Twenty-four visits to Stockholm: a concise history of the Rockefeller Nobel Prizes

Part IV: John H. Northrop, 1946 Prize in Chemistry

By Joseph Luna

So far in this series, it seems as if we’ve focused on foreigners. For a young institution like Rockefeller in the early 20th century, it took time for original Nobel level work to emerge, and so it’s not too surprising that the first three visits to Stockholm was for work done before the recipient arrived at Rockefeller, and in far off places: France/Canada, Austria, and the great state of Missouri. That changed in 1946, when two Rockefeller scientists won Nobel prizes in Chemistry, the elder of whom was a true New Yorker, a Yonkers born and Columbia University-trained, eighth generation Yankee, named John Northrop.

His biography borders on Rooseveltian: John’s father, a zoologist, was tragically killed in an explosion two weeks before young Jack was born in 1891. His mother, a trained botanist, raised him alone in Yonkers and taught at both Columbia and Hunter College. With a mother deeply interested in nature, Jack’s young adulthood was spent largely outdoors, quite a feat for a city boy. He hunted and fished, was at home on a horse or in a canoe, and loved to travel. His youthful adventures took him as far as the American southwest, where in 1913-14 he spent time prospecting for gold along the Colorado River. World War I halted that.

Academically, Northrop was no less bold. He arrived at Rockefeller as a postdoc in 1915, and worked under Jacques Loeb, the pre-eminent German physiologist recently recruited as a member. With Loeb, Northrop worked on problems as varied as the effects of temperature on Drosophila heredity to the mechanism behind the light sensitivity of horseshoe crabs. Northrop distinguished himself as an ardent and outspoken practitioner against the impulses then present throughout biology and believed, like his mentor, that all biological processes were firmly rooted in the testable laws of physics and chemistry. Such thinking came in handy when he turned his attention to enzymes.

Even the very word enzyme presented a conundrum. Meaning “in” (en-) “leaven” (-zyme) or “in yeast,” the term was coined in the 1870s to broadly describe the activity of living cells to conduct chemical reactions. As Pasteur had vividly demonstrated throughout the second half of the 19th century, the specific actions of micro-organisms were responsible for a number of complex chemical reactions, such as yeast in converting sugar to alcohol in wine, and in beer-making. Underlying many reactions, the thinking went, was a microbe, as a tiny, living and necessary chemist. The demonstration by biochemist Eduard Buchner in 1897 that yeast extracts devoid of any living cells could still carry out fermentation dealt a major blow to this idea, but it opened an important and almost existential question: if life was not required, then what exactly was an enzyme?

Over the next two decades, enzymology remained shrouded in mystery and frustration. Proteins were the likely candidates, but no one was able to convincingly purify and characterize an active enzyme to exclude the possibility of some contaminating microbe or vital “seed” catalyst. An intrepid Cornell chemist named James Sumner looked at the problem and reasoned that since the purest forms of many substances would form ordered crystals, then perhaps a pure preparation of an enzyme might do the same. Many thought this idea both foolish and impossible, but after almost a decade of trying, Sumner succeeded at crystallizing urease from jack beans, and in 1926 published that urease was a pure protein.

The scientific establishment may have balked, but Sumner found a vocal compatriot in Northrop. Within three years, Northrop had succeeded in crystallizing the pepsin protease from swine, and demonstrated beyond any doubt that pepsin was also a protein. Working with Moses Kunitz, he achieved similar success with trypsin a few years later. In both cases, there was no evidence that anything other than protein was required for enzymatic activity. At a time when most proteins were considered passive carriers or structural supports, the finding that some were capable of carrying out chemical reactions was a genuine surprise. Alongside Wendell Stanley’s work on virus crystallization, the boundary between life and non-life was blurred by their efforts with the realization that tiny molecular machines are responsible for life’s processes. As Loeb instilled, all was chemistry.

Fitting to his outsized persona, both Northrop and Jacques Loeb are also notable for being Rockefeller scientists profiled in literature. Written by Sinclair Lewis in 1925, Arrowsmith is arguably one of the great American novels of medical science and won the Pulitzer Prize in 1926.  Northrop was the inspiration for a character named Terry Wickett, while Loeb inspired Wickett’s inscrutable but scientifically pure mentor, Max Gottlieb. Like Northrop, Terry is brash and outspoken, comfortable outdoors, rugged and unyielding in his pursuit of science. Or in his words: “What kind [of scientist] are you going to be? One of the polite birds that uses the Institute for social climbing and catches him a rich wife, or one of the roughnecks like me and Gottlieb?”