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Sword and Shield: The Dual Uses of Pathogen Research

What to Do About the Inextricability of Bioprotection and Bioterrorism

SOURCE: AP Photo/Pat Wellenbach

Jonathan Moreno weighs in on the wisdom of scientists publishing data from studies that create deadly viruses in his recent posting “Bird Flu Blues.” As he asserts, some of the hardest questions in the process of scientific discovery aren’t about science, but philosophy. Is it wise, from what we know now, for scientists to publish their data from experiments involving the lethal H5N1 virus without restraint?  If such restraint were imposed, would that jeopardize efforts by public health officials to prepare for pandemic flu?  Would restraint imposed in one country serve to invite other countries to “get into the game,” as we have seen in stem cell research?

Questions like these are bound to arise more often as scientific discovery and technological development proceed inexorably. “I worry about how this develops,” said California Sen. Diane Feinstein in an interview with the Washington Post. “I’m worried because of what increased technology will make it capable of doing.”

“Each step in the laboratory toward understanding what makes a pathogen tick… ratchets up the dual-use dilemma.” The knowledge can be used for protection, or aggression.

Feinstein was not talking about H5N1 experiments—about mutations created in a biosafety laboratory that allow the deadly virus to infect through the air—but about what the newspaper headlined as “an emerging global apparatus for drone killing.” Remotely piloted drones are quietly but surely changing the face of warfare. Advances in electronics, physics, optics, materials, and other fields represent the “increased technology” Sen. Feinstein alludes to, technology that is certain to evolve because it goes to the heart of national security. Thus funding will be plentiful.

Defense agency funding has flowed generously into biology for two decades and massively since 9/11 and the anthrax attacks that followed. One of the predictable consequences of the federal largess has been the rise of a national biodefense industry with its hub in Arlington, Virginia. Bioprotection against bioterror attacks is offered as the justification for the buildup. Of course, bioprotection is also advanced by microbiologists, virologists, public health agencies, and drug and vaccine manufacturers as justification for experimenting with dangerous microbes.

The problem is that each step in the laboratory toward understanding what makes a pathogen tick and what modifications would make it more robust or enable it to go airborne or evade immunity (in the event evolution consents to such modifications outside the lab) ratchets up the dual-use dilemma.  The National Science Advisory Board for Biosecurity (NSABB) defines dual-use research as “biological research with legitimate scientific purpose, the results of which may be misused to pose a biologic threat to public health and/or national security.”  Because the human immune system is our most vital biodefense shield, technology that mimics its function and discloses its vulnerabilities also ratchets up the dual-use dilemma. As we know, technology rarely stays safely at home.

When asked by the New York Times about what information should be shared from his experiments with the H5N1 virus, Dutch scientist Ron Fouchier said three types: information about the fact that the virus can be genetically modified to go airborne between mammals; information necessary to direct surveillance in the field to these mutations; and information necessary to prepare ourselves “by evaluating vaccines and antivirals.”

As we explain in a chapter of our book The Stem Cell Dilemma, technologies for “rapid vaccine assessment” do exist thanks to the Defense Advanced Research Projects Agency. DARPA banks on high risk, high reward projects. The agency that brought us the Internet, stealth technology, and global positioning system, or GPS, satellites routinely excludes from funding consideration “research that primarily results in evolutionary improvements to the existing state of practice.” In 2002, DARPA’s Defense Sciences Office launched an engineered tissue constructs program. The stated goal of the program was “to develop an interactive and functional human immune system” in the laboratory from “a common stem cell source” using tissue-engineering technologies. Such a system would be used to develop and test new vaccines rapidly in a human immune system replica rather than in mice and rats.

The program morphed into “Modular Immune In Vitro Constructs,” or MIMIC, in 2009, one of three prongs of a new DARPA program called “Blue Angel” designed to speed up the development of vaccines in response to the H1N1 pandemic. The MIMIC machine was developed by VaxDesign, Inc., an Orlando, Florida-based company established by former DARPA program manager William Warren. In 2006, Warren and members of his scientific team filed patent applications in the United States, Canada, and Europe for an “Automated artificial immune system” to test vaccines, drugs, and biologics. According to the application, “Functional equivalency to the human immune system is achieved by building engineered tissue constructs (ETCs) housed in a modular, immunobioreactor system.” The MIMIC, which is manufactured by robots, enables researchers to test the immune response to an experimental vaccine or drug developed to fight natural or engineered viruses or other pathogens. Each well in MIMIC’s 96-well plastic plate is said to represent a human immune system complete with B cells, T cells, and dendritic cells, the progeny of blood-forming stem cells.

The success of VaxDesign’s immune system-mimicking technology was borne out when the French multinational firm Sanofi Pasteur, the world’s largest vaccine manufacturer, purchased the company in 2010. VaxDesign and Sanofi scientists have filed patents claiming propriety interest in using additional immunological components, such as lymph node germinal centers, to enhance the performance of the machine. Step by step, the human immune system is being mechanized.

We write in our book: “What would it mean to capture the power of the human immune system, a system that took evolution millennia to create? The drive to disclose the secrets of the stem cell is relentless. Just as war accelerated the harnessing of the power of the atom, the prospects of bird flu as well as bioterror accelerate the application of molecular and stem cell biology for bioprotection.”

As if on cue, just before the second edition of our book was published last fall, DARPA announced a partnership with the National Institutes of Health and the U.S. Food and Drug Administration in launching its Microphysiological Systems program. The five-year $140 million program ($70 million from DARPA and $70 million from NIH) “will develop a platform that uses engineered human tissue to mimic human physiological systems” including the immune system. Human cell types found in different human physiological systems will be arranged in 3D constructs so they can “talk to each other” on a chip. Biochips equipped with embryonic stem cells, induced pluripotent stem cells, progenitor cells, or cells found in specific tissues and organs will be used to predict whether a drug or vaccine is safe and effective.  A candidate vaccine designed to be protective against Fouchier’s airborne H5N1 virus could be tested and, in theory, perfected.

Such knowledge platforms would be of incalculable value to medicine and public health. They would also be an incalculable hazard were they to fall into the wrong hands, hands capable of engineering lethal agents. With the expansion of biological knowledge around the world, these hands are proliferating, too. The complementarity of sword and shield, arrow and armor, bullet and vest, and bomb and shelter is represented today by engineered viruses and engineered immune systems. The click-click cadence of the dual-use ratchet will surely grow louder.

William Hoffman is co-author with Leo Furcht, MD of The Stem Cell Dilemma: The Scientific Breakthroughs, Ethical Concerns, Political Tensions, and Hope Surrounding Stem Cell Research (Arcade Publishing, 2011). Both are in the Department of Laboratory Medicine and Pathology, University of Minnesota.

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