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Ebola Is Now Curable (wired.com)
1232 points by jelliclesfarm 10 days ago | hide | past | web | favorite | 153 comments

There is no news I enjoy reading more than that a clinical trial had to be ended early because the treatment was so effective that it would be unethical to continue with alternative treatments (or a placebo).

Actually, it's quite terrifying when you remember that stopping a clinical trial early is a great way to create statistical fraud. https://blogs.sciencemag.org/pipeline/archives/2019/08/08/st... cites an example of a drug whose clinical trial was stopped early due to obviously effective success... only to discover later on that the "obviously effective" was a statistically spurious event, and the drug did not confer any benefits whatsoever.

It's only a "great way to create statistical fraud" if you assume that the statisticians, and the FDA, are either stupid or corrupt. And contrary to popular belief, they tend to be competent enough to at least cope with the sort of hair-brained schemes HN believes would fool them.[0]

Stopping a trial early and it's statistical implications should, by the way, be somewhat familiar with web developers: it's commonly done with A/B tests, and the related problem is the "One-armed bandit" (https://en.wikipedia.org/wiki/Multi-armed_bandit#Empirical_m...)

[0]: Legend says they are even familiar with correlation != causation, and some have mastered the advanced skill of knowing that trial size matters, which is why they started, a few years back, to test drugs on more than one person.

> It's only a "great way to create statistical fraud" if you assume that the statisticians, and the FDA, are either stupid or corrupt.

This is a legitimate issue in the scientific community. The FDA made it a requirement to publish drug trial criteria beforehand to prevent trials from stopping prematurely or adding more participants. This resulted in a massive drop in drugs with positive results: "...before the registry was created, more than half of the published studies of heart disease showed positive results. After the registry was created, only 8 percent had positive results". [0]

The FDA and scientific community isn't as "pure" as your flippant dismissal would suggest. The FDA can only do so much, and trial runners have misaligned incentives.

[0] https://www.npr.org/templates/transcript/transcript.php?stor...

> It's only a "great way to create statistical fraud" if you assume that the statisticians, and the FDA, are either stupid or corrupt.

Considering how much money is in pharmaceuticals, I'd definitely go with corrupt, especially considering this explains how a majority of the world works now and also since there's currently an outbreak and likely want to capitalize on it.

I'm not at all saying this is the case, but that if something like that did come out then I really wouldn't br surprised considering it seems to be a weekly occurrence that you hear about corrupt behavior now.

The issue with cynicism and corruption conspiracy theories is that they become a self-fulfilling prophecy.

If everyone is corrupt, then it’s OK if you are, etc.

There is no fair application of the rule of law, there’s no reason for rule of law, only the rule of men. Better hope they’re on your side!

My point is that clear corruption as we think of it (fraud, bibery, self dealing) in most Western countries is NOT considered normal. Ie. It happens but we’ve built institutions to counteract it. The FDA is notoriously bureaucratic in order to detect and prevent corruption, and for the few cases to slip through, to correct it.

When you hear about corruption stories, that’s about the system WORKING against those cynics that are testing it for their own benefit.

Cynicism is self destructive. If our institutions are broken, we must work to repair them.

Are you familiar with what PJ O'Rouke says about politicians?

Have a listen to this https://www.youtube.com/watch?v=JbIqKqojOZU

He is the author of Parliament of Whores

Parliament of Whores is an international best-selling political humor book by P. J. O'Rourke published by Atlantic Monthly Press in 1991. Subtitled "A Lone Humorist Attempts to Explain the Entire US Government"

I feel like Hanlon's razor is applicable here.

> Stopping a trial early and it's statistical implications should, by the way, be somewhat familiar with web developers: it's commonly done with A/B tests

AFAIK stopping an A/B test early is the way to go if you want to convince yourself (or your customer) that something has an effect, even though it hasn't.

Yes, if you "peek" at the results of an A/B test before it's done in order to decide whether to stop early, the numbers you "peeked" at have much lower statistical power than if you foreswore stopping early. Obviously, failing to take that into account when drawing conclusions about the effectiveness of the treatment is a colossal mistake.

However, the decrease in statistical power is still quantifiable, and with the right math you can still calculate an accurate 95% confidence interval on the effect size (which will be much wider than the wrong math where you naively don't account for the "peeking"). And of course, it's totally possible that the treatment is so effective that even the accurate calculation shows that the lower bound on the effect size is so much higher than the control group that the responsible thing to do is to stop the trial early.

Here's some the math on how much lower the statistical power is if you "peek": https://www.evanmiller.org/bayesian-ab-testing.html

The word is harebrained unless you think hair has a brain.

I was a contractor working on an IS at the FDA in the early 2000's. Shortly before the VIOXX scandal (https://www.drugwatch.com/vioxx/). The number of cheats they were specifying to go around safeguards was scary. Fortunately, they fired the company I worked for and awarded the contract to the company employing the husband of one of the FDA managers. ISYN. A relief to leave.

rule #1 of hn: anyone on hn is smarter than everyone not on hn no matter the domain. we could solve all the world's problems by just getting everyone into hn!

rule #2 of hn: High signal to noise is preferred over low signal to noise. HN > twitter.

To be fair, and when it comes to health and biology, Twitter >> HN. The comments on most bio-related posts here make me cringe.


I read HN regularly, but for health and biology related information, I'd much rather turn to the various professional communities on Twitter. HN is at best "Lies my Bio 101 Professor Told Me" most of the time, and at worst a worked example of physicist/engineer's syndrome.

We have the best brains!

>>the sort of hair-brained schemes HN believes would fool them

Is there much value in an ad-hominem reply?

Or in generalizing it to an entire community? The irony seems hard to avoid when such a generalization is made without mentioning any statistical foundation, while pontificating about statistics.

> Is there much value in an ad-hominem reply?

> Or in generalizing it to an entire community?

I don't like this style either but sometimes I think we deserve it for being a smug echo chamber.

Basically, much the same thing could have been said in a different way and I would have upvoted it.

> we deserve it for being a smug echo chamber.

This and more. Almost every comment here is made with absolute confidence and authority, much more than is warranted. The tone of the person who said that "it's a great way to commit statistical fraud" without a caveat sounded like a know-it-all who knows better than the FDA and the scientists who made this cure in the first place or that they're outright unethical.

Most times such comments get upvoted. Sometimes they get downvoted when they're called out on their BS. So there's some balance.

Have you read any thread that involves statistics? I havent really detected that low an opinion for the FDA in particular but I recognised the broad outline painted.

I could add quite a few more generalisations myself while I'm at it, HN isn't solely populated by hyper intelligent, well reasoned, logical doctors, who form their ideas completely independently of everyone else. There's going to be group think, there's going to be like minded individuals attracted to one another, that's human nature, deal with it.

I don't even think it's an ad-hominem. HNers are generally argumentative gits (generalisation), who like finding an exception/hack/new way of looking at something (generalisation). I have no problem with some of those schemes being described as 'hairbrained' (sic although actually... [1]), but that's why I come here, because if people didn't think that way they wouldn't be Hackers.

[1] https://www.thefreedictionary.com/harebrained

> sic although actually...

Not sure if that was for comedic effect but I laughed out loud! A brilliant demonstration of the behaviour you describe.

It's a fair question, this shouldn't be downvoted even though I also think the original generalization was fair.

While I agree in general, the article indicates this was stopped after 681 of a planned 725 patients, which seems okay.

Additionally, my understanding from a quick read is that the SPMS trials were aiming to delay progression in disability, rather than eliminate the effects altogether. That seems trickier to measure, and also more subject to just... not spending enough time looking at it.

Ebola, on the other hand, has a binary outcome (dead vs cured) with a timeline of a couple weeks, IIRC.

> Ebola, on the other hand, has a binary outcome (dead vs cured) with a timeline of a couple weeks, IIRC.

Doesn't it leave (cured) people potentially permanently damaged as well? eg whatever organs were damaged, are still damaged

I think what the parent meant was that it's terminal, so if you're alive then you win, even if you're not in the condition you were before.

> While I agree in general, the article indicates this was stopped after 681 of a planned 725 patients, which seems okay.

Are you talking about the European trial, referring to “358 patients with SP-MS were allocated placebo and 360 were allocated interferon beta-1b; 57 patients (31 placebo, 26 interferon beta-1b) were lost to follow-up.”?

If so, your interpretation isn’t quite right. It’s not saying they stopped 57 patients short, it’s saying those 57 people didn’t participate at all, but that’s irrelevant to the early ending. The trial stopped short of it’s intended completion time, not short of a number of patients. The blog post indicates it was stopped 2 years early, out of a planned 2-3 year study period.

That trial wasn't a "statistically spurious event", it was a flawed trial

> the reason the first trial came to an exaggerated impression seemed to be the number of patients who might not have fully progressed to SPMS

Stopping early can lead to statistical fraud, which is why the bar is so high on doing so. But it has to be balanced with the recognition that, if the interim results are correct, continuing the trial will lead to a significant number of avoidable deaths.

And for what it's worth, given the believed cause of the flawed trial being cited, it sure sounds like if the trial had run to its conclusion it still would have produced flawed results.

Having worked in clinical trialling, what I saw made me realise that the final stats may be worth much less because of mismanagement of data.

I can give some hare-raising examples[0] but for obvious reasons... The one I can give is it was known that docs who prescribed this to multiple patients and saw an apparent improvement the attributed to the new drug, would switch the patients on the old drug to the new and not inform us. Obviously they couldn't or they'd invalidate the trial and they knew it. And it was done entirely with the patient's best interests at heart. Docs care about their lives.

That may have been rare and a flaw in the trial protocol, but much worse stuff was done via utter incompetence. And I mean including at the top of these giant drug companies. Run by idiots, really.

Wider lesson: just cos you hand over a process to a third party does not mean it's going to be done right.

[0] tribute to the thread elsewhere

I think it's hilarious that in this one HN thread we have a complete word swap of terms. You said Hare when it should be Hair and they did the opposite.


It's supposed to be hair-raising because it's alarming and surprising etc. Nothing to do with taking care of hares :)

Switching extra patients to a new drug would make the trial more conservative though... so perhaps don’t worry so much.

In general it’s worth remembering that RCTs are estimating the effect of an intention to treat ( the randomisation) not the treatment itself.

> ...would make the trial more conservative though...

If the doc correctly divines that the drug is improving things, yes, but there is noise in the signal so it may be just noise causing the few apparent improvements the doc sees. If so, doc's action may be smothering a less-then-obvious signal.

There's too much at stake for that to be acceptable.

> ...are estimating the effect of an intention to treat ( the randomisation) not the treatment itself.

I don't understand - the protocol applies the drug (aka the treatment) and results are measured. I don't understand 'intention to treat'. What is 'intention' here, so tech term I am not familiar with?

There’s quite a large statistical literature on stopping rules for trials. Any trial that is stopped would have had to plan this in advance and an evaluation of his policy would be an important thing for the data monitoring and ethics committee to review, but shouldn’t be a cause for concern. OP is right to celebrate

Just do stats all the way down.

There are 6 possibilities:

1- stop early, effective

2- stop early, ineffective

3- passed all trials, effective

4- passed all trials, ineffective

5- failed trials, effective

6- failed trials, ineffective

Assign a utility value (lives saved, risks, cost,...) and a probability to each situation and do the maths.

P(1) = P(3) + P(5)

P(2) = P(4) + P(6)

So, if (P(3) + P(5))U(1) + (P(4) + P(6))U(2) > P(3)U(3) + P(4)U(4) + P(5)U(5) + P(6)U(6) it is better to stop early.

The risk of fraud can be taken into account.

Statistics Done Wrong has a great chapter on this: https://www.statisticsdonewrong.com/regression.html

FYI people design trials with breakpoints, bandits etc. The issue isn't early stopping, the issue is inappropriate analysis of early stopping.

It's not that terrifying, there are many drugs approved that are not even more effective than cheaper, older drugs on the market. It takes a wild-scale deployment with 1000's of patients to find rare side effects and to measure the true population-level effectiveness of a drug. This is contrary to the clinical-trial level "efficacy" of a drug, which is with a more limited in terms of N= and in terms of diversity, population.

Really, the whole drug approval process is filled with uncertainty. Partly it's how the sausage is made in biotech, but also pharma companies love this method as it allows them to put forward non-inferior drugs with higher margins. We can reform the process, and should, but there will still be statistical uncertainty for 100's of new candidates, until they reach the post-market study phase.

It seems that if this is the case for this new drug it would be fairly noticable that the death rate jumps back up to 50%

That works both ways too, the mortality rate went from 50-75% to 6% if they sought treatment immediately. Which is a significant indicator of success.

Doesn't giving the drug to everyone in the trial at least add some statistical information (i.e. what is the likelyhood on it working for everyone vs. it being a spurious event)?

That's not statistical fraud.

It can be important to ethically stop a trial based on the information available, even if the information available later turns out to be incorrect.

Right but its Ebola. Under the conditions of certain, painful death its difficult to imagine a scenario the risk of no benefits outweighs the cost of taking the drug.

These are, for the record, most often specified pre-trial (as are the stopping thresholds for harm)).

no, when certain conditions lead to certain outcomes like cancer, infections and so on, you cannot really go wrong when results come in early and are so positive they are massively significantly different vs the usual course. effect size.

Indeed you can go very wrong by not doing so. Medical ethics is a balance of risk and benefit, not "What is best for statistical power?" Equipoise is required for trials, and is often a precondition of being able to do studies in these settings.

Heck, a lot of recent work on novel trial designs like stepped-wedge are specifically designed to balance equipoise and statistical needs.

It's great news, but they're observing a 30% mortality rate for the "cure". Absent medical intervention there is still a nontrivial survival rate (mortality rate of 75-90%). With supporting medical treatment before this new treatment - fluid support, etc - I think it's up to 50%? It sounds like the monoclonal antibody treatment has improved odds of survival from 1:10-1:2 to 2:3.

edit: The 6% figure is population restricted to early interventions. I am uncomfortably out of my limited knowledge here, but I think that early intervention numbers are better across the board. I'd want to compare the 6% number to the control. And I don't want to see a control! It is such a good result no matter how you look at it that they wisely halted the trial.

If I were facing a 75-90% chance of dying, I think I’d be pretty happy to reduce that to 6-30%.

But I wouldn’t call the disease “cured”.

That's probably why they use the word "curable"

But that is cureable, just not guaranteed. You are more likely to live than die with this treatment.

Or cure just mean for the people which it works for, they are cured. Contrast with medicines slowing down the effects such as HIV medicine.

In other words, cure is probably the right word, just not for everybody.

Particularly if I was in the 30% that still dies from it.

Although if I were to die from it I wouldn't probably be able to call it anything.

Just as a point of comparison:

Toxic epidermal necrolysis, a severe form of Stevens-Johnson Syndrome, has about a 30% mortality rate. I understand it to be a first world problem typically caused by taking certain strong medications. It's a severe and often deadly allergic reaction.

(I'm not going to provide links because both Wikipedia entries have disturbing photos. I've verified that I'm spelling both correctly so you can google it if you want. However, you probably would be hard pressed to find an article about either condition that didn't have similarly graphic photos.)

To clarify: epidermal means it's a skin condition. Skin conditions that kill people tend to not be pretty and the symptoms are highly visible.

Unpacking the name totally is even more brutal!

"necro" -- "death"

"lysis" -- "busting open"

"epidermal" -- "skin"

"syndrome" -- "no known cause"

However, it's a little unclear why TEN is a point of comparison to Ebola, as one is a transmissible disease and one is something that happens to unlucky people typically in response to common small-molecule drugs. I guess TEN sounds like a probable side effect of antiviral immune therapy, but it's not mentioned in the article. And it seems a little tricky to separate the side effects from the disease when dealing with hemorrhagic diseases in particular

Joking aside that's not what syndrome means. Things that have no known cause as of today are usually called idiopathic.

The comparison is to show that even in technologically advanced societies, there are diseases with 30% survival rates.

A doctor once told me that so much of our higher survival rate is based on a few key drugs and supportive care to keep us alive while the body heals itself. We seem to possess remarkably few cures for the majority of diseases out there, we are mostly able to treat symptoms to buy time for our bodies to self-repair.

To add, the reason it has such a high mortality rate is TEN/SJS are almost isomorphic to 2nd and 3rd degree burns over a high percentage of your body, which is also very commonly fatal. The "30%" mortality rate is greatly dependent on how bad the SJS/TEN manifests.

Is syndrome = "no known cause" a common definition?

I imagine parent is being a bit tongue in cheek. A syndrome is any group of symptoms that seem to occur together. Often something is called a syndrome before its cause is determined. However, even after a cause is found or if it was known, the name often persists. E.g. AIDS was named before it was traced back to HIV. It persists as the name for the late stages of an HIV infection.

So while it is often the case that when a syndrome is initially named its cause is unknown, the two are really referring to different levels of abstraction of a disease. The syndrome is its effects, irrespective of whether we know its cause.


Edit: one usage is for a set of commonly concurrent symptoms, possibly with no known cause. Another common usage is a set of concurrent symptoms with multiple known causes (e.g. toxic shock syndrome).

Necrotic rashes are no joke. TEN/SJS is literally treated in the burn ward.

Puh. The photos are really disturbing. I really recommend anyone not to do what I just did...

I was about to reply and say they weren't too bad, 2 of them really not, 2 of them a couple of stages on from really bad sunburn. I was picturing that scene from Raiders of the lost Ark before hand, it's not that bad.

Raiders of the Lost Ark is more accurate in real life, unfortunately. I don't know why they show such sanitized versions of the diseases (for SJS they show a photo of someone with Erythema Multiforme Major). The photo for TEN is almost certainly after a great deal of "clean up".

We really need some kind of image-less Wikipedia for things like this.

elinks browser for the win! I bet images can be blocked by extension as well.

You're solving entirely the wrong problem. The issue is linking to the article, not "how do I personally view a page a certain way?"

"Not pretty" is an understatement.

Toxic epidermal necrolysis (TEN) is the most lethal on a scale of 4 related necrotic skin conditions[1]: TEN, SJS, EMMajor, EMMinor. The medical industry sees all 4 as kind of a sliding scale, similar to how burns are classified as different degrees and can be clinically distinguished but are still burns. They are categorized based on the percentage of your skin that becomes necrotic, and additionally which tissue types are affected.

My understanding is that herpes is one of the most common causes, although maybe that's only true for EMM and not TEN/SJS. For some reason, as we age, sometimes our body changes its reaction to herpes or other infections, becoming hypersensitive, resulting in one of the 4 previously mentioned necrotic skin conditions.

I'm sharing this, because even though my symptoms were literally staring the doctors in the face, it took years before a studious dermatologist figured out I had recurrent EMMajor. If you have "cankers" or "rashes" associated with your herpes outbreaks, ask your doctor about it, even if the rashes aren't painful. Recurrent EMMajor can be life-threatening without treatment[2] and can progress with further attacks.


[2]https://www.nhs.uk/conditions/erythema-multiforme/ (warning: disturbing pictures)

It's interesting to note that even APAP/paracetamol/acetaminophen can cause TEN or SJS, although very very rare. [1]

For those bipolar folks out there, remember even lamotrigine can cause SJS (still very rare), which is why you should always ramp up the dose gradually. [2]

[1] https://www.fda.gov/drugs/drug-safety-and-availability/quest...

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905385/

Almost every bipolar medication has some very scary side effects (either in the medium or the long term). Sadly receiving treatment for it is a constant balance of "If you do not treat it it might destroy your life" and "if you do treat it it might destroy your life".

The results were most striking for patients who received treatments soon after becoming sick, when their viral loads were still low—death rates dropped to 11 percent with mAb114 and just 6 percent with Regeneron’s drug, compared with 24 percent with ZMapp and 33 percent with Remdesivir.

Of the 11 people who've been treated for Ebola in the US, only 2 have died.

That's a small sample, but only an 18% mortality rate with the best available treatment, before this cure.

Several of those people got the therapies being tested in this trial.

Article says 6% unless I'm misunderstanding something.

Their best-overall reduced down to 29%.

The 6%-figure was for a sub-population of victims who received one of the treatments early. There's probably a sub-sub-population of young-adult victims who're in good health and received early treatment who had a near-0% rate, too.

From glancing at Wikipedia's numbers, it seems that the average Ebola victim faces about 50% odds, so this'd improve that to about 29%.

But, with-or-without this treatment, people who receive care, especially early, enjoy better odds than their peers who don't.

Other treatments mentioned in the same paragraph cut mortality rates to 34% or 29%.

If I'm reading this right, the 29% and 6% are the same drug. It has a 6% mortality rate when administered very early in the illness.

> The monoclonal antibody cocktail produced by a company called Regeneron Pharmaceuticals had the biggest impact on lowering death rates, down to 29 percent, while NIAID’s monoclonal antibody, called mAb114, had a mortality rate of 34 percent. The results were most striking for patients who received treatments soon after becoming sick, when their viral loads were still low—death rates dropped to 11 percent with mAb114 and just 6 percent with Regeneron’s drug, compared with 24 percent with ZMapp and 33 percent with Remdesivir.

An Ebola cure is impressive but what's just as impressive if not more is the method of getting to the cure. Virus based infections have notoriously been hard to cure once infected. The fact that antibodies can now be engineered to cure a virus-based infection is mind-blowing to me.

This is awesome that we've seen another horrendous disease go from incurable to curable in my lifetime. While ebola hasn't touched my community like AIDS/HIV has, reading this cracked my RBF and I smiled.

It is great news, and also evidence of how much better it is to be aware of diseases that happen in remote, poor parts of the world. If the rich world had ignored Ebola because it was happening to poor people (mostly, so far), then it could have become an AIDS/HIV sized epidemic (including in the rich world) before these treatments were developed. Plus the good karma of not just sitting there while your neighbor's house burns to the ground, of course.

Not everything needs to be rich vs poor, I know your message is positive however we are not living in such a dire world where this needs to be pointed out.

A 6% to 30% fatality rate depending on how early the treatment is not what I would call a cure. However, at best 6% fatality rate is still huge progress.

That fatality rate could be the difference between "Meh, I'll probably die anyway and there's nothing anyone can do about it" and "Get me to the doctor asap!" in people's minds -- especially if it is known that early treatment dramatically increases the odds of survival.

FWIW Early AIDS treatments were pretty bleak in terms of success but that didn't stop people from making it better. It seems like ebola treatments have advanced much faster than they did with AIDS so I'll take it as a net win :)

30% is still huge progress!

Much-needed Outline.com of the article: https://outline.com/MJaPqX

Wired.com is almost literally unreadable. It's a caricature of all that's wrong with modern web design. Is everyone else seeing what I'm seeing? http://u.cubeupload.com/temp9871/wired.png

I recently got into the habit of swinging Firefox's reader view (https://support.mozilla.org/en-US/kb/firefox-reader-view-clu...) on a hair trigger. A single click on any of my devices, it cuts an awesome swathe through the internet jungle. For now.

I like it enough that I automatically prepend `about:reader?url=` to many links I come across. Navigating the web into something I almost enjoy in Reader Mode. I will rue the day that sites start mucking about with it.

With JavaScript disabled, the Wired article loads fine and the outline.com article doesn't load at all. I'd say you have that backwards.

Outline.com is one site which, if you allow JS for it, provides access and a consistent, reader-friendly view for many, many others. (Sadly, not all.)

There are other options -- Reader View in Firefox and w3m in console are two I use frequently. For browsers other than Firefox, Outline is useful and I'm grateful it exists.

Turn off javascript for wired.com and it works well. I use uMatrix to do it.


I use uBlock Origin to do it. It took me years to find it was the small </> button in the bottom right corner. Don't forget to save the settings for this website afterwards.

Thank you! I've now disabled uMatrix, looks like I can do it all through uBlock Origin. I never realised that I could disable JS that way before.

> all that's wrong with modern web design

Not quite - you forgot the GDPR popup on top of the subscribe popup, as well as the autoplaying video ad with sound!

A fact that many people miss about Ebola is that while its survival rate is very low when untreated, it becomes relatively high (I think in the 80%) with simple things like IV hydration. Basically you are going to lose a LOT of water through that infection. Feeding you water (and minerals) directly in the veins gives a surprisingly high survival rate.

What makes Ebola so dangerous is the ease at which infection spreads within the medical staff and how quick it can occupy all your beds and "simple" IV devices.

Depending on how it is made, a cure may not change much. If it relies on medical attention, then it probably won't change the high death rate of people outside medical care, which is what allows an epidemic to start.

As the article says, the mortality rate with current best treatment option is about 50%.

Then why in the article says that when untreated the mortality is over 75%?

That's what I am saying:untreated it is very high, treated (even without a cure against the infection) it is much lower.

WHO: two of the four drugs we thought would work did not work as well as expected.



Both appear to be reasonable descriptions of the facts, mostly differing in being appropriate based on whether you had or had not already adopted the WHO’s positive expectations.

Off topic, but does this meme/way of writing have a name?

It's used a lot in Youtube comments and it weirdly grates me.

Well, if I may have a bad disease, don't really need four different cures; one is enough, and two is great.

Aren't monoclonal antibodies harder and thus more expensive to manufacturer though?

The only reason they need to be monoclonal is for drug safety regulations. It's easier to estimate efficacy with a drug of known composition, and safety is much easier too because immune responses to different proteins are tricky to predict.

With a polyclonal, manufacturers would need to prove safety on every single antibody and guarantee composition of the mixture.

Does it really matter?

Well, most of the countries impacted by ebola are quite poor, but I think even ignoring humanitarian concerns, it's probably in wealthier countries' best interests to pay for it strictly from an epidemiological perspective

One thing I've often said about infectious disease epidemiology is the Bush Doctrine ("We fight them over there so we don't have to fight them here") is terrible for insurgencies, but excellent for microbes.

Plus, also incentives research.

Its good that it exists but it might be very expensive to use it across a broad population. Unlike the older pills that were expensive due to patent exclusivity, here fundamentally each pill is more expensive to make.

The title calling it "curable" feels a bit misleading. To explain...

Ebola's a viral infection, like the common cold or the flu. If someone gets sick with it, then usually their immune system should fight it off naturally, just like the common cold or the flu. And just like a cold/flu, there hasn't really been a cure for it; instead, Ebola sufferers would be put on bed-rest with fluids to resist dehydration, fever management, etc., while the body fights it off.

However, Ebola's symptoms tend to be severe. Glancing at Wikipedia's figures, it seems that about 50% of people who get it die -- which probably varies a lot by the exact strain, health of the victim, support received while sick, etc.. Many victims end up making a full recovery, though some end up taking more long-term damage from the trauma.

As I'm reading it, they've observed that some victims tend to fight off Ebola with relative success. So, they appear to be trying to copy those survivors' defenses via [monoclonal antibodies](https://en.wikipedia.org/wiki/Monoclonal_antibody), then pass that on to Ebola sufferers.

Since they're basically optimizing a victim's immune system with specially selected antibodies, the victim still suffers Ebola and fights it off as usual, just they're getting some pretty powerful backup in that fight.

And apparently the results are pretty good so far! The article reports:

> The monoclonal antibody cocktail produced by a company called Regeneron Pharmaceuticals had the biggest impact on lowering death rates, down to 29 percent, while NIAID’s monoclonal antibody, called mAb114, had a mortality rate of 34 percent. The results were most striking for patients who received treatments soon after becoming sick, when their viral loads were still low—death rates dropped to 11 percent with mAb114 and just 6 percent with Regeneron’s drug, compared with 24 percent with ZMapp and 33 percent with Remdesivir.

The article exaggerates a bit by citing the mortality rates for people who don't receive any support; that seems like an unreasonable figure since this treatment is an advanced form of support, so presumably it'll improve the odds of those who do get support.

So, if mortality rates are about 50%, then presumably they can drop that to about 29% overall, with people who seek treatment earlier enjoying the greatest benefit with mortality rates dropping to 6%.

Realistically speaking, this seems to suggest that this "cure" reduces an individual's odds-of-death by a bit shy of 50%; that leaves a lot to be desired. Still, it's awesome because:

1. Any progress on something like this is awesome.

2. This sort of technology can rapidly improve, so the current positive results may just be the beginning.

Let's consider the real-world implications here.

Someone in your family, or village shows symptoms of Ebola. You get them diagnosed ASAP and there's still a one in three chance you're never going to see them again.

However, a confirmed case now has everybody's attention. Everyone who was exposed now has a 94% chance of surviving. Double the morbidity of the swine flu, yes. Still a quite stressful time for everybody, full of uncertainty and loss. But not the cultural-PTSD-inducing, apocalyptic catastrophe it was before.

For a disease with a notoriously high mortality rate of at least 25% in the best of cases, a treatment that reduces this to 6% when started early enough seems like a cure to me. It just isn't 100% effective yet, and treatment needs to be started as early as possible, which is not dissimilar to a lot of other cures.

Wellll, an crude guess from 5 years ago made the point that 50% is in African countries, and US healthcare may drop it to 30% on its own: https://www.livescience.com/48263-ebola-mortality-us-africa....

It's important to note that the Liberia outbreak was a strain with a particularly high survival rate as well as asymptomatic carriers. This is part of the reason that it spread while most outbreaks tended to burn themselves out due to a much higher mortality rate (80-90% is not uncommon).

Canada removed virologists and their students who helped develop ZMapp from the lab because they are Chinese


This is great news. The headline here "Ebola is Now Curable" seems premature when the observed mortality rate is @30%.

What I am specifically interested in is whether the rate of new infections can be curtailed to below the self-sustaining threshold.

Did anyone else run into the nightmare subscribe pop up on wired?

I really wanted to actually read the article but I just had to go back to the comments. The page was unusable, I got some subscription/popup endless loop, had to close a popup every 5 seconds. I assume it's because of some limitations of the built-in Chrome browser in materialistic app, but still, come on wired.

Didn’t it just get more deadly a few headlines ago?

Is there a reason to not just take all those drugs at once?

Wouldn't that give the best results?

I want to know how long it will take for Ebola to evolve a resistance to this therapy.

> I want to know how long it will take for Ebola to evolve a resistance to this therapy.

Maybe never. A lot of time in any case, probably. Ebola is a plant's virus adapted to trees. Evolved to use bats (and probably arboreal snakes also) but can't survive for a long time in primates, and can't survive in soil at long term. We are a dead end for it. Would need infected humans munching some inedible leaves of a tropical tree or visiting hollow trunks where bats live.

News cases of Ebola in the future will be from a new strain, but this does not imply evolution or resistance. Is just that the number of ebola specimens in contact with humans is limited.

In practical terms, there will be a resistance that develops eventually. Even though the reservoir is hypothesized to be bats, that doesn't have much significance because of its ability spread from person to person without a vector.

What is notable about Ebola is that its virulence keeps dropping while its ability to spread has significantly increased. The larger issue is that Ebola is in areas that don't have the resources to handle any serious outbreak. It's becoming more likely that Ebola is going to be self sustaining soon.

I'm kind of amazed that a comment expressing interest in when this therapy will be obsolete, see that 96% of bacteria are resistant to Penicillin G now, gets a negative response. Drugs are only effective when the pathogen is still sensitive to them.

For a resistance to develop, ebola that has been exposed to the treatment inside a hospital has to escape back into the wild. There are significant barriers in the way of that.

If everyone on penicillin was kept in an isolation chamber, the effectiveness over time would be different.

As someone who works in a hospital, we can bleach every single patient room, wear all the PPE we want, but pathogens will always spread; the only question is when, not if. Even in an isolation chamber a resistance to penicillin would develop independently of each other as penicillin resistance is usually predicated on a mutation in the penicillin binding protein.

Nothing's perfect, but ebola levels of paranoia drastically slow down any chance of spread.

While partial resistance can be encouraged in a single person, that doesn't matter if it dies inside them. And if a resistance mutation happens in the wild, away from drugs, there's no reason to expect it to spread at all.

There's a significant amount of fake news around the Ebola outbreak epicenters, such as aid workers trying to take people's blood and other conspiracy theories. We have to keep in mind some of these places recently had a genocide and/or are generally unstable.

> Ebola is a plant's virus adapted to trees.

I never heard that and I can't find that in Wikipedia. Do you have a link with more information about that?

Is a plausible hypothesis. As we all know viruses do not fosilize easily, the origin of the virus is unknown (apart that is linked with tropical forest canopies in Africa). But there are several traits that would suggest a plant patogen that jump later to animals, maybe via plant sucking arthropods, and stablish later in bigger animals eating this arthropods. I could be wrong, I don't remember when I read it, but I remember that the idea triggered a click, and makes a lot of sense to me. I'm not expert in viruses evolution in any case so take this with a pinch of salt.

Ebolavirus is a genus comprising at least five species that can create similar outbreaks. I don't know if the treatment protects from all of them (Probably not). Is a fast mutating kind of creatures also. I guess that each future outbreak will need to rebuild an specifical treatment. The good news is that we know how to rebuild it fast, there is a new awareness of the problem, and african people are fixing some cultural traditions that helped to spread the virus in the past.

There are also other two genuses closely relative to Ebolavirus: Marburgvirus (produces a similar haemorrhagic fever in humans), and the spanish surprise Lloviu cuevavirus (poorly known but assumed harmless). Treatment designed for Ebola probably will not protect from Marburg disease, but I'm speculating.

If you ever find a source for the virus for plant origin, I'd like to read it. (I'm not a biologist, but I'm curious. For example, I know about the relation with the Marburg disease.)

This therapy is intended for use in an intensive care environment. If the patient is able to pass on their infection in that environment, something is very wrong.

Treating Ebola patients in intensive care environments without a single breach in containment protocol is astonishingly difficult, even for trained and experienced teams.

Its an RNA virus, so like flu it evolves all the time. RNA viruses replicate because there is no check on the NA helix when a cell replicates, unlike DNA which by virtue of being a double helix, a basic checksum method to ensure consistency of the DNA helix which the adaptive immune system relies on to do its job.

It is why flu vaccines can be ineffective by the end of the flu season. It takes about 2 weeks to grow a flu virus in sterile eggs, the most "high tech" solution known to man currently. Every time someone with flu sneezes, they are emitting new multiple strains of the flu virus.

The other problem with Ebola is it can hide in parts of the body where the adaptive immune system does not work, places like the eye and testes. So even though the virus may not show up in test results, it could reappear when someone's immune system is weakened sometime in the future. There are other ways to kill it though. Just for reference, someone I know works at Porton Down in the UK, MOD facility, they told me Ebola is nothing compared to some of the viruses and bacteria they have in their facilities. In other words there are far worse things to be worried about than Ebola.

Viruses tend to evolve pretty quickly. In fact, Ebola's already not just one strain, so differing Ebola strains are likely more prone to different versions of this treatment.

In practice, it'll probably work out to be sorta like the issue with flu vaccinations, where health organizations will have to predict which strains are likely to be out there and then prepare accordingly.

Still, even if Ebola somehow rapidly evolved to completely ward off the current treatments, it's moreso the technology that created these treatments that's a breakthrough. So, if Ebola adapts, presumably they'd just update the treatments.

That said, the current treatments probably aren't very optimized yet, either. These are early successes; future results seem liable to be much better.

How you would know that? You only could know after it happened. Evolution is random.

Well, going out on a limb here, there should still be some way to give a statistical apprehension of how likely such mutation could be over time. But I'm not aware if there's any feasibility of doing that today.

The title is a bit of a clickbait as it clearly states that they didn't manage to cure it 100%

Awesome. And humanity got a little better.

There has never been a better time to be alive. We're so lucky.


I really have to apologize if this is not a HN-quality comment, but I initially read this as a startup rebrand announcement.

Ebola is now Curable (YC 17)

I did that too. "Who the f... calls their business Ebola?".

May I suggest to you two HN's noprocrast feature. I think, you spend way too much time here. ;)

Actually, the electronic bola industry has prospective revenues coming out the wazoo

Thus the need for a rebrand!

So how many people ebola ever killed? Compared to, for instance, cancer or traffic accidents?

If you are making the point that we'd better address cancer or traffic accidents, then your argument falls under the false dichotomy fallacy. This is probably why you've been downvoted.

If your were not making this point, then I don't have the answer. :-)

Besides cancer numbers are a bit inflated because people are living more now. If you live long enough the odds of getting cancer is quite high. Whilst it's always good to extend life even more, even if it was a dichotomy, that seems less pressing than a diseases that are killing in their prime or even before they had a chance of having a good go.

It's an epidemic right? It is about the speed of spread, not number of victims.

> Patients receiving Zmapp in the four trial centers experienced an overall mortality rate of 49 percent, according to Anthony Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases. (Mortality rates are in excess of 75 percent for infected individuals who don’t seek any form of treatment.)

That doesn't sound like a "cure" to me. Significant progress to be sure, but in my mind to be considered a "cure" the mortality rate would have to drop to near zero.

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