Lois R. Ember

C&EN Washington

The American humorist Will Rogers once quipped: "You can't say civilization isn't advancing. In every war they kill you in a new way."

"Crusaders' Catapult" by Gustave Doré (1833-83). [Corbis Images/Leonard de Selva]

The 20th century—ruled by chemistry and physics—raised the specter of nuclear holocaust. In the 21st century and perhaps beyond, biology will dominate. If the 20th century was "the age of the atom," the next century "will be the age of the gene," says Jonathan B. Tucker, Robert Wesson Fellow at the Hoover Institution, Stanford University, and former United Nations inspector in Iraq.

And just as weapons based on the physical sciences may eventually extend the battlefield beyond Earth into outer space, a biological arsenal could take the battlefield into inner space.

If today's alarmists are correct, conflicts in the new millennium may include exquisitely tailored and precisely targeted biological weapons wreaking havoc—if not death. Of course, they may be needlessly "hyperventilating."

At least for the foreseeable future, any rogue nation or terrorist group resorting to biological weapons (BWs) will use "off-the-shelf" disease-producing agents available through commercial culture collections or diverted from national arsenals, says Raymond A. Zilinskas, senior scientist-in-residence in the Washington, D.C., office of the Monterey Institute of International Studies and a former UN inspector in Iraq.

"There will be biological attacks within the next three to five years involving product tampering and infection of salad bars but not involving modern biotechnology," Zilinskas says. "These will cause considerable local casualties, but they won't overload the system."

Even if wayward states and terrorists acquire genetically engineered bioweapons, scientists and engineers may be clever enough to create sensors, monitors, and diagnostics that will be able to detect early and rapidly the presence of biological warfare agents in the body and in the environment. Such real-time detection could effectively discourage or disarm bioattacks.

Some of these sophisticated gizmos are now being conceived and tested in research at universities and private firms sponsored by the Defense Advanced Research Projects Agency (DARPA). The agency is, so to speak, the Pentagon's in-house think-tank for futuristic concepts and engineering geared to military needs that often find application in the civilian market. "If you know how to do it, it's too near-term for DARPA," explains Stephen S. Morse, program manager for advanced diagnostics in DARPA's Defense Science Office.

Morse [Photo by Kevin MacDermott]

In the near future, scientists may increasingly lend their expertise to the development of viable instruments of censure—such as treaties—that effectively discourage nations or terrorist groups from attempting to use these weapons of mass destruction. If effective, such instruments would reinforce the taboo against the use of disease as weapons that has existed through millennia and across cultures.

Biowarfare: Past and future

That deep-seated taboo, on which current arms-control and disarmament regimes have been built, has been breached in wars of yore. A millennium ago, combatants fouled their enemies' water supplies with animal corpses. Much later, warriors catapulted diseased bodies into towns under siege to spread infection and hasten surrender.

Fast forward to this century and witness more refined biological weapons being developed and tested by the U.K., the U.S., and the U.S.S.R. during World War II and its aftermath, the Cold War. These bioweapons were designed to be effective over large areas, and their targets were all living things: people, livestock, and crops.

"That is the past," says Julian P. Robinson, codirector of the Harvard Sussex Program at Sussex University, Brighton, England. "In the future, as our ability to modify fundamental life processes continues its accelerating advance, we will be able to find not only new ways of destroying life but also ways of manipulating life." Couple advances in biotechnology with those in nanotechnology, and infinite permutations for good and ill become imaginable.

As Robinson explains, such manipulation could involve "getting into the molecular processes of, for example, cognition, development, reproduction, even inheritance—getting into them and changing their course or their rate." If used for nefarious purposes, these advances in biotechnology offer "unprecedented opportunities for new forms of violence, coercion, repression, or subjugation," he warns. For example, harvesting the findings of the Human Genome and the Human Diversity projects could lead to the development of genetically engineered pathogens, toxins, and biomodulators as weapons targeted to specific ethnic groups.

That is the dark side of the biotechnology revolution. But advances in biotechnology and genomics also hold the promise of yielding "great benefits for medicine and for feeding the world's burgeoning population," Tucker says.

If the benefits of this new technology are to be exploited while its misuse is to be avoided, "determined and persistent efforts by politicians, diplomats, and scientists will be required," Tucker says. Scientists can help prevent a biological arms race, he says, by "promoting international cooperation in the peaceful applications of microbiology and biotechnology."

Today, an international coterie of scientists is lending its expertise to efforts to put backbone into the Biological Weapons Convention (BWC). The 1972 treaty prohibits the development, production, and stockpiling of biological weapons, but it contains no verification provisions. There is now an ongoing effort to correct that omission and to strengthen the treaty by adding a compliance-verification protocol. The effort is faltering—inhibited, some U.K. and European delegates claim, by a U.S. pharmaceutical industry fearful of losing proprietary information.

In its current form, the treaty serves the functions of asserting "the norm of abstention from BW armament," of reasserting "the taboo against resort to its actual use," and of providing "a nucleus around which international action against transgressors can crystallize," Robinson explains. Whether a reinforced treaty will enhance those functions "remains to be seen," he adds.

It certainly won't if an inspection regime is not implemented effectively "and enforced with economic and, if necessary, military sanctions," Tucker declares.

Joshua Lederberg, former president and now Raymond and Beverly Sackler Foundation Scholar at Rockefeller University and 1958 Nobel Laureate in Medicine or Physiology for his work on bacterial genetics, agrees. "Beyond the BWC, we need to strengthen the consensus for investigation by all means, not just the verification machinery, and, above all, we need meaningful enforcement against transgression." Iraq's Saddam Hussein taught us that.

Science and deterrence

In addition to lending their expertise to the development of treaties, chemists and other scientists may also help deter a biological arms race by developing such defenses against biological weapons as "broad-spectrum antimicrobial drugs," Tucker says. And they might consider the creation of "a new professional ethic—analogous to the Hippocratic oath—that forbids the misuse of human genetic information to inflict injury or death," he adds.

"Just as science and technology represent enabling factors in the creation of weapons of mass destruction, they also represent disabling factors," points out Steven M. Block, professor of biological sciences and of applied physics at Stanford University. Block is the author of "Living Nightmares: Biological Warfare Threats Enabled by Molecular Biology," a chapter in "The New Terror: Facing the Threat of Biological & Chemical Weapons," published by Hoover Institution Press.

Block

Science and technology will eventually produce sensors able to detect the presence or release of biological agents or devices that aid in forecasting, remediating, and lessening bioattacks, Block says. But, he stresses, "no technology is a panacea."

Science and technology, however, can be tools to help government officials deal with an increasingly insecure world. But it is ultimately the responsibility of politicians—theoretically the voice of the people—to use the disciplines wisely.

Science and technology will play an important if circumscribed role in preventing the misuse of biotechnology and genomics. But more important, perhaps overshadowing all other measures, is the need for an enhanced and proficient intelligence capacity, Zilinskas says. Also needed are effective, enforceable export controls on biological agents and equipment and national criminal codes that penalize abuse of the technology, Robinson adds.

Tucker also suggests the negotiation of "an international treaty that criminalizes the acquisition and possession of BW by individuals, including terrorists and heads of states." He calls for an enhanced role for the World Health Organization in the global monitoring of infectious disease outbreaks, surveillance that might deter hostile uses of disease-producing organisms. And he suggests international regulation of "germ commerce . . . to ensure that cultures of dangerous pathogens from commercial culture collections are sold only to legitimate biomedical researchers."

It is nearly impossible to halt the diffusion of technologies—such as biotechnology—that have dual uses and are rapidly evolving in the global community. But the suggestions of Zilinskas, Robinson, and Tucker offer what Graham S. Pearson, formerly at the U.K.'s defense establishment at Porton Down and now a visiting professor at the University of Bradford, West Yorkshire, calls "the web of deterrence."

Exploiting science

Still, science and technology "will continue to be at the core of the threat and of the response to weapons of mass destruction," says Amy Sands, deputy director of the Monterey Institute of International Studies' Center for Nonproliferation in California. So it becomes necessary to exploit these disciplines "to find ways to prevent and counter weapons of mass destruction," she says.

Sands [Photo by Lois Ember]

As a starting point, science and technology can foster deterrence by improving the ability to detect and identify activities surrounding the acquisition or production of these weapons and to verify arms-control agreements, Sands notes. Marshaling the resources of science and technology may also enhance the response to a threat or to the use of bioweapons and help to manage the crisis resulting from use, she adds.

The biothreat has indeed spawned technological innovation. One has to look no farther than the burgeoning developments in sensors and systems that signal the presence ofbiological warfare agents to affirm that. These new instruments are being created to protect troops on the battlefield and civilian targets of terrorists in metropolitan areas. But they probably will also be able to aid in intelligence and in eventual inspections under the BWC.

Even if they are never put to the test, such instruments clearly serve a psychological function. Knowledge of their existence may be enough to deter an enemy from using biowarfare organisms.

Most sensors and systems now on drawing boards detect biological agents in the ambient environment. Eventually, however, scientists may be adroit enough to develop "agents for blocking, inactivating, or destroying microbes and toxins once they enter the body," says Richard L. Garwin, Philip D. Reed Senior Fellow for Science & Technology at the Council on Foreign Relations, New York City, and IBM Fellow Emeritus at the Thomas J. Watson Research Center, Yorktown Heights, N.Y. Such agents "would be a major advance in public health," he adds, "and would help to limit casualties from biological weapons attack and bioterrorism."

Many of the sensors to survey the environment and some of the diagnostics to scan the human body are based on sensitive techniques similar to those now being used in laboratories—polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays (ELISA)—to amplify DNA or protein signals. "In most cases," Stanford's Block says, "the challenge is not merely to make the sensor smaller, cheaper, and easier to use, but also to make it far more robust." To not "cry wolf," is how he explains it.

Near-term developments for battlefield detection of BW agents include "a standoff laser system capable of detecting a BW aerosol cloud at a distance of several kilometers," Tucker says. Tucker also mentions "near real-time point detectors that would provide sufficient advance warning of a BW attack so that troops could put on protective gear before they are exposed." These detectors are based on monoclonal antibody and gene-probe-array technologies.

Pie-in-the-sky research

For futuristic developments, the Pentagon turns to DARPA. The agency's mission is to take on those farsighted R&D projects that are or may be too high risk for the armed services to tackle yet offer the potential for high payoff. Such results often include civilian spin-offs, but those are bonuses. DARPA's focus is on the Pentagon's needs.

The fairly recent biological warfare defense program within DARPA's Defense Science and Special Projects Offices is responsible for developing the sensors and advanced diagnostics needed to spare life in a disease-contaminated environment. "If sensors could detect the presence of a biological agent during the release event, many lives could be saved," explains Mildred Donlon, program manager for environmental sensors. "If such sensors could be developed—sensors that have sensitivity similar to existing smoke detectors—mass violence could be thwarted in the 21st century."

The charge to Donlon's group is to develop a rugged, lightweight sensor capable of detecting a multitude of biological and chemical agents very rapidly and with high sensitivity and accuracy. And, if these criteria aren't daunting enough, another is added: low cost. "It is a long road ahead" to create such a widget, Donlon says.

DARPA is taking a systems approach to meet the criteria of detecting diverse materials—existing and emerging chemical agents, bioregulators, toxins, and existing and emerging microbes—with speed, sensitivity, and specificity. The agency is underwriting the development of a miniaturized time-of-flight mass spectrometer (MS) system for broadband detection of chemical and biochemical agents. The MS project team is led by Johns Hopkins University's Applied Physics Lab (APL) in Laurel, Md. To detect specific microbes, DARPA is funding the development of a handheld multiplexed upconverting phosphor flow cytometer and lateral flow devices at SRI International, Menlo Park, Calif., along with RNA chip technology at the Department of Energy's Argonne National Laboratory in Illinois.

"Rind" by M. C. Escher [© 1999 Cordon Art B.V., Baarn, The Netherlands.
All rights reserved]

The APL MS system is designed for automated environmental detection and works for chemical and biochemical materials. By utilizing databases of spectral information being developed at the University of Maryland, College Park, and at other university and government sites, the MS is proving itself useful for the initial classification of viruses, bacteria, and toxins.

The MS system can measure biochemical tags characteristic of broad classes of pathogens and other markers—such as proteins—characteristic of specific bacteria and viruses. But it can't yet measure what Donlon terms the "absolutely characteristic biomarker"—the long DNA and RNA chains of bacteria and viruses. DARPA, therefore, is funding approaches that chemically or enzymatically produce oligonucleotides for direct fingerprinting of these microorganisms.

Although improving steadily, MS technology is not yet able to definitively identify microorganisms down to the strain level. Therefore, Donlon explains, DARPA is funding the development of enhanced flow cytometers with upconverting phosphor reporters, and RNA chip technology with fluorescent and—in the future—MS readout.

SRI International is developing reporter materials based on mixed rare-earth oxides that exhibit efficient near-infrared two-photon absorption followed by visible-light fluorescent emission. Small, lightweight, and cheap semiconductor lasers supply the near-infrared light that is absorbed by the oxides serving as reporter molecules, or probes. Because the upconverting phosphor probes can be excited by these small lasers, the whole system can be miniaturized and sent into the field. The key now is to develop highly specific and reliable probes for identifying discrete microorganisms.

The RNA chip technology now under development at Argonne in collaboration with several universities uses a three-dimensional gel-pad chip and ribosomal RNA (rRNA) as the target moiety. Because rRNA is so prevalent within cells, there is no need for signal amplification using PCR methods. The gel pads act as tiny test tubes for annealing the complementary probes—selected regions of the 16S and 23S rRNA—and the rRNA oligonucleotides of the cells of interest. The chip, as designed, is able to distinguish organisms that may differ by a single base pair.

Donlon's program is geared to detecting pathogens in the environment. Another DARPA program, managed by Stephen S. Morse, is developing advanced diagnostics to detect natural and modified disease microorganisms in the body. These diagnostics are grounded in biology but need to be suitable for integration into engineered systems.

As Morse notes, a good defense is one that is equally effective against a natural but unanticipated disease outbreak as well as a terrorist event. And he reminds us, "Nature is the ultimate terrorist," a much better innovator to date than humans, and "is likely to remain so for the foreseeable future." Whether natural or bioengineered, medical consequences follow exposure to pathogens.

With many pathogenic threat agents, it is often too late to save exposed individuals once telltale but nonspecific symptoms appear. And in the event of an attack, medical personnel and drugs are likely to be strained. It becomes necessary to rapidly identify and treat those who have been exposed before they exhibit flulike symptoms and to reassure the "worried well"—those who have not been exposed but fear that they might have been. Developing tools to do both is the charge of Morse's program.

"The rapid and sensitive identification of the pathogen or its components or products is the traditional and essential focus of diagnostics," Morse explains. But, he notes, "host responses may provide important clues, especially in the early stages when it may be virtually impossible to detect the pathogen in the body. Even if we can't detect the pathogen, we may be able to detect its footprints" in the release of cytokines or nitric oxide, for example.

Knowing these footprints would be valuable not only for pinpointing exposure but also for monitoring therapy. Such knowledge might also lead to a better understanding of the disease process.

The development of sensitive probes for the rapid identification of threat agents—especially novel or bioengineered agents—is a rate-limiting step, as is sampling, Morse points out. The goal is noninvasive or easy-to-take samples that need no processing and can be obtained rapidly.

EG&G, now called PerkinElmer, is developing a portable analyzer for rapid fluorescent detection of antibodies to threat agents. The company is leveraging its commercially available time-resolved-fluorescence instrument found in some research and clinical labs. These devices use rare-earth elements as fluors to alter the fluorescence lifetimes, which means that the background is lower.

For military use, PerkinElmer "is expanding the portfolio of assays to include the biothreat agents and markers of concern to us," Morse says. The company is now miniaturizing and automating the process and should, in a year or two, be able to demonstrate its value for identifying a multitude of agents, Morse says.

Just as sampling is a problem, reagents are another rate-limiting step. Researchers led by George Georgiou at the University of Texas, Austin, and elsewhere are devising ways to rapidly generate antibody mimics as diagnostic reagents to pathogens isolated from the environment or from a biopsy. These researchers have constructed ways of making Escherichia coli bacteria express artificially a library of antibodies to threat agents. The antibodies are then separated by flow cytometry and cloned to produce specific reagents capable of identifying newly isolated pathogens.

By tethering a ligand (an antibody or nucleotide) to the common antibiotic gramicidin, researchers at the Australian Membrane & Biotechnology Research Institute, Sydney, have developed an artificial pore in a synthetic lipid bilayer membrane that switches on and off in response to the presence of a threat agent. Once fully developed, the system will be a robust and sensitive biosensor able to detect low concentrations of a threat agent, Morse says. The group is now working on increasing the sensor's specificity and sensitivity to be able to detect single-bacterium binding events.

Although the Australian system detects the pathogen, a system being studied in Maine detects a host response: nitric oxide release. The level of NO is relatively stable in individuals and rises very early and substantially in infection. "The caveat," Morse says, "is that baseline levels of NO vary from person to person." The question then is, How universally applicable will an NO monitor be?

"Nitric oxide is a major mediator of a number of biological processes," Morse says. Monitoring exhaled NO may be useful as an early and specific marker of exposure to pathogens, but a lot of basic biology has to be worked out before it will prove valuable. Researchers at the University of Maine and its partner, Sensor Research & Development Corp., both in Orono, in collaboration with the Maine Medical Center, Portland, have some preliminary NO data from healthy fifth-graders and from hospital emergency-room patients with respiratory infections. They are expanding their clinical protocols to follow the time course of NO's rise in specific infections.

The researchers are measuring NO with a commercial chemiluminescent NO analyzer and a prototype lightweight, pager-size sensor developed at the university. A portable NO monitor "will be developed and tested in the next few years," Morse says.

"Reading the body's signals—and understanding their importance—is an exciting area of research that is likely to prove especially fruitful over the next decade," Morse says.

The Monterey Institute's Zilinskas agrees. "The improved technologies that DARPA is working on will elevate the level of our public health system to detect and identify all infectious agents," he says.

"The major benefit is that we will be able to respond to infectious diseases caused by emerging pathogens like the human immunodeficiency virus in 1981, and transmitted pathogens—like the West Nile virus in New York this summer," Zilinskas says. "And by doing so, our ability to respond in a timely manner to terrorist activities with biological agents will also be enhanced."

Prevailing doomsday scenarios notwithstanding, Sands also remains optimistic about science's contributions. She believes "significant progress" will be "made in our technical abilities to collect and analyze intelligence, to detect and identify materials, to monitor significant activities remotely and nonintrusively for arms-control agreements, to evaluate and communicate enormous quantities of information, and to develop new weapons systems and strategies needed in today's fluid and evolving environment."

Despite the technical thrusts enumerated by Sands, Allison C. de Cerreño, director of the Science & Technology Policy Program at the New York Academy of Sciences and coauthor of "Scientific Cooperation, State Conflict: The Roles of Scientists in Mitigating International Discord," takes a more cautious position. "The ability of science and technology to prevent [an] attack will be limited," she believes, because biological weapons attacks in the future are more likely to be directed at the general population rather than at soldiers on a battlefield. Scientists, she explains, may be able to develop early warning systems, but it will "be very difficult to prevent" a determined nation or terrorist organization from using "such weapons against a populace."

C. de Cerreño also believes the role of scientists will be "somewhat limited" in lessening damages or preventing deaths after an attack because of other sociological factors. She cites the example of developing a vaccine against anthrax but the economically and politically infeasible inoculation of the entire U.S. population to protect against a possible attack. "Thus, political and economic factors have an impact on how much science and technology can help in dealing with the aftermath of such an attack," she concludes.

C. de Cerreño [Photo by Jane Hoffer]

But scientists can perform a vital function by "explaining to politicians and policymakers how new advancements in their particular field of science could be used for mass violence," says Marie Chevrier, associate professor of political economy at the University of Texas, Dallas. "Equally," she adds, "scientists also have a responsibility to acknowledge how complicated and difficult it would be to successfully harness their science for mass violence in a single or very few tries."

The venues for scientists to ply their advice have been vitiated over the past five years, however. Congress abolished the Office of Technology Assessment and, because of budget cuts, the State Department chose to reduce the number of scientists on its own payroll. IBM's Garwin believes that the White House Office of Science & Technology Policy could fill in the gaps. OSTP, he says, "should help to identify a focus in the government" that could "help to provide assessments of options and programs in the national interest."

Garwin thinks scientists in the State Department—those few remaining—"should provide an interface with the rest of the scientific community and the government to identify threats and to quantify the potential responses." He also thinks State Department scientists could "interact with other countries to spread protection against biological warfare and bioterrorism."

Better science advice today might have helped to put into clearer perspective the likelihood of a bioterrorism attack, especially one using supertoxic, genetically engineered organisms. Right now, U.S. policy is based on the premise of when, not if. But Chevrier points out that "translating many scientific applications for mass violence would entail combining expertise from several scientific disciplines that do not ordinarily work together."

The Japanese cult Aum Shinrikyo proves Chevrier's point. The cult had the resources to buy any expertise it needed. It apparently acquired microbiologists knowledgeable in production techniques but no one with knowledge of the aerial dispersal of stabilized biological agents. Thus, try as it might—and the cult tried at least 10 times in 1995—it could never deliver a viable agent that maimed or killed. Dispersal information is a closely held secret of the U.S. and Russia.

Chevrier

Hammering out a protocol

One objective of a strengthened BWC is to make it very difficult for a country to assemble the people, equipment, and other resources needed to develop a clandestine biological weapons program that could, if deployed, kill large numbers of people, Chevrier explains. And even if such a program could be assembled, keeping it secret would most likely be more difficult in the 21st century because of potential advances in communications and detection technology.

A strengthened treaty won't by itself prevent the use of biological weapons. But, asks Malcolm Dando, professor of international security at England's University of Bradford, "what would be the consequence of not strengthening the BWC at this time, or of accepting a worthless protocol of the type advocated by the U.S. pharmaceutical industry?"

Dando believes it would send the wrong message—that prohibition is not important—"at just the time when the genomics revolution is bound to spread increasing dual-use capabilities around the world." He is codirector of a project on strengthening the BWC, spearheaded from the University of Bradford.

Barbara H. Rosenberg, professor of the natural sciences at the State University of New York, Purchase, echoes Dando's sentiments. "Establishment and maintenance of international norms are very important. The BWC established such a norm," she says.

Rosenberg

The treaty, Rosenberg says, raises the cost to a nation or group wanting to acquire and use biological weapons. But if countries now negotiating a compliance-verification protocol to the treaty—the so-called Ad Hoc Group meeting in Geneva—"don't demonstrate a willingness to give it teeth, now that they have the opportunity to do so, that will amount to a show of no confidence in the norm."

The Pharmaceutical Research & Manufacturers of America (PhRMA), representing major U.S. drug and biotechnology firms, supports the treaty but objects to a protocol including routine (nonchallenge) inspections by foreign delegations without cause. PhRMA fears loss of proprietary trade secrets.

"We're willing to submit declarations. We have agreed to challenge inspections and to a clarification process—but not to visits—if something is wrong with the declarations," explains Sara L. Radcliffe, manager of biologistics and biotechnology at PhRMA. "But we have objected most strongly to nonchallenge [routine] visits to our facilities with no evidence of violation of the treaty provisions."

Assuming a protocol can be hammered out in Geneva and ratified by a sufficient number of nations, then Pearson's web of deterrence can be centered on the fortified treaty. And science and technology can contribute to helping prevent mass violence in the 21st century by making early detection of a BW attack more likely and, therefore, less attractive to military forces, Dando says.

In addition, improved global epidemiological surveillance will make covert use of bioweapons more difficult and less likely. And "improved protection and therapy will reduce the salience of BW to military forces, and ideas of BW use will be less likely to trickle down to terrorists," Dando contends.

The challenge to science

But the genomics revolution marches on, unchecked by law or politics. Dando believes that advances in biotechnology and genomics ultimately "will have to be controlled by the development of law—international first and then implemented as necessary in national law."

Like every major technology of this millennium, biotechnology is a double-edged sword. In the past, technologies like electronics, metallurgy, and nuclear power have been exploited for peaceful and, eventually, for hostile purposes. Will biotechnology escape this historic trend? Robinson wonders.

The Greek historian Thucydides asked, How are we "to divine the unseen future that lies hidden in the present?" William A. Haseltine, chairman and CEO of Human Genome Sciences, Rockville, Md., thinks biotechnology may find a way.

Haseltine believes that understanding the genomes of infectious disease organisms and of humans "offers many more opportunities to prevent and effectively treat biological attacks than it does to create new means to mount such attacks." He argues that "prior to systematic genome analysis, the impact of biotechnology favored offense, specifically creating new antigenic variants to evade vaccines and organisms resistant to antibodies." But, he continues, "with the advent of systematic genomics, the tide has now changed."

Haseltine

Newfound knowledge is helping "to design broad-spectrum antibacterial drugs, vaccines that are species- rather than strain-specific, and potent new means of enhancing natural protective responses to invading microorganisms," Haseltine explains. Combined, these advances should offer protection to humans from bioweapon attacks.

The impact in medicine of the genomic discoveries is not yet apparent, but it will be felt in the new millennium. "I'm hopeful that our ability to defend ourselves against such attacks will outstrip anyone's ability to create new, more deadly organisms," Haseltine says.

A world of rapid technological advances, integrated global markets, and weakened nation-states makes for less security. And in a less secure world, the distinction between national defense and domestic security is likely to be blurred, maybe even obliterated. The first century of the next millennium may see socioeconomic and political changes unimaginable today. The convergence of forces and the rapid pace of change will only increase the challenges to science and technology in the realm of national security.

[Medical Frontiers][Providing Clean Water]

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