Home Sample Blog Description 2019-05-16T00:00:00-04:00 Alan Dove, PhD https://turbidplaque.com/grav/blog The Filtrate: 16 May 2019 https://turbidplaque.com/grav/blog/2019-filtrate-0516 2019-05-16T00:00:00-04:00 2019-05-16T00:00:00-04:00 It's Thursday, so it's time once again to look back over the news that caught my eye during the past week and say "wow, humanity is so screwed."

China is grappling with an epidemic of African swine fever, and the virus is winning. ASF spreads easily, kills pigs fast, and there's no treatment or vaccine available. So far it's led to the culling of over 1 million pigs in China, and appears to have jumped the borders into adjacent countries that are even less equipped to deal with it.

There is a vaccine for dengue fever now, but as discussed here on the Turbid Plaque, and in more depth by Trudy Rey on Virology Blog, it's got some problems. The underlying issue, which researchers have struggled to solve for decades, is that exposure to one strain of dengue may make someone more susceptible to subsequent infections with other strains. The upshot is that if you've never had dengue, the virus is literally safer than the vaccine, and if you have had dengue, you're probably too old to get the vaccine.

Have you ever noticed some random piece of infrastructure - high-tension wires, cell phone towers, manhole covers - and then for awhile you can't stop noticing it everywhere? That, times a thousand, is probably how it feels for the authors of this new UN report on how the world is mismanaging its supply of sand. We're not running out of it, exactly, just moving it around in ways that aren't sustainable, at mind-boggling scales.

Regardless of the problems the world is facing, though, we can look to science to find the best solutions. We just have to come up with some ideas, then test them side-by-side in randomized controlled trials. Unless, of course, people are fundamentally averse to such trials. When given the choice between having an untested solution imposed on them and letting someone conduct a proper experiment to test it, people from diverse backgrounds consistently took the first option. Way to go, human brain.

If you want to do some science anyway, perhaps you need an autoclave. Too bad they're expensive, heavy, and take up so much space. As these folks demonstrate, though, standard pressure cookers work just as well for most purposes. I was surprised that the ones they tested operate at such low pressures, but they were focusing on the budget models. My own recommendation: get the All American. It's the traditional rattle-top design, reaches a full 15 psi, requires no gaskets, and is built like a tank. Great for cooking, too.

The Filtrate: 9 May 2019 https://turbidplaque.com/grav/blog/2019-filtrate-0509 2019-05-09T00:00:00-04:00 2019-05-09T00:00:00-04:00 Malarial fevers, herpes viruses, and The Filtrate: they all just keep coming back.

It's often said that politicians and diapers should both be changed regularly, and for the same reasons. According to the folks who run the NIH, the same applies to lab and branch chiefs at the institution, which is about to implement term limits for those powerful positions. The terms would still last 12 years, so don't expect change overnight, but advocates see this as a way to get some fresh - and maybe more diverse - faces into these prestigious research posts.

You know who doesn't need to be any more diverse? The microsporidia. They're a great example of how one can study biology for decades, then suddenly stumble across a paper about some novel branch of life and say "WTF, nature?" Seriously, check them out. They're eukaryotes that have streamlined their genomes so much their life cycle is almost viral, and they seem to infect everything.

As diverse as microsporidia are, though, they're not likely to supplant viruses anytime soon. Indeed, a new analysis using high-throughput sequencing and a massive amount of bioinformatic data mining reveals that viral dominance of the Earth extends across all of the oceans. The researchers found over 195,000 viral populations clustered into five distinct ecological zones. The zones are a surprise, contradicting the view of the global oceans as a big, evenly mixed solution and suggesting that viruses are concentrated by, or perhaps driving, a higher order segregation of the marine ecosystem.

What do you get when you cross a lab mouse with a deer? No, not a deer mouse, but something very useful for studying prion diseases: a cervidized mouse. These animals carry just enough deer DNA to be susceptible to chronic wasting disease, a prion disease now afflicting deer (cervids) in North America and elsewhere. The cervidized mice enabled researchers to develop a promising vaccine against the disease. Delivering it to the deer, however, may be hard.

Compared to deer, humans are pretty easy to immunize, or at least we should be. Unfortunately, an internet-assisted epidemic of stupidity has swept the world in recent years, which is why we're now experiencing a measles epidemic. So how do we vaccinate against that? It's going to take some social science to figure it out, and these folks have made an interesting start. Their "5C" scale measures people's senses of "confidence, complacency, constraints, calculation, and collective responsibility," and could help identify pockets of vaccine hesitancy before the viruses do.

The Filtrate: 2 May 2019 https://turbidplaque.com/grav/blog/2019-filtrate-0502 2019-05-02T00:00:00-04:00 2019-05-02T00:00:00-04:00 It's time once again for a weekly aliquot of The Filtrate. Like a real vacuum filtration apparatus, we keep working when everything else sucks.

For years, researchers have been warning that some of the compounds used in food processing might not be good for us. The data have now persuaded the American Academy of Pediatrics to take a stand against certain additives, including the notorious bisphenol-A, some plastics, and a range of artificial colors. Their technical analysis and policy statement make interesting reading. In case you think this is strictly a recent problem, though, check out Deborah Blum's biography The Poison Squad.

Some viruses stimulate immune responses against highly variable parts of their capsids. This is why we have to get new flu shots every year, for example. It's possible for the immune system to generate antibodies against more conserved parts of these viruses, yielding "universal" immunity to multiple strains, but it happens rarely. These folks came up with a nifty strategy to hide the normal antigenic targets and focus immune attention on conserved epitopes. It seems to work in their animal model.

A strong antibody response is the usual goal in vaccine development, but for some viruses that might not be enough, or even desirable. This paper shows that vaccinating mice against chikungunya virus works well in adult animals, stimulating a strong antibody response and protecting the mice from serious disease. When the vaccinated mice get old, though, the protective antibodies appear to make them more susceptible to the virus than unvaccinated controls. Chikungunya vaccine developers should watch out for this, or risk replicating the Dengvaxia disaster.

Until we have effective vaccines against vector-borne diseases, insect repellents are one of the best lines of defense. The classic DEET remains popular, but how does it work? In three different ways, apparently. Aedes aegypti mosquitoes, at least, seem to think that DEET smells bad, tastes terrible, and feels icky on their feet. Finally, something we can agree on.

Deal or no-deal? That seems to be the question Brits are obsessed with lately, and European science funding agencies aren't happy with the situation. Among other traumas, UK researchers receiving some EU funds may now need to figure out how to move their grant administration offshore. Good luck with that, folks. We'll just chuckle smugly to ourselves and ... try to read the Mueller report. Okay, nevermind the smug part.

The Filtrate: 25 April 2019 https://turbidplaque.com/grav/blog/2019-filtrate-0425 2019-04-25T00:00:00-04:00 2019-04-25T00:00:00-04:00 Welcome to the second issue of The Filtrate, motto: "All the news that fits through a 0.2µm RSS feed."

This paper describes a new animal model for studying one of the most annoying aspects of dengue fever virus: post-vaccination infection enhancement, in which prior immunity to one strain of the virus can actually make people develop much more serious symptoms when infected by another strain. The new model appears to provide a robust system for testing future dengue vaccines to make sure they don't cause this problem. That could help avoid a repeat of the Dengvaxia fiasco, which killed several kids, terrified millions of parents, and set the entire field back by years.

While dengue fever is spread by mosquitoes, many other tropical diseases are waterborne, and a huge problem in combating them is tracking sewage upstream. These folks used open source geographical information system algorithms and databases to map the watersheds of tens of thousands of villages across Indonesia, with immediate applications to public health.

Besides the infections we already know about, researchers are on the lookout for new pathogens that could move from animals into people. The traditional model of zoonosis, as this phenomenon is called, stipulates that an animal pathogen has to clear a series of barriers to establish itself in humans. An insightful new paper argues that the first barrier, adapting to the human genetic environment, is by far the most important. That should help a lot in focusing our surveillance efforts.

In less inspiring news, The University of Texas M.D. Anderson Cancer Center - and possibly other research centers - purged several ethnic Asian researchers from the payroll at the behest of federal officials. After Science broke the news, administrators went into damage control mode to deny racial profiling, but the facts alone are disturbing.

Are you organizing a meeting? Writing a news story? Convening a panel? Instead of using the lazy approach and just Googling up the same old white dudes everyone else contacts for these things, reinforcing structural biases, why not make an actual effort to diversify? This database should help.

We conclude with a bedtime story. Triatoma sanguisuga, the kissing bug, is best known as the vector for Chagas disease, a nasty tropical parasite endemic to Latin America. Now the vector, at least, has made it as far north as Delaware, where concerned parents found one biting their child's face while she was in her bedroom. Sleep tight.

The Filtrate: 17 April 2019 https://turbidplaque.com/grav/blog/2019-filtrate-0417 2019-04-17T00:00:00-04:00 2019-04-17T00:00:00-04:00 "Gee, I should blog about that," says Alan a few times a day. Then the link goes into an immense pile of similar bookmarks, never to be seen on these pages. Let's try something different: a list of papers I've found interesting in the past week, with brief comments about each.

What if we could use social media data mining for something besides predatory capitalism? These folks found that they could predict the spread of dengue fever in a tropical city from those data, which is both inspiring and a little bit eerie.

When a drug patent ends, the drug becomes a lot less profitable. Sometimes it becomes so unprofitable that companies stop making it. Other times the sole remaining supplier jacks the price up so high nobody can afford it. This paper explores the problem, and proposes forming public-private partnerships to fix these broken drug markets.

Animal welfare laws ensure humane treatment for laboratory animals, but in many countries these laws don't extend to wildlife. This policy analysis argues that research journals should fix that loophole themselves, rather than waiting for national legislatures to act.

It's called a poverty trap: debt causes stress, which leads to bad decision-making, which causes people to incur more debt. A natural experiment allowed researchers to quantify this phenomenon, and revealed that programs that reduce the number of debts owed by poor people can improve their decision-making skills.

Speaking of economics, how should we measure a nation's wealth? The traditional Gross Domestic Product number doesn't work well for developed nations; massive online choice experiments might yield a better index.

By now we should all realize that burning fossil fuels is destroying the planet and killing people. This study looks at the problem the other way around, estimating the benefits we could reap if we kicked the fossil fuel habit. It would be pretty awesome. If we could.

Sometimes a paper's title makes me say "wait ... WHAT?" This one's about the effects of an infection-generated electric field. Yes. Infection-generated. Electric field. Just read the paper. I can't make this stuff up.

A Walk on the Wild Side at Tufts Veterinary School https://turbidplaque.com/grav/blog/2019-tufts-wildlife-clinic 2019-02-24T00:00:00-05:00 2019-02-24T00:00:00-05:00 On a blustery day in mid-December, TWiV co-host Vincent Racaniello and I, along with friend-of-the-show Islam Hussein, visited the picturesque campus of the Tufts University School of Veterinary Medicine in Grafton, MA. Our primary job there was to record an episode of TWiV in front of a live audience, featuring Tufts researcher Jon Runstadler and members of his lab. You can check out that episode now on the TWiV site. Before the recording session, though, we got to tour New England's only veterinary school, which occupies the former site of a state mental hospital.

While the fistulated cow, athletic treatment center (think racehorses), and abandoned 19th century psychiatric dormitories were all interesting in their own ways, the highlight of the tour was the school's wildlife clinic. The small, purpose-built facility sits amid a cluster of huge, well-ventilated wooden structures resembling tobacco barns. As we later learned, these are outdoor flight cages, where birds recovering from various injuries can take wing without encountering the hazards of the wider world.

In the airy lobby, we met Maureen Murray, Assistant Director of the clinic. A compact, soft-spoken woman, Murray exudes the quiet competence of someone accustomed to restoring order from chaos. She explained the mission of the clinic, which accepts injured wild animals brought in from across the state. As she spoke, it occurred to me that she's exactly the kind of person I would want bandaging my wing if I'd been hit by a car.

The facility resembles a scaled-down hospital emergency department, but with the distinct dander-and-disinfectant smell of a veterinarian's office. A large screen lists the current cases, with a system of abbreviations similar to those used by birders: BAOW for Barred Owl, CAGO for Canada Goose, and so on. Each line carries a brief description of the patient's chief complaint. Injuries from automotive encounters and dog maulings predominate.

This is a teaching hospital. The small pathology lab features a microscope with multiple binocular heads, so groups of students can view specimens together. While we were there, one veterinarian in training was studying at a desk in the hall; veterinary students are always studying. Meanwhile, in a radiology suite about the size of a modest bedroom, several staffers and trainees gathered around an Eastern cottontail rabbit recently rescued from a family dog's jaws, X-raying its hindquarters to assess the damage.

Yes, they repair broken bunnies.

Their generosity even extends to invasive species, at least sometimes. In a concrete-floored waterfowl recovery room with a built-in wading pool, a mute swan eyed us imperiously while paddling back and forth. Murray said that once it recovered, it would be sent to a park near where it had been found.

That raised the tricky subject of discharging patients. To limit the spread of disease and minimize interference in local ecology, the clinic takes pains to send animals back to the areas where they originated. Often, that means dragooning students who are heading somewhere for other reasons into playing zoological chauffeur....

Mastering the MeSH https://turbidplaque.com/grav/blog/2018-mesh-terms 2018-11-15T00:00:00-05:00 2018-11-15T00:00:00-05:00 When I was a graduate student at Columbia University, I had the extraordinary privilege of working in the same building as one of the world's greatest medical research libraries. When I saw a reference to a paper I wanted to read, I could usually lay my hands on a copy of it within minutes, no matter how obscure the journal or how long ago it was published. Often, the slowest part of the process was waiting for the elevator.

Besides hosting miles of shelves packed with the combined output of hundreds of medical journals, the library also had a lounge with the latest issues of all of those same journals. Whenever I was sufficiently motivated (which was less often than it should have been, but still), I could sit in a comfy chair and catch up on Science, Nature, or the Journal of Virology.

Today, of course, we have the Internet. It's not always better. Yes, the world of online ressearch is faster and vastly more accessible than the basement of the Hammer building, assuming one has keys for the Web's various walled gardens. That's fine for very focused reading. If I want to find all of the papers about Zika virus and microcephaly published in the past year, I can look them up in milliseconds, and start digging through them moments later. That's lovely.

What's missing, though, is the serendipity. Whenever I looked up an old paper deep in the stacks, I would pull a volume off the shelf, blow away some dust, and open the pages to the original publication, bound in its journal just as it was when it came out. It was quite common to glimpse the paper right before or after it, realize that the publisher had run them together in the pages for a reason, and decide that this, too, was worth reading. The same thing happens when paging through the latest issue of any printed journal.

The Internet excels at answering the questions we ask it. Where it fails is in telling us what questions we ought to be asking.

Individual journals have tried to combat this with helpful suggestions alongside articles, but the implementation varies tremendously, the interfaces are often clunky, and in many cases they're just basing what "You might also like..." on an algorithm no more sophisticated than the PubMed search that brought the reader there in the first place. There is, however, another way.

It's called Medical Subject Headings (MeSH). Readers who are already deeply enMeSHed may not get much from this post, but on the assumption that I'm not the last person to figure out how useful this system is, I'll continue.

When looking at the abstract of an article on PubMed, see if one of the expandable options below it mentions "MeSH terms." If so, expand it, click one of the terms, and choose the option to search PubMed for that. The result will be a human curated bibliography of related papers. Yes,...

A Fair Few Flu Cases https://turbidplaque.com/grav/blog/2018-swine-flu-fair 2018-11-08T09:00:00-05:00 2018-11-08T09:00:00-05:00 Since at least 1918, when the "Spanish Flu" swept across the world, leaving a trail of corpses in its wake, Americans have blamed influenza outbreaks on other countries. These days we like to point fingers eastward, invoking images of ancient agricultural practices and chaotic live animal markets in China and Southeast Asia. With a whiff of smugness, we tell ourselves that those are obviously the kinds of places where we can expect the next global flu pandemic to make the leap into humans.

Unless it happens in Maryland, that is. As public health officials reported recently in MMWR:

On September 17, 2017, the Maryland Department of Agriculture (MDA) was notified by fair and 4-H officials of ill swine at agricultural fair A, held September 14–17. That day, investigation of the 107 swine at fair A revealed five swine with fever and signs of upper respiratory tract illness. All five respiratory specimens collected from these swine tested positive for influenza A virus at the MDA Animal Health Laboratory, and influenza A(H3N2) virus was confirmed in all specimens by the U.S. Department of Agriculture National Veterinary Services Laboratory (NVSL). On September 18, MDA was notified by fair and 4-H officials that swine exhibitors were also ill.

By the time the outbreak burned out, H3N2 swine flu had infected at least 40 people at three fairs around the state. Over 1/3 of the patients had only indirect contact with pigs. In one case, a child who had simply been wheeled through the exhibit hall in a stroller caught it. Fortunately nobody died, though two children infected by this virus had to be hospitalized.

This spillover event didn't set off the next 1918-scale flu disaster, but it certainly had a lot of the necessary elements.

Flu viruses have a unique and complex ecology. Birds are the main reservoirs for influenza, and the avian strains of it don't grow very well in humans. Bird flu can infect poultry workers who are exposed to lots of the virus, but it seldom spreads to other people. We're dead-end hosts for it. However, if it first makes an intermediate stop in pigs it can mutate and adapt to mammalian lungs. The resulting swine flu strains can more easily infect humans.

Once a flu strain becomes established in humans, it spreads seasonally and accumulates minor mutations, a process called genetic drift. That's how it evades the antibodies people built up against it the previous year, allowing it to re-infect the same hosts again. Occasionally an entirely new strain will make the leap from animals (usually pigs) to humans, and displace one of the strains that was circulating before. These genetic shifts are where major flu pandemics come from. That's why flu virologists are so intensely interested in pigs.

Indeed, the Maryland outbreak isn't the first time this particular strain of swine flu, called variant H3N2, has come to the attention of public health officials.

Flu strains are classified by their two major antigenic proteins, hemagglutinin (H)...

75 Years of Molecular Biology https://turbidplaque.com/grav/blog/2018-75-years-of-molecular-biology 2018-10-25T00:00:00-04:00 2018-10-25T00:00:00-04:00 In the November 1943 issue of the journal Genetics, Salvador Luria and Max Delbrück settled a long-running but arcane debate among bacteriologists. The original paper is freely downloadable, and is an amazing document to read today.

There's a delightful innocence in the simplicity of the experimental design, the lengthy explication of the theory behind the work, and the humbleness of the authors' conclusions. There is no hint that the paper is describing the dawn of molecular biology, a field that would revolutionize humanity's relationship with nature in ways that are still unfolding 75 years later.

Luria and Delbrück didn't set out with such grand ambitions. The question they wanted to address was simply how bacteria became resistant to infection with bacterial viruses, or phages. There were two competing theories at the time, based on previous experiments.

One school of thought was that a culture of bacteria grown in the absence of phages would acquire random mutations over time, some of which would by chance confer immunity to a phage. Once that particular phage was introduced, only bacteria with pre-existing resistance to it would survive. That aligned nicely with traditional evolutionary processes observed in "higher" (more complex) organisms.

The other theory was that bacteria could acquire resistance as a result of a phage infection. In this view, a more deterministic mechanism was at play, in which the selective pressure itself (phage) actually caused the adaptive mutation. If this model was correct, it would mean bacteria followed a fundamentally different evolutionary playbook from more complex organisms. That may sound like a weird idea today, but because of the way previous experiments had been designed, a lot of the early data actually seemed to favor it. Luria, in fact, was an enthusiastic supporter of this theory.

To test these two hypotheses, the researchers devised a brilliantly simple experiment. They grew separate cultures of bacteria, each originating from a single cell, then exposed these distinct populations to bacteriophage T1.

If the resistance was due to random mutations arising beforehand, one would expect tremendous variation between cultures, with some having a lot of survivors and some being wiped out completely. Essentially, the bacteria would be playing slot machines. There would be a lot of losers but occasionally some really, really big winners.

If the bacteria exhibited acquired immunity as in the second model, however, one would expect a consistent proportion of the population from each independent culture to survive the phage infection. Here, the bacteria would be investing in the bond market. The outcomes would be distributed in a boring, highly consistent pattern.

The results were absolutely clear. There was immense variance between cultures, proving that resistance was arising randomly before the bacteria encountered the phage. Bacteria, in other words, underwent the same natural selection and evolution process as more complex organisms.

That conclusion settled the eggheaded debate the authors had started with, but its echoes reached a lot farther. Luria and Delbrück's result implied that all life, from bacteria to humans, operated on...

What the Heck Is This 'Polio-Like' Disease? https://turbidplaque.com/grav/blog/2018-polio-like-illness 2018-10-18T00:00:00-04:00 2018-10-18T00:00:00-04:00 Most people have by now seen the news about a mysterious "polio-like" illness paralyzing children across the US. To date, the CDC has confirmed 62 cases of the condition, called acute flaccid myelitis (AFM), in 22 states since August. Another 65 people are suspected to have it, but haven't had the diagnosis officially confirmed yet. 90% of the patients are under 18; the median age is 4. All of the cases have so far tested negative for poliovirus.

So what's going on? The headlines, at least, aren't too far off base. The term "polio-like" is pretty accurate here. A person with AFM loses the use of one or more limbs suddenly, for no obvious reason. They just go limp. Some recover, regaining full or partial use of the paralyzed limbs, while others don't. That's exactly what happens in paralytic poliomyelitis.

There are good reasons to suspect that a similar virus might be involved, too. The first documented outbreak of AFM in the US was in 2014, with a total of 120 confirmed cases in 34 states between August and December. There was a strong - but not absolute - correlation between those cases and enterovirus D68 infection. EV-D68 is a picornavirus, the same viral family that includes poliovirus. Some of the current cases have also tested positive for EV-D68, but the correlation seems a lot weaker this time.

One striking aspect of these outbreaks is that they're cyclical. The CDC data show this quite clearly, with distinct spikes in AFM incidence every other autumn since 2014. There's a more or less constant trickle of cases between peaks too.

And that's pretty much all the hard data we have. Beyond that we're left with educated guesses about what's going on. Here are mine.

First, I'd be surprised if periodic AFM outbreaks are a new phenomenon. The CDC didn't track non-polio AFM before 2014, so it's entirely possible that this cycle of outbreaks has been happening for a long time without anyone realizing it. While the individual cases are undoubtedly devastating to the families involved, the actual numbers are small in national terms, and the cycle wouldn't have been obvious. Sometimes a kid becomes paralyzed for no obvious reason. Sometimes they get better, sometimes not. Until the CDC started keeping track, it was just one more medical mystery.

Second, the pattern here strikes me as very picornaviral. Before vaccines drove it to the brink of extinction, poliovirus caused regular seasonal outbreaks. The virus spreads very easily, especially among children, and in an unvaccinated population nearly 100% will become infected. 99% of them will develop no symptoms worse than mild diarrhea. However, even 1% of a population becoming paralyzed is an immense social trauma; in the pre-vaccine era, everybody knew someone who'd been put in a wheelchair or iron lung by polio.

Now let's look at those two things together. Something, perhaps a virus, has likely been causing small, cyclical outbreaks of AFM every couple of years for a long time. During much...