Vogelstein
Ihle
Schlessinger
Witthuhn
Pericak-Vance
Roses
Kinzler
Saunders
Strittmatter
| Editor's Note: Since 1993, the newsletter Science Watch has
ranked the year's most cited scientists and research papers. Based on records
compiled by the Philadelphia-based Institute for Scientific Information
(ISI), analysts prepared such rosters for 1994. Researchers
are ranked by their number of "hot papers." An article is considered "hot"
if it has garnered a substantially greater number of citations, within
a two-year period, than other papers in similar disciplines. For
instance, the 1994 ranking was based on the period between November 1992
and December 1994. In each of the last two years, Bert Vogelstein, a molecular
biologist from Johns Hopkins University, has accumulated more "hot papers"
than any other researcher (The Scientist, May 2, 1994, p[age 14).
Another list notes the most cited papers published in 1994, based on the
number of ciations each received in the same year.
The February 1995 kScience Watch article in which these listings appear is reprinted here with permission of the newsletter and ISI. |
Vogelstein and collaborators authored nine hot papers describing the p53 tumor-suppressor gene or other genetic alterations underlying tumorigenesis. Two were published in 1994 and scored enough citations to be included with the current listing of the year's hottest articles (see table below): paper No. 4, on the isolation of the hMLH1 gene, which plays a role in a high percentage of hereditary colon cancer cases; and paper No. 23 (not shown), which examines the interaction between p53 and the tumor suppressor WAF/CIP1.
But this year the Vogelstein team has company. In fact, two groups emerged strikingly. The first--from St. Jude Children's Research Hospital in Memphis--placed three members into the hot spotlight: James N. Ihle and Olli Silvennoinen, who share the top spot with Vogelstein, and their coauthor Bruce A. Witthuhn, who came in second. In the last two years this group has helped produce nine high-impact papers, all dealing with the Jak-Tyk family of cytoplasmic tyrosine kinases. One 1994 paper from this group--published in collaboration with researchers at Regeneron Pharmaceuticals in Tarrytown, N.Y., and INSERM in Paris--grabbed the No. 2 position.
The other hot team that came to the forefront is from Duke University. Over the last two years, members of this group have contributed to several highly cited papers on genetic defects associated with Alzheimer's disease and amyotrophic lateral sclerosis (ALS). One of these papers, a report on mutations in the Cu/Zn superoxide dismutase gene in familial ALS (D.R. Rosen et al., Nature, 362:59-62, 1993) was the most- cited paper of 1993 (The Scientist, April 4, 1994, page 15). Margaret A. Pericak-Vance coauthored that report and seven others in the ranking of hot scientists, giving her the top spot among the Duke researchers.
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Vogelstein |
Ihle |
Schlessinger |
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Witthuhn |
Pericak-Vance |
Roses |
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Kinzler |
Saunders |
Strittmatter |
Two researchers from the Bristol-Myers Squibb Pharmaceutical Research Institute in Seattle--Peter S. Linsley and Jeffrey A. Ledbetter--collaborated on five hot papers on T-cell action. Both also contributed separately to one other highly cited paper, giving them a total of six each. Finally, Tadamitsu Kishimoto of Osaka University, Japan--the only non-United States-based researcher on the list--contributed to six papers on gp130, interleukin-6, and other aspects of cytokine signal transduction. One of these reports, published in Science in early 1994, placed at No. 3 in 1994's list of most-cited papers.
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Citations, of course, take time to accumulate, a fact that confers an obvious advantage to papers published early in the year. Nevertheless, 1994's overall citation champ--paper No. 1, a Science report on the identification of the protein p16-- got off to a notably fast start, appearing in mid-April. The paper provides evidence that p16, which is involved in the control of the cell cycle, is a tumor-suppressor gene.
The p16 protein inhibits an enzyme called cyclin-dependent kinase 4 (Cdk4), one of several cyclin-dependent kinases (Cdks) that play a role in transitions between phases of the cell cycle. Other papers among 1994's most-cited dealt with Cdks and the emerging link between cell-cycle control and cancer genes. Paper No. 5, for example, describes deletions of the Cdk4 gene that are involved in melanomas, gliomas, lung cancers, and leukemias. The authors conclude that the Cdk4 inhibitor is a strong candidate for the melanoma- susceptibility gene.
Cdks are also central to paper No. 7, which discusses the identification of a Cdk inhibitor called p27kip1. This inhibitor, the authors speculate, may enforce order during the G1 phase of the cell cycle.
Other aspects of gene defects and cancer figure prominently among the top 10 of 1994's most-cited papers. Vogelstein, Kinzler, and their colleagues, who report the identification of the hMLH1 gene in paper No. 4, represent one of two notable teams pursuing genetic mutations involved in hereditary non- polyposis colon cancer. The other team, led by Richard Kolodner of the Dana-Farber Cancer Institute, isolated the hMLH1 gene and published their results simultaneously in Nature. The Kolodner report also garnered ample notice, winding up at No. 6.
Paper No. 8 continues the thread of a very busy field that Science Watch tagged as one of 1993's hottest topics: SH3 domains, protein modules that are found in many intracellular signaling proteins. This article describes the structure of a specific SH3 domain along with one of its binding ligands and offers a general model of SH3-ligand interactions.
In paper No. 9, a team of Japanese researchers describes a trinucleotide repeat in hereditary dentatorubral- pallidoluysian atrophy (DRPLA), a neurological disorder characterized by combinations of epilepsy, cerebellar ataxia, and dementia. The authors observe that since DRPLA shares many clinical and genetic features with Huntington's disease and spinocerebellar ataxia 1 disorders--two ailments that also involve an unstable expansion of trinucleotide repeats--the mechanism of neuronal degeneration may be similar in all three diseases.
Rounding out the 1994 list is paper No. 10, which describes an expression screen method used to isolate three cDNA inhibitors of DNA synthesis from senescent cells. As the authors observe, the role of these inhibitors in senescence has yet to be determined. However, they conclude, it should be possible to apply this method to clone other negative regulatory genes, such as those involved in tissue-specific differentiation and tumor suppression.
Although Science Watch eliminated reviews from the year-end tally, a few related reviews did attract significant attention in 1994. In particular, three reviews on immune-system signaling, which appear in the same volume of Cell (76, 1994), each accumulated nearly 50 citations. These reviews covered cytokine signal transduction (T. Kishimoto et al., pp. 253- 62), signal transduction by lymphocyte antigen receptors (A. Weiss et al., pp. 353-62), and traffic signals for lymphocyte recirculation and leukocyte emigration (T.A. Springer, pp. 301-14).