Synthetic Poliovirus: Bioterrorism and Science Policy Implications
CRS Report for Congress
Synthetic Poliovirus: Bioterrorism and
Science Policy Implications
Frank Gottron
Science and Technology Policy Analyst
Resources, Science, and Industry Division
Summary
In July 2002, an online scientific journal published a report describing how to make
the virus that causes polio from mail-ordered pieces of DNA. This sparked widespread
concern that the same process could be used by terrorists to make this or other biological
agents. Most bioterrorism experts agree that it would be much easier, cheaper, and
quicker to obtain most such agents from naturally occurring sources. Smallpox and
Ebola are frequently cited as exceptions; however, these agents would be significantly
more difficult to synthesize than poliovirus. To limit the threat posed by this type of
research, policymakers have discussed approaches that include: increasing oversight of
the DNA suppliers, limiting access to the genetic information of select pathogens, and
regulating the publishing of information deemed possibly helpful to terrorists. This
report will be updated as events warrant.
In July 2002, a group of scientists from the State University of New York at Stony
Brook led by Dr. Eckard Wimmer published a report in the online journal Science Express
describing that they had constructed infectious poliovirus from mail-ordered pieces of
DNA.1 This research was funded by the Department of Defense through the Defense
Advanced Research Projects Agency (DARPA). The publication of this report has
intensified the debate on how best to balance the need for openness in science with the
need to protect national security.
Technical Background
The disease poliomyelitis (or polio) is caused by poliovirus. Like many viruses, the
genetic material of poliovirus is made of RNA (ribonucleic acid) instead of DNA
(deoxyribonucleic acid) which comprises human genes. Poliovirus is essentially a small
1 Science Express 10.1126/science.1072266. This report was subsequently published as J. Cello,
A. V. Paul, and E. Wimmer. “Chemical Synthesis of Poliovirus cDNA: Generation of Infectious
Virus in the Absence of Natural Template.” Science. Vol. 297. August 9, 2002. pp. 1016 - 1018.
Congressional Research Service ˜ The Library of Congress
piece of RNA encapsulated in a protein shell. As with all viruses, poliovirus cannot
reproduce on its own; it must hijack its host’s protein-making enzymes to reproduce.
After infecting the host cell, poliovirus forces the host cell to produce so many viral
copies that eventually the cell bursts. This releases the viral copies, freeing them to infect
other cells.2
To make poliovirus in the laboratory, the scientists first assembled a DNA version
of the viral RNA genome. This was done because DNA is much easier to manipulate in
the laboratory than RNA, and short, prefabricated, custom-made DNA pieces are readily
available by mail order from laboratory supply companies. The complete genetic
sequence of poliovirus has been known since 1981 and can be downloaded from the
Internet from sites that cater to researchers.3 Polio is one of the smallest of all viruses
with a genome of only about 7,500 bases. For comparison, smallpox has about 185,000
bases and humans have over 3 billion bases. Because only short pieces of custom-made
DNA are available for mail order, the scientists ordered over one hundred DNA snippets
at a cost of about $100,000.4 These snippets were painstakingly strung together in the
correct order. Although theoretically simple, this process is technically demanding and
requires a great deal of thorough double checking done by skilled molecular biologists.
When the scientists finished the DNA version of the complete viral genome, they used an
enzyme to make an RNA version of their DNA template.
When placed in a test tube with appropriate chemicals and protein-making enzymes,
the pieces of RNA did what they do in nature: made duplicates of themselves. This
included the required protein shells which spontaneously enclosed the viral RNA. The
researchers proved that the new viral particles were functional by showing that mice
infected with this virus developed polio and became paralyzed.
Reaction to the Publication
The publication of this research produced an instant debate among the public, other
scientists, and the federal government about the merits of this type of research, the ethics
of doing or publishing this type of research, and the ramifications it may have on public
health and bioterrorism defense.
Public reaction to this research was largely negative. The public was taken by
surprise; there had been no previous indication in the popular press that such a thing could
be remotely possible. These experiments seemed to arm terrorists with yet another tool
to use against the American people.5 Some commentators, perhaps underestimating the
technical barriers imposed by the underlying biology, suggested that this experiment could
2 S. J. Flint, L. W. Enquist, R. M. Krug, V. R. Racaniello, and A. M. Skalka. Principles of
Virology: Molecular Biology, Pathogenesis, and Control. ASM Press. Washington DC. 2000.
pp. 750-753.
3 For example, GenBank which is maintained by the National Institutes of Health.
4 G. Cook. “Researchers Build a Polio Virus, Project Highlights a New Terror Risk.” Boston
Globe. July 12, 2002. p. A1.
5 For example, see “Surfing for a Satan Bug: Why are We Making Life So Easy for Would Be
Terrorists?” New Scientist. July 20, 2002. p. 5.
easily be repeated with more dreaded diseases such as smallpox or Ebola.6 One
newspaper went so far as to mail-order some Ebola DNA claiming it to be an “Ebola kit.”7
Some scientists attacked this research on scientific and ethical grounds. Some
experts said that there was no scientific need to have done this “inflammatory”8 research,
since nearly all scientists believed that this approach would work.9 Dr. Wimmer, the
study’s director, disagreed, reportedly stating, “This approach has been talked about, but
people didn’t take it seriously. Now people have to take it seriously.”10 Dr. Donald
Kennedy, the editor of Science, argued that the public debate following the publication
justified his decision to publish this work.11 However, some may feel that the wide
dissemination of this knowledge was too high a cost for sparking a debate that could have
been started through more benign means.
Some scientists also questioned the ethics of publicizing a recipe for recreating a
disease that the World Health Organization and the United Nations Children’s Fund have
almost eliminated from nature. As the human-genome-sequencing pioneer Dr. J. Craig
Venter reportedly stated, “To make a synthetic human pathogen is irresponsible.”12
The publication of this research also drew the attention of Congress. H.Res. 514,
introduced by Rep. D. Weldon on July 26, 2002, “express[es] serious concern regarding
the publication of instructions on how to create a synthetic human polio virus.” It called
on the scientific and publishing community to adopt guidelines to avoid similar
publications in the future. It also requested that the executive branch examine all policies
including national security directives, to ensure that information that may be useful in the
development of chemical, biological, or nuclear weapons is not made accessible to
terrorists or countries of proliferation concern. This resolution, referred to the House
Science, Energy and Commerce, and Armed Services Committees, received no further
action.
Implications for Bioterrorism
Some people worry that poliovirus could be made easily by a terrorist group and used
against the United States. Most bioterrorism experts agree that this is unlikely, however,
6 For examples see G. Dyer. “Polio Lab Stunt Looks a Lot like an Ego Trip.” Newsday. August
“A Recipe For Trouble?” U.S. News and World Report. July 22, 2002.
7 G. Walsh. “Deadly Ebola Virus ‘Kit’ for Sale over Internet.” Sunday Times (London). August
8 J. Craig Venter quoted in “New Life for Polio? Scientists Synthesize a Once-feared Virus.”
Pittsburgh Post-Gazette. July 19, 2002. p. A12.
9 “Synthetic Bioterror” New York Times. July 18, 2002. p. A20; and S. Block. “A Not-so-cheap
Stunt.” Science. Vol. 297. August 2, 2002. p. 769.
10 “DNA Firm Had Warned Government Genetic Material Used to Create Polio Virus.” Boston
Globe. July 20, 2002. p A3.
11 D. Kennedy. “Response.” Science. Vol. 297. p. 770. August 2, 2002.
12 “New Life for Polio? Scientists Synthesize a Once-feared Virus.” op. cit.
because poliovirus would make a poor and ineffective weapon.13 Because childhood
polio vaccination is still required in the United States, the population is well protected
against any outbreak. Also, even without a vaccination program, poliovirus would be an
unlikely choice for terrorists, since it is weakly infective, has low mortality and morbidity,
and causes symptoms only in a low percentage of infected people.
A related concern is the use of this technique to make other more dangerous viruses.
Dr. Wimmer suggested that this same technique could be used to make other viruses with
small genomes such as HIV, hepatitis B and C, and yellow fever.14 However, it would be
easier, cheaper, and quicker to obtain these viruses from naturally occurring sources.15
One obvious exception is that it would be difficult to obtain the smallpox virus
Variola major from nature. The only two acknowledged sources are under guard, one in
Russia and the other in the United States. Therefore, making Variola major from scratch
may be easier than obtaining it from these sources. Based on the costs and length of time
required to produce poliovirus, making Variola major the exact same way would take
more than $2 million for mail-ordered DNA and about 50 years to string it together based
on current technology.16 Bioterrorists could shorten the time considerably by increasing
the number of well-trained team members, but it would still likely take many years. Also,
because the infectious mechanisms of Variola major are more complicated than those of
poliovirus, this exact technique would not work. Molecular biological methods that
would probably work for Variola major are known to some experts in the field, but these
methods are considered much more technically demanding than those used for poliovirus.
Because of these issues, most experts believe it would be much easier to make Variola
major by modifying an easily obtained and closely related virus such as camelpox.17
Although Ebola virus is theoretically available in nature, some experts believe that
it is difficult to obtain.18 Ebola’s genome is only twice the length of polio’s, but its
infectious mechanisms are as complex as those of smallpox. It may be possible to make
in the lab, but as one expert reportedly put it, “few people in the world have that skill.”19
Policy Issues
The publication of the poliovirus study has intensified the debate on how best to
13 S. Block. “A Not-so-cheap Stunt.” op. cit.
14 “Boffins Build Deadly Virus.” Belfast Telegraph. July 12, 2002.
15 “Surfing for a Satan Bug.” op. cit. and “Synthetic Bioterror.” op. cit.
16 CRS estimate based on simple extrapolation of the time and cost required to synthesize
poliovirus by Dr. Wimmer’s group. Improvements to current technology may greatly decrease
the time and cost required to manufacture a virus in this manner.
17 “Scientists Build Polio Virus– Could Terrorists Do It, Too?” Dallas Morning News. July 12,
18 This is largely based on the inability of the Japanese doomsday cult Aum Shinrikyo to acquire
it from nature despite their attempts. See David Kaplan. “Aum Shinrikyo” in Toxic Terror. Ed.
Jonathan Tucker. MIT Press. Cambridge MA. 2000. p. 213.
19 C.J. Peters in “Study: Virus Can Be Made with Ease.” Chicago Tribune. July 12, 2002. p. 10.
balance the need for openness in science with the need to protect national security.
Several approaches to strike the appropriate balance have been proposed.
One such proposal is to increase oversight of custom DNA suppliers. Ironically,
shortly before the publication of the synthetic polio report, Integrated DNA Technologies,
the suppliers of mail-ordered DNA for the study, had reportedly written to the Department
of Defense suggesting that some oversight of the industry was needed. One suggestion
was that orders should be screened for specific sequences and that suspect orders should
be investigated by some federal agency.20 However, others argue that it would be hard to
implement such a strategy. Because of the nature of DNA sequences, it may be difficult
to identify that a short sequence belongs to an individual pathogen of concern rather than
to a completely different unrelated and harmless organism.21 Some also fear that a
terrorist could easily circumvent any such regulations by splitting orders among several
companies or by making the specific red-flag-raising sequences themselves. Additional
steps, such as regulating and tracking the sale of DNA-synthesizing machinery, and
encouraging a “know thy customer” expectation for DNA suppliers may help increase the
effectiveness of increased industry oversight.22
A different approach would be to limit access to the genetic information of
pathogens of concern. However, current federal policy is to not classify basic research
information funded or held by the government, if it does not have national security
implications. The genetic sequences of pathogens has been viewed, hitherto, as falling
outside this category. Currently, the entire genomes of many potentially dangerous
viruses are accessible on the Internet. Some have suggested removing this sequence
information from these databases and not publishing future sequences of any potential
biological weapons. However, some feel that legitimate and beneficial research will be
hurt by this. For example, Dr. Paul Keim has reportedly stated that it would have been
impossible for him to develop the method that is being used to distinguish between
closely related strains of anthrax in the investigation of the anthrax mailings without open
access to the genome information.23 However, in an editorial, the journal New Scientist
responded to this fear by arguing,
“Removing the genomes of certain pathogens from public databases need not impede
any bona fide research. Legitimate labs could apply for licenses to access the
information. Even if complete control will never be possible, we could make the24
information harder to get a hold of.”
Some policymakers may feel that although removing this information now would not
recall the copies already obtained online, it would stop any future terrorists from getting
20 “Regulatory Issues: Company That Provided DNA for Man-made Polio Virus Says Oversight
Needed” Genomics & Genetics Weekly. August 9, 2002. p. 9.
21 “Deadly Ebola Virus ‘Kit’ for Sale over Internet.” op. cit.
22 Sigma-Genosys has such an informal policy already in place in that they reportedly subject
large orders sent to residential addresses to “some checks,” ibid.
23 D. Mackenzie. “Should the Genetic Sequences of Deadly Diseases Be Kept Secret?” New
Scientist. July 20, 2002 p. 77.
24 “Surfing for a Satan Bug.” op. cit.
them as easily. This approach would be more effective for the pathogens of concern that
have not yet had their sequences published.
Another approach that has drawn support of some policymakers is the development
of guidelines to prevent the publication of information that could help terrorists. The
House Committee on Science held a hearing to explore options of such policies.25 The
option generally preferred by some scientists and the publishing industry would be to have
the scientific community develop and implement a set of guidelines. The American
Society for Microbiology has adopted formal guidelines26 for the prepublication review
of papers in its journals that deal with agents deemed by the Centers for Disease Control
and Prevention “to have the potential to pose a severe threat to public health and safety.”27
Under these guidelines, peer reviewers flag manuscripts that contain details of methods
or materials that might be misused. These papers are subjected to greater scrutiny by the
editors and the Publications Board. The manuscript can be rejected if it is felt that it may
pose a threat to public safety. It should be noted however that these policies would likely
still have allowed for the publication of the polio paper, since polio is not a select agent.
Because science publishing is an international and competitive business, even if most
publishers agree to adhere to standards, others might publish the papers if they deem that
there is a market niche that they could capture by choosing not to adhere to any standards
other than scientific merit. The National Academy of Sciences plan to hold a conference
on this topic in 2003.
The Bush Administration is conferring with federal agencies and representatives
from academia and scientific publishers to examine the possibility of withholding from
the public some nonclassified but sensitive information held by federal agencies.28 The
Secretary of Health and Human Services and the Administrator of the Environmental
Protection Agency have been given original classification authority.29 Before receiving
this power, these entities did not have a mechanism for limiting distribution of any
information developed through intramural or extramural research. Some scientists say
that this type of clearly defined mechanism is preferable to a new ambiguous category like
“sensitive but unclassified.” While many scientists share the desire to limit potential
terrorists’ access to some information, some fear that implementation of new policies
might result in a tendency to not publish many important findings if there is any question
of sensitivity.30
25 House Science Committee. “Conducting Research During the War on Terrorism: Balancing
Openness and Security.” October 10, 2002. Hearing Charter and witness testimony available
at: [http://www.house.gov/science/hearings/full02/oct10/charter.htm]
26 [http://www.journals.asm.org/misc/Pathogens_and_Toxins.shtml]
27 Also known as the Select Agent List. This list is defined in 42 CFR 72.
28 “Conducting Research During the War on Terrorism.” op. cit.
29 Designation Under Executive Order 12958. Federal Register. Vol. 66. No. 239. p. 64347
December 12, 2001 and Designation Under Executive Order 12958. Federal Register. Vol. 67.
No. 90. p.31109. May 9, 2002.
30 For more information on this topic see CRS Report RL31354 Possible Impacts of Major
Counter Terrorism Security Actions on Research, Development, and Higher Education.