It’s time to end flu season, once and for all.
Viruses have become easy to engineer. Flu season is an annual reminder that our biodefenses need a major upgrade.
Flu Season
It’s flu season again here in the US. Ads are reminding people to get their shots. The kids are coughing. Doctor visits are spiking. People are calling in sick.
The figures vary from year to year but in general, tens of millions of people will get sick and tens of thousands will die this flu season.
Influenza never stops spreading and it mutates quickly. A universal flu vaccine — one of the holy grails of public health — is in clinical trials. In the meantime, flu vaccine development is still a cat and mouse game. National influenza centers in over 100 countries conduct year-round surveillance. Scientists gather annually to review the data and recommend what vaccine to produce for the upcoming season. In the US, the FDA makes the final decision. Effectiveness rarely tops 50% — a coin toss.
Some years are worse than others. But no outbreak in modern times compares to the 1918 flu season. The so-called Spanish flu infected 500 million people (the world population at the time was about 2 billion) and it killed as many as 100 million — far more casualties than WWI.
Granted, society wasn’t well-equipped in 1918 to fight Spanish flu or any other disease outbreak. Medical care was crude. Viral diagnostics didn’t exist. Neither did antibiotics or antiviral drugs. Today we have molecular medicine, the internet and other communication networks, the WHO and even the Strategic National Stockpile.
It’s possible that Spanish Flu represents “peak pandemic” — not just for the flu but for any infectious agent. But it’s also possible that something far more dangerous than influenza is looming on the horizon: A designer plague, one that is custom-engineered to do harm. In this case, Spanish flu is just the record to beat.
We are completely unprepared for this.
Virology 101
Before I elaborate, first some virology basics.
Viruses are small amounts of DNA or RNA encased in a protein shell called a capsid. They’re not traditionally alive because, without a cell to infect, they’re inert. They’re like malware loaded on a USB memory stick — harmless, until you plug them into your laptop.
The capsid determines what cells the virus can attach to and ultimately infect. Viruses come in many configurations because cells don’t have standardized ports to plug into. There are billions of virus species — they’re the most diverse organisms on the planet. This said, we don’t know that much about this diversity yet. Less than 10,000 viruses have been sequenced.
Viruses are absolutely everywhere. A drop of seawater can contain millions of viruses. Air currents mix viruses on a global scale and then rain them down on us in huge numbers, every day, all the time. The vast majority of viruses can’t infect us or make us sick.
It’s a common misconception that viruses are universally evil. Like all life, their primary role is just to replicate themselves. Any illness or death that they do cause is collateral damage, nothing intentional. Meanwhile, because chunks of cellular DNA can sometimes be packaged along with the virus genome and delivered to another host cell upon infection, viruses play a crucial role in evolutionary processes. We wouldn’t exist without them.
Over the last century, scientists have learned to domesticate viruses. They’ve killed or weakened them so they can be used as vaccines, eradicating diseases like smallpox and polio. They’ve used them as model organisms for doing basic molecular biology research. And they’ve harnessed them as reliable delivery systems for gene research and gene therapies.
But the science of virology is on the cusp of a seismic shift, one that will forever change the field — because viruses are now becoming programmable.
Synthetic Biology and Virology
Over the last two decades, a field known as synthetic biology has emerged that makes biology much easier to engineer. It’s based on digital technologies — design software tools, biological datasets, laboratory robots, and DNA sequencing and synthesis technologies.
Synthetic biology makes it possible to create a biological virus in much the same way that a software developer today might create an app for a mobile phone. This is possible because the virus genome is small enough to be completely synthesized from scratch. This was first done in 2002, for poliovirus. Back then, it took about 18 months and $500,000 to make a small virus genome. Today, it can be made in a couple of weeks for a few thousand dollars. The barriers to making synthetic viruses have come crashing down.
In the right hands, this is a great thing — one that ushers in an era of better vaccines, antibiotics, and gene-based therapies made inexpensively and faster than ever before. But it also means that the risks have never been greater that someone, somewhere will do something evil or colossally stupid with viruses.
Author Rob Reid gave a mind-blowing talk about exactly this concern at the TED conference in Vancouver, Canada, earlier this year. I highly recommend watching it. If it doesn’t freak you out, make sure you have a pulse.
Spanish flu killed about 5% of the global population — about 400 million deaths if it happened today. But we have no idea what the worst-case scenario would actually be for an engineered pandemic. CladeX, a recent mock pandemic exercise that tracked the spread of a designer virus, suggested mortality would be closer to 10 or 15%.
One popular mobile game, Plague Inc., takes this idea even further—all in the name of fun, of course. But under the hood is a surprisingly-realistic modeling and visualization engine similar to what scientists actually use to fight epidemics. Only here the engine is used to challenge player to design a plague capable of eradicating every last person. If anyone survives, you lose.
I think you’ll enjoy this spooky promotional video.
Here’s the crazy thing. Building an industrial-grade version of Plague Inc. would not be very difficult to do. Some of the tools scientists use are already freely available. And the performance of the model could be significantly enhanced by layering on the real-time transportation information that is so widely available today, such as flight information. Bolt on some DNA engineering tools and various genomic databases and one would have a design tool perfect for creating everything from a global pandemic to a precision bioweapon suitable for a targeted attack.
Then it would just be a matter of printing the genome, booting it to produce virus particles, and validating the design — all of which is becoming faster and cheaper to do because of synthetic biology.
Could we see push-button pandemics in the future?
Reality Check
Not so fast. It’s not exactly easy to do this type of engineering —at least, not yet. The connections between virus design — build — test and optimize have large frictions. Plus, it’s also really difficult to make biology do what we want it to do, good or bad. Then there’s the fact that the lab environment is not the real world. A doomsday virus that works brilliantly in silico and the lab might fizzle out quickly when released. But what I’ve sketched out here is not science fiction. Nothing has to be invented here to make this scenario a reality.
Thankfully, there are already checkpoints in the synthetic biology industry that are meant to prevent exactly this sort of abuse. Try ordering even a small string of DNA matching a known harmful virus or toxin and alarms will be tripped. But there’s still lots of room for improving the safeguards.
We haven’t got the right systems in place yet to monitor the spread of any infectious agents, natural or engineered, nor the tools to effectively counter them in a clinically-relevant time frame. This means we’re highly vulnerable to an attack or accident.
Recently, my two-year-old son got what we suspect was the flu. He was feverish and lethargic. It was hard to keep him hydrated. When we took him to the doctor, she did a basic assessment. She didn’t take any samples or do any of the rapid diagnostic tests that are available for the flu. She didn’t prescribe any medicine other than a broad-spectrum antibiotic for a mild ear infection. The entire experience was subjective and underwhelming. What if the infection was caused by something more serious?
We have the technology to do better than this. It’s time that we deployed it.
Future Perspectives
According to a recent report card, experts warn that even a small natural outbreak could overwhelm the current bio-defenses. In a world where synthetic viruses can be made and tuned in a few weeks or days, we have to level up our diagnostic and treatment technologies. There would be no natural immunity. And many of today’s defenses would be near-useless against a synthetic pathogen.
We need to significantly ramp up R&D investments in the virome, synthetic virology, and biological security. We need continuous and autonomous monitoring systems that are always on guard — a technological enhancement to natural immunity. We need this new immune system built into the entire stack of design software tools, databases, DNA print services, and the standalone DNA printers that are in development. We need virus detectors everywhere just like we have smoke detectors everywhere. And we need rapid drug development processes that can produce novel vaccines and virus-fighting medicines quickly when they are needed.
If we put these systems in place, we’ll all sleep a bit better. Because the next Spanish flu may not be the biggest threat to our species.
Viruses that produce severe and obvious disease like flu will be identified quickly and aggressively countered by global health organizations. But viruses with long latency periods exist, too. If these were engineered to be highly infectious and spread widely before launching some kind of illness or degenerative process — think dementia, weaponized — we could be caught off guard. By the time the slow infection was discovered, it might be too late to develop a cure.
Any investments we make to bolster biosecurity efforts will likely be recouped. According to World Bank estimates, the global cost of moderately severe to severe pandemics is about $570 billion annually. A fraction of this amount, if directed to proactive and coordinated R&D programs, would significantly move the needle on global biosecurity. The returns would go well beyond just protecting human health. They would also improve agriculture and food security, too, since there are plenty of pathogens that have devastating effects on important animals and plant crops.
Let’s get to work.
Andrew Hessel is a co-founder of the Genome Project-write. He’s also the President of Humane Genomics, an early-stage biotechnology company specializing in synthetic virus engineering for oncology. His son made a full recovery from his flu or flu-like illness.
