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  • 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.

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33.放射線の長期的な生物学的影響、統計、放射線リスク (33. Long-Term Biological Effects of Radiation, Statistics, Radiation Risk)

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    林宜悉 に公開 2021 年 01 月 14 日
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