Field of Science

Showing posts with label pandemic. Show all posts
Showing posts with label pandemic. Show all posts

Should the government allow scientists to create new super-viruses?

Let's suppose a bunch of scientists proposed to take one of the most infectious human viruses—influenza, say—and turn it into a super-bug. Is this a good idea?

Or to put it another way: should scientists be artificially mutating viruses so that they have the potential to become a worldwide pandemic?

Right about now you might be asking: is anyone actually doing this, and if so, what on earth are they thinking?

And yet, several of the world's most prominent influenza researchers have been engaged in exactly this enterprise for several years now. They call their work "gain of function" experiments, because they manipulating viruses to give them new (and very dangerous) functions.

I wrote about this last year, after a group led by Ron Fouchier at Erasmus Medical Center in the Netherlands and Yoshihiro Kawaoka of the University of Wisconsin announced, in a letter to Nature, that they were going to create a new strain of H7N9 influenza virus that had the potential to turn into a human pandemic. Sure enough, just a few months later, Fouchier published results showing they had done just that, although they reported that their newly engineered strain had only "limited" transmissibility between ferrets (the animal they used for all their experiments).

Fouchier and Kawaoka had already done the same thing with the deadly H5N1 "bird flu" virus, causing a huge outcry among scientists and the public. As reported in Science magazine almost three years ago, Fouchier admitted that his artificially mutated H5N1 was "probably one of the most dangerous viruses you can make."

And yet he did it anyway—and then did it again, with H7N9.

Many other scientists were and are extremely concerned about these experiments, which some of us consider dangerous and irresponsible. This past July, a large group of scientists known as the Cambridge Working Group (of which I am a member) released a statement calling for a hiatus, saying:
"Experiments involving the creation of potential pandemic pathogens should be curtailed until there has been a quantitative, objective and credible assessment of the risks, potential benefits, and opportunities for risk mitigation, as well as comparison against safer experimental approaches."
Just two days ago, the U.S. government responded, announcing that it was going to take a serious look at whether creating these superbugs is a good idea. The Office of Science and Technology Policy (OSTP) is creating two committees to "assess the potential risks and benefits" of these experiments, particularly those involving the influenza, SARS, and MERS viruses.

Until the committees come up with recommendations, the government is halting any new funding for these experiments and asking for a voluntary "pause" on existing work.

Not surprisingly, Fouchier and his colleagues have argued that their work has benefits; that it has "contributed to our understanding of host adaptation by influenza viruses, the development of vaccines and therapeutics, and improved surveillance." Yet these arguments are tenuous at best. Fouchier and company have failed to show that the mutations they found in ferret experiments are likely to occur in the natural course of human outbreaks, which means that using their viruses for vaccine development would be a huge mistake.

And to claim that creating super-viruses in the lab will lead to "improved surveillance" is, frankly, laughable. Surveillance means getting out in the field and collecting samples from sick people. Gain-of-function laboratory experiments have basically nothing to do with surveillance.

Harvard's Marc Lipitsch has been one of the prominent voices arguing against this line of research, writing just last week that the scientific benefits of these experiments are very limited, for reasons detailed in his article. Lipitsch is also one of the founding members of the Cambridge Working Group.

According to the announcement from The White House, the first committee to evaluate the merit of these experiments will meet in just a few days, on 22 October. Meetings will continue throughout the winter, with recommendations expected sometime in the spring of 2015.

We have enough problems with influenza, and now with Ebola too, without scientists creating incredibly deadline new viruses that might accidentally escape their labs. Let's hope that the OSTP does the right thing and shuts down these experiments permanently.

Scientists are creating a dangerous flu strain, just to prove they can

In an outrageous display of chutzpah, a group of flu researchers led by Ron Fouchier of Erasmus Medical Center in the Netherlands announced today, in a letter to the journal Nature, that they were planning to engineer the new H7N9 avian flu strain to give it new, possibly much more deadly capabilities.  Fouchier is the same scientist who, two years ago, adapted the highly pathogenic H5N1 flu strain so that it could be passed from human to human, which it cannot do in its natural form.  The resulting outcry delayed publication of his paper, but it eventually did appear.

Now they want to do the same thing, and much more, with the new H7N9 influenza virus, which has killed 43 people in China to date, and which epidemiologists are tracking with great concern.

They should track Fouchier and his lab instead.

Wait a second, protests Fouchier.  He promises that
"All experiments proposed by influenza investigators are subject to review by institutional biosafety committees. The committees include experts in the fields of infectious disease, immunology, biosafety, molecular biology and public health; also, members of the public represent views from outside the research community."
Sorry, but I'm not reassured.  Fouchier's group wants to do this research because it's all they know how to do - and, I suspect, because they enjoy the publicity.  Despite their claims that the research is vital to our understanding of the flu, none of their past work, including their work on H5N1, has changed our ability to respond to a pandemic.  As flu expert Michael Osterholm said in a report by the Associated Press:
"H5N1 surveillance is as haphazard today as it was two years ago. Should we do the work if it's not actually going to make a difference?"
Precisely.  Fouchier and his colleagues can't do surveillance, nor do they work on vaccine development.  They have laboratories where they can engineer the flu virus to make new strains, so that's what they want to do. Two years after their controversial H5N1 experiments, they haven't contributed to any improvement in our ability to control a pandemic, nor have they shown how to develop a better flu vaccine.  The benefits of creating a deadly new H7N9 virus are marginal, at best.

What about the risk? As reported in the Daily Mail, Fouchier and his colleague Yoshihiro Kawaoka themselves said
"H7N9's pandemic risk would rise 'exponentially' if it gained the ability to spread more easily among people."
Really?  And from this they conclude that it's a good idea to engineer a virus that can do exactly that - spread more easily among people? Are we supposed to take this risk because of some theoretical benefit from a vague "better understanding" of how mutations in the virus change its pathogenicity?

Although Fouchier is in Rotterdam, the NIH funds part of his work through the National Institute of Allergies and Infectious Diseases (NIAID).  Dr. Anthony Fauci, the head of NIAID, offered the reassurance that a special panel will review this H7N9 project, and
"If the risk is felt to be too high by this outside review, they will recommend it won't be done and we won't fund it."
Despite this additional oversight, I remain skeptical. These special panels tend to include other scientists who are very sympathetic with the work they're reviewing, as was demonstrated two years ago when the H5N1 work was published despite the grave concerns expressed by many outside the field.  I predict they will approve Fouchier and Kawaoka's experiments.

Here's a thought: put me on the panel: I've published multiple research papers on the influenza virus (including this paper in Nature and this paper on H5N1 avian flu), so I think it's fair to say I'm qualified.  But somehow I doubt they will do that.

Whatever happened to swine flu?

What happened to the flu pandemic?  In 2009, a new flu strain swept across the world. The new strain, called H1N1, emerged from pigs and jumped over to humans sometime in late 2008, and then swept through the human population starting in the spring of 2009.  Panic ensued.  Egypt responded by slaughtering all of its pigs, about 300,000.

Was the panic justified?  If so, where are all the victims?

I first wrote about this soon after the outbreak began, and we now know that hundreds of millions of people were infected, somewhere in the range 11% to 21% of the population.  That's an awful lot of sick people.  However, H1N1 turned out to be a very mild flu: many people experienced little more than a few days of sniffles, much like a common cold.  This surprising mildness of swine flu led to great confusion.  Conspiracy theorists claimed that the threat had been overblown, hyped by vaccine manufacturers and their government co-conspirators.  A wacky German lawmaker, Wolfgang Wodarg, even claimed that the swine flu vaccine caused cancer, a claim that was picked up and amplified by famed internet snake oil salesman, Joseph Mercola.

The swine flu now seems routine, just another human flu circulating among the population. As I wrote back in 2010, the seasonal flu vaccine now includes the H1N1 pandemic strain, so if you get your flu shot, you're protected.  But as this figure from the CDC shows, the current season has been dominated by H3N2. 
See the little tiny brown bits at the top of each bar?  Those are swine flu cases.  The swine flu has nearly vanished.

This is a big surprise, because in all three of the previous pandemics: 1918 ("Spanish" flu), 1957, and 1968, the new pandemic strain completely replaced the older strain.  That hasn't happened this time, and it looks like the old strain, H3N2, is winning.  That's rather unfortunate, because H3N2 is a much nastier flu than the swine flu.  And this year we had a big spike in deaths due to flu, all because of H3N2.

So no, the panic back in 2009 wasn't justified, but the warnings beforehand, about the possibilities of a pandemic, were legitimate.  All we knew in early 2009 was that a new pandemic strain had jumped from pigs to humans, and we didn't know for several months how bad (or mild) it would be.  The human species got lucky this time.

Can anyone say when the next pandemic will arrive?  Well, no.  Look at the past century: 4 pandemics, separated by 39 years, 11 years, and 41 years.  From that record it seems we should be safe for a while.  But until 2009, the pandemics had always pushed out the previous flu.  We're still living with the 1968 flu strain, and no one knows when a new flu will truly replace it.

Meanwhile, get your flu shot, because the flu mutates so fast that we need a new vaccine every year to keep ahead of it.  Work continues to try to develop a permanent flu vaccine - one that we will only have to take once in a lifetime.  If you like that idea, then keep supporting NIH, which is the biggest source of funding for flu research.

Oh right: we just cut NIH across the board because Congress couldn't get its act together.  I guess we may have to wait a bit longer for a better flu vaccine.

Is the government hiding something about the next flu pandemic?

Remember the flu pandemic? The one that swept the world just two years ago? You might be forgiven if this has slipped your mind - after all, it doesn't seem like such a big deal now. That's because we got lucky: despite many dire warnings about the danger of another 1918 "Spanish flu", when the 2009 pandemic arrived, it was far milder than previous pandemics. Hundreds of millions of people got the flu in 2009, but for most of them, it wasn't so bad. In fact, the new flu is less severe the old flu - the strain that was circulating before the new pandemic hit.

Now we have two flus circulating: the "old" H3N2, and the 2009 pandemic flu, called H1N1. (And the vaccine protects against both of them, so get your flu shot! Your friends, neighbors, and co-workers will all benefit.)

We really dodged a bullet in 2009. Despite our best efforts, it took 7 months (April to November) before a new vaccine was ready. Before we realized how mild it was, people were desperately snapping up stores of Tamiflu, an anti-viral medicine that only barely helps to treat the flu. If it had been like 1918, Tamiflu wouldn't have helped much, and tens of millions would have died.

The 2009 pandemic originated in pig farms in Mexico. We don't know precisely where it made the first leap into humans, but it appears that two different strains joined together in a pig somewhere to create the new H1N1. The flu has a nasty habit of jumping the species barrier, hopping to humans from both pigs and chickens.

So now that we know all this, next time will be different, right? The world's influenza scientists are monitoring pigs and chickens closely now, keeping a close eye on any new flu strains. Right? RIGHT???

Er, no. Not exactly. For one thing, surveillance in pigs appears to be nonexistent. I checked to see how many flu sequences from pigs in Mexican have been desposited in the public archive at GenBank since 2009 (using this terrific database). The result? One, in 2009. Nothing from 2010 or 2011. Hello, is anyone awake at the CDC and the WHO?

This despite the fact that scientists have serious concerns that the deadly H5N1 avian flu (the "bird flu") could combine its genes with H1N1 and create a really nasty new flu strain. And scientists have long had concerns that pigs could be the mixing vessels for new flu outbreaks - exactly what happened in 2009.

But wait… maybe they are monitoring the flu, but they're just not telling us. That would feed into all the fringe government conspiracy groups that claimed the 2009 pandemic was an intentionally engineered government-funded enterprise (see this BMJ article for more). I don't believe any of those conspiracy theories - most of them are just nuts - but read on.

Sharing data about flu viruses has been a touchy subject with the WHO and the CDC for years. As reported by the University of Minnesota's CIDRAP,
"In late 2006, virus sharing became an international flash point when Indonesia broke a long tradition of free international sharing of flu virus specimens by withholding its H5N1 virus samples as a protest against the high cost of commercial vaccines derived from such samples. The controversy has drawn attention to the problem of equitably distributing vaccines in the event of a pandemic."
A few months ago, the WHO finally agreed on a new set of principles on data sharing, which states that
"The WHO GISRS laboratories [which includes the CDC] will submit genetic sequences data to GISAID and Genbank or similar databases in a timely manner."
Excellent! If they do it.

As every biomedical scientist knows, GenBank is a free, public database of genetic sequence data that contains millions of sequences, from humans, bacteria, viruses, you name it. But GISAID is another database, in Switzerland - one that I initially supported - just for flu data. The original mission of GISAID was that data deposited there would go to GenBank as well, with little or no delay. But in a classic bait-and-switch move, the GISAID board changed that policy after the database was up and running, and now they can sit on data as long as they want.

OK, you say, but it's a private database, so they can do what they want. True enough. But here's the surprising bit: the CDC deposits most of its flu sequences ONLY in GISAID, where they can milk them for scientific results for years without sharing them with others. As one of GISAID's original supporters, I have an account there, and here's what I found.

So far, the CDC has deposited sequences from 6,801 flu isolates in GISAID, of which only a tiny handful are in GenBank. 3201 of these originated in the U.S., so there can't be any foreign government insisting that they be kept secret. These provide critical data that could help scientists predict what is coming in the next flu season. But you can't get these sequences without a GISAID account. And even if you have a GISAID account, as I do, you have to agree not to release the data as a condition of getting a look.

So why does the CDC deposit sequences in GISAID? I think it's precisely because of the restrictions. CDC's scientists don't want others to look at "their" data, because they're afraid someone else might discover something important and publish it before them.

The CDC, of course, is part of the U.S. government, and all its work is funded by the public. But it seems that the CDC flu scientists have forgotten their public health mission - or at least, they appear to be more concerned about their own careers (and the papers they might publish) than about making sure the world is ready for the next pandemic.

And by the way, even these sequences don't seem to include anything from pigs in Mexico. Hello, CDC? You are looking at swine flu now, aren't you?

Perhaps I'm being a bit harsh. I love the CDC: they do a terrific job most of the time, providing vital services to protect the public from infectious diseases. But their internal scientists sometimes seem to operate within a cocoon, and I'm afraid that's happening here. This culture of secrecy has got to stop, and I suspect that will only happen under pressure from the outside. The CDC Director, Thomas Frieden, needs to tell his flu people to start sharing what they know with the rest of the world. And they can start by putting their data in GenBank.

Opening up influenza research with a new kind of journal

Today is the launch of a new type of online publication, a cross between website and a "real" journal, called PLoS Currents: Influenza. What is it? Well, it's a website for immediate publication of new findings about the influenza virus. Submissions are screened by a panel of moderators (I'm one of them) and if they are appropriate, we will publish them immediately - no delays - and they will be freely available for anyone to read. They will also be given a permanent, searching PubMed identification, just like a regular journal paper.

What's the difference between this and a regular journal? Well, first of all, submissions won't be thoroughly reviewed, which means they don't "count" as journal papers, but it also means you can publish them later in a peer-reviewed journal. The Public Library of Science has already bought into this model - they're sponsoring PLoS Currents, after all - and we expect other journals to do so also. So why publish, you might ask? That's easy: in a highly competitive field such as influenza research, different scientists are often racing to answer the same question. By publishing super-rapidly in PLoS Currents, you will get a citable, time-stamped reference that establishes your discovery, and most importantly, establishes when you made it.

The big win here, we hope, is that scientists will be empowered to announce their results to the world without worrying about being "scooped" - a common fear that leads to many results being kept secret for months while papers are prepared and revised. This in turn will speed up scientific progress overall, which is the real goal behind PLoS Currents.

Also, because we aren't looking for complete manuscripts (although those are fine too), we'll accept new observations, new data, and more speculative ideas (as long as they have some data to support them) in PLoS Currents.

We're also pioneering a new way to author papers, using the Google Knol software. After writing your contribution in Google Knol, submission will require little more than a few mouse clicks. To launch the journal, four of its moderators (with colleagues) have posted the first few contributions just these week. Check it out here.

If PLoS Currents: Influenza is successful, it will open the door to an almost unlimited set of new publications in virtually any scientific field. We chose influenza because, with the recent emergence of the new H1N1(A) pandemic flu strain, it became clear to many of us that waiting the typical 3-4 months (at best) for results to appear was just too slow. Similar delays occur in virtually every other area of biomedical research, and it's time we took fuller advantage of the web to speed things up.

It’s the 2009 Mexican flu - or is it S-OIV H1N1(A)?

Millions of people have already been infected by the new pandemic influenza virus, and the number may well climb over a billion. The CDC recently estimated that up to 40% of U.S. citizens may be infected over the next year, a startlingly high number. Close to home (for me), several children in my neighborhood came down with influenza just last week. They all recovered, fairly quickly. They almost certainly had the new H1N1 pandemic strain, which seems to be spreading rapidly despite the fact that flu season is normally in the winter. A postdoc in my lab was the first person I know who caught the new pandemic flu – he came down with it in early May, and was very sick for a week. (He stayed home, and no one else was infected, as far as I know.)

But the media are still calling this “swine flu”, in headlines all over the world. Government authorities decided early on to call it 2009 H1N1(A), a catchy name if there ever was one. In one of the earliest scientific publications, CDC scientists called it S-OIV, for “swine-origin influenza virus”.

Nice try, but the media aren't buying it. The problem with the name "swine flu" is that it’s not a swine flu any more. Once an influenza virus has become established in humans, it’s a human flu. If you catch the “swine flu”, you’ll get it from another human – not from a pig. So what to call it?

The choice of a name is actually pretty clear: each of the three 20th-century flu pandemics was named after the geographic location where people believed it originated: the 1918 Spanish flu, the 1957 Asian flu, and the 1968 Hong Kong flu. As best we can tell, the new H1N1(A) virus originated in Mexico, and therefore we should call it the 2009 Mexican flu. This will be accurate and consistent with historical precedent.

And by the way, this idea has already been proposed, but the Mexican government objected, so government health authorities, including the WHO, immediately backed down and looked for a more politically acceptable name. Several countries have already started using the term Mexican flu, including Belgium and Israel, as the AP reported yesterday – although the English-speaking world is still using “swine flu.”

As a side note, we now know that the Spanish flu should have been called “American flu” or possibly “Kansas flu” (where it really started), but during World War I, the U.S. didn’t want to admit that it had a serious health crisis, nor did any of the European countries involved in WWI. The Spanish got stuck with the name – incorrectly – because they didn’t try to hide the fact that they had a pandemic on their hands.

So a note to headline writers in the media: I don’t blame you for calling it swine flu and ignoring alternative names such as S-OIV and H1N1(A). But it’s misleading to use the term “swine flu”, which is already used to refer to influenza viruses circulating among pigs. Calling it “swine flu” also led to the foolish decision by some countries to slaughter large numbers of pigs, which was completely ineffective at controlling the spread of the new virus.

It’s a human flu, and it started in Mexico, so let’s call it Mexican flu.