This is how the future arrived.
Many members of the scientific community would say our time line is too fast. But consider that since the beginning of this century, rapidly accelerating technology has shown a distinct tendency to turn the impossible into the everyday in no time at all.
Last year, IBM's Watson, an artificial intelligence, understood natural language well enough to whip the human champion Ken Jennings on Jeopardy.
As we write this, soldiers with bionic limbs are returning to active duty, and autonomous cars are driving down our streets. Yet most of these advances are small in comparison with the great leap forward currently under way in the biosciences - a leap with consequences we’ve only begun to imagine.
According to Ronald Kessler, the author of the 2009 book In the President’s Secret Service, Navy stewards gather bedsheets, drinking glasses, and other objects the president has touched - they are later sanitized or destroyed - in an effort to keep would‑be malefactors from obtaining his genetic material. (The Secret Service would neither confirm nor deny this practice, nor would it comment on any other aspect of this article.)
And according to a 2010 release of secret cables by WikiLeaks, Secretary of State Hillary Clinton directed our embassies to surreptitiously collect DNA samples from foreign heads of state and senior United Nations officials.
Clearly, the U.S. sees strategic advantage in
knowing the specific biology of world leaders; it would be surprising if
other nations didn’t feel the same.
Most of the enabling technologies are in place,
already serving the needs of academic R&D groups and commercial biotech
organizations. And these technologies are becoming exponentially more
powerful, particularly those that allow for the easy manipulation of DNA.
But now, thanks to advances in genetics, we know
that each cancer is unique, and research is shifting to the development of
personalized medicines - designer therapies that can exterminate specific
cancerous cells in a specific way, in a specific person; therapies focused
like lasers.
Gartner, an information-technology research-and-advisory firm, has coined the term hype cycle to describe exactly this sort of phenomenon: a new technology is introduced with enthusiasm, only to be followed by an emotional low when it fails to immediately deliver on its promise.
But Gartner also discovered that the cycle doesn’t typically end in what the firm calls “the trough of disillusionment.”
Rising from those ashes is a “slope of
enlightenment” - meaning that when viewed from a longer-term historical
perspective, the majority of these much-hyped groundbreaking developments
do, eventually, break plenty of new ground.
The Finnish start-up
Oncos Therapeutics has already treated
close to 300 cancer patients using a scaled-down form of this kind of
targeted technology.
We would do well to begin planning for that
possibility sooner rather than later.
In 1965, Gordon Moore famously realized that the number of integrated-circuit components on a computer chip had been doubling roughly every year since the invention of the integrated circuit in the late 1950s.
Moore, who would go on to co-found Intel, predicted that the trend would continue “for at least 10 years.”
He was right. The trend did continue for 10
years, and 10 more after that. All told, his observation has remained
accurate for five decades, becoming so durable that it’s now known as
“Moore’s Law” and used by the semi-conductor industry as a guide for future
planning.
While linear growth is a slow, sequential proposition (1 becomes 2 becomes 3 becomes 4, etc.), exponential growth is an explosive doubling (1 becomes 2 becomes 4 becomes 8, etc.) with a transformational effect.
In the 1970s, the most powerful supercomputer in
the world was a Cray. It required a small room to hold it and cost roughly
$8 million. Today, the iPhone in your pocket is more than 100 times faster
and more than 12,000 times cheaper than a Cray. This is exponential growth
at work.
The amount of Internet data traffic in a year, the number of bytes of computer data storage available per dollar, the number of digital-camera pixels per dollar, and the amount of data transferable over optical fiber are among the dozens of measures of technological progress that follow this pattern.
In fact, so prevalent is
exponential growth that researchers now suspect it is found in all
information-based technology - that is, any technology used to input, store,
process, retrieve, or transmit digital information.
...can be transformed into the ones and zeroes of binary code, allowing for the easy, electronic manipulation of genetic information.
With this development, biology has turned a corner, morphing into an information-based science and advancing exponentially. As a result, the fundamental tools of genetic engineering, tools designed for the manipulation of life - tools that could easily be co-opted for destructive purposes - are now radically falling in cost and rising in power.
Today, anyone with a knack for science, a decent
Internet connection, and enough cash to buy a used car has what it takes to
try his hand at bio-hacking.
Personalized bioweapons, the focus of this story, are a subtler and less catastrophic threat, and perhaps for that reason, society has barely begun to consider them. Yet once available, they will, we believe, be put into use much more readily than bioweapons of mass destruction.
For starters, while most criminals might think twice about mass slaughter, murder is downright commonplace.
In the future, politicians, celebrities, leaders
of industry - just about anyone, really - could be vulnerable to
attack-by-disease. Even if fatal, many such attacks could go undetected,
mistaken for death by natural causes; many others would be difficult to pin
on a suspect, especially given the passage of time between exposure and the
appearance of symptoms.
Until recently, this was no simple matter. In 1990, when the U.S. Department of Energy and the National Institutes of Health announced their intention to sequence the 3 billion base pairs of the human genome over the next 15 years, it was considered the most ambitious life-sciences project ever undertaken. Despite a budget of $3 billion, progress did not come quickly.
Even after years of hard work, many experts
doubted that the time and money budgeted would be enough to complete the
job.
In the history of the world, perhaps no other
technology has dropped in price and increased in performance so
dramatically.
Once a detailed genetic blueprint had been built, the attacker could begin to design, build, and test a pathogen, which starts with genetic databases and software and ends with virus and cell-culture work. Gathering the equipment required to do all of this isn’t trivial, and yet, as researchers have upgraded to new tools, as large companies have merged and consolidated operations, and as smaller shops have run out of money and failed, plenty of used lab equipment has been dumped onto the resale market.
New, the requisite gear would cost well over $1 million.
On eBay, it can be had for as little as $10,000.
Strip out the analysis equipment - since those processes can now be
outsourced - and a basic cell-culture rig can be cobbled together for less
than $1,000. Chemicals and lab supplies have never been easier to buy;
hundreds of Web resellers take credit cards and ship almost anywhere.
If you wanted a more hands-on approach to learning, you could just immerse yourself in any of the dozens of do-it-yourself-biology organizations, such as Genspace and BioCurious, that have lately sprung up to make genetic engineering into something of a hobbyist’s pursuit.
Bill Gates, in a recent interview, told a reporter that if he were a kid today, forget about hacking computers: he’d be hacking biology.
And for those with neither the lab nor the learning,
dozens of Contract Research and Manufacturing Services (known as
CRAMS) are willing to do much of the serious science for a fee.
Those barriers to entry are now almost gone.
The radical expansion of biology’s frontier raises an uncomfortable question:
Genetic engineering sits at the edge of a new era.
The old era belonged to DNA sequencing, which is
simply the act of reading genetic code - identifying and extracting meaning
from the ordering of the four chemicals that make up DNA. But now we’re
learning how to write DNA, and this creates possibilities both grand and
terrifying.
Back then, DNA-synthesis technology was too
crude and expensive for anyone to consider writing a minimal genome for life
or, more to our point, constructing a sophisticated bioweapon, and
gene-splicing techniques, which involve the tricky work of using enzymes to
cut up existing DNA from one or more organisms and stitch it back together,
were too unwieldy for the task.
The latest technology - known as synthetic biology, or “synbio” - moves the work from the molecular to the digital. Genetic code is manipulated using the equivalent of a word processor. With the press of a button, code representing DNA can be cut and pasted, effortlessly imported from one species into another. It can be reused and repurposed.
DNA bases can be swapped in and out with
precision. And once the code looks right? Simply hit Send. A dozen different
DNA print shops can now turn these bits into biology.
Blue Heron took Venter’s A’s, T’s, C’s, and G’s and returned multiple vials filled with frozen plasmid DNA. Just as one might load an operating system into a computer, Venter then inserted the synthetic DNA into a host bacterial cell that had been emptied of its own DNA.
The cell soon began generating proteins, or, to use the computer term popular with today’s biologists, it “booted up”: it started to metabolize, grow, and, most important, divide, based entirely on the code of the injected DNA.
One cell became two, two became four, four became eight. And each new cell carried only Venter’s synthetic instructions. For all practical purposes, it was an altogether new life form, created virtually from scratch.
Venter called it,
But Venter merely grazed the surface.
Plummeting costs and increasing technical simplicity are allowing synthetic biologists to tinker with life in ways never before feasible. In 2006, for example, Jay D. Keasling, a biochemical engineer at the University of California at Berkeley, stitched together 10 synthetic genes made from the genetic blueprints of three different organisms to create a novel yeast that can manufacture the precursor to the antimalarial drug artemisinin, artemisinin acid, natural supplies of which fluctuate greatly.
Meanwhile, Venter’s company Synthetic Genomics is working in partnership with ExxonMobil on a designer algae that consumes carbon dioxide and excretes biofuel; his spin-off company Synthetic Genomics Vaccines is trying to develop flu-fighting vaccines that can be made in hours or days instead of the six-plus months now required.
Solazyme, a synbio company based in San Francisco, is making biodiesel with engineered micro-algae. Material scientists are also getting in on the action: DuPont and Tate & Lyle, for instance, have jointly designed a highly efficient and environmentally friendly organism that ingests corn sugar and excretes propanediol, a substance used in a wide range of consumer goods, from cosmetics to cleaning products.
At Harvard, George Church has supercharged
evolution with his Multiplex Automated Genome Engineering (MAGE) process, which
randomly swaps multiple genes at once. Instead of creating novel genomes one
at a time, MAGE creates billions of variants in a matter of days.
Since we can control the environments these organisms will live in - adjusting things like temperature, pressure, and food sources while eliminating competitors and other stresses - we could soon be generating creatures capable of feats impossible in the “natural” world. Imagine organisms that can thrive on the surface of Mars, or enzymes able to change simple carbon into diamonds or nanotubes.
The ultimate limits to synthetic biology are
hard to discern.
A 2010 synbio report by the Presidential Commission for the Study of Bioethical Issues said as much:
Just as worrisome as bio-error is the threat of bioterror.
Although the bacterium Venter created is essentially harmless to humans, the same techniques could be used to construct a known pathogenic virus or bacterium or, worse, to engineer a much deadlier version of one.
Viruses are particularly easy to synthetically engineer, a fact made apparent in 2002, when Eckard Wimmer, a Stony Brook University virologist, chemically synthesized the polio genome using mail-order DNA. At the time, the 7,500-nucleotide synthesis cost about $300,000 and took several years to complete. Today, a similar synthesis would take just weeks and cost a few thousand dollars.
By 2020, if trends continue, it will take a few
minutes and cost roughly $3. Governments the world over have spent billions
trying to eradicate polio; imagine the damage terrorists could do with a $3
pathogen.
Although Aum did manage to cause considerable harm, it failed in its attempts to unleash a bioweapon of mass destruction.
In a 2001 article for Studies in Conflict & Terrorism, William Rosenau, a terrorism expert then at the Rand Corporation, explained:
That was then; this is now.
Today, two trends are changing the game. The first began in 2004, when the International Genetically Engineered Machine (iGEM) competition was launched at MIT. In this competition, teams of high-school and college students build simple biological systems from standardized, interchangeable parts.
These standardized parts, now known as BioBricks, are chunks of DNA code, with clearly defined structures and functions, that can be easily linked together in new combinations, a little like a set of genetic Lego bricks.
iGEM collects these designs in the Registry of Standard Biological Parts, an open-source database of downloadable BioBricks accessible to anyone.
The 2011 grand-prize winner, a team from the
University of Washington, completed three separate projects, each one
rivaling the outputs of world-class academics and the biopharmaceutical
industry. Teams have turned bacterial cells into everything from
photographic film to hemoglobin-producing blood substitutes to miniature
hard drives, complete with data encryption.
Two years later, 32 teams submitted 724 parts. By 2010, iGEM had mushroomed to 130 teams submitting 1,863 parts - and the registry database was more than 5,000 components strong.
As The New York Times pointed out:
(iGEM itself does require students to be mindful
of any ethical or safety issues, and encourages public discourse on these
questions.)
Phone phreakers like John Draper (a.k.a “Captain Crunch”) discovered back in the 1970s that AT&T’s telephone network could be fooled into allowing free calls with the help of a plastic whistle given away in cereal boxes (thus Draper’s moniker).
In the 1980s, early desktop computers were subverted by a sophisticated array of computer viruses for malicious fun - then, in the 1990s, for information theft and financial gain. The 2000s saw purportedly uncrackable credit-card cryptographic algorithms reverse-engineered and smartphones repeatedly infected with malware.
On a larger scale, denial-of-service attacks
have grown increasingly destructive, crippling everything from individual
Web sites to massive financial networks. In 2000, “Mafiaboy,” a Canadian
high-school student acting alone, managed to freeze or slow down the Web
sites of Yahoo, eBay, CNN, Amazon, and Dell.
A year later, the nation of Georgia, before the
Russian invasion, saw a massive cyberattack paralyze its banking system and
disrupt cellphone networks. Iraqi insurgents subsequently repurposed
SkyGrabber - cheap Russian software frequently used to steal
satellite television - to intercept the video feeds of U.S. Predator drones
in order to monitor and evade American military operations.
Given the anonymous nature of the online crowd,
it is all but impossible for law enforcement to track these efforts.
You, now a supervisory special agent in the Weapons of Mass Destruction Directorate within the FBI’s Biological Countermeasures Unit, knew that biotechnology had been expanding too quickly for the bureau to keep pace, so he decided the only way to stay ahead of the curve was to develop partnerships with those at the leading edge.
Toward that end, the FBI started hosting free bio-security conferences, stationed WMD outreach coordinators in 56 field offices to network with the synbio community (among other responsibilities), and became an iGEM partner.
In 2006, after reporters at The Guardian successfully mail-ordered a crippled fragment of the genome for the smallpox virus, suppliers of genetic materials decided to develop self-policing guidelines. According to You, the FBI sees the organic emergence of these guidelines as proof that its community-based policing approach is working.
However, we are not so sure these new rules do
much besides guarantee that a pathogen isn’t sent to a P.O. box.
The report specifically highlighted the dangers of synthetic biology:
Malevolent non-state actors are not the only danger to consider.
Forty nations now host synbio research, China among them. The Beijing Genomics Institute (BGI), founded in 1999, is the largest genomic-research organization in the world, sequencing the equivalent of roughly 700,000 human genomes a year. (In a recent Science article, BGI claimed to have more sequencing capacity than all U.S. labs combined.)
Last year, during a German E. coli outbreak,
when concerns were raised that the disease was a new, particularly deadly
strain, BGI sequenced the culprit in just three days. To put that in
perspective, SARS - the deadly pneumonia variant that panicked the world in
2003 - was sequenced in 31 days. And BGI appears poised to move beyond DNA
sequencing and become one of the foremost DNA synthesizers as well.
Iran, North Korea, and Pakistan will almost
certainly be hiring.
In total, Kessler reports, the Service coordinated some 40,000 agents and officers from 94 police, military, and security agencies.
Bomb-sniffing dogs were deployed throughout the
area, and counter-sniper teams were stationed along the parade route. This
is a considerable response capability, but in the future, it won’t be
enough. A complete defense against the weapons that synbio could make
possible has yet to be invented.
In 2004, the poisoning of the Ukrainian presidential candidate Viktor Yushchenko involved TCCD, an extremely toxic dioxin compound. Yushchenko survived, but was severely scarred by chemically induced lesions.
In 2006, Alexander Litvinenko, a former
officer of the Russian security service, was poisoned to death with the
radioisotope polonium 210. And the use of bioweapons themselves is hardly
unknown; the 2001 anthrax attacks in the United States nearly reached
members of the Senate.
This is particularly difficult to defend against. No amount of Secret Service vigilance can ever fully secure the president’s DNA, because an entire genetic blueprint can now be produced from the information within just a single cell. Each of us sheds millions and millions of cells every day. These can be collected from any number of sources - a used tissue, a drinking glass, a toothbrush.
Every time President Obama shakes hands with a constituent, Cabinet member, or foreign leader, he’s leaving an exploitable genetic trail.
Whenever he gives away a pen at a bill-signing
ceremony, he gives away a few cells too. These cells are dead, but the DNA
is intact, allowing for the revelation of potentially compromising details
of the president’s biology.
These are more difficult to recover. A strand of hair, for example, is dead, but if that hair contains a follicle, it also contains living cells. A sample gathered from fresh blood or saliva, or even a sneeze, caught in a discarded tissue, could suffice.
Once recovered, these living cells can be
cultured, providing a continuous supply of research material.
Genetic material remains present on old clothes, high-school papers - any of the myriad objects handled and discarded long before the announcement of a presidential candidacy.
And even if presidential DNA were somehow fully
locked down, a good approximation of the code could be made from cells of
the president’s children, parents, or siblings, living or not.
The first signs of Ronald Reagan’s Alzheimer’s may have emerged during his second term. Some doctors today feel the disease was then either latent or too mild to affect his ability to govern.
But if information about his condition had been
genetically confirmed and made public, would the American people have
demanded his resignation? Could Congress have been forced to impeach him?
Any live cells recovered from a dirty glass or a crumpled napkin could, in theory, be used to manufacture synthetic sperm cells. And so, out of the blue, a president could be confronted by a “former lover” coming forward with DNA evidence of a sexual encounter, like a semen stain on a dress.
Sophisticated testing could distinguish an IVD fake sperm from the real thing - they would not be identical - but the results might never be convincing to the lay public. IVD sperm may also someday prove capable of fertilizing eggs, allowing for “love children” to be born using standard in vitro fertilization.
Such “magic bullets” can target cancer cells with precision.
But what if these bullets were trained to attack
healthy cells instead? Trained against retinal cells, they would produce
blindness. Against the hippocampus, a memory wipe may result. And the liver?
Death would follow in months.
If the pathogen were designed to zero in
specifically on the president’s DNA, then nobody else would even fall ill.
No one would suspect an attack until long after the infection.
A disease engineered to amplify the production of cortisol and dopamine could induce extreme paranoia, turning, say, a peace-seeking dove into a warmongering hawk. Or a virus that boosts the production of oxytocin, the chemical likely responsible for feelings of trust, could play hell with a leader’s negotiating abilities.
Some of these ideas aren’t new. As far back as
1994, the U.S. Air Force’s Wright Laboratory theorized about chemical-based
pheromone bombs.
Forget kidnapping rich foreign nationals for ransom; kidnapping their DNA might one day be enough. Celebrities will face a new kind of stalker. As home-brew biology matures, these technologies could end up being used to “settle” all sorts of disputes, even those of the domestic variety.
Without question, we are near the dawn of a
brave new world.
Deploying sensing technologies is another possibility. Already, bio-detectors have been built that can sense known pathogens in less than three minutes. These can get better - a lot better - but even so, they might be limited in their effectiveness.
Because synbio opens the door to new, finely targeted pathogens, we’d need to detect that which we’ve never seen before. In this, however, the Secret Service has a big advantage over the Centers for Disease Control and Prevention or the World Health Organization: its principal responsibility is the protection of one specific person.
Bio-sensing technologies could be developed
around the president’s actual genome. We could use his living cells to build
an early-warning system with molecular accuracy.
The Secret Service reportedly already carries
several pints of blood of the president’s type in his motorcade, in case an
emergency transfusion becomes necessary. These biological backup systems
could be expanded to include “clean DNA” - essentially, verified stem-cell
libraries that would allow bone-marrow transplantation or the enhancement of
antiviral or antimicrobial capabilities. As so-called tissue-printing
technologies improve, the president’s cells could even be turned, one day,
into ready-made standby replacement organs.
Anyone truly determined to get the president’s
DNA would probably succeed, no matter the defenses. And the Secret Service
might have to accept that it can’t fully counter all bio-threats, any more
than it can guarantee that the president will never catch a cold.
These ideas may seem counterintuitive, but we
have come to believe that open-sourcing this problem - and actively engaging
the American public in the challenge of protecting its leader - might turn
out to be the best defense.
Certainly, considering what’s at stake, the country would bear the expense, but is that the best solution? After all, over the past five years, DIY Drones, a nonprofit online community of autonomous aircraft hobbyists (working for free, in their spare time), produced a $300 unmanned aerial vehicle with 90 percent of the functionality of the military’s $35,000 Raven.
This kind of price reduction is typical of
open-sourced projects.
It would allow the life sciences to follow in
the footsteps of the computer sciences, where “red-team exercises,” or
“penetration testing,” are extremely common practices. In these exercises,
the red team - usually a group of faux-black-hat hackers - attempts to find
weaknesses in an organization’s defenses (the blue team). A similar testing
environment could be developed for biological war games.
Because the life sciences are now advancing faster than computing, little short of an internal Manhattan Project-style effort could put the Secret Service ahead of this curve. The FBI has far greater resources at its disposal than the Secret Service; almost 36,000 people work there, for instance, compared with fewer than 7,000 at the Secret Service.
Yet Edward You and the FBI reviewed this
same problem and concluded that the only way the bureau could keep up with
biological threats was by involving the whole of the life-sciences
community.
For one thing, as the U.S. State Department’s DNA-gathering mandate makes clear, the surreptitious collection of world leaders’ genetic material has already begun. It would not be surprising if the president’s DNA has already been collected and analyzed by America’s adversaries. Nor is it unthinkable, given our increasingly nasty party politics, that the president’s domestic political opponents are in possession of his DNA.
In the November 2008 issue of The New England Journal of Medicine, Robert C. Green and George J. Annas warned of this possibility, writing that by the 2012 election,
It’s also not hard to imagine the rise of a biological analog to the computer-hacking group Anonymous, intent on providing a transparent picture of world leaders’ genomes and medical histories.
Sooner or later, even without open-sourcing, a
president’s genome will end up in the public eye.
It would also let the White House preempt the media storm that would occur if someone else leaked the president’s genome.
In addition, constant scrutiny of the
president’s genome would allow us to establish a baseline and track genetic
changes over time, producing an exceptional level of early detection of
cancers and other metabolic diseases. And if such diseases were found, an
open-sourced genome could likewise accelerate the development of
personalized therapies.
In 2008, some 14,000 people were working in U.S. labs with access to seriously pathogenic materials; we don’t know how many tens of thousands more are doing the same overseas. Outside those labs, the tools and techniques of genetic engineering are accessible to many other people.
Back in 2003, a panel of life-sciences experts, convened by the National Academy of Sciences for the CIA’s Strategic Assessments Group, noted that because the processes and techniques needed for the development of advanced bio agents can be used for good or for ill, distinguishing legitimate research from research for the production of bioweapons will soon be extremely difficult.
As a result,
In our view, it’s no longer a question of “might be.”
Advances in biotechnology are radically changing the scientific landscape. We are entering a world where imagination is the only brake on biology, where dedicated individuals can create new life from scratch.
Today, when a difficult problem is mentioned, a commonly heard refrain is There’s an app for that.
Sooner than you might believe, an app will be replaced by an organism when we think about the solutions to many problems. In light of this coming synbio revolution, a wider-ranging relationship between scientists and security organizations - one defined by open exchange, continual collaboration, and crowd-sourced defenses - may prove the only way to protect the president.
And, in the process, the rest of us...
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