The Industrialization of Biology and Its Impact on National … · The industrialization of biology, ... Biodangers meeting at the Center for Biosecurity and this project report

Center for Biosecurity of UPMC

June 8, 2012

The Industrialization of Biology and Its Impact on National Security

Center for Biosecurity Project Team

Gigi Kwik Gronvall, Ph.D

Senior Associate

Ryan Morhard, JD

Legal Analyst

Kunal Rambhia, MS

Senior Analyst

Anita Cicero, JD

Chief Operating Officer and Deputy Director

Tom Inglesby, MD

Chief Executive Office and Director


CONTENTS PAGE

Summary of Findings: The Industrialization of Biology and Its Impact on National Security 1

Purpose, Methods, and Analysis 2

Finding 1: Biology Is on the Cusp of Becoming a Pervasive Industrial Technology 4

Biological Approaches Gaining Industrial Significance

Increased Computing Power Available

Data Management Challenges

Engineering-Grade Knowledge Needed

Finding 2: Industrialization and Peer Competition Are Altering the “Biotech Ecosystem” 7

Biotechnology Has Low Barriers to Entrance

Movement Toward Large Interdisciplinary Teams

Peer Competition Increasing

Shifts in Biotech Ecosystem Connected to Drug Shortages

Critical to Remain Competitive

Hidden Costs of Outsourcing

Intellectual Property Barriers

Finding 3: Biological Dangers Are Persistent 15

Options for Harm

Threats from Skilled Individuals

Agriculture Is Vulnerable

Consequential Accidents

Finding 4: Bioscience Has Untapped Potential to Empower National Security 18

Reduced Time to Protection

More Powerful and Accessible Diagnostics

Treating the Patient, Regardless of Pathogen

Drug Targets Currently Underutilized

Drug Shortages Less Likely

Medical Practice Slow to Change

Regulatory Approach Needs to Be Right, or It Could Block Progress

Regulation Being Outpaced by Technological Change

Public Engagement—A Must for Technologies to Flourish

Summary 22

References 23

Appendices

A: List of November 9, 2011, Biodangers Meeting Participants 29 B: Experts Interviewed by the Center for Biosecurity 31

SUMMARY OF FINDINGS

Center for Biosecurity of UPMC | January 2012 Page 1 Industrialization of Biology and National Security

The Industrialization of Biology and Its Impact on National Security:

Summary of FindingsThe Center for Biosecurity of UPMC (the Center) conducted a horizon-scanning project to provide senior

leaders from the United States and the United Kingdom with awareness and understanding of the medium-

term future of biotechnology and biological dangers, resulting strategic concerns for homeland and national

security, and possible approaches that both countries may take to address biological dangers.

Biology is on the cusp of becoming a pervasive industrial technology.

Economically and strategically important industries are increasingly relying on biological manufacturing

processes for fuel, agriculture, medicines, and products that traditionally have been made using chemistry.

The industrialization of biology, akin to the introduction of steam engines or computers in ushering in a

new technological age, has major national security implications in terms of peer competition, sources for

precursor materials, availability of critical pharmaceutical drugs, and the global accessibility of powerful

technologies. There are technical barriers, including software development and the difficulty in managing

large datasets, that could potentially limit the pace, but not the end result, of biotechnology industrialization.

As a consequence of biological industrialization, the “who, what, and where” of bioscience—what project participants termed the biotech ecosystem—is changing.

Concerns were expressed about the need for established centers of biotechnology, including the U.S. and

U.K., to adapt to the global competitive market for bioscience. Peer country competitors, including Brazil,

China, Russia, and India, have made substantial economic gains from biotechnology and are competing

with other bioscience regions for manufacturing resources, consumer markets, and skilled workers, with

implications for national security.

Industrialization will inevitably increase the potential for misuse of biology.

The advent of powerful new technologies expands both the possibilities for nefarious use by malicious actors

and the number of potential actors who are technically able to misuse bioscience. Collectively, the global

accessibility of powerful biotechnologies, information, and training; the “de-skilling” of molecular techniques;

and the beneficent uses of biotechnology indicate that most biological dangers will be impervious to central

control or regulation on a global scale. It will also be difficult to maintain appropriate individual vaccines and

therapies for an increasing range of biological dangers, whether they stem from misuse, accident, or nature.

Biotechnologies have untapped potential to empower national security.

In this new industrial biotechnology future, national-level strategies are required to stay competitive

and to maintain domestic biotechnology capabilities for national security. Advances in the biosciences

and biotechnologies should enable the development of diagnostics, the rapid development of medical

countermeasures, and the means to evaluate the effectiveness of those countermeasures. It should also

provide positive contributions to diagnostics to aid in the rapid detection of natural or deliberate disease and

to help guide response. Shepherding these technologies requires good management and funding of science

and technology and the right regulatory approach.

PURPOSE AND METHODS


Purpose

The Center for Biosecurity of UPMC (the Center) conducted a horizon-scanning project to provide senior

leaders from the United States and the United Kingdom with an expert assessment of key bioscience

developments in a 5- to 10-year timeframe, the resulting concerns for homeland and national security, and

suggestions for what the U.S. and U.K. may do to address them. The Center also examined the drivers of

likely advances, barriers to advancement, and ways in which dangers might be mitigated.

Methods and Analysis

Interviews: The Center interviewed 46 leaders (listed in Appendix B) from the biosciences and related

fields from academia, government, and the private sector, including venture capitalists. Our goal was to

ascertain the experts’ judgments about evolving capabilities in the life sciences and the accessibility of those

capabilities.

Our discussions focused on trends in capabilities as opposed to details about specific technologies, because

technologies are interdependent, and the experts with whom we spoke often work at the interface of

categorically distinct technologies, such as synthetic biology and bioinformatics. Our analysis also captured

insights into newly emerging technologies that are not widely visible.

We asked in interviews how bioscience capabilities are likely to evolve over the next 5 to 10 years and

about the drivers that could affect the trajectory of that evolution. Such drivers include, but are not limited

to, commercial market and medical research interests, regulatory pressure, investments in education,

intersections with other technologies, government support of national industries, and the effects of the

global economic downturn. We focused on how accessible new capabilities would be to nation states, small

groups, or individuals—for entrepreneurship, or recreation (ie, do-it-yourself biology, aka DIY Bio, or citizen

science), or for malevolent purposes. We asked about potential dangers and homeland security concerns that

could emanate from these capabilities, and how such dangers or concerns could be mitigated by the U.S.,

the U.K., or through a collaborative partnership.

U.K. Synthetic Biology Workshop: The Center for Biosecurity participated in the September 29, 2011,

Synthetic Biology Workshop organized by Imperial College and the U.K. Home Office, which was a “science-

led forward look at the potential negative impacts of synthetic biology.” The participants were a diverse

group of U.K. scientists. The deliberations of this meeting informed the subsequent November 9, 2011,

Biodangers meeting at the Center for Biosecurity and this project report.


PURPOSE AND METHODS


Review of published literature and previous reports: The Center analyzed and included relevant data

from available published horizon-scanning assessments of technology, which included the following: (1)

U.S. National Research Council report Globalization, Biosecurity, and the Future of the Life Sciences (2006),

which described such scientific trends as acquiring novel molecular diversity, directed design, and intentional

manipulation of biological systems; (2) commercial, medical, and industrial applications; and (3) the 2011

report Life Sciences and Related Fields: Trends Relevant to the Biological Weapons Convention, which

described the weaponization potential of bioscience capabilities.1,2

November 9, 2011, Biodangers meeting: The Center completed a preliminary analysis report that

synthesized the results of both the literature review and our expert interviews. Those findings were used

to facilitate the discussion in the November 9, 2011, Biodangers meeting at the Center for Biosecurity in

Baltimore, MD, USA. That meeting was attended by participants from U.S. and U.K. academic institutions,

private industry, the U.S. government (USG), and the U.K. Home Office, which funded the travel of the U.K.

participants. Appendix A lists all meeting participants. Senior staff and leadership from the U.K. Home Office,

the Defense Threat Reduction Agency (DTRA), the Department of Homeland Security (DHS), the Center, and

The Tauri Group participated.

The meeting served as a forum for in-depth discussion of the direction of biotechnologies, the challenges

and priorities for the USG and U.K. Home Office in promoting positive uses of biotechnologies, and

potential biosecurity needs that the U.S. and U.K. could pursue in the medium-term, either collaboratively

or separately. Diverse views were encouraged in this discussion, and while there was no requirement for

consensus, there was substantial agreement around many findings.

Final report: This final report presents the Center’s scientific and policy assessment of this issue, informed by

our expert interviews, literature review, and U.S. and U.K. meeting discussions. The views expressed do not

necessarily reflect specific views of the meeting participants or sponsors.

Offset quotes: Throughout this report, the offset quotes that appear in the text were from individual

meeting participants. They are anonymous as per agreement with the project participants.

Funding: This project was funded by the DTRA Chemical and Biological Technologies Directorate DTRA/RD-

CB) through The Tauri Group.


Finding 1. Biology is on the cusp of becoming a pervasive

industrial technology. Biology is on the cusp of becoming fully industrialized. Economically and strategically important industries

increasingly rely on biological manufacturing processes for fuel, agriculture, medicines, and products that

have traditionally been made using chemistry.

This section of the report describes the growth of biotechnology industries, as well as technical barriers that

could potentially limit the pace, but not likely the end result, of biotechnology industrialization.

In the 1800s, we saw huge changes from the invention of the steam engine and the ability to create and distribute energy. In the 1900s, we saw revolutionary changes from electronics and the ability to manipulate information. The major change in this century will be biological control over manufacturing. From an engineering perspective, biology is about making things—it’s a manufacturing technology. It puts atoms precisely where they should be.

Biological Approaches Gaining Industrial Significance

Industry is increasingly reliant on biological approaches. Biological processes have long been

used for industrial purposes. Agriculture, biologics,

pharmaceuticals, and fermented products (such

as beer and wine) all require biological processing

steps. Yet, the industrial use of biology is extending

into areas that have traditionally required either

chemical engineering or resource-intensive

harvesting from nature. For example, artemisia

plants have been used for medicinal purposes since

at least 200 BC but on a small scale; now, a synthetic

version of artemisinin can be mass produced, so that

the World Health Organization (WHO) may use it in

sub-Saharan Africa to treat malaria patients.3

Medicines are only part of the industrialization of

biology. Analysts have forecasted that by 2015,

one-fifth of the U.S. $1.8 trillion chemical industry

could be dependent on synthetic biology.4 Over the

course of the next decade, the synthetic biology

market has the potential to grow to US$3.5 billion

based on its industrial relevance.4 This is due to

investment in biofuels and chemical processes,

such as bioisoprene to make tires traditionally

produced from natural rubber, or valencene,

an orange flavoring used in perfumes and food

products, or any number of detergents, adhesives,

and building materials. Mining is another example:

Biological organisms are currently used in gold

mining, because it is cost-effective, safer, and less

environmentally damaging compared to traditional

extracting methods using cyanide.5 In the future,

synthetic organisms may be designed for extracting

rare earth metals, essential for lasers, magnets, and

electronics. Rare earth metals are not rare in nature,

but the expense of extraction and toxic byproducts,

coupled with aggressive market strategies, has

resulted in the U.S. purchasing most rare earth

materials from China, even though there are

plentiful domestic natural resources.6

In addition to mining, there is a potentially vast

body of information relevant to other industries

that may be gained from the harvesting and study

of natural organisms. Extremophiles, for instance,

are organisms that thrive in habitats unsuitable for

most life forms. They can be found in environments

FINDING 1


of high heat, dryness, or salinity, or in habitats of

low pH or high pH, or in places with high levels of

radiation—all habitats that require adaptations that

could inform industrial manufacturing processes

and environmental remediation. Further, it may not

always be necessary to harvest from the natural

environment: There is a great amount of genetic

flexibility within organisms that could be tapped in a

laboratory for industrial applications.

Increased Computing Power Available

Increased computing power is driving new bioscience approaches and applications. In the

coming years, biological systems are expected to

become more predictable to scientists, and thus

more amenable to engineering. Increased computing

power available to scientists and engineers, along

with inexpensive DNA sequencing and synthesis

technologies, will allow many permutations of

biological systems to be synthesized and tested.

Computational biology is consequently expanding

as a field, along with its requirements for applied

mathematics, software engineering, data storage,

and algorithm development.

According to the scientists interviewed, the effects of

increased data-crunching power are only beginning

to be realized; they expect that enhanced computing

power and accessibility will lead to improvements

in drug development and diagnostic tests, as

well as improved modeling of biological systems,

interpretation of genomic datasets, and manipulation

of smart materials.

The bio community doesn’t yet understand how much computer power will be available and what it means.

In addition to computing with petaflops in high-

resource settings, computing power is also more

accessible to all scientists. A 2011-era smart phone

has more processing power than all the computers in

the Apollo 11 Lunar Lander, which put 2 people on

the moon.7 Computing power may help to form new

industries around next-generation investigative tools,

which will include advanced sequencing capabilities,

improved management of biomedical databases,

and electronic medical and high-volume automated

image-screening technologies.8

Just as computing power stands to transform our

understanding of biological systems, biological

systems themselves may provide computational

power. Nature has evolved to use genetic material

to both store and act on information; this process is

now being put to industrial use.

Nanotechnology is about building tiny machines, and biology worked that out a long time ago.

There are already in existence computers that use

DNA instead of silicon to perform calculations.

These biological computers, sometimes called

matter computers, have already performed simple

calculations, such as square roots, in a test tube,9

and they may eventually contribute to the industrial

potential of self-healing plastics or point-of-care

diagnostics that do not require refrigeration. As

recently demonstrated in vitro, an RNA-based

circuit was able to distinguish cancer cells from

noncancerous cells and trigger the cancer cells to

self-destruct.10

Data Management Challenges

Managing and interpreting an explosion of data will be a challenge. Technical challenges ahead

include that of storing massive amounts of biological

information. Right now, more than 2% of the

electricity in the U.S. is consumed by datacenters.11 It

is expected that to support the technology of today,

the equivalent of about 45 new coal plants will be

needed to power U.S. datacenters by 2015 if there

are not dramatic improvements in efficiency.

In addition to the costs of storage, there are

technical challenges in manipulating such large

amounts of information. One of these challenges is

software-based. While there have been great strides

in advancing the multiprocessing capabilities of

computers, software development to take advantage

of multicore processing has lagged behind.

FINDING 1


The cloud includes almost limitless data storage and processing, but the software infrastructure isn’t there to harness parallel processing capability.

Further, information for bioinformatics analysis has

to be in a computable form, but often it is not.

Scientists have to be able to generate data in a form

that is accessible for others to compute if potential

benefits for medical diagnostics, health records,

genetic analysis, and environmental monitoring are

to be realized.

Engineering-Grade Knowledge Needed

Engineering-grade knowledge of biological systems

is needed. To be able to use DNA and other

biological molecules for engineering and industrial

purposes, their functions must be understood at the

smallest scale, which is a new requirement.

There are also many areas of biological science that

require resource-intensive efforts, such as gene

characterization, which won’t be substantially sped

up through reductions in the costs associated with

sequencing or by enhanced computing power. True

understanding of biological systems may be slowed

by the time it takes to understand these biological

systems at the detailed level needed for engineering.

What can I do with 10, 20, 50 genes? It comes down to knowing what each part does, and too few scientists are doing the hard work to figure that out.

One scientist noted that when inexpensive DNA

sequencing became available to researchers in 1996,

a large number of scientists adopted sequencing

as “the thing to do.” While sequencing studies are

valuable, too few scientists are engaging in the time-

intensive work of learning how individual proteins

function and how complexes of proteins interact.


Finding 2: Industrialization and peer competition are altering the

“biotech ecosystem.”The “who, what, and where” of bioscience industries—what project participants termed the biotech

ecosystem—is changing. Several project participants were concerned that not enough is being done in some

established centers of biotechnology to adapt to the changing biotech ecosystem and remain competitive.12

In contrast to other industries that require substantial natural resources, such as arable land, oil, or natural

gas, biotechnology has few barriers to entrance, and emerging markets can become competitive quickly.

This section of the report describes how the biotech ecosystem is changing, and how peer country

competitors have made substantial economic gains from biotechnology in a short period of time and are

competing with established bioscience regions for manufacturing resources, consumer markets, and skilled

workers—actions that all have implications for national security.

The center of gravity is going to change dramatically where biology is practiced, and that will catch people by surprise. We’re going to see a tremendous shift to the developing countries, to the growing economies, and less and less attractiveness of biology in the industrialized world. It’s going to surprise people how quickly that future is going to come.

Biotechnology Has Low Barriers to Entrance

Entry barriers to bioscience and biotechnologies are low. While bioscience research practice

has recently trended toward use of large,

multidisciplinary teams, the field is still open to

individuals or small groups. Due to increasing

accessibility of biological techniques (referred

to as “de-skilling”), scientific experimentation is

increasingly open to and practiced by amateurs.

Citizen science, or DIY Bio, has gained popularity

in recent years and has led to the creation of

community laboratories in Brooklyn, San Francisco,13

and Manchester, England.14

Some analysts have predicted that these laboratories

will result in innovative new biotechnologies, but

most scientists interviewed for this analysis had more

modest expectations.15 They observed that more

DIY Bio enthusiasts are working on such projects as

DNA barcoding, a taxonomic method to determine

species that is useful for detecting intentionally

mislabeled fish,16 or on mining personal genetic data.

Another example of amateur involvement in

biotechnology is iGEM, the International Genetically

Engineered Machine Competition. This is a

competition in which undergraduates from around

the world build simple synthetic biological systems

from standard, interchangeable parts, called

BioBricks, and operate them in living cells. iGEM

grew from 5 teams in 2004 to 165 teams in 2011,

with 8 to 12 students per team. A Slovenian team

won in 2010 for designing a DNA-guided assembly

line. The 2011 winner was a team from the University

of Washington for its project called Make It or Break

It: Diesel Production and Gluten Destruction, the

Synthetic Biology Way.17 Though iGEM projects are

carried out by students, many of them entirely new to

bioscience, the projects have been sophisticated, and

they demonstrate the accessibility of biotechnology

techniques to interested, dedicated groups.

The ability of small groups to accomplish meaningful

biological projects has implications for the

FINDING 2


geographic location of bioindustries.

No matter where I am in the world, I have access to almost the same tools that you have inside the Venter Institute. They might not have the concentration of minds who do lots of different things who are brought together under a common vision. But there are a lot of really smart people out there who will do amazing things or do horrible things.

The 2010 iGEM win of the team from Slovenia,

which is not among the top 10 countries in science

and engineering, demonstrates that a few people

performing at a high level can outdo groups with

more resources.18

Movement Toward Large Interdisciplinary Teams

High-resource laboratories are moving toward large, interdisciplinary teams that span expertise in biological systems and applied mathematics. Work

in the biological sciences is increasingly international

and interdisciplinary. Major advancements in

biotechnology are increasingly being accomplished

by teams of biologists, engineers, chemists,

statisticians, computer scientists, biophysicists,

mathematicians, material scientists, and researchers

from other disciplines, working together in large

teams. One example of this shift was the Venter

synthetic cell project, which took 20 people 10 years

to complete, at a cost of US$40 million.19 Another

example of big biology is the Human Microbiome

Project. Launched in 2008 by the U.S. National

Institutes of Health, it is a 5-year, US$157 million

effort to understand the complexity and diversity of

microbes that live in or on the human body.20,21

Multidisciplinary biological studies that incorporate

mathematicians and engineers may now be

considered the substrate for biotechnology

industrialization, but this is a radically different

organizational approach than has been used in

the past, which focused on supporting individual

scientific investigators.

Universities and government agencies, at

least in the U.S., have real difficulties in

nurturing and managing multidisciplinary

teams.

Funding sources may not appreciate the value

or might not be able to properly evaluate

FIGURE 1: Number of Biotech Articles Published by Region. Peng W. Trends in biotech literature 2009-2010. Nature Biotechnol. 2011;29:781. Adapted with permission.

FINDING 2


interdisciplinary work. It is also a challenge to

educate professionals from the biological sciences

and from engineering so they are able to participate

and engage in multidisciplinary work and can

understand the technical terms, perspectives, and

constructs of other fields. New models of operating,

educating, funding, and collaborating will have to be

developed to maintain competitiveness.22

Peer Competition Increasing

Peer competition is changing the biotech ecosystem. Project participants agreed that peer

competitor countries are making substantial strategic

investments and taking risks to promote innovation

in the biosciences, and they are gaining from these

strategies.

China’s government is spurring investments in

biotechnology, and the sector is seen as a key source

of economic development for the future. During its

twelfth 5-year plan period, the Chinese government

will spend 20 billion yuan (US$3.15 billion) on

innovation in medicine, cultivation of genetically

modified organisms, and prevention and control of

infectious diseases, according to the China National

Center for Biotechnology Development. The goal

is to have biotechnology account for 15% of the

nation’s GDP by 2020. Currently, it accounts for 3%

of China’s GDP.23

China’s investments to date were not appraised

uniformly by those we interviewed: One government

expert classified the Chinese biotechnology

enterprise as “lavish and fast-moving” and

emphasized that the U.S. is lagging behind. Other

experts interviewed were more sanguine, predicting

that the U.S. will maintain an edge due to its patent

and venture capital systems.

One tangible and successful example of China’s

commitment to a biotechnology future is the Beijing

Genomics Institute (BGI), which boasts 128 Illumina

HiSeq 2000 sequences, or 3 times the number

that most sequencing centers have. They have

more than 4,000 employees, including more than

1,000 bioinformaticians, and they have tremendous

government support, as evidenced by a 2009

government loan equal to US$1.5 billion.

BGI was a key player in the analysis of the 2011

E. coli O104:H4 outbreak, and its scientists have

analyzed more than 50,000 samples, including tens

of thousands of whole human genomes and exomes.

FIGURE 2: U.S. Drug Sales by Volume. Beyond Borders Global Biotechnology Report 2011. Ernst and Young. http://www.ey.com/GL/en/Industries/Life-Sciences/Beyond-borders--global-biotechnology-report-2011. Accessed January 5, 2012. Adapted with permission.

FINDING 2


They are currently able to sequence the equivalent

of 2,000 full human genomes in a single day.23

While China’s gains in biotechnology are impressive,

venture capitalists and biotechnology industrialists

emphasized that China is not the only competitor.

China is the 800 pound gorilla, but even if we focus on the 800 pound gorilla, we can’t lose focus on the 600 pound gorillas, which include Russia, Brazil, and India.

Russia is planning to have a 5% share in the global

biotechnology market by 2020.24 The experts we

interviewed found those predictions to be credible,

based on Russia’s past technology investments.

A venture capital industry expert contrasted the

deliberate, focused strategies of other countries

with those of the U.S., noting that his firm funded a

biofuels company “that could one day produce oil at

$20 a barrel,” but was turned down for investment

by the U.S. Department of Energy. They have since

moved operations into Russia and the Middle East.

Brazil, Russia, India, and China, in addition to

being centers of innovation, have growing markets

for biotechnology and pharmaceutical products,

which will draw increased attention from private

companies. Brazil, Russia, and India are expected

to add US$5 billion to US$15 billion to the

pharmaceuticals market through 2013, and all 3

countries have had double-digit pharmaceutical

growth over the past few years.25,26

Shifts in Biotech Ecosystem Connected to Drug Shortages

Pharmaceutical drug shortages are a growing problem. As a consequence of the shifting biotech

ecosystem, most pharmaceutical drugs are imported.

and thus may not be available in an emergency. U.S.

and U.K. dependence on foreign manufacturing

capability has already been a factor in drug

shortages, especially for cancer therapies. In an

October 31, 2011, executive order, President Barack

Obama stated that “[s]hortages of pharmaceutical

drugs pose a serious and growing threat to public

health,” and he gave the U.S. Food and Drug

Administration (FDA) broadened powers to require

additional reporting to predict shortages and

expedited regulatory reviews of substitutes.27

Critical ingredients for most antibiotics are now

FIGURE 3: 1Venture Capital Investment in Life Sciences. VC investment in China life science climbs 300%, tops $1 billion. ChinaBio Today. February 4,2011. http://www.chinabiotoday.com/articles/20110204_1. Accessed January 5, 2012. Adapted with permission.

2National Venture Capital Association. Stats and Research. http://www.nvca.org. Accessed January 5, 2012. Adapted with permission.

FINDING 2


made almost exclusively in China and India, as is

prednisone (steroid), metformin (for diabetes 2), and

amlodipine (antihypertensive). Indian companies

currently hold 22% of the world generic drug market.

If there is a serious dislocation of international supply chains, conventional pharmaceuticals would not be available. We’d see panic in society. Major hospitals receive 2 to 3 deliveries a day to minimize shelf inventory.

Meeting participants suggested a potential synthetic

biology solution to this problem: First, identify those

critical industrial chemicals that if in short supply

would create shortages of critical drugs; then, apply

biological processes and techniques to synthesize

those chemicals; finally, stockpile the organisms

that produce those critical chemicals rather than the

chemicals themselves.

An attractive aspect of funding such an approach is

that the regulatory requirements that have to be met

to establish a particular level of purity for an organic

product created through a synthetic biology process

are not as stringent as those required when replacing

entire drugs and drug pathways.

Critical to Remain Competitive

The U.S. and the U.K. must prepare for a changing ecosystem while remaining competitive. Among

those interviewed, there was a great deal of concern

that the U.S. and U.K. are not doing enough to

remain competitive in a biological future, and that

future industries would be formed by and cater to

other markets. This issue is also highlighted in the

recent U.K. government life sciences strategy.28

Project participants were concerned that the U.S.

and the U.K. did not have the workforce required for

a biological future.

Nearly all applicants to my company arrive from outside the country—mostly from China and Russia. Where is all the training going on? It doesn’t seem to be here in the U.S.

Many scientists interviewed thought that U.S. and

U.K. training is not producing enough people geared

toward the engineering, math, and biotechnology

professions. There were also concerns that

continuing education for professional scientists is not

effective, and there is a need for training biologists

to take advantage of the large datasets that are

available to them.

FIGURE 4: Many Chinese Scientists Are Looking to Split Time Between U.S. and China. George Baeder and Michael Zielenziger, “The Life Sciences Leader of 2020.” Monitor Group, 2010, http://www.monitor.com/tabid/67/ctl/ArticleDetail/mid/691/CID/20101611134152307/CTID/1/L/en-US/Default.aspx. Accessed January 5, 2012. Adapted with permission.

FINDING 2


In the Biodangers meeting, some scientists

complained that U.S. immigration policy makes

it overly difficult for U.S. companies to retain

highly skilled foreign talent. Once postdocs are

trained, they may have to return to their home

countries regardless of their wishes or their levels

of training. Current U.S. law allows for the award

of approximately 120,000 employment-based visas

per fiscal year, of which no more than 7% can be

awarded to any single country, regardless of that

country’s population. Thus, highly skilled workers

from such populous countries as India or China could

end up waiting indefinitely for a U.S. visa. In fact,

the waiting time for permanent resident visas for

educated workers from India is now 70 years.29

Other data, however, indicate that the decline of the

U.S. economy and the rise of emerging economies,

rather than U.S. immigration policy, are to blame

for the loss of foreign talent. A survey of Chinese

and Indian immigrants who studied or worked in the

U.S. for at least 1 year before returning home found

that the majority—86.8% of Chinese and 79% of

Indians—were motivated to leave the U.S. by career

opportunities in their home countries.30

Regardless of cause, failure to retain highly educated

and skilled talent is a boon to other economies. For

the U.S., in 2006, foreign nationals were named in

25.6% of all patent applications filed in the U.S., in

65% of Merck’s patent applications, and in 60% of

Cisco’s.31

Hidden Costs of Outsourcing

Is biotechnology outsourcing damaging the biotech ecosystem? While BGI has been a huge

success for China, its success in sequencing has

raised concerns among the scientists we interviewed

about the consequences of outsourced sequencing.

Some say we should do cheap sequencing in

China and do “added value” in the U.K. But

if we give up basic skills, we’re giving up the

foundation of our work. It is not a concern

because it is China, but because they have a

monopoly.

Many agreed that wholesale outsourcing could be

detrimental to the entire biotechnology ecosystem

and could lead to such unintended consequences

as the loss of competent workers who gravitate to

places where the work is being performed. One

meeting attendee described how his company

FIGURE 5: Top-10 Pharmaceutical Markets. George Baeder and Michael Zielenziger, “The Life Sciences Leader of 2020.” Monitor Group, 2010. http://www.monitor.com/tabid/67/ctl/ArticleDetail/mid/691/CID/20101611134152307/CTID/1/L/en-US/Default.aspx. Accessed January 5, 2012. Adapted with permission.

FINDING 2


outsourced their regulatory studies to save money,

but found that by doing so, the company lost

substantial training opportunities for their staff. If

not planned carefully, outsourcing may lead to the

loss of key precursor materials and the knowledge

and capability to develop products.32 For capabilities

and products important to national security, this is a

concern.

Intellectual Property Barriers

Innovation and industrialization are affected by intellectual property issues. Both the scientists

we interviewed and the meeting participants

raised concerns about intellectual property and

patents. They voiced a worry that current patent

structuring does not encourage the collaboration

and cross-licensing that has proven successful in the

electronics industry. There have also been delays

in getting patents: In 2010, the U.S. Patent and

Trademark Office reported a backlog of more than

750,000 patent applications, an accumulation that

had doubled over the previous decade.33 Delays in

granting patent rights resulting from this backlog

could ultimately cost the U.S. economy billions of

dollars annually in foregone innovation.34

The Biotechnology Industry Organization (BIO),

the world’s largest biotechnology organization,

maintains that patents often are the “most important

and sometimes only asset of a biotech company.”35

Complicating the issue, however, is an ongoing

debate over the patentability of genes and DNA,

a capability said by biotechnology experts to

be “essential for encouraging innovation,” but

condemned by others as not only costly, but

unethical.36,37

Multiple project participants expressed strong

concerns that the U.S. patent system is not

adequately fostering U.S. biotechnology innovation

and that China is now poised to surpass the U.S. and

lead the world in patent application filings.38,39

The U.S. will lead the way on biotechnology innovation; there is a strong venture capital system and a robust, entrepreneur-friendly patent system. They just need to make sure they don’t lose ground.

Recently enacted patent reform legislation in the U.S.

may mitigate these trends. The Leahy-Smith America

Invents Act, which was signed into law in September

2011, provides perhaps the most significant changes

FIGURE 6: U.S. Patents Filed by BRIC Countries. United States Patent and Trademark Office. Extended Year Set—Patents by Country, State, and Year All Patent Types. December 2010. http://www.uspto.gov/web/offices/ac/ido/oeip/taf/cst_allh.htm. Accessed January 5, 2012.

FINDING 2


to the U.S. patent system since the 19th century.40

The legislation introduces a first-inventor-to-file

priority rule, prevents patents from claiming or

encompassing human organisms, and reforms

administrative patent challenge proceedings at the

U.S. Patent and Trademark Office. BIO applauded

the passage of the patent reform legislation, as did

many leading manufacturers, scientists, researchers,

academic institutions, and businesses small and

large.41 Only time will tell whether these reforms

are sufficient to enable biotechnology innovators to

compete globally.

FIGURE 7: Shares of World Researchers and Per Million Inhabitants (2007). Kumar N, Asheulova N. Comparative analysis of scientific output of BRIC countries. Annals of Library and Information Studies. September 2011;58:228. Adapted with permission.


Finding 3: Biological dangers are persistent.Biological industrialization is not going to diminish the potential for misuse of biology. Rather, the reverse

is true. The advent of powerful new technologies expands both the possibilities that could be explored for

nefarious use by malicious actors and the number of potential actors who are technically able to misuse

bioscience.

The angles of the attack are almost infinite and very difficult to anticipate.

Collectively, the global accessibility of powerful biotechnologies, information, and training, along with the

“de-skilling” of molecular techniques and the almost entirely beneficent use of biotechnology, suggest that

most biological dangers will be impervious to central control or regulation on a global scale. It will also be

difficult to maintain appropriate individual vaccines and therapies for an increasing diversity of biological

dangers, whether they stem from misuse, accident, or nature.

This section of the report describes how project participants assessed the technical requirements of doing

harm with new biological techniques.

What we are dealing with is the globalization and commoditization of knowledge. Even if you start with the most sophisticated, cutting-edge research that requires major investments and state actors, this migrates eventually into the community. Almost anybody nowadays can pick up textbooks on methods or read current papers on methods and techniques that 10 years ago were the stuff of Nobel prizes. The knowledge is becoming commoditized.

Options For Harm

Well-resourced groups have many technical options for harm. Without the addition of any

new biotechnologies, well-resourced people with

scientific training could do a great deal of damage,

according to those we interviewed. In the scientific

literature spanning the past decade or more, there

are many examples of legitimate scientific work that

could be misused in order to make pathogens more

effective as biological weapons. Indeed, it is well

known that the published literature of the past 10 to

15 years includes descriptions of making antibiotic

resistant bacteria;42,43 of engineering viruses that

can escape vaccines, as occurred in the well-known

mousepox/IL-4 experiments of 2001;44 and for

manipulating the genetics of the causative agent

of anthrax disease, Bacillus anthracis, in a way that

allows the organism to escape its vaccine.45

Extinct pathogens, such as 1918 pandemic influenza

virus, have already been resurrected.46 It also is

thought that variola major, the causative agent of

smallpox, which has been eradicated from nature,

could similarly be synthetically created, though it

would be a complicated endeavor.47 Smallpox and

influenza, of course, have caused infections in living

memory. In contrast, the scientists working in the

emerging field of paleovirology have been able to

resurrect extinct retroviruses that are millions of

years old and then demonstrate their ability to infect

human cells in vitro.48 The consequences of human

infection with a previously extinct virus are not

known.

The experts interviewed for this project had more

specific concerns about how biotechnology could

FINDING 3


be misused by skilled scientists and engineers if

funding was plentiful and there was tolerance for

experimentation. They were especially concerned

about food crops, bioengineering novel systemic

disruptions, the expansion of the host range of

animal viruses, and the use of organisms to attack

physical infrastructure, including silicon or rubber.

Another concern raised was a cyber-attack with

biological consequences, as would occur if

biological data used for industrial, pharmaceutical,

or surveillance purposes was tampered with in

such a way as to derail decisions and compromise

production through application of incorrect data.

Threats from Skilled Individuals

The threats posed by individuals depend on their skill level. Though there are many technically

possible misuses of biology, most of the scientists we

interviewed thought it unlikely that either individuals

or small groups would adopt such approaches.

“Old bugs,” such as anthrax, tularemia, and foot-

and-mouth disease (FMD), were the biggest worries

among those interviewed. In general, they think

there are enough relatively simple paths to making a

biological weapon to render more technically difficult

approaches unattractive and, therefore, less likely to

be pursued.

The bad guys aren’t going to waste their time with sophisticated pie-in-the sky stuff.

The rise of DIY Bio has caused concerns in the media

and among policymakers about bioweapons.49,50 Yet,

most of the scientists we interviewed are not worried

about DIY Bio’s potential for harm.

People like to equate them to hackers. But you take a hacker and hook them up to the Internet, they have the power of the Internet. DIY people do not have the power of biology.

However, there was a great deal more concern about

an expert with the intent to harm—that is, a “bio”

Unabomber.

While one person might not be able to accomplish

the same biotechnological feats as an experienced

team in the same amount of time, new techniques

and falling prices for services provide skilled

individuals with shortcuts. This potential threat

should not be discounted.

Agriculture Is Vulnerable

Agriculture is vulnerable to engineered or natural threats. Agriculture is vulnerable to nonengineered

pathogens, engineered pathogens, and introduction

of alien species. In our interviews, a great deal of

concern was expressed about biological warfare

affecting crops or livestock.

There are many known agricultural threats. The

U.S. Department of Agriculture (USDA) oversees

more than 33 of the 80+ select agents and toxins,

including the now-eradicated rinderpest virus,

bovine spongiform encephalopathy (BSE, or mad

cow disease), and peste des petits ruminants virus.

In addition to those known threats, new strains and

variants occur regularly in nature. Without adequate

fielding of diagnostics, they are often not detected

until entire herds or fields are infected.

The archetypal concern for agricultural threats is

FMD. FMD is endemic in many parts of the world

and is a relatively hardy organism that can survive

transport.

Foot-and-mouth disease is the one I worry about in terms of bringing a country to its knees.

The economic damage of an FMD attack could

be considerable: The 2001 U.K. outbreak that

was caused by a natural, nonengineered FMD

virus resulted in US$10 billion in losses and the

slaughter of more than 4 million animals. The costs

of a similar outbreak in the U.S. could run as high

as US$24 billion plus the lives of approximately 13

million slaughtered animals. An outbreak could be

extremely difficult to stop: The USDA calculated that

an FMD outbreak could spread to 25 states in just 5

days.51

FINDING 3


In addition to engineered pathogens, alien species

could be introduced to a new environment, causing

tremendous food and economic loss.

A recent example of a natural occurrence illustrates

this phenomenon: Megacopta cribaria, or stink bugs,

were accidentally introduced into the U.S. about

15 years ago and are now present throughout the

U.S. and are killing off soybean plants.52-54 Naturally

spreading plant pathogens could also be introduced

expeditiously through a deliberate act, though

one current worry—wheat stem rust Ug99, now

spreading in Africa, Asia, and the Middle East—is

likely to arrive in Europe and the U.S. relatively soon

without assistance. A combination of chemicals can

currently kill the fungus, and there is intense work

going into making genetically resistant seeds, but

the clock is ticking.

The effects of agricultural disease, through natural

occurrence or intentional introduction, are not bound

by borders, as illustrated by the case of naturally

occurring South American Leaf Blight (Microcyclus),

which is the reason rubber is not produced in the

western hemisphere, where the rubber tree was

originally cultivated. This fungus is currently a threat

to Malaysia and Thailand, where rubber production is

a major part of their economies.55

Consequential Accidents

Biological accidents could be consequential. Powerful biotechnologies could also result in

powerful accidents. Perhaps the most consequential

known biological accident occurred in 1977. The

seasonal outbreak of influenza that year was caused

by an H1N1 strain that was identical to a 1950

influenza strain that had clearly escaped from the

laboratory. 56-58 Other consequential accidents

occurred with SARS virus in Taiwan, China, and

Singapore in 2003-04, but while the escaped virus

caused harm, it did not spread around the globe.59-63

Fortunately, biosafety training and awareness have

increased dramatically since 1977, and modern

biosafety laboratories have greatly enhanced

engineering for biological containment. However,

vigilance and training to prevent accidents are still

required, especially as biosafety standards are still

not uniform worldwide.

Some meeting attendees were concerned that

the risk of a laboratory accident increases with

interdisciplinary work, which also speaks to the need

for additional biosafety training. People entering the

field of biology from other disciplines may not have

had the training or experience to be safe and take

adequate biosafety precautions.

In summary, while biotechnology has the potential

to offer exciting new industries, therapies, and

products, if misused, the advances merely expand

the range of threats. Biological dangers will persist.


Finding 4: Biotechnology has untapped potential to empower

national security.Through peer competition and increasingly accessible and powerful technologies, biological industrialization

may have negative effects on national security. However, if advances in biotechnology are accompanied by

a national strategy that ensures competitiveness and maintains domestic capabilities, then national security

stands to benefit from the growing industrialization of bioscience.

In this section, we describe how advances in bioscience could improve national security by, for instance,

enabling the rapid development of diagnostics and medical countermeasures that will be more effective in

countering biothreats than what we have now. Also necessary to our ability to reap the benefits of bioscience

industrialization will be effective approaches to public engagement, increased and improved scientific

education, and regulatory approaches that encourage innovation.

If you had a dangerous technology and were afraid of what could happen as it gets widely known about and released, there are 2 approaches you could take. One would be to try to lock it up and make sure that nobody found out about it. And the other approach is to run like hell [to stay ahead]. And I think the approach here has to be that we run like hell. There’s no way that we’re going to keep the things that we’re talking about secret. We just have to be better at it than anybody else. And we’d just better get on with it.

Reduced Time To Protection

The time to develop drugs, vaccines, and therapies will be reduced. New bioscience

knowledge and greater computing power is

expected to reduce the time required for all stages

of medical countermeasure development, which

will concomitantly reduce the risk and financial

burden of producing vaccines and drugs. From the

beginning of the drug development process, drug

target selection will be aided by systems biology

approaches.64 Animal models, which now have great

limitations in reproducing the human condition, will

be more predictive due to improved humanization

of receptors and biological processes. Increasingly,

human stem cells will also be used as an in vitro

model, offering a better predictor of toxicity.

For manufacturing, an advance already taking hold

is the cell-free manufacturing of biologics. This

approach should make the regulatory process less

burdensome, as batch testing of individual product

lots may no longer be necessary and the process may

be more akin to the process for chemicals.65

Also, clinical trials may be enrolled increasingly

through online communities, which should speed

enrollment and produce greater statistical power to

obtain results quickly. An example of such an online

community is the for-profit company PatientsLikeMe

(www.patientslikeme.com), which has 118,003

participants with more than 500 disease conditions.

The company sells voluntarily collected patient

information to many of the Top 20 pharmaceutical

companies and engages its members in industry- and

government-sponsored clinical trials.66-68

More Powerful and Accessible Diagnostics

Diagnostic tests will become more powerful and accessible. Scientists involved in this project

believe that advances in diagnostic tests will

supply both healthcare providers and patients with

FINDING 4


more information and may produce unexpected

diagnoses. Such advances will also enable rapid

detection in the event of a disease outbreak and will,

therefore, facilitate rapid response.

For diagnostics in the future, it’s not going to be a guessing game. It’ll be [a matter of], “Tell me what’s there, and I’ll figure out if it’s significant.”

Certainly, there will be more diagnostic platforms

available, including mass spectrometry, microfluidics,

paper-based or cell phone–integrated tests, and

multi-analyte and host-side tests. For high-resource

settings, the low costs of sequencing could result in

routine whole-pathogen sequencing for diagnosis.

Human SNP (single nucleotide polymorphisms)

analysis and perhaps even whole-genome

sequencing of patients may be performed more

commonly to aid in diagnosis and preventive care.69

Costs for the human genome have decreased 10-

fold over the past 10 years and are expected to

decrease another 10-fold in the next 10 years. The

recent announcement of a combined Venter/X Prize

of US$10 million for more accurate medical-grade

whole-human genome sequencing could shorten this

timeline.70 There is already notable consumer interest

in this type of data: Testament to that is the success

of 23andMe, a company that, for $99, will mail out a

saliva collection kit to people who wish to have their

SNPs analyzed in a CLIA-certified laboratory in order

to learn about their personal disease risks. Since it

was formed in 2007, the company has analyzed the

DNA of 100,000 customers.71

Focus on the Patient, Regardless of Pathogen

Focus on the host, not the pathogen. Efforts are

under way to better understand the host reaction

to disease, with the goal of modulating individual

immunological responses to disease. If that can

be done, then genetic modulation of individuals’

immune systems may increase resistance to disease

or reduce morbidity. This line of investigation has the

potential to shift the focus of medical response away

from the approach of fighting a pathogen with drugs

tailored specifically to that purpose to an approach

based on host immune response more generically.

It will allow the medical treatment of the “unknown,

unknown,” which is critical to national security in the

face of myriad possible variations of the biological

threat.

Drug Targets Currently Underutilized

Important drug targets may already be discovered and waiting for development. Finding new drug

candidates may not require additional discovery.

Discussion in the Biodangers meeting suggested

that some biotech and pharmaceutical companies

now have in their possession libraries of millions of

compounds, many of which have not been tested

against pharmaceutical targets or not developed.

Governmental pressure to open up pharmaceutical

collections for neglected diseases could yield

promising candidates.

Drug Shortages Less Likely

Manufacturing can be distributed, which will make shortages less likely. The industrial base is moving

toward a dose-on-demand approach to manufacture

of pharmaceutical drugs, which could mean

that manufacturing will be more geographically

distributed and will allow for production of smaller,

targeted doses. The vision is to develop an agile

capacity to manufacture a variety of batches of drugs

that could respond to specific market needs. As a

result of this trend, current national strategies for

stockpiling medical countermeasures may become

outmoded with advances in technologies.

We should be investing in an ability to manufacture countermeasures. And the good news is that biology is going to be the enabling technology that’s going to let us do that.

FINDING 4


Medical Practice Slow To Change

Medical practice may not change as quickly as progress is made in the biological sciences. Technological change is likely to be much easier

than adoption. Extensive documentation of the

slow pace of change in medical practice indicates,

for instance, that even when information about new

developments is readily available, translation to

practice can take as long as 17 years.

As an example: Spine surgery for pain relief has

demonstrated no added benefit over other, less

invasive interventions, yet 600,000 of those surgeries

are still performed each year.72 For patients with

cardiac stents, the news is bleaker: 3 years after the

end of the COURAGE study, a well-publicized clinical

trial studying heart patients, the important changes

to recommended medical practice derived from

the study’s results have resulted in only negligible

changes to the care delivered to patients.73

Regulatory Approach Needs To Be Right, or it Could Block Progress

The wrong regulatory approach could limit advances in bioscience. Project participants

expressed a great deal of concern about application

of inappropriate regulation that could limit the

potential for bioscience advances, and they noted

that the right regulatory approach that promotes

innovation will be essential if bioscience benefits are

to be realized.

There is a tendency for regulators to focus on stopping the risk rather than coping with the risk.

Many of the scientists we interviewed believe that

current regulations are short-sighted or ill-informed.

The example cited most often was the prohibition

against genetically modified organisms (GMOs) in

the EU, a regulatory decision that has direct costs: If

GMOs were allowed, it has been estimated that the

profit margins of European farmers would increase

by US$443 million to US$929 million each year.74

Regulation Being Outpaced by Technological Change

Technology is outpacing the ability to regulate. The resources currently required for evaluating and

regulating biotechnologies and products are not

sufficient, which does not bode well for the future,

as more technologies emerge. In the U.S., FDA-

regulated products account for approximately 25

cents of every dollar spent by American consumers

each year, but the FDA mandate is considerably

more expansive than its budget.75

Confounding the problem, new technologies and

products may be dramatically different from old

models, a problem already apparent with diagnostic

tests. Instead of one diagnostic test for one disease,

diagnostic tests that detect thousands of pathogens

are now possible, but testing and validating them is a

new challenge.

Protection of individually identifiable information

will also present challenges. Genetic information

will become more important to diagnosis and drug

development, but as identification gets easier,

genetic privacy will be more difficult to control or

protect.

Public Engagement—A Must for Technologies to Flourish

Engaging the public is a must. Without public

support, emerging biotechnologies may not be

allowed to develop or could be banned entirely,

as evidenced by prohibitions against GMOs in

the EU and bans on stem cell research in the U.S.

Clearly, public action can be a powerful impediment

to technological advancement. Many project

participants were concerned that not enough was

being done to engage the public about the future

direction of bioscience research and industrialization

and the potential benefits to society.

As scientists, we need to get smarter about dealing with the public.

FINDING 4


For national security, it is important to make the case

for continued scientific research into new ways to

diagnose infectious diseases and to prevent or treat

using new medical countermeasures. These benefits

will not be realized without ongoing commitment to

bioscience advances.


SummaryBig teams do not have exclusive rights on the future of biotechnology. Individuals and smaller groups can do the same thing as big life sciences teams on a small scale.

This report is an expert assessment of where bioscience, biotechnology, and the industrial use of

biotechnologies are heading in 5-10 years and the resulting concerns and opportunities for national security.

The “Age of Biology”—a moniker perhaps first applied at the start of the Human Genome Project in 1990—now

is a reality with substantial governmental and private industry support. Industries that traditionally relied on

chemical engineering are increasingly reliant on biological approaches, and new industries are being formed as

the availability of computational power intersects with the biosciences.

According to the experts we talked to, biological approaches are transforming manufacturing and other

industries akin to the way that steam engines or computers transformed nationally important industries. As

history has shown in previous industrial revolutions, the center of economic gravity can shift precipitously

along with these technological changes, and this is also occurring with biology industrialization. The global

biotech ecosystem of available scientific talent, investment, and education is shifting. Peer competitors

have been able to leapfrog into established markets with safer and cheaper biotechnologies. Established

centers of biotechnology, including the U.S. and the U.K., must adapt in order to remain part of this new

industrial revolution, not only with scientific contributions, but by realistically assessing the risks and rewards

of the technologies to the public, and with regulatory changes that encourage innovation and private sector

investment.

The global industrialization of biology holds additional dangers: the accessibility of new, powerful

biotechnologies and information will inevitably increase the potential for misuse of biology. While experts had

few concerns about people unskilled in the biosciences using this technology for harm, they were concerned

about malevolent use by skilled individuals, especially if they had significant resources. To counter this danger,

the only option they foresaw was to tap the potential of biology industrialization to increase protections

against misuse. Abstaining from biotechnology development increases national security vulnerabilities, such

as diminished medical countermeasures and the loss of economically important industries, but investments in

biotechnology, such as in development of medical countermeasures, diagnostic tests, and medical treatments,

are not only economically beneficial but also yield national security dividends.

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APPENDIX A


Appendix ANovember 9, 2011, Biodangers Meeting Participants

Parney Albright Ph.D, Laboratory Director,

Lawrence Livermore National Laboratory

Rainer Breitling Ph.D, Professor, University of

Glasgow

Mark Buller Ph.D, Professor, Saint Louis University

Anita Cicero, JD, Chief Operating Officer and

Deputy Director, Center for Biosecurity of UPMC

Bernard Courtney, Chief Scientist, The Tauri Group

Jamie Davies, Ph.D, Professor, University of

Edinburgh

Cos DiMaggio, Managing Partner, The Tauri Group

Doug Drabkowski, Transition Branch Chief and

Acting Deputy Director, Chemical and Biological

Defense Division, Science and Technology

Directorate, Department of Homeland Security

Ray Elliott, Ph.D, Senior Scientific Advisor, Syngenta

John Glass, Ph.D, Senior Scientist, JCVI Synthetic

Biology Group

Michael Goldblatt, JD, Ph.D, President and CEO,

Functional Genetics

Richard K. Gordon, Office of the Assistant to the

Secretary of Defense for Nuclear and Chemical and

Biological Defense Programs

Gigi Kwik Gronvall, Ph.D, Senior Associate, Center

for Biosecurity of UPMC

D. A. Henderson, MD, Distinguished Scholar, Center

for Biosecurity of UPMC

Thomas Inglesby, MD, Chief Executive Officer and

Director, Center for Biosecurity of UPMC

Tom Knight, Ph.D, Senior Research Scientist,

Massachusetts Institute of Technology

Susan Coller Monarez, Threat Characterization and

Attribution Branch Chief (Acting), Chemical and

Biological Defense Division, Science and Technology

Directorate, Department of Homeland Security

Ryan Morhard, JD, Legal Analyst, Center for

Biosecurity of UPMC

Stephanie Okimoto, Science and Technology Liaison

to the United Kingdom, Department of Homeland

Security

Tara O’Toole, MD, MPH, Under Secretary for

Science and Technology, Department of Homeland

Security

Jason Paragas, Ph.D, Special Advisor to the

Director, Chem Bio Division, Defense Threat

Reduction Agency

George Poste, Ph.D, Chief Scientist, Complex

Adaptive Systems Initiative, Arizona State University

Kunal Rambhia, MS, Senior Analyst, Center for

Biosecurity of UPMC

Alan Rudolph, Ph.D, MBA, Director for Chemical

and Biological Technologies Directorate, Defense

Threat Reduction Agency

Ari Schuler, Senior Policy Analyst/Acting Special

Assistant to the Undersecretary for Science and

Technology, Office of the Under Secretary, Science

and Technology Directorate, Department of

Homeland Security

APPENDIX A


David Shepherd, Project Manager, Biological

Information and Analysis Program, Department of

Homeland Security Science and Technology Chem-

Bio Defense Division

Bernard Silverman, Ph.D, Chief Scientific Adviser,

Home Office, United Kingdom

Joyce Tait, Ph.D, Science Advisor, Innogen Centre,

University of Edinburgh

Seamus Tucker, Head of CBRNE Office of Security

and Counter-Terrorism, Home Office, United

Kingdom

Iain Williams, Head of Science Secretariat, Home

Office, United Kingdom

APPENDIX A


Appendix BList of Experts Interviewed by the Center for Biosecurity

Parney Albright, Ph.D, Laboratory Director, Lawrence

Livermore National Laboratory

Sameer Bade, Microsoft Research

Les Baillie, Ph.D, Cardiff University

David Berry MD, Ph.D, Flagship Ventures

Mark Buller, Ph.D Professor, Saint Louis University

Rainer Breitling, Ph.D Professor, University of

Glasgow

Mario Caccamo, Ph.D, Genome Analysis Centre

Michael Callahan, MD, Defense Advanced Research

Projects Agency

Jane Calvert, Ph.D, Innogen School of Social Science

and Political Science

Robert Carlson, Ph.D, Biodesic

Tony Cass, Ph.D, Imperial College London

Faye Davis, Ph.D National Defense University

Ian Dobson, BP BioFuels

Andrew Ellington, Ph.D, University of Texas

Ray Elliott, Ph.D, Senior Scientific Advisor, Syngenta

Yali Friedman Ph.D, Journal of Commercial

Biotechnology

Emma Frow, Genomics Forum

John Glass, Ph.D, Senior Scientist, JCVI Synthetic

Biology Group

David Gilbert, Ph.D, Brunel University

Michael Goldblatt, JD, Ph.D, President and CEO,

Functional Genetics

Chris Hankin Ph.D, Imperial College London

Richard Jackson, Ph.D, University of Sheffield

Stephen Johnston, Ph.D, The Biodesign Institute

Ellen Jorgensen, Ph.D, GenSpace

Jim Karkanias, Microsoft Research

Jean-Claude Kihn, Ph.D, Goodyear Tire and Rubber

Company

Tom Knight, Ph.D, Senior Research Scientist,

Massachusetts Institute of Technology

Michael Kurilla, MD, Ph.D, National Institute of

Allergy and Infectious Disease

Paul-Jean Letournaeu, Wolfram-Alpha

Chris Lowe, Ph.D, University of Cambridge

Thomas Monath, MD, Kleiner Perkins Caufield Byers

Philip New, BP Biofuels

Danny O’Hare, Ph.D, Imperial College London

APPENDIX B


Tara O’Toole, MD, MPH, Under Secretary for

Science and Technology, Department of Homeland

Security

Jason Paragas, Ph.D, Special Advisor to the

Director, Chem Bio Division, Defense Threat

Reduction Agency

Joseph Perpich, MD, JD, JGPerpich, LLC

George Poste, Ph.D, Chief Scientist, Complex

Adaptive Systems Initiative, Arizona State University

David Rejeski, Wilson International Center for

Scholar

David Relman, Ph.D, Stanford University

Alan Rudolph, Ph.D, MBA, Director for Chemical

and Biological Technologies Directorate, Defense

Threat Reduction Agency

Bernard Silverman, Ph.D, Chief Scientific Adviser,


Willem ‘Pim’ Stemmer, Ph.D, Amunix, Inc.

Martin Storksdieck, Ph.D, Director, Board on

Science Education, National Research Council

David Studholme, Ph.D, University of Exeter

Joyce Tait, Ph.D, Science Advisor, Innogen Centre,

University of Edinburgh

Iain Williams, Ph.D, Head of Science Secretariat,


Center for Biosecurity of UPMC

621 E. Pratt StreetSuite 210Baltimore, MD 21202Tel: 443.573.3304 • Fax: 443.573.3305

www.upmc-biosecurity.org

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