ust when you thought you'd never have to read another word about the end of the just-departed millennium, Science Watch weighs in with its customary look back at the hottest of recent research. Above are the scientists who, as of the end of 1999, had published the highest number of highly cited reports over the last two years, according to the latest update of ISI's Hot Papers Database. The following page features a table of the papers published in 1999 (excluding review articles) that received the most citations by year's end.

   For the second year in a row, John C. Reed of the Burnham Institute, La Jolla, California, tops the list of hot scientists. Reed's nine Hot Papers published over the last two years focus on various aspects of apoptosis, or programmed cell death. One of these is a 1999 report from the Journal of Cell Biology on cytochrome c and its role in the cascade of cellular events leading to apoptosis. Ranking among 1999's most-cited papers, this report is listed at #22 in the table on the following page.

   Six highly cited papers secure the next spot on the list for Charles J. Sherr, a Howard Hughes Medical Institute (HHMI) investigator based at St. Jude Children's Research Hospital in Memphis, Tennessee. His Hot Papers discuss growth-factor receptors and their role in cell signalling, particularly in respect to cellular proliferation and tumor growth. Five of these reports were coauthored by another of the featured scientists, Martine F. Roussel, who is Sherr's laboratory colleague at St. Jude.

   Another HHMI researcher, Stephen J. Elledge, based at the Baylor College of Medicine in Houston, Texas, shares the #2 spot on the list by virtue of six Hot Papers (the order of names in the second and third tiers is determined by total citations to each author's highly cited papers). Among his coauthors on five of the reports is Baylor colleague J. Wade Harper, whose name rounds out the list of hot scientists. Three of Elledge and Harper's Hot Papers on cell regulation–specifically, on the biochemical machinery of ubiquitination, a process involving cellular degradation–were published in 1999 and finished the year among the citation elite (see table, paper #5, #18, and #20).

   Atop the grouping of authors with five Hot Papers is Lewis L. Lanier of the DNAX Research Institute in Palo Alto, California. Lanier's papers discuss the white blood cells known as natural killer (NK) cells, agents of the immune system that have come under scrutiny for their role in organ rejection and other processes. The papers examine the action of NK-cell receptors and other facets of NK-cell activation.

   Two Science Watch perennials–Bert Vogelstein of HHMI, and his Johns Hopkins colleague Kenneth W. Kinzler–appear in yet another yearly roundup thanks to their coauthorship of five Hot Papers on the molecular biology of colorectal cancer and other malignancies. One of these papers, a 1998 report on the pathway of the adenomatous polyposis coli (APC) tumor-suppressor gene, is currently #9 in the Biology Top Ten and is discussed by correspondent Jeremy Cherfas within this issue.

   Another pair of colleagues completes the 1998-99 cohort of hot scientists: Tak W. Mak and Josef M. Penninger, both of the University of Toronto and the Amgen Institute, Canada. Both fielded five Hot Papers; they appear as coauthors on four. Most of these papers center on cellular pathways in apoptosis, but one 1999 report discusses a molecule known as osteoprotegerin ligand (OPGL), a member of the tumor necrosis factor family. This paper, reporting on OPGL's role in regulating lymphocyte development and other processes, appears at #14 on the year's most-cited list. And Penninger was coauthor of the 1999 paper that, with its 55 citations tallied by December, took the top spot for the year: a report on a key cell-death factor that resides within the membrane boundaries of the cellular structures known as mitochondria (see table, paper #1).