Cyclins at the MBL - Early Work with Cyclins

Though cyclins were not officially discovered and named until 1982, much of cell cycle research prior to 1982 helped to inform Tim Hunt’s Nobel Prize winning experiments.

German cell biologist Theodor Boveri reported on one of the first milestones in work with the cell cycle in 1902, with his article "Über mehrpolige Mitosen als Mittel zur Analyse des Zellkerns" (On multipolar mitosis as a means to analyse the cell nucleus). In that article, Boveri discussed his work with sea urchins. In sea urchins, a fertilized egg divides into four separate cells at one time, rather than first dividing in two and then in two again. Those four sea urchin cells then grow and develop into embryos. Boveri noticed that if a single sea urchin egg is fertilized by two sperm (dispermic), it was more likely that the resulting four cells would develop into deformed embryos. When Boveri further researched why that occurred, he found that each cell requires a full set of chromosomes in order to  develop normally. In dispermic eggs, some cells only received partial chromosomes and thus could not develop normally. Boveri’s discovery marked one of the first milestones in cell division research. Knowing that cells require full chromosomes pushed later researchers to study how those chromosomes are divided and how the cell cycle occurs (Surridge, 2002).

Following Boveri’s work, several other individuals contributed to the understanding of the cell cycle and the division of genetic material that occurs during the process. In 1951, Swedish geneticist Gunnar Ostergren brought together research from many individuals to illustrate the movement of chromosomes during meiosis, when chromosomes must precisely move in order to produce cells with the correct reduced chromosome numbers (Franz, 2002). In 1953, researchers James Watson and Francis Crick described the structure of DNA, the genetic material synthesized during the cell cycle (Mitchell, 2002). That same year, Alma Howard and Stephen Pelc precisely described the process by which DNA is duplicated during the cell cycle. And five years later, in 1958, MBL scientist Matthew Meselson and Franklin Stahl described the process for DNA synthesis.

By 1960, researchers understood how certain parts of the cell cycle worked, but little was known about the control mechanisms of the cell cycle. The cell cycle has a sequential rhythm where processes start and stop rapidly apparently under the cell’s control. In 1970, Potu Rao and Robert T. Johnson published research which indicated that the sequential steps of the cell cycle were controlled by chemical signals (Nath, 2002). That same year, Lee Hartwell (who would go on to win the Nobel Prize in Physiology or Medicine with Tim Hunt) identified the genes that control the sequential steps of the cell cycle, cell division cycle or cdc genes (Patterson, 2002). The following year, Yoshio Masui and Clement Markert identified maturation promoting factor (MPF), which mediates pauses in the cell cycle (Greaves, 2002). MBL researchers would later go on to isolate MPF for further study.

By 1978, more was known about cell cycle control, however, it was still unclear what controlled the large majority of the sequential steps necessary. That is where the MBL and researcher Joan Ruderman came in.