Hacking the President’s DNA

[Eugen Leitl]

http://www.theatlantic.com/magazine/archive/2012/11/hacking-the-presidents-dna/309147/?single_page=true

Hacking the Presidentbs DNA

The U.S. government is surreptitiously collecting the DNA of world leaders,
and is reportedly protecting that of Barack Obama. Decoded, these genetic
blueprints could provide compromising information. In the not-too-distant
future, they may provide something more as wellbthe basis for the creation of
personalized bioweapons that could take down a president and leave no trace.

By Andrew Hessel, Marc Goodman and Steven Kotler

Miles Donovan

This is how the future arrived. It began innocuously, in the early 2000s,
when businesses started to realize that highly skilled jobs formerly
performed in-house, by a single employee, could more efficiently be
crowd-sourced to a larger group of people via the Internet. Initially, we
crowd-sourced the design of Tbshirts (Threadless.com) and the writing of
encyclopedias (Wikipedia.com), but before long the trend started making
inroads into the harder sciences. Pretty soon, the hunt for extraterrestrial
life, the development of self-driving cars, and the folding of enzymes into
novel proteins were being done this way. With the fundamental tools of
genetic manipulationbtools that had cost millions of dollars not 10 years
earlierbdropping precipitously in price, the crowd-sourced design of
biological agents was just the next logical step.

In 2008, casual DNA-design competitions with small prizes arose; then in
2011, with the launch of GEbs $100 million breast-cancer challenge, the field
moved on to serious contests. By early 2015, as personalized gene therapies
for end-stage cancer became medicinebs cutting edge, virus-design Web sites
began appearing, where people could upload information about their disease
and virologists could post designs for a customized cure. Medically speaking,
it all made perfect sense: Nature had done eons of excellent design work on
viruses. With some retooling, they were ideal vehicles for gene delivery.

Soon enough, these sites were flooded with requests that went far beyond
cancer. Diagnostic agents, vaccines, antimicrobials, even designer
psychoactive drugsball appeared on the menu. What people did with these
bio-designs was anybodybs guess. No international body had yet been created
to watch over them.

So, in November of 2016, when a first-time visitor with the handle Capbn
Capsid posted a challenge on the viral-design site 99Virions, no alarms
sounded; his was just one of the 100 or so design requests submitted that
day. Capbn Capsid might have been some consultant to the pharmaceutical
industry, and his challenge just another attempt to understand the radically
shifting R&D landscapebreally, he could have been anyonebbut the problem was
interesting nonetheless. Plus, Capsid was offering $500 for the winning
design, not a bad sum for a few hoursb work.

Later, 99Virionsb log files would show that Capbn Capsidbs IP address
originated in Panama, although this was likely a fake. The design
specification itself raised no red flags. Written in SBOL, an open-source
language popular with the synthetic-biology crowd, it seemed like a standard
vaccine request. So people just got to work, as did the automated computer
programs that had been written to bauto-evolveb new designs. These algorithms
were getting quite good, now winning nearly a third of the challenges.

Within 12 hours, 243 designs were submitted, most by these computerized
expert systems. But this time the winner, GeneGenie27, was actually humanba
20-year-old Columbia University undergrad with a knack for virology. His
design was quickly forwarded to a thriving Shanghai-based online
bio-marketplace. Less than a minute later, an Icelandic synthesis startbup
won the contract to turn the 5,984-base-pair blueprint into actual genetic
material. Three days after that, a package of 10bmilligram, fast-dissolving
microtablets was dropped in a FedEx envelope and handed to a courier.

Two days later, Samantha, a sophomore majoring in government at Harvard
University, received the package. Thinking it contained a new synthetic
psychedelic she had ordered online, she slipped a tablet into her left
nostril that evening, then walked over to her closet. By the time Samantha
finished dressing, the tab had started to dissolve, and a few strands of
foreign genetic material had entered the cells of her nasal mucosa.

Some party drugball she got, it seemed, was the flu. Later that night,
Samantha had a slight fever and was shedding billions of virus particles.
These particles would spread around campus in an exponentially growing chain
reaction that wasbother than the mild fever and some sneezingbabsolutely
harmless. This would change when the virus crossed paths with cells
containing a very specific DNA sequence, a sequence that would act as a
molecular key to unlock secondary functions that were not so benign. This
secondary sequence would trigger a fast-acting neuro-destructive disease that
produced memory loss and, eventually, death. The only person in the world
with this DNA sequence was the president of the United States, who was
scheduled to speak at Harvardbs Kennedy School of Government later that week.
Sure, thousands of people on campus would be sniffling, but the Secret
Service probably wouldnbt think anything was amiss.

It was December, after allbcold-and-flu season.

The scenario webve just sketched may sound like nothing but science
fictionband, indeed, it does contain a few futuristic leaps. 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, IBMbs 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 biosciencesba leap with consequences webve only begun to
imagine.  Personalized bioweapons are a subtler and less catastrophic threat
than accidental plagues or WMDs. Yet they will likely be unleashed much more
readily.

More to the point, consider that the DNA of world leaders is already a
subject of intrigue. According to Ronald Kessler, the author of the 2009 book
In the Presidentbs Secret Service, Navy stewards gather bedsheets, drinking
glasses, and other objects the president has touchedbthey are later sanitized
or destroyedbin an effort to keep wouldbbe 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 didnbt feel the same.

While no use of an advanced, genetically targeted bio-weapon has been
reported, the authors of this piecebincluding an expert in genetics and
microbiology (Andrew Hessel) and one in global security and law enforcement
(Marc Goodman)bare convinced we are drawing close to this possibility. 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.

The evolution of cancer treatment provides one window into whatbs happening.
Most cancer drugs kill cells. Todaybs chemotherapies are offshoots of
chemical-warfare agents: webve turned weapons into cancer medicines, albeit
crude onesband as with carpet bombing, collateral damage is a given. But now,
thanks to advances in genetics, we know that each cancer is unique, and
research is shifting to the development of personalized medicinesbdesigner
therapies that can exterminate specific cancerous cells in a specific way, in
a specific person; therapies focused like lasers.

To be sure, around the turn of the millennium, significant fanfare surrounded
personalized medicine, especially in the field of genetics. A lot of that is
now gone. The prevailing wisdom is that the tech has not lived up to the
talk, but this isnbt surprising. 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 doesnbt typically end in what the firm calls bthe trough of
disillusionment.b Rising from those ashes is a bslope of
enlightenmentbbmeaning that when viewed from a longer-term historical
perspective, the majority of these much-hyped groundbreaking developments do,
eventually, break plenty of new ground.

As George Church, a geneticist at Harvard, explains, this is what is now
happening in personalized medicine. bThe fields of gene therapies, viral
delivery, and other personalized therapies are progressing rapidly,b Church
says, bwith several clinical trials succeeding into Phase 2 and 3,b when the
therapies are tried on progressively larger numbers of test subjects. bMany
of these treatments target cells that differ in only onebrarebgenetic
variation relative to surrounding cells or individuals.b 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.

These developments are, for the most part, positivebpromising better
treatment, new cures, and, eventually, longer life. But it wouldnbt take much
to subvert such therapies and come full circle, turning personalized
medicines into personalized bioweapons. bRight now,b says Jimmy Lin, a
genomics researcher at Washington University in St. Louis and the founder of
Rare Genomics, a nonprofit organization that designs treatments for rare
childhood diseases based on individual genetic analysis, bwe have drugs that
target specific cancer mutations. Examples include Gleevec, Zelboraf, and
Xalkori. Vertex,b a pharmaceutical company based in Massachusetts, bhas
famously made a drug for cystic-fibrosis patients with a particular mutation.
The genetic targeting of individuals is a little farther out. But a
state-sponsored program of the Stuxnet variety might be able to accomplish
this in a few years. Of course, this work isnbt very well known, so if you
tell most people about this, they say that the time frame sounds like science
fiction. But when youbre familiar with the research, itbs really feasible
that a well-funded group could pull this off.b We would do well to begin
planning for that possibility sooner rather than later.

If you really want to understand whatbs happening in the biosciences, then
you need to understand the rate at which information technology is
accelerating. 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 bfor at least 10 years.b 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 itbs now known as
bMoorebs Lawb and used by the semi-conductor industry as a guide for future
planning.

Moorebs Law originally stated that every 12 months (it is now 24 months), the
number of transistors on an integrated circuit will doubleban example of a
pattern known as bexponential growth.b 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.

In the years since Moorebs observation, scientists have discovered that the
pattern of exponential growth occurs in many other industries and
technologies. 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 technologybthat
is, any technology used to input, store, process, retrieve, or transmit
digital information.

Over the past few decades, scientists have also come to see that the four
letters of the genetic alphabetbA (adenine), C (cytosine), G (guanine), and T
(thymine)bcan 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 lifebtools that could easily be co-opted for destructive purposesbare 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.

These developments greatly increase several dangers. The most nightmarish
involve bad actors creating weapons of mass destruction, or careless
scientists unleashing accidental plaguesbvery real concerns that urgently
need more attention. 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
industrybjust about anyone, reallybcould 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.

Moreoverbas webll explore in greater detailbthese same scientific
developments will pave the way, eventually, for an entirely new kind of
personal warfare. Imagine inducing extreme paranoia in the CEO of a large
corporation so as to gain a business advantage, for example; orbfurther out
in the futurebinfecting shoppers with the urge to impulse-buy.

We have chosen to focus this investigation mostly on the presidentbs
bio-security, because the presidentbs personal welfare is paramount to
national securityband because a discussion of the challenges faced by those
charged with his protection will illuminate just how difficult (and
different) bsecurityb will be, as biotechnology continues to advance.

A direct assault against the presidentbs genome requires first being able to
decode genomes. 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.

This started to change in 1998, when the entrepreneurial biologist J. Craig
Venter and his company, Celera, got into the race. Taking advantage of the
exponential growth in biotechnology, Venter relied on a new generation of
gene sequencers and a novel, computer-intensive approach called shotgun
sequencing to deliver a draft human genome (his own) in less than two years,
for $300 million.

Venterbs achievement was stunning; it was also just the beginning. By 2007,
just seven years later, a human genome could be sequenced for less than $1
million. In 2008, some labs would do it for $60,000, and in 2009, $5,000.
This year, the $1,000 barrier looks likely to fall. At the current rate of
decline, within five years, the cost will be less than $100. In the history
of the world, perhaps no other technology has dropped in price and increased
in performance so dramatically.

Still, it would take more than just a gene sequencer to build a personally
targeted bioweapon. To begin with, prospective attackers would have to
collect and grow live cells from the target (more on this later), so
cell-culturing tools would be a necessity. Next, a molecular profile of the
cells would need to be generated, involving gene sequencers, micro-array
scanners, mass spectrometers, and more. 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 isnbt
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 equipmentbsince those processes can now be outsourcedband 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.

Biological knowledge, too, is becoming increasingly democratized. Web sites
like JoVE (Journal of Visualized Experiments) provide thousands of how-to
videos on the techniques of bioscience. MIT offers online courses. Many
journals are going open-access, making the latest research, complete with
detailed sections on materials and methods, freely available. 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 hobbyistbs pursuit. Bill Gates, in a recent interview, told a
reporter that if he were a kid today, forget about hacking computers: hebd 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.

>From the invention of genetic engineering in 1972 until very recently, the
high cost of equipment, and the high cost of education to use that equipment
effectively, kept most people with ill intentions away from these
technologies. Those barriers to entry are now almost gone. bUnfortunately,b
Secretary Clinton said in a December 7, 2011, speech to the Biological and
Toxin Weapons Convention Review Conference, bthe ability of terrorists and
other non-state actors to develop and use these weapons is growing. And
therefore, this must be a renewed focus of our efforts b& because there are
warning signs, and they are too serious to ignore.b

The radical expansion of biologybs frontier raises an uncomfortable question:
How do you guard against threats that donbt yet exist? 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 codebidentifying and extracting meaning
from the ordering of the four chemicals that make up DNA. But now webre
learning how to write DNA, and this creates possibilities both grand and
terrifying.

Again, Craig Venter helped to usher in this shift. In the midb1990s, just
before he began his work to read the human genome, he began wondering what it
would take to write one. He wanted to know what the minimal genome required
for life looked like. It was a good question. 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.

Exponential advances in biotechnology have greatly diminished these problems.
The latest technologybknown as synthetic biology, or bsynbiobbmoves 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.

In May 2010, with the help of these new tools, Venter answered his own
question by creating the worldbs first synthetic self-replicating chromosome.
To pull this off, he used a computer to design a novel bacterial genome (of
more than 1 million base pairs in total). Once the design was complete, the
code was ebmailed to Blue Heron Biotechnology, a Seattle-area company that
specializes in synthesizing DNA from digital blueprints. Blue Heron took
Venterbs Abs, Tbs, Cbs, and Gbs 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 todaybs biologists, it
bbooted upb: 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 Venterbs
synthetic instructions. For all practical purposes, it was an altogether new
life form, created virtually from scratch. Venter called it bthe first
self-replicating species that webve had on the planet whose parent is a
computer.b

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, artemisinic acid, natural
supplies of which fluctuate greatly. Meanwhile, Venterbs 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.  Bill Gates, in a recent interview, told a
reporter that if he were a kid today, forget about hacking computers: hebd be
hacking biology.

Other synthetic biologists are playing with more-fundamental cellular
mechanisms. The Florida-based Foundation for Applied Molecular Evolution has
added two bases (Z and P) to DNAbs traditional four, augmenting the old
genetic alphabet. At Harvard, George Church has supercharged evolution with
his Multiplex Automated Genome Engineering 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.

Finally, because synbio makes DNA design, synthesis, and assembly easier,
webre already moving from the tweaking of existing genetic designs to the
construction of new organismsbspecies that have never before been seen on
Earth, species birthed entirely by our imagination. Since we can control the
environments these organisms will live inbadjusting things like temperature,
pressure, and food sources while eliminating competitors and other
stressesbwe could soon be generating creatures capable of feats impossible in
the bnaturalb 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.

All of this means that our interactions with biology, already complicated,
are about to get a lot more troublesome. Mixing together code from multiple
species or creating novel organisms could have unintended consequences. And
even in labs with high safety standards, accidents happen. If those accidents
involve a containment breach, what is today a harmless laboratory bacterium
could tomorrow become an ecological catastrophe. A 2010 synbio report by the
Presidential Commission for the Study of Bioethical Issues said as much:
bUnmanaged release could, in theory, lead to undesired cross-breeding with
other organisms, uncontrolled proliferation, crowding out of existing
species, and threats to biodiversity.b

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.

During the 1990s, the Japanese cult Aum Shinrikyo, infamous for its deadly
1995 sarin-gas attack on the Tokyo subway system, maintained an active and
extremely well-funded bioweapons program, which included anthrax in its
arsenal. When police officers eventually raided its facilities, they found
proof of a years-long research effort costing an estimated $30
millionbdemonstrating, among other things, that terrorists clearly see value
in pursuing bioweaponry. 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:

    Aumbs failure suggests that it may, in fact, be far more difficult to
carry out a deadly bioterrorism attack than has sometimes been portrayed by
government officials and the press. Despite its significant financial
resources, dedicated personnel, motivation, and freedom from the scrutiny of
the Japanese authorities, Aum was unable to achieve its objectives.

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.  Viruses are particularly easy
to synthetically engineer. In 2002, Eckard Wimmer synthesized the polio
genome from mail-order DNA.

Over the years, iGEM teams have pushed not only technical barriers but
creative ones as well. By 2008, students were designing organisms with
real-world applications; the contest that year was won by a team from
Slovenia for its designer vaccine against Helicobacter pylori, the bacterium
responsible for most ulcers. 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.

As the sophistication of iGEM research has risen, so has the level of
participation. In 2004, five teams submitted 50 potential BioBricks to the
registry. Two years later, 32 teams submitted 724 parts. By 2010, iGEM had
mushroomed to 130 teams submitting 1,863 partsband the registry database was
more than 5,000 components strong. As The New York Times pointed out:

    iGEM has been grooming an entire generation of the worldbs brightest
scientific minds to embrace synthetic biologybs visionbwithout anyone really
noticing, before the public debates and regulations that typically place
checks on such risky and ethically controversial new technologies have even
started.

(igem itself does require students to be mindful of any ethical or safety
issues, and encourages public discourse on these questions.)

The second trend to consider is the progress that terrorist and criminal
organizations have made with just about every other information technology.
Since the birth of the digital revolution, some early adopters have turned
out to be rogue actors. Phone phreakers like John Draper (ab
kb
a bCaptain
Crunchb) discovered back in the 1970s that AT&Tbs telephone network could be
fooled into allowing free calls with the help of a plastic whistle given away
in cereal boxes (thus Draperbs moniker). In the 1980s, early desktop
computers were subverted by a sophisticated array of computer viruses for
malicious funbthen, 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, bMafiaboy,b a Canadian high-school student acting alone, managed to
freeze or slow down the Web sites of Yahoo, eBay, CNN, Amazon, and Dell.

In 2007, Russian hackers swamped Estonian Web sites, disrupting financial
institutions, broadcasting networks, government ministries, and the Estonian
parliament. 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 SkyGrabberbcheap Russian
software frequently used to steal satellite televisionbto intercept the video
feeds of U.S. Predator drones in order to monitor and evade American military
operations.

Lately, organized crime has taken up crowd-sourcing parts of its illegal
operationsbprinting up fake credit cards, money launderingbto people or
groups with specialized skills. (In Japan, the yakuza has even begun to
outsource murder, to Chinese gangs.) Given the anonymous nature of the online
crowd, it is all but impossible for law enforcement to track these efforts.

The historical trend is clear: Whenever novel technologies enter the market,
illegitimate uses quickly follow legitimate ones. A black market soon
appears. Thus, just as criminals and terrorists have exploited many other
forms of technology, they will surely soon turn to synthetic biology, the
latest digital frontier.

In 2005, as part of its preparation for this threat, the FBI hired Edward
You, a cancer researcher at Amgen and formerly a gene therapist at the
University of Southern Californiabs Keck School of Medicine. You, now a
supervisory special agent in the Weapons of Mass Destruction Directorate
within the FBIbs 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. bWhen I got involved,b You says, bit was pretty clear the
FBI wasnbt about to start playing Big Brother to the life sciences. Itbs not
our mandate, and itbs not possible. All the expertise lies in the scientific
community. Our job has to be outreach education. We need to create a culture
of security in the synbio community, of responsible science, so the
researchers themselves understand that they are the guardians of the future.b

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 isnbt sent to a P.O. box.

In any case, much more is necessary. An October 2011 report by the WMD
Center, a nonprofit organization led by former Senators Bob Graham (a
Democrat) and Jim Talent (a Republican), said a terrorist-sponsored WMD
strike somewhere in the world was probable by the end of 2013band that the
weapon would most likely be biological. The report specifically highlighted
the dangers of synthetic biology:

    As DNA synthesis technology continues to advance at a rapid pace, it will
soon become feasible to synthesize nearly any virus whose DNA sequence has
been decoded b& as well as artificial microbes that do not exist in nature.
This growing ability to engineer life at the molecular level carries with it
the risk of facilitating the development of new and more deadly biological
weapons.

Malevolent non-state actors are not the only danger to consider. Forty
nations now host synbio research, China among them. The Beijing Genomics
Institute, 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, SARSbthe deadly pneumonia variant that panicked the world in
2003bwas sequenced in 31 days. And BGI appears poised to move beyond DNA
sequencing and become one of the foremost DNA synthesizers as well.

BGI hires thousands of bright young researchers each year. The training is
great, but the wages are reportedly low. This means that many of its talented
synthetic biologists may well be searching for better pay and greener
pastures each year, too. Some of those jobs will undoubtedly appear in
countries not yet on the synbio radar. Iran, North Korea, and Pakistan will
almost certainly be hiring.

In the run-up to Barack Obamabs inauguration, threats against the incoming
president rose markedly. Each of those threats had to be thoroughly
investigated. In his book on the Secret Service, Ronald Kessler writes that
in January 2009, for example, when intelligence emerged that the
Somalia-based Islamist group albShabaab might try to disrupt Obamabs
inauguration, the Secret Servicebs mandate for that day became even harder.
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 wonbt be enough. A complete defense against the weapons that
synbio could make possible has yet to be invented.

The range of threats that the Secret Service has to guard against already
extends far beyond firearms and explosive devices. Both chemical and
radiological attacks have been launched against government officials in
recent years. 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.

The Kremlin, of course, has been suspected of poisoning its enemies for
decades, and anthrax has been around for a while. But genetic technologies
open the door for a new threat, in which a head of statebs own DNA could be
used against him or her. This is particularly difficult to defend against. No
amount of Secret Service vigilance can ever fully secure the presidentbs 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 sourcesba used tissue, a
drinking glass, a toothbrush. Every time President Obama shakes hands with a
constituent, Cabinet member, or foreign leader, hebs 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
presidentbs biology.

To build a bioweapon, living cells would be the true target (although dead
cells may suffice as soon as a decade from now). 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.

Even if Secret Service agents were able to sweep up all the shed cells from
the presidentbs current environs, they couldnbt stop the recovery of DNA from
the presidentbs past. DNA is a very stable molecule, and can last for
millennia. Genetic material remains present on old clothes, high-school
papersbany of the myriad objects handled and discarded long before the
announcement of a presidential candidacy. How much attention was dedicated to
protecting Barack Obamabs DNA when he was a senator? A community organizer in
Chicago? A student at Harvard Law? A kindergartner? And even if presidential
DNA were somehow fully locked down, a good approximation of the code could be
made from cells of the presidentbs children, parents, or siblings, living or
not.

Presidential DNA could be used in a variety of politically sensitive ways,
perhaps to fabricate evidence of an affair, fuel speculation about birthplace
and heritage, or identify genetic markers for diseases that could cast doubt
on leadership ability and mental acuity. How much would it take to unseat a
president? The first signs of Ronald Reaganbs Alzheimerbs 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?

For the Secret Service, these new vulnerabilities conjure attack scenarios
worthy of a Hollywood thriller. Advances in stem-cell research make any
living cell transformable into many other cell types, including neurons or
heart cells or even in vitrobderived (IVD) bsperm.b 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 bformer loverb 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 thingbthey would not be
identicalbbut the results might never be convincing to the lay public. IVD
sperm may also someday prove capable of fertilizing eggs, allowing for blove
childrenb to be born using standard in vitro fertilization.  In the hope of
mounting the best defense, one option is radical transparency: release the
presidentbs DNA.

As mentioned, even modern cancer therapies could be harnessed for malicious
ends. Personalized therapies designed to attack a specific patientbs cancer
cells are already moving into clinical trials. Synthetic biology is poised to
expand and accelerate this process by making individualized viral therapies
inexpensive. Such bmagic bulletsb 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.

The delivery of this sort of biological agent would be very difficult to
detect. Viruses are tasteless and odorless and easily aerosolized. They could
be hidden in a perfume bottle; a quick dab on the attackerbs wrist in the
general proximity of the target is all an assassination attempt would
require. If the pathogen were designed to zero in specifically on the
presidentbs DNA, then nobody else would even fall ill. No one would suspect
an attack until long after the infection.

Pernicious agents could be crafted to do their damage months or even years
after exposure, depending on the goals of the designer. Several viruses are
already known to spark cancers. New ones could eventually be designed to
infect the brain with, for instance, synthetic schizophrenia, bipolar
disorder, or Alzheimerbs. Stranger possibilities exist as well. 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 leaderbs
negotiating abilities. Some of these ideas arenbt new. As far back as 1994,
the U.S. Air Forcebs Wright Laboratory theorized about chemical-based
pheromone bombs.

Of course, heads of state would not be the only ones vulnerable to synbio
threats. AlbQaeda flew planes into buildings to cripple Wall Street, but
imagine the damage an attack targeting the CEOs of a number of Fortune 500
companies could do to the world economy. 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 bsettleb all sorts of disputes,
even those of the domestic variety. Without question, we are near the dawn of
a brave new world.

How might we protect the president in the years ahead, as biotech continues
to advance? Despite the acceleration of readily exploitable biotechnology,
the Secret Service is not powerless. Steps can be taken to limit risks. The
agency would not reveal what defenses are already in place, but establishing
a crack scientific task force within the agency to monitor, forecast, and
evaluate new biotechnological risks would be an obvious place to start.
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 betterba lot betterbbut even so, they might be limited in their
effectiveness. Because synbio opens the door to new, finely targeted
pathogens, webd need to detect that which webve 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 presidentbs actual genome. We
could use his living cells to build an early-warning system with molecular
accuracy.

Cultures of live cells taken from the president could also be kept at the
readybthe biological equivalent to data backups. The Secret Service
reportedly already carries several pints of blood of the presidentbs type in
his motorcade, in case an emergency transfusion becomes necessary. These
biological backup systems could be expanded to include bclean
DNAbbessentially, 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
presidentbs cells could even be turned, one day, into ready-made standby
replacement organs.

Yet even if the Secret Service were to implement some or all of these
measures, there is no guarantee that the presidential genome could be
completely protected. Anyone truly determined to get the presidentbs DNA
would probably succeed, no matter the defenses. And the Secret Service might
have to accept that it canbt fully counter all bio-threats, any more than it
can guarantee that the president will never catch a cold.

In the hope of mounting the best defense against an attack, one possible
solutionbnot without its drawbacksbis radical transparency: release the
presidentbs DNA and other relevant biological data, either to a select group
of security-cleared bioscience researchers or (the far more controversial
step) to the public at large. These ideas may seem counterintuitive, but we
have come to believe that open-sourcing this problemband actively engaging
the American public in the challenge of protecting its leaderbmight turn out
to be the best defense.

One practical reason is cost. Any in-house protection effort would be
exceptionally pricey. Certainly, considering whatbs 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
militarybs $35,000 Raven. This kind of price reduction is typical of
open-sourced projects.

Moreover, conducting bio-security in-house means attracting and retaining a
very high level of talent. This puts the Secret Service in competition with
industryba fiscally untenable positionband with academia, which offers
researchers the freedom to tackle a wider range of interesting problems. But
by tapping the collective intelligence of the life-sciences community, the
agency would enlist the help of the group best prepared to address this
problem, at no cost.

Open-sourcing the presidentbs genetic information to a select group of
security-cleared researchers would bring other benefits as well. It would
allow the life sciences to follow in the footsteps of the computer sciences,
where bred-team exercises,b or bpenetration testing,b are extremely common
practices. In these exercises, the red teambusually a group of faux-black-hat
hackersbattempts to find weaknesses in an organizationbs defenses (the blue
team). A similar testing environment could be developed for biological war
games.

One of the reasons this kind of practice has been so widely instituted in the
computer world is that the speed of development far exceeds the ability of
any individual security expert, working alone, to keep pace. Because the life
sciences are now advancing faster than computing, little short of an internal
Manhattan Projectbstyle 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.

So why go further? Why take the radical step of releasing the presidentbs
genome to the world instead of just to researchers with security clearances?
For one thing, as the U.S. State Departmentbs DNA-gathering mandate makes
clear, the surreptitious collection of world leadersb genetic material has
already begun. It would not be surprising if the presidentbs DNA has already
been collected and analyzed by Americabs adversaries. Nor is it unthinkable,
given our increasingly nasty party politics, that the presidentbs 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, badvances in
genomics will make it more likely that DNA will be collected and analyzed to
assess genetic risk information that could be used for or, more likely,
against presidential candidates.b Itbs 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 leadersb genomes and medical
histories. Sooner or later, even without open-sourcing, a presidentbs genome
will end up in the public eye.

So the question becomes: Is it more dangerous to play defense and hope for
the best, or to go on offense and prepare for the worst? Neither choice is
terrific, but even beyond the important issues of cost and talent attraction,
open-sourcingbas Claire Fraser, the director of the Institute for Genome
Sciences at the University of Maryland School of Medicine, points outbbwould
level the playing field, removing the need for intelligence agencies to plan
for every possible worst-case scenario.b

It would also let the White House preempt the media storm that would occur if
someone else leaked the presidentbs genome. In addition, constant scrutiny of
the presidentbs 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.

The largest factor to consider is time. In 2008, some 14,000 people were
working in U.S. labs with access to seriously pathogenic materials; we donbt
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 CIAbs 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, bmost panelists
argued that a qualitatively different relationship between the government and
life sciences communities might be needed to most effectively grapple with
the future BW threat.b

In our view, itbs no longer a question of bmight be.b 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 Therebs 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 organizationsbone defined by open exchange, continual collaboration,
and crowd-sourced defensesbmay prove the only way to protect the president.
And, in the process, the rest of us.  Andrew Hessel is a faculty member and a
former co-chair of bioinformatics and biotechnology at Singularity
University, and a fellow at the Institute for Science, Society, and Policy at
the University of Ottawa. Marc Goodman investigates the impact of advancing
technologies on global security, advising Interpol and the U.S. government.
He is the founder of the Future Crimes Institute and Chair for Policy, Law &
Ethics at Silicon Valley's Singularity University. Steven Kotler is a New
York Timesbbest-selling author and an award-winning journalist.