Speaker 1: On her second day of life, Kimberly Cowley had congestive
Speaker 1: heart failure. Considering the vast array of health issues she
Speaker 1: had been born with hearing in vision loss, a rare
Speaker 1: condition known as tetrology of fullow caused by a combination
Speaker 1: of four heart defects, any one of which is a killer.
Speaker 1: Expectations of survival were low. Against all odds, Kimberly survived,
Speaker 1: but the road has been long and often painful. Born
Speaker 1: in Hamilton, Canada, in nineteen sixty four, Kimberly spent the
Speaker 1: first two months of her life in the hospital. Her
Speaker 1: parents were young and shortly after marriage. Her mother became sick.
Speaker 1: She thought it might be a bout of flu, and
Speaker 1: then once she learned she was pregnant, she thought maybe
Speaker 1: that was why she felt unwell. It was neither. Her
Speaker 1: mother later learned that it had been rubella, having come
Speaker 1: into contact with an infected relative in her first trimester
Speaker 1: in nineteen sixty four. The rubella vaccine was still five
Speaker 1: years away from being available when Kimberly was diagnosed with
Speaker 1: congestive heart failure. That second day in the hospital, her
Speaker 1: parents realized the problems were much bigger than they had thought.
Speaker 1: Those first two months were a whirlwind of tests. All
Speaker 1: Kimberly's parents were told was that they would have to
Speaker 1: wait until later in life to see how this translated
Speaker 1: in reality. Like most children, Kimberly started school at age five,
Speaker 1: but in all other ways, she was profoundly different from
Speaker 1: the other kids in her class. Physically, she was the
Speaker 1: size of a small three year old, and school was
Speaker 1: an immense challenge. Given no special tools, Kimberly was expected
Speaker 1: to learn at the same rate as her classmates while
Speaker 1: missing most of two of her senses. After eight hours
Speaker 1: of concentrating to hear, see, and keep up, she craved
Speaker 1: silence and to be left alone, meaning after school friends
Speaker 1: were few and far between, often lonely. She grew up
Speaker 1: being bullied and picked on for her differences. Kimberly's parents
Speaker 1: were at a loss, not knowing what to do or
Speaker 1: how to cope. I needed advocates, and they just weren't.
Speaker 1: She said. My mother had been a bully at school
Speaker 1: herself and continued that behavior with me. She was unable
Speaker 1: to relate to my disability. It was hard to get
Speaker 1: close to my father or brothers too, because they didn't
Speaker 1: try to get close to me. Things became much worse
Speaker 1: emotionally for eleven year old Kimberly. When she was scheduled
Speaker 1: to have heart surgery. Her classmates taunted her, telling her
Speaker 1: she was going to die. One parent was allowed to
Speaker 1: go into the operating room with Kimberly while anesthesia was
Speaker 1: being administered, but neither of her parents chose to provide
Speaker 1: this comfort. She went in alone. When she woke up,
Speaker 1: she smiled despite the incredible pain, knowing she was alive,
Speaker 1: proving her schoolmates and the unfeeling world around her wrong.
Speaker 1: Her surgeon called her a wilful, stubborn survivor. These days,
Speaker 1: Kimberly lives quietly. She has worked in the past, but
Speaker 1: seldom full time. She exercises daily or risks losing her mobility,
Speaker 1: and is a passionate archer. When she ventures out of
Speaker 1: her home, it's an exercise and extreme concentration. Kimberly uses
Speaker 1: a long cane to help her get around. Her life
Speaker 1: is also about tools. Her laptop has magnification, her Kindle
Speaker 1: reader is on the second largest font, and she paints
Speaker 1: her nails with a magnifying glass clipped to her glasses.
Speaker 1: You get used to being stared at Kimberly said, the
Speaker 1: only difference between now and when I was a child
Speaker 1: is that now I don't care. I just smile. I
Speaker 1: like who I am and how far I have come.
Speaker 1: I'm looking forward to the next adventures in my life.
Speaker 1: She said, I'm a vaccination crusader. If I can save
Speaker 1: just one life by telling, teaching, and pushing for vaccination,
Speaker 1: that I know it's all been worth it.
Speaker 2: Oh, Aaron, that got me, I know, I know.
Speaker 1: It's a Yeah. That firsthand was from Kimberly Cowley and
Speaker 1: I found it on a website called Measlesubella Initiative dot
Speaker 1: org and I will post a link to the full account.
Speaker 1: So that was excerpts. And also, according to this website,
Speaker 1: Kimberly is working on a book, so that would be
Speaker 1: awesome to check out. Yeah, yeah, Hi, I'm Aaron Welsh.
Speaker 2: And I'm Erin Alman Update and.
Speaker 1: This is this podcast will kill you Today.
Speaker 2: I'm already crying. It's gonna be a great episode.
Speaker 1: Setting the stage, setting the tone for this episode today. Yeah, yes,
Speaker 1: today we are covering rubella also known as German measles,
Speaker 1: although I don't know how many people still call it
Speaker 1: that nowadays.
Speaker 2: In like textbooks. I feel like you still hear it.
Speaker 1: Yeah, yeah, well, we'll be mostly calling it rubella Rubella,
Speaker 1: that's what it's called. Yeah ah well, I guess to
Speaker 1: start us off, it's quarantiny time.
Speaker 2: It's definitely definitely quarantiny time.
Speaker 1: What are we drinking this week?
Speaker 2: We're drinking choo rubella.
Speaker 1: Very well done, air, thank you? And what is in
Speaker 1: the chow Rebella? I don't know, Okay, I can tell
Speaker 1: you gin cherry juice, grenadine, a splash of soda water,
Speaker 1: and also a fancy liqueur that's like a raspberry liqueur
Speaker 1: called chambourd Chambard. Yeah, I liked the bottle was really pretty.
Speaker 2: A very ruby rubella drink. I feel like that's appropriate
Speaker 2: Ruby Rebella.
Speaker 1: Yeah exactly. We will post the full recipe to the
Speaker 1: chow Rebella on our website. This podcast will kill you
Speaker 1: dot Com as well as all of our social media channels,
Speaker 1: and that is also where you will be able to
Speaker 1: find the non alcoholic Placybrita.
Speaker 2: Oh yeah, we got you covered.
Speaker 1: We got you all right? Is there some there's some business?
Speaker 1: I guess we should run down the list of usual
Speaker 1: suspects before we dive in.
Speaker 2: For example, we have incredible merch for sale on our
Speaker 2: website This podcast will kill You dot com. Just click
Speaker 2: on merch you can find it. We have incredible offerings
Speaker 2: by the artists Abigail Irvin Penner as well as Hollysullivan.
Speaker 2: Really truly, I just got some of the Holly Sullivan's
Speaker 2: Framed Prince and I am obsessed with them. They're so cute,
Speaker 2: my gosh.
Speaker 1: And there are stickers of both which like, if you're
Speaker 1: running out of wall space for pictures, which I definitely am, you.
Speaker 2: Have water bottle space.
Speaker 1: We also have a good Reads list if you want
Speaker 1: to read more on any of the subjects that we
Speaker 1: talk about, in addition to a bookshop affiliate account, and
Speaker 1: when we post the references to all of these episodes,
Speaker 1: we will also post links, when available, to the books
Speaker 1: that we mentioned on the podcast.
Speaker 2: Yep is that all of our business?
Speaker 1: I think that's it. Okay, let's dive in.
Speaker 2: Let's this is going to be a big fun not fun,
Speaker 2: a big episode.
Speaker 1: It's going to be a big one. It's going to
Speaker 1: be very interesting. There's a lot I feel like to
Speaker 1: uncover that I had no idea about before diving in.
Speaker 2: Oh, I can't wait to hear the history. But we'll
Speaker 2: start where we always do, with the biology right after
Speaker 2: this break. Obviously, we have two major points to talk
Speaker 2: about today in the biology, and that is rubella infection
Speaker 2: like in children and adults, and of course congenital rubella syndrome,
Speaker 2: which I think most people listening probably know already. The
Speaker 2: major complication of rubella infection is the effects that it
Speaker 2: can have on a fetus if someone is infected during pregnancy,
Speaker 2: especially and specifically early in pregnancy. When we did our
Speaker 2: Triple E episode Eastern equine encephalitis like back in season three,
Speaker 2: I said during that episode that rubella was another and
Speaker 2: one of the only non arthropod born alpha viruses in
Speaker 2: the family Togaviridae. But apparently in twenty eighteen that was
Speaker 2: changed and Rubella was reclassified. So it's not really anymore
Speaker 2: a toga virus. It's in its whole own family called Motonaviridae,
Speaker 2: in the genus Rubavirus. Huh okay, I know. So this
Speaker 2: is a self correction, because nobody has corrected me on
Speaker 2: that yet. I'm shocked. In any case, we are talking
Speaker 2: today about a virus. It is a single stranded positive
Speaker 2: RNA virus. Unlike a lot of other RNA viruses that
Speaker 2: we've talked about, it's pretty stable antigenically, so that's a
Speaker 2: large part of why we have a pretty effective vaccine spoilers. So,
Speaker 2: in general, Rubella virus is transmitted via aerosols, much like measles,
Speaker 2: which I feel like rubella and measles often go hand
Speaker 2: in hand in terms of our conversations, even though they're
Speaker 2: really not that similar. But in this case Rubella, it's
Speaker 2: really large particle aerosols, so it doesn't linger in the
Speaker 2: air the way that measles does.
Speaker 1: Okay, So that explains the lower are not.
Speaker 2: Exactly right. So it is a respiratory virus, and like
Speaker 2: every virus on the planet, it has to infect a
Speaker 2: cell in order to replicate. In the case of rubella,
Speaker 2: it generally first infects the cells of our respiratory tract
Speaker 2: and then the lymph tissue, which it's very easy to
Speaker 2: access from like our nose and nasal passages, but very
Speaker 2: very quickly. Within five to seven days after exposure, Rubella
Speaker 2: is able to disseminate throughout our blood stream, so it
Speaker 2: causes a viremia, meaning you can detect virus in our
Speaker 2: blood if you took a sample, and it leads to
Speaker 2: a pretty widespread systemic infection. What that means is that,
Speaker 2: unlike some other viruses and pathogens that we've discussed, rubella
Speaker 2: has a very wide tropism, meaning it can infect a
Speaker 2: huge range of our cell types, not just a few
Speaker 2: types of cells.
Speaker 1: That's very interesting.
Speaker 2: It really is. We don't still know exactly what receptor
Speaker 2: it uses on our cells to gain entry into our cells,
Speaker 2: but we know that it must be something that's present
Speaker 2: on like almost every cell type, if that makes sense.
Speaker 1: So that makes me wonder about other species. So, like,
Speaker 1: I know that rubella is human specific, it is, but
Speaker 1: if it infects all like, what is it then about
Speaker 1: all of these human cells?
Speaker 2: Right?
Speaker 1: Makes it not able to infect other animals?
Speaker 2: Right? It's a really good question. So what is it
Speaker 2: using in our bodies to be able to infect almost
Speaker 2: all of our cells? But really just humans? I mean, experimentally,
Speaker 2: you can infect other animals. So it's not that it's
Speaker 2: impossible for other animals to become infected. It's just that
Speaker 2: in general, other animals, they're not good reservoirs. They're not
Speaker 2: like walking around in the world infected with Rubella virus.
Speaker 1: Ooh, so I wonder whether it's like just the transmission
Speaker 1: dynamics and like human behavior, and or maybe like it
Speaker 1: just doesn't cause disease the way that it doesn't. That's
Speaker 1: so interesting, so interesting.
Speaker 2: Right, yeah, I know it gets even more interesting, quite honestly,
Speaker 2: But keep that in mind, right, Like, this is a
Speaker 2: virus that can infect pretty much any cell type. Additionally,
Speaker 2: we know that, like many many viruses, at least part
Speaker 2: of the pathogenic effect of rubella is by directly killing cells. Essentially,
Speaker 2: so whind cells get infected with virus and the virus
Speaker 2: replicates inside those cells, that cell will undergo apoptosis, meaning
Speaker 2: that cell will die. So at least in part that
Speaker 2: is responsible for the damage. That means it's not just
Speaker 2: our immune reaction or our immune response that's causing the
Speaker 2: symptoms that we see. But we'll put a pin in
Speaker 2: that because that's not the whole story, and we'll move
Speaker 2: on to the symptoms at least in grown humans. I
Speaker 2: want to skip ahead. Okay, okay, in general, in children
Speaker 2: or adults who get infected, we are talking with Rebella
Speaker 2: about a very very mild self limited illness. If you
Speaker 2: have symptoms at all. In general, it starts with a rash,
Speaker 2: not a fever.
Speaker 1: Oh that's the other podcast.
Speaker 2: It's starting with a fever asterisk. Unless it starts with
Speaker 2: the rash, we there go perfect. So in the case
Speaker 2: of rebella, it generally starts with a rash. This rash
Speaker 2: is very similar actually to the one that we see
Speaker 2: with measles, which I think is a large part of
Speaker 2: why there's this overlap. It starts on the face. It
Speaker 2: generally spreads downwards towards the feet, encompassing almost your whole body.
Speaker 2: They're just the rash looks like small red spots, maybe
Speaker 2: with some bumps. But differences between the rubella rash and
Speaker 2: measles are that it spreads much more quickly, like within
Speaker 2: twenty four hours. It generally lasts only a couple of days,
Speaker 2: like two to three days, and the rash doesn't coalesque
Speaker 2: or darken the way that measles rashes tend to do.
Speaker 1: Okay, I also read somewhere it was tingly.
Speaker 2: Oh interesting. I took the cares that, oh, you can
Speaker 2: feel it tingling.
Speaker 1: That's ad tingly rash, I mean. Granted, this description was
Speaker 1: from the mid mid eighteen hundred so, like, you know, I.
Speaker 2: Wonder is that a description of how the rash feels
Speaker 2: or is it something about like is that how you
Speaker 2: describe rashes like a tingly rash versus a lacy rash?
Speaker 2: I don't know.
Speaker 1: I assumed it was it tingles, but well, because does
Speaker 1: does measles tingle? I can't remember, or does it like
Speaker 1: itch or burn?
Speaker 2: I don't think so.
Speaker 1: I didn't think so. So I thought that was one
Speaker 1: of the designating like interesting or differentiating characteristics.
Speaker 2: Really, yeah, really, I didn't read it. Doesn't mean it's
Speaker 2: not possible, but very differently from measles that rash is
Speaker 2: often it okay in terms of the symptoms of rubella
Speaker 2: if you have that at all, maybe you might also
Speaker 2: have a slight fever, maybe you might have some swollen
Speaker 2: lymph nodes, but really that's about it. It's a very
Speaker 2: mild illness. And again that's if you even have symptoms.
Speaker 2: The older that you are when you get infected, the
Speaker 2: more likely that you'll have symptoms beyond the rash. But
Speaker 2: kids are more likely to like have the rash for sure,
Speaker 2: like have any symptoms whatsoever. And if you have symptoms,
Speaker 2: number one is going to be the rash okay. In
Speaker 2: some cases you can have things like arthralgias or joint pain,
Speaker 2: which can last for several weeks, but it's really rare,
Speaker 2: and even more rare are severe manifestations like encephalitis the
Speaker 2: way that we do see with measles. We're talking though,
Speaker 2: like one to three per six thousand cases, so this
Speaker 2: is a very rare complication. But also other complications that
Speaker 2: you can get from a wide variety of viral and
Speaker 2: other infections, things like yon beret myocarditis, which is when
Speaker 2: the virus infects your heart, optic neuritis if it affects
Speaker 2: your eyes. These things are all possible, but they're not
Speaker 2: specific to rubella, and they're very very unlikely with a
Speaker 2: rubella infection specifically gotcha, but that's not the big story
Speaker 2: when it comes to rubella. The big story is congenital
Speaker 2: Rubella syndrome or CRS. This is what happens when a
Speaker 2: person gets infected with rubella, and usually this has to
Speaker 2: be a primary infection, so someone is being exposed and
Speaker 2: infected for the first time in their life while they
Speaker 2: are pregnant, specifically during the first trimester, which is the
Speaker 2: first twelve weeks of pregnancy. Now, if we remember back
Speaker 2: to our philidamide episode, when I talked about the embryologic
Speaker 2: period of development, the first like ten weeks or so,
Speaker 2: I talked a lot about how anything that has effects
Speaker 2: on a developing fetus during this period when it's an embrya,
Speaker 2: not even a fetus, has huge downstream developmental effects. Rubella
Speaker 2: is one of those infections that can infect a fetus,
Speaker 2: especially at this early early stage. Essentially, what happens is
Speaker 2: when a pregnant person gets infected with rubella. As we
Speaker 2: already talked about, that virus spreads really rapidly throughout our bodies,
Speaker 2: and one of the places that it spreads and can
Speaker 2: infect is the placenta in the place central tissue, and
Speaker 2: then it can travel through that placenta and go on
Speaker 2: to infect pretty much any cell in that developing embryo
Speaker 2: or fetus. Now, what exactly happens inside an infected fetus
Speaker 2: is still not entirely clear, which I think is fascinating.
Speaker 1: So yeah, I'm so surprised by.
Speaker 2: That, me too. But we do know some things, and
Speaker 2: they're really interesting. There's kind of three main ways that
Speaker 2: rubella has effects. We know that in grown humans. One
Speaker 2: of the main effects of rebella that causes symptoms is
Speaker 2: direct cell death, right, But in the case of the
Speaker 2: developing fetus, that doesn't seem to be a main mechanism
Speaker 2: by which damage is induced. Isn't that weird?
Speaker 1: I wonder does this have something to do with the
Speaker 1: fact that we still don't know the receptor and that
Speaker 1: like maybe I don't know, I mean it does is
Speaker 1: it cell death? Okay? So if rubella virus can infect
Speaker 1: all those different cells that we have, does it cause
Speaker 1: cell death in all of those cells or is it
Speaker 1: just a subset?
Speaker 2: Very good question. I don't know. And here's an on
Speaker 2: top of that. We think that at least part of
Speaker 2: the reason that a fetus is susceptible when it is,
Speaker 2: and part of why. So this is an interesting I
Speaker 2: was gonna say this later, but I'm going to say
Speaker 2: it now. If a baby is born with congenital rubella syndrome,
Speaker 2: they still harbor rubella virus for months, if not years,
Speaker 2: And so in a fetus and a newborn rubella is
Speaker 2: not an acute infection. It's a chronic infection. So it's
Speaker 2: acting very differently in a fetus than it is in
Speaker 2: a person. Yes, so how much does that have to
Speaker 2: do with the fact that the immune system is still
Speaker 2: under development? Gosh, who knows, right, Like, what are those
Speaker 2: mechanisms and what's the interaction with a you know, well
Speaker 2: developed immune system versus a fetal immune system. It gets complicated,
Speaker 2: but erin, it's about to get more complicated. So I
Speaker 2: have to keep going.
Speaker 1: Wait, but can I ask two questions before try.
Speaker 2: So?
Speaker 1: Okay? My first question is if it can infect all
Speaker 1: these different types of cells?
Speaker 2: Uh huh?
Speaker 1: Can it also be transmitted through means other than respiratory?
Speaker 1: Is respiratory just the primary way?
Speaker 2: Great question? And yes, yeah, so you can culture virus
Speaker 2: from a whole bunch of different bodily fluids poop pe
Speaker 2: i conjunctive fluid, even by scraping off the skin. Like
Speaker 2: the virus is in your skin, especially when you have
Speaker 2: a rash, it's actually in the rash and in non
Speaker 2: rashy skin. So the virus is definitely everywhere. It's in
Speaker 2: your blood, but it's at highest level in the respiratory tract.
Speaker 1: Okay, that makes sense. Yeah, And my other question is
Speaker 1: in later trimesters or later on in the pregnancy, if
Speaker 1: someone becomes infected, does the fetus have an immunity, like,
Speaker 1: are there any effects?
Speaker 2: Pause that question, Okay, I'll answer that.
Speaker 1: I'll address that.
Speaker 2: Thank you, We will get there erin, let's not jump
Speaker 2: our guns.
Speaker 1: Sorry, I got really excited.
Speaker 2: I know you did. So all I told you was
Speaker 2: what is not the main cause of the effects that
Speaker 2: we see in a developing fetus. I want to tell
Speaker 2: you what we think are okay, because we know something okay,
Speaker 2: and because it gets even weirder. Infection in the fetus
Speaker 2: results in decreased cell growth and division. So even if
Speaker 2: it's not killing cells directly, it's stopping cells from dividing.
Speaker 2: That's what a fetus does, divide cells. But I mean
Speaker 2: that what that means is that in a developing fetus
Speaker 2: you have a reduction in cell mass, and that can
Speaker 2: result in not enough cells recruited to shape embryologic parts
Speaker 2: the way that they should be developed.
Speaker 1: Okay, So that it's just a non it's almost a
Speaker 1: side effect of Like, there are so many downstream effects
Speaker 1: from a rebella infection that's not just oh, the rebella
Speaker 1: virus targets those.
Speaker 2: Cells, and there's more talk about downstream effects another cell type.
Speaker 2: Even though we know that rebella can infect a lot
Speaker 2: of different cells. One of the big problems is when
Speaker 2: rubella in a developing fetus infects the endothelial cells of
Speaker 2: the blood vessels. Those are the cells that line blood vessels.
Speaker 2: We end up talking about those a lot on this podcast.
Speaker 2: Interesting infection of those cells causes damage to fetal blood vessels,
Speaker 2: which can downstream cause damage enough that they cause ischemia
Speaker 2: or tissue death in organs that are supplied by those
Speaker 2: blood vessels. So you can have downstream effects of damage
Speaker 2: to organs because of damage to these blood vessels in
Speaker 2: the fetus.
Speaker 1: Okay, I have a question. Okay, does the timing of
Speaker 1: infection during the first trimester matter or is it just
Speaker 1: sort of any time.
Speaker 2: Absolutely, the timing matters. So the timing matt The timing
Speaker 2: is everything in terms of the effects that you see,
Speaker 2: in terms of the severity everything. So there's a lot
Speaker 2: of details in a lot of the papers that I
Speaker 2: will post in terms of like the exact number of
Speaker 2: weeks for when you have this effect versus that effect.
Speaker 2: But in general, it goes like this infection within the
Speaker 2: first twelve weeks almost always is going to result in
Speaker 2: infection of the fetus. So infection of a pregnant person
Speaker 2: during the first twelve weeks of pregnancy for the first
Speaker 2: time with Rebella is going to end up infecting the fetus.
Speaker 2: In those first twelve weeks. Almost all of those infections,
Speaker 2: or a large proportion of those infections, are going to
Speaker 2: result in some kind of fetal malformation or problem down
Speaker 2: the line after like sixteen eighteen weeks especially. It's not
Speaker 2: that infection doesn't occur, it just doesn't have those long,
Speaker 2: long term effects or downstream effects. And this is really weird.
Speaker 2: There's like a period of time in the second trimester
Speaker 2: where infection itself tends to be like lowest, and then
Speaker 2: in the third trimester the fetus could become infected, but
Speaker 2: the most that you might see would be like some
Speaker 2: growth restriction. Okay, but at almost any point in pregnancy
Speaker 2: a fetus could become infected. It's just that only in
Speaker 2: that early period of time are you going to see
Speaker 2: the effects. So let's talk a little bit more specifically
Speaker 2: about what you see, because then we can talk about
Speaker 2: even more specifically about the timing. Okay, So, because this
Speaker 2: is a virus that can affect almost every cell, really
Speaker 2: almost any part can be affected almost any organ really everything,
Speaker 2: but classically there are kind of three large scale ways
Speaker 2: in which congenital Rubella syndrome can affect an infant born
Speaker 2: with it. One is with transient, kind of short lived
Speaker 2: manifestations that tend to happen if the viral load in
Speaker 2: that baby is very high at the time of birth,
Speaker 2: and we'll talk about what those look like. The second
Speaker 2: is with permanent manifestations, so that means something that happened
Speaker 2: during development that doesn't change, that affected the development of
Speaker 2: that fetus. And then finally there are and this actually
Speaker 2: blew my mind because I never learned this previously, there
Speaker 2: are late onset problems that can happen that are not
Speaker 2: detectable at the time of birth but become apparent later on.
Speaker 2: So we'll go through each of those. The transient ones,
Speaker 2: because this virus is infecting everywhere, they can be really
Speaker 2: wide ranging. An infant can be borne with jaundice, so
Speaker 2: that means kind of yellowed skin, which usually has to
Speaker 2: do with anemia or homolysis, so like red blood cells
Speaker 2: lycing within their body because of infection, hepatitis, so infection
Speaker 2: of the liver, enlargement of the liver, or spleen. A
Speaker 2: kind of classic description of a baby born with CRS
Speaker 2: includes a blueberry muffin rash, which means purple spots on
Speaker 2: the skin.
Speaker 1: Interesting.
Speaker 2: Yes, and this is actually caused by This is very interesting.
Speaker 2: It's caused by eruthropuesis, which is the process of making
Speaker 2: red blood cells in the skin because you have anemia
Speaker 2: elsewhere and infection of the bone marrow potentially, so basically
Speaker 2: the baby is not making enough red blood cells, so
Speaker 2: other organs are like recruited to help make blood cells
Speaker 2: and then you end up with this type of rash.
Speaker 1: WHOA.
Speaker 2: You could also have pneumonia, myocarditis, diarrhea, like a lot
Speaker 2: of different things can happen. These manifestations do tend to
Speaker 2: clear on their own. However, it comes with the caveat
Speaker 2: of these infants are very sick, and on top of that,
Speaker 2: you don't generally have only these transient manifestations. These babies
Speaker 2: are oftentimes born with things like growth restriction or other
Speaker 2: more permanent manifestations. So mortality in babies born with this
Speaker 2: type of congeneral rubella can be as high as thirty
Speaker 2: five percent in some cases.
Speaker 1: Oh my gosh, it's very sad.
Speaker 2: And I didn't even mention, but infection with rubella, especially
Speaker 2: super early on, can also cause pregnancy loss. But I
Speaker 2: have no idea what the proportion of that is because
Speaker 2: I was not able to find numbers on like the
Speaker 2: incidents of that compared to infection that results in these
Speaker 2: things that we can see in a baby that's born. Okay,
Speaker 2: so now we have these permanent manifestations, and that means
Speaker 2: that something went wrong during development. The most common consequence
Speaker 2: is deafness. This happens in like two thirds of babies
Speaker 2: born with congeneral rubella, and it can be of varying
Speaker 2: levels so complete to just mild hearing loss. You also
Speaker 2: can have neurologic complications, including developmental delays, a huge range
Speaker 2: of heart defects. The heart, aside from the ear, is
Speaker 2: like the most second most common organ involved. I think
Speaker 2: one half of babies born with congeneral rubella have some
Speaker 2: type of heart defect. And then the third most common
Speaker 2: is vision defects, which can be cataracts. Those are the
Speaker 2: most common. About a quarter of babies born with congeneral
Speaker 2: rubella have some degree of cataracts. But you can also
Speaker 2: have anopathy glaucoma, a whole number of vision problems. All
Speaker 2: of these happen either from problems during organogenesis, so the
Speaker 2: making of organs like your heart, or from tissue destruction
Speaker 2: and scarring like in the case of hearing loss and
Speaker 2: some brain damage that can occur. Okay, then we have
Speaker 2: the long term or delayed manifestations, and this is truly wild.
Speaker 2: These are things like type one diabetes, which occurs at
Speaker 2: anywhere from fifty to two hundred times, depending on the
Speaker 2: paper you read, the rate of the general population. What right,
Speaker 2: So babies born with congeneral rebella can go on to
Speaker 2: develop type one diabetes. Also thyroid dysfunction, a number of
Speaker 2: different like autoimmune related thyroid dysfunction, vascular problems. The most
Speaker 2: severe and most rare complication would be a pan encephalitis,
Speaker 2: so infection of the entirety of your brain, and that
Speaker 2: is often fatal. But these can occur years down the line.
Speaker 1: Why why why?
Speaker 2: Why? Yeah? But yeah, So your question earlier about the
Speaker 2: specific timing part of the reason. And I found this
Speaker 2: very interesting because I was trying to I was worried
Speaker 2: you were going to ask me a lot of real
Speaker 2: specifics about like how does cataracts occur? And how does okay?
Speaker 2: So I went down some rabbit holes to try and
Speaker 2: figure out, like what specific things are causing each of these,
Speaker 2: like the three most common effects that we see, which
Speaker 2: are deafness, heart defects, and cataracts or vision problems. And
Speaker 2: part of the reason that hearing loss is one of
Speaker 2: the most common effects is because, in contrast to some
Speaker 2: of the other more serious deficits, the effects that can
Speaker 2: produce hearing loss can happen later. The organ of in
Speaker 2: your ear is vulnerable to the effects of the virus
Speaker 2: up to the first sixteen weeks, whereas most of like
Speaker 2: the heart defects. The heart defects are uncommon after like
Speaker 2: eight weeks or so, and then cataracts are uncommon after
Speaker 2: like weeks nine to eleven, et cetera. So that's part
Speaker 2: of the reason why the ear tends to be affected
Speaker 2: the most out of all imporn with CRS. Interesting, the
Speaker 2: good news is there's a vaccine.
Speaker 1: There's a vaccine and.
Speaker 2: Erin I can't wait to hear about like the development
Speaker 2: and things like that. But it's a live attenuated vaccine.
Speaker 2: So it's a live strain of rubella virus that's been
Speaker 2: grown in a lab so that it doesn't cause infection.
Speaker 2: One dose produces immunity in ninety five percent of people
Speaker 2: that has been shown to last upwards of twenty one years,
Speaker 2: which is phenomenal.
Speaker 1: It's a good one.
Speaker 2: It's a very good one. So in general, that's the
Speaker 2: only good news that I have. So erin, what's up
Speaker 2: with this? Can you tell me about it? Like? Where
Speaker 2: did this virus come from? Why is it only in humans?
Speaker 2: How did we come up with a vaccine? And why
Speaker 2: isn't it gone yet? I don't know.
Speaker 1: My gosh, these are lots of questions, and I don't
Speaker 1: know if I'm going to be able to answer all
Speaker 1: of them, but I'll do the best that I can.
Speaker 1: Right after this break, So Aarin, you asked, where does
Speaker 1: this come from?
Speaker 2: Yeah, we don't really know. Why are you me or something?
Speaker 2: I know? I know?
Speaker 1: Okay, here's what I'm gonna do in the in the
Speaker 1: history section, just to sort of like prepare you for
Speaker 1: the fact that there's gonna be thousands of years of
Speaker 1: like me not talking about the history. I'm going to
Speaker 1: start with the evolutionary history and what we do know
Speaker 1: about it, Okay, and then basically I have to jump
Speaker 1: right to almost modern history. What because in terms of
Speaker 1: ancient history, Rubella was unlikely to be distinguished from the
Speaker 1: other relatively mild or often mild rash causing illnesses, right,
Speaker 1: I mean, as you describe, the symptoms aren't super specific.
Speaker 1: So unfortunately that means like no mentions of ancient Egyptian
Speaker 1: papyri or Hippocrates or whatever.
Speaker 2: Well, I'm done listening to that, just kidding.
Speaker 1: Okay, But as I mentioned, yeah, there seems to be
Speaker 1: this big question mark over the origins of the Rubella virus.
Speaker 1: I did read in one paper that looked at the
Speaker 1: molecular epidemial of Rubella viruses and the different Rubella virus
Speaker 1: genotypes across the Asian continent, and they said that, oh,
Speaker 1: it's thought to have originated there, like somewhere in Asia.
Speaker 2: Okay, all right.
Speaker 1: But then I found a paper that was published like
Speaker 1: super recently in Nature in October twenty twenty, so like, whoa,
Speaker 1: just a couple months ago, cool, just for us, And
Speaker 1: they reported the first known relatives of the Rubella virus,
Speaker 1: which they isolated from several different species of mammals. What
Speaker 1: this is interesting? So yeah, Ruhugu virus, which is most
Speaker 1: closely related to Rebella was found in a species of
Speaker 1: bat called the Cyclops leaf nose bats, which I believe
Speaker 1: were in Uganda, and they appeared otherwise healthy, And it
Speaker 1: was wasn't just like this isolated infection and one bat.
Speaker 1: It was found in around fifty percent of the individuals
Speaker 1: that they sampled. What yes, And they found the other virus,
Speaker 1: which they called rostrella virus in animals and a zoo
Speaker 1: in Germany that had gotten sick and eventually died from
Speaker 1: a severe acute neurological disease. What the animals were a donkey,
Speaker 1: a cappy bara, and a red necked wallaby.
Speaker 2: What sarin?
Speaker 1: I know, I know, I know. And so when they
Speaker 1: were searching for the cause of this these these deaths,
Speaker 1: they found Rostrella virus in the brain tissue of all
Speaker 1: three of these animals. And then they subsequently sampled other
Speaker 1: animals around the area to see if they could find
Speaker 1: the same thing, and they found this virus in about
Speaker 1: half of the yellow necked field mice that they tested.
Speaker 2: So they found these two like brand new viruses, and
Speaker 2: then they were like, where what are these And they
Speaker 2: figured out that closely related to rubella.
Speaker 1: Really closely related, so like if you look at their genomes,
Speaker 1: they're like very similar in terms of like coding regions
Speaker 1: and stuff and the arrangement of those what yeah, like.
Speaker 2: Did they come from rubella or did they come from
Speaker 2: a shared common ancestor? How old are these?
Speaker 1: Let me so, I don't know how old they are.
Speaker 1: Let me pull up the paper to see what sort
Speaker 1: of their the evolutionary implications or timeline or whatever if
Speaker 1: I'm reading this correctly, So all three of them came
Speaker 1: from a shared common ancestor, but Rustrella virus diverged before
Speaker 1: those two. Wow, so it went first Rustrella went off
Speaker 1: the tree, then Ruhugu, and then like Rubella split secondly. Yeah,
Speaker 1: I don't know about the timeline or anything. Ye maybe
Speaker 1: it was in the paper and I just missed it.
Speaker 1: But yeah, But basically, so from this paper there were
Speaker 1: a couple of take homes. One was that given the
Speaker 1: ability for these viruses, especially Rustrella, to infect a diversity
Speaker 1: of mammal species. And now I'm adding my own little
Speaker 1: thing about what we know about the Rubella virus to
Speaker 1: infect all different kinds of cell types, like that's yeah,
Speaker 1: the Rubella virus may have initially spilled over from wildlife
Speaker 1: into humans, and that this does raise some concerns for
Speaker 1: future zoonotics spillover events, although I do want to give
Speaker 1: a psa as we always do, to say that bats
Speaker 1: are not evil, and the more funds and effort we
Speaker 1: put into this type of research and bat conservation, the
Speaker 1: less likely spillover events are going to occur anyway. Okay,
Speaker 1: but the other really cool implication from this paper is
Speaker 1: that these new viruses give us the ability to do
Speaker 1: more comparative studies or to explore different animal models so
Speaker 1: that we can better understand things about why this virus
Speaker 1: has such wide ranging impacts on the body or on
Speaker 1: the fetus.
Speaker 2: And yeah, so, yeah, that's really fascinating.
Speaker 1: Yeah so now we need to launch ourselves quite a
Speaker 1: bit forward in time to around the eighteenth century.
Speaker 2: Wow. Yeah, yeah.
Speaker 1: The debate over whether or not these rashy illnesses were
Speaker 1: different diseases or just different forms of the same disease
Speaker 1: was still kind of like ongoing, although there had been
Speaker 1: some clarity reached regarding at least measles and scarlet fever
Speaker 1: being separate, and a handful of researchers had started talking
Speaker 1: about a third separate illness, one that they called rutilm
Speaker 1: I am going to be terrible pronouncing this, which is
Speaker 1: German for to reddin according to Google Translate. Throughout much
Speaker 1: of the eighteenth century and into the early nineteenth century,
Speaker 1: it was in fact to mostly German researchers who seemed
Speaker 1: interested in characterizing this new disease, hence the name by
Speaker 1: which it would be popularly known in many places outside
Speaker 1: of Germany. German measles again not a name that we
Speaker 1: still use. It is not, but it did. But it
Speaker 1: was very It was like much more heavily in use
Speaker 1: than ruten and bella.
Speaker 2: Yeah.
Speaker 1: Throughout the eighteen hundreds, there was growing acceptance that this
Speaker 1: disease was a separate like a truly separate entity from
Speaker 1: measles and scarlet fever. But even with all of this
Speaker 1: discussion and research and a description in the early eighteen
Speaker 1: hundreds that basically covers many of the key features of rubella,
Speaker 1: people in the medical science community remained a bit hesitant
Speaker 1: to accept that this was actually a separate disease. But
Speaker 1: finally the tides seemed to be turning when in eighteen
Speaker 1: sixty six, following continued epidemics and other smaller reports of
Speaker 1: the disease, a British Royal Artillery surgeon published an article
Speaker 1: describing a current outbreak of the disease known as routine
Speaker 1: rutiln in India. He closed out this article with a
Speaker 1: paragraph proposing a name change. Quote. The name of a
Speaker 1: disease is always a matter of some importance. It should
Speaker 1: be short for the sake of convenience and writing, and
Speaker 1: euphonious for ease and pronunciation. I agree with that part,
Speaker 1: but that's only because I'm terrible at pronouncing anything. To continue,
Speaker 1: it should, if possible, indicate a definite group of pathological conditions.
Speaker 1: Rutel is harsh and foreign to our ears. Rubiola notha
Speaker 1: and Rosalia idiopathica are too long and yet to be proved.
Speaker 1: I therefore propose rubella as a name for the disease.
Speaker 2: But also, that's just so English centric? Is that not
Speaker 2: that I can't pronounce German?
Speaker 1: So let's call it this thing that I'm going to
Speaker 1: make up entirely. Yeah, yes, but the name did catch on.
Speaker 1: People were like, yeah, sure, let's do it. Although the
Speaker 1: term German measles would stick around for much longer in
Speaker 1: many places to kind of an annoying degree because it
Speaker 1: caused a whole lot of confusion. It's not from Germany,
Speaker 1: and it's also not a type of measles, and at
Speaker 1: times it also caused anti German sentiment. For instance, in
Speaker 1: World War One, although it lagged behind other diseases such
Speaker 1: as influenza and typhus, rubella did do some damage. US
Speaker 1: Army hospitals admitted more than seventeen thousand soldiers for rubella,
Speaker 1: and rubella was the cause of over two hundred and
Speaker 1: eleven thousand days lost from duty. Wow, and the high
Speaker 1: prevalence of this disease led to lots of German measles
Speaker 1: jokes about Germany, and in World War Two the disease
Speaker 1: was nicknamed the liberty itch or victory measles like freedom
Speaker 1: fries and victim measles.
Speaker 2: Yeah, oh my god.
Speaker 1: Okay, for the next big development in rubella history, we
Speaker 1: have to jump ahead again, this time to the early
Speaker 1: twentieth century, around nineteen forty one. Far let's do a
Speaker 1: bit of context building here, my favorite thing to do
Speaker 1: in terms of infectious disease and medicine. So it's kind
Speaker 1: of hard to imagine just how much the field of
Speaker 1: medicine had changed in one hundred years from like eighteen
Speaker 1: forty one to nineteen forty one.
Speaker 2: I want a compilation of every time that you've said that.
Speaker 1: I know, I know, and I'm like, I feel self
Speaker 1: conscious saying it because I'm like, God, surely people are
Speaker 1: sick of hearing the same thing.
Speaker 2: I love it though.
Speaker 1: It helps me get into the mindset of like why,
Speaker 1: like why nineteen forty one was an important year? Why
Speaker 1: that year? Why things happen when they happen? And yeah, yeah, anyway, So,
Speaker 1: germ theory had a lot to do with advancing knowledge
Speaker 1: regarding some of the most common or prevalent diseases in
Speaker 1: that time, but medical technology, allowing for close observation and
Speaker 1: measurement of things previously only able to be described qualitatively,
Speaker 1: turned the art of medicine into a science. Definitely have
Speaker 1: said that before. Oh yeah, And a great deal of
Speaker 1: this change can be described by a single word specialization.
Speaker 1: The growing body of knowledge regarding human anatomy and disease
Speaker 1: processes and treatments made it possible for different highly specialized
Speaker 1: fields to develop. Okay, now, onto the infectious disease context.
Speaker 1: Germ theory had been around for decades, but the pace
Speaker 1: of discoveries in terms of uncovering new pathogens or new
Speaker 1: treatments or vaccines was still incredibly high. Around nineteen forty one,
Speaker 1: we had a smallpox vaccine, a call or a vaccine,
Speaker 1: a typhoid vaccine, and others, and we were more easily
Speaker 1: able to tell you, oh, this disease is likely caused
Speaker 1: by a bacterium versus a virus versus a parasite. Antibiotics
Speaker 1: were on the cusp of widespread use just a couple
Speaker 1: of years away, and as a result of our increased
Speaker 1: understanding of how different diseases were transmitted and improved sanitation infrastructure,
Speaker 1: the world was facing lower rates of death due to
Speaker 1: infectious disease than ever before, But of course there was
Speaker 1: still an incredibly long way to go. Things like tuberculosis
Speaker 1: and polio still sickened or killed many people, and it
Speaker 1: also made them terrified. So a potential vaccine or treatment
Speaker 1: for these feared diseases held a lot of promise and
Speaker 1: hope for people. But I think it's important to remember
Speaker 1: that not all diseases were as equally feared or like.
Speaker 1: The need for a vaccine for every disease was not
Speaker 1: as self evident as it may be is today.
Speaker 2: Yeah, which is it's very interesting, especially in the context
Speaker 2: of rubella exactly.
Speaker 1: So it was like you know when you are when
Speaker 1: you have tuberculosis or polio outside your door, like you
Speaker 1: don't have room or even reason to be scared of
Speaker 1: something as mild and routine like rubella, right, which is
Speaker 1: what it seemed at the time.
Speaker 2: Yeah.
Speaker 1: And so while epidemics of rubella were tracked and control
Speaker 1: attempts were made, and research on the causative agents still continued,
Speaker 1: it didn't really take front and center the way other
Speaker 1: things did. But that would change starting in nineteen forty one.
Speaker 1: Oh Australian pediatric ophthalmologist Norman McAllister greg there's your specialization, yep,
Speaker 1: had been he'd been practicing for close to twenty years
Speaker 1: when in nineteen forty and nineteen forty one he started
Speaker 1: to notice an unusual number of parents bringing in their
Speaker 1: babies with the same concerns unusual cataracts or eye infections
Speaker 1: or other rare eye disorders. And you know, he had
Speaker 1: been in the field for a while, and so he
Speaker 1: recognized that the rate of these conditions that he was
Speaker 1: seeing was uncommonly high, and he wondered whether there was
Speaker 1: some sort of link that was connecting them. And maybe
Speaker 1: it was unusual for the time, but he was the
Speaker 1: type of doctor that listened to their patients' concerns and
Speaker 1: to their hypotheses as to why their kid was sick
Speaker 1: and what had caused it. He exhibited patience and empathy,
Speaker 1: at least from what I've read about him. And one day,
Speaker 1: Greg which was HiT's his last name, But it's really
Speaker 1: just funny for me to be like Greg Greg. I
Speaker 1: see there are two g's here, but like Greg Greg.
Speaker 1: So one day Greg overheard a couple mothers of his patients,
Speaker 1: so children with rare cataracts, talking in the waiting room
Speaker 1: about what they thought had caused their child's poor eyesight.
Speaker 1: One of the mothers wondered out loud whether it could
Speaker 1: have been the rubella infection that she had early in
Speaker 1: her pregnancy, and the other mother also mentioned that she
Speaker 1: too had gotten sick with rubella while pregnant, and instead
Speaker 1: of immediately dismissing this as another superstition, which there were
Speaker 1: plenty of superstitions, as no doubt many other physicians would
Speaker 1: have done, he considered it a plausible idea, despite the
Speaker 1: fact that at that point the idea of an infectious
Speaker 1: disease affecting a fetus had not really been considered, much
Speaker 1: less explored fascinating Aaron, and so he asked around to
Speaker 1: other colleagues whether they had seen similar cataracts in babies
Speaker 1: or young children, and if they said yes, he reached
Speaker 1: out to the parents of those children to ask whether
Speaker 1: the mother had experienced a rubella infection during pregnancy. And
Speaker 1: what he was finding was that a substantial proportion of
Speaker 1: those women said yes, a proportion that was at least
Speaker 1: great enough for him to spanned his efforts and conduct
Speaker 1: an actual, official, planned study into this phenomenon. Wow. And
Speaker 1: through this additional research, he found that a rubella infection
Speaker 1: during pregnancy, especially early on in pregnancy, was associated with
Speaker 1: a suite of eye problems, but that it wasn't limited
Speaker 1: to just the eyes. There was there also seemed to
Speaker 1: be cardiac involvement in some of the children. In nineteen
Speaker 1: forty one, he compiled his findings into a report that
Speaker 1: he presented at the October meeting of the Ophthalmological Society
Speaker 1: of Australia. Some Australian newspapers also happened to pick up
Speaker 1: this story, and Greg found himself the recipient of tons
Speaker 1: of phone calls from people who had been infected with
Speaker 1: rubella during pregnancy and their child had either sight or
Speaker 1: hearing or heart or developmental issues, and so public and
Speaker 1: scientific interest in this possible link between rubella infection during
Speaker 1: pregnancy and congenital defects grew, and the bigger picture of
Speaker 1: congenital rubella syndrome took shape, Although that term wouldn't be
Speaker 1: really used until the nineteen sixties. Rubella has been likely
Speaker 1: infecting humans for thousands of years, and so I think
Speaker 1: it's natural to ask the question, why did it take
Speaker 1: until nineteen forty one for people to make the connection
Speaker 1: between a rubella infection during pregnancy and congenital abnormalities? What
Speaker 1: was so special about that year or about doctor greg.
Speaker 1: I set up some of the historical context earlier, especially
Speaker 1: the role that specialization in medicine likely played, but there's
Speaker 1: more to the story. First, Norman greg was notable in
Speaker 1: that he listened to the mothers in his office and
Speaker 1: pursued ly that others may have dismissed due to the
Speaker 1: fact that a nothing like it had been observed before,
Speaker 1: and b it was originally put forth by women. Most
Speaker 1: of whom weren't medically trained in any way or even
Speaker 1: maybe had received formal education. In his writings and interview
Speaker 1: use Greg acknowledged the contribution of these mothers, whose strong
Speaker 1: interest in their child made them observant and willing to
Speaker 1: recount any information that might be relevant. In addition, Greg
Speaker 1: was not just a pediatric ophthalmologist, whose specialization meant he
Speaker 1: saw a ton of patients from a wide geographic area.
Speaker 1: He was also a university researcher, meaning he could he
Speaker 1: could undertake an epidemiological study and do some stats to
Speaker 1: see whether his research questions were answered and if so,
Speaker 1: what those answers were. And the other notable thing, not
Speaker 1: necessarily about Greg, but about the time period, was that
Speaker 1: World War II was underway and the assembly and movement
Speaker 1: of troops led to widespread Rubella epidemics, not just in
Speaker 1: Australia but across the globe as well. And those rubella
Speaker 1: epidemics in the military, of course, spilled over into the
Speaker 1: broader public, and so the increase in the frequency of
Speaker 1: those unusual cataracts he was seeing was likely the result
Speaker 1: of those Rubella epidemics.
Speaker 2: Yeah, that makes sense, whoa eric.
Speaker 1: I know, it's interesting. I just like to put myself
Speaker 1: in the shoes of like, you know, why why then
Speaker 1: why this person? Yeah, you know, it's cool to think about.
Speaker 2: Yeah. I think the whole epidemics thing about rubella is
Speaker 2: very interesting too, because it's definitely like majority of disease
Speaker 2: of childhood, but in all populations there before vaccines, there
Speaker 2: was going to be some proportion of people of child
Speaker 2: bearing age who are still susceptible. So then what causes
Speaker 2: an outbreak in kids versus in adults versus in people
Speaker 2: who are pregnant, Like, it's just so interesting to think
Speaker 2: about all of the different factors that would have had
Speaker 2: to combine to lead to these not just rubella, but
Speaker 2: congenital rubella outbreaks. Like, ugh, it's very.
Speaker 1: Interesting, right, especially at a time when you know, I
Speaker 1: think the other really key thing is that rebella at
Speaker 1: least then, like people knew it was a virus, but
Speaker 1: they didn't know which virus, and diagnosis based on like
Speaker 1: clinical presentation was iffy. A lot of the times. It
Speaker 1: was usually a process of elimination. Have you gotten measles before?
Speaker 1: Have you gotten scarlet fever? Before? Yes? Okay, this is
Speaker 1: probably Rebella's reubella.
Speaker 2: Well, and on top of that, there's such a high rate,
Speaker 2: especially in adults of no symptoms whatsoever, like a completely
Speaker 2: asymptomatic infection. It's like, right, yeah, it's it's about fifty
Speaker 2: percent in kids that are okay asymptomatic, and in adults
Speaker 2: it can be as high as like six or seven
Speaker 2: to one, So a really high rate. So the fact
Speaker 2: that he was able to like find statistical significance in
Speaker 2: his samples of like asking people, hey, did you get
Speaker 2: rubella when you were pregnant or whatever, like that's oh man.
Speaker 1: Yeah, it's it's amazing to think about if it is.
Speaker 1: But what did the rest of the world think of
Speaker 1: Greg's hypothesis.
Speaker 2: Craig, I don't know. Well.
Speaker 1: While researchers and clinicians in Australia were pretty quick to
Speaker 1: accept doctor Greg's findings as fact and start informing people
Speaker 1: about the dangers of rebella infection during pregnancy, the rest
Speaker 1: of the world wasn't so keen or so quick to
Speaker 1: believe him or his research, which does have some merit.
Speaker 1: Greg's datus had only included children with congenital defects. The
Speaker 1: methodology behind how he collected the data was unclear, and
Speaker 1: there was still some doubt that rebella could be reliably
Speaker 1: distinguished from measles and scarlet fever, and his critics argued
Speaker 1: that Greg's findings were suggestive of a link, but not conclusive. Okay,
Speaker 1: but I think it's also interesting that scientifically, the idea
Speaker 1: that compounds or pathogens could cross the placenta was not new.
Speaker 1: It was something that embryologists and pathologists had known for
Speaker 1: probably at least a few decades, but most clinicians at
Speaker 1: the time probably didn't receive training or specific education in
Speaker 1: embryology the way they do now. And still nothing like
Speaker 1: this had ever really been observed before in humans in
Speaker 1: terms of a virus, and so this got some people
Speaker 1: thinking that viruses represented this whole new realm to be
Speaker 1: feared in terms of negative effects during pregnancy. Huh so anyway,
Speaker 1: but despite this initial doubt, the link became more accepted
Speaker 1: as clinicians did their own tracking of patients or patient
Speaker 1: case histories in places like North America and Europe, and
Speaker 1: data supporting the link just seemed to grow and grow
Speaker 1: and grow, and the boundaries of congenital Rubella syndrome also
Speaker 1: seemed to be like you know, grow as well or
Speaker 1: expand as well, and from there it trickled out into
Speaker 1: the public. For some people who had had a child
Speaker 1: with congenital rubella syndrome, it was a relief to know
Speaker 1: why that had happened, to have some sort of an answer,
Speaker 1: because it relieve some of the anxiety or worry they
Speaker 1: may have carried in terms of deciding whether to have
Speaker 1: another child, or may have relieved some of the guilt
Speaker 1: that they may have carried with them. With the dangers
Speaker 1: of rubella uncovered and yet no vaccine for its prevention,
Speaker 1: doctors considered what to do to minimize the risk of
Speaker 1: infection in pregnant people. Stop epidemics in their tracks, inform
Speaker 1: the public of the risks of this virus, which had
Speaker 1: previously been thought to be minimal. Prophylaxis really seemed like
Speaker 1: the only way to actually ensure the safety to pregnant people.
Speaker 1: Others recommended that people should try to become infected while
Speaker 1: young to gain lifelong immunity, like you know, rubella parties
Speaker 1: like those were actually a thing, although others strongly recommended
Speaker 1: against that, considering like there could be severe consequences of infection,
Speaker 1: like why invite a pathogen when there could be something
Speaker 1: that you don't know happens until there was a vaccine.
Speaker 1: There was also the recognition that rubella and thus congenital
Speaker 1: rubella syndrome was not entirely unavoidable, and some of the advice,
Speaker 1: like keep away from small kids was completely impractical for
Speaker 1: some mothers who maybe already had a couple of school
Speaker 1: age and kids. Yeah, that was like, yeah, what are
Speaker 1: the supposed to do, like live in a hotel for
Speaker 1: nine months?
Speaker 2: Oh? That's like, well, I just this is a little
Speaker 2: bit off topic. But like after a c section, you're
Speaker 2: not supposed to like lift over twenty pounds, So if
Speaker 2: you have a toddler, it's like, well, what if you
Speaker 2: can't touch them? Yeah, but it's yeah, oh dear, Yeah.
Speaker 1: And so recognizing this in the popular media, the headlines
Speaker 1: shifted towards a concern that the continued epidemics of rubella
Speaker 1: would lead to what was framed as an enormous social
Speaker 1: problem where an institutions or long term care facilities would
Speaker 1: be overwhelmed and families would be hugely stressed. This time,
Speaker 1: the prevailing view in the US was that children with
Speaker 1: CRS were seen as tragedies and the parents and families
Speaker 1: of those children as the victims of those tragedies. Now,
Speaker 1: of course, our society has evolved a bit in empathy,
Speaker 1: but this framing wasn't just because of a lack of
Speaker 1: empathy back then. It was also because during that time
Speaker 1: period we lacked the knowledge and resources to adequately care
Speaker 1: for people who were differently abled. Often the solution was institutionalization,
Speaker 1: which was a huge financial strain, and public schools weren't
Speaker 1: equipped also to provide additional resources that that's going to
Speaker 1: make education possible for children with congenital rebella syndrome.
Speaker 2: Yeah, and especially when you think about deafness and hearing loss,
Speaker 2: that often wasn't able to be diagnosed until much later
Speaker 2: in life, which is still the case in some parts
Speaker 2: of the world, which is hugely detrimental to learning about.
Speaker 2: Whereas now, if you're able to identify it early on,
Speaker 2: you can already get you know, things in place to
Speaker 2: be able to help that child with what they need.
Speaker 2: So that's that's huge for sure, yep.
Speaker 1: And all of these things also were compounded by the
Speaker 1: social stigma and shame that was associated with having a
Speaker 1: child with congenital defects. Why didn't you take better care
Speaker 1: of yourself during pregnancy, like all of these accusational you know,
Speaker 1: questions of like pointing fingers and assigning blame to people
Speaker 1: who like it's blame the mothers to mothers primarily Yes, yeah,
Speaker 1: and you know, the emotional turmoil would have affected everyone
Speaker 1: in the family. And of course, what parent doesn't want
Speaker 1: the best for their child, for their child to be
Speaker 1: healthy and to have no limits on what they can
Speaker 1: do and achieve. The media attention on congenital rubella syndrome
Speaker 1: reached new heights in the early nineteen sixties when an
Speaker 1: enormous rubella epidemic was underway in the US. But although
Speaker 1: it was like quite a sizable epidemic, this was not
Speaker 1: the first rubella epidemic in decades. In nineteen fifty eight,
Speaker 1: for example, there was another rebella epidemic across the US,
Speaker 1: but it didn't make nearly as many headlines. So let's
Speaker 1: consider why this early nineteen sixties rebella epidemic might have
Speaker 1: caused such alarm.
Speaker 2: I can take some guesses.
Speaker 1: Yes, if you've listened to the podcast before, there are
Speaker 1: two possible reasons you could guess right away. Number one
Speaker 1: was polio Jonas Salk's polio vaccine had been developed and
Speaker 1: deployed a little over ten years before, and so the
Speaker 1: specter of polio and the paralysis that it could cause
Speaker 1: was still pretty fresh in the minds of many people.
Speaker 1: And secondly, even more recently, Aaron the litamide. That's right,
Speaker 1: the lidimide, and if you haven't listened to our Leo
Speaker 1: or thelytamide episodes, go check those out for more historical
Speaker 1: context on that situation. But the litamide had this enormous
Speaker 1: impact on the US, even though the US largely escaped,
Speaker 1: not entirely, as we talked about in the episode, but
Speaker 1: people read the news articles and testimonials of parents and
Speaker 1: saw the pictures of children born with limb alformations.
Speaker 2: Yeah, that makes sense, and.
Speaker 1: Essentially it put this image to their fears of what
Speaker 1: could happen with rubella epidemic, especially since unlike polio, there
Speaker 1: was no vaccine, and unlike the lidamide, it was not
Speaker 1: safely off the shelves.
Speaker 2: Right. Yeah. Yeah.
Speaker 1: The thltamide scandal of a few years before turned this
Speaker 1: rubella epidemic from what would have been a largely private
Speaker 1: matter to a public one. The rubella epidemic that began
Speaker 1: in nineteen sixty three and continued through nineteen sixty five
Speaker 1: was enormous. Approximately twelve point five million people became infected
Speaker 1: with th rebella whoa, and an estimated twenty thousand babies
Speaker 1: were born with congenital rebella syndrome.
Speaker 2: Oh my gosh.
Speaker 1: With around there are death, tons of different numbers quoted,
Speaker 1: but one I saw was eleven thousand miscarriages and therapeutic abortions.
Speaker 2: Wow.
Speaker 1: Which brings me to the next big step in the
Speaker 1: history of rebella. It was the combination of both the
Speaker 1: thilatamide scandal and this rubella epidemic of the early nineteen
Speaker 1: sixties that led to more open discussion of abortion and
Speaker 1: ultimately widespread abortion law reform in the US.
Speaker 2: Really, yes, no way, I had no idea.
Speaker 1: I know, I know me either. I stumbled across it
Speaker 1: when I was looking for like books on reubella. Wow. Huh. So,
Speaker 1: as we talked about in our birth control episode, birth
Speaker 1: control isn't new. Abortions aren't new. They're not a twentieth
Speaker 1: century invention at all. Although I think we tend to
Speaker 1: think of roversuade as being the moment where abortion came
Speaker 1: into the open, and it had only been practiced in
Speaker 1: back alleys and in people's basements up to that point.
Speaker 1: That's not quite accurate. During the depression, for instance, safe
Speaker 1: abortion clinics practiced openly, but with the conservative moral backlash
Speaker 1: really only beginning in the nineteen forties and nineteen fifties,
Speaker 1: which was also a very politically conservative time. Abortions didn't stop,
Speaker 1: of course, but they just became more unsafe and more
Speaker 1: secretive and more like, you know, there were more moral
Speaker 1: implications to it. In the early nineteen sixties, you could
Speaker 1: still seek an abortion in some states through applying for
Speaker 1: one and having a hospital abortion review committee look over
Speaker 1: your case. It was basically like a panel of generally
Speaker 1: male doctors.
Speaker 2: Yeah, a bunch of dudes deciding whether or not you
Speaker 2: get to Oh, my goodness.
Speaker 1: And then often, at least like in some instances, you
Speaker 1: would have to undergo several physical or gynecological exams with
Speaker 1: members of that abortion review committee.
Speaker 2: Absolutely not, isn't that?
Speaker 1: Yeah, Yeah, that's appalling. And throughout the nineteen forties and
Speaker 1: nineteen fifties, abortion was painted as an incredibly dangerous thing
Speaker 1: to do, is often resulting in death, and those seeking
Speaker 1: or performing abortions were criminals or immoral, or deficient or
Speaker 1: evil in some way. The lidamide and I highly recommend
Speaker 1: people read about Sherry Finkbine sometime and this because that
Speaker 1: also plays a huge role in the history of abortion
Speaker 1: and abortion law reform. But the litamide and the rubella
Speaker 1: epidemic of the early nineteen sixties turned this discussion of
Speaker 1: abortion into one of a right to be informed and
Speaker 1: make an informed choice, to choose what a woman felt
Speaker 1: was right for herself and for her family. It began
Speaker 1: to be considered as necessary or right, and its illegality
Speaker 1: was considered more immoral than its legality. Interesting, and it
Speaker 1: is true that the image of people seeking abortions changed
Speaker 1: during this time. It became more of a middle class problem,
Speaker 1: and so that did definitely put a spin on like
Speaker 1: it had to be a white, middle class.
Speaker 2: Educated Yeah, they're the only ones who can seek abortions.
Speaker 1: Huh ye. Early legal battles in abortion often sued physicians
Speaker 1: and hospitals that provided false information or refused to provide
Speaker 1: any at all, which prevented the patient or the person
Speaker 1: seeking the abortion from making their own decisions about their body,
Speaker 1: or their family, or their own life. For instance, a
Speaker 1: woman would go to a doctor and say I don't
Speaker 1: feel well, something's wrong with me, and he would be
Speaker 1: in his brain thinking, oh, that looks like rubella, but
Speaker 1: it's probably not. It might not be. I don't want
Speaker 1: to worry her unnecessarily, and so then he might note
Speaker 1: it on her chart but not ever tell her what HM.
Speaker 1: So that would happen, or would be a doctor saying, actually,
Speaker 1: I'm not sure if it was rubella. These early legal
Speaker 1: battles were all about information and access to information and
Speaker 1: a patient's right to access that information.
Speaker 2: Right. Yeah.
Speaker 1: Some of these lawsuits came to be known as wrongful
Speaker 1: birth or wrongful life suits, and they ended up revolutionizing
Speaker 1: abortion law in the US. But there is one quick
Speaker 1: note that I want to make about rubella, abortion and
Speaker 1: people of color during this period. Often whether or not
Speaker 1: an abortion committee granted someone the approval to seek a
Speaker 1: therapeutic abortion depended on a recorded positive diagnosis of rebella.
Speaker 1: But as we discussed in our Rocky Mountain spotted fever episode,
Speaker 1: skin rash diagnoses in people of color is notoriously difficult
Speaker 1: and lacking in guidance in the medical literature. But there
Speaker 1: is a medical student named Malone Muquende, who is working
Speaker 1: on a book that is going to address this and
Speaker 1: the problem of not having like accurate pictures or like
Speaker 1: information in medical literature. It's like twenty twenty. I can't
Speaker 1: believe that it's but it's incredible.
Speaker 2: I'm so yeah, yeah, I can't wait for that book.
Speaker 1: So anyway, but this added one more layer of discrimination
Speaker 1: and bias against people of color in the medical realm,
Speaker 1: you know, just as per usu as per usue. Anyway.
Speaker 1: In addition to propelling abortion law reform forward, the Rebella
Speaker 1: epidemic in the US in the nineteen sixties also propelled
Speaker 1: scientific research forward. The virus that caused rubella was identified
Speaker 1: nineteen sixty two, and the first test for rubella, like
Speaker 1: whether someone was newly infected or had been previously infected,
Speaker 1: was developed in nineteen sixty five by a stand plot Plotkin.
Speaker 2: I read some of his papers.
Speaker 1: Yeah, But the biggest goal was a vaccine, which was
Speaker 1: seen as the best solution scientifically and culturally in light
Speaker 1: of abortion. Since rebella epidemics tended to occur every four
Speaker 1: to six years, nineteen seventy was sort of this looming
Speaker 1: deadline when the next big epidemic was expected to happen. Fortunately,
Speaker 1: a live attenuate vaccine was developed in nineteen sixty six
Speaker 1: by scientists at the NIH who agreed to share it
Speaker 1: widely on the condition that it not be patented. Awesome,
Speaker 1: and I know, Aarin you were like, I can't wait
Speaker 1: to hear about the story of the vaccine, but like,
Speaker 1: that's basically all I have for the development.
Speaker 2: That I mean, that's what I wanted to know, Like
Speaker 2: what was the impetus because exactly, yeah, because in the
Speaker 2: context of like such a mild generally illness, I was
Speaker 2: really interested in, like what were the factors driving the
Speaker 2: vaccine development? So you answered those question.
Speaker 1: And so once this vaccine was available, there was a
Speaker 1: massive vaccination campaign in the US and the late nineteen sixties,
Speaker 1: and despite Nixon's ridiculous budget cuts and basically like having
Speaker 1: to depend on an army of volunteers, it would prove
Speaker 1: to be one of the most successful vaccination campaigns in history,
Speaker 1: hopefully to be upset by the COVID vaccine.
Speaker 2: Fingers cross, fingers.
Speaker 1: Crossed by the spring. So here's a quote. By the
Speaker 1: spring of nineteen seventy two, seventy five percent of all
Speaker 1: school children, and more than half of all children between
Speaker 1: one and four years old had been immunized against rebella.
Speaker 2: From nineteen sixty six you said it was developed.
Speaker 1: Sixty nine is when this campaign started.
Speaker 2: And then sixty Wow, so in three years. Yeah's pretty phenomenal,
Speaker 2: it's huge.
Speaker 1: A few years later, the rubella vaccine would be combined
Speaker 1: with the measles and mumps vaccine, and by I don't know,
Speaker 1: the nineteen eighties, for many people, rubella simply came to
Speaker 1: mean just the R in MMR.
Speaker 2: Yep. That's absolutely, which is fascinating.
Speaker 1: How fast we forget these things?
Speaker 2: Oh yeah.
Speaker 1: Over the next few decades, massive vaccination campaigns decreased the
Speaker 1: global prevalence of reubella and congenital reubella syndrome dramatically, and
Speaker 1: it was eliminated in the US in two thousand and four. However,
Speaker 1: lapsed vaccination rates I can hear you, I could hear
Speaker 1: that intake of breath, Aaron, anticipating the bad news to come.
Speaker 2: However, yep, yep.
Speaker 1: Lapsed vaccination rates and lack of access to vaccinations in
Speaker 1: other places has led to rubella and congenital reubella syndrome
Speaker 1: continuing to be a huge problem in many places, which
Speaker 1: is where I end my story and passed the mic
Speaker 1: to you, Aaron.
Speaker 2: Oh great, love to pick it up on happy notes
Speaker 2: that you're welcome. We'll take a quick break first and
Speaker 2: then dive in, so this will be relatively quick and
Speaker 2: like kind of mostly good news. Erin that's good, nice,
Speaker 2: not good, great news, but decent.
Speaker 1: Good, not great, excellent, not great.
Speaker 2: So let me just hit you with numbers straight off
Speaker 2: the bat, all right, and we're just gonna talk really
Speaker 2: about the last twenty years from like two thousand to
Speaker 2: twenty twenty.
Speaker 1: Okay, cool.
Speaker 2: So, as of early twenty nineteen, one hundred and sixty
Speaker 2: eight out of one hundred and ninety four countries that
Speaker 2: the World Health Organization like monitors had introduced rubella vaccination
Speaker 2: as part of their childhood vaccination series. One sixty eight
Speaker 2: out of one ninety four, so that's a lot. Yeah,
Speaker 2: global coverage was estimated. So that means the total number
Speaker 2: of kids who get vaccinated was estimated at sixty nine percent,
Speaker 2: which was up from in two thousand twenty one percent.
Speaker 1: Wow.
Speaker 2: Yeah, so that's pretty great.
Speaker 1: Yeah.
Speaker 2: Because of that, the and this is going to get interesting,
Speaker 2: the total reported cases of rubella, not congenital rubella syndrome,
Speaker 2: but rubella declined by ninety seven percent, oh, in the
Speaker 2: last twenty years, in the last twenty years, from over
Speaker 2: six hundred and seventy thousand cases reported in two thousand
Speaker 2: to just over twenty six thousand cases reported in twenty eighteen.
Speaker 2: And here's what's really important about that. Reporting has gotten
Speaker 2: worlds better for rubella in that time period.
Speaker 1: It's even it's likely that it's even more than a
Speaker 1: ninety seven percent decrease.
Speaker 2: Right, So we've had a huge increase in the number
Speaker 2: of countries that report. In two thousand, only fifty three
Speaker 2: percent of countries reported their rubella numbers, and in twenty eighteen,
Speaker 2: ninety one percent of countries we're reporting something. Granted, this
Speaker 2: is all going to be an underestimate, blah blah, we
Speaker 2: always say that that's always true, but still that's major, yeah, right,
Speaker 2: like fifty percent more or like forty percent more countries
Speaker 2: are reporting, and we have a ninety seven percent decline
Speaker 2: in rubella cases. WHOA, Right, that's amazing, it's incredible. And
Speaker 2: that's because of vaccines.
Speaker 1: Okay, because of vaccines.
Speaker 2: For congenital rubella syndrome. The story is not quite as
Speaker 2: beautifully perfect, but it's still very reassuring. In two thousand,
Speaker 2: there were one hundred and fifty six cases reported. Do
Speaker 2: you think there were only one hundred and fifty six
Speaker 2: cases erin No, definitely not. In twenty eighteen there were
Speaker 2: only four hundred and forty nine cases reported, So that's
Speaker 2: an increase. But again here the percent of countries reporting
Speaker 2: increased from thirty nine percent to seventy one percent. Wow,
Speaker 2: so that means that seventy one percent of countries are
Speaker 2: doing some kind of surveillance to look for congenital rubella
Speaker 2: and identify it and then reporting those numbers to the
Speaker 2: World Health Organization. That's excellent, It's very excellent. So in
Speaker 2: our Measos episode, when was that season two?
Speaker 1: Yeah, I think it would.
Speaker 2: Go anyways, way back when we talked a lot, I'm
Speaker 2: pretty sure if I remember correctly, about the Global Vaccine
Speaker 2: Action Plan and the Measles and Rubella Initiative, which are
Speaker 2: these groups of plans that the World Health Organization kind
Speaker 2: of helps coordinate administer across all the regions where most regions,
Speaker 2: not every region, but most regions had a goal to
Speaker 2: eliminate measles and rubella by the year twenty twenty.
Speaker 1: All this year.
Speaker 2: So yeah, here we are. We're recording at the end
Speaker 2: of twenty twenty. This episode will be out in early
Speaker 2: twenty twenty one. We have not achieved those targets. We
Speaker 2: don't have the data from twenty twenty yet, but as
Speaker 2: of the twenty nineteen Global Vaccine Action Plan Reports, I
Speaker 2: will post a link to the full reports which has
Speaker 2: every region. That the five different regions, which is the
Speaker 2: African Region, the American Region, the Eastern Mediterranean Region, the
Speaker 2: European Region, and the Southeast Asian Region and the Western
Speaker 2: Pacific Region. So those are all the regions. Each of
Speaker 2: them have their own reports. Each of them had slightly
Speaker 2: different goals. Each of them are at slightly different places
Speaker 2: on meeting those goals. No one has met their goals completely,
Speaker 2: but every region has made major progress for the most
Speaker 2: part on getting towards those goals. And the Americas were
Speaker 2: declared free of endemic rubella in twenty fifteen, and as
Speaker 2: far as I can tell, they have maintained this status.
Speaker 2: But like you said, Aaron, because of lack of low
Speaker 2: vaccine rates in certain places. The report actually combines measles
Speaker 2: and rubella, and so some countries in the Americas have
Speaker 2: had endemic transmission. I think so far is just of
Speaker 2: measles and not rubella. But I mean that just kind
Speaker 2: of means that Rebella could be not far behind. Right.
Speaker 1: Sure, all it takes is just one exactly right.
Speaker 2: Yeah, but still that's pretty major progress. And I feel
Speaker 2: like this year, especially, any progress is something that we
Speaker 2: should celebrate. Yes, we need some victories, agreed. So yeah,
Speaker 2: I mean that's pretty much the status of rubella. It's
Speaker 2: just sort of these vaccination campaigns and trying to make
Speaker 2: sure that every kid has access to a rubella vaccine.
Speaker 1: I mean this is a more uplifting ending than many
Speaker 1: of our episodes.
Speaker 2: I think so too.
Speaker 1: Yeah. Yeah, good, I'm glad. Okay, I guess is a
Speaker 1: time for sources.
Speaker 2: Yeah, I think so.
Speaker 1: I read a book called Dangerous Pregnancies, Mother's Disabilities, and
Speaker 1: Abortion in Modern America, and this is by someone named
Speaker 1: Leslie Reagan who is at the University of Illinois.
Speaker 2: Really yeah, interesting.
Speaker 1: Yeah, it was a very interesting read. I yeah, I
Speaker 1: really enjoyed it. It was it did totally open my
Speaker 1: mind to like, oh my gosh, I had no idea
Speaker 1: about the link between us fascinating. And then I want
Speaker 1: to shout out the Nature paper I mentioned by Bennett
Speaker 1: at All from twenty twenty called Relatives of Rubella Virus
Speaker 1: in Diverse Mammals. And then finally just a couple other
Speaker 1: like older papers. I pulled the history from one by
Speaker 1: Cooper from nineteen eighty five called the History and Medical
Speaker 1: Consequences of Rebella and by Forbes from nineteen sixty nine
Speaker 1: Rubella Historical Aspects. And there were a few more that
Speaker 1: I'll post as well.
Speaker 2: I found a very phenomenal book chapter in Remington and
Speaker 2: Kline's Infectious Diseases of the Fetus and Newborn Infant written
Speaker 2: by none other than Reef and Plotkin, Oh Plotkin, that
Speaker 2: was very thorough. And then a number of other papers
Speaker 2: as well, which we'll link to on our website, this
Speaker 2: Podcast will Kill You dot Com. Just click on our
Speaker 2: episodes tab and you can find the sources from every
Speaker 2: single episode we've ever done.
Speaker 1: Sixty single one, sixty four four yesh wow. Well, thank
Speaker 1: you to Bloodmobile for providing the music for this episode
Speaker 1: and all of our episodes.
Speaker 2: And this Podcast Would Kill You is a member of
Speaker 2: Exactly Right network. So if you love us, check out
Speaker 2: all the other exactly right podcasts.
Speaker 1: There's so many. Heck, yes, they make this stuff happen.
Speaker 1: They make it possible. And you know who else makes
Speaker 1: it possible is you. Listeners, do thank you, thank you,
Speaker 1: thank you from the bottoms of our hearts. Seriously, from
Speaker 1: the bottom of our hearts. For the bottoms of our hearts.
Speaker 2: Well, so the bottom is the ventricles, which are the
Speaker 2: the ventricles of our hearts, the ventricles of our hearts,
Speaker 2: specifically the left ventricle.
Speaker 1: You heard it here first, listeners, thank you from the
Speaker 1: left ventricle of our hearts.
Speaker 2: That the powerful one.
Speaker 1: Oh oh my gosh. Well, okay, let's end this thing.
Speaker 1: Until next time, wash your hands.
Speaker 2: You fill the animals a