April 25 2014 CQ Researcher Article with Rina

Some consider syn-thetic biology a natural evo-lution of genetic engineering, while others, such as synthetic biolo-gy pioneer J.. Others worry that no fed-eral regulations specifically

Synthetic Biology

Should scientists try to create new life forms?

scientists are manipulating the structure of cells to create new life forms designed to perform specific functions, such as detecting arsenic in drinking water or producing biofuels from algae More than 500 companies,

universities and other organizations worldwide are conducting

re-search in the new field, known as synthetic biology, and

develop-ing products with the technology Proponents say it will safely

revolutionize everything from food and fuel production to medicine

and manufacturing But the field is largely self-regulated, leading

critics to warn that synthetic biology — especially when used on

an industrial scale — poses potential environmental and health risks

that as yet are unexplored Additionally, some ethicists question

whether scientists should be creating new life forms And others

fear that the proliferation of do-it-yourself labs, where the public is

free to experiment with synthetic biology, could enable terrorists to

use the technology to create bioweapons

Children are tested for malaria at a clinic in western Thailand A synthetic version of the antimalarial drug artemisinin is expected to prevent hundreds of thousands of deaths from malaria each year, mostly of children in Africa and Asia, but could put local farmers who raise wormwood plants, from which the natural product is derived, out of business.

CQ Researcher • April 25, 2014 • www.cqresearcher.com

Volume 24, Number 16 • Pages 361-384

R ECIPIENT OF S OCIETY OF P ROFESSIONAL J OURNALISTS A WARD FOR

E XCELLENCE A MERICAN B AR A SSOCIATION S ILVER G AVEL A WARD

I N S I D E

T HE I SSUES 363

B ACKGROUND 370

C HRONOLOGY 371

C URRENT S ITUATION 376

A T I SSUE 377

O UTLOOK 379

B IBLIOGRAPHY 382

Published by CQ Press, an Imprint of SAGE Publications, Inc. www.cqresearcher.com

T HE I SSUES

363 • Is synthetic biology safe?

• Does synthetic biology

pose a national security risk?

• Should the government

regulate synthetic biology?

B ACKGROUND

370 Mendel’s Peas

Modern biology began with

the 19th-century experiments

of German monk Gregor

Mendel

372 Genetic Engineering

The development of genetic

engineering led to synthetic

biology

374 Synthetic Biology Emerges

The first DNA synthesizer in

Research is moving forward

even as critics continue to

raise concerns

378 Biomanufacturing

Synthetic biology is a key

el-ement of future biotech

379 Fits and Starts?

Synthetic biology could mark

a scientific revolution or have

a limited impact

S IDEBARS AND G RAPHICS

364 More Groups Studying

Synthetic BiologyThe number of companiesconducting such researchtripled from 2009 to 2013

365 North America Dominates

Synthetic Biology MarketThe industry’s market value isprojected to increase nearlysevenfold by 2016

368 Support for Synthetic

Biology Regulation FallsAmericans are almost evenlysplit over regulation

and difficult tradeoffs

Selected sources used

383 The Next Step

Additional articles

383 Citing CQ Researcher

Sample bibliography formats

Cover: Reuters/Sukree Sukplang

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acid-April 25, 2014 Volume 24, Number 16

Synthetic Biology

I n November, more than

200 teams of students

from around the world

competed in a science

con-test, devising novel ways to

detect arsenic in drinking

water, insert engineered

micro-organisms into bees’

digestive tracts to protect

them from toxins and even

engineer the common E coli

bacteria to cheaply and

effi-ciently recycle gold from

elec-tronic waste

Since it began a decade

ago, the International

Ge-netically Engineered Machine

(iGEM) competition has

in-volved 15,000 students,

teach-ers and advisteach-ers who are

ex-perimenting with synthetic

biology, a broad-based,

emerg-ing and largely self-regulated

field considered by many as

one of the most promising

areas of science

More than 500 companies,

universities and other

organi-zations worldwide are

con-ducting research and

devel-oping products using synthetic

biology Some consider

syn-thetic biology a natural

evo-lution of genetic engineering,

while others, such as synthetic

biolo-gy pioneer J Craig Venter, see it as the

beginning of a revolutionary new era

Among the technology’s “modest” goals,

Venter said, are “replacing fossil fuel

energy, ridding the world of most of

what we know as agriculture [and]

changing how we produce clean water

and medicines.” 1

But some environmentalists say the

health and environmental risks of the

technology, especially its use for

in-dustrial purposes, are unknown

Crit-ics warn that many experimenting with

synthetic biology are computer tists and engineers, not biologists orecologists who would understand theeffects of synthetic organisms on theenvironment Others worry that no fed-eral regulations specifically cover syn-thetic biology, and that amateur scien-tists can order synthetic genetic materialover the Internet and experiment with

scien-it in do-scien-it-yourself labs Securscien-ity cials are concerned that the technolo-

offi-gy could be used by terrorists Andsome ethicists are uneasy about scien-tists creating life forms

The technology is difficult todefine “If you were to ask fivesynthetic biologists to define theirfield, you’ll get six different an-swers,” one prominent researchcenter has said 2

Synthetic biology builds onthe science of genetic engi-neering, which inserts existinggenes from one species intoanother “Generally, there’s nobright line between geneticengineering and synthetic bi-ology,” says Gregory E Kaeb-nick, a research scholar at theHastings Center, a Garrison,N.Y.-based bioethics research

institute, and author of

Hu-mans in Nature — The World

As We Find It and the World

As We Create It. However, headds, synthetic biology is some-times described as “especiallydramatic genetic engineering

— or ‘extreme genetic neering,’ as the critics some-times say.”

engi-That’s because synthetic ology takes genetic engi-neering one step further:Rather than inserting an ex-isting gene from one organ-ism into another, syntheticbiology “represents the abil-ity to synthesize — or cre-ate — genetic informationoutside of a standard cell,”explains D Keith Roper, program di-rector of the National Science Foun-dation’s (NSF) Division of EngineeringEducation and Centers, which fundsmany synthetic biology programs Thenresearchers can “insert that genetic in-formation into a cell, like reprogram-ming code in a computer,” to get thecell to do different, potentially bene-ficial things For example, scientists aretrying to reprogram simple organismssuch as bacteria, yeast and micro-scopic algae to ward off viruses orcreate renewable fuel

Synthetic biology has advanced

rapidly From 2009 to 2013 the

num-ber of companies worldwide

con-ducting synthetic biology research

tripled — from 61 to 192 — while

the number of universities doing such

research grew from 127 to 204 In the

United States, 39 states and the

Dis-trict of Columbia have at least one

fa-cility working on synthetic biology 3

(See graph, above.)

Experts project that the global

syn-thetic biology market value will grow

from its current $1.6 billion to $10.8

bil-lion by 2016, with some companies

already manufacturing products — such

as pharmaceuticals, synthetic rubber,

jet fuel and perfume fragrances —

using parts and processes created

through the technology 4 (See graph,

p 365.) The United States has the most

organizations working in the field,

fol-lowed by the United Kingdom,

Ger-many, Japan and China 5In January,

Great Britain announced it was

es-tablishing three new synthetic biology

research centers, calling the technology

“one of the most promising areas ofmodern science.” 6

In the United States, Massachusettsand California have the greatest con-centration of synthetic biology labs, part-

ly because the NSF has spent $4 lion a year since 2006 on syntheticbiology research in those two states

mil-— part of a 10-year program TheNSF-funded Synthetic Biology Engi-neering Research Center (Synberc), acollaboration of the field’s top scien-tists, operates from hubs at universi-ties in the Boston and San Franciscoareas Other federal agencies have spentanother $500 million to $1 billion since

2006 on synthetic biology research 7There are two types of synthetic bi-ology, both with “tremendous poten-tial” in medicine, materials fabrication,agriculture and environmental protec-tion, says Kenneth Oye, director of theMassachusetts Institute of Technology(MIT) Program on Emerging Tech-nologies

The first type “seeks to create tificial life,’ ” he says, “the development

‘ar-of novel organisms from scratch.” In

2010, Venter made history by creatingthe first self-replicating synthetic lifeform after inserting an artificial genomeinside a bacterium

In the second type of syntheticbiology, researchers are “moving awayfrom customized design of each neworganism to a modularized parts-orientedapproach” that resembles convention-

al industrial processes, says Oye Byreducing the skill levels and dramati-cally cutting the costs associated withbiological engineering, he says, scien-tists have been able to create “stan-dardized inventories of parts” that can

be repurposed for different uses, lowing the industrial-scale manufac-turing of synthetic biology products

al-“A lot of what my lab does is reducethe cost of things,” says George Church,

a professor of genetics at Harvard ical School, and a leading synthetic bi-ologist A technology developed at hislab, called Multiplex Automated GenomeEngineering (MAGE), has reduced “amillionfold” the cost of analyzing an or-ganism’s DNA sequence and synthesiz-ing new genes, he says

Med-Using the MAGE technology, Churchsays, researchers can generate a fewbillion modified genomes per day, eachone 4.7 million base pairs long 8Thissuper-accelerated evolutionary processenables them to splice new geneticparts into cells, creating artificial mu-tations, then identify desirable mole-cules that allow the cell to live or die

or out-compete other cells “We’returning productivity into a Darwiniansurvival of the fittest,” says Church.Another Synberc scientist, StanfordUniversity assistant professor of bio-engineering Drew Endy, and his col-leagues created “BioBrick” parts —standardized microscopic parts oftencompared to toy Lego blocks, thatcontain pieces of DNA that can beconnected to one another and insert-

ed into a bacterium or yeast to

per-* No data collected.

** Includes such organizations as the National Academy of Sciences and the

Synthetic Biology Project at the Woodrow Wilson International Center for Scholars.

Source: “Tracking the Growth of Synthetic Biology: Findings for 2013,” Woodrow

Wilson International Center for Scholars, http://tinyurl.com/pfuhrph

More Groups Studying Synthetic Biology

The number of organizations conducting research on synthetic

biology rose to more than 500 worldwide between 2009 and 2013

Nearly 200 companies were conducting such research in 2013,

more than three times the 2009 total.

University Company Research

Institution

ment Lab

Govern-Military Lab

Policy &

nance**

Gover-Community Lab

2009 2013

form a task, such as signaling the

pres-ence of a toxin by turning green

Dif-ferent combinations of DNA

ingredi-ents can even be printed out as a

sequence of genetic material on a 3-D

printer 9 A strong proponent of open

access to synthetic biology, Endy helped

create an online catalogue offering “off

the shelf” synthetic genetic parts that

can be ordered via the Internet and

used to create new products

But simplistic talk of 3-D printers and

Legos may give the public the

unreal-istic idea that synthetic biology is

sim-ple, widening “the gap between the

ex-pectations of the scientist and exex-pectations

of the public,” cautions Eleonore Pauwels,

a public policy scholar at the Woodrow

Wilson International Center for Scholars,

a think tank in Washington The

pub-lic’s expectations for dramatic scientific

advances might be dashed, she says,

be-cause tinkering with living cells has

many unknowns

For instance, even the common E coli

bacteria — the most studied living

or-ganism (other than viruses) and

con-sidered the workhorse of genetic

en-gineering due to its low cost and

relative simplicity — is not well

un-derstood “There may be 4,000 genes

in E coli, give or take,” but no one

knows what about a third of those

genes do, says Leonard Katz, Synberc’s

research and industry relations director

With so many unknowns, some

en-vironmentalists say not enough research

has been done on the environmental

impact of synthetic biology “[T]here has

been very limited consideration of the

risks and benefits that synthetic

organ-isms may pose to the biological world,”

said a report by the Bronx, N.Y.-based

Wildlife Conservation Society 10

Ecologists worry about negative

ef-fects of an accidental release of

syn-thetic organisms, and environmental

justice advocates say some synthetic

biology products, such as those used

to create synthetic vanilla and the

anti-malarial drug artemisinin, could ruin

small farmers who grow the natural

components of those products (See

sidebar, p 374.)International law enforcement agen-cies also fear that terrorists might usesynthetic biology to create biologicalweapons 11 “Synthetic biology pre-sents capacities for destruction that areakin to those of breaking the atom,”

says ethicist Kaebnick “But breakingthe atom depended on huge govern-mental infrastructure It was innatelyeasier to monitor and control, but syn-thetic biology could be undertaken bysmall-scale labs.”

In 2012, more than 110 environmental,consumer and religious groups calledfor a moratorium on commercial ap-plications of synthetic biology until reg-ulations specifically governing the newtechnology are developed 12 (See “At

Issue,” p 377.) Others warn about entific hubris When Venter announcedthe creation of the first self-replicatingsynthetic life form, religious organiza-tions charged him with “playing God.”

sci-In response to Venter’s creation, ident Obama asked the Presidential Com-mission for the Study of Bioethical Is-

Pres-sues to study the new technology Thepanel proposed several ethical princi-ples to guide public policy: public benef-icence; responsible stewardship; intel-lectual freedom and responsibility;democratic deliberation, and justice andfairness Along with “responsible stew-ardship,” it also urged concern for theenvironment and future generations.However, the commission concluded in

2010 that the technology’s risks, so far,were limited 13

Four years later, as new synthetic ology products hit the market, it re-mains unclear whether the public willembrace the technology A 2013 pub-lic opinion poll found that 45 percent

bi-of respondents had heard “nothing atall” about the technology In initial in-quiries, the risks and benefits were seen

as roughly equal by poll participants,but after hearing more details manyraised concerns about bioterrorism, po-tential harm to humans and the moralimplications of creating life 14

“It’s the overall alteration of things

to create new forms that is sometimesconcerning,” says ethicist Kaebnick

North America Dominates Synthetic Market

North America accounted for about 40 percent of the synthetic biology industry’s global market value in 2011 Europe controlled

30 percent Researchers project that the industry’s market value will increase nearly sevenfold by 2016, from $1.6 billion in 2011 to

$10.8 billion.

Source: “Sustainability Initiative Initial Findings & Recommendations,” Synberc, Feb 4, 2014, http://tinyurl.com/o5rzygy, using data from John Bergin, “Synthetic Biology: Emerging Global Markets,” BCC Research, Wellesley, Mass., November 2011, http://tinyurl.com/p4sob2e

Synthetic Biology Market Value in 2011, by Region

(in $ millions)

North America ($657.1) Europe ($485) Asia ($440.9) Rest of World ($61.4)

Total: $1,644.4

(in $ millio

Others say synthetic biology has a

long way to go to meet its promises

The science “is really fascinating and

promising and definitely worth

pur-suing,” says law professor Jonathan

Kahn of Hamline University in St Paul,

Minn., who specializes in the social

justice implications of biotechnology

But, he adds, “I feel it’s been way

overhyped.”

As synthetic biology continues to

emerge, here are some of the key

questions that scientists,

environmen-talists and ethicists are debating:

Is synthetic biology safe?

Proponents of synthetic biology say

safeguards are in place to reduce

po-tential risks to human health and the

environment, but critics have raised

concerns

A 2012 article in the journal Nature

said research is needed on how

es-caped microbes “might alter habitats,

food webs or biodiversity” and on

whether the organisms might quickly

evolve or their genes might transfer

into other natural organisms “Once leased, synthetic organisms cannot beretrieved,” the authors warned “It isimperative that funding and researchcommunities take action to prevent fu-ture ecological disasters.” 15

re-The report called for dedicated, term government funding — a mini-mum of $20 million to $30 millionover a decade — to assess environ-mental risks posed by synthetic or-ganisms The National Science Foun-

long-dation (NSF) estimates that about 10 to

15 percent of its $4 million annualfunding for Synberc — or about half

a million dollars a year — is spent tostudy risk, containment, safety, securi-

ty and related issues

Jim Thomas, research programmanager at the Ottawa-based ETCGroup, a Canadian research and ad-vocacy nonprofit that monitors the so-cial and economic impact of technol-ogy, doesn’t question the use ofsynthetic biology to better understandliving systems and to increase knowl-edge of genetics But given how much

scientists don’t know about how lifeworks, he says, not enough researchhas been conducted on whether com-mercialized synthetic biology posesdangers to the environment or toworkers who would be exposed toartificial organisms in the manufactur-ing process

Synthetic biology is “a useful tool,”

he says, but “we draw a line at thelab door.”

Roper of the NSF says researchersare being proactive about reducing thepotential risks posed by organisms pro-duced through synthetic biology “Thepossibility of these reprogrammedcells finding an environmental nichewhere they could out-compete natur-

al organisms presents a potential risk,”

he says But, he adds, during decades

of altering organisms’ makeup throughgenetic engineering, safeguards have beenput in place to minimize accidental re-leases “After 50 years of dealing withthis question for micro-organisms thathave had their information contentreprogrammed to some extent, wehave yet to find an example that hashad the ability to displace a naturalorganism.”

Rina Singh, senior director, industrialand environmental, of the Washington-based Biotechnology Industry Organi-zation (BIO), a trade association, sayssafety fears are overblown “When youfirst hear you can engineer a microbe,you have fear in people,” she says “Theystart seeing visions of aliens we might

be creating.” Existing measures to trol traditional genetically modified or-ganisms can safely be applied to syn-thetic biology, she says

con-Thomas is not reassured “Thebiosafety concerns around geneticallymodified organisms are amplified manytimes [with synthetic biology],” he ar-gues, citing the example of the cornborer and corn rootworm — pests thatboth developed resistance to a com-mon insecticide after widespread use

of genetically engineered corn designed

to protect the corn crops Just as with

Glowing Plant, a synthetic biology company in San Francisco, has developed

plants that emit light But environmental groups began a letter-writing campaign

last year urging the U.S Department of Agriculture to halt the introduction of the

plants until their production is regulated Congress has yet to look into

safety concerns raised about synthetic biology.

genetically modified corn, he says, there

may be unintended consequences from

synthetic biology 16 With synthetic

bi-ology, Thomas says, “There will be

larger numbers of organisms being

modified, and the degree of

modifi-cation novelty is much higher than in

anything that’s existed before.”

Syn-thetic organisms could spread and

mu-tate in unexpected ways, ETC says

Also of concern, Thomas says, is the

harm to small farmers in developing

countries whose crops and livelihoods

are threatened by mass production of

synthetic biology products

Some applications are more

worri-some than others, say critics of

syn-thetic biology Pharmaceuticals, they

say, already go through a stringent

reg-ulatory process, but something like

syn-thetic microscopic algae, seen by

in-dustry as a promising source of

biofuel, has many unknowns

“If you’re engineering a yeast and

keeping it in a tank where you can

kill it if something goes wrong, that’s

less worrisome than having large ponds

of cyanobacteria [blue-green algae]

where ducks or winds can spread it

around the world,” says Jaydee

Han-son, policy director of the nonprofit

International Center for Technology

Assessment, based in Washington, D.C.,

which analyzes the impact of

tech-nology on society

“We know there are serious

eco-logical effects as we change nature,

so we need to do this carefully,”

Han-son continues “We have plenty of

mis-takes we can look out on and say,

‘gee, we probably shouldn’t have let

people import all those snakes [that

are now] covering the Everglades.’

Those are things we can see With the

algae they’re engineering, we can’t see

them, but we can breathe [them] in.”

Harvard’s Church points out, “We

breathe in algae every day It’s all over

the place.” Nevertheless, in their book

Regenesis — How Synthetic Biology Will

Reinvent Nature and Ourselves, Church

and science journalist Ed Regis

sug-gest requiring licenses for all aspects

of synthetic biology, including smalllabs; designing cells that would self-destruct outside of the lab; and rigor-ous testing of synthetic organisms incontained ecosystems that simulate thenatural world 17

As for algal biofuels, Singh says,

“Some companies are exploring openpond systems, but they’re a little fur-ther into the future because of thetype of infrastructure we’re talkingabout A lot of the microalgaes [micro-scopic algae] are already known in na-ture, so you’re not talking about some-thing foreign — you’ve engineered it,

so you have good control It’s not anew bug or anything like that.”

Testifying before the Presidential mission in 2010, synthetic biologist Ven-ter said the unintentional spread of syn-thetic organisms might be prevented byimplanting them with “suicide” genesthat would trigger if the organisms es-caped or by engineering the organism

Com-to depend on a sole source of foodthat does not exist in nature 18 Butwhether manufacturers would be re-quired to include these safety measures,and whether the government wouldmonitor them, is unclear

And biosafety expert Allison Snow,

co-author of the 2012 Nature piece

and professor of evolution, ecologyand organismal biology at Ohio StateUniversity, says ecologists don’t knowwhether suicide genes can spread toother organisms “The consequenceswould depend on the type of suicidegenes used,” she said in an email “Forexample, are the genes turned on by

a specific chemical or temperature? Fornow, I think it is too early to knowwhether suicide genes raise environ-mental concerns because the specifics

of how these genes would work arenot available to my knowledge.”

Val H Smith, a professor of

ecolo-gy and environmental bioloecolo-gy at theUniversity of Kansas and an expert onalgal blooms, agrees, especially sincemany synthetic biology researchers are

engineers or computer scientists —not ecologists or biologists

So far, although algae has beenscreened, hybridized and redesigned,

he notes, no unique new algal ganism has been created from scratch.But once such organisms are devel-oped, “My strongest concern is that if

or-an accidental release occurs, then genesfor enhanced productivity could po-tentially be transferred horizontally fromgenetically modified algae into normal

‘wild-type’ strains,” he said in an email.The potential environmental effectsare unknown

The ETC Group, along with the vironmental group Friends of the Earthand the International Center for Tech-nology Assessment, supports “The Prin-ciples for the Oversight of SyntheticBiology,” a document backed by 111environmental, conservation, consumerand religious organizations around theworld 19 It calls for a moratorium ondevelopment of commercial applica-tions of synthetic biology until regu-lations are developed specifically gov-erning the new technology, based onthe “precautionary principle.” Widelyused by European regulatory agencies,the precautionary principle requirescompanies to prove their products aresafe for human health and the envi-ronment before they can be approvedfor widespread use In the United States,the onus often is on the government

en-to prove a product is dangerous fore it can be regulated

be-“While synthetic biology may be auseful tool in helping to better under-stand biological systems, it carries toomany risks and unanswered questions to

be allowed outside the lab at this time,”Friends of the Earth said in announcingthe principles in March 2012 20

Does synthetic biology pose a tional security risk?

na-Defense officials are among thosewho worry that synthetic organismscould fall into the wrong hands Re-searchers, international consortia and

the FBI are working to control

“dual-use” organisms — those developed for

beneficial purposes but also having

potential to do harm

At the Geneva-based U.N

Biologi-cal Weapons Convention (BWC)

Im-plementation Support Unit, Acting

Di-rector Piers Millet says efforts are

under way to reduce the potential risk

of synthetic biology

“The possibility of a reliable,

engi-neered, reproducible biotech platform

that reduces the time to go from an

idea to an application, cheaper, faster

and by more people could change the

world,” he wrote in an email “The

same power could also enable

those with more malign motivations.”

He cites a 2012 BWC report that

iden-tified worrisome potential

develop-ments, such as the creation of novel

means of delivering biological agents

and toxins and new mechanisms that

could disrupt the healthy functioning

of humans, plants and animals 21

Mil-let said he knew of no evidence that

such actions have occurred

Like Millet, Edward You, an FBI

supervisory special agent, is actively

involved in the world of synthetic

bi-ology, as part of the agency’s

direc-torate on weapons of mass tion “We haven’t identified nefariousintent, but there’s risk and vulnerabili-ty,” he says “As promising and power-ful as synthetic biology is, the poten-tial for misuse exists.”

destruc-To reduce the risk, the bureau has

56 agents creating relationships withscientists, universities, companies anddo-it-yourself (DIY) community labsaround the country to instill sensitiv-ity to security concerns “How do weget as many ‘white hats’ as possible,

so they’ll come up with tools to dress these concerns and identify the

ad-‘black hats’ themselves?” asks You “How

do we skew it so legitimate researchbecomes overwhelmingly difficult forbad actors to use these capabilities?

The best way is making as salient

a web of detection as possible We’regetting self-assessment from the sci-entific community themselves Oncethey get our message, it expands theirawareness, the tables are turned andthey educate us.”

The FBI has been a sponsor of theInternational Genetically EngineeredMachine (iGEM) competition since 2009and each year hosts a biosecurity work-shop at the gathering Students learn

about international treaties such as theBWC and bioweapons criminal statutes

“It’s not a sense of being burdensomeand onerous but a sense of empower-ing them,” says You Drawing on aquote popularized in the “Spiderman”comic books, he says, “We tell themwith great power comes great respon-sibility They really glom onto that, and

it heightens their sense of scientific izenship.”

cit-Ultimately, though, You edges, “We don’t have the mandate,

acknowl-we don’t have the authority and acknowl-wesure don’t have the resources to ad-dress this rapidly expanding field.”Thus, he says, “Our whole approach

is building relationships between thescientific and security communities.”MIT’s Oye says the risk from “dualuse” is “moderate” at this point because

“there are many ways of doing harm

to other people, and the methods ofsynthetic biology are rarely the mostconvenient or efficient approaches.”However, over the longer term, he says,

“The reductions in skill thresholds andwider access to power technologies dopose legitimate security issues.”Much of the concern has to do withthe open-access attitude of many syn-thetic biologists and the spread ofcommunity do-it-yourself (DIY) syn-thetic biology labs such as the 40small-scale labs that make up the so-called DIYbio network of community

laboratories (See sidebar, p 372.) Tom

Burkett, who co-founded one suchlab, Baltimore Underground ScienceSpace (BUGSS), says the lab has se-curity measures in place

“The DIYbio community has ally been extremely proactive aboutsecurity, because it was a pretty earlycriticism,” says Burkett BUGSS con-trols all materials coming in and out,

actu-he says, and ensures tactu-he materials are

on an approved safety list “I’veworked in academic and industrial labs,and I’ve worked in DIYbio, and I cansay the procedures we do in a lot ofways are safer.”

* Developed jointly by industry and government

Source: “Awareness & Impressions of Synthetic Biology,” Hart Research Associates,

March 6, 2013, http://tinyurl.com/kx5mgfe

Support for Synthetic Biology Regulation Falls

The proportion of Americans favoring government regulation of

synthetic biology research dropped 7 percentage points between 2010

and 2013, while the share of those supporting voluntary guidelines

grew by the same amount In 2013, Americans were almost evenly

split on the issue.

Both You and Millet say they have

worked with the DIYbio movement, which

Millet calls “a safe, community-driven

space to explore modern biology.”

Nonetheless, he continues, “They,

and we, need to ensure that they are

exploring [synthetic biology] safely and

securely These communities have made

tremendous efforts to start off in the

right direction I think it is the

re-sponsibility of their governments to

provide them with the resources they

need to be able to ensure these spaces

are no less safe or secure than an

aca-demic facility.”

Katz, of Synberc, acknowledges

that his organization’s goal of making

biology easier to engineer can be risky

and that scientists are unlikely to come

into contact with those who might be

bent on doing harm “How do we

know somebody’s not using this in

some negative way?” he asks “My

be-lief is scientists are ethical and have

good intentions and are trying to do

something that’s beneficial We have

safety issues that we deal with We’re

not working on anything dangerous,

and we have containment that we

prac-tice in the lab But there are

unin-tended consequences.”

“The idea that scientists are good

guys [so] we don’t have to worry is

preposterous,” says the Hastings

Cen-ter’s Kaebnick “But any system of

monitoring synthetic biology and

try-ing to protect society from bad uses

is going to have to depend on good

guys in science — and there are a

lot of good guys Somehow we have

to come up with ways to empower

[them] and it has to depend on some

sort of professional self-monitoring It’s

unrealistic to think the government

should do this.”

NSF’s Roper says steps already are

being taken to reduce the risks The

departments of Health and Human

Ser-vices and Agriculture maintain lists of

potentially dangerous micro-organisms

and genetic materials, which only

le-gitimate labs and institutions may use

under very tight security The merce Department tracks the move-ment of nucleic acids across state bor-ders, and most manufacturers of DNAparts have voluntarily agreed to screenthe orders they receive

Com-“[Government agencies] are lookingfor parts associated with pathogenici-

ty and infectivity,” says Oye “They arealso looking at the characteristics ofcustomers and making judgments onthe legitimacy and capabilities of cus-tomers For example, a pharmaceuti-cal company would be treated differ-ently from a garage hobbyist.”

On the international front, in tion to the BWC, the Australia Group

addi-is a voluntary network of nations icated to limiting the spread of chem-ical and biological weapons, includingthose potentially made in the futurethrough synthetic biology But only 42countries — including the United States

ded-— have joined China, a significantplayer in the synthetic biology realm,

is not among the signatories

Should the federal government regulate synthetic biology?

No federal regulations specificallycover synthetic biology Generally, syn-thetic biology products and processesdeveloped in the United States fallunder the same set of voluntary guide-lines, policies and rules that governgenetic engineering These are imple-mented by the multi-agency Coordi-nated Framework for the Regulation

of Biotechnology, under which

feder-al agencies look at the safety of anend product, regardless of how it wasdeveloped

The Coordinated Framework workswell, says BIO’s Singh “It’s not regu-lating the process, but the end use forthe consumer,” she says

Crops, whether genetically engineered

or created via synthetic biology, are ulated by the Department of Agricul-ture, while food products and cosmet-ics would fall under the rules of theFood and Drug Administration The Oc-

reg-cupational Safety and Health tration (OSHA) takes care of workplacesafety and the Department of Commercekeeps an eye on interstate shipment ofinfectious agents For its part, the En-vironmental Protection Agency (EPA)oversees the introduction of “new” or-ganisms under the Toxic SubstanceControl Act, although defining what is

Adminis-“new” is no simple matter Complex teria are used, depending on the ex-tent of genetic manipulation and howdifferent the result is from naturally oc-curring organisms 22

cri-There also are federal regulations erning the growing of micro-organisms

gov-in uncontagov-ined areas, says the NSF’sRoper “Before any organization, insti-tution or industry is allowed to ex-pose or introduce any micro-organismsthat could in any way alter the envi-ronment, they are required to outlinetheir plans for use and provide con-tainment and surveillance plans,” hesays There are also various levels ofgovernment safety review boards inplace, he adds

The presidential commission on thetic biology in 2010 decided self-regulation and a “culture of individualand corporate responsibility” was suf-ficient for the emerging field, and found

syn-“no reason to endorse additional eral regulations or a moratorium onwork in this field at this time.” 23 In-stead, the panel endorsed a 2009 de-cision by the National Institutes ofHealth (NIH) to treat synthetic biolo-

fed-gy the same as traditional genetic gineering 24

en-The NIH process stemmed from a

1975 gathering of scientists at theAsilomar Conference Center in Pacif-

ic Grove, Calif., to hash out safety cerns about the emerging field of ge-netic engineering The conferencerecommended a peer-review oversightgroup, the Recombinant DNA Adviso-

con-ry Committee, which continues to makenonbinding recommendations to theNIH director on related research, in-cluding synthetic biology

But some experts say the Asilomar

Conference’s self-regulatory approach

is no longer adequate if it ever was

Writing in the Valparaiso University

Law Review, Hamline University law

professor Kahn noted, “In the early

1970s, genetic research was largely

con-ducted in the confines of universities,

and there was no biotechnology

indus-try of which to speak Professors of

mol-ecular biology were primarily researchers,

not patent holders or CEOs.” 25 Today,

top academic researchers spin off

for-profit ventures or sell their patents to

large corporations, whose financial goals

may conflict with the public interest,

he says “My concern is that the

re-search is moving towards [being just]

commercially valuable rather than

sci-entifically valuable Sometimes these

co-incide, and sometimes they don’t.”

Hanson, of the International

Cen-ter for Technology Assessment, says,

“It’s not a synthetic biology problem,

it’s a problem with weak regulation to

begin with.” He and other critics were

already unhappy with regulation of

genetic engineering even before

syn-thetic biology emerged Noting that

food and cosmetics are prime

candi-dates for synthetic biology, he says,

“Cosmetics and dietary supplements

are the weakest part of the FDA

reg-ulatory program The next weakest is

food safety Since genetically modified

organisms are mostly regulated through

fiction, we’d like it stronger than that.”

Moreover, unlike say, corn, a

nat-ural plant that has been genetically

modified, new organisms created by

synthetic biology may behave even

more unpredictably, and their safety

should be controlled through special

regulations, say critics

For example, say critics, a Kickstarter

crowdsourcing campaign funded

devel-opment of plants that glow, as “the first

step toward sustainable lighting.”

Thou-sands of individuals have preordered

seeds and starter kits to grow their own

glowing plants, which will be shipped

this summer 26“The industry argues that

whatever regulations exist are perfectlyadequate, and that you don’t need any-thing more,” says Thomas of the ETCGroup “The glowing-plants episodeshows that’s not true There are no reg-ulations relevant to this [plant] This iscrazy, frankly, and points to how far be-hind the regulatory side is.”

Thomas prefers that the United Statesadopt the tougher regulatory approachused in Europe, where governmentshave adopted the precautionary prin-ciple “If you have a new chemicaland have no data [on its safety], youcan’t have market approval,” he says

As for small-scale DIYbio labs, kett says regulation of community labslike his in Baltimore is “inevitable.”

Bur-“I would like to have a say in whatthat is,” he says, not sounding veryhopeful

Meanwhile, public opinion is vided: 45 percent say synthetic biolo-

di-gy should be regulated by the

feder-al government and 43 percent sayvoluntary guidelines should be devel-oped by government and industry 27With the capabilities for synthesiz-ing and sequencing genetic materialspreading so rapidly, biosafety andbiosecurity concerns will only getmore worrisome But, “given the paral-ysis and deadlock in Congress, it’s nec-essary for lots of things to happenwithout changes in statute,” MIT’s Oyesays “You have to develop new regu-lations within existing statutory frame-works because of our paralysis.”

Mendel’s Peas

The age of modern biology began

in the 19th century, with thepainstaking experiments of the Ger-man monk Gregor Mendel “Mendel

is pivotal to genetics in the way that

Charles Darwin is pivotal to biology

as a whole,” wrote Colin Tudge in The

Impact of the Gene — From Mendel’s Peas to Designer Babies. 28

Beginning in 1854, Mendel spenteight years growing 34 varieties ofpeas, selecting them for particularcharacteristics such as the color ofseed coat and the position of flowers

He hybridized 10,000 plants anddemonstrated the proof of dominantand recessive “characters” that werepassed on from parent to offspring 29

“He hypothesized that characters areconveyed from generation to generation

by individual Mendelian factors (which

we now call genes),” wrote Tudge 30

To Mendel’s disappointment, his search was received with a yawn bycontemporary biologists Not until 1900

re-— 16 years after his death re-— was hispaper rediscovered and its full signif-icance understood

In 1909 Danish botanist WilhelmJohannsen suggested the term “gene”replace what had been called Mendelianfactors 31Although scientists were bythen observing thread-like chromo-somes under a microscope, the make-

up of the chromosome’s genes mained a mystery In 1943 Austrianphysicist Erwin Schrödinger said in afamous series of lectures that became

re-an influential book What Is Life? that

“the gene was a message written incode.” 32 The insight that genes carryinformation became a cornerstone ofmolecular biology

In 1944 scientists discovered thatgenes were not proteins, as many hadargued, but nucleic acids ResearchersOswald Avery, Colin MacLeod andMaclyn McCarty of the Rockefeller In-stitute for Medical Research demon-strated that hereditary traits could bepassed from one bacterial cell to an-other by the DNA (deoxyribonucleicacid) molecule “With that finding, sci-entists knew for the first time the com-position of the basic entities that con-trolled the heredity and development of

Continued on p 372

Danish botanist Wilhelm Johannsen

coins the word “gene.”

1911

American geneticist Alfred Sturtevant

maps genes of fruit fly

1912

French biologist Stéphane Leduc

uses term “synthetic biology“ to

describe his cell experiments

1943

Erwin Schrödinger, an Austrian

particle physicist, hypothesizes that

genes carry information

1944

Researchers find that genes are

made of nucleic acids

1953

Biochemists James D Watson and

Francis Crick discover double helix

Paul Berg, a biochemistry researcher

at Stanford University, splices DNA

from one virus to another

1972

Geneticist Stanley Cohen at Stanford

and biochemist Herbert Boyer at the

University of California, San

Francis-co, transfer DNA between species

1975

Safety guidelines created for genetic

engineering at Asilomar conference

San Francisco-based Genentech

ge-netically manipulates E coli bacteria

a bacterium for digesting crude oil

in the event of oil spills

1985

Kary Mullis, a biochemist at CetusCorp in Emeryville, Calif., developspolymerase chain reaction for massreplication of DNA

•

2000s Synthetic biology takes off.

2000

Geneticist Francis Collins of theNational Institutes of Health andsynthetic biologist and entrepre-neur J Craig Venter announce se-quencing of human genome

2001

GreenFuel Technologies Corp isfounded in Cambridge, Mass., tomake synthetic biofuel from algae;

firm files for bankruptcy in 2009

2003

Bioengineers at the MassachusettsInstitute of Technology (MIT) de-

velop The Registry of Standard

Bi-ological Parts, a list of syntheticDNA parts available off the shelf

2004

MIT students initiate the InternationalGenetically Engineered Machinecompetition

2005

Synthetic biologist Jay Keasling’sbiotech firm, Amyris, in Emeryville,Calif., creates synthetic version ofantimalarial drug artemisinin

2006

For fun, five MIT undergrads use

synthetic biology to reprogram E.

coli to smell like bananas or green The National ScienceFoundation establishes the multi-university Synthetic Biology Engi-neering Research Center

winter-2008

Biologists Mackenzie Cowell andJason Bobe, based in Boston, foundDIYBio, a network of amateur syn-thetic biologists

2010

Venter creates genome of firstsynthetic self-replicating life form.Report by Presidential Commissionfor the Study of Bioethical Issuesconcludes that no special regula-tions are needed, as yet, governingsynthetic biology

2012

A global group of 111 mental, conservation, consumerand religious organizations endorsethe “Principles for the Oversight ofSynthetic Biology,” which calls for

environ-a morenviron-atorium on the development

of commercial applications of thetic biology until regulationsspecifically governing the technologyare developed

syn-2014

Researchers synthesize the firstchromosome of a baker’s yeast .Evolva, a Swiss-based biotech firm,begins commercial production ofsynthetic vanillin

life on earth,” wrote journalist Ed Regis

in What is Life? Investigating the Nature

of Life in the Age of Synthetic Biology. 33

Biochemists James D Watson and

Francis Crick won fame in 1953 by

identifying the double-helix structure

and reproductive function of DNA

Genetic Engineering

T he birth of genetic engineering

and genomics in the 1970s was

“potentially as revolutionary as the birth

of agriculture in the Neolithic Era,” cording to synthetic biology pioneerVenter 34 For the first time, scientistscould cut genes from one species andsplice them into another, a processcalled recombinant DNA

ac-With genomics — the study of theentire genetic structure or genome oforganisms rather than individual genes

— scientists could identify which tions of an organism’s DNA corre-spond to particular genes, say, for dis-ease resistance or other desirable traits

sec-Before advances in genomics, “only in

a few, rare cases did [scientists] know

which genes — which particular

stretch-es of DNA — they should be ferring into the organisms they want-

trans-ed to transform,” wrote Tudge 35Biochemistry researchers Paul Berg ofStanford and Herbert Boyer of the Uni-versity of California, San Francisco, andgeneticist Stanley Cohen, also of Stan-ford, first used recombinant DNA, forwhich Berg won the Nobel Prize in 1980.The first commercial application ofgenetic engineering involved transfer-

ring the human insulin gene into E.

coli in 1978, allowing insulin to be

mass produced (Most E coli strains

I n a former jar-lid factory known as King Cork & Seal on

Baltimore’s gritty east side is a small community lab known

as BUGSS (Baltimore Underground Science Space) It’s part

of a growing do it yourself biology (DIYbio) network of 40

groups and community labs around the world.

The labs have garnered scary headlines suggesting that rogue

amateur scientists creating mayhem by synthesizing and

re-leasing new organisms As a Wall Street Journal headline

an-nounced in 2009: “In Attics and Closets, ‘Biohackers’ Discover

Their Inner Frankenstein.” 1

Indeed, the diffusion of synthetic biology poses some

legit-imate security concerns People with nefarious intent could

ac-quire genetic materials and lab equipment over the Internet and

synthesize organisms for any number of bad purposes, such as

poisoning water supplies But experts say implementing such a

plot is complicated and that potentially dangerous genetic

ma-terials are carefully screened and tracked by suppliers.

A 2013 study of DIYbio by the Woodrow Wilson

Interna-tional Center for Scholars, a Washington think tank, found that

the public has “a miscomprehension about the community’s

ability to wield DNA and manipulate life.” 2 DIYbio

practition-ers do not appear to be lonpractition-ers working secretly in their homes,

the study found “The capacity to inflict harm that most

peo-ple are concerned about is way beyond anyone’s capabilities

to do alone in a basement at this point in time,” says study

co-author Todd Kuiken, a senior research associate with the

Wil-son Center “The DIY name is misleading It’s not do-it-yourself.

It requires others to do it with you.”

Still, the report noted, “As with any broad and

decentral-ized movement, there is no way to know what every member

is doing at any given time This makes it difficult to assess

safety and security risks and to rule them out with certainty.”

The study included results of a 2013 survey of 359

partic-ipants in the loose-knit DIYbio community It found that only

24 worked exclusively at home, nearly half worked at a munity lab and 35 percent at hackerspaces (gathering spots for computer buffs).

com-At BUGSS, anyone can experiment and learn hands-on netic engineering and synthetic biology skills, under the tute- lage of Tom Burkett, a biology professor at the Community College of Baltimore County DIY labs provide easy access to specialized equipment and expertise without enrolling in col- lege courses Membership in BUGSS is $850 for a year, with steep discounts for students and teachers.

ge-The genetic materials used in the lab are carefully tracked and are all classified as Level 1, or no more dangerous than

“things that can be worked with on your dining room table,” Burkett says.

Burkett and Steve Stowell, who cofounded BUGSS in 2012, equipped the lab with second-hand items from eBay and from companies going out of business.

Burkett first got the idea for BUGSS after participating in the International Genetically Engineered Machine (iGEM) science competition in 2010, where he met Stowell, who works in “smart grid” technologies for the electric power industry They both were part of Team Baltimore, consisting of people from local academic institutions and others interested in synthetic biology.

“iGEM opened my eyes to the DIYbio community,” Burkett says This year for the first time, the iGEM competition is open to community labs, and BUGSS hopes to field a team.

On a recent Saturday, Burkett guided 10 workshop participants

on how to clone a gene The youngest, 13-year-old Marissa Sumathipala, who wore red shoes, a purple-checked shirt and braces on her teeth, says she wants to pursue a career in the life sciences She already is making a mark in science compe- titions with such projects as “The epigenetic effects of a micro-

BioHobbyists Embrace DIYbio

“These hackerspaces are going to be the life blood of innovation in the future.”

Continued from p 370