As several others have already noted, after almost 12 years, Scienceblogs is shutting down at month’s end. Though I’ve done most of my writing elsewhere over the last few years, I’d certainly like to keep the archives of this blog up somewhere, and maintain it as a place to post random musings that don’t fit anywhere else. But admittedly, the primary thing that has kept me here has been inertia–moving is just so hard, y’all. So throwing this out there to anyone who would like to assist in a move. I have a domain and so can set up another WordPress blog elsewhere and export/import the contents, but when Scienceblogs initially moved to WordPress it was…not smooth, and that was with a professional. Which I am not, at least in this area. If anyone with experience wants to help me out (yes, paid), please leave a comment or drop me a line.
Spring, 2004. I was in the second year of my post-doc, with kids ages 4 and 2. Because I was no longer a student, the full brunt of my student loan payments had hit me, which were collectively almost double the cost of my mortgage. To put it generously, money was tight. Truthfully, we were broke as fuck and struggling each month to stay above water.
I’m from a blue-collar background. My dad was a factory worker for 40 years. My mom had a teaching degree, but “paused” her career to have me (followed by my sister and brother), and was then diagnosed with multiple sclerosis shortly after my brother’s birth. Hers was rapidly progressive and she was unable to return to teaching–leaving the family with one income and a lot of unexpected medical bills.
So when it came to navigating academia, it goes without saying that I was out of my element. But I knew I had 2 years of funding for my fellowship, and that time was quickly coming to an end. I needed to figure out a next step.
My PI suggested applying for both additional fellowships as well as professorships–though we figured I wouldn’t land the latter, at least the application process and (maybe) interviews would be good practice. At the time I started looking, there was only one assistant professor position in my niche that was advertising (I had missed much of the big interviewing season–also something I didn’t understand at the time). I applied, and somehow, a few weeks later I was invited to the University of Iowa for an interview.
The departmental secretary emailed me to set up travel. She explained that they had booked a hotel for a 2-night stay, and they’d reimburse me for my airfare–just send her the receipts after the interview.
We were barely keeping up on bills as it was, with 2 kids in full-time daycare and my student loans. We had no credit card availability. We had no family we could borrow from–they were all as broke as we were or worse. We couldn’t afford date nights out. Hell, we couldn’t afford frozen pizza in. Where was I supposed to find $300+ for a flight in two weeks?
I almost canceled. “Thanks anyway, but I’m too poor to come out.”
Luckily, what I did have was my 1996 Dodge Neon, purchased early in my post-doc for $2000 from an elderly woman who was no longer able to drive. It got about 40 miles per gallon on the highway, Iowa City was only about an 8.5-hour drive away, and gas was still under $2/gallon. I told the secretary I’d just drive it instead of fly in. I’m sure she thought I was phobic of flying or something (why drive otherwise??), but she said that was fine and arranged my meetings. When I left for my interview, I packed a sandwich, snacks, and drinks for the drive because stopping places for food added up.
All of this to say–I completely agree with Holly Bik’s thread on academic reimbursement.
Serious proposal: If we want more minorities / 1st-gen students to stay in science, we NEED to fix the travel reimbursement pyramid scheme
— Holly Bik (@hollybik) September 27, 2017
I was able to drive, but what about those who need to travel cross-country or internationally? How to pay for meetings to network and find opportunities when you’re barely scraping by between paychecks? To travel for field work necessary for a degree or project?
As a professor, I’ve tried as much as possible to put student travel on my grants, or help them search for university or other funding sources to attend conferences. Sometimes it’s only partial coverage, which is better than zero but still is a financial burden on my trainees. We always apply for the travel grants (and have gotten a few). But even when it’s paid, it’s typically not comped up-front–and can take months to come back. As Bik notes, it’s just one more way the system is rigged against those who don’t have access to some kind of familial assistance–and that includes a lot of people we’re trying to recruit into the field, or retain once they’re here.
I don’t know how to fix it. I know some places are better than others. At least at my current institution, reimbursement tends to be relatively quick (~3-4 weeks or so) and will do direct deposit (some places still, inexplicably, insist on paper checks, which drags out the process even further). I know budgets are tight everywhere. I know that not every professor can afford to pay for all their students up-front either. I sent 5 trainees to the American Society for Microbiology meeting in 2016 in addition to myself, and even after 13 years as a professor, I still can’t afford to just pay all of that in advance. Our financial people have often been sympathetic, but tell us their hands are tied due to all sorts of regulations.
As with so many areas of academia, we need to do better. From Bik’s thread, some places seem to be able to front costs–why can’t that be universal? It seems like a small thing when you have money, but for many struggling academics it’s the difference between “making it” and leaving the field. If administrators are truly committed to diversity, they’d find some way to make this work more smoothly.
I recently finished a 2-year stint as an American Society for Microbiology Distinguished Lecturer. It’s an excellent program–ASM pays all travel expenses for lecturers, who speak at ASM Branch meetings throughout the country. I was able to attend Branch meetings from California and Washington in the West, to Massachusetts in the east, and south as far as El Paso, Texas, with many in-between. Each Lecturer selects several topics to speak on, and the Branch chooses from those which they want to hear. Mine included basic research (zoonotic disease, antibiotic resistance) as well as science outreach and advocacy topics (zombies, vaccines).
My talk on vaccines covered vaccine hesitancy and denial, the concerns some parents have regarding vaccination, and the way social media and celebrities contributed to the spread of vaccine misinformation. Inevitably, someone would ask in the Q&A or speak to me afterward inquiring, “But what can I do? I don’t feel I know enough about why people reject vaccines, and feel helpless to combat the fears and misinformation that is out there.” These were audiences of microbiologists and other types of infectious disease specialists–people who are very likely to be educated about vaccines and vaccine-preventable diseases, but who may not have followed the saga of disgraced former physician Andrew Wakefield, or aren’t familiar with the claims of the current anti-vaccine documentary, Vaxxed, or other common anti-vaccine talking points.
To help fill this gap, I recently published a paper in Open Forum Infectious Diseases,” Vaccine Rejection and Hesitancy: a Review and Call to Action.” As the title suggests, in it I give a brief overview of some of the figures in the anti-vax movement and the arguments they commonly use. I don’t go into rebuttals directly within the paper, but the supplemental information includes a subset of both anti-vax literature as well as several published rebuttals to them that interested individuals can look up.
I also briefly review the literature on vaccine hesitancy. Who fears or rejects vaccines, why do they do so, and how might we reach them to change their minds? This is really an area where many individuals, even if they’re educated about vaccines and infectious disease, lack a lot of background. As I note in the paper, many science-minded people still think that it’s enough to just educate people about vaccines properly, and that will be enough. While accurate information is indeed important, for many individuals on the vaccine-hesitant spectrum, it’s not only about misinformation, but also about group identity, previous experience with the health care field, and much more.
Still, vaccine advocates can get involved in a number of way. One of the easiest is simply to discuss your own vaccine history in order to normalize it. I regularly post pictures of my own vaccinations on social media (including my public Facebook and Twitter accounts), and those of my kids*. In over 17 years of parenthood, their vaccinations have all been…boring. These “uneventful vaccination” stories are the ones which rarely get told, as the media focuses on “vaccine injury” stories, in which the injuries may or may not actually be caused by vaccines. Those interested in promoting vaccines can write letters to the editor, get involved with local physicians to speak with hesitant families, break out and be political about vaccine exemptions; there are a number of ways that we can work to encourage vaccination and keep our children and our communities healthy (again, explored in more detail in the manuscript).
I hope this paper will serve as a starting point for those who want to be a vaccine advocate, but just aren’t sure they know enough background, or know where or how to jump in. Whether you’re an expert in the area or not, everyone can do small things to encourage vaccines and demonstrate your trust in them. Those of us working in the area thank you in advance for your help.
Smith TC. Vaccine Rejection and Hesitancy: a Review and Call to Action. Open Forum Infectious Diseases, 2017, in press.
*AKA, how to get your kids’ pictures into a scientific paper.
A claim that scientists need to quit making:
I’ve written about these types of claims before. The first one–a claim that antimicrobial peptides were essentially “resistance proof,” was proven to be embarrassingly wrong in a laboratory test. Resistance not only evolved, but it evolved independently in almost every instance they tested (using E. coli and Pseudomonas species), taking only 600-700 generations–a relative blip in microbial time. Oops.
A very similar claim made the rounds in 2014, and the newest one is out today–a report of a “super vancomycin” that, as noted above, could be used “without fear of resistance emerging.” (The title of the article literally claims “‘Magical’ antibiotic brings fresh hope to battle against drug resistance”, another claim made in addition to the “no resistance” one in the Scripps press release by senior author Dale Boger). This one claims that, because the modified vancomycin uses 3 different ways to kill the bacteria, “Organisms just can’t simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two.”
A grand claim, but history suggests otherwise. It was argued that bacteria could not evolve resistance to bacteriophage, as the ancient interaction between viruses and their bacterial hosts certainly must have already exploited and overcome any available defense. Now a plethora of resistance mechanisms are known.
Within the paper itself, the limitations are much more clearly laid out. Discussing usage of the antibiotic, the authors note of these conventional semisynthetic vancomycin analogs:
“However, their use against vancomycin-resistant bacteria (e.g., VRE and VRSA), where they are less potent and where only a single and less durable mechanism of action remains operative, likely would more rapidly raise resistance, not only compromising its future use but also, potentially transferring that resistance to other organisms (e.g., MRSA).”
So as they acknowledge, not really so resistance-proof at all–only if they’re used under perfect conditions and without any vancomycin resistance genes already present. What are the odds of that once this drug is released? (Spoiler alert: very low).
Alexander Fleming, who won the 1945 Nobel Prize in Physiology or Medicine, tried to sound the warning that the usefulness of antibiotics would be short-lived as bacteria adapted, but his warnings were (and still are?) largely ignored. There is no “magic bullet;” there are only temporary solutions, and we should have learned by now not to underestimate our bacterial companions.
The news over the past 24 hours has exclaimed over and over:
HIV’s supposed “Patient Zero” in the U.S., Gaetan Dugas, is off the hook! He wasn’t responsible for our outbreak!
This is presented as new information.
It is not, and I think by focusing on the “exoneration” of Dugas, a young flight attendant and one of the earliest diagnosed cases of AIDS in the U.S., these articles (referencing a new Nature paper) are missing the true story in this publication–that Dugas was really a victim of Shilts and the media, and remains so, no matter how many times the science evidence has cleared his name.
First, the idea that Dugas served to 1) bring HIV to the U.S. and 2) spark the epidemic and infect enough people early on that most of the initial cases could be traced back to him is simply false. Yes, this was the hypothesis based on some of the very early cases of AIDS, and the narrative promoted in Randy Shilts’s best-selling 1987 book, “And the Band Played On.” But based on the epidemiology of first symptomatic AIDS cases, and later our understanding of the virus behind the syndrome, HIV, we quickly understood that one single person in the late 1970s could not have introduced the virus and spread it rapidly enough to lead to the level of infections we were seeing by the early 1980s. Later understanding of the virus’s African origin and its global spread made the idea of Dugas as the epidemic’s originator in America even more impossible.
When we think of Dugas’s role in the epidemiology of HIV, we could possibly classify him as, at worst, a “super-spreader“–and individual who is responsible for a disproportionate amount of disease transmission. Dugas acknowledged sexual contact with hundreds of individuals between 1979 and 1981–but his numbers were similar to other gay men interviewed, averaging 227 per year (range 10-1560). And while Shilts portrayed Dugas as a purposeful villain, actively and knowingly spreading HIV to his sexual partners, that does not jibe with both our scientific knowledge of HIV/AIDS or with the assistance Dugas provided to scientists studying the epidemic. Dugas worked with researchers to identify as many of his partners as he could (~10% of his estimated 750), as the scientific and medical community struggled to figure out whether AIDS stemmed from a sexually-transmitted infection, as several lines of evidence suggested. There’s no evidence Dugas was maliciously infecting others, though that was the reputation he received. Dugas passed away from complications of AIDS in March of 1984–weeks before the discovery of HIV was announced to the general public.
Furthermore, the information in the new publication is not entirely novel. Molecular analyses carried out in part by Michael Worobey, also an author on the new paper, showed almost a decade ago that Dugas could not have been the true “Patient Zero.” The 2007 paper, “The emergence of HIV/AIDS in the Americas and beyond,” had the same conclusions as the new paper: HIV entered the U.S. from the Caribbean, probably Haiti, and was circulating in the U.S. by the late 1960s–when Dugas was only about 16 years old, and long before his career as a flight attendant traveling internationally. So this 2007 molecular analysis should have been the nail in the coffin of the Dugas-as-Patient-Zero ideas.
But apparently we’ve forgotten that paper, or other work that has followed the evolution of HIV over the 20th century.
What is unique about the new publication is that it included a sample from Dugas himself, via a plasma contribution Dugas donated in 1983, and other samples banked since the late 1970s. The new paper demonstrated that Dugas’s sample is not in any way unique, nor is it a “basal” virus–one of the earliest in the country, from which others would diverge. Instead, it was representative of what was already circulating among others infected with HIV at that time. In supplemental information, the authors also demonstrated how notation for Dugas in scientific notes changed from Patient 057, then to Patient O (for “Outside California”) to Patient 0/”Zero” in the published manuscript–which Shilts then named as Dugas and ran with in his narrative.
The media then extended Shilts’s ideas, further solidifying the assertion that Dugas was the origin of the U.S. epidemic, and in fact that he was outright evil. The supplemental material notes that Shilts didn’t want the focus of the media campaign initially to be about Dugas, but was convinced by his editor, who suggested the Dugas/Patient Zero narrative would result in more attention than the drier critiques of policy and inaction in response to the AIDS epidemic by the Reagan administration.
And the media certainly talked about it. A 1987 edition of U.S. News and World Report included a dubious quote attributed to Dugas: “‘I’ve got gay cancer,’ the man allegedly told bathhouse patrons after having sex with them. ‘I’m going to die, and so are you.’” NPR’s story adds “The New York Post ran a huge headline declaring “The Man Who Gave Us AIDS. Time magazine jumped in with a story called ‘The Appalling Saga Of Patient Zero.’ And 60 Minutes aired a feature on him. ‘Patient Zero. One of the first cases of AIDS. The first person identified as the major transmitter of the disease,’ host Harry Reasoner said.”
This is the real scandal and lingering tragedy of Dugas. His story was used to stoke fear of HIV-infected individuals, and especially gay men, as predators seeking to take others down with them. His story was used in part to justify criminalization of HIV transmission. So while science has exonerated him again and again, will the public–and the media–finally follow?
The 2013-2016 West African Ebola virus outbreak altered our perception of just what an Ebola outbreak could look like.
While none of the three primary affected countries–Liberia, Sierra Leone, and Guinea-have had a case since April 2016, the outbreak resulted in a total of over 28,000 cases of Ebola virus disease (EVD)–65 times higher than the previous largest EVD outbreak, and more than 15 times the total number of cases of all prior EVD outbreaks combined, from the virus’s discovery in 1976 to a concurrent (but unrelated) outbreak in the Democratic Republic of Congo in 2014.
In March 2016, cases were identified once again in both Liberia and Guinea, just after the outbreak had been declared over. Both countries were declared Ebola-free in June 2016; Guinea for the second time and Liberia for the fourth time. The last series of cases in these countries demonstrated just how different this epidemic was from prior ones, changing what we thought we knew about the virus:
Previous research suggested Ebola could persist in the semen for 40 to 90 days. But that window has been eclipsed in this epidemic by a considerable amount. A probable case of sexual transmission occurred approximately six months after the patient’s initial infection last year in Liberia. Another study found evidence of Ebola in the semen of 25% of surviving men tested seven to nine months after infection. And it takes only a single transmission to kick off a fresh recurrence of the disease.
A recent paper extended this window of virus persistence in the semen even longer–over 500 days. It also explains how the outbreaks began in both countries after being declared Ebola-free–so where did the virus come from?
In a convergence of old-fashioned, “shoe leather” epidemiology/tracing of cases and viral genomics, two converging lines of evidence led to the identification of the same individual: a man who had been confirmed as an EVD case in 2014, and had sexual contact with one of the new cases. Author Nick Loman discussed via email:
The epidemiologists told us independently that they had identified a survivor and we were amazed when we decoded the metadata to find that case was indeed the same person. The sequencing and epidemiology is tightly coordinated via Guinea’s Ministry of Health who ran National Coordination for the Ebola outbreak and the World Health Organisation.
It shows that the genomics and epidemiology works best when working hand-in-hand. If we’d just had the genomics or the epidemiology we’d still have an element of doubt.
The sequencing results also suggested that it was likely that the new viral outbreak was caused by this survivor, and unlikely that the outbreak was due to another “spillover” of the virus from the local animal population, according to author Andrew Rambaut:
If the virus was present in bats and jumped to humans again in 2016, it might be genetically similar to the viruses in the human outbreak but not have any of the mutations that uniquely arose in the human outbreak (it would have its own unique mutations that had arisen in the bat population since the virus that caused human epidemic).
It might be possible that the virus jumped from humans to some animal reservoir in the region and then back to humans in 2016 but because we have the virus sequence from the patients acute disease 15 months earlier we can see that it essentially exactly the same virus. So this makes it certain the virus was persisting in this individual for the period.
So the virus–persisting in the survivor’s semen for at least 531 days–sparked a new wave of cases. Ebola researcher Daniel Bausch noted elsewhere that “The virus does seem to persist longer than we’ve ever recognized before. Sexual transmission still seems to be rare, but the sample size of survivors now is so much larger than we’ve ever had before (maybe 3,000-5,000 sexually active males versus 50-100 for the largest previous outbreak) that we’re picking up rare events.”
And we’re now actively looking for those rare events, too. The Liberia Men’s Health Screening Program already reports detection of Ebola virus in the semen at 565 days following symptoms, suggesting we will need to remain vigilant about survivors in both this and any future EVD epidemics. The challenges are clear–we need to investigate EVD survivors as patients, research participants, and possible viral reservoirs–each of which comes with unique difficulties. By continuing to learn as much as we can from this outbreak, perhaps we can contain future outbreaks more quickly–and prevent others from igniting.
[Obvious warning is obvious: potential spoilers for A Song of Ice and Fire novels/Game of Thrones TV series below].
While no one will claim that George R.R. Martin’s epic series, “A Song of Ice and Fire,” is historically accurate, there are a number of historical parallels that can be drawn from the characters and plotline–particularly from medieval Europe. While most of those relate to epic battles or former monarchs or other royalty, another of Martin’s characters, so to speak, is the disease greyscale (1).
Greyscale is a contagious disease that seems to come in at least two distinct forms: greyscale, an endemic and slow acting, highly contagious illness that can affect either adults or children; and the grey plague, a rapidly-spreading epidemic that can wipe out entire swaths of cities in a short period of time. Both versions of the illness have a high fatality rate (no exact details are given, but it seems to be close to 100%, especially in adults). Recovery from greyscale makes one immune to outbreaks of grey plague, so they seem to be caused either by the same microbe or ones which are very closely related.
The Epidemiology of Greyscale
Greyscale is a disfiguring disease. As its name suggests, it transforms the skin into a hardened, scaly tissue. As the skin dies, it becomes grey in color with permanent cracks and fissures. Infection that spreads across the face can cause blindness.
Like many diseases we consider to be “childhood” diseases (measles, mumps, smallpox, chickenpox, etc.), children seem to be spared the worst of the disease and are the most likely to recover from the illness, though recovery still appears to be quite rare. The disease is most common in Essos, but can also be found occasionally throughout Westeros, including north of the Wall (more on that below).
Greyscale is believed to be transmitted primarily person-to-person via direct skin contact. We see this in the books with the infection of Jon Connington and on the TV show with Jorah Mormont, as both characters are transporting/protecting Tyrion Lannister and apparently are exposed to the pathogen during a battle with the Stone Men (2, 3). The Stone Men are victims in the last stage of greyscale infection, where the skin is entirely calcified and there is involvement of muscle, bone, and internal organs, including the brain. Late signs of greyscale infection include violent insanity, leading sufferers to violently attack anyone who comes near. As these Stone Men are highly feared as sources of the disease, greyscale appears to be contagious for the entire duration of infection, from the development of symptoms to near-death.
If a person has been exposed to greyscale, but is not yet showing symptoms, they can check for impending infection by pricking their toes and fingers each day. Once they’re no longer able to feel the knife, that’s bad news–greyscale infection is likely, as insensitivity to touch is one of the early signs. Once the scaling begins, the victim no longer feels any pain in the affected areas, making the Stone Men essentially invulnerable to pain.
The incubation period of greyscale seems to be very short. As soon as Jorah and Tyrion realize they are safe and the Stone Men are defeated, Jorah rolls up his sleeve and we see that the initial small patch of greyscale has already appeared.
Another prominent victim of greyscale, Shireen Baratheon, is thought to have acquired greyscale via contact with a fomite (an inanimate object that serves as a vehicle to transmit an infectious agent between people)–in her case, a beloved wooden doll clothed in Baratheon House colors from when she was an infant. Her father, Stannis, implies that this may have been a form of bioterrorism–that Stannis received the doll from a Dornish trader on Dragonstone. He tells his daughter, “No doubt he’d heard of your birth, and assumed new fathers were easy targets” (S05E04). “I still remember how you smiled when I placed that doll in your cradle, and you pressed it to your cheek,” where evidence of greyscale is still present (4).
A number of remedies have been proposed to treat greyscale, but none of them are proven effective. They include treating it with boiling water containing limes; chopping off of the infected limbs; religious means/magic; and maybe fire–in A Dance with Dragons, Tyrion touches a Stone Man with his torch, and the Stone Man shrieks in pain (even while having bone showing through his skin, which apparently doesn’t bother him). Whether fire could be a cure is unclear.
Also in A Dance with Dragons, we read of Tyrion’s musings on treating greyscale: “He had heard it said that there were three good cures for greyscale: axe and sword and cleaver. Hacking off afflicted parts did sometimes stop the spread of the disease, Tyrion knew, but not always. Many a man had sacrificed one arm or foot, only to find the other going grey. Once that happened, hope was gone.” As such, the infectious agent seems to enter into the bloodstream and spread throughout the body at some point during the infection, and at this point, local measures such as amputation are no longer useful. Other home remedies, such as cleansing the infected area with vinegar, are also employed. In fact, Jon Connington, once he realizes he’s been infected, soaks his hand in bad wine instead of vinegar, because he believes that if he asks for vinegar, it will be an obvious “tell” that he has the disease.
In the TV series (S05E04), Stannis says to Shireen regarding her infection, “I called in every Maester in this side of the world, every healer, every apothecary. They stopped the disease and saved your life.” However, no details are given on the show regarding how it was stopped (medicine? magic?), or if a mechanism exists that could be used on an adult instead of an infant. When Daenerys asks Jorah if there is a cure, he tells her simply that he doesn’t know, and she directs him to leave, find one, and return to her.
Largely, those with greyscale are shunned and sent elsewhere, especially to the ruins of Valyria (5) where a whole colony of Stone Men live. Shireen asks Stannis, “Are you ashamed of me, Father?”, understanding that her obvious greyscale scars are a sign of stigma for their entire family. Stannis tells his daughter, “Everyone advised me to send you to the ruins of Valyria to live our your short life with the Stone Men before the sickness spread throughout the castle. I told them all to go to hell.” (Father of the Year before that whole burning stuff, Stannis!)
Similarly, both the books and show note the existence of greyscale beyond the wall among the Wildlings–and that the free folks’ response to greyscale infection is exile and/or death. In the books, a wildling named Val sees Shireen, and notes Shireen has a condition they call “the grey death,” which is always fatal in children–because they’re given either hemlock, a pillow, or a blade rather than be allowed to live. She also suggests that greyscale may become quiescent and return later, saying “The grey death sleeps, only to wake again. The child [Shireen] is not clean.”
On the TV version, the wildling Gilly takes the place of Val, and while she is not as frightened of Shireen’s greyscale, she notes she’s also had experience with the illness. She tells the tale of two of her sisters, who contracted greyscale (exactly how, we’re not told). Though he did not kill them as Val suggested, Gilly noted that her father “made them move out of the keep, into the hut outside. None of them were allowed to go near them, but we heard them, especially at night. They started to sound not like themselves.” Gilly saw them again “only once, at the end. They were covered with it. Their faces, their arms. They acted like animals. My father had to drag them out to the woods on a rope.” Shireen doesn’t find out what happened to them after that, but we can guess it’s not good.
What are some real-life parallels?
Clearly greyscale is another invention of Martin’s that doesn’t quite match up to any real infectious disease (6), and I’ll leave that linked article to summarize some of the pros and cons of the alternative diagnoses. But given the other historical parallels, leprosy (Hansen’s disease) is probably the closest real-life affliction to greyscale, due to the route of transmission (I’ll elaborate on that below), symptoms, incubation period, and particularly the cultural response to those who are affected.
Like those with leprosy, sufferers of greyscale can become disfigured, are considered “unclean” and shuffled off to the far corners of the map, feared and then ignored by their family and friends. Connington, when hiding his infection, noted that “Queer as it seemed, men who would cheerfully face battle and risk death to rescue a companion would abandon that same companion in a heartbeat if he were known to have greyscale”–a similar phenomenon to what still can happen today with stigmatized diseases such as leprosy. A case of greyscale is a source of stigma for both the sufferer (even if they survive, like Shireen) and for the family, as there will always be those who fear contagion.
Though evidence is gathering that leprosy is actually transmitted via the respiratory route (like its cousin, tuberculosis), for centuries people believed it could be spread by touch, as greyscale is. So even though the transmission route for the two diseases really isn’t the same, the *presumption* that leprosy can be spread by touch is still incredibly common. The lengthy period between infection and outward symptoms of the affliction is also similar, taking years from exposure to the final stages of infection that we see in the Stone Men. Leprosy can also take years or decades to progress, and while untreated leprosy is not typically a cause of death itself, it can lead to death indirectly due to secondary infections and other issues.
One of the early signs of leprosy is also numbness in an affected area as nerves are damaged by the infection, as Tyrion tried to evaluate after his exposure to the Stone Men, as well as a general thickening and stiffness of the skin. It doesn’t get to the level that’s seen with the Stone Men–one of the biggest problems with leprosy is actually secondary infections, which can lead to loss of digits or even whole limbs rather than a whole-body calcification of the skin–but many of the hallmarks of greyscale are very similar to leprosy.
While leprosy is now treatable with antibiotics, it wasn’t all that long ago that we had our own leper colonies in the U.S. (you can read about one of them here, also on a near-deserted island where the afflicted were largely left to fend for themselves with some occasional governmental assistance, similar to Valyria/the Sorrows). Martin himself even notes that Valyria is “like a leper colony.” Leprosy, and its stigma, remains an issue in some countries still today, and the purposeful isolation of those who have leprosy and exclusion from society persists.
However, while there are many similarities, leprosy doesn’t have an epidemic form equivalent to the grey plague. Described in A Dance with Dragons, it’s suggested that the grey plague wiped out half of Oldtown in the southwest of Westeros, and was only stopped by closing the gates and preventing anyone from entering or leaving. And like the Black Plague, the grey plague’s arrival in Pentos (a city in Essos) came by ship, and its spread into the city was possibly aided by rats. So is there an airborne form of greyscale that causes the grey plague? Could it be similar to Yersinia pestis, the bacterium that causes the Black Plague: transmitted by rats and fleas (or skin to skin in the case of greyscale) in its more mild form, but occasionally ending up in the lungs of an unfortunate victim and spread via the air after that, causing massive epidemics? Is it zoonotic, spread via rats? Will we see the grey plague on the TV series or not?
While comparisons to other real infections are interesting, my real question is–what is Martin going to do with greyscale? How does it feature into the larger end game, when we move beyond just a human “Game of Thrones” into the battle for humanity itself against the White Walkers and their army of undead wights? With all the time spent on the affliction in both the books and particularly in the show, there has to be some payoff somewhere, right?
In some ways, the wights beyond the wall and Stone Men are similar–undead, or nearly-dead, aggressive hunters of humans, with no sense of humanity left. When we last saw Jorah in the TV version, he had confessed his affliction to Daenerys, and she sent him off to find a cure. Will he find Dany after her arrival in Westeros and bring with him an army of (now healthy?) Stone Men–healed by fire perhaps, to fight against those brought back to life by ice? Will he return to Valyria–an area largely abandoned except as a place of exile for the Stone Men since The Doom a thousand years ago–and learn the truth of what happened there? Could Valyria provide a key to ending both greyscale and perhaps also the White Walkers? Or is the haunting poem Tyrion and Jorah recited as they rowed down the Rhoyne toward the ruins of the city foreshadowing what’s going to happen to Westeros?
It’s interesting that most stories open with an infection that ushers in the apocalypse: The Stand; The Passage series; The Walking Dead; World War Z; I Am Legend; the MaddAddam trilogy; the Planet of the Apes reboot; The Last of Us video game; even back a century or two to the Scarlet Plague or The Last Man. I could go on and on. Martin is known for taking many fantasy tropes and turning them on their heads, so instead of having a plague begin the downfall of society, could greyscale serve to save it somehow? With reportedly two seasons left in the TV series after Sunday’s Season 6 finale, we’ll have less time to wait and find out than it takes a newly-infected greyscale patient to turn into a Stone Man.
(1) The information provided on greyscale in this article is a mix of literature from the books and the show. Note that the show, to my recollection, hasn’t delved into the grey plague, so information on that malady comes exclusively from the books. Also note some of the victims of greyscale differ in the books versus in the show (eg Jorah Mormont taking Jon Connington’s place in the TV version).
(2) Though Jorah denies any contact with the Stone Men initially, and it isn’t 100% clear if he was touched during the scene, he does back off from Daenerys when she moves toward him in S06E05, when he discloses his condition (which is now all the way up his forearm). This suggests he does believe he acquired it through direct contact with a Stone Man.
(3) Though these sufferers are uniformly called Stone Men, and the ones seen on-screen appear to be male, presumably there are also Stone Women. Possibly loss of hair as the skin calcifies could lead to a more androgynous look.
(4) I should note there are some alternative views about exactly how Shireen’s greyscale infection was acquired, and about the use of greyscale as a biological weapon.
(5) Or on “the Sorrows” in the novels.
(6) I don’t agree with several things in that article, written by a dermatologist. It concludes based mainly on symptoms and a bit on epidemiology that greyscale is something more like smallpox or HPV and largely rules out a leprosy-like illness. It also notes the potential for an infectious agent that’s only infectious to those with an underlying genetic susceptibility, but I don’t think there’s much evidence to suggest that.
Find other posts in today’s carnival on the science of Game of Thrones!
Wrong link–try this one!
We’ve been expecting it, and now it’s here.
Yesterday, two article were released showing that MCR-1, the plasmid-associated gene that provides resistance to the antibiotic colistin, has been found in the United States. And not just in one place, but in two distinct cases: a woman with a urinary tract infection (UTI) in Pennsylvania, reported in the journal Antimicrobial Agents and Chemotherapy, and a positive sample taken from a pig’s intestine as part of the National Antimicrobial Resistance Monitoring System (NARMS), which tracks resistant bacteria related to retail meat products. Not surprising, not unexpected, but still, not good.
Colistin is an old antibiotic. Dating back to the 1950s, it’s been used sparingly over the decades because it can cause serious damage to the kidneys and nervous system. It’s also typically administered intravenously in humans, so you can’t just pop a colistin pill and be sent home from the doctor. Newer preparations appear to be safer, and because of the problem with antibiotic resistance in general and limited treatment options for multidrug-resistant Gram-negative infections in particular, colistin has seen a new life in the last decade or so as a last line of defense against some of these almost-untreatable infections.
Because of its sparing use in humans, resistance has not been much of an issue until recently. And while human use is relatively rare compared to other types of antibiotics, in animals, the story is different. Because colistin is old and cheap, it’s used as an additive to feed in Chinese livestock, to make them grow faster and fatter. (We do this here in the U.S. too, but using different antibiotics than colistin). So as would be expected, use of this antibiotic led to the evolution and spread of a resistant strain, due to the presence of the MCR-1 gene. By the first time they saw this resistance, it was already present in 20% of the pigs they tested near Shanghai, and 15% of the raw meat samples they tested. In this case, the gene is on a plasmid, which makes it easier to spread to other types of bacteria. To date, most of the reports of MCR-1 have been in E. coli, but it’s also been found in Salmonella and Klebsiella pneunoniae–all gut bacteria that can be spread from animals via contaminated food products, or person-to-person when someone carrying the bacterium doesn’t wash their hands after using the bathroom.
So a question becomes, how exactly did it get here? And that’s very difficult to say right now. The hospital where the human case was reported notes that the patient reported no travel history in the past 5 months (so it’s unlikely that she traveled to China, for instance, and picked up the gene or bacterium carrying it there). The hospital says they’ve not found other MCR-1 positive isolates from other patients, but also that they’ve only been testing specimens for 3 weeks, so…yeah. Hard to say. People and animals (like the tested pig) can carry E. coli or other species that harbor MCR-1 in their gut without becoming ill, so it may have been in the population for awhile (as they’ve seen in Brazil) before it came to the attention of medical researchers. Perhaps it’s been circulating in some of our meat products, or spreading in a chain of miniscule transfers of shit from person to person to person to person, for longer than we realize. Or both.
I was asked on Twitter yesterday, “Should I panic today or put that off until next week?” I’m not an advocate of panic myself, but I do think this is yet another concern and another hit on our antibiotic arsenal. It’s not widespread in this country and as mentioned, colistin is luckily not a first-line drug, so it won’t affect all *that* many people–for now, at least.
There are already papers out there showing bacteria that have both NDM-1 (or related variants) and MCR-1 genes. NDM-1 is a gene that provides resistance to another class of last-resort antibiotics, the carbapenems. (Maryn McKenna has covered this extensively on her blog). When carbapenems fail, treatment with colistin sometimes works. But if the bacterium is resistant to both colistin and carbapenems, well…not good. That hasn’t been reported yet in the U.S., but it’s only a matter of time, as McKenna notes.
It doesn’t mean that we’re out of antibiotics (yet) or that everyone who has one of these resistant infections will be unable to find a treatment that works (yet). But we’re inching ever closer to those days, one resistant bacterium at a time.
Like cockroaches, the conspiracy theorists suggesting the Zika virus outbreak is anything but a normal, naturally-occurring event have begun to come out of the woodwork. To be expected, the theories they’re espousing make no sense scientifically, and each theory is incompatible with the others, but why should anyone expect that conspiracy theorists would actually use logic?
Claim One: the current Zika virus outbreak is due to the release of genetically-modified mosquitoes by British company Oxitec. The suggestion is that GMO mosquitoes were released in the same area of Brazil now experiencing Zika outbreaks, and somehow these mosquitoes caused the outbreak. The mosquitoes are engineered to require the antibiotic tetracycline in order to survive development in the wild, so when a wild female mosquito breeds with a male GMO mosquitoe, it’s essentially is a death sentence to the female’s offspring. Theorists argue that livestock use of tetracycline leaves this antibiotic in the environment, allowing some offspring to survive. Somehow, Zika is inserted into this.
What’s wrong with it? There’s absolutely nothing that makes sense to relate this to Zika. Even if these GMO mosquitoes can reproduce, that doesn’t mean they’re suddenly infected with the Zika virus. This article probably lays it out the best as far as a suggested mechanism, but even then it’s a convoluted mess, suggesting a transposon* (a “jumping gene”) moved from the mosquito into Zika virus (but where did the Zika come from in the first place though? was it already in Brazil?), then that transposon made Zika more virulent and gave the virus “an enhanced ability to enter and disrupt human DNA” (what??), which then leads to microcephaly. All without absolutely any citations from the scientific literature to back up this scenario, of course.
And that’s even assuming that the area where the testing occurred was the same as where the mosquitoes were released. It’s not, as both The Mad Virologist and Christie Wilcox point out. Both have many more details taking down this theory as well.
Who’s claiming this? Really credible places, like Brazilian Shrunken Head Babies (not even joking).
What’s wrong with it? Pretty much everything. First, the vaccine isn’t recommended until relatively late in pregnancy; even one of the links cited by the “shrunken heads” page notes that it’s suggested in the 27th to 36th week of pregnancy. This is very late in pregnancy to have such a severe effect on brain/skull development. For other microbes that cause microcephaly (such as cytomegalovirus or rubella), infection occurring in the first half of the pregnancy (before 20 weeks) is usually associated with a higher likelihood of adverse developmental outcomes, not one very late like Tdap. And of course, this theory completely contradicts the “Zika-GMO mosquito” one, which suggests that Zika is the cause.
Biologically, this makes zero sense–and furthermore, why wouldn’t other countries be seeing this spike, if Tdap is truly the cause? Women in the U.S. and other countries also receive this vaccine during pregnancy, but we haven’t seen an increase in microcephaly cases. Furthermore, a recent study has demonstrated yet again that Tdap is very safe during pregnancy.
Claim Three: Rockefeller something something bioterrorism something, maybe. They’ve taken the fact that an organization, the American Type Culture Collection (ATCC), has Zika virus available on their website, and twisted that into apparently some kind of deliberate release, maybe? It’s all pretty shadowy. [Updated: this site very clearly says the Rockefellers invented it to kill people. If that were true, they did a pretty shitty job].
What’s wrong with it? Even the Freethought Project post basically unravels its own conspiracy theory, but still posted this for some reason, noting “It seems that while the virus is available online, it is not extremely easy to get, and would likely require some extremely creative fraud in order to make it happen,” but concluding that “…it definitely does seem that it would be possible for a group or individual that is determined enough to make their way through the website’s security measures.”
I seriously doubt that.
For those of you who don’t know, ATCC is basically a global clearinghouse for biological samples–they offer tissue culture lines, bacteria, viruses, etc. Researchers need these for a number of reasons, such as having positive controls for assays, or to be sure they’re using the same cells as another investigator whose work they want to replicate or expand upon. I’ve used them many times to get both bacteriophage as well as isolates of bacteria for my research projects. And they won’t ship to just some random person.
When I moved institutions and set up my new laboratory, on my first ATCC order, they contacted the director of biosafety at my institution to be sure my lab was equipped and ready to handle the organisms I had requested. When that was assured, we still had to establish a Material Transfer Agreement in order for the items to actually be shipped–a legal document between ATCC and my university, signed by an “authorized representative” of my institution. It was only after jumping through all of these hoops that I was finally able to get the requested samples.
Even if someone had chosen to order Zika, an obscure, mostly-asymptomatic virus that until this outbreak was not associated with any serious ill effects, and perpetuated the “extremely creative fraud” mentioned by the Freethought Project…why? They’d need to initially infect themselves or others in order for the mosquitoes to subsequently become competent vectors of the virus. The mosquitoes would feed on them when there was adequate virus in the blood, and presumably the insects would then be released–to what end? To spread a previously-thought-relatively-harmless virus into a new population? Again, nonsensical.
[Updated: this doesn’t mean that “Rockefeller owns the patent on Zika virus,” as sites like this are claiming. As far as I can ascertain, there are no patents involving Zika. What it means is that the virus was deposited by Jordi Casals, who was an eminent virologist and had a large collection of viruses that he accumulated throughout his career, including Zika (but many others, as a search of ATCC shows). Rockefeller makes no money on this–in fact, now some journals require deposition of strains to ATCC or similar banks as a condition for publishing.]
Claim four: Zika simply doesn’t exist and/or isn’t causing microcephaly, and the “outbreak” is a ploy to push the not-yet-extant Zika vaccine/get people to blindly obey the government. (hat tip to Mary Mangan for this one).
What’s wrong with it? Pretty much everything. Rappoport has made a meta-conspiracy theory, claiming the increase in microcephaly is caused not by Zika, but by a combination of pesticide use and manufacturing, the Tdap and GMO mosquitoes mentioned above, mosquito sprays, and poverty/sanitation/malnutrition (the boogeymen of every anti-vaccine advocate). While he’s correct that the link between Zika and microcephaly isn’t yet 100% confirmed (as I mentioned yesterday), he’s taking at face value the claim that there actually is an increase in microcephaly at all–something which is also not been confirmed. So like many science deniers, he’s taking the parts of the research that fit his biases (look at how toxic Brazil is! Of course it’s causing health problems in babies!) and ignoring the parts he doesn’t–that if there is an increase in microcephaly, Zika might be a driving force. In his mind, the virus is irrelevant and just a mechanism to make the public into “sheep” who will fall in line with government recommendations.
I’m sure this will not be the last of the conspiracy theories. Like those we saw with Ebola, these have the potential to cause real harm. Outcry over the GMO mosquito program can curtail use of another agent to control the Aedes aegypti mosquito–the primary vector not only of Zika, but also yellow fever, chikungunya, and dengue. I know those who benefit from these type of conspiracies will never stop churning them out (Mike Adams, I’m looking at you), but we need to bring them to the light and show just how little scientific support any of this has. It won’t inoculate everyone against these ideas, but hopefully it will provide enough community immunity that they’re unable to spread far and wide.
*Christie Wilcox pointed out another great observation on just how implausible this is–that the potential to insert a 8.4kb double-stranded DNA transposon into a 10.8kb single-stranded RNA virus is…not possible. So, yeah, just to add to the ridiculousness of that idea.