I should start by saying that I have other Arabidopsis papers cited about the same number of times (E.S. Coen and E.M. Meyerowitz, "The war of the whorls—genetic interactions controlling flower development," Nature 353[6339]:31-7, 5 Sept. 1991 and M.F. Yanofsky, et al., "The protein encoded by the Arabidopsis homeotic gene agamous resembles transcription factors," Nature 346[6279]:35-9, 5 July 1990). So the answer to why the Science paper is highly cited should derive from a consideration of all of these papers—what they have in common that seems to have struck a chord.

The Science paper (and the others) reports a surprising discovery that began to answer a long-standing set of questions in plant biology, and that has led to additional work in many laboratories. And, they were published enough years ago that there has been time for a substantial number of citations to accumulate. In the case of the Science paper, the long-standing general question was, "how do plant hormones work?" Much of the work in plant physiology from the 1920s on was directed to discovering plant hormones or growth substances, and to trying to find their mode of action. This Science paper reported the first molecular cloning of a plant hormone receptor, the receptor for the gaseous hormone ethylene. Ethylene is made in plants when they experience stress, and also in some plants when fruits mature and when organs (especially in flowers) senesce. The plant responds to its own ethylene by changing its cellular activities; the changes depend on the cell type and the developmental stage. This paper reported that the receptor for ethylene is a relative of the bacterial two-component chemotaxis receptors, and further, showed the early evidence that the receptor acts negatively—when it binds ethylene, the protein does nothing; when not bound by ethylene it represses the ethylene responses. This surprising sort of negative action may also characterize the action of other plant hormones, such as gibberellins, but the receptors for this hormone class have not yet been identified.

The identification of the protein class that served as ethylene receptors allowed a large number of specific experiments in our lab and others, which have led to a reasonable (though still incomplete) view of ethylene action. Proteins related to the ethylene receptors (there are five ethylene receptors in Arabidopsis) have been shown to be receptors for cytokinins, another class of previously mysterious plant hormones. One practical aspect of our work is the ability to control ethylene perception by plants, and therefore to control processes such as flower senescence (see Wilkinson et al. Nature Biotech. 15: 444, 1997).

One additional consideration that relates to this work is the history of the discovery of ethylene as a plant hormone; Neljubov reported its effects in the 19th century. The 1998 Nobel Prize for Medicine and Physiology was given for the discovery that the gas nitric oxide is an animal hormone: in the words of the Nobel press release "Signal transmission by a gas, produced by one cell, which penetrates membranes and regulates the function of other cells is an entirely new principle for signalling in the human organism." Those of us who work on plants did not find this to be a new principle, as the award was near the 100th anniversary of Neljubov's very well-known paper.

  What were the circumstances that led you to do this research?

The circumstances are a good example of the pleasures of the Arabidopsis field, in which the norm of behavior is sharing and collaboration. Tony Bleecker, a graduate student in Hans Kende's lab at Michigan State, had isolated a mutation that dominantly prevented ethylene response, and hypothesized that the mutation was in the ethylene receptor. My lab at the time (1980s) was establishing the basic molecular genetics of Arabidopsis, including RFLP genetic maps and methods for gene cloning. Hans told me that Tony would be coming to my lab as a postdoc, to clone the gene, and of course I agreed. Tony came and started the chromosome walk, and was joined in it by Caren Chang, who as a graduate student in my lab had established the RFLP map and had first cloned and sequenced an Arabidopsis gene, and was in my lab again as a postdoc at the time. Caren and Tony cloned the gene (Caren did it after Tony had left to start his own lab at Wisconsin; Shing Kwok, the other author on the paper, was a technician in the lab who then went on to graduate school at Yale and now works for a biotech company). Tony and Caren are now tenured professors, at the University of Wisconsin and the University of Maryland, respectively, and both still work on ethylene. We don't work on it any longer in my lab—after this work, the cloning of the five receptors, and a paper by my graduate student Jian Hua (Hua et al Cell 94: 261, 1998—Jian is an assistant professor at Cornell now) proving that the receptors worked negatively, I was happy to leave the work to Caren and Tony, and their students.

I should add one more historical aspect—as part of the ethylene receptor cloning, Tony and Caren found a gene that was not the receptor, but which had an interesting structure—it was a leucine-rich repeat transmembrane receptor serine-threonine kinase called TMK1 (Chang et al., Plant Cell 4:1263, 1992). This was the first member of what turned out to be the major group of cell-cell signaling molecules in plants; later members included the rice disease resistance gene Xa21, the brassinosteroid hormone receptor, and many others. History may be repeating itself in relation to animal work, in this instance as for the ethylene receptors - a recent Science paper (Manning et al. Science 298:1912, 2002) on the human genomic complement of kinases included the quote "some unpredicted domains are found, such as the previously unpublished leucine-rich repeat (LRRK) family..."

Elliot Meyerowitz
California Institute of Technology
Pasadena, California, USA