Da The Scientist

Manhattan Project for Bioterrorism
What would it look like?
By Norman G. Anderson and N Leigh Anderson



A new "Manhattan Project" to combat bioterrorism has been proposed by US
Senate Majority Leader Bill Frist and many others. But what would such a
project look like? And is it a good idea? For some answers, it is worth
reviewing the history of the original Manhattan Project.

We have between us spent almost 38 years in national laboratories at Oak
Ridge, Tenn., and Argonne, Ill., which were both derived from the
Manhattan Project. The Project had a clear central objective, a decisive
test for success or failure, leadership by technically competent
hands-on scientists, access to all discoverable intellectual property,
simple direct lines of command, an absolute minimum amount of paperwork,
budgets and facilities to match requirements, overwhelming dedication to
projects and none to profit, an urgent time line, and a willingness and
capability to change directions quickly as new information required it.
No one had a company on the side, or expected to benefit personally from
his or her research and development. In the immediate postwar era, part
of this environment survived, and surprising collegiality with ideas and
data flowed with few constraints. This is now rarely the case.

The experiment of using Project laboratories for the discovery of
infectious agents and facilitating the production of vaccines against
them has been tried. In the early 1960s the National Cancer Institute,
based on the belief that many human cancers were due to viral
infections, set up a large national program to find these viruses and to
produce vaccines to protect the entire US public against cancer –
exactly what is required for biodefense now.

The result was the NIH-AEC Zonal Centrifuge Project,1 a joint project of
the National Institutes of Health and the Atomic Energy Commission. It
was based on the zonal centrifuge (which one of us [N.G.A.] had already
invented at Oak Ridge) and on the engineering talents and facilities of
the highly classified Gas Centrifuge Group of the Oak Ridge Gaseous
Diffusion Plant. We developed more than 50 centrifuge systems, including
the K-II centrifuge for vaccine purification,2 which has come into wide
use and largely accounts for the fact that influenza vaccines are pure
enough and therefore safe enough to be administered in supermarkets
without medical supervision.

This history suggests to us that a Manhattan Project type of effort is,
at least in theory, possible. Viruses are the natural focus for such a
project, as they represent the greatest risk in terms of natural and
artificial engineering, and because no broad-spectrum antivirals
analogous to antibiotics exist. Could this type of project be set up today?

The hurdles are significant. Biodefense activities are administered
through more than 26 positions, in more than 12 agencies, all appointed
by the president and confirmed by the Senate, with more than $5.5
billion spent in FY2004.3 Contrast this with the Missile Defense Agency,
which has one head, appointed by the Secretary of Defense, and an FY
2004 budget of $7.7 billion.

The current situation means that no one person or even a manageable
group of persons is conversant with the basic problems and technical
details of rapid detection and response to a new lethal infectious
agent. Also lacking are free access to the relevant technologies, and an
administrative authority with the talent and budgets now required to
provide for our defense. A new agency is needed to spearhead the
project, which would focus on three core objectives.

First, it must create and maintain the capability to detect and
completely characterize any new virus infecting humans anywhere on the
planet, and do so within days. This will require a revolution in
virology, but one that is technically within our grasp.4 Second, it must
assemble and update a comprehensive list of all human viruses (the human
"virome") and determine how each functions in causing human disease.
This provides a comprehensive foundation for understanding viral threats
and anticipating the evolving capabilities of potential viroterrorists.
Third, and most challenging, it must continuously produce and test
subunit vaccines against all known human viruses, even if they are never
used. Means must be developed for rapid scale-up of vaccine production
on timescales commensurate with a real pandemic.

Clearly the vaccine component faces immense obstacles in terms of Food
and Drug Administration approval, clinical testing, and ethical
constraints. Nevertheless, it could provide the only defense available
in a true pandemic or viroterrorist attack, reducing the detection and
response times to weeks, instead of years, and providing the US
population with biodefense in real time.

References

1. NG Anderson "The development of zonal centrifuges," Natl Canc Inst
Monogr 1966, 21: 526.
2. NG Anderson et al, "K-series centrifuges. I. Development of the K-II
continuous-sample-flow-with-banding centrifuge system for vaccine
purification." Anal Biochem 1969, 32: 460-94. [PubMed Abstract]
[Publisher Full Text]
3. A Schuler et al, "Executive positions of influence in biodefense: the
BioPlum book," Biosecur Biodefense 2004, 2: 328-41. [Publisher Full Text]
4. NG Anderson et al, "Global screening for human viral pathogens,"
Emerg Infect Dis 2003, 9: 768-74. [PubMed Abstract][Publisher Full Text]

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