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Emerging
Technologies
Genetic Engineering
and
Biological Weapons

the sunshine project

TWN
THIRD WORLD NETWORK

EMERGING TECHNOLOGIES
Genetic Engineering and Biological Weapons

is published by
The Sunshine Project
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Austin TX 78701, USA
and
Third World Network
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Copyright © Sunshine Project and TWN, 2004

Printed by Jutaprint
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the sunshine project
Many biological weapons are rapidly destroyed by bright sunlight.
The Sunshine Project works to bring facts about biological weapons
to light! It is an international non-profit organization with offices in
Hamburg, Germany and Austin, Texas, USA. It works against the
hostile use of biotechnology in the post-Cold War era. Through its
research and publications it seeks to strengthen the global consensus
against biological warfare and to ensure that international treaties
effectively prevent development and use of biological weapons.
www.sunshine-project.org
tsp@sunshine-project.org

TWN
Third World Network

Third World Network (TWN) is a network of groups and indi­
viduals involved in bringing about a greater articulation of the
needs and aspirations and rights of people in the Third World
and in promoting a fair distribution of world resources and forms
of development which are humane, in harmony with nature,
and which fulfills people's needs.
www.twnside.org.sg
twnet@po.j aring.my

Contents
Page

Summary

1

Introduction

1

2

Single Gene Transfer and Similar Genetic
Engineering of BW Agents

4

Emerging Technologies I: Novel Infectious Agents
Pathogenicity Factors

9

Emerging Technologies II: Synthesis of
Biowarfare Agents
Artificial poliovirus
Another route to smallpox
Recreating the Spanish flu

71
11
12
13

5

Emerging Technologies III: New Types of Weapons
Food Weapons
Terminator Technology
Insect fighters

17
17
21
23

6

Ethnic Specific Biological Weapons
Techniques to translate genetic sequence into
a weapons effect
Ethnic specific genetic markers
Conclusions

24

Conclusions and Recommendations

34

References

37

Endnotes

41

3
4

7

7

25
25
31

Summary

Emerging diseases are often discussed as a global public health threat
but the threat of these diseases is paralleled by another - that posed
by emerging technologies.
Rapid developments in biotechnology, genetics and genomics pose a
variety of environmental, ethical, political, and social questions. And
because they open up tremendous new possibilities for biological
warfare, these technological developments have grave implications
for peace and security.

In this report, we give a systematic overview of the impact of bio­
technology on biological weapons (BW) development, focussing on
existing technologies and recent discoveries whose implications are
still poorly understood. Much of what we present may sound like
science fiction, but in fact it is far more science than fiction - and in
some cases it is already a reality.
The most frightening developments can currently be witnessed in
the US, where new technology is being exploited to create new types
of biological and biochemical weapons, including material degrad­
ing microorganisms and psychoactive chemicals, raising the spectre
of a new biological and chemical arms race.

Genetic engineering can contribute to offensive BW programs in a
variety of ways. With genetic manipulation, classical biowarfare

agents such as anthrax or plague may be made more efficient weap­
ons. Barriers to access to agents such as smallpox, Ebola or the Span­
ish flu1 are being lowered by genetic and genomic techniques.

Completely new types of weapons are also becoming possible, in­
cluding the use of food crops as tools for biological warfare. Even
ethnically specific weapons, hitherto thought to be impossible, have
become a real possibility. We present data here showing that ethnic
specific genetic sequences do exist in considerable high numbers.
Alarmed by the rapidly increasing technical possibilities, the Inter­
national Committee of the Red Cross recently appealed to govern­
ments to take concrete steps to avert the hostile use of biotechnology.
A broad array of political measures will be needed to counter the
threat of hostile exploitation of biotechnology.
First and foremost, the Biological Weapons Convention (BWC) needs
to be strengthened through multilaterally agreed, legally binding veri­
fication measures. In addition, three immediate steps are of specific
importance:
• All projects that violate the Chemical and Biological Weapons
Conventions must be immediately abandoned, specifically develop­
ment of so-called "non-lethal" chemical weapons, anti-material
biowarfare agents, and fungi for the war on drugs. Failure to do so
will encourage other countries to follow suit with R & D projects on
biotechnological weapons, leading to an unravelling of two key dis­
armament treaties.
• There is an urgent need to ensure that governments restrict them­
selves and ensure maximum transparency in their biodefence pro­
grams, to prevent a race for offensive capabilities under cover of de­
fence. All governments should adopt the 'Government Undertaking
on Biodefense Programs', recently brought forward by the Sunshine
Project.2 It contains, among others, a provision that ''biodefense pro­
grams will not, for any purpose, utilize or construct, including single-gene

changes, novel biological agents with an enhanced offensive potential" such
as treatment resistance, environmental stability, or enhanced patho­
genicity.

• For some particularly dangerous technologies, restrictions on re­
search are required. These research prohibitions, which are an inher­
ently more effective approach than imposing limits on publication,
should apply in specific fields:
a) that may easily be abused for hostile purposes,

b) where no effective global arms control or non-proliferation efforts
are presently feasible, and
c) where other technical avenues to reach the same peaceful scien­
tific goal are available.

Introduction

Biological arms control is currently in one of its worst crisis since
before the signing of the Biological Weapons Convention (BWC) in
1972. Efforts to strengthen the BWC through comprehensive declara­
tion and verification measures failed in 2001 due to US resistance.3 At
the same time, the US has massively expanded its biodefense pro­
gram and embarked on the exploitation of biotechnology for weap­
ons development.4

Mark Wheelis and Malcolm Dando, biologists and biological weap­
ons experts, recently warned that "the US may already be plunging reck­
lessly forward into the military applications of biotechnology, whose legacy,
we predict, will be as troubling to our children as is our parents' nuclear
legacy to us" (Wheelis & Dando 2002).
Wheelis and Dando further argue the imminent danger of a new bio­
logical arms race: "This U.S. exploration of the utility of biotech for
bioweapons development is unwise, for the rest of the world will be obliged
to follow suit. In its rush to stay ahead technologically, the United States
runs the risk of leading the world down a path toward much-reduced secu­
rity" (Wheelis & Dando 2003).

We concur and present here further discussion on specific technolo­
gies and civilian and military research that endanger security. The
danger that such experiments in biotechnology and biomedicine will
lower the threshold for the use of bioweapons (BW) is also seen by

1

government researchers: "The wide range of effects that can be designed
into [biowarfare] agents will expand options for [their] employment signifi­
cantly and ultimately may decrease the current threshold for use of biologi­
cal warfare... advances in biotechnology research may lead to a coming revo­
lution in BW development for technologically proficient rogue nations...".5
The authors - from the US Defense Intelligence Agency - fail to men­
tion that the threshold is most obviously and aggressively being low­
ered by the US itself.

Alarmed by the failure of the BWC Verification Protocol, rapidly in­
creasing technical possibilities, and the renewed interest in biological
warfare capabilities, the International Committee of the Red Cross
recently issued an appeal to all political and military authorities "to
work together to subject potentially dangerous biotechnology to effective
controls". It continues: "We urge you to consider the threshold at which we
all stand and to remember our common humanity."6

This dramatic appeal is based on the inescapable facts that the revo­
lution in biotechnology does indeed lead to a dramatically increased
biowarfare risk and that governments have achieved little in reining
in these risks. Whereas thirty years ago, biotechnology was restricted
to a small number of advanced research laboratories, today it is ubiq­
uitous.
This global distribution of modern biotechnology has led to a world­
wide availability of knowledge and facilities useful in biowarfare
programs. In some countries, even high school students now con­
duct experiments in genetic engineering. High-tech facilities for the
production of vaccines, single-cell-protein or biocontrol agents are
widely distributed and will continue to spread as biotechnology or,
at least, certain biotechnologies, find commercial uses in a larger
number of markets.

Within the more generalized spread of biotechnology, there are spe­
cific new applications that are particularly troublesome. A relatively

2

clear-cut problem is the genetic engineering of classical biowarfare
agents to make them more effective. But new genetic and genomic
techniques provide for additional, new, warfare possibilities. Once
eradicated, viruses such as smallpox or the deadly 1918 influenza
virus (which killed 20-40 million people in a global epidemic) may
now be synthesised in the laboratory.

Genetically engineered crops and insects can be used for the produc­
tion - and secret delivery - of harmful biological substances and, in
human genomics, even ethnically specific biological weapons are
becoming a real possibility.

The following chapters give a systematic overview on these issues —
some of the examples are already a reality, others are hypothetical in
the sense that they have not, to our knowledge, been utilized for hos­
tile purposes but the science behind them is very real.

3

Single Gene Transfer and Similar Genetic
Engineering of BW Agents

In the debate over genetic engineering and biological weapons it has
often been stated that natural pathogens are sufficiently dangerous
and deadly so that genetic engineering is not necessary for effective
biological warfare. This is true: biological weapons can indeed be used
without even any systematic knowledge on microbiology, as shown
by their effective use in past centuries.7 Genetic engineering, how­
ever, has been employed in offensive biowarfare programmes in or­
der to make biowarfare agents more effective. In the former Soviet
Union a variety of such experiments were undertaken. Below are three
examples:
• Bacteria causing unusual symptoms: Researchers from Obolensk
near Moscow inserted a gene into the bacterium Francisella tularensis,
the causative agent of tularemia and a well known biological weapon
agent. The gene made the bacteria produce beta-endorphin, an en­
dogenous human drug, which caused changes in the behaviour of
mice when infected with the transgenic bacteria.8 According to the
published results, the endorphin gene was not introduced into a fully
virulent strain, but only into a vaccine strain. If inserted into virulent
Francisella tularensis, the victims would not show the usual symp­
toms of tularemia, but instead unusual symptoms that could obscure
diagnosis and delay therapy. Development of symptom-altered BW
agents has been identified as one possible application of genetic en­
gineering by the US Department of Defence.9

4

'Invisible' Anthrax: In the 1990s, Russian researchers altered the im­
munological properties of anthrax, making existing vaccines and de­
tection methods ineffective against a new genetically engineered
type.10 They also developed a new vaccine against the artificial strain.
Following the Russians, the US Department of Defence is now also
genetically engineering anthrax.11 According to the US, the classified
experiments are to test if the Russian microbe can defeat the US an­
thrax vaccine.
Treatment resistant plague: According to scientists involved in of­
fensive biowarfare research in the former Soviet Union, plague bac­
teria (Yersinia pestis) were developed in the former Soviet BW pro­
gram that were resistant to 16 different antibiotics.12 Today, the ge­
netic introduction of antibiotic resistance into bacterial pathogens is
routine work in almost any microbiology laboratory.

These are some of the examples of genetic engineering in offensive
biowarfare programmes that have become public. It is safe to assume
that theses are only a portion of what has been attempted, as offen­
sive bioweapons programmes are obviously not publicized.
Despite these examples, it should not be assumed that genetic engi­
neering will play a major role in the early steps of a national biowarfare
programme.13 The development of reliable, effective biological weap­
ons requires an intense and resource demanding research programme
that must solve - step by step - three increasingly complex problems:
procurement of virulent strains of suitable agents, mass production
of agents without loss of pathogenicity, and development of effective
means of delivery.
The third step is especially demanding and has rarely been solved
(with notable exceptions such as the former biowarfare programmes
of the US and USSR). Even after several years of an active biowarfare
programme, in the early 1990s, Iraq possessed only rudimentary
means of delivery. From this perspective, genetic engineering is sim­
ply another step in the development of a biowarfare potential, which

5

may not be taken before the first three essential steps are solved.

On the other hand, the limited biowarfare suitability of almost any
natural pathogen should not be dismissed. In the classic military point
of view, a microorganism must fulfil a variety of demands. It must be
producible in large amounts, act quickly, and be environmentally ro­
bust. The disease also needs to be treatable, to permit protection of an
aggressor's own troops. Bacillus anthracis, for example, essentially
fulfills the military specification, although anthrax victims may be
treated up to several days after exposure with antibiotics. Therefore,
only a minority of the infected persons will die from an anthrax at­
tack in circumstances where appropriate medical response is possi­
ble, as was shown by the anthrax attacks in 2001 in the USA.
A very simple genetic intervention such as increased antibiotic resist­
ance, however, could provoke much more deadly results by impair­
ing timely and effective treatment. The technical possibilities for such
manipulations are many, and are growing by the day. In many basic
science research projects, methods to overcome current technical limi­
tations in the military use of pathogenic agents have been demon­
strated - sometimes unwittingly.

Countless examples from the daily work of molecular biologists could
be presented here, but one particularly interesting example is the trans­
fer of "suntanning" genes. Many microorganisms are rapidly de­
stroyed by bright sunshine (hence the Sunshine Project) and are thus
only of limited use as a biowarfare agent. Many biological weapons
are much more effectively used at night or dawn in order to avoid the
destructive effect of the ultraviolet light. But "suntanning" genes may
be introduced into microorganisms to confer UV resistance. In one
experiment, genes coding for the synthesis of carotinoids have been
transferred into harmless bacteria (Sandmann et al. 1998). Another
possibility would be to engineer toxins into microorganisms that are
naturally UV-protected (Manasherob et al. 2002).

6

Emerging Technologies I: Novel
Infectious Agents

Afore complex genetic interventions, such as multiple gene trans­
fers and "tailor-made" novel agents are becoming possible. Harmless
bacteria may be equipped the capability to cause illness and death,
and even inter-species hybrids ('chimera') involving large gene se­
quences are a real possibility.
Two years ago, Australian scientists inadvertently created a virus that
turned out to be lethal for mice. In a genetic experiment, mousepox
virus was altered to create a sort of fertility control vaccine, intended
to be used to control mouse infestations in Australia.

In a first experiment, proteins from the surface of mouse egg cells
were inserted into the virus to trigger an immune response against
the egg cells. Because the immune response was insufficient, the re­
searcher tried to boost it in a second experiment by adding another
gene. Completely unintended and unforeseen, all mice infected with
the new virus strain died, even if they had been vaccinated against
mousepox. It turned out that the additional gene had the unforeseen
effect of turning off the immune system of the mice, making them
vulnerable to lethal infection by the otherwise harmless virus (Jackson
et al. 2001).
It is safe to assume that many other experiments have unwittingly
created more pathogenic variants, without that fact having become
public. In most instances, the result of such "failed" experiments end

7

up in the laboratory freezer or simply go down the sink.

According to a British government paper in 2001 the mousepox ex­
periment exemplifies that "the risk of unexpected outcomes with ge­
netically modified micro-organisms must increase with the increase in the
number of laboratories both in developed and developing countries that rou­
tinely apply recombinant technologies to micro-organisms...unforeseen
consequences...could be disastrous for example if such organisms escaped
from the laboratory. This emphasises the importance of carefid risk analysis
and appropriate procedural and physical containment measures."'4
In the Australian experiment, a new way to enhance the pathogenic­
ity of usually harmless viruses had been demonstrated. The research­
ers were aware of the potential military abuse of their work and di­
rectly contacted the Australian ministry of defence, to discuss how to
proceed with their findings. When they decided to foster transpar­
ency and publish the work, it started a global debate about possible
abuse of genetic engineering.
While the Australian research group accidentally stumbled across this
effect, US scientists wittingly repeated the same experiment and de­
liberately took the lethal approach further.

In October 2003, Mark Buller of the University of St Louis told a sci­
ence conference that his group performed the same experiments with
cowpox virus - a virus that may also affect humans. Buller also in­
creased the lethal efficacy of the engineered virus by 'optimising' the
genetic insert. Buller's mousepox strain killed 100 per cent of infected
mice, even when they were vaccinated and also treated with the anti­
viral drug cidofovir.15
In another example, British researchers pleaded guilty in 2001 to
charges that they improperly handled a genetically engineered hy­
brid of the viruses causing hepatitis C and dengue fever. British au­
thorities characterized the virus as "more lethal than HIV

8

'Dengatitis' was deliberately created by researchers who wanted to
use fewer laboratory animals in a search for a vaccine for Hepatitis C.
Under unsafe laboratory conditions, the researchers created and nearly
accidentally released a new hybrid human disease whose effects, for­
tunately, remain unknown but which may have displayed different
symptoms than its parents and thus have been difficult to diagnose,
and have required a new, unknown treatment regime.

Pathogenicity factors
A key research area for biomedicine - and biodefence - is the identi­
fication of pathogenicity or virulence factors, meaning those proteins
or genes that contribute to an infectious microorganism's ability to
cause illness or spread from host to host. It is a scientifically challeng­
ing area and it is still far from easy to determine what makes one
bacterium so deadly while a close relative is completely harmless or
even beneficial.17 While the field remains difficult, research applica­
tions can already be witnessed.
As early as 1986, a US-based research team transferred the lethal fac­
tor from anthrax bacteria into harmless gut bacteria (E. coli). As ex­
pected, the gut bacteria started to produce the corresponding protein
that turned out to be as lethal as the natural toxin from anthrax bacte­

ria.
And in the view of an ever increasing number of bacterial genomes
that are completely sequenced - including some of the most deadli­
est organisms such as Yersinia pestis, Variola major, or Bacillus anthracis,
the causative agents of plague, smallpox and anthrax, respectively it can be expected that in the coming years, genes will be identified
that may turn harmless bacteria into deadly weapons. A lot of effort
is currently put into unravelling virulence related genes, many of them
in the course of officially defensive military sponsored research.

9

Earlier this year, for example, the US Department of Energy, which
runs US weapons laboratories such as Lawrence Livermore and Los
Alamos, solicited grant proposals for "the identification ... of proteins
expressed from virulence genes in biological pathogens relevant to the
[Chemical Biological Nonproliferation Program] mission."™

Also possible are genetic alterations that increase the ability of a mi­
croorganism to invade human cells. As early as 1997, a US patent was
granted for a US Department of Defence funded project on "invasive
microorganisms".19 This patent describes how innocuous bacteria may
be genetically altered to invade cells and deliver "molecules of inter­
est" into these cells. While the patent probably aims at beneficial
"molecules of interest", i.e., pharmaceutical substances, it may also
be used in other ways.

10

4 Emerging Technologies II: Synthesis of
Biowarfare Agents

1 oday access to highly virulent agents and strains is increasingly
regulated and restricted. Smallpox viruses, eradicated outside the
laboratory more than 20 years ago, are today (most likely) present in
only two high security laboratories in the US and Russia. But it is
only a question of time before the artificial synthesis of agents or agent
combinations becomes possible.

Artificial poliovirus
Poliovirus was recently synthesized by a US research team at the State
University of New York in Stony Brook. The researchers built polio­
virus "from scratch" through chemical synthesis (Cello et al. 2002).
Starting with the gene sequence of the agent, which is available online,
the researchers synthesized virus sequences in the lab and ordered
other tailor-made DNA sequences from a commercial source. They
then combined them to form the full polio genome. Ln a last step, the
DNA-sequence was brought to life by adding a chemical cocktail that
initiated the production of a living, pathogenic virus. The experiment
was funded by the US Defense Advanced Research Projects Agency
(DARPA).

In principle, this method may be used with other viruses that have a
similarly short genetic sequence (genome). This is true for at least
five viruses that are considered to be potential biowarfare agents, in­
cluding Ebola, Marburg and Venezuelan Equine Encephalitis. Ebola
11

and Marburg are very rare viruses that may be difficult to acquire for
potential bioweaponeers. Using the method that has now been pub­
lished for polio, Ebola might be synthesized in a laboratory. At present
the method is mastered by only a few highly trained experts, although
this is unlikely to remain so for long.

Another route to smallpox
Poliovirus is not terribly well suited to be a biological weapon,20 but
the experiment exemplifies possibilities that generate real problems
if similar techniques become applicable to agents such as smallpox.
Today it is unlikely (though not completely impossible) that coun­
tries apart from Russia and the USA have access to smallpox virus.
This is the basis of the current threat assessments with regard to small­
pox, which rate the likelihood of a smallpox attack very low. Should
it become possible in a few years to build smallpox virus in the labo­
ratory, the situation would be turned upside down. The relative se­
curity that can be assumed today (at least for most countries in the
world) will evaporate.
The method to artificially create poliovirus can not be directly trans­
ferred to smallpox virus. The smallpox genome, with more than
200,000 base pairs, is far larger than that of poliovirus, and even if it
would be possible to create the full smallpox sequence in vitro, it can­
not be as easily be "brought to life" as poliovirus. But there may be
other ways to build smallpox artificially. It would, for example, be
possible to start with a closely related virus such as monkeypox or
mousepox and to alter specifically those base pairs and sequences
that differ from the human smallpox.
In 2002, the first steps in such a technique were demonstrated. It was
documented for the first time that the sequence of a (pathogenicity
related) gene in the smallpox-related Vaccinia virus can be transformed
into the sequence of the corresponding smallpox gene through a tar­
geted mutation of 13 base pairs (Rosengard et al. 2002). It is probably

12

only a matter of a few years until this kind of technique may be appli­
cable to full genomes, meaning the current smallpox threat assess­
ment (and that for some other agents) will have to be reconsidered.

Currently, the full sequences of at least two different smallpox strains
are available in the internet,21 and most recently a new internet site
dedicated to poxvirus genomic sequences has been launched (Upton
et al. 2003). According to a spokesperson22 of the National Center for
Biotechnology Information in the USA, there appears to be a view in
the scientific community that the smallpox sequences "are already
out there" and withdrawing it from databases like GenBank would
rather hinder vaccine research than provide any additional security.

Recreating the Spanish flu
Influenza as a bioweapon does not sound like a particularly grave
threat. Annual outbreaks kill many people, particularly the elderly;
but a case of the flu is generally perceived as an uncomfortable nui­
sance rather than a grave threat. But flu viruses can be devastating.
In 1918 and 1919, the so-called "Spanish flu" killed an estimated 2040 million people worldwide and, since then, the highly changeable
flu virus has resurfaced in a variety of particularly virulent forms.
The strain of influenza virus that caused the 1918 global epidemic
("pandemic") was exceptionally aggressive. It showed a high capac­
ity to cause severe disease and a propensity to kill fit young adults
rather than the elderly. The mortality rate among the infected was
over 2.5%, as compared to less than 0.1% in other influenza epidem­
ics (Taubenberger et al. 1997). This high mortality rate, especially
amongst the younger, lowered the average life expectancy in the USA
by almost 10 years (Tumpey et al. 2002). Creation of this particularly
dangerous influenza strain, as it is currently pursued by a US research
team, may thus pose a serious biowarfare threat.

A recent commentary in the Journal of the Royal Society of Medicine

13

(Madjid et al. 2003) noted that influenza is readily transmissible by
aerosol and that a small number of viruses can cause a full-blown
infection. The authors continued: "... the possibilityfor genetic engineer­
ing and aerosol transmission [of influenza] suggests an enormous potential
for bioterrorism". The possible hostile abuse of influenza virus is seen
as a very real threat by public health officials in the USA. Ln Septem­
ber 2003, a total of 15 million dollar was granted by the US National
Institutes of Health to Stanford University to study how to guard
against the flu virus "if it were to be unleashed as an agent of bioterrorism''.23

US scientists led by a Pentagon pathologist recently began to geneti­
cally reconstruct this specifically dangerous influenza strain. In one
experiment a partially reconstructed 1918 virus killed mice, while virus
constructs with genes from a contemporary flu virus had hardly any
effect.
Attempts to recover the Spanish flu virus date back to the 1950s when
scientists unsuccessfully tried to revive the virus from victims buried
in the permafrost of Alaska.24 In the mid 1990s, Dr Jeffrey Taubenberger
from the US Armed Forces Institute of Pathology started to screen
preserved tissue samples from 1918 influenza victims. It appears that
this work was not triggered by a search for flu treatments, or the search
for a new biowarfare agent, but by a rather simple motivation Taubenberger and his team were just able to do it.

hi previous experiments they had developed a new technique to ana­
lyse DNA in old, preserved tissues and for now looking for new ap­
plications: "The 1918 flu was by far and away the most interesting thing
we could think of"25 explained Taubenberger the reason why he started
to unravel the secrets of one of most deadliest viruses known to hu­
mankind.
A sample of lung tissue from a 21-year-old soldier who died in 1918
at Fort Jackson in South Carolina,26 yielded what the Army research­
ers were looking for - intact pieces of viral RNA that could be ana­
lysed and sequenced. In a first publication in 1997, nine short frag­

14

merits of Spanish flu viral RNA were revealed (Taubenberger et al.
1997). Due to the rough tissue preparation procedure in 1918, no liv­
ing virus or complete viral RNA sequences were recovered.

Genetic techniques helped to isolate more Spanish flu RNA from a
variety of sources. By 2002, four of the eight viral RNA segments had
been completely sequenced, including the two segments that are con­
sidered to be of greatest importance for the virulence of the virus the genes for hemagglutinin (HA) and neuraminidase (NA).

The project did not stop at sequencing the genome of the deadly 1918
strain. The Armed Forces Institute of Pathology teamed up with a
microbiologist from the Mount Sinai School of Medicine in New York.
Together, they started to reconstruct the Spanish flu. In a first attempt,
they combined gene fragments from a standard laboratory influenza
strain with one 1918 gene.27 They infected mice with this chimera,
and it turned out that the 1918 gene made the virus less dangerous
for mice (Basler et al. 2001).28
In a second experiment, published in October 2002 (Tumpey et al.
2002), the scientists were successful in creating a virus with two 1918
genes. This virus was much more deadly to mice than other constructs
containing genes from contemporary influenza virus.29 This experi­
ment is only one step away from taking the 1918 demon entirely out
of the bottle and bringing the Spanish flu back to life.

The scientists were aware of the dangers of their creation. The experi­
ments were conducted under high biosafety conditions at a labora­
tory of the US Department of Agriculture in Athens, Georgia. Possi­
ble hostile use of their work was an issue considered by the scientists:
"...the available molecular techniques could be used for the purpose
of bioterrorism'' (Tumpey et al. 2002:13849).
There is no sound scientific reason to conduct these experiments. The
most recent experiments (Tumpey et al. 2002) allegedly seeked to test
the efficacy of existing antiviral drugs on the 1918 construct - but

15

there is little need for antiviral drugs against the 1918 strain if the
1918 strain would not have been sequenced and recreated in the first
place. It is true that biodefense research - and any kind of civilian
medical research - is always a race with its counterpart, the evolution
of naturally occurring infectious agents or the development of
biowarfare agents. But in this race it should be avoided to create the
threats that are allegedly the motivation for the research. A self-made
vicious circle is created: ‘'The technologies are in place with reverse genet­
ics to generate any influenza virus we wish ... studies are envisaged using
genes of the 1918 Spanish Influenza virus..."30

These arguments were recently brought forward to justify another
maximal biosafety laboratory for biological defence work in Texas,
USA. Without Taubenberger's pioneering work, the money for the
lab could have been saved and better invested in combatting natu­
rally occurring diseases such as tuberculosis, malaria or HIV.
Other papers argued that the experiments may help to elucidate the
mechanisms of influenza evolution and virulence (Taubenberger et
al. 1997, Basler et al. 2001), but this argument is deeply flawed, too.
Since 1918, a large amount of different influenza viruses with differ­
ent virulence and pathogenicity properties have been isolated and
characterised by researchers around the world - a more than abun­
dant source for generations of scientists to study influenza evolution
and virulence. A resuscitation of the Spanish flu is neither necessary
nor warranted from a public health point of view.
There may be many reasons for the individual scientists to work on
this project, not least the scientific prestige - the 'Spanish flu' subject
matter practically guaranteed a series of publications in prestigious
journals. From an arms control perspective it appears to be particu­
larly sensitive if a military research institution embarks on a project
that aims at constructing more dangerous pathogens - if Jeffery
Taubenberger worked in a Chinese, Russian or Iranian laboratory,
his work might well be seen as the 'smoking gun' of a biowarfare
program.

16

Emerging Technologies III:
New Types of Weapons

NTany other new weapons may become possible in the decades to
come. The deciphering of the human genome, synthetic genes and
organisms, new approaches to gene therapy and drug delivery, and
the sheer volume of genetic engineering experiments with potentially
pathogenic microorganisms will increase the availability of much
more sophisticated biological agents with a potential for hostile use,
not only in classical warfare scenarios, but also for "peacekeeping",
"military operations other than war", "low intensity conflict", and
covert operations. To illustrate the possibilities, examples of future
weapons based on current technologies follow.

Food Weapons
So called "edible vaccines" and "biopharming" (i.e., the production
of vaccines or other bioactive substances in edible crops) can be put
to hostile use. In the past decade, genetically engineered plants have
been investigated as a means to produce and deliver vaccines. There
are already a variety of research reports demonstrating that engi­
neered plants can elicit an immune response in humans (Haq et al.
1995, for review see Streatfield/Howard 2003), and clinical trials on
humans are currently underway to test vaccines produced in edible
crops.31 These vaccines may be isolated from the plant for further
processing or directly delivered to the patients by consumption of
the engineered plant.
17

Vaccines are only one type of bioactive substances being produced in
edible crops. Several US companies are using genetically engineered
crops to produce industrial enzymes, growth hormones, and other
potent pharmaceutical compounds. These techniques pose a serious
risk to human health and the environment, especially when the highly
active pharmaceuticals are introduced into edible crops.32

The possibility of abuse of these crops and/or the underlying tech­
nology for hostile purposes is serious. In long term conflicts, it may
be tempting to weaponize engineered crops, spiking them with, for
example, disease-inducing (e.g., cancer) or debilitating compounds
(e.g., affecting human or animal fertility) or built-in deficiencies that
could lead to crop failure.
Such "weaponized" germplasm may thereafter be introduced in the
target country's seed supply and consequently its food supply through
covert actions or simply by means of seed sales or humanitarian aid.
This may not be possible with crops that are exported by the target
country, as, given today's global market, the spiked food/feed could
end up in the aggressor's food supply. But for most countries it will
be possible to identify food or feed crops in the target country that
are not exported.

There are routes to possibly achieve similar effects without sophisti­
cated knowledge to engineer a specific crop with a specific compound.
Theft of a few corn kernels from one of the many trials with edible
plants producing bioactive substances may be enough. Pharmaceuti­
cals such as blood ciotters or blood thinners may not be a weapon of
choice, but introduction into the food supply would not be techni­
cally difficult. Profusion of such artificial traits would likely produce
panic and could be very difficult and expensive to eradicate. Public
concern would be amplified if the trait in question was a potent growth
hormone, which has been field trialed in the US, or a drug called
trichosanthin, which has also been tested.
Trichosanthin, considered to be a potential anti-cancer agent, has the

18

same mode of action as the biowarfare agent ricin33 and is a strong
abortion-inducing compound. In the US, trichosanthin production in
tobacco plants was induced by a genetically engineered plant virus.
That same virus also easily infects crops such as tomatoes and pep­

pers.
A 'contraceptive corn' developed by the US company Epicyte is un­
likely to be usable for hostile purposes but it illustrates the potential
abuse of pharming. Epicyte genetically engineered corn to produce
an antibody against human sperm. The company wants to produce
large amounts of the antibody in order to extract it for use in a contra­
ceptive gel.
Consumption of the engineered corn or the extracted antibodies is
unlikely to confer sterility - but a similar approach would yield dra­
matically different results. Introduction of a gene for human sperm
cell antigens into a crop could create (an easily abused) contraceptive
vaccine, preventing women who eat the engineered corn from repro­
ducing.

Edible weapons pose a serious problem for BW non-proliferation ef­
forts. No biological arms control effort could stop a person from steal­
ing a handful of kernels, growing more, and introducing them into a
country's food supply. The technology and especially its products
are inherently difficult to control - the past years witnessed a variety
of cases where specific genetically engineered crop varieties showed
up in unexpected places. In one case, a corn variety that was not per­
mitted for human consumption by US regulatory agencies showed
up in a broad variety of human food supplies - despite it being ap­
proved for animal feed only.34
Considering how easy and effective the hostile abuse of these geneti­
cally engineered crops is once they are developed, a complete ban on
the production of hazardous compounds in edible crops appears to
be justified. This may not stop a criminal from willfully creating an
"edible weapon", but it would tremendously raise the threshold com­

19

pared to wandering into a corn field and grabbing some cobs.
In addition, it will be technologically more challenging for a future
biowarfare program to develop its own "food weapon" if the tech­
nology is not further developed. With each experiment and each field
trial, more knowledge on how to turn food crops into dangerous
weapons will be accumulated, simultaneously creating pathways to
weapons.

A complete ban on this particular technology will not cause severe
scientific or industrial setbacks. All bioactive compounds that are
currently produced in edible crops may as well be produced through
other means that are less prone to hostile use. Some small biotech
companies that specialize in biopharming may face problems, but
others that focus on different technologies will benefit from such a
move.

Fertility Control
Currently, a variety of new methods for fertility control are under de­
velopment, for use as contraceptives in humans but also for the bio­
logical control of pest animals. Some of them - such as the Australian
mousepox experiment - pursue strategies that are based on vaccines,
i.e., they try to direct an animal or human immune response against
egg or sperm cells to prevent pregnancy and reproduction.
It is too early to conclude that these experiments will be successful,
but if so, "fertility vaccines" present opportunities for abuse. If live
vaccines are used (as in the mousepox example) that can be transmit­
ted from individual to individual, a large population (of animals or
people) may easily be prevented from reproducing, with enormous
long term social and economic consequences.

Applied to 'invasive alien' or introduced species, such vaccines pose
serious ecological threats (if the vaccine spreads to the target's geo­
graphic origin) but also significant risk of abuse to cause deliberate

20

harm. This is particularly the case if such vaccines are developed to
eradicate species of food of economic importance - for example, a
"vaccine" to control feral pigs, goats, rabbits, or other mammals that
pose an ecological problem where they have been introduced might
be transported to deliberately damage agriculture in other areas.

Terminator Technology
So-called "terminator technology" renders seed infertile to guaran­
tee a seed corporation's yearly sales. It may eventually be abused for
economic warfare. If terminator crops become widespread, it would
be easy for a country or a company that controls the technique to stop
sales to a specific country or region for political or economic pur­
poses. After some years of planting such seeds, only limited quanti­
ties of other seeds would be available, thus agriculture could be para­
lysed, leading to serious economic crisis and/or famine.

Current Projects in the US
The Sunshine Project has previously documented a series of recent of­
fensive projects in the United States that draw on new developments
in biotechnology. Military exploitation of new biotechnological possi­
bilities, most notably with so-called "non-lethal" weapons, have fueled
new weapons desires, even in countries that have renounced the use
of biological weapons such as the US (and, in the case of "non-lethal"
chemical weapons, Russia).

The following three cases have been researched and previously pub­
lished by the Sunshine Project, hence here we present only short sum­
maries. Further reading is available on our website.

o Material degrading microorganisms:35
Natural microorganisms are capable of degrading nearly every kind of
material. These organisms are sometimes used for environmental

cleanup purposes ("bioremediation") but are generally too slow and
unreliable for weapons purposes. Genetic engineering, however, is
enabling development of organisms effective enough for use as bio­
logical weapons.
The British government recently warned: "Bioremediation technologies
clearly have the potential for development of a means of warfare or for hostile
use against material crucial for normal civilian life or military operations,
such as oils, rubbers and plastic."36

This potential has raised the interest of several US government research
institutions, including the US Naval Research Laboratory, where mi­
croorganisms that degrade a variety of materials (plastics, rubber, met­
als, etc.) were genetically engineered to make them more powerful and
focused for bioweapons purposes.

• Fungi against drug producing plants:37
About a decade ago, the United States increased efforts to identify
microorganisms that kill drug-producing crops. In the late 1990s, this
research focused largely on two fungi. Testing of Pleospora papaveracea
to kill opium poppy, conducted in Tashkent, Uzbekistan with US fi­
nancing and scientific support, was completed in 2001. Pathogenic
Fusarium oxysporum strains developed in the United States to kill coca
plants were scheduled for field testing in Colombia in 2000, but inter­
national protests led to a halt to this project.

• Military use of psychoactive substances:
So called "non-lethal" chemical weapons were developed by the US
military in the 1950s, especially a hallucinogenic substance called "BZ".
But BZ was considered to be unreliable, leading to its removal from
the US chemical arsenal in the late 1960s.
Today, modern neurobiology is developing an increasingly compre­
hensive knowledge of a broad range of specific neuroreceptors and
psychoactive substances that trigger (or inhibit) them. Military temp­
tation to exploit these discoveries have made "non-lethal" chemical
weapons again attractive for the military. A case in point was the use

22

of a gas in the Moscow theatre hostage situation in 2002. Projects at the
US Army's Aberdeen Proving Ground and at the US Marine Corps
Research University have recently investigated the military utility of a
variety of incapacitating agents, including calmatives, seizure induc­
ing agents and other psychoactive substances.
The US and Russia are also developing delivery devices for chemicals
with a range of more than 2.5 kilometers - a distance that makes sense
only for warfare scenarios, and not for domestic law enforcement pur­
poses.

Insect fighters
The idea to use insects to deliver biological warfare agents is not new.
Insects were systematically explored as a mechanism to spread a va­
riety of diseases (e.g., plague) in the World War II Japanese BW pro­
gram and the postwar US program. In many cases, such insect vector
BW was dismissed as too complicated and unreliable. But genetic
engineering may open a new way to use insects as weapons.

In the same way as genetically engineered plants may be misused as
"food weapons", insects may be engineered to produce toxic com­
pounds and deliver them through their natural feeding habit - e.g.,
in the saliva of mosquitoes. Again, these compounds may exert a broad
range of possible effects, from non-life-threatening illness to sterility
to widespread fatal illness in a target population.
Techniques to use insects to deliver vaccines have already been de­
veloped and patented.38 The idea to develop what one company calls
"flying syringes" is based on the hope of circumventing costly vacci­
nation programmes in which every individual must be inoculated by
trained medical personnel. Genetically engineered mosquitoes or
other biting insects could instead deliver minute quantities of vac­
cine through the saliva every time they bite.

23

Ethnic Specific Biological Weapons

Current wisdom holds that population specific biological weapons
are practically and theoretically impossible. Practically, many con­
sider the use of genetic variability to kill or affect populations as an
impossibility. Others, including geneticists, argue that no suitable eth­
nic specific genes exist in the first place. Both notions are wrong.
New technologies are indeed available to translate specific genetic
sequences into markers or triggers for biological activity. And a re­
cent analysis of human genome data in public databases revealed
that hundreds, possibly thousands, of target sequences for ethnic spe­
cific weapons do exist. It appears that ethnic specific biological weap­
ons may indeed become possible in tire near future.
Weapons targeting specific population groups do not need to be
deadly. They could cause temporary incapacitation, illness, sterility,
permanent fatigue, or any other condition that may not be fatal but
desirable from an aggressor's perspective. They may be used in an
all out war, in the battlefield or against civilian population, or they
may be used in covert operations, in conflict situations, and with long­
term effects, in order to destabilise, harm economically or weaken an
enemy society.

24

Techniques to translate genetic sequence into a weapons
effect
The development of ethnic weapons with very specific effects would
be easiest with techniques that use a genomic marker as a trigger for
an activity that is unrelated to the location of the marker, i.e., the
effect would be triggered even if the sequence is in a non-coding or
non-translated region of the genome. As far as we are aware, this
kind of technology does not yet exist.
There are, however, techniques available that can inhibit genes with
a specific sequence. They target mRNA, the molecule that transmits
information from the DNA to the place of protein synthesis within a
cell. One of these techniques, called RNA interference (RNAi), uses a
mechanism by which a specific RNA sequence is degraded by the
cell if an externally applied RNA molecule of the same sequence is
entering the cell (for review, see Cerutti 2003).

A similar approach called antisense technology inhibits further mRNA
processing by binding endogenously produced mRNA to an exter­
nally applied DNA molecule with the corresponding sequence. The
latter technology is currently under development by the US company
Ibis Therapeutics.39
Both technologies lead to the inhibition of a specific target gene with
a specific sequence. If the sequence of the target gene varies from one
population to another, this can be used to interrupt the gene in one
population and not in the other. Military abuse of this technology
would require the identification of population specific sequences in
genes that are active and vital for the body function.

Ethnic specific genetic markers
Do such genetic markers exist? Markers that are present in one popu­
lation (at least to a certain percentage) but not in another? Many hu­

25

man geneticists are eager to emphasize that genetic diversity within
a population is far greater than between populations. This view is
also reflected in a 2001 background paper prepared by the British
Government for the last Review Conference of the BWC. It states that
"there is as yet no indication of differences that could be used as the basis for
'genetic weapons' which would target particular ethnic groups. "w

99.9% of the genetic sequence of any two human individuals is said
to be identical — but the remaining 0.1% accounts for a total of 3
million "letters" of the human genome. There are thought to be sev­
eral tens of thousands coding genes in the human genome, thus it is
possible that every single gene between one individual and another
could be slightly (or greatly) different, even if there is 99.9% homol­
ogy in overall genetic sequence.
Some of this huge genetic diversity breaks out in differences between
populations. These genetic populations (using the term in its biologi­
cal sense) appear to often correspond with (culturally-determined)
ethnic groups (for a detailed discussion on human genetics and the
pitfalls of racial genetic profiling in general see Sankar & Cho 2002,
Aldhous 2002, Schwartz 2001, Wood 2001).

From a biological weapons perspective, population specificity would
mean more than just a small variation in allele frequencies in differ­
ent ethnic groups — no effective weapon could be designed that tar­
gets a genetic constitution that is also present to any significant ex­
tent in the population of the aggressor.
From a military perspective, population specificity would mean that
these genetic sequences are not or only to a very limited extent present
in one (the aggressor's) population while the same sequences are
present in a significant percentage of an opposing population.41

While it would certainly be desirable to have a very high percentage
— up to 100% — of the target population bearing the target genetic
marker, this is by no means a prerequisite for a militarily useful

26

weapon. If as litte as 10% or 20% of a target population would be
affected, this would wreak havoc among enemy soldiers on a battle­
field or in an enemy society as a whole. Thus, in discussing genetic
markers for ethnically-specific weapons, sequences would be needed
that have a frequency close to 0% in one population while having a
significant frequency in another. For the purpose of this paper, we
assume that a frequency of 20% or higher may be enough from a mili­
tary perspective.

Cytochrome P450 genes
The many genes in the cytochrome P450 system have been suggested
as possible targets for ethnic specific weapons, for two reasons. They
show high ethnic diversity, and they are involved in the detoxification
of toxic substances. The notion is that ethnic groups with specific
polymorphisms in a cytochrome P450 gene may be less able to de­
toxify a specifically designed biological or chemical weapon and thus
be more susceptible to its action.

In our view, these genes are probably useless as a basis for ethnic weap­
ons, as diversity in most of these cases relates to different percentages
of certain alleles in different population, not situations in which one
population has a certain allele while the other does not.

Hence, a significant part of the aggressor's population would be po­
tentially vulnerable. In addition, the P450 system comprises many
dozens of enzymes with overlapping activities. Targeting a chemical
or biological compound to one specific P450 enzyme would be very
challenging.

A systematic search in two databases revealed that genetic sequences
that fulfill these specifications not only exist, but they do so in unex­
pectedly high numbers. Our analysis focused on so called single nu­
cleotide polymorphisms - SNPs - that are by far the most common
source of genetic variation. SNPs are basically single-letter variations

27

man geneticists are eager to emphasize that genetic diversity within
a population is far greater than between populations. This view is
also reflected in a 2001 background paper prepared by the British
Government for the last Review Conference of the BWC. It states that
"there is ns yet no indication of differences thnt could be used as the basis for
'genetic iveapons' which would target particular ethnic groups."40
99.9% of the genetic sequence of any two human individuals is said
to be identical — but the remaining 0.1% accounts for a total of 3
million "letters" of the human genome. There are thought to be sev­
eral tens of thousands coding genes in the human genome, thus it is
possible that every single gene between one individual and another
could be slightly (or greatly) different, even if there is 99.9% homol­
ogy in overall genetic sequence.

Some of this huge genetic diversity breaks out in differences between
populations. These genetic populations (using the term in its biologi­
cal sense) appear to often correspond with (culturally-determined)
ethnic groups (for a detailed discussion on human genetics and the
pitfalls of racial genetic profiling in general see Sankar & Cho 2002,
Aldhous 2002, Schwartz 2001, Wood 2001).
From a biological weapons perspective, population specificity would
mean more than just a small variation in allele frequencies in differ­
ent ethnic groups — no effective weapon could be designed that tar­
gets a genetic constitution that is also present to any significant ex­
tent in the population of the aggressor.

From a military perspective, population specificity would mean that
these genetic sequences are not or only to a very limited extent present
in one (the aggressor's) population while the same sequences are
present in a significant percentage of an opposing population.41

While it would certainly be desirable to have a very high percentage
— up to 100% — of the target population bearing the target genetic
marker, this is by no means a prerequisite for a militarily useful

26

weapon. If as litte as 10% or 20% of a target population would be
affected, this would wreak havoc among enemy soldiers on a battle­
field or in an enemy society as a whole. Thus, in discussing genetic
markers for ethnically-specific weapons, sequences would be needed
that have a frequency close to 0% in one population while having a
significant frequency in another. For the purpose of this paper, we
assume that a frequency of 20% or higher may be enough from a mili­
tary perspective.

Cytochrome P450 genes
The many genes in the cytochrome P450 system have been suggested
as possible targets for ethnic specific weapons, for two reasons. They
show high ethnic diversity, and they are involved in the detoxification
of toxic substances. The notion is that ethnic groups with specific
polymorphisms in a cytochrome P450 gene may be less able to de­
toxify a specifically designed biological or chemical weapon and thus
be more susceptible to its action.

In our view, these genes are probably useless as a basis for ethnic weap­
ons, as diversity in most of these cases relates to different percentages
of certain alleles in different population, not situations in which one
population has a certain allele while the other does not.
Hence, a significant part of the aggressor's population would be po­
tentially vulnerable. In addition, the P450 system comprises many
dozens of enzymes with overlapping activities. Targeting a chemical
or biological compound to one specific P450 enzyme would be very
challenging.

A systematic search in two databases revealed that genetic sequences
that fulfill these specifications not only exist, but they do so in unex­
pectedly high numbers. Our analysis focused on so called single nu­
cleotide polymorphisms - SNPs - that are by far the most common
source of genetic variation. SNPs are basically single-letter variations

27

man geneticists are eager to emphasize that genetic diversity within
a population is far greater than between populations. This view is
also reflected in a 2001 background paper prepared by the British
Government for the last Review Conference of the BWC. It states that
"there is ns yet no indication of differences thnt could be used as the basis for
'genetic weapons' which would target particular ethnic groups.''40
99.9% of the genetic sequence of any two human individuals is said
to be identical — but the remaining 0.1% accounts for a total of 3
million "letters" of the human genome. There are thought to be sev­
eral tens of thousands coding genes in the human genome, thus it is
possible that every single gene between one individual and another
could be slightly (or greatly) different, even if there is 99.9% homol­
ogy in overall genetic sequence.

Some of this huge genetic diversity breaks out in differences between
populations. These genetic populations (using the term in its biologi­
cal sense) appear to often correspond with (culturally-determined)
ethnic groups (for a detailed discussion on human genetics and the
pitfalls of racial genetic profiling in general see Sankar & Cho 2002,
Aldhous 2002, Schwartz 2001, Wood 2001).
From a biological weapons perspective, population specificity would
mean more than just a small variation in allele frequencies in differ­
ent ethnic groups — no effective weapon could be designed that tar­
gets a genetic constitution that is also present to any significant ex­
tent in the population of the aggressor.
From a military perspective, population specificity would mean that
these genetic sequences are not or only to a very limited extent present
in one (the aggressor's) population while the same sequences are
present in a significant percentage of an opposing population.41

While it would certainly be desirable to have a very high percentage
— up to 100% — of the target population bearing the target genetic
marker, this is by no means a prerequisite for a militarily useful

26

weapon. If as litte as 10% or 20% of a target population would be
affected, this would wreak havoc among enemy soldiers on a battle­
field or in an enemy society as a whole. Thus, in discussing genetic
markers for ethnically-specific weapons, sequences would be needed
that have a frequency close to 0% in one population while having a
significant frequency in another. For the purpose of this paper, we
assume that a frequency of 20% or higher may be enough from a mili­
tary perspective.

Cytochrome P450 genes
The many genes in the cytochrome P450 system have been suggested
as possible targets for ethnic specific weapons, for two reasons. They
show high ethnic diversity, and they are involved in the detoxification
of toxic substances. The notion is that ethnic groups with specific
polymorphisms in a cytochrome P450 gene may be less able to de­
toxify a specifically designed biological or chemical weapon and thus
be more susceptible to its action.

In our view, these genes are probably useless as a basis for ethnic weap­
ons, as diversity in most of these cases relates to different percentages
of certain alleles in different population, not situations in which one
population has a certain allele while the other does not.
Hence, a significant part of the aggressor's population would be po­
tentially vulnerable. In addition, the P450 system comprises many
dozens of enzymes with overlapping activities. Targeting a chemical
or biological compound to one specific P450 enzyme would be very
challenging.

A systematic search in two databases revealed that genetic sequences
that fulfill these specifications not only exist, but they do so in unex­
pectedly high numbers. Our analysis focused on so called single nu­
cleotide polymorphisms - SNPs - that are by far the most common
source of genetic variation. SNPs are basically single-letter variations

27

in the human DNA sequence.

In the past years, several million SNPs have been identified by pri­
vate and public entities. The SNP Consortium (TSC), representing a
group of large pharmaceutical companies and not-for-profit organi­
sations, keeps a public database on many SNPs. Another SNP data­
base, the SNP500Cancer database, is maintained by the Cancer Ge­
nome Anatomy Project of the US National Institutes of Health.42

Both databases provide data on allelic frequencies in different
populations. We analysed a total of nearly 300 SNPs, all in coding
regions or genes,43 from both databases. An unexpectedly high number
of these SNPs are indeed population specific: 6.7% of the SNPs in one
database (see Table 1 on page 29 ) and 1.6% of the SNPs in the other
include one allele that is not present at all in one population while it
has a frequency of more than 20% in another population.
This finding is consistent with results from Stephens et al. (2001) who
identified a total of 1,452 SNPs out of 3899 SNPs (37.2%) to be popu­
lation specific, although the majority of these were rare SNPs. How­
ever, Stephens et al. (2001) also noted that "not all population-specific
alleles were observed at a low frequency. In the African-American and Asian
samples, some population-specific alleles were found at frequencies >25%."

In some cases, the frequency differences can be very high. For exam­
ple, in our analysis of 105 SNPs from the TSC database, one SNP
(TSC0493622) has a 0% : 94% ratio between major populations (see
Diagram 1 on page 30). The G-allele of this SNP was present in 94%
of the African-Americans and in 0% of the Asians sampled. The na­
ture and function of the gene encoded by this genetic region is still
unknown.

Another example for a relatively high frequency difference is a poly­
morphism at the human melanocortin 1 receptor locus (MC1R), an
enzyme involved in skin color formation. In a study by Rana et al.
(1999) one allele was not identifiable in any African, but showed a

28

0 :>
= 1%
(n)

0:>
= 10%
(n)

17

5

18

4

Chrom.
#

No. of
SNPs with
TSC-ID and
frequency data
on 2 or more
populations

1

2

0 : = > 20%
(n)(pop:pop)

TSC-ID

2

1 (A:C)

1166809

2

1 (A:AA)

0493622

1 (A:AA)

0231219

1 (A:AA)

0207612

1 (C:AA)

1104025

3

8

1

1

4

12

1

1

5

9

1

1

6

9

3

3

7

8

2

1

8

11

2

2

1 (C,A:AA)

0668661

9

7

2

1

1 (A:AA)

0815601

10

6

0

Total
(n)
(%)

105
(100%)

21
(20%)

14
(13.3%)

7
(6.7%)

Table 1: Ethnic-specific SNPs in the TSC database
From the database of The SNP Consortium (TSC),44 SNPs were analysed for an
ethnic specific allele distribution. The TSC database distinguishes between Cauca­
sian, Asian and African-American samples.45 From 105 randomly selected SNPs46 in
coding regions of the human genome, 21 had an allele frequency of 0% in one
population but were present in at least one other population, 14 of these with a
frequency > 10% and 7 of these with a frequency > 20%.
pop - population; A-Asian; C - Caucasian, AA-African American (e.g. A:C means
that the minor allele is not present in the Asian population and has its highest fre­
quency in Caucasians).

29

Distribution of Allele Frequency

Allele Frequency (%)

Diagram 1: Frequency of the minor allele of the 21 ethnic
specific SNPs in the TSC database
The majority of the population specific SNPs had a rather low frequency for one
allele of less than 20%, but some SNPs with higher frequencies were also iden­
tified. 14 SNPs had an allele frequency of 19% and less, while only 7 SNPs had
an allele frequency of 20% and higher. For SNPs with ethnic specific alleles in 2
populations, the higher frequency value was choosen for this diagram.

frequency of 70% in East and Southeast Asians.

Some caution should be applied not to overestimate or interpolate
our results. Both datasets as well as the work of Stephens el al. (2001)
are based on a limited number of individuals for each population
group.47 Hence, alleles with a very low frequency in any one popula­
tion may have been missed. Therefore it is possible and likely that
some of the alleles that were not identified in one population group
may well be present at low frequencies in these groups, so that many
of the SNPs that were included in our analysis as they showed a 0%
frequency for the minor allele would have to be excluded as their
real frequency may be higher than 0%.

On the other hand, it is safe to assume that a certain percentage of the
SNPs included in our analysis will prove to be population specific
even if larger numbers of individuals were screened. There are ex­
amples of unsuccessful searches for alleles in large populations. The

30

gene for thiopurine methyl transferase (TPMT) is an enzyme involved
in metabolism of certain pharmaceuticals. Allele *3A, which is the
predominant mutant TPMT allele in individuals of European herit­
age, has not been identified in East Asian populations despite the
analysis of a total of 1068 individuals in five independent studies (see
van Aken et al. 2003 for review).

To summarize, in can be estimated that a considerable number of eth­
nic specific SNPs do exist. Recent numbers suggest that SNPs occur
with a frequency of about every 200 base pairs in the coding sequences
of human genes (Schneider et al. 2003). Given the total number of
about 3 billion base pairs, some 15 million SNPs may exist in the hu­
man genome. If in a conservative estimate only 0.1% (as compared to
the 6.7% and 1.6% determined in our analysis of the two datasets) of
these do occur population specific frequencies (here defined as 0% in
one population and > 20% in another), some 15,000 possible target
sequences may exist for future bioweaponeers.

It should be noted that some of the ethnic specific SNPs we identified
in our analysis have a known function and are indeed readily ex­
pressed in human tissue. For example, the SNP rs2894804 from the
SNP500Cancer database is located in a gene called GSTA1, coding for
glutathione S-transferase. This enzyme functions in the detoxifica­
tion of xenobiotics, including carcinogens, therapeutic drugs and en­
vironmental toxins. It was present in the African-American popula­
tion with a frequency of 23% while it was not identified in any of the
other three populations.

Conclusions
It must be stressed that ethnic or population specific weapons are
still a future threat and may not be accomplished within the coming
decade. However, the notion that they are impossible and would vio­
late the laws of nature is wrong and outdated. Practical steps can and
must be undertaken today to prevent the future development of these
kind of weapons. A key step would be to restrict the amount of ethnic

specific genomic data to an absolute minimum. We are, however, cur­
rently witnessing a scientific development that is actually doing the
opposite - creating vast amounts of genetic data for different
populations and ethnic groups. This happens in a variety of contexts.
• Pharmacogenetics and pharmacogenomics: In order to elucidate
genetic influence on drug safety and efficacy, an increasing number
of studies on pharmacogenetically relevant genes are being under­
taken. These include studies on genes for enzymes involved in drug
metabolism such as the cytochrome P450 system and many others,
but also genes coding for drug transporters or drug target proteins.
For the safe implementation of pharmacogenetics on a global basis or
in multicultural societies, reliable data on allele frequencies relevant
to all populations is needed. Hence many pharmacogenetic studies
investigate ethnic specific genetic differences relevant to drug action
and are thereby generating large data sets that genetically profile on
an ethnic basis. This problem may be circumvented by using pooled
samples from a representative cross-section of all relevant popula­
tion for the analysis of SNPs. Techniques are available today to calcu­
late allele frequencies in pooled samples from up to several 100 indi­
viduals. Through this method, all relevant alleles in a pooled sample
of all relevant populations could be determined without generating
ethnic specific genetic data. The field of pharmacogenetics is specifi­
cally risk-prone, as the relevant genes are directly involved in drug
metabolism or drug action and may thus be much more easily con­
verted into triggers/markers for the action of biological or chemical
agents than other genetic markers.
• The HapMap Project: In October 2002, an international project
to create a map of haplotypes48 in the human genome was launched.49
In this US$100 million public-private undertaking, genetic variations
in four populations will be investigated - US residents with Euro­
pean ancestry, Han Chinese, Japanese and Yorubas in Nigeria. The
HapMap project will provide vast amounts of genetic markers spe­
cific for any of the four populations. In the light of the possibility of

32

hostile abuse of these genetic markers the HapMap project should be
reconsidered.
• Forensic genetics: Genetic fingerprinting enables the matching
of a suspect's DNA with that found at a crime scene. However, law
enforcement is striving to get more information out of crime scene
DNA, including the "race" or ethnicity of the culprit. First steps have
been taken in the direction of ethnic affiliation estimation by use of
population-specific DNA markers (Shriver et al. 1997). The US Na­
tional Institute of Justice recently issued a $496,000 grant to the Uni­
versity of Arizona to predict skin colour from DNA samples,50 and
the US-based company DNAPrint Genomics Inc. is offering to deter­
mine "race proportions" from crime scene DNA, although the tech­
nique is still prone with difficulties (Brenner 1998). It appears that
these applications - if successful at all - could be of less concern from
a bioweapons perspective, as they do not necessarily rely on markers
that show a 0 : x percent distribution in different populations. In the
course of the development of more sophisticated approaches for fo­
rensic ethnic affiliation estimation, however, if a systematic search
for ethnic specific markers is undertaken, it may reveal markers abus­
able for bioweapons purposes.

• Others: Some human genetic studies touch on critical genetic
data in politically tense areas, such as work on ethnic (Bhattacharyya
et al. 1999) or even caste (Bamshad et al. 2001) associated genes in
India, or genetic differences between the Basque and non-Basque
population in Spain (Arrieta et al. 1997). A thorough assessment of
benefits - if any - of this research and the associated risks of abuse
appears to be necessary.

33

Conclusions and Recommendations

To summarise, genetic engineering can clearly contribute to making
classical biowarfare agents more effective. It can ease access to them,
enable the construction of novel BW agents and open the avenue for
a broad array of new types of weapons. It is of crucial importance for
scientists and policymakers around the world to address the increas­
ing threats and redouble efforts to strengthen the ban on biological
weapons and to control critical technologies.

While the science behind the examples given in this paper is a reality,
in most cases the hostile utilization of it (hopefully) has not occurred,
so far. For example, terminator technology or fertility control tech­
nology do not appear to have been exploited for hostile applications,
but it is obvious that once such technologies are more broadly ex­
ploited (particularly in commerce), they may become easily acquired
and used with malign intentions.
Molecular biology and genetic engineering are still in their infancy.
More technical possibilities will arise in the years to come that can be
abused for hostile purposes. More efficient classical biowarfare agents
will most likely play only a marginal role, even if the genetically en­
gineered superbug is still routinely featured in newspaper reports.
More likely and more alarming are the new types of weapons for
newly-prevalent types of conflicts and warfare scenarios, for exam­
ple, low intensity warfare and covert operations, for economic war­

34

fare or for sabotage. To prevent the hostile exploitation of biology
now and in the future, a bundle of measures must be taken. First and
foremost, the Biological Weapons Convention needs to be strength­
ened through multilaterally agreed, legally binding verification meas­
ures. In addition, three immediate steps are of specific importance:

• All projects that violate the Chemical and Biological
Weapons Conventions must be immediately abandoned.
In the United States, such projects include the development of mate­
rial degrading microbes, development of so-called "non-lethal"
(bio)chemical weapons (including delivery devices), and continued
development of biological agents to eradicate narcotic crops.
Other corm tries that are engaged in similar projects - such as Russia,
which maintains stockpiles of incapacitating chemical weapons and,
likely, an R & D program on them - must also halt such research.

These agents undermine the Chemical and Biological Weapons Con­
ventions, thereby lowering the political threshold for the use of bio­
logical weapons, and causing likely tremendous environmental and
health impacts.
Pursuit of these agents as weapons would be a step down a slippery
slope, that, following the same logic, could easily lead to the use of
other biochemical and biological warfare agents in conflict.

Failure to stop these projects will encourage other countries to follow
suit with R & D projects on biotechnological weapons, leading to an
unravelling of key disarmament treaties.
o
There is an urgent need to ensure that governments restrict
themselves and ensure maximum transparency in their biodefence
programmes, to prevent a race for offensive capabilities under cover
of defence.

35

We call on all governments to adopt the 'Government Undertaking
on Biodefense Program', which has recently been brought forward
by the Sunshine Project.
It contains, among others, a provision that "biodefense programs will
not, for any purpose, utilize or construct, including single-gene
changes, novel biological agents, with an enhanced offensive poten­
tial" such as treatment resistance, environmental stability, or enhanced
pathogenicity.


Research restrictions are necessary in certain situations, for ex­
ample, in cases where a military abuse appears to be imminent, where
no effective multilateral arms control or non-proliferation efforts are
presently feasible, and where other technical avenues to reach the
same scientific goal are (potentially) available.

These criteria apply specifically to the production of bioactive com­
pounds (pharmaceuticals, vaccines) in edible crops, but may also be
relevant for some aspects of pharmacogenetics, where the generation
of huge amounts of ethnic specific genetic data may be avoided by
choosing other techniques that serve the same research purpose.
The current "bioterrorism" discussion in the scientific community fo­
cuses entirely on restricting the publication of certain research results.
This is shortsighted, and may easily be abused to conceal illicit re­
search, particularly since it may be better not to generate dangerous
information in the first place. Full transparency in all aspects of bio­
medical research and development should be guaranteed.

36

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40

Endnotes
1.

In 1918, a particularly aggressive influenza virus spread around
the globe and killed 20-40 million people. This influenza
pandemia was dubbed the 'Spanish flu'.

2.

See www.sunshine-project.org. In Germany, a petition supported
by a variety of organisations including the Sunshine Project is
currently underway to encourage the government to formally
adopt high transparency and strict limits for its biodefense pro­
gram.

3.

For further reading on recent BWC developments see:
http://fas.org/bwc/index.html

4.

Specifically, it has become public in the past months that the US
is pursuing development of so called non-lethal chemical weap­
ons, material degrading microorganisms and an array of ques­
tionable 'biodefense' activities. See www.sunshine-project.org ,
Wheelis & Dando (2002, 2003) and Steinbrunner & Harris (2003)
for further reading.

5.

Petro JB, Plasse TR, McNulty JA (2003). Biotechnology: Impact
on biological warfare and biodefense. Biosecurity and
Bioterrorism Volume 1, Number 3

6.

Appeal of the International Committee of the Red Cross on Bio­
technology, Weapons and Humanity. September 2002 (online at
www.icrc.org).

7.

Before Pasteur and Koch discovered bacteria as disease causing
agents in the late 19th century, biological weapons were used.
For example, in the 14th century, Mongol invaders catapulted
plague victims into besieged cities. In the 18th century Britain
distributed smallpox-infected blankets to native Americans.

8.

Borzenkov VM, Pomerantsev AP, Ashmarin IP (1993). The addi­
tive synthesis of a regulatory peptide in vivo: The administration
41

of a vaccinal Francisella tularensis strain that produces beta­
endorphin Biull Eksp Biol Med 116(8):151-3 (Article in Russian).

9.

Jane's Defence Weekly, 13. August 1997, page 6: US DoD reveals
horrific future of biological wars.

10. Pomerantsev AP, Staritsin NA, Mockov YV, Marinin LI (1997).
Expression of cereolysine ab genes in Bacillus anthracis vaccine
strain ensures protection against experimental hemolytic anthrax
infection. Vaccine 15:1846-1850.

11. New York Times, 4 September 2001.
12. A. Hay, quoted in 'The bugs of war', news feature in Nature
411:232-235.
13. An exception may be sophisticated non-state actors which may
seek to apply modern genetics for their own hostile interests,
especially for low level or private conflicts. This refers less to
non-state actors such as Al Qaeda but rather to companies and/
or single individuals who due to their professional background
have the capability to do so.

14. Background paper on new scientific and technological develop­
ments relevant to the convention on the prohibition of the devel­
opment, production and stockpiling of bacteriological (biologi­
cal) and toxin weapons and on their destruction. BWC/CONF.V/
4/Add.l, 26 October 2001.
15. US develops lethal new viruses. New Scientist, 29 October 2003.
16. Arthur C "Scientists made virus 'more lethal than HIV', The In­
dependent, 24 July 2001.

17. For review, see the complete volume 264 of Curr Top Microbiol
Immunol (2002), edited by Hacker J & Kaper JB, which focuses
on 'Pathogenicity Islands and the Evolution of Pathogenic Mi­
crobes'.

42

18. http://www.science.doe.gov/sbir/Solicitations/ FY%202003/
NN.htm#Tl
19. US Patent 5662908 from 2 Sept. 1997, assigned to Stanford Uni­
versity in Palo Alto, California.

20. In more than 95% of infected persons, only mild flu-like symp­
toms — if any — are caused by the virus. With only about 1% of
the infected having the risk of severe illness, polio does not rank
high on a bioweaponeer's wish list.

21. One sequence of smallpox (Variola virus) with the GenBank code
X69198 (identical with NC_001611) was published by a team from
Russia's former offensive biowarfare program, and a second se­
quence (Variola major virus strain Bangladesh 1975) with the
GenBank code L22579 was published by an American team.
22. Personal communication on 26 June 2003 by Dr D. Wheeler, NCBI,
to Jan van Aken, Sunshine Project.
23. Stanford University News Release 17 September 2003, online at
http:/ / mednews.stanford.edu/ news_releases_html/2003/
sep tre 1 ease / b i o ter ror%20f1 u. h t m
24. Spanish flu keeps its secrets. Nature science update at
ww w.na tu re.com / nsu /990304/990304-5.html
25. Profile: Jeffery Taubenberger at
www.microbeworld.org/htm/aboutmicro/what_m_do/pro­
files/ taubenberger.htm

26. AFIP scientists discover clues to 1918 Spanish flu,
www.dcmilitary.com/ army/ stripe/archives/ mar28/
str_flu032897.html
27. The so-called "nonstructural" gene (NS)
28. It should be noted that for this experiment, a standard influenza
strain was used that was specifically adapted to mice and that
43

was lethal to mice. The scientists reasoned that the 1918 gene
probably weakened the lethality for the mice as it stemmed from
a human-adapted strain.
29. This time, the 1918 genes for hemagglutinin (HA), neuramini­
dase (NA) and matrix (M) were used, single and in combination.
Only the combination of the 1918 HA and NA genes caused a
dramatic increase in lethality if compared to constructs contain­
ing genes from a more recent human influenza virus. The scien­
tists concluded: "These data suggest that the 1918 HA and NA
genes might possess intrinsic high-virulence properties."(Tumpey
et al. 2002:13853).
30. Letter (4 February 2003) from Robert G. Webster, Professor of
Virology at St. Jude Children's Research Hospital to Stanley
Lemon, Dean, School of Medicine, University of Texas Medical
Branch (UTMB), in support of the UTMB application to construct
a National Biosafety Laboratory.
31. See, for example, ProdiGene press release, 12 August 2002:
ProdiGene and NIH beginning phase I study on oral vaccine
derived from transgenic corn. At www.prodigene.com
32. For a detailed discussion of possible effects on the environment
and human health see the background paper "Manufacturing
drugs and chemicals in crops" published by Friends of the Earth;
http://www.foe.org/camps/ comm/safefood /biopharm/
BIO PH A RM_R E PORT.pd f
33. Both, ricin and trichosanthin, are ribosomal inhibitor proteins.

34. For an overview on the escape and potential risks of StarLink
com see Washington Post, 19. March 2001, 'Biotech Corn Is Test
Case For Industry'.
http: / / www.washingtonpost.com/ac2/wp-dyn/ A230922001Marl8?language=printer

44

35. For further reading, see Sunshine Project Backgrounder #9
(http://www.su nshine-project.org/ publications/bk/
bk9en.html)
36. See endnote 14.
37. For extensive reading on Agent Green see the Sunshine Project
Backgrounder No. 4 and additional materials at www.sunshineproject.org.
38. See European patent PCT/GB95/02639 and US patent applica­
tion 20020124274 (September 5,2002) by Imperial College of Sci­
ence Technology and Medicine (London) for a 'delivery system".
39. www.ibisrna.com

40. See endnote 14.
41. It must, however, be questioned how good the 'zero' frequency
of the target allele on the aggressor's side has to be. This may
depend heavily on the effect of the ethnic weapon and on the
political system of the aggressor. Dictatorships may well accept
more "collateral damage" in their own society than others. And
if the effects are non-Iethal and long-term - such as sterility - it
may be more acceptable for an aggressor to have some victims
on its own side. If used in a battlefield, an aggressor could also
screen and select its soldiers according to this specific sequence,
or could apply specific countermeasures.

42. This program studied the genome of 102 individuals of self-de­
scribed heritage: 24 of African/African American heritage, 31 of
Caucasian heritage, 23 of Hispanic heritage, and 24 of Pacific Rim
heritage. In this database, we analysed 193 randomly selected
SNPs (all validated SNPs in chromosomes 6 and 10). A total of 24
SNPs (12%) showed an allelic freqency of 3 (10%) in at least one
population with a 0% frequency in at least one other population.
3 of these (1.6%) had a frequency of 20% or higher in one popula­
tion. http://snp500cancer.nci.nih.gov/snplist.cfm .

45

43. As discussed above, it appears to be a prerequisite for militarily
useful genetic markers to have them appear in coding sequences
or genes that are active in the human body, rather than in appar­
ently silent parts of the human genome. If new technologies are
developed that can use even apparently inactive genomic se­
quences as a trigger for the desired effect, this would make it
easier to translate these genetic differences into weapons.
44. http:/ /snp.cshl.org/ as of June 24, 2003.
45. For a description of the panel see:
http: //snp.cshl.org/allele_frequency_project/panels.shtml

46. All SNPs in coding (both synonymous and non-synonymous)
regions with a TSC-ID number and with allele frequencies pro­
vided for at least two different populations from the first 100MB
of chromosomes 1-10 were included in the analysis.
47. The SNP500Cancer Database is based on 23-31 individuals per
population group; the TSC-database is based on different pan­
els, most of which included 12-42 individuals per population
group; Stephens et al. included 18-21 individuals per population
group.
48. Haplotypes are blocks of closely linked SNPs in a genome and
are currently viewed as the best tool to study human genetic
variation.
49. See http://hapmap.cshl.org/ for details.
50. NIJ grant number 2002IJCXK010.

46

EMERGING TECHNOLOGIES
Genetic Engineering and Biological Weapons
ig diseases are often discussed as a global public health
jut the threat of these diseases is paralleled by another
erging technologies. Rapid developments in biotechnology,
enetics and genomics pose a variety of environmental, ethical,
olitical, and social questions.

The revolution in biotechnology has lead to dramatically increased
biowarfa
isks and governments have achieved little in reining in
ereas thirty years ago, biotechnology was restricted
lerof advanced research laboratories, today it is

es of weapons are becoming possible, including
| as tools for biological warfare. Even
weapons, hitherto thought to be impossible,
al possibility. Data is presented here showing
cigenetic sequences do exist in considerable

ining developments can currently be witnessed
e new technology is being exploited to create
logical and biochemical weapons, including

material degrading microorganisms and psychoactive chemicals,
raising the spectre or a new biological and chemical arms race.
This report gives a systematic overview of the impact of bio­
technology Oh- biological weapons development, focusing on
existing technologies and recent discoveries which have
implications that are still poorly understood.

Many of the examples presented may sound like science fiction,
but they are in fact far more science than fiction — and in
some cases they are already a reality. Others are hypothetical in
the sense that they have not, to our knowledge, been utilised for
hostile purposes, but the science behind them is very real.
This report also highlights the broad array of political measures
and concrete steps which governments will need to take to
counter the threat of the hostile exploitation of biotechnology.

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