The strange story of a scientist killed by the Plague


On September 13, 2009, Malcolm Casadaban, a University of Chicago professor of genetics and cell biology, was taken by ambulance to a hospital and died just a few hours later. Cause of death: The Plague, with a capital P.

Casadaban had been working with Plague bacteria as part of his research, but, despite that fact, this wasn't an open-and-shut case. Casadaban's bacteria were genetically modified, weakened so they couldn't infect humans. Scientists have been handling this sort of wishy-washy Plague for decades, without much incident. Until Casdaban, no-one had ever been killed by lab-acquired Plague. In fact, 1959 was the last time lab Plague had even made anyone sick.

The Centers for Disease Control wanted to know what made Casadaban different. And this is where the story gets weird. Turns out, Casadaban had his own weakness—a genetic mutation, common in people of European descent. In fact, this particular mutation is common because it protects against naturally acquired strains of the Plague. If your ancestors lived through a Plague outbreak, you're more likely to carry it. But, the same mutation also seems to leave you particularly susceptible to weakened, laboratory Plague bacteria.

An autopsy found the researcher had a medical condition called hemochromatosis, which causes an excessive buildup of iron in the body, according to the CDC report. The disorder affects about 1 in 400 people and goes unnoticed in about half of patients.

Casadaban's illness is important because of the way the plague bacterium had been weakened. Yersinia pestis needs iron to survive. Normally it gets this iron by stealing it from a host's body with proteins that bind to it and help break it down. To make the bacterium harmless, scientists genetically stripped it of the proteins needed to consume iron.

"It's like having a lion, where we took out all its teeth and all its claws," Alexander said. "But in the case of Dr. Casadaban, the lion didn't even need to have teeth. There was so much iron that it was freely available and easy to get."

The hemochromatosis that contributed to Casadaban's fate has been credited with protecting people from strains of plague that circulate in the wild. Sharon Moalem, an evolutionary biologist and author of "Survival of the Sickest," posited that the disorder shifts iron from certain white blood cells, where it is typically sought by the plague bacterium.

Bloomberg: Plague death came within hours, spurred by scientist's medical condition

Morbidity and Mortality Weekly Report: Fatal laboratory-acquired infection with an attenuated Yersinia pestis strain—Chicago, Illinois, 2009


    1. Given that we already know he was a scientist working on this disease, and that hemochromatosis affects 1 in 400 people according to the post? 1/400 x the chance of being exposed.

      My question is, given that some number of scientists have been working on this disease for decades, what is the probability that this sequence of events (hemochromatosis, work in this field, exposure, death) will occur at least one time? Probably not that small.

  1. So we’ve genetically modified a Plague virus so that it is especially lethal to people of European stock?

    I believe I speak for white folks across the globe, when I say: OH SHIIIIIIIIIIIIIIIIIIIIIIIIIIITTTTTTTT!!!!1!

    1. Yersinia Pestis is a bacteria not a virus. totally differenet kinds of organisms. Things like antibiotics will kill bacteria but not viruses.
      And the disorder affects one is 400 not all European stock.

    2. So basically Europeans have some resistance to the plague, but more susceptible to lab-mutated plague? Well, fuuuu.

      Thankfull it only affects 1 in 400 people then.

    1. Growing up in New Mexico, we were taught “don’t play with dead animals!” Good advice anywhere, but we were specifically taught it to avoid plague. Checking your dogs and cats for plague fleas was encouraged too.

      In the last 10 years, NM has had plague, hanta, and anthrax outbreaks. When I hear people complain about growing us with chicken pox, I want to say “Bah! I grew up with Black Death, hemorrhagic fever, and bio-warfare agents.” 100% organic and natural death on a stick.

  2. One of the basic flaws of time travel.. Diseases neither era has an immunity to.
    No butterfly crushing necessary.

  3. So answer me this. Ireland has the highest proportion of hemochromatosis sufferers in the world. I’m not aware that the plague was worse here. AND we had both a major famine and mass emigration in the 19th century. How do these facts (and whatever else) combine to us such a disproportionate rate?

    1. The original version of the plague could get iron on its own. No hemochromatosis needed. You got sick either way.

      The weakened version just happen to infect some guy that could only kill someone with his condition.

    2. Donal, both of the things you cited may have contributed to the increased incidence. Inherited haemochromatosis is a recessive gene, and as populations decrease in a geographical area, recessive genes often become expressed in a higher percentage of the population, leading to a higher incidence of them being active in the next generation.
      Inherited haemochromatosis is characterized by a marked increase in the capacity for intestinal absorption of iron, And potatoes are very low in bioavailable iron, as is cow’s milk (which is high in calcium, which inhibits iron absorption) — potato(es) and a bowl of cow’s milk being a typical meal before the famine. So haemochromatosis is likely to have been a survival advantage for the poor and hungry before and during the Famine — with the population dwindling as those who could not survive well on a low-iron diet emigrating.

    3. bardfinn is on the right track. The evolutionary advantage for hemochromatosis is not entirely clear, although the high prevalence of the mutation would seem to indicate that it exists. The benefit may have been in reduced incidence of iron deficiency (most common cause of anemia worldwide) in carriers. There are also indications that hemochromatosis may decrease levels of iron in macrophages, cells that are especially targeted by certain microorganisms (such as TB), thus perhaps decreasing one’s susceptibility to TB. Or, there may be some other advantage altogether.

      In this case, however, the reason that it is important is that the strain of yersinia pestis being used for research was attentuated (ie made less infectious) specifically by disabling it’s iron uptake proteins. Iron is a micronutrient essential for bacterial growth, and given that iron is tightly regulated in the body (ie usually its bound up tightly), bacteria need specific proteins in order to scavenge it.

      In this patient, however, because of his hemochromatosis, there was a lot of iron “lying around” – the bacteria didn’t need it’s special enzyme – and was able to replicate. Thus this patient specifically had a condition that neutralized the attentuation of this bacteria. To prove it, the scientists investigating this death took the bacteria that was growing in the researcher’s bloodstream, grew it up, and re-injected it into mice, which were (as one would expect) resistant.

      In wild type plague (with functioning iron uptake proteins), whether you live or die is probably going to have less to do with hemochromatosis than overall immune function and health (and this patient also had diabetes to boot, a known immunosuppressing condition). Thus, with wild type plague you wouldn’t (necessarily) expect to see much higher death rates in populations (such as Iceland) with hemochromatosis.

  4. Guys, I had a friend die of plague when she was thirteen. No kidding. She got it from a chipmunk in New Mexico, where it’s endemic among rodents, but it didn’t manifest until a few days later, when she was in the Carolinas.

    Doctors there had never seen plague, and she died in a few days—I believe it went to her lungs. Terrible, painful way for a person to go. My heart goes out to this man’s family.

  5. Completely off topic, but the analogy that doctor gave was tragically horrible. I just read this book, The Emperor of All Maladies, and the doctor who wrote it couldn’t spin a metaphor for shit. It was actually incredibly annoying.

    “It’s like having a lion, where we took out all its teeth and all its claws,” Alexander said. “But in the case of Dr. Casadaban, the lion didn’t even need to have teeth. There was so much iron that it was freely available and easy to get.”

    lol wat?

    This is why I’m taking a creative writing minor alongside my science major.

    1. Thanks – I got stuck there too. Instead of creating another metaphor for the weakness expressed by the hemachromatosis, he simply stayed with the literal meaning. That was terrible. It was as if the lion had its teeth and claws ripped out but then its brain was distracted.

  6. I realize not everyone is of European descent but how does this make sense

    a genetic mutation, common in people of European descent
    The disorder affects about 1 in 400 people?

  7. I just wanna know why dudes are playing with the Plague in laboratories. What good is supposed to come of toying with deadly bacteria?

    1. @Anon #25 “What good is supposed to come of toying with deadly bacteria?”

      Because it helps us understand the biology of the interactions between the bacteria and ourselves, which determines how and why certain bacteria are so deadly. Understanding important things like how bacteria kill people is good in itself, and might even be directly useful in designing drugs or vaccines.


      Because it’s fucking awesome!

  8. This is creepy. And not only for what it’s about, but I saw my new GYN for the first time last week, who happens to have the same surname, and when I tried to look up more about her, this story came up and I read about it then. Dont’ think there’s any relation, but I do believe in synchronized event-patterns.

  9. Ok – here’s an idea. So some people of European descent possess this genetic mutation which lends a resistance to the natural Plague strain. And the mutation can also cause hemochromatosis, where the individual exhibits elevated levels of iron in the blood.

    What if the incidences of Multiple Schlerosis in the Northern Hemispere, amongst Caucasians, purportely caused by an excess of iron in the bloodstream, which in turn creates a “leaky gut syndrome” of the blood-brain barrier, was actually the result of a genetic mutation passed down from your ancestors? Not the town drinking water or your mineral supplements or your proximity to the iron-rich Canadian Shield.

    Now if we could just explain away the the high incidence of Dementia and Schizophrenia in Finns and Scandihoovians.

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