Basic Medical Research Award
I thank the Lasker Foundation and the jury for this enormous honor, which goes on beyond anything I could ever have imagined. There's a wonderful comment of Sir Isaac Newton that I think reflects my life in science: "I know not what I may appear to the world, but to myself I seem to have been only like a boy playing on the sea-shore, and diverting myself in now and then finding a smoother pebble or a prettier shell than ordinary, whilst the great ocean of truth lay all undiscovered before me." I feel ever so lucky that we picked up the mif4 mutant pebble that informed about what is a genuinely beautiful machine that Mother Nature uses to assist the folding of proteins in cells. I feel incredibly lucky not only to have been allowed to understand the general action of this machine but to have had the thrill to actually see it at near atomic resolution and ultimately, along with others, dissect how it works. Seeing GroEL on a graphics display for the first time in fall 1993 side-by-side with Zbyszek Otwinowski who solved the structure and is here today, and the late Paul Sigler, was a spiritual experience.
But I love Science for all the moments between these once or twice-in-a lifetime moments. I love Newton's "sea-shore" the quiet contemplation of how something might work, the collaborative discussions with Ulrich and Ming (who is here today from Taiwan) in those early times, and with everyone in my lab everyday, where I work at the bench side-by-side with everyone. And I love the personal dirtying of my own hands in my own experiments, where failure is the common outcome, but where I invest my being, as if a boy on the sea-shore.
We have recently directed our focus to the neurodegenerative paralyzing motor disease ALS, to a form caused by protein misfolding, and I hope that we or others are able to pick up the shell that will be the understanding of the basic mechanism by which a misfolded protein causes neurotoxicity. That might lead to a rationally designed therapy for this devastating condition. I once again thank you all for honoring me today.