):
the team, which is just like him and two other
people walked from mid Yell to the south shore of
the vau Vae is apparently a Shetland word for a
little cove or something road themselves across. He means ourselves
rode themselves across to north of Vo and walked for
several miles across the heather to the home of K six.
(05:51):
And then he was hoping this one particular connection was
going to answer everything, and he writes, alas no, because
this girl who was going to tie it all together
for it was not in fact at this other place.
So anyways, it's a great story.
Speaker 2 (06:07):
I love that. I love that description too, And I
had to look up what is a voe? So I'm
sad that we now know a voe is a bay,
a small bay. I can tell you that kind of
vs V Barricela's osterro virus research. That is not how
we do it now, but it looked kind of interesting
(06:29):
to be able to do that.
Speaker 1 (06:31):
You never you never wrote, did you? How much rowing
did you do in your research?
Speaker 2 (06:35):
Absolutely not so. Anyway, he was trying to see whether
he could get a second, a reproducible finding, so to speak,
because he heard that the person in the other location
had shingles, and then he thought, well, there's going to
be maybe another traceable cluster of cases. So back to
(07:00):
your question about why islands, islands are really important in
epidemiology of infectious diseases, and so the reason is because
the populations are tiny and in that particular geography, as
you just said, you row your boat, you walk three
miles or ten miles or whatever, there's a lot less
(07:22):
contact in a very rural situation. So you can have
the situation in epidemiologic terms where there's a fair number
of susceptibles and you can actually then take the so
called index case and you can map literally house to
house the cases.
Speaker 1 (07:45):
Yeah, but then I think he sort of dug further
and figured out more connections, right, and it did suggest,
although it wasn't conclusive, well, that it's the same virus
and that you can catch chicken pox from someone with ching.
Speaker 2 (08:00):
Right, he went a great distance, so to speak, towards
actually proving that hypothesis.
Speaker 1 (08:08):
I picture him with like a wall, like a map,
but with like pushpins that maybe like red yarn, you know,
like a like in a detective show or something.
Speaker 2 (08:16):
Sure, well, epidemiology is basically a detective story most of
the time. So yes, I think that's exactly what he did.
They went around house to house, took records and ask people.
Speaker 1 (08:31):
Yeah, so this is like a very colorful and you know,
kind of low key heroic thing he's doing to try
and learn something for the benefit of humanity. But he
is doing this longer term study based on his practice
right where he's closely tracking all of the chicken pox
(08:55):
cases and all of the shingles cases over many, many years,
and he winds up giving a lecture, publishing a paper
that is the summation of that work, and he does
wind up solving this mystery. Tell me about that paper.
Speaker 2 (09:10):
That paper is about his long term study. And he
apparently studied everyone in his practice who got shingles. So
not only did he make the diagnosis, he made a
chart of each person and marked on this chart here's
where this person lesions were, this is where the other
person's lesions were. And so he had an enormous set
(09:33):
of data on where the shingles rash appears on people's bodies,
and he also had all of the chicken pox data.
And what he was able to conclude is it's a
one way traffic. Shingles causes vericella. Vericella does not cause jingles, right,
(09:54):
chicken pox. Yeah, So that was his finding, his fundamental observation.
And it's a one way traffic. So that means where
does the virus come from when you've got shingles?
Speaker 1 (10:08):
Uh huh. It doesn't come from someone with chicken pox,
and it doesn't come from someone with shingles, right.
Speaker 2 (10:13):
That's also what he observed. And so he had all
this massive data sets of people who had shingles and
were in close contact with somebody or several other somebodies
and they didn't get shingles, but if there were kids around,
they got chicken pox, but not vice versa.
Speaker 1 (10:32):
So from that beautiful data set he can show clinically
what's happening. And from this clinical finding, he presents in
this paper a hypothesis of what's going on at the
micro level, at the cellular scale.
Speaker 2 (10:46):
What does he hypothesize the hypothesis is what we now
know to call latency. That is, when you have chicken pox.
In the course of your chicken pox episode, the virus
you can imagine, is in those little boxes all over.
And what is also in the skin Right next to
(11:09):
where those boxes are, which are full of virus, there
are nerve endings. And so the virus has created a
great scheme for persisting by taking not just the opportunity
to form skin lesions, but to go backwards up the
(11:30):
nerve axons to the nerve cell body, which is in
what's called sensory ganglia, all up and down the spinal
cord and cervical spine and face. But developing the hypothesis
of how the virus got to the sensory ganglia, he
outlined what he called suppositions. I like the phrase suppositions.
Speaker 1 (11:56):
There's a nice humility to it, right, I don't know,
but let's suppose.
Speaker 2 (12:01):
Yeah. So he created a set of suppositions that have
subsequently been found right. But also because they were suppositions,
a number of them were not right.
Speaker 1 (12:16):
What did he get wrong?
Speaker 2 (12:18):
Well, for starters, he thought chicken pox was a pox virus,
which it isn't. It's a herpes virus related to herpes
simplex type one and type two.
Speaker 1 (12:29):
Let's talk for a minute about just herpes viruses, and
in particular the persistence, right the fact that they have
this from the point of view of virus clever, from
the point of view of a human host, insidious quality
of hanging around forever. Tell me more about that.
Speaker 2 (12:49):
First of all, these viruses are ancient, and they sort
of evolved into different subgroups over millions of years. And
if you look at every specie, they all have their
herpes viruses too. It's not just us. You have a
guinea pig, that guinea pig has guinea pig herpyes virus.
(13:09):
So it is. It is a story that encompasses the
entire family of viruses. And what we know is that
for the most part. The other thing the virus as
agent has to keep in mind is don't make the
person too sick, right, accommodate if you can, just don't
(13:33):
even cause any symptoms at all. Just arrange to be
periodically showing up at a mucosal surface. In fact, a
few cells, dump a few virus particles into the saliva
or whatever, and so be it.
Speaker 1 (13:50):
Everybody's happy. Everybody's happy, right, problem.
Speaker 2 (13:55):
No problem, so in fact, you know, chicken pox is
a bit unusual in the It does typically cause symptoms,
but very very mild. When it's not mild, it is
potentially lethal. And so that's why all of us in
the field work so hard to develop vaccines, vaccine for
chicken pox and vaccine for shingles.
Speaker 1 (14:17):
So when you look back at Hope Simpson's work, what
do you make of it?
Speaker 2 (14:24):
Well, I think it's pretty straightforward for me to say
why I and my colleagues so much admired the work
that he did and the suppositions that he came up
with because he was looking from an evolutionary perspective. He
was asking why does this happen? And what he proposed,
(14:50):
which is definitely true, is that the virus gives itself
a kind of second chance to spread. So, if you
look at it from an evolutionary perspective, and you're thinking
from the point of view of the virus, how to
sustain your life if you will, your life cycle in
(15:11):
a community is as important as how to sustain it
in one person. And so you have to imagine a
rural community if chicken pox isn't reintroduced as a kid
with chicken pox showing up from somewhere. That is it
for the virus unless unless there's another way for it
(15:36):
to introduce itself again, so to speak. And that is
where the Shingles think. So that is why his work
in Yale was really important. He was actually showing that
life cycle as it rolls out in a community.
Speaker 1 (15:54):
Yeah, like the virus as agent. Right, it's giving the
virus agency.
Speaker 2 (16:00):
Which we know not to do. But it's so.
Speaker 1 (16:03):
Tempting, I mean, whatever that's a word. I mean, I
think there's a non anthropomorphic way, Like, I don't care
what anybody says, it's clever that the virus is doing that.
It's very clever.
Speaker 2 (16:13):
Certainly my point of view. Yeah, So it's an evolutionary
strategy of the virus. That's one reason why this work
is important. And the other reason, I think is back
to the suppositions. He did not assume that the story
was fully understood, and that was that he knew and
(16:36):
identified the gaps. So there's a way in which you
can say we've been filling in the gaps that he
placed out there as suppositions.
Speaker 1 (16:45):
I think there's something also really elegant, maybe even romantic,
if I'm being honest about the family doctor, the general
practitioner as epidemiologist. You know, he's he's there every day
treating patients. And the thing that he did, I mean
besides going to yell, which is very dramatic, but the
(17:06):
less dramatic but maybe ultimately more important thing that he
did is keep this meticulous data as you say, about
where the where the rashes are and what the household
connections are. I mean that transforms his work from you know,
helping individuals to like making this significant breakthrough in human
knowledge exactly.
Speaker 2 (17:28):
And picking picking a question. I mean, there's always a
science of great challenge is pick a question where you
can really gather some data that's going to lead somewhere.
That's as much of a contribution as a researcher as
actually finding answers to some of those questions.
Speaker 1 (17:53):
Thank you for your time. It was great to talk
with you. You too, And Trevin is a retired clinician
and microbiologist at Stanford. In a minute, I'll talk with
a physician and researcher who was a friend of the
late Edgar Hope Simpson and who has spent decades studying
shingles and pain.
Speaker 3 (18:26):
Anyone who has done any work on shingles. Probably the
first name they will come across is Edgar Hope Simpson.
Speaker 1 (18:34):
Is it true that you knew him?
Speaker 3 (18:36):
Oh? Yes, I can't tell you precisely when, but I'll
tell you how.
Speaker 1 (18:41):
Robert Johnson is a physician who spent decades treating shingle's patients.
He no longer has a clinical practice, but he still
does research at the University of Bristol.
Speaker 3 (18:50):
It was about nineteen ninety four. There were a group
of us who were going to be presenting in a
symposium and somebody said, is Simpson still alive? And I said,
I have no idea. Let's have a look and telephone directory.
So we looked up and there was Hope sinstance siahen sister.
So we phoned him. I think it was about eight
(19:11):
o'clock one evening, and there was a fairly brusque answer.
I Hope Simpson here, I said, is that doctor Egger
Hope Simpson? He said yes, And I said, could I
ask you? Are you still interested in shingles?
Speaker 1 (19:25):
Oh?
Speaker 3 (19:25):
Yes, he said, And that was the start of it.
And he was brilliant. He was the most humble man
you can imagine, an enormous breadth of knowledge. Everyone had
stories about him, both from the medical point of view,
as a friend and in particular as a general practitioner.
(19:46):
He was clearly extremely caring, and they told me that
he'd be known to ski in the winter out to
a patient for an emergency call. He was obviously a
very dedicated a character.
Speaker 1 (20:03):
So I want to talk about shingles as a disease
and about your work with shingles. What happens in the
body when you get shingles.
Speaker 3 (20:14):
What happens is that the virus, which has been dormant
in nerve tissue near to the spinal cord and near
to the certain areas of the brain, has found itself
able to reactivate without getting an immune response adequate to
prevent its spread. And then the virus replicates it, It
(20:37):
increases its numbers, it multiplies and spreads along the peripheral
nerve that runs from the area where it was latent
and eventually reaches the skin, where you get the typical
rash of shingles.
Speaker 1 (20:51):
So I had chicken pucks decades ago, and right now
inside my nerve cells inside my body, there is that
virus still just hanging out weeding more or less and
if there is some moment when my immune system is
compromised in some set of factors, a line I will
(21:11):
get shingles.
Speaker 3 (21:12):
Yes, you're absolutely right. In a lifetime, about thirty percent
of us will get shingles, and if one lives into
one's eighties, which these days is very common, it's about
a fifty percent chance of getting shingles.
Speaker 1 (21:25):
Tell me more about the symptoms of having shingles. What
is it like to have shingles?
Speaker 3 (21:29):
Very frequently one has several days of pain or tingling sensation,
maybe feeling a little bit unwell, but then the rash
appears and the diagnosis becomes clear. Almost always, the acute disease,
the first three or four weeks is painful, and it
can be extremely painful. In some people, the lucky ones,
(21:54):
the rash the pain over a period of ten days
to three weeks disappear. There's often a little bit of
scarring and that's the end of it. But in others
that's not the case. The pain persists. It can be intermittent,
but it can go on for weeks, months, or even years,
(22:14):
and when it reaches three months from the rash appearance,
we call it post Pettit euralgia.
Speaker 1 (22:21):
So post herpetic neuralgia is the technical term, the term
of art for basically long term pain after you have shingles.
You can sort of unpack it right, post her petic
after herpes and neuralgia is a pain from from the nerves,
right from the nerve, absolutely, and it seems like that
is I mean, shingles is the thing you don't want.
(22:44):
Post herpetic neuralgia, long term pain from shingles is the
thing you really don't want, right, So let's talk some
more about that. I know you're working on that. What
is the mechanism of post her petic neuralgia. Why is
it that some people get it and some people don't.
Speaker 3 (23:00):
I'd say I don't know, but I will try and
give you a full answer without waffling too much. There
is definite damage to nerve tissue, nerve fibers right from
the skin to the spinal cord and indeed within the
spinal cord. But the problem starts with the clinical side,
(23:24):
because there is no single pain syndrome of post de
pendant euralgia. You can have numbness, or you can have
a severely increased sensitivities to touch. You can have a
reduction in sensitivity to heat and cold, or you can
have an increase. You can have a continuous burning pain,
(23:45):
you can have severe intermittent lancinating, page shooting, electric shock
like pains, And if you take that forward to months
and years, you can see what it can do to
a patient.
Speaker 1 (23:59):
Let's talk about eatment and prevention, right, Okay, what can
you do to avoid getting shingles in.
Speaker 3 (24:05):
The first place? Don't have chicken pox, And the only
way you can be fairly confident in not having chicken
pox is to be vaccinated against it, which in the
States you have done pretty routinely since nineteen ninety five.
But it's going to be some years before we see
any marked effect on that in shingles because those people
(24:28):
are still, relatively speaking young as far as the age
for getting shingles is concerned. So vaccination against chicken pox
is one, the next one is vaccination against shingles.
Speaker 1 (24:42):
If you are not fortunate enough to prevent shingles, what
is the treatment both for the initial disease and for
post herpetic neuroalgia.
Speaker 3 (24:55):
Right, Well, one may have a capacity to actually even
when shingles has started prevent post to pedant euralgea. It's
a bit uncertain. Anti virals we hoped would have a
massive effect on that. And the anti viral drugs are
remarkable for treating the acute symptoms and any serious disease,
(25:18):
But how much they influence development of post to pedant
euralgia's always remained a bit of a gray area. It's
very hard to see why they wouldn't. But if they do,
it hasn't reduced the incidence of post pedant euralgia overall
very much.
Speaker 1 (25:34):
If they work, we can't see it.
Speaker 3 (25:37):
Well, that's sort of how it is. Yes, Having said that,
I wouldn't want to underplay the value of the antiviral drugs.
My personal view is that almost everybody who gets shingles
should receive them.
Speaker 1 (25:50):
I know you're working now on a study looking at
it at another way of treating shingle's patients with lasting pain.
Tell me about that.
Speaker 3 (25:58):
We're now looking. In England, we have a study based
on Bristol looking at amitriptlen that was originally an antidepressant drug,
but in very low doses it has an effect on
europathic pain. And another neurologist called David Bouscher from Liverpool
(26:19):
in England had published a study all three decades ago,
perhaps basically showing that probably low dose ami triptlen given
early in the course of jingles reduced the incidents of
post dependant eualgia dramatically. David Bouscher was a character and
(26:41):
he did push the case of herpes oster extremely well
as far as people getting interested in research in it.
It was a very interesting paper and very indicative that
further research was needed, but it didn't prove the case.
Speaker 1 (27:00):
This is a very odd the decades or antidepressant yes,
or drug that was developed as an antidepressant, yes, why
why might it help reduce postropedic neuralgia.
Speaker 3 (27:14):
Well, again it's not fully understood, but it does have
certain effects which can affect transmission of impulses within nerves
and excitability of damaged nerve tissue, possibly effects within the
spinal cord at inhibition of pain from impulses which traveled
(27:40):
down from the brain out towards the spinal cord and
the peripheral nerves. There are all sorts of possible mechanisms,
but I think it would be wrong with me to
say we know the answer.
Speaker 1 (27:52):
I want to talk about pain a little bit more
more broadly. And you know, when you mentioned an antidepressant
as a treatment for pain, there's one universe where there
is some very direct mechanism in the peripheral nervous system.
I mean, there is also a universe where pain is
related to our psychological state. And as a doctor who
has treated pain a lot, I'm curious about your view
(28:14):
on that. More generally, on pain, you know, as part
of this broader complex of well of a person psychological state. Oh.
Speaker 3 (28:24):
Absolutely, pain is biopsychosocial. There's a pathology, the biobit, there's
the psychology, and there's the social the environment that we
live in, and all these things play a part in
pain and how we respond to it. And you know,
just go back to Hope Simpson for a second. When
(28:45):
Hope Simpson talked about management of patients in general practice
with shingles, he said the main thing was to care
for the patient, to take an interest in the patient,
to follow the patient up, to encourage them. And this
is so true. My wife and I started a herpesoster
(29:06):
clinic here in Bristol or many years ago now, and
we saw mainly post a petit euralgia patients, but we
were very happy to see acute patients that general practitioners
referred us who had unusual features or severe pain, or
were particularly distressed. And it was really the persistence and
(29:28):
the interest shown in the patients which made a huge
difference to their progress. The treatments we had available were
pretty limited, and you just had to persevere. We worked
through the treatments with them, We discussed the treatments with them,
and I think it makes a world of difference how
(29:48):
you treat the patient overall. And one of the things
that is essential is to encourage them to get back
to social interactions, to go out and meet people, not
to hide away nursing the pain.
Speaker 1 (30:05):
Why Why is that so important?
Speaker 3 (30:07):
Because pain is multifactorial, and if you can address one
or more of the bio psychosocial elements, you're going to
get improvement. Well, the bio we weren't so good on,
although we did have drugs and we did have other treatments.
The psycho, I don't know much about that, but the social, yes,
(30:28):
you could definitely influence that. Encouragement and taking a concern
about the patient's problem is essential.
Speaker 1 (30:41):
It was really lovely to talk with you. I thank
you for being so generous with your time. Thank you,
Andrew Knowledge, Thank you very much. Robert Johnson is a
researcher at the University of Bristol. Thanks to both my
guests today, Anne Arvin and Robert Johnson. By the way,
last week's show, in case you missed it was all
so about a herpes virus. That show was about the
(31:03):
epstein bar virus EBV, which also has some very insidious
long term effects. Next week on the show, the HIV
epidemic that changed the world and the scientists who are
racing to understand it. We have something, We have something.
Incubation is a co production of Pushkin Industries and Ruby
(31:26):
Studio at iHeartMedia. It's produced by Kate Ferby and Brittany Cronin.
The show is edited by Lacey Roberts. It's mastered by
Sarah Bruguier, fact checking by Joseph Friedman. Our executive producers
are Lacey Roberts and Matt Romono. I'm Jacob Goldstein. Thanks
for listening.
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