生命科學與醫學獎
2013

2013年度邵逸夫生命科學與醫學獎頒予布蘭戴斯大學榮休教授傑弗理・霍爾 (Jeffrey C Hall)、布蘭戴斯大學生物學教授暨霍華德休斯醫學研究所 (HHMI) 研究員邁克爾・羅斯巴殊 (Michael Rosbash)、及洛克菲勒大學學術事務副校長兼教授邁克爾・楊 (Michael W Young)，以表彰他們發現晝夜節律的分子機制。

所有生物都有一定的節律，人類晚間出現睡意、飛行時差帶來困擾、花朵晝開夜合，這都是熟悉的現象。這些晝夜 (circadian拉丁文「日常」的意思) 的節律雖然耳熟能詳，但生物時鐘的本質一直是晦澀的，直至已故的西摩・本澤 (Seymour Benzer) 藉著研究果蠅，發現了一個基因，它經過變異，可以把生物時鐘調快、調慢、甚至關掉。雖然這個發現本身並沒有說明生物時鐘如何運作，但它踏出了第一步，為硏究控制晝夜節律的機制打開了大門。今屆邵逸夫生命科學與醫學獎的得獎者傑弗理・霍爾、邁克爾・羅斯巴殊和邁克爾・楊，沿著這個方向展開硏究，利用基因變異果蠅，做了一系列開創性的實驗，從而揭示了操控晝夜節律的分子機制。這個機制，不僅只存在於果蠅，而更加重要的是，這樣的調控機制也存在於人類。

Circadian rhythms of activity and physiology are evident across the animal kingdom as well as in plants and some bacteria. The scientific study of biological clocks goes back almost 300 years to a French astronomer called Jean-Jacques d’Ortous De Mairan, who discovered that the diurnal closing of Mimosa leaves persisted under conditions of constant darkness. Whether this was due to mysterious “magnetic rays”, or to the presence of an equally mysterious internal clock in the plant was controversial, but it later became clear that light-independent twenty-four hour clocks could also be found in animals. The mechanisms underlying such clocks were a long-standing puzzle until the Shaw Prize Laureates of 2013, Jeffrey C Hall, Michael Rosbash and Michael W Young discovered two key components of the endogenous clock mechanism of the fruit fly, Drosophila melanogaster. Over the course of the last twenty-five years, thanks to the work of these pioneers, details of the clock mechanism in animals have steadily emerged. It is a much more complicated molecular machine than any theorist had imagined.

The crucial first step for the molecular understanding of biological clocks came in 1971, when Ronald Konopka and Seymour Benzer identified three mutant strains of fruit flies that showed heritably altered circadian rhythms. Mapping the mutations revealed a single gene, Period, or Per, that could be mutated to give either shorter or longer cycles of activity, or no rhythmic activity cycles at all. Clearly, Per was intimately connected with the clock. But how the clock worked could only be a matter for speculation until the Per gene was cloned, a challenging feat that was achieved in 1984 by Michael Young at Rockefeller University and, independently, by a collaboration between Jeffrey Hall and Michael Rosbash at Brandeis University. But the deduced protein sequence of Per did not at first reveal its nature or function.