The Ebola Wars | Hacker News Reader

The Ebola Wars

newyorker.com

192 pointscwal37107 comments

> The town [of Kenema] sits in fertile, hilly country, dotted with small villages, ninety miles southwest of the place where the borders of Sierra Leone, Guinea, and Liberia converge in a triskelion. This border area was the cradle of the Ebola outbreak.

I was unfamiliar with the word triskelion in this description. So I looked it up on Wikipedia [1]. Turns out it is an ancient motif or symbol consisting of three interlocking legs or spirals.

So then I checked the border area between these three countries and indeed, it is quite well described as a triskelion although the top border is more like 180 degrees than 120. I have uploaded a cropped Google Map to imgur showing the area [2]. The town of Kenema is in the southwest corner. Guinea is the NE section, Sierra Leone is the western part and Liberia is the SE area.

[1] http://en.wikipedia.org/wiki/Triskelion

[2] http://imgur.com/cOPx4Ty

The description of the conditions in Liberia, Guinea, and Sierra Leone and the over-whelming odds that the doctors there are facing was heartbreaking to read.

The Ebola outbreak in West Africa is as much a function of poverty as it is of the Ebola Virus. One of these all of us can fight.

As someone who has spent extensive time in West and Central Africa, poverty is as much a second order (or third or fourth) effect as the Ebola outbreak, and much harder to fight. System fragility (whether it's relative to disease, famine, or other natural disasters), is a function of poor leadership more than anything. What is scary is that there is plenty of evidence that government to government aid does more harm than good, and Western attempts at fixing the problems only make things worse.[1]

[1]See any of Bill Easterly's writing - http://williameasterly.org/

By "poor leadership" did you mean "warlord rulers taking the vast majority of the aid money thrown in their general direction"?

"Warlord" implies a military bent. Many of the worst culprits are bureaucrats - spending most of their time wearing $10,000 suits while being wined and dined by Western leaders and skimming millions into the accounts of their inner circle. Power is not always held by physical force.

I am profoundly moved by the heroism Dr Khan and his nurses showed and the example they've set for future generations of medical professionals. I hope it's publicized when Dr. Khan's family finishes setting up the foundation in his name

http://www.thelancet.com/journals/lancet/article/PIIS0140-67...

How? Throwing money at the problem doesn't yield results (as is typically the case). The issues in Africa seem to be fundamental; they are issues of culture, resources, and structure.

A sample of the Ebola now raging in West Africa has, by recent count, 18,959 letters of code in its genome; this is a small genome, by the measure of living things.

Does this mean mean Ebola is essentially about 38 kilobytes?

38 kilobits = 4.7 kB, but yes.

Here's the complete genome of the pandemic strain (scroll down a bit):

http://www.ncbi.nlm.nih.gov/nuccore/KJ660346

Here's the paper sequencing it. ([edit]: I just realized the New Yorker article is largely about this exact paper -- I commented before reading, sorry). Note that five of the authors died before publication; there's a short tribute accompanying it.

http://www.sciencemag.org/content/345/6202/1369.full

http://news.sciencemag.org/health/2014/08/ebolas-heavy-toll-...

Here's another phylogeny of this strain, including github repo:

http://currents.plos.org/outbreaks/article/phylogenetic-anal...

There's something fascinating about looking at that code, even though I can't decompile it just by reading the characters.

P.S.: It's 37918 bits, about 4.6 kB

the notes to decoded pieces itself fascinating :

/note="immunosuppressive region; other site"

...

/note="transmembrane anchor; transmembrane region"

it's even more fascinating. (biochemist here) I think the immunosuppressive regions is a small protein called sGP which ebola causes the cell to produce a ton of. It's not attached to ebola virions, so in a way it's a DDOS on the immune system, by creating a foreign component that the immune system gets distracted by instead of going after ebola.

following the doc link for

524..2671 /gene="NP" /note="Ebola nucleoprotein; Region: Ebola_NP; pfam05505" /db_xref="CDD:147601"

"http://www.ncbi.nlm.nih.gov/pubmed/9657001?dopt=Abstract"

"DNA vaccines expressing the envelope glycoprotein (GP) or nucleocapsid protein (NP) genes of Ebola virus were evaluated in adult, immunocompetent mice. The vaccines were delivered into the skin by particle bombardment of DNA-coated gold beads with the Powderject-XR gene gun. Both vaccines elicited antibody responses as measured by ELISA and elicited cytotoxic T cell responses as measured by chromium release assays. From one to four vaccinations with 0.5 microgram of the GP DNA vaccine resulted in a dose-dependent protection from Ebola virus challenge. Maximal protection (78% survival) was achieved after four vaccinations. "

The article is from 1998. Interesting why there is still no vaccine. And this is on the virus structure - GP envelope - with attached antibody from human survivor http://www-als.lbl.gov/index.php/contact/163-structure-of-th...

There are a few vaccines that work in animals, they just haven't been funded to go through the trials needed to be widely used in humans. There is a good interview on Montana public radio with one of the leading researchers that touches on this:

http://mtpr.org/post/getting-closer-ebola-vaccine

(Rocky Mountain Lab in Montana is where a large portion of the ebola research in the nation if not world the world happens and mtpr had gotten some really good interviews as a result.)

Errr, right now one vaccine is being tested on humans in Stage I trials: http://www.niaid.nih.gov/news/newsreleases/2014/Pages/EbolaV...

I can remember seeing pictures of some Malians getting it.

> a small protein called sGP which ebola causes the cell to produce a ton of

Is that why people die? Cells make too much of that stuff?

Correct. Victims bodies are tricked into generating large amounts of cells. This causes the hemorrhaging which is the ultimate cause of death.

Fun fact: The victim's body continues producing cells for several hours after death. In rare cases this (in conjunction with post-death bloating) causes the cadaver to "explode"

That is false: http://en.wikipedia.org/wiki/Ebola_virus_disease#Pathophysio...

What if the noncoding dna sequences are comments and the genome is just extremely well documented FOSS?

I bet they're more like commented out sections of old code, now so far out of date as to be incomprehensible, but perhaps a key to past approaches.

UCSC has the sequenced strains loaded in their genome browser, too, if it interests you

http://genome.ucsc.edu/cgi-bin/hgTracks?db=eboVir3

Oops, thanks for the bits to bytes correction.

It is simply incredible to me that it could be so small (in an information sense).

This article (gzipped) is 22KB, more than 4 times as much information.

Yeah, but don't forget the complexity of the hardware you need to run ebola versus a website. Our bodies provide most of the implementation details.

Absolutely, but that's true of most information as well. For example, the information in the article is relative to the context of understanding our language and the body of assumed knowledge and references of a reader of the New Yorker.

My understanding of biology is very limited. I've heard how physically small microbes are in every article out there. But never how information-small they are. Fascinating from a software developer's perspective.

I wonder what code golf for a virus would look like.

Like viriods, which make a virus look huge by comparison:

> Viroids are plant pathogens that consist of a short stretch (a few hundred nucleobases) of highly complementary, circular, single-stranded RNA. Viroid genomes are extremely small in size, ranging from 246 to 467 nucleotides (nt), and consisting of fewer than 10,000 atoms. In comparison, the genome of the smallest known viruses capable of causing an infection by themselves are around 2,000 nucleobases in size. The human pathogen hepatitis D virus is similar to viroids.

> Viroid RNA does not code for any protein. Their replication mechanism uses RNA polymerase II, a host cell enzyme normally associated with synthesis of messenger RNA from DNA, which instead catalyzes "rolling circle" synthesis of new RNA using the viroid's RNA as template. Some viroids are ribozymes, having catalytic properties which allow self-cleavage and ligation of unit-size genomes from larger replication intermediates.

Source: http://en.wikipedia.org/wiki/Viroid

In case you were wondering what a ribosyme is

> A ribozyme (ribonucleic acid enzyme) is an RNA molecule that is capable of catalyzing specific biochemical reactions, similar to the action of protein enzymes.

Source: http://en.wikipedia.org/wiki/Ribozyme

The action of ribozymes led to the RNA world hypothesis, as the mechanism for how you could have a simple system from which DNA and proteins can come as later optimizations on particular aspects. Some ribozymes are able to go as far as catalyze the building of their own RNA structure in the right environments (albeit, with limited success so far).

Right. It's so much context dependent that the "hardware" of a different animal may react very differently to it - perhaps even ignoring it altogether.

The genetic information is really the 4.8 kB of "code" PLUS the entire information already contained in the cellular hardware reading it. One doesn't make sense without the other.

At the very bottom, the whole thing depends on the laws of quantum mechanics in this universe, governing the minute details of molecular interaction. That, too, should be considered to go into the "code". Make a tiny change to the Plank constant, and the Zaire ebolavirus code will do something very different.

Thank you for saying that! Its so often repeated that our DNA contains the entire program for a human being. That's patently false. The cellular machinery provides almost all of the OS; DNA is just a script.

I liken DNA to a paper tape containing one of two punches: MAN or MOUSE. Feed it into a bio-replicator and get a man or a mouse. Does the paper tape define the man? Of course not.

> I liken DNA to a paper tape containing one of two punches: MAN or MOUSE

I don't think that really captures it. Yes, it requires external machinery to actually do anything, but DNA is much more information dense and carries much more of an exact definition of the organism to be produced.

Personally, I prefer the analogy of compiler source code. Sure, it can't do anything on its own. But it defines how an working external system (another compiler or an functional cellular environment) can produce a second possibly different system

Yet the dynamic biochemistry of the cell is orders of magnitude larger and more complex than DNA. So its larger than a paper tape, sure, but the comparison is pretty good really.

Paper tapes can't catalyze their own creation and modification. DNA can with the addition of ribonucleotides.

Mitochondria for example are (mostly?) independent of your DNA.

And yet the paper tape of a plant or animal genome (as opposed to a virus) also contains the instructions for the OS and the bio-replicator, which is part of what's so fascinating about it.

I don't think that's accurate at all. The DNA has no effect on the cellular soup - the RNA etc - that are the bioreactor. That you got from some ancestral Eve. It changes perhaps over time, like anything else through random chance. But its independent of the DNA, which is a tiny part of the whole.

The interpreter is ridiculously complicated in order to make up for the conciseness of the programming language.

you could make that argument for certain hardware optimizations, too (like SSE, GPU, PPU, etc). A computer is not a raw turing machine.

No, the article does not contain more information. It contains more data, but when dealing with genomics you must keep in mind the fact that various codons translate to various proteins, and each of the proteins serve various functions depending on their shape... and proteins can assume different shapes, which changes their effects. This is the importance of protein-folding research.

You hit near it when you gzipped the article -- consider a genome to be an incredibly compressed format, able to explode into a truly stunning amount of information, stored in a relative paucity of raw data.

How did you get 38 kilobits?

18959 units of 4 possible values (nucleotides) is equal to 37918 units of 2 possible values aka bits.

4740 bytes, actually.

There are only four nucleotides ("letters") in RNA. You can encode them with two bits.

Yes, but also no. I work at The Broad Institute and I deal with these genomes all the time. Long story short: there's tons of redundant data in these genomes because of the imperfect nature of sequencing so the real file size is many times bigger than that. Though in theory if we had perfect sequencing then it'd be around that size.

For some reason I think of X-ray crystallography: A large number of different pictures go into reaching a conclusion which is much simpler to convey.

Yes. I wonder if being so incredibly small means that replication is more efficient and intense and is therefore a strong factor behind why it's so virulent.

I don't think that's the most important factor. Influenza, along with ebola and rabies, is small, while smallpox is big.

http://www.lehigh.edu/~jas0/viralgenomes.html

something like that: http://www.ncbi.nlm.nih.gov/nucleotide/NC_002549 (I get 21K)

What I get from this article is that they let the most important candidate for the drug die without taking it, but then two random Americans got it because no one was watching.

Is the lesson here to always steal people's vaccines without asking?

This is a good point. A dose of ZMapp was being stored on the very same premises where Dr. Khan lay dying. But instead of giving him the treatment on the spot, considerable risk was instead taken to deliver it to two Americans in another country 250 miles away.

However it would be unfair to say that this was because the Americans' lives were valued more than Dr. Khan's. He was being cared for by Doctors Without Borders. For quite rational reasons they decided to withhold the treatment [1]. The Americans were under someone else's care and thus weren't subject to DWB's decision.

My main ethical disagreement is with DWB's decision not to inform Dr. Khan of ZMapp's existence while knowing that it would be used by others.

[1] http://www.nzherald.co.nz/world/news/article.cfm?c_id=2&obje...

I think this was just a bad timing. When deciding to withhold treatment for Dr. Khan they weren't aware that the next patients in line were two white men - a situation they explicitly wanted to avoid.

Couple old, enjoyable blog posts from Bunnie Huang on viral genomes from CS standpoint: http://www.bunniestudios.com/blog/?p=353 http://www.bunniestudios.com/blog/?p=1676

On the author of this piece, some useful context

http://www.nytimes.com/2014/10/20/books/the-hot-zone-author-...

You idiots wouldn't recognize propaganda if it were wearing a name tag... "I'd like to poke them in their prying eyes with things they'd never see if it smacked them in their temples." -Arctic Monkeys

i now have a strange fear of the letter "o"

Good thing we've been cutting science funding across the board! Doubt the NIH and NSF grants were helping science much anyway.

As a matter of fact, science should be privately funded and privately run. What idiot thought it was a good idea to make scientific research a government mandate?

To thy weary, I say: The market shall provide.

P.S. Yes, I am bitter about the current state of science. I've written about it in great detail before [1][2], but the current fascination with free-market everything has truly made me lose hope for this iteration of society. The free market will work, until it doesn't. Some activities which are absolutely crucial, will not be profitable until it's too late. Medical research is a good example, but there are others (energy sources to replace oil, overproduction of consumer waste, pollution etc.)

Seems like today's societies must learn by sticking their fingers in the proverbial wall socket. So be it.

1. https://news.ycombinator.com/item?id=8337837

2. https://hn.algolia.com/#!/comment/forever/prefix/0/by%3AFD3S...

The CDC was and is plenty funded to deal with this threat. If you think they didn't spend it well, well, join the club.

No amount of money is ever "enough" if it not managed responsibly. I'd really appreciate it if those who think the answer is always more government money would start putting more pressure on their goverment to spend it responsibly. I mean that quite straight, not as a snark. It would go a long way towards getting me on the bandwagon of more government spending if it didn't appear to me that the people making this claim didn't always take every opportunity to dodge away from the question of responsibility in practice.

It is not. Sorry, $6B annual budget is not a lot in the context of their responsibility, which is substantially greater than ebola [edit: or even outbreak containment in general, for that matter]. In fact, ebola (as evidenced by the lack of transmission to Duncan's own family or any additional caregivers of his [edit: not to mention a lack of host reservoir in NA]) probably and appropriately very low on the CDC's radar, since it is _not_ a public health threat in the US.

late edit: To put it in perspective, approximately $3B was the total operating expenses for just Massachusetts General Hospital, alone, in 2012. Or just 50% greater than the 2014 budget for UCSF. Or just half of what Apple spent on SG&A in the 12 months prior to Sept 27.

Then my point is even more important given the proportion of it actually spent on infectious diseases. If that's so allfired important than why were they doing anything else with that money?

The answer, of course, is that it wasn't considered so important until a couple of months ago, and thus, it wouldn't matter how much money was thrown at them, it wouldn't have solved the fundamental priority problem.

Contra to some of the press, I took the time to read the CDC's summary budget from the government's website. It wasn't hard to find ("Center for Disease Control" budget). It's full of things that sound superficially wonderful, but none of it matters if it's being spent incompetently or with priorities not connected to the real world, and throwing "more" at such an organization is not a good investment.

You can't get away from it. It isn't about more, it's also about what. What matters a lot. Again, I'd be less vocal about not just handing the government more if the advocates of more would pay more attention... much more attention... to what, and how well. But I can't help but notice the advocates of "more" seem to consider that an attack, when in all seriousness they really ought to be leading the charge. If you are an advocate of giving the government more, shouldn't you consider it very important to your own position that what the government already has be used well? You give away an enormous weapon when you leave it solely to your opponents to point out problems!

I am not trying to be difficult, but I don't understand your point. Ebola is a vanishingly unimportant concern as far as infectious diseases go. This current "outbreak" has resulted in 2 transmissions in the US to date. The reason it appears that the system failed is that the system correctly reacted to a low value threat, but it was amplified into a hysteria because of dynamics in media economics and US political cycles.

If I were the CDC, I'd be spending a boatload on SARS, MERS, MERSA, MDR/XDR TB, any number of the highly virulent seasonal influenza strains, social programs to promote vaccinations (pertussis, for example, kills more babies in the US annually than there have been total US cases of Ebola), annual rabies tracking programs, general education (good hygiene practices)... so many others. And the good news is they are doing this, as I'm sure your research into their budget shows.

edit: thus the downvoter exemplifies the problem, without saying a single word.

OK, I'll down vote you and explain why: your studied inability or unwillingness to do math, to whit, what a disease like Ebola can do in a 3rd World urban environment (or village/small town ones different than the former locations of outbreaks), specifically double the number of infections approximately every 3 weeks.

Right now this Ebola outbreak gives every sign of having the potential to be the most significant public health event in a number of centuries. Like, maybe we'll end up having to go back to the 1346–1350 Black Death for comparison, unless we can develop, test, produce and distribute a vaccine very quickly.

Malaria kills 500K-1M people EVERY DAMN YEAR in subsaharan Africa (http://www.who.int/malaria/media/world_malaria_report_2013/e...).

The CDC's worst case, last I heard, was 1.4 total million infected with Ebola in January. At the current estimate of 70% lethality, there's your 1M million people 10-16 days after infection.

Then it all doubles in 3 weeks. And another 3 weeks.

Do the math.

If you want to be conservative, dial the starting point back, it won't matter for long. But when I did my own calculations, I found 20,000 cases as of a week or two ago (a fairly conservative guess at the true number) would get you to 1.4 million in January.

> The CDC's worst case, last I heard, was 1.4 total million infected with Ebola in January.

That was a "no new action" estimate in late September based on data through late August [1]. There has been considerable new action since late August (in part based on the report, or, to the extent that the action in some cases preceded the report, at least an understanding of the general principles behind it.)

[1] http://www.cdc.gov/mmwr/preview/mmwrhtml/su6303a1.htm

Your assumption for those numbers is that it will keep doubling everywhere it goes, correct? For example, Nigeria seems to have stamped it out in Lagos, refuting the idea that it automatically breaks out exponentially in "3rd World urban environments".

Here's what I said, emphasis added:

"what a disease like Ebola can do in a 3rd World urban environment"

Nowhere did I say or ever imply that it "automatically breaks out exponentially" in such environments, just that in this outbreak, it has, and I would hope you would not deny it could in others.

At some point, the danger of handling the bodies of those who die of Ebola will sink into the public consciousness there. The worst case scenario assumes no modification of burial practices.

Note that the article dragonwriter linked says safe burials would have the outbreak ending soon after January:

If, by late December 2014, approximately 70% of patients were placed either in ETUs or home or in a community setting such that there is a reduced risk for disease transmission (including safe burial when needed), then the epidemic in both countries would almost be ended by January 20, 2015

Indeed, there can and eventually inevitably will be changes that decrease R-nought, presumably below 1 where it will then "burn out". Eventually the afflicted region(s) will be decided into those whose behaviors, for whatever reason, do not divided transmission, and those that do, with the latter containing a few survivors (of the myriad other things that kill weakened people as well as of Ebola).

But I'm pretty sure we don't know all that's going on with this outbreak in non-village settings, how mobility of people in this Western region vs. the prior outbreaks in Central Africa is affecting things, how ingrained these burial practices are, etc. We hypothesize, but only time will tell which, if any of these are correct.

You now say with emphasis, "we don't know", but I have to say, I think my post is less speculative than the one I replied to.

You seem to be talking past each other. He/she is saying that Ebola is not a threat to the US, which is the scope of the legal mandate of the CDC.

Ah, perhaps so.

However, one of the things I'm concerned about is what happens if or when it hits Latin America, which would then have very direct consequences on the US.

The response to Ebola vs. the other things isn't that different. I see no reason to believe the CDC is caught flatfooted by "Ebola", which is indeed as you say a relatively minor issue that one could almost consider a practice warmup for the "real thing", but will suddenly be a well-oiled machine when the real crisis hits. That is not how human organizations work.

If the CDC is suddenly able to handle Spanish-Influenza-Bird-Flu-2015 with stunning competence, it will only be because we got lucky and got a wakeup call with our complete unpreparedness for and blithering incompetence with Ebola.

Unless, of course, enough people keep covering for the CDC because by golly, they're government so of course they're competent, ignore your lying eyes, in which case we will learn nothing and have the same CDC when the real crisis hits. And next time, it probably won't be Ebola. (Unless someone somewhere gets the bright idea of just how much havoc they could wreak with a simple trip through New York via Liberia... which will be vicious anti-government smearing right-wingnut fear mongering right up until the moment it happens....)

For someone talking about "Vanishingly unimportant concerns" to then go on about SARS, which has caused zero transmissions in years and never reached the point the current Ebola outbreak has reached is...curious.

Common sense is priceless.

You're changing the subject. The parent was discussing budget cuts to NIH and NSF, which fund basic research into diseases and cures, including ebola.

CDC is largely a health policy organization. To the extent it does research, it is research to inform and guide government policy. Not fundamental scientific understanding of disease.

They're spending the money on cute Ebola-fighting robots: http://spectrum.ieee.org/automaton/robotics/medical-robots/r...

Sorry in advance that this going a little off topic (though, I would argue it's somewhat pertinent given the historically notable scientific illiteracy in the Ebola coverage/public response). This is a political site, but the author is an expert in healthcare policy: http://www.balloon-juice.com/2014/10/17/resiliency-is-not-ef...

I tend to agree with you and him on the topic that capitalism as practiced in the US currently is a quarter-to-quarter exercise. It doesn't disincentive externalized and systemic risks enough.

Bleah. The author ignores the very real opportunity costs in preparing "too much" for low probability events.

Very well written article, but does anyone else think that the cartoonish image advertisements don't really fit well with the purpose of the article?

The photo of an aid worker removing the body of a dead woman also looks surreal...

It's a New Yorker thing - they've had whimsical cartoons mixed with serious reportage in their printed editions for decades, if not over a century. It is odd but I suspect it gets people to read more articles than they otherwise might.

The cartoons are a big part of the New Yorker:

http://en.wikipedia.org/wiki/The_New_Yorker#Cartoons

Found this article in google how big data can help Ebola statistics. https://www.promptcloud.com/blog/the-big-data-cure/

newyorker should help setup a fund to donate to doctors/nurses who are working in the frontline of Ebola.

Or just link to an existing fund with a pretty great track record and truly heroic volunteers: http://www.doctorswithoutborders.org/

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