personal digital cyberarian regularly assures me that my own branch densities are as respectable as those of my elderly peers. So science has survived and thrived. It is different now. Its practi- tioners are different. It is cheaper, faster, and more open to more people. It has become a dynamic enterprise linking the physical world, the virtual world, and the world of human imagination in ways that were only dimly perceived at the end of the last century. Now at midcentury, we are faced with the rise of powerful artifi- cial intelligence systems. These systems not only make possible much of our speculative scientific work, but some are beginning to formulate hypotheses of their own. The next 50 years for science and for the AAAS are likely to be spent making room within in silico re- search for in silico researchers. I happily leave that emotional and evolutionary challenge to you. Thank you and good afternoon. The author, a Maryland-based microbiologist who has abandoned the lab for the Internet, wonders whether H. G. Wells was right in asserting that "we are inclined to underestimate the certainties of the future." E. McSweegan, 1692 Barrister Court, Crofton, MD 21 114-2602, USA. E-mail: edwardmc@qis.net This essay is a wovlc offiction. Names, chavactevs, places, and incidents either ave the pvodzict of the azdthov k imagination ov ave used fictitiously. Any vesemblance to actual pevsons, living ov dead, events, or locales is entirely coincidental. Traditional and Cybernetic Sciences Combine t o Combat Human Viruses by CAURNEL MORGAN Two researchers from different labora- tories, with different scientific ap- proaches, and from different eras are trying to demonstrate the strength of diuersity in combating human disease. Robert Jackson is a 108-year-old scientist with an M.D. in psychia- try and a Ph.D. in virology from the American Mental Health Re- search Institute (AMHRI). Dara Olu, of the American Biological Research Institute (ABRI), is a 23-year-old who has earned a Ph.D. in the emerging field of pixel biology from the ABRI, with an area of specialization in pixel genomics. She also has degrees in business and politics. Whereas Jackson runs a traditional brick-and-mortar laboratory at the AMHRI, Olu directs her independent laboratory in cyberspace. Together, Drs. Jackson and Olu head a team of scientists that is applying a novel approach to the treatment of viral infections. A number of viruses have been successful in attacking humans because of their capacity for rapid mutation. The eradication of virus- es that caused certain cancers, acquired immunodeficiency syndrome (AIDS), and other diseases were complicated by the viruses' ability to mutate in a relatively brief period of time after infecting humans. In the 20th century, the standard approach to studying human viruses was to isolate a viral culprit after an epidemic had occurred. When this approach was used, some viruses were well on the way to their second or third generation of mutations before effective therapeutics could be designed. However, the fight against viral infections was dramatically altered from the last decade of the 20th century into the first two decades of the 21st century. During this period a number of DNA analogs with nonphosphodiester backbones were developed. These various forms of engineered nucleic acid (ENA) were used very effectively as antiviral agents (Jackson 20 13). Dr. Jackson pioneered the use of ENA antiviral technology. A number of DNA derivatives were designed in which the phosphodi- ester linkage has been replaced but the deoxyribose retained. How- ever, only a few of these appear to be good structural DNA mimics. The first two successful attempts to replace the entire deoxyribose ~hos~hate backbone resulted in mor~holino derivatives and the L L polyamide nucleic acid (PNA), which contains a pseudopeptide backbone (for review, see Jackson 2007). These designs determined that the deoxyribose backbone is not essential for DNA mimics. ENAs have been demonstrated to form double and triple helices with themselves and natural nucleic acids (that is, DNA and RNA). The antiviral property lies in the ability of the ENA to bind to viral nucleic acid in a sequence-specific manner. This approach permit- ted Jackson and other virologists to target mutant forms of viruses as soon as their nucleic acid sequences could be determined (Jack- son 2009). Today, a large variety of engineered nucleic acid (ENA) is used to form sequence-specific double and triple helices with viral nucleic acid. Once formed these complexes can halt the ability of the viral genes to serve as templates that direct the host cells to make viral pro- teins. One obstacle to applying ENA as an antiviral agent in vivo is that ENA entry into host cells typically occurs at a slow rate under normal conditions. However. the inclusion of a nuclear localization seauence (NLS) can dramatically increase the rate of sequence-specific ENA en- try into cell nuclei. NLS-mediated ENA uptake occurs several times more efficiently than with ENA alone. Additionally, destruction of the 2464 24 DECEMBER 1999 VOL 286 SCIENCE www.sciencemag.org