The Executioner We Can’t Live Without: special molecules that kill rotten proteins

Pamela Weintraub in Nautilus:

AaronLast summer, as I interviewed Aaron Ciechanover, who won a Nobel Prize in Chemistry in 2004, his country was at war. Three Israeli boys had just been murdered in the West Bank by Palestinians, then a Palestinian boy had been burned to death in retribution by Israelis. While we sat in his lab at the Technion-Israel Institute of Technology in Haifa, to the north of the bombs, missiles were flying over Jerusalem and Tel Aviv, and a Gaza invasion loomed. The mounting conflict troubled but didn’t ruffle Ciechanover, one of Israel’s greatest scientists and statesmen, who patiently and colorfully explained to me one of biology’s most remarkable processes, how a molecular Pac-Man races through our bodies and devours damaged proteins.For over 40 years, Ciechanover has worked to understand these molecular machines, called shredders. Built around a core molecule called ubiquitin, shredders destroy ruined proteins so that our bodies can replace them with fresh parts and not, says Ciechanover, rot like a side of meat, “brownish-greenish and stinking,” in the sun. Ciechanover shared the Nobel Prize with Avram Hershko, his mentor at Technion, and Irwin Rose, a biochemist at the University of California, Irvine. Scientists already understood the genetic code, how genes coded for the creation of proteins. But the shredder helped control the overall process: the degradation of damaged goods, DNA repair, cell division, and immune defense. The shredder enabled biologists to see the wizard behind the screen.

In your Nobel notes, you said that you learned “to become a long books author rather than a short story writer.” What do you mean?

Science is changing, so I don’t blame the current scientists for being short-range thinkers. But I’m a risk taker. I am an adventurist. I was in medicine and I decided that I don’t want to do it. I took a big risk, but I thought that I should go after my gut feeling and after excitement and after what I really want to do. I’m not in science in order to publish. I’m in science in order to be excited by the discovery. In order to do that, you need to be a marathon runner. Mother Nature doesn’t make itself available to us easily. You need to be patient. You need to take a long risk. You need to be in the business for many years. You need to run slowly but fast—slowly in terms of patience, but fast in order to be competitive. It looks contradictory, but it’s not contradictory. And you really want to dig deep into it. You don’t want to scrape the surface and then move to another one and to another one and to another one. People ask me, “OK, so 40 years you work on ubiquitin, what’s next?” I say, “The next 20 years, if I should still survive them, will be devoted to the same very woman.” Because we are still scratching her surface. That’s the beauty of nature. You dig and dig and dig. You’ll never come to an end.

More here.