Was it ‘crazy’ to re-create a virus that killed 50 million people? | Hacker News Reader

Was it ‘crazy’ to re-create a virus that killed 50 million people?

washingtonpost.com

59 pointsgivan40 comments

I went and pulled the original article. The characterization of recklessness is in my opinion unfair here. It's not like these researchers were cooking this up on their kitchen counters:

"All experiments with 1918-related viruses were performed in biosafety level 3 (BSL3) agriculture containment laboratories. In vitro experiments were conducted in Class II biological safety cabinets, and transmission experiments were conducted in HEPA-filtered ferret isolators (Imai et al., 2012). The research program, procedures, occupational health plan, documentation, security, and facilities are reviewed annually by the University of Wisconsin-Madison Responsible Official and at regular intervals by the CDC and the Animal and Plant Health Inspection Service (APHIS) as part of the University of Wisconsin-Madison Select Agent Program. More detailed information on biosecurity and biosafety is described in the Supplemental Experimental Procedures."

Also, if you read the discussion, there's this point:

"We found that a 1918-like avian virus exhibited pathogenicity in mice and ferrets higher than that of an authentic avian virus. Moreover, we demonstrated that acquisition of only a few amino acid substitutions can confer respiratory droplet transmission to 1918-like avian influenza viruses in a ferret model, suggesting that the potential exists for a 1918- like pandemic virus to emerge at any time from the avian virus gene pool."

The body of the paper goes through all the details of which specific amino acid changes are needed. This is important information for understanding how these proteins function. What is it about those few amino acid changes that confers droplet transmission? Others can now study the individual proteins and build off this work.

Reference: http://www.cell.com/cell-host-microbe/pdf/S1931-3128(14)0016...

Do you really think BSL3 is enough for pandemic flu strains?

My only experience was in 1977 at, say, BSL minus 2 or so ^_^ (e.g. mouth pipetted non-pathogenic E. Coli K-12, something that horrified a friend a decade later), but reviewing the Wikipedia entry the threshold for going from 3 to the rare and expensive 4 is said to be treatablity. It think it's a stretch to say pandemic flu is "treatable"....

It is treatable. http://en.wikipedia.org/wiki/Cytokine_storm, but also normal flue treatment is vary helpful.

Also, WWI had significant impact on yhe diseases evolution. In peacetime mild strains spread better as overly sick people tend to stay home, but you have little choices in trench warfare.

PS: Actual fatality rates are hard to pin down as Aspirin poisoning was a significant issue.

Ah, I should be more clear, my emphasis in part is on pandemic, as in problems of scale. E.g. forget about extreme efforts like flying a pregnant woman from the U.K. to Sweden because the former was out of beds to provide external oxygenation of the blood. The very basics could become rather hard if enough people are hit at any given point in time.

I wasn't aware cytokine storms had moved past the hypothesis stage, but per Wikipedia it sounds like it. Still, treatment of them at scale....

And the other thing is how do you define treatment? Besides Tamiflu and the other neuraminidase inhibitor currently marketed, who's efficacy is very questionable, treatment isn't as I normally define it, it's entirely supportive, including of course zapping secondary bacterial infections.

The 1918 pandemic aspirin poisoning hypothesis is interesting, but I think highly speculative, given all the places zapped that had limited if any aspirin availability, or so I assume for all those Pacific islands: https://en.wikipedia.org/wiki/1918_pandemic_influenza#Devast...

> …but also normal flue treatment is vary helpful.

I'm loathe to comment on typos, but in this case do you mean "very" or something about it varying?

You can read more about it in the supplementary material (which sadly may be pay walled). I'm not qualified to judge. It certainly sounds like adequate safeguards: fully redundant systems, access controls, air locks (or whatever they call them, I'm doing his from memory on the go). It is hard to read the description and come away thinking they were reckless.

They don't have to be reckless. Something merely has to go wrong.

Ferrets are used in scientific study? I didn't know that. As a ferret owner: :-(

I have a Rex (velveteen) Rabbit. Not only are they used in cosmetics research, but they're also used for making hats. It's sad, but it's for the greater... slaughter of animals?

At least feel comfort in it might save a life. My pets brethren get chemicals used on them to see how well it defurs them, and those that don't get slaughtered like chickens and skinned.

Seriously, if you want to be haunted watch a video of how factory farmed rabbits are killed. For animals that really don't make noise, you'd be surprised they're capable of making such haunting screams. I've had a rabbit 5 years and I have dogs, and mine has yet to make more than a whimper.

As someone who has personally slaughtered and processed rabbits on a small family farm it's certainly a shock when you first hear that scream. Ideally you never do though since a "clean" butcher has the animal largely unaware due to a sudden violent blow to the skull resulting in immediate death (or as close as possible).

  rabbitmqctl stop

From my days in pharma, I remember they are used extensively for testing anti-nausea medicines because they are some of the few animals that actually experience the symptoms nausea (many mammals vomit, but nausea is actually more rare).

Ferrets, as I recall, are also a good model airway for neonatal intubations. Pretty sure the animals are sacrificed afterward.

As I understand it they're the best animal model for many upper respiratory infections, including influenza.

Ideally they only get the sniffles, but with highly lethal strains ... I once knew a ferret owner, they're wonderful pets.

ferret owners make good pets too? Nice!

Heh. That too!

Seriously, a good ferret owner will socialize with their ferrets, the animals need that sort of thing.

This seems link bait-y to me: "That said they created a life-threatening virus that is only 3 percent different from the 1918 Spanish flu"

I bet the flu itself changed that much in nature between 1918 and now all on its own.

For reference 4% difference is between humans and apes.:

http://news.nationalgeographic.com/news/2005/08/0831_050831_...

I'm not saying creating a deadly virus is ethical. Personally, I think it is under sufficiently tight controls...since these things exist in nature and if we don't understand them, we risk a repeat of 1918.

This page has a nice, succinct definition of how the various kinds of mutations can contribute to influenza changes. In short, a percentage difference isn't that informative. It matters greatly what is actually different:

http://nieman.harvard.edu/Microsites/NiemanGuideToCoveringPa...

Cool. Thanks for the link. :)

Most people would read this article and be left with the impression that man made strains of influenza escaping from a lab are a greater risk than the natural processes that allow influenza to mutate so effectively in the wild. Hard to see that as anything more than taking advantage of people's ignorance. We are very lucky that it's been almost 100 years since we had to deal with a serious influenza pandemic.

You can be sure that some governments have significant amount of deadly viruses at their disposal [0]. I've heard anecdotes that Russian facilities storing black death amongst other bio weapons routinely lose power due to lack of funding [1].

So stockpiles of stuff are readily available, thus the question transforms from "Is it ethical to have this stuff?" into "Is it ethical for researchers to have access to this stuff?". I think that, with appropriate security measures being taken, it is imperative for researchers to access viruses that pruned significant portion of human population. If you look at this from evolutionary standpoint plagues killed everyone with immune system that was not prepared to deal with that infection, thus shaping the course of evolution of human species.

TL:DR: To understand where we are evolutionary we need to understand where we came from. I think deadly viruses that wiped out significant portion of human population are important part of that evolutionary path. Moreover, even if a virus escapes, I do not think danger is significant, because infection already pruned some part of human population with immune system not capable of handling it.

[0] "http://www.telegraph.co.uk/health/healthnews/8267370/We-must...

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

I think the problem with Spanish flu is the fact that it selectively blows away populations with strong, healthy immune systems — i.e. the sorts of people who tend NOT to be "pruned" over the decades by infection.

Yes, it's purported to be a positive feedback loop in the immune system known as Cytokine storm (http://en.wikipedia.org/wiki/Cytokine_storm#Role_in_pandemic...).

"Biohazard" [6.2831] is a very interesting read about the soviet biological warfare programme. Written by one of its key members.

[tau] http://www.amazon.com/Biohazard-Chilling-Largest-Biological-...

I was initially keen to read this, as it appears to be one of the only works on the topic. However, the author's scientific credibility and "authenticity" (for lack of a better term) has been called into question: https://en.wikipedia.org/wiki/Ken_Alibek#Criticism

> So stockpiles of stuff are readily available, thus the question transforms from "Is it ethical to have this stuff?" into "Is it ethical for researchers to have access to this stuff?"

How do you figure? People, organizations, and states do unethical things all the time. How does the fact that some governments are doing something put the question of "Is it ethical" off the table?

After all, we know that some researchers already have access too, that's what the OP is about. So by your reasoning, does that mean the question of "is it ethical for researchers to have access" is off the table too, since some already do?

"...is only 3 percent different from the 1918 Spanish flu, which likely killed more people than the Black Death."

Well, Spanish flu killed, tops, 5% of world population, whereas Black Death is likely to have killed at least 20% of the world population. I think this is more significant than 100 million vs ~90 million.

Note that between these two events we, oh, learned the germ theory of disease, and hypothesized the rat -> flea -> human path of plague transmission; 1918 was pre-antibiotics but we'd still learned a whole bunch of things that radically improved medicine, public health, etc.

Modern, or circa 1918 (after Typhoid Mary was permanently quarantined) public health measures alone could likely keep a plague epidemic from taking such a huge percentage of people.

Note researchers are doing vaguely similar sorts of things WRT to the Black Death: https://en.wikipedia.org/wiki/Black_Death#DNA_evidence

I think the comparison was to draw attention to just how deadly the Spanish Flu was. In history class we were taught about the Black Death as this huge and earth shattering pandemic, yet we hear nothing about the Spanish Flu. A lot of people don't realize just how deadly it was.

Given what he's done I certainly hope he's not crazy. A better question is whether creating deadly viruses is ethical.

EDIT: I should also note that I'm not judging whether what he's done is ethical (it's discussed at great length in the article) but if I had to take sides, I'm leaning towards being in favor of his work ... most research will have some degree of risk and in this case, I'm certain we'd rather not see another flu pandemic in the wild.

That's a very hard to answer question.

The risk is obvious, and e.g. a pandemic strain which followed the Ford swine flu mess is thought to have originated from a Soviet bioweapons lab.

But there's great risk in our not understanding just what the bleep made the 1918 flu pandemic so lethal for such unusual age groups.

Either could result in 10s of millions needlessly dying.

And another pandemic will happen sooner or later, regardless. It would be nice if we had the foresight to plan ahead and maybe figure out a way to minimize loss of life before it's too late.

As a member of an academic institution, it is very likely his research had to go before the institutional review board that governs how to conduct research in an ethical manner. IRB's are far from perfect, but they are charged with weighing risk vs benefit to society.

It would be crazy not to. We understand the potential for influenza to mutate rapidly and since there's no reason to believe the Spanish Flu was anything other than the result of this natural storm of mutations so we can conclude sooner or later influenza will hit the mutation jackpot again. We have to do everything possible to prepare for this in advance because once it hits there is precious little time left to save people. By most accounts the vast majority of deaths from the Spanish Flu occurred over a shockingly short period of about 12 weeks. Maybe modern public health standards can slow the next mutation down but I think we have to assume the worst is possible. If we don't do this research now there simply won't be time for any miracles to happen in 12 weeks.

No crazier than people working on nuclear power. The field itself should be studied. But we should probably keep a close eye on it because of the possible danger to society. AFAIK the controls in place to contain deadly disease is pretty advanced and they take a lot of precautions.

I thought that the "Spanish Flu" evolved from horses, not birds.

There are 7 billion of us, so we can take a hit of 50 million. Gimme a shot.

I've got a brilliant business idea.... Devise a highly deadly, highly contagious virus in a lab and the antivirus, unleash said virus... Let it run a month or so, then oh we just found the cure but it's gonna be expensive....

There is no security precaution adequate for something like this.

Yes, of course naturally occurring viruses are a major ongoing threat and we need to keep studying that threat to find better ways to counter it. But there are plenty of things we can do in that regard that don't involve actually creating lethal viruses.

I think we have far too many regulations on medical research. I think the current tangle of regulations costs many lives and should be dialed way down. But a free society depends on people voluntarily refraining from behaving like assholes. If we want a free society, we have to avoid behaving as though everything legal must be okay.

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