larly broad-spectrum agents, seems even more distant. These deficiencies are critical, as the chances for use of a multi-drug-resistant recombinant organism in future attacks is high. Here again, the deciphering of the genomes of major pathogens and the analysis of their function by the new field of bioinformatics will reveal new potential drug targets—most notably, targets that are present only in bacteria or viruses and not in human cells (such that broad-spectrum drugs can be developed that are likely to have few adverse effects on the human host).

The need has never been greater for research, in both the public and private sectors, aimed at development of novel antimicrobials. However, recent analysis indicates that most, if not all, major pharmaceutical companies have over the past 3 to 5 years decreased their investments in drug discovery related to antibiotics, and few are exploring antiviral agents. These changes have resulted from higher regulatory hurdles, competing priorities, and a shrinking market. Thus, new classes of antimicrobials will not emerge in the next decade without a major strategic shift.

Bioterrorism attacks might not be restricted to the dissemination of known pathogens. Variants that have been engineered by current molecular-biology-based methods to alter or mask surface antigens—so as to avoid detection by the immune system—could also be used in such attacks. The following question arises: How quickly and by what means could a new vaccine be developed and deployed to protect against a novel pathogen?

Before that need is upon us, we should act now to tackle several challenges to overcome the critical shortfall of research in vaccinology:

• The genome sequences of all plausible organisms that could potentially be used in a bioterrorism attack, including naturally occurring variants, need to be determined. This information will greatly facilitate the identification of any engineered variations in a weaponized strain.

• DNA-based vaccines (including vaccines that use defective viruses as carriers) should be more fully investigated for human application, as their use represents a potential quick path from determination of the genome sequence to the availability of a vaccine. Recombinant human antibody technologies should be explored, including novel delivery systems.

• Recombinant protein expression provides another pathway for the development of relevant antigens, but more research is needed to determine ways to make recombinant proteins as effective as immunogens.

• More effective adjuvants are needed.

• The development of vaccines against toxins, as opposed to pathogenic organisms, should also be explored.