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visit MIT OpenCourseWare at ocw.mit.edu. MICHAEL SHORT: So
as a quick review of all the different
biological effects, we've pretty much
taken it up to here. We've explained the
physical and chemical stages of what happens when
radiation interacts with mostly bags of water with
some solutes in them, better known as organisms at
dynamic equilibrium. Everything from the sort of
femptosecond level, ionization of water almost
certainly, because that's most of what
biological things are, to the formation of many, many,
many, many, many different radiolysis byproducts eventually
that end up as just a few that we care about, the
longer-lived radiolytic byproducts that will
then diffuse away from the original
damage cascades and go on to eat something
else, likely DNA or something that you don't want to get
oxidized or chemically changed. We talked a little bit
about radiolysis in reactors and how you can actually
measure it directly which was only done really a few
years ago which is pretty cool. Just to remind you
of this experiment, there's a tiny
high-pressure cell of high-pressure,
high-temperature water. There is a foil sample with a
very thin region and protons firing through it, so that
they both irradiate the sample and induce radiolysis in
the water at the same time. And this way, you can test
the effect of radiolysis in the water here versus just
plain, old, high-pressure, high-temperature corrosion here. And the results are
pretty striking, where you can clearly see
the boundary where the proton beam was as well as
the increased thickness of the oxide and corrosion
layer formed when radiolysis is turned on, so to speak. We went through DNA damage, and
we ended with pseudoscience. So I want to bring up a couple-- no, we don't have time for that. But we spent the last 15
minutes of class railing against pseudoscience and making
sure that you check your facts, but we pointed out
a number of things wrong with some of the studies. So aside from just that
guy misreading everything on that entire blog, of
the studies that you felt weren't very convincing, what
do you remember about them? Some of those studies were
totally fine, but some of them were not. AUDIENCE: The ones with
particularly small sample sizes. MICHAEL SHORT: That's what I
was hoping someone would say. Yeah, the case
study of four women who got breast
cancer in the pocket where they held their
cell phones, four, right? Or in a study of 29 humans, 11
of them got brain tumors here. It's pretty easy to cherry
pick small amounts of data. I did want to say that just
because radio frequency photons aren't ionizing, doesn't
mean they can't hurt you. If you've ever-- no, no one's
ever been inside a microwave. I wonder if anyone's
ever felt the effects of an external microwave
being by something like this, the active denial system. One of my favorite weapons ever,
because it doesn't actually permanently hurt anyone. It just heats up the
outer layer of your skin. It fires these non-ionizing
photons at RF frequency and effectively makes you
feel like you're on fire. So if there's a whole mess
of troops charging at you-- let's say at the DMZ from
North and South Korea-- all you've got to do
is turn on this thing, and they all think
they're on fire, because their body is sending
them signals that I'm on fire. And then you turn it
off, and they're OK. So no loss of life,
no permanent damage, a lot of maybe
psychological, but whatever, you can't see that. AUDIENCE: Active denial. MICHAEL SHORT: Active denial
system, great name for it, isn't it? Yeah, I think non-lethal
weapons are really the way of the future is just make
it unpleasant to engage in warfare, and
people probably won't. But then no one has to
get hurt, which is nice. But then onto the sources of
data, because like Sarah said, sample size is everything,
especially when you're trying to figure out, are
small amounts of radiation bad for you? This simple question
hasn't really been answered suitably yet,
and that's because, thank god, we don't have enough
people exposed to small but measurable
amounts of radiation to draw meaningful
conclusions from this data. I think that's a good thing,
is if we were certain about whether small
amounts of radiation, like one millisieverts,
could cause cancer, then there would have been
millions or billions of people exposed, and so it's kind of a
good thing that they weren't. But the sources of this
data, the first source was radium dial workers,
like you may have heard of, the folks that would lick
the paint brushes with glow in the dark radium watches. They ended up setting the first
occupational limit for dose, because they were
the first large group to be exposed to radiation
in a controlled setting. Things like uranium miners,
radon breathers, better known as us, but especially
folks that smoke anything. Medical diagnostics, so anyone
that gets a medical procedure, you can follow up with them
to find out what's, let's say, the extra incidence
of cancer and figure out, if you have a
high-dose medical procedure, does it induce secondary
cancer down the line? But like we said last time,
down the line is the key here. I'd take a whole
bunch of radiation now, if it was going to
save my life now, and maybe make it messed up in 20 years. Because then you get
20 more years of life or however long you get. And then from
accidents, survivors of the atomic bombs, not just
the folks at the epicenter, but in the whole fallout
regions and nearby, as well as nearby nuclear accidents
and the criticality events like the demon core that you
guys analyzed on the exam. Luckily, there aren't
a lot of those, either. But they were pretty severe,
the ones that got exposed. And speaking of accidents,
has anyone ever heard of the Kyshtym disaster? This is the third-worst
nuclear accident that we know of in history,
after Chernobyl and Fukushima, and worse than
Three Mile Island, because Three Mile Island
was an almost accident. There was some partial
melting of the core. There was almost no
release of radioactivity. And the definition of a nuclear
accident in the public sense is release of radioactivity. There's actually two
quantities that folks in PRA, or Probabilistic
Risk Analysis, are most interested in. Has anyone heard of these
terms, CDF and LERF? Core Damage Frequency and
Large Early Release Frequency. All the fancy probability
fault trees and everything goes into calculating
the probability that the core gets damaged. So that could be an
accident in one right. Or the probability of a
radioactivity release. And that is an accident. So if no one's
ever heard of this, there's a city in Russia-- I don't know why it says
Russland, maybe came from a different language-- called Kyshtym, where
they had the Mayak nuclear and reprocessing plant. And there was a tank
full of radioactive waste that was exploded. It was a chemical explosion,
but full of strontium, all sorts of other
radionuclides that blew up with about
100 tons worth of TNT, and ended up contaminating
a rather large area with this plume called the-- I think it's called the East
Chelyabinsk Radioactive Trace-- or the-- what is it? The south-- South-something
Urals Radioactive Trace. And that area is still
contaminated today, because the disaster was
covered up, or rather wasn't-- nothing was said. These towns here, they didn't-- weren't actually towns back
in 1957 when this happened. They were just
given designations, like Chelyabinsk-40
or Chelyabinsk-65, because the largest nearby
city was Chelyabinsk, and the villages nearby
were just numbered. So that was just the post code
for the secret nuclear city. The US had a few, Russia
had something like 120. And they still have
a lot of cities where entry is restricted, or
it's still awfully difficult to go there. Like when you have to declare
where in Russia are you going to get a visa, if you
say one of these cities, there's going to
be some questions. And this is where I'm going. AUDIENCE: To one
of those cities. MICHAEL SHORT:
Best possible logo for a conference being held
in Siberia in February. Right on the end-- right on the edge
in this town called Kyshtym, the nearest
town to the Mayak plant. So I'll be taking my camera. I don't know if I'll
be allowed to use it, but we're going to
find out anyway. It's being held in a sanatorium. And does anyone know
what a sanatorium is? Like, I'm honestly
asking a question. I don't know what
a sanatorium is or why the nuclear conference
is being held there. But it should be pretty cool. So yeah, Siberia in February,
right near the South Urals Radioactive Trace,
should be interesting. Those of the first group
of folks that were exposed were the people painting
radium watch dials. And the reason radium
was so damaging is because radium is in the same
column of the periodic table as calcium. It's a bone-seeking element. So which of the
tissues do you think would be most damaged
by ingestion of radium? AUDIENCE: The bones. MICHAEL SHORT: Bones-- what
part of the bone, specifically? AUDIENCE: The marrow. MICHAEL SHORT: The marrow. The rapidly dividing
part of the bones. If you remember from the-- I don't have it on
this presentation, but the relative tissue
factors for different tissues, the hard part of
the bone is a 0.01. It's basically like
a nobody cares. Bone marrow, however,
is a different story, because it's always rapidly
dividing, producing red blood cells, platelets, lymphocytes. It's making your blood, the
solid portion of your blood. And so it's a pretty
important tissue. So you get radium-- anyone also know, what
does radium tend to emit? Which kind of particles? AUDIENCE: Alphas. MICHAEL SHORT: If you have to
take a guess-- yeah, alphas. It's a pretty heavy element. It emits alphas. And alphas have that radiation
quality factor of 20, meaning alphas have
very short range, but they're the most
damaging type of radiation when ingested. So this was really bad news. There was a lot of incidents
of illness and cancer from folks painting
radium watch dials. And then the first data
from bones after death, because there were a lot
of those, established, how much radium were you
allowed to get exposed to? And this came out to about
0.6 milligray per week. Anyone have any
idea what that would be in millisieverts per week? With a quality factor
of 20 and a bone marrow factor of about 0.12? AUDIENCE: 1.73? MICHAEL SHORT: Yeah. On the order of like singles
of millisieverts per week. Not bad. Anyone know how much
dose you typically get in a year in background? Yeah? AUDIENCE: A few. MICHAEL SHORT: A few
millisieverts a year. Yeah. So this was the first
occupational safety limit for radiation risk. It is-- actually, it comes out
to larger than 50 millisieverts per year, which is what the
normal occupational workers are allowed. How about you radiation workers? What's your limit? AUDIENCE: 5 rem. MICHAEL SHORT: 5 rem,
which comes out to? AUDIENCE: Like 50
millisieverts-- MICHAEL SHORT: 50
millisieverts per year. OK, there you go. Large population
sizes that do exist that get a whole
lot of radiation, however, is anyone that
smokes an anything, because when you take
plant matter, which has a high surface
area, concentrate it, so anything that it brings up
from the roots in the soil, or that settles out on
the leaves in the air gets concentrated
in the dry fraction, and then gets
burned and inhaled. A lot of those heavy metals that
are radon byproducts and such are fairly reactive. They'll stick around
in your tissues and give you a whole
lot of alpha dose. So when you have
populations of people who have or haven't
smoked, you actually can figure out the number
of extra attributable deaths to things like indoor
radon, depending on if you live in a
smoky atmosphere or not. And so to distinguish the
types of biological effects that we're worried about,
we can group these into two. There's short-term effects,
which manifest themselves in hours, days, or weeks. We'll call that immediate. And then there's
long-term effects, which tend to manifest in
shortest, years, and longest, decades. So things like acute
radiation sickness is due to rapid cell death of a
few different kinds over time. And which kind depends
on the route of exposure, the isotope, the
type of radiation, and the total amount of
dose to those tissues. And if you guys
have all-- what are some of the symptoms of
acute radiation sickness? Like, did anyone read
what happened to the folks in the demon core? AUDIENCE: That
their hair fell out. MICHAEL SHORT: Hair fell out. What else? AUDIENCE: They vomit. MICHAEL SHORT: Vomiting. AUDIENCE: Diarrhea. MICHAEL SHORT: Diarrhea. All the fun ones, yeah. Well, we'll explain why
these sorts of things happen with acute
radiation exposure. Now if you don't get that
much radiation exposure, but you do get enough
to mutate cells you have what's called
delayed somatic effects, anything from cancer,
to straight up mutations, to birth defects. Any sort of permanent and
reproducible modification to a cell's DNA that
can induce mutations. So let's first talk about
the short-term effects because they're a little
easier to understand. And because the doses were much
higher, you don't need as much of a population size in order
to figure out, did this affect-- did this amount of
dose have an effect? So for things up to
a quarter of a gray, pretty much nothing happens. That's quite a toasty dose. For gammas, that would be
like getting five times your occupational yearly
limit instantaneously. Yeah. This is not something
you'd want to happen. But it's not going to cause
any significant ill effects. Up to a gray, you'll start
to see a few symptoms, like nausea and anorexia. They probably tend
to go together. If you're feeling
gastrointestinally horrible, you probably don't
want to eat much. And you will see things
like bone marrow damage, like we talked about
with the radium workers. Fewer red and white blood
cells, less platelets, also means easier to bleed. So a lot of the effects
of radiation damage are not primary,
they're secondary. Just like most radiation
damage to cells itself is not damage
to the DNA, but it's radiolysis of the water nearby
the DNA, and eventual chemical migration to cause damage
to the DNA chemically. In this case, it's not
like radiation takes out your platelets. Radiation takes out
the cells that create the platelets, the bone marrow. Meaning that platelets, if
they live about three weeks, you'll tend to see a
drop in platelet count when your production
system gets lower. This should sound strikingly
similar to series radioactive decay because the same equations
can be used to model it. Let's say you have a normal,
stable platelet count. Eh, I'm not going
to get on the board. I told you guys we wouldn't
get to derivey anymore. But you've got some
source of platelets, which would be your bone marrow. And you've got some
sink of platelets, which would be normal cell death. So let's say there's a half-life
or a lifetime of platelets. If you kill a little
bit of the source, then you'll see the
sink start to decay. But the source will
start to grow back over time from cell division. And you'll see the
level pop back up again. And you can model it
with the same first-order linear ordinary
differential equations. Same ODEs as series
radioactive decay, you can use to guess
how many platelets you should have in your body at any
time following a certain dose. 1 to 3 grays is when
things get bad from-- go to bed from worse pretty quick. Nausea, anorexia,
and infection-- tell me, why do you
think infection results from radiation damage? Yeah. Let's hear everything, yeah. Front to back, let's hear it. AUDIENCE: I was saying
the immune system is most likely compromised
because of bone marrow being compromised. MICHAEL SHORT: Yep. The immune system's compromised. What else? AUDIENCE: You're-- AUDIENCE: [INAUDIBLE] MICHAEL SHORT: Is everyone
going to say the same thing? OK. I have another story. So I agree with you guys. But it also has to do
with these platelets. Anytime anything happens to
you ever, cells tend to die. You clap your hands, you
probably kill a few cells. You bump into something, you
probably kill a few cells. You swallow some
metal shavings, you're going to kill a lot of cells. But your body has
got mucous membranes, and all sorts of things,
and platelets in order to repair that damage. All of a sudden, if your
blood thins out, and can start leaking from
different places, or it's a lot harder to
repair like physical leaks in your body,
bacteria can get in. So the normal amount
of bacteria you're exposed to every day,
which is enormous-- there's theorized
to be something like 10 times as
many bacteria cells in your body as human cells. They're all over the place. They're just a lot smaller. Well, they can get into places
that they wouldn't normally get in. So what would
normally be a pinprick in a simple immune response,
with a suppressed immune system and a lower platelet count,
becomes a much more dangerous thing. You could undergo
something called sepsis. That's basically blood
turning to sewage because you get a massive blood infection. This is, again let's say, a
secondary or even a tertiary effect, but very real. Hematologic damage more severe-- hema refers to blood. That's basically
saying the same thing. Recovery probable,
though not assured. Why probable, and
why not assured? AUDIENCE: Everybody
reacts differently. MICHAEL SHORT: That's true. Everyone reacts differently. It also matters how
much treatment you get. So if you get a crazy
compromised immune system, we have hospitals,
and sterile bubbles, and all sorts of things
that you can be put in. But if you don't get
to a hospital in time to reduce the onset
of massive infection, that's what could happen. Then you go higher 3
to 6 gray, everything as above, plus diarrhea,
depilation, hair loss, temporary sterility. Think the temporary
sterility one's obvious. Why do you think diarrhea
and hair loss would occur? AUDIENCE: Isn't it like
the fact that your-- the cells of your
like intestines-- then you can't like hold it
in anymore because the damage. MICHAEL SHORT: Yeah. Exactly. The most sensitive
cells are the ones that are rapidly dividing
to make villi and stem cells in your intestines. Hair follicles, gonads, anything
that's dividing all the time, is going to feel the
effects of radiation damage much more severely. And barring any mutation,
which may take a long time to manifest, the wrong
damage to DNA, and the cell just can't divide. So it dies. And if those cells
die, then that means that you can't
uptake nutrition. And your body just flushes
everything out in diarrhea. Fatalities will occur in
the range of 3 and 1/2 gray without treatment. And this is what's
called the typical LD50. Does anyone know
what an LD50 is? AUDIENCE: The lethal dose. MICHAEL SHORT: The
lethal dose for? AUDIENCE: 50% of the population. MICHAEL SHORT: Right. So about 50% of the people
exposed to 3.5 gray will die. This doesn't take into account
difference in treatment, difference in person, or
everything, it's altogether. And I'll go into what an
LD50 for different things is in a second. And then over 6 gray, you
get immediate incapacitation. Hits the nervous system. You get so many
cells leaking out that the chemical signals
for your neurons, sodium, and potassium, and other ions. Well, if all your
cells die and leak out, then all of a sudden
you're flooded with the ions that are
normally kept in a very careful equilibrium to signal. So you can actually get
sudden unconsciousness in a matter of seconds to
minutes from doses over 10 gray. So you just-- you just
go out like a light, like that, and may not recover. What's an LD50? It's the-- it's whenever
an effect gets an onset by 50% of the population. And there are different
something-something 50 doses, depending on, let's say, whether
something's therapeutic, toxic, or lethal. The example I like
to give is selenium. Does anyone know anything
about selenium in the diet? It's one of those trace minerals
that you need to survive, but can also kill you. If you need to get,
about on average, 5 micrograms of
selenium in order to produce certain enzymes that
keep things going in the body. 5 micrograms is not a lot. But you know that in order to
have a little bit of selenium, it's got a therapeutic effect. Once you get around
5 micrograms, most people will see some
sort of biological benefit. If you get 5 milligrams,
starts to become toxic. And this is the case with
pretty much anything. Vitamins-- anyone ever had-- this is probably
going to be a no-- anyone ever eaten raw
seal liver before? Or polar bear livers? I don't know. No one's gone up,
way, way up north? AUDIENCE: Vitamin C. MICHAEL SHORT: Anyone--
do you know why? Or-- AUDIENCE: Because they
have too much vitamin A-- MICHAEL SHORT: Indeed. Vitamin A, something that you
need a whole lot to survive. It's so concentrated
in the livers the seals and polar bears that if you were
to just eat a polar bear liver, you would die of
vitamin A poisoning. [INTERPOSING VOICES] AUDIENCE: --you'd be dead. MICHAEL SHORT: So I didn't
hear all those things at once. One of the time. AUDIENCE: If anyone ever offers
you that, you just say no. MICHAEL SHORT: Just
take a little taste. You know, it's all
about the amount, right? What were you guys saying? AUDIENCE: If we had eaten
it, wouldn't we have died? MICHAEL SHORT: Well, no. It's not like you take
a taste and you die. Again, it's all about
the amount of exposure. One little taste is not going to
flood your system with vitamin A. But you eat an entire
polar bears liver, you're going to have a bad day. AUDIENCE: Why does it
have so much vitamin A? MICHAEL SHORT: Wait, what? AUDIENCE: Why does it
have so much vitamin A? MICHAEL SHORT: I don't know
why polar bears have so much vitamin A. No idea, actually. But then beyond that, you
can get lethal effects, where you might get sick from
eating too much of something. But then again, you know-- anyone ever heard
of the old hold your wee for a Wii contest? Where we found out
really the LD50 of water? Yeah. So you drink way too much water
without any other solutes, you deplete your body
from electrolytes. And then you can also die. So I ran into this
experience personally. I don't have to ask
any of you guys. I went hiking with
my dad in Nepal, in 2009, and the last
vacation I've taken-- that's a long time ago. It's kind of cool. At MIT, it's fun
enough here that I haven't felt like I've
needed a vacation in, what, like seven years? I'm actually kind of
taking one this year because I'm going
somewhere for research and just sticking around. But we went hiking in Nepal
I eat something I probably shouldn't. In fact, everyone eventually
ate something they probably shouldn't. And I had what
could be described as massive GI syndrome-- Delhi belly, whatever
you wanted to call it. My brother likes to call
it poop and mouth disease, because sanitation and
stuff is not the best there. And so I was in a
pretty bad state. And instead of drinking water
to replenish all of the water that was leaving out of every
direction from the body, drinking saltwater. We took tablets that had the
same isotonic concentration of electrolytes, amino acids,
as those being lost by the body, because when water
goes in the body, everything osmotically
equilibrates. If you take in
lots of pure water, it will-- a little
bit of sodium, potassium, other electrolytes
will dissolve into that water. If it's going out
in any direction, it's going to leave your body,
depleting you of electrolytes. So I had seven wonderful
days lying in bed, drinking about a liter of warm
salt water every 15 minutes or so in order to maintain
not just the water, but the electrolytes
that your body needed. Freaky, huh? AUDIENCE: Sounds
like a fun vacation. MICHAEL SHORT: Yeah, it
was a great vacation. Is there any wonder why I
don't want to take another one? If I go back there, I'm
having nothing but Clif bars. It's hard to say no when folks
that live up in the mountains offer you what little
food they have, but you should really say
no for your own safety. Anyway, yeah, there's
an LD50 for water-- by any mechanism, from
electrolyte depletion to-- there was a
contest on the radio called hold your wee for a Wii. When the Nintendo Wii
came out, they said, how much water could you drink
without going to the bathroom? And someone's bladder exploded. AUDIENCE: Like
literally exploded? MICHAEL SHORT: Yeah. That's what I heard. Either it would be
a bladder explosion or an electrolyte depletion. So whatever the
mechanism, the LD50 just tells if somebody--
if a population ingests a certain amount of
something, or takes in a certain amount
of radiation, how much will cause 50% to die. Or for much lower
doses, 50% will see some therapeutic
effect by any mechanism. It doesn't distinguish
by mechanism. So the four phases of
radiation damage, this is where all those Latin and
bio roots really come in handy. The prodromal phase is
the initial symptoms of exposure, which may or may
not happen one to three days after exposure. For massive exposure,
you're not going to see this, because
you're not going to live one to three days. For very minor exposure,
you may not even see these prodromal effects,
like a drop in blood cell count, or GI syndrome,
because the dose might not be severe enough for your body
not to be able to cope with it. The latent phase this,
is the tricky one. An apparent recovery from
the prodromal systems. So getting a medium dose
of radiation-- let's call, that like 2 to 5 gray-- will cause some nausea,
vomiting, and headache. And then you get better. And then you get worse in
the manifest illness phase, because a lot of the things
that radiation will do can be immediate. If you suddenly cause the
body to release serotonin and induce the
vomiting reflex, that goes away once that serotonin
is consumed or dealt with. I don't know how the
body would deal with it. And you might think
you're getting better. But the cells that
divide rapidly have still incurred that damage. And you won't see that damage
until they fail to divide in their normal amount of time. So things like GI
syndrome and hair loss might not show up for
a few days afterwards, because it's not like your hair
will just instantly fall out, like there's some cell that is
holding onto your hair follicle and then will just release
it when irradiated. But those follicles
won't continue to produce the keratin
at the same rate, or in a different way, or I
can't speak that intelligently about exactly the
mechanism of hair loss, but it will take a little
bit of time to get there. And the final phase is a binary. Do you recover or do you die? Could take days, to months,
to years to figure that out. And these weren't
in the reading, but I wanted to pull some
much better tables about what happens in each of these phases
as a function of radiation dose. So when does vomiting onset? There are actually
patterns to be seen here. So for mild, it may take a
couple of hours after exposure. You may not stimulate
the immediate release of the hormones that
induce vomiting. But then as the dose gets
more and more severe, could be anywhere from hours
to less than 10 minutes. So you can use the onset of
things like vomiting, diarrhea, headache, loss of
consciousness in severe cases, to gauge the amount
of dose someone has absorbed in some
unknown accident. Because it's not like if
you're in some severe nuclear accident, and you don't
happened to be wearing a very large range
dosimeter, how do you know how much dose you've got? And how do you know how
to treat the person? Time can be your
best weapon there, because except for
very lethal doses, where you could go unconscious
in seconds or minutes, you've got some
time-- hours to days-- to treat what happened. And if you can say, all right,
I know the time of exposure, and I know the time
of onset of headache, of diarrhea, of vomiting,
you can figure out, roughly maybe within plus or minus a
gray, how much dose you had and what to treat. There are probably smarter
ways of doing this, but with nothing else,
you've got time as a variable to help you figure this out. Why do you guys think that your
body temperature would go up upon exposure to huge
amounts of radiation? What's with the fever? What is the fever a response to? Or could it be a response to? AUDIENCE: Infection. MICHAEL SHORT: Infection. So any sort of sudden
massive infection would mount an immune response. And that would cause
a fever because you've got all sorts of cells
doing things, expending energy, trying to rid your
body of the infection. What else? That's OK, something for you
to read up on for the-- not for the-- for the practice homework. The one that I can't
make due because it's after the last day of classes. What about-- let's see-- headache, I don't think
we've explained that well. We'll get into the
diarrhea stuff. Let's go into the latent phase. What tends to happen? Well, looks like you get
better, but blood work will tell you otherwise. And you can then
tell how much dose you were exposed to after
a certain amount of time by things like lymphocyte
and granulocyte count, different immune system
blood cells, also platelets, also all sorts of other things. You can tell by a drop in
certain blood cell levels how much dose you've had. And you can sustain
a certain drop in platelets and immune cells
without any ill effects. Something like 30% to 40% of
your platelets could go away, you're not a
hemophiliac, temporarily. You're still going to be OK. You can form blood
clots in result-- what is it-- response to
a nosebleed or a bruise, and these things aren't
going to be life-threatening. Diarrhea, for low doses,
you don't really get any. So it looks like intestinal
cells may be a little bit more robust than bone marrow. Except with really
severe doses, you'll start to see that pop up once
those cells fail to divide. Once, let's say, the
existing villi die off, new ones don't replace them,
and you lose your ability to uptake nutrition. And then depilation, hair loss. Beginning on day
15 or later, you might think you're
out of the woods, and then all of a sudden,
your hair starts to fall out. And that'll help tell you
about how much dose you've had once again. And then the
critical phase, what happens when things go from
bad, to better, to worse? How quickly does this happen? You tend to get things
like infections, more severe infections,
disorientation. On longer times, like seven
days, your platelet count-- it's pretty
proportional to dose. Same thing with the number of
lymphocytes, lower, and lower, and lower. And then the onset time
is smaller and smaller. And then you can
see the lethality of these different
doses, depending on the person, the treatments,
the susceptibility, any sort of
pre-existing conditions, which you might not know. Do you have a question? AUDIENCE: Yeah. I was going to ask,
for cancer patients, when you hear about
them losing their hair, are they actually getting doses
in like the 2 to 4 gray range? MICHAEL SHORT: Cancer, yeah. AUDIENCE: Because
it's so concentrated. MICHAEL SHORT: Radiation
doses are pretty intense. So the dose to the
tumor, for example, in proton therapy, which
is the only one I've really read about, can be in
the kilogray level. But the idea there is you fry
the tumor, you kill it soon. Like you go beyond the
lethal dose for those cells, while inducing
much less damage in the rest of the
surrounding person. And that's the nice
quirk of protons, is you can do that in
a very narrow range. The straggle on 250
MeV proton beams is on the order of like,
microns, less than millimeters, which is pretty cool. But a lot of the hair loss can
come from the chemotherapy. Chemotherapy is better
known as poison. It's just a poison that affects
tumor cells slightly more strongly than the
rest of your cells. But it is nasty stuff. And it's the chemo that can
cause the hair loss as well. Yeah. So would you attribute the hair
loss to radiation or to chemo? I would say chances are
it's chemo, depending on where the tumor is. I mean, if you have a
localized proton beam coming in to treat a tumor
there or there, you're not going to get much
hair loss up here. But chemo penetrates
throughout the whole body. As far as if you're getting
X-ray therapy of a brain tumor, that I don't know. I really haven't
looked into that. So good question. And then the time and
severity of these symptoms. Well, this is something I'd like
you guys to read on your own, because it's tons of
words on a screen. But it's something
I suggest you read. It's not done that
carefully in the reading, which is why I provided it
here for you in the slides. And then going on to what
these radiation symptoms mean, I wanted to translate a
little bit of the Latin, Greek, whatever, roots into
something you can understand. These hematopoietic symptoms--
anything to do with the blood, decreased platelets,
immune suppression, all that kind of stuff. And the origin is the stem
cell system in your bone marrow breaks down and you
don't make as much of all the components of
blood as you normally should. The gastrointestinal
comes from the stem cells in the villi, those
high surface area structures in your
intestines that absorb the nutrition, which
are also normally covered in a thick layer of
mucus to keep all the bacteria from getting out. Because nutrients,
like, let's say, minerals or small proteins,
are a hell of a lot smaller than bacteria, they
can diffuse or transport through the mucus much faster. So you can uptake the nutrition
and not let the bad stuff in. And the neuro or
cerebrovascular stuff is straight up blasting
of endothelial cells. Your, let's say-- yeah-- I think that's skin cells. A term called edema,
which is fluid leakage. Has anyone ever seen pictures
of folks with massive edema in the legs? Like, folks that, let's
say, haven't gotten out of bed for years and their
legs swell up like this? That's just fluid leaking
into the intracellular spaces. I'd say take a look. I don't think I'm going
to show pictures of it because it's kind of
nasty on the screen. But if you want to know
what edema looks like, then I suggest you look it up. There's plenty of horrific
stuff on Google Images. And so what happens in
these hematopoietic cells? About 1 gray can knock
out about a third of your bone marrow cells,
and that's actually OK, because those surviving cells
are redividing quite quickly. And that means that you won't
have that much of a drop in blood cells, because let's
say you kill off a bunch of the bone marrow cells ,
but they redivide in a shorter lifetime than, let's say, the
red blood cells or platelets live. You're not going to see that
much of a dip in the blood cell levels, which are ultimately
your main line of defense against sepsis. Things like destruction of
bone marrow, yeah that would-- that would be a bad thing. There's a whole
lot of words here. I'd say this is better
for you to read. I want to go through an
explanation of some pictures of what tends to happen
to, in this case, mouse bone marrow tissue
after a lethal dose, 9.5 gray. That's what it looks
like beforehand. That's what you're left with,
is very, very few cells. So that would be definitely
what a lethal dose looks like, because the ability to make
all the things that bone marrow makes has been almost
eliminated in this tissue. So a visual of what these
sorts of things look like. For the gastrointestinal
systems-- I'm going to skip right
ahead and show you what healthy and irradiated
villi tend to look like. So I've been-- does
anyone not know what I mean when I say villi? OK, good. So the little high
surface area structures in your intestine
that are normally great absorbers of nutrition,
mostly due to their surface area, but also due
to their structure and their biological function. And you tend to kill those off
with a fair bit of radiation. So this is what it looks like
after four days, and seven days, and then 12 days. Things can recover. As long as you don't kill all
the cells, they will divide and they will reconquer. And if the organism
can live long enough to allow for that natural
healing to take place, then you can survive an
acute dose of radiation. So when we talk about why do
you need hospital treatment, it's basically to stand in for
your body's normal functions while your body regenerates
those functions. But for extremely severe cases--
let's go back to that table of how many, let's
say, leukocytes, or what not you have--
or lymphocytes-- if you get down
to the zero level, you've completely knocked
out your body's ability to produce those. You might have a few
cells left here or there. But at that point, there's
not much anyone can do but make you comfortable. And then in this case, I
think this was a human one-- yeah, OK. So a healthy intestine
from a human. It's got a rather small whatever
that part is in the submucosa level. Lots of villi, lots
of surface area. After radiation damage, when
you have massive cell death, notice that the structures
out here are pretty much gone. And there's a lot of
scarring or-- what's the word that they use? Severe fibrosis. Why would your body make
scar tissue in response to radiation damage? So anytime your body senses that
a whole lot of cells are dying, it's going to respond
by attempting to repair. So like if you get, let's say,
a small bit of surgery done, you could be left
with some scar tissue. That's cells that have died,
and when those cell contents leak out, they signal to the
nearby cells, fix something. I can't speak any more
intelligently about that, but the body does. And scar tissue is not what
you want in your intestines because that interferes with-- what is it? Nutrition uptake
as well as killing the structures that are doing
that uptake to begin with. Then there's the
neurovascular stuff. Massive cell death from a
huge amount of absorbed energy can just cause those
cells to die and leak out, causing a lot of edema. That can cause a drop in blood
pressure, which is also not good for you. This could be part of what leads
to some of the unconsciousness. If you have a drop in blood
pressure due to any reason, then that can make
you go unconscious. And there's pretty much not a
prodromal or a latent phase. If you hit the
neurovascular syndrome, you're pretty much going
to go to the critical phase right away, within
seconds, minutes, or small number of hours. Here's another question,
why the skin lesions? Because mature skin cells
live about three weeks. If you kill off the skin
cells in the dividing layer, and you don't reform new ones,
and those skin cells die, you end up with the
grossest word in this class, moist desquamation. It kind of sounds
like what it is. That's like
sloughing off of skin and leaving open
sores because you don't have the ability to
regenerate that skin, which is normally your first line
of defense to everything, and you've got
fluid leaking out. And it's just-- yeah--
it's moist desquamation. Why the vomiting? Well, this question hasn't
been fully answered yet. As far as back when I've
looked at the literature around to 2011, there is a hypothesis
that intestinal cells will secrete serotonin in
certain conditions, including when they start dying,
which would then stimulate a center in your medulla, the
sort of automatic reflex center of the brain, to
induce vomiting. Why might this be a good thing? We're not talking about
radiation, but why would you want to stimulate
this vomiting reflex? AUDIENCE: In case
whatever's going wrong is because of something you ate. MICHAEL SHORT: Yeah. So let's say you eat
a wet aged steak. You know, something that's
left out on the table, or in the fridge, or let's
say, behind the fridge, or left to marinate in the sun. And you eat it,
and those bacteria start killing everything. If those cells in
your intestine die, they've got to send
some signal far away to the brain to tell you to get
everything out of the stomach. And that's what happens. So the body has developed
these long distance hormonal signaling mechanisms
to say, something is going wrong,
expel everything, because it's
probably bad for you. So radiation damage to these
cells, which will kill them, may trigger the same effects. If those cells have little
pockets or organelles that contain these hormones
and cause instantaneous secretion by cell death, that
might do the same thing, too. But as far as this
paper, it's a hypothesis. It's not necessarily proven. But it does correlate inversely
with the amount of time to vomiting, in terms of
dose and time to vomiting. So that much we do know. And then onto the
long-term effects. There's two that are
really important, is cancer risk and
birth defect risk. You won't tend to see this
happen, despite popular media. But you will see a lot
of bad stuff happen. These are extremely difficult
to wrap our heads around. And the reason for that is
the population size required in order to do a proper
study with proper statistics, and give confidence to
the saying, let's say, a dose-- in order to,
let's say, a dose of 1 milligray would have some
amount of excess risk, you'd need to expose
61.8 million people, plus a similarly sized control
to distinguish whether or not 0.1 milligray has an
additional amount of risk. So let's say for
gammas to whole body, what's 0.1 milligray in
terms of increased risk dose in sieverts-- sorry-- 1 milligray? 1 millisievert. Tissue factor is 1, gamma
radiation quality factor is 1, that's 1 millisievert. That's 20 years of exposure--
or 20 years of allowed exposure at the same time. Or 10 years of exposure
at the same time, where 100 microsievert exposure
at once has been said to say, maybe that's the onset of
detectable amount of damage. Pretty difficult, and our
sources of data for these doses are a lot smaller-- with the exception of
very high irradiations than we need to make
any real conclusions. The largest sample size
we have besides smokers would be atomic bomb survivors. So folks have followed all of
the survivors of the Hiroshima and Nagasaki bombings. Not just the people nearby, but
in the surrounding countryside. And tried to follow, how many
excess cancers were there as a result of the radiation? For anyone exposed within 3
kilometers for less than 5 milligray, you can attribute,
basically, either one or none. So by following
this group of people and finding out how many of them
got cancer compared to control groups, you can
try and figure out, how much extra cancer
was due to radiation? And to graph this-- this
is actually in the-- I think the ICRP
publication, graphing the amount of relative
risk, or to use the words from the last studies
we saw, the Odds Ratio-- the OR-- of getting
cancer, an odds ratio of 1 means exactly the same
amount of risk with versus without the radiation. And the actual raw data
points are plotted here. And there's a couple of
lines drawn through here. And this is the source of
a lot of the controversy behind radiation
damaged nowadays. The black line is the LNT, or
the Linear No-Threshold model, which is a hypothesis that
says every amount of radiation is bad, and it is
linear with dose. I, for one, don't
believe this model. This is, to me, a
fear-based model. It's certainly easy to
make policy based on this, because you can-- I think your average congressman
can understand a linear graph. Not sure whether
they could understand p-values and statistics. But they're-- they
don't have to. It's what they ask
scientists to testify about. When you look at
the actual data, there's this kind
of funky shaped line along with plus or minus
1 sigma error bars. It doesn't really show a
linear threshold, does it? It actually looks like
it might be super linear for very small doses. And then it tails off, and
then it picks up again. But this right here is a
zoom-in of this data rich area of the graph. It actually looks like
for really high doses, it might be a little
super linear again, where things get
much, much worse. Hopefully you don't have
anyone exposed to, let's say, 2 gray of dose, but the
real controversy is here, in the small dose region. We don't really know enough to
say whether very small doses are hurtful or not-- or harmful or not. In fact, they might
even be helpful. So you guys, I think, were
the first class that I-- no-- I had you last year-- no. You guys remember
the answer to what is the idea that a
little bit of radiation might be good for you? From the cash class? Anyone remember
what that's called? AUDIENCE: Hormesis? MICHAEL SHORT: Hormesis, yeah. This idea that a little
bit of something bad could actually be good for you. This is also a theory,
and to my knowledge, has not been proven to be true. But it is evident in
some other studies, along with different fields
of research beyond radiation. For example, there
had been an experiment where rats were kept
in shielded lead boxes as opposed to just
out on the bench where they got less radiation. And the rats that
had less radiation had less incidence of cancer. However, it's
extremely difficult to remove all other confounding
variables from this data. And that's the trick there,
is when trying to tease out, are small amounts of
radiation bad for you? You also have to tease
out confounding variables or other things that might
be obscuring your data. Why the hormetic effect? So what are some of
the ideas behind why hormesis might happen? So there are some theories,
and some controlled studies showing that if you
irradiate cells very lightly, they mount an immune response. There are proteins
and things circulating throughout your cells that
are there to repair DNA. And if you stimulate the
production of those repair mechanisms, then the repair
will be more rapid given the same amount of stimulus. So in this case there are-- let's see-- I'm just
going to say proteins-- I can't say anything more-- that will actually
travel along DNA, looking for certain
types of kinks or breaks and repair them. If those repairs happen
before cell division, then the mutation is avoided. If you have more of
those repair mechanisms, it takes a little bit
more energy to make them, but you also have
less of a chance of a mutation manifesting
itself past division number one. So this is kind at the
cellular level idea why might hormesis
be true, because you stimulate your body's
ability to defend against this kind of stuff. And so there you go. Cells can actually
signal each other. So let's say a cell undergoes
DNA damage and can't divide. These cells can
actually send what they call kill signals
in the intercelluar space to the nearby cells,
stimulating them to mount some sort of response. Either release
something or divide more to make up for the dead
cells, which could be good or which could be bad. If you make more of these
DNA repair mechanisms, that's probably a good thing. If you stimulate
the nearby cells to divide faster, well what are the
two things that could happen? Yeah? AUDIENCE: More mutations. MICHAEL SHORT: Why do
you say more mutations? AUDIENCE: Well, I
mean, If you have cells that were in a radiation
environment, that are exposed to that radiation
you're dividing faster, each division has a
certain chance of mutation. More divisions overall means
more mutations [INAUDIBLE] MICHAEL SHORT: Exactly, yeah. If there are cells nearby that
have been exposed or mutated and you induce
faster division, you may induce faster
incidence of the-- what is it-- of manifestation
of this mutation. But also, if-- let's
say, a few cells die and the other ones
divide to make up-- take up the slack, that
might be a good thing. This is a normal way
that you repair injury, is upon cell death, the
cells nearby divide faster, fill in the gaps, and try
and repair the tissue. So it's both a good thing
and can be a bad thing, depending on what the nearby
cells have been exposed to. And so there's also this-- they
call that the bystander effect, where, interestingly, you
can have biological effects in cells that receive no
radiation exposure if they're near cells that have
received radiation exposure. There are some awesome
experiments showing this. We had one here, back when
we had a professor that did medical physics. She had created an
accelerator with a microbeam, like a micron-wide
proton beam, when you could irradiate single
cells and watch what happens to the cells nearby. So to study in a controlled
way, this bystander effect. So if you irradiate one
cell on a glass slide, how do the other ones respond? So you know which
one was irradiated and you can watch what
happens to the other ones-- pretty slick. That accelerator,
actually, parts of that live on the DANTE
proton accelerator that we now use for
physics and things. But a lot of the parts from
those machines are still here, just the microbeams and
the cell parts aren't. And then I highlighted
a few of these passages in sort of the DNA
damage bystander effect. One of the reasons is
when cells nearby divide, they scale up their metabolism. They have to burn
more energy in order to undergo division faster. And that can undergo what's
called oxidative metabolism. Cells can produce energy
aerobically or anaerobically. When you're dividing very
quickly, all of a sudden, you start burning more
oxygen to divide faster, to do whatever you have to do. And that oxidative metabolism
also creates free radicals just from normal wear and
tear to your cells. And those oxidative
byproducts may also induce mutations in
the same primary way that radiation does. Radiation does hydrolysis,
makes oxidative species that damage DNA. Chemical oxidative metabolism
can produce the same sorts of things that can damage
DNA in the same way, just a different initial effect. I'm going to stop here,
even though we only have a few slides to go,
because it's exactly five of.
