Someone call Elon Musk, I have bad news. Things were going well at The Chicken House Solar Generating Plant when a sudden illness wiped out 99% of the chickens. There were only 50 chickens working at the plant, so that remaining 1/2 of a chicken is exhausted.
Maybe we should back up. Last time, we built a 1 km² solar generating plant on top of a chicken house in Texas. It was just a famous (locally) historic monument, now it’s a monument and a power generating plant. We had to violate a few building codes to put a 1 km² solar array on top of a chicken coop, but Elon knows a few people so the permits weren’t a problem.
Enough! Who is this Marek, evil destroyer of chickens?
Well, Marek himself doesn’t run around with an axe and a chicken baster. Instead he has a disease (Marek’s Disease), but it was rarely lethal. Now it’s mostly fatal and that might be our fault. I mean the fault of humans in general, not you and me and Elon.
First, a little background for those of us who either didn’t grow up with chickens or who don’t currently employ chickens for light engineering tasks.
Latest Insights into Marek's Disease Virus Pathogenesis and Tumorigenesis (Bertzbach et al. 20201)
Marek’s disease virus (MDV) mainly infects chickens and causes one of the most prevalent cancers in the animal kingdom.
MDV is among the diseases with the highest economic impact in modern poultry production worldwide, together with other viral diseases, such as Newcastle disease, infectious bronchitis and infectious bursitis. Chickens are exposed to MDV around the globe and the virus is present in a large proportion of flocks.
So it’s mostly found in chickens, and most chickens have it. It sounds pretty serious, but our HMO doesn’t cover it because our HMO doesn’t cover chickens. I will discuss this with the head of Chicken and Human Resources later.
Can we do anything about it? Well, there are vaccines for it, and they work, but there’s a little issue that might explain why our second shift all called in dead.
Marek's disease in chickens: a review with focus on immunology (Boodhoo et al. 20162)
Marek’s disease (MD), caused by Marek’s disease virus (MDV), is a commercially important neoplastic disease of poultry which is only controlled by mass vaccination. Importantly, vaccines that can provide sterile immunity and inhibit virus transmission are lacking; such that vaccines are only capable of preventing neuropathy, oncogenic disease and immunosuppression, but are unable to prevent MDV transmission or infection, leading to emergence of increasingly virulent pathotypes.
We have vaccines for Marek’s Disease and poultry farms use them extensively, but those vaccines don’t prevent transmission of the disease. That’s why it’s still present in most commercial flocks and 100% of chicken-staffed solar power plants.
The vaccines keep the chickens from dying, but they still get infected and pass on the infection. It also sounds like these authors think the disease is getting increasingly deadly. Does anyone have a theory about this?
Use of Marek's disease vaccines: could they be driving the virus to increasing virulence? (Davison and Nair, 20153)
Vaccination of newly-hatched chicks with live vaccines has been widely used to successfully control MD since the early 1970s. However, vaccinated chickens still become infected and shed MDV. Vaccine breaks have occurred with regularity and there is evidence that the use of MD vaccines could be driving MDV to greater virulence.
What the heck? So there are regular occurrences of strains that the vaccines don’t stop, and the increasing deadliness of those strains might actually be due to the vaccines?
Up till now almost all of the issues at the plant have been standard industrial accidents, and since they all involved live chickens and high voltage the most common outcome has been tasty fried chicken.
So what’s the broader impact? Should we hire more chickens, or people this time? We’ll need to replace all the uniforms because people wear pants.
Imperfect vaccines and the evolution of pathogen virulence (Gandon et al. 20014)
This paper was looking at the potential impact of not-so-sterilizing vaccines on human populations.
Vaccines rarely provide full protection from disease. Nevertheless,partially effective (imperfect) vaccines may be used to protect both individuals and whole populations. We studied the potential impact of different types of imperfect vaccines on the evolution of pathogen virulence (induced host mortality) and the consequences for public health. Here we show that vaccines designed to reduce pathogen growth rate and/or toxicity diminish selection against virulent pathogens. The subsequent evolution leads to higher levels of intrinsic virulence and hence to more severe disease in unvaccinated individuals.
Oh, so that might be what happened with MDV. Is this serious?
This evolution can erode any population-wide benefits such that overall mortality rates are unaffected, or even increase, with the level of vaccination coverage.
So a leaky vaccine can, in theory, completely fail to reduce mortality. And it potentially could increase mortality, if, like with the vaccines for Marek’s, we give them to just about everybody.
That’s not the best news. Plant management skimped on the health insurance, but all the chickens have solid life insurance payouts (because… ZAP!) and Elon’s not going to be happy with taking a financial hit here.
In contrast, infection-blocking vaccines induce no such effects, and can even select for lower virulence. These finding have policy implications for the development and use of vaccines that are not expected to provide full immunity, such as candidate vaccines for malaria.
Okay, so infection blocking vaccines don’t have this risk, but non blocking vaccines like the ones for MDV do. Did anyone try to actually do this in the lab?
Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens (Read et al. 20155)
Could some vaccines drive the evolution of more virulent pathogens? Conventional wisdom is that natural selection will remove highly lethal pathogens if host death greatly reduces transmission. Vaccines that keep hosts alive but still allow transmission could thus allow very virulent strains to circulate in a population.
Vaccines that keep the infected chickens alive allow the super deadly variant to spread, so the infected chickens become lethal little super-spreaders. Any chickens not vaccinated are basically gonna die.
This theory proved highly controversial when it was first proposed over a decade ago, but here we report experiments with Marek’s disease virus in poultry that show that modern commercial leaky vaccines can have precisely this effect: they allow the onward transmission of strains otherwise too lethal to persist.
Oh crap. They actually did it in the lab.
The imperfect-vaccine hypothesis attracted controversy, not least because human vaccines have apparently not caused an increase in the virulence of their target pathogens. But most human vaccines are sterilizing (transmission-blocking) or not in widespread use or only recently introduced.
Wait, did they say “most human vaccines are sterilizing”? Not all? So there are human vaccines that could potentially have this same issue? And widespread use of a vaccine could be a risk?
This could be serious. Some of the chicken pensioners have been saying that back in their day Marek’s Disease wasn’t that big of a deal, they just had a few drinks, put on some wet socks and went to bed early. But nowadays it’s turning chicken retirement communities into ghost towns.
MDV became increasingly virulent over the second half of the 20th century. Until the 1950s, strains of MDV circulating on poultry farms caused a mildly paralytic disease, with lesions largely restricted to peripheral nervous tissue. Death was relatively rare. Today, hyperpathogenic strains are present worldwide.
Note for the chickens: “hyperpathogenic” means “really deadly.” Unlike “hyperloop” which means “really useless.” Don’t tell Elon I said that, he’s really attached to his loop thing.
Our data do not demonstrate that vaccination was responsible for the evolution of hyperpathogenic strains of MDV, and we may never know for sure why they evolved in the first place.
But whatever was responsible for the evolution of more virulent strains in the first place (and there may be many causes), our data show that vaccination is sufficient to maintain hyperpathogenic strains in poultry flocks today.
So the researchers didn’t prove definitively that the vaccines directly caused the evolution of more deadly strains because it’s very hard to nail down the exact mechanism of evolution of a virus. But regardless of what is causing the evolutionary change, they are sure the vaccines keep these deadlier strains alive.
[In case that distinction isn’t clear, here’s another example: the lion doesn’t cause gazelles to mutate, thereby making the species faster. Those mutations happen randomly, for other reasons. The lion just kills all the slow gazelles.]
As of 2020 this theory of the vaccine keeping the deadlier strains alive, which was controversial twenty years ago, has been getting wider and wider acceptance:
Latest Insights into Marek's Disease Virus Pathogenesis and Tumorigenesis (Bertzbach et al. 2020)
Widespread vaccination has drastically reduced the incidence of Marek’s disease. However, MDV outbreaks are reported sporadically and vaccine breaks do occur.
Moreover, vaccinated chickens are still susceptible to infection with MDV field strains and shed these into the environment. These ‘imperfect’ vaccines allow the virus to evolve and acquire a higher virulence.
Enough! Elon just wants an executive summary because he’s really important and busy and has a hair appointment and a date with a hottie
The short version is this:
Marek’s Disease was a small financial problem for the poultry industry 50 years ago so we started vaccinating chickens. But the vaccines don’t prevent infection, they just prevent the symptoms.
Viruses evolve, but normally more deadly variants die out instead of spreading. Basically if the virus kills a chicken, that chicken doesn’t spread the virus (because he’s pushing up daisies instead of out clubbing). By keeping the chicken alive we allow the more deadly variant to spread.
And as a result we now have to vaccinate all the chickens (or they all die). We have basically transformed Marek’s Disease into a permanent revenue stream for vaccine manufacturers by using non-sterilizing vaccines.
This is great news if you sell vaccines for a living, and really, really bad news if you raise chickens.
Or if you hire them to run your solar plant.
For a little bit of engineering and some light humor, check out how the chickens responded to this outrage:
Bertzbach LD, Conradie AM, You Y, Kaufer BB. Latest Insights into Marek's Disease Virus Pathogenesis and Tumorigenesis. Cancers (Basel). 2020 Mar 10;12(3):647. doi: 10.3390/cancers12030647. PMID: 32164311; PMCID: PMC7139298.
https://pubmed.ncbi.nlm.nih.gov/32164311/
Boodhoo N, Gurung A, Sharif S, Behboudi S. Marek's disease in chickens: a review with focus on immunology. Vet Res. 2016 Nov 28;47(1):119. doi: 10.1186/s13567-016-0404-3. PMID: 27894330; PMCID: PMC5127044.
https://pubmed.ncbi.nlm.nih.gov/27894330/
Davison F, Nair V. Use of Marek's disease vaccines: could they be driving the virus to increasing virulence? Expert Rev Vaccines. 2005 Feb;4(1):77-88. doi: 10.1586/14760584.4.1.77. PMID: 15757475.
https://pubmed.ncbi.nlm.nih.gov/15757475
Gandon S, Mackinnon MJ, Nee S, Read AF. Imperfect vaccines and the evolution of pathogen virulence. Nature. 2001 Dec 13;414(6865):751-6. doi: 10.1038/414751a. PMID: 11742400.
https://pubmed.ncbi.nlm.nih.gov/11742400/
Read AF, Baigent SJ, Powers C, Kgosana LB, Blackwell L, et al. (2015) Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens. PLOS Biology 13(7): e1002198.
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002198