生命科学与医学奖
2013

2013年度邵逸夫生命科学与医学奖颁予布兰戴斯大学荣休教授杰弗理・霍尔 (Jeffrey C Hall)、布兰戴斯大学生物学教授暨霍华德休斯医学研究所 (HHMI) 研究员迈克尔・罗斯巴殊 (Michael Rosbash)、及洛克菲勒大学学术事务副校长兼教授迈克尔・杨 (Michael W Young)，以表彰他们发现昼夜节律的分子机制。

所有生物都有一定的节律，人类晚间出现睡意、飞行时差带来困扰、花朵昼开夜合，这都是熟悉的现象。这些昼夜 (circadian拉丁文「日常」的意思) 的节律虽然耳熟能详，但生物时钟的本质一直是晦涩的，直至已故的西摩・本泽 (Seymour Benzer) 藉著研究果蝇，发现了一个基因，它经过变异，可以把生物时钟调快、调慢、甚至关掉。虽然这个发现本身并没有说明生物时钟如何运作，但它踏出了第一步，为硏究控制昼夜节律的机制打开了大门。今届邵逸夫生命科学与医学奖的得奖者杰弗理・霍尔、迈克尔・罗斯巴殊和迈克尔・杨，沿著这个方向展开硏究，利用基因变异果蝇，做了一系列开创性的实验，从而揭示了操控昼夜节律的分子机制。这个机制，不仅只存在於果蝇，而更加重要的是，这样的调控机制也存在於人类。

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.