An immigrant family in Brooklyn
George Wald was born in New York City on November 18, 1906, the son of Jewish immigrants. His father, Isaac Wald, came from a village near Przemyśl in what was then Austrian Poland; his mother, Ernestine Rosenmann, came from a small village near Munich in Bavaria. The family settled in a working-class neighbourhood of Brooklyn, and George went to the local public schools.
He was good with his hands from the start. One early triumph, his biographer John Dowling records, was a homemade crystal radio that let him and the neighbourhood children listen to the 1919 World Series. He attended Manual Training High School, the school that became Brooklyn Technical High School, and was part of its first graduating class in 1923. The school taught students to build things, and Wald later felt that this training mattered enormously to his science, because it let him design and help build the specialised equipment his experiments needed. As a teenager he also loved vaudeville, and with a school friend he put together an act that they performed at Jewish community centres around the city.
From pre-law to the laboratory
His success on stage made law seem a natural career, so he entered Washington Square College of New York University as a pre-law student. College opened up art, classical music and literature to him, and for two summers he worked on a passenger ship sailing between New York and Buenos Aires. Law bored him; he wanted something, as he put it, more substantial and more natural, and he switched to pre-medicine. By his senior year medicine had lost its appeal too, until he read Sinclair Lewis’s novel Arrowsmith and fell for the idea of a life in biological research. He graduated in 1927.
At Columbia University he took genetics with Thomas Hunt Morgan and met Selig Hecht, the leading researcher on vision of his generation. Hecht had shown that seeing obeys the laws of photochemistry: some light-sensitive substance in the eye is broken down by light and rebuilt in the dark. Wald studied vision in fruit flies and, with Hecht, the way human eyes adjust to darkness, earning his doctorate in zoology in 1932. Hecht was interested in the equations; Wald wanted to get his hands on the molecules themselves. Years later he said that everything he did or wrote was, in a sense, still addressed to his old teacher.
Vitamin A in the eye
In 1932 a National Research Council fellowship took Wald and his first wife, Frances Kingsley, to the Berlin laboratory of the biochemist Otto Warburg. The eye’s rod cells contain a reddish-purple pigment, rhodopsin or visual purple, that bleaches in light. Wald suspected from its colour that it contained a carotenoid, the family of yellow and orange compounds that includes vitamin A. He extracted retinas and ran a simple chemical colour test. The solution turned bright blue and had the light-absorption profile of vitamin A. Doctors had long known that a lack of vitamin A causes night blindness, but nobody knew why. Now there was a direct link: the vitamin was sitting in the very tissue that catches light.
Warburg sent him to Zürich, where the chemist Paul Karrer had just worked out the structure of vitamin A. There Wald confirmed the vitamin in the retinas of cattle, sheep and pigs. He then moved to Otto Meyerhof’s laboratory in Heidelberg. It was 1933, Hitler had come to power, and Germany was turning hostile to Jews; both Meyerhof and Wald were Jewish, and his fellowship ordered him home by the end of the summer. Before he left, a shipment of 300 frogs arrived while everyone else was on holiday. Wald took them, and in their retinas he found a new yellow substance he called retinene. Rhodopsin, he proposed, was a protein carrying retinene; light released it, it was turned into vitamin A, and in the dark the process ran backward to rebuild the pigment. He called this the visual cycle and described it in a note to Nature.
The molecule that catches light
Wald joined Harvard in 1934 and stayed for his whole career, becoming a full professor in 1948. For the next three decades his laboratory, joined after the war by Ruth Hubbard, later his second wife, and by his long-time co-worker Paul Brown, took the visual cycle apart piece by piece. After a British group showed that retinene is the aldehyde form of vitamin A, now called retinal, Brown showed that simply mixing retinal with the protein opsin makes rhodopsin. The team could then build the eye’s light sensor in a test tube.
The crucial clue was shape. Retinal can bend at different points along its chain, and Wald, Hubbard and Brown showed that only one bent form, 11-cis retinal, fits into the pigment properly. Hubbard’s experiments then showed that the only thing light does in vision is to straighten that molecule into its all-trans form. Everything else follows: the protein changes shape, the cell fires, and the straightened retinal must be bent back again before the pigment can be reused. It was the first role found for this kind of molecular switch anywhere in biology. In 1965 Wald suggested in the journal Science that a single activated rhodopsin might trigger a chain of enzyme reactions, like blood clotting, to amplify the signal. Researchers confirmed in the 1980s that this is exactly how it works, and rhodopsin became the best understood member of the vast family of receptors that most modern medicines act on.
Colour, fish and frogs
Wald’s curiosity ran wide. Summers at the Marine Biological Laboratory in Woods Hole led him to a second form of vitamin A in freshwater fish and to a different visual pigment, porphyropsin. Salmon, which spawn in fresh water, use it; eels, which spawn in the sea, use the ordinary form; tadpoles switch from one to the other as they become frogs. From chicken retinas he extracted iodopsin, a pigment from the cone cells that see colour.
In the 1960s he turned to human colour vision. Using careful measurements on volunteers with normal and defective colour vision, and a microspectrophotometer that Paul Brown built to read the light absorbed by single cells, the laboratory measured the three types of cone pigment in the human eye, sensitive to blue, green and red light. All three used the same 11-cis retinal; they differed only in their proteins. That insight explained the inherited forms of colour blindness and set up the later work that identified the genes for each cone pigment.
What it means for sight today
Wald’s discoveries were the first time anyone had shown exactly what a fat-soluble vitamin does in the body, and they gave a mechanism to a disease that still harms millions. The World Health Organization calls vitamin A deficiency the world’s leading preventable cause of childhood blindness and estimates that 250,000 to 500,000 deficient children go blind every year. Night blindness is one of its earliest signs. Programmes that give children vitamin A rest on the understanding his work supplied: without the vitamin, the retina cannot make the pigment it needs to see.
The visual cycle he mapped is also the map that eye doctors and gene therapists use today. In December 2017 the US Food and Drug Administration approved Luxturna, a gene therapy for inherited blindness caused by faults in the RPE65 gene, which makes the enzyme that resets used vitamin A to its light-ready shape in the back of the eye. Research on retinitis pigmentosa, macular degeneration and other retinal diseases still starts from the chemistry of rhodopsin and retinal that his laboratory worked out.
A teacher and a public voice
Wald was one of Harvard’s most celebrated teachers. From 1960 until his retirement in 1977 he taught a general introductory course, The Nature of Living Things, known as Nat Sci 5, which opened with a lecture on the origin of life and began its second term with one on the origin of death. Thousands of undergraduates took it, and some changed careers because of it. In 1966 Time magazine named him one of the ten best teachers in the country. He shared the Nobel Prize in Physiology or Medicine in 1967 with Ragnar Granit and Haldan Keffer Hartline.
The Vietnam War horrified him. He signed a 1965 open letter against it, and in 1969 a speech he gave at a teach-in at the Massachusetts Institute of Technology, A Generation in Search of a Future, was reprinted widely and translated into more than 40 languages. From then on he campaigned against the war, nuclear weapons and the arms race, which he saw as part of being a biologist, someone concerned with life. Told that the arms race was a fact of life, he answered that these were the facts of death, and that he did not accept them. In 1986, invited to Moscow with other Nobel laureates, he pressed Mikhail Gorbachev about the exile of the physicist Andrei Sakharov and his wife Yelena Bonner.
Jewish roots
Wald was born to two Jewish immigrant parents, one from Galicia and one from Bavaria, and grew up among the Jewish working families of Brooklyn; his first audiences as a teenage performer were at Jewish community centres. He was secular, and Wikipedia records that he was an atheist. His Jewish identity nonetheless shaped his early career in the most direct way: he was a young Jewish scientist in Germany in 1933, working in the laboratory of a Jewish Nobel laureate, Otto Meyerhof, when the Nazis took power and he was called home. He is listed among the Jewish Nobel laureates by the Jewish Virtual Library.
Family and legacy
Wald married Frances Kingsley in 1931; they had two sons, Michael and David. In 1958 he married the biochemist Ruth Hubbard, his long-time collaborator, and they had a son, the musician and writer Elijah Wald, and a daughter, Deborah. He collected Rembrandt etchings and art from Africa and the Americas. After retiring he gave up laboratory work for political causes and travelled widely until the last two years of his life. He died at his home in Cambridge, Massachusetts, on April 12, 1997, at the age of 90.
His legacy is the chemistry of seeing. Every textbook account of how light becomes a nerve signal, every vitamin A programme that saves a child’s sight, and every gene therapy aimed at the visual cycle builds on the experiments he began with a bottle of retinal extract in Berlin and a box of frogs in Heidelberg.
Sources & further reading
George Wald, Biographical, NobelPrize.org · John E. Dowling, George Wald 1906–1997, Biographical Memoir, National Academy of Sciences · George Wald, Jewish Virtual Library · Vitamin A deficiency, World Health Organization · FDA Approves Gene Therapy for Inherited Blindness Developed by Penn and CHOP, Penn Today · George Wald, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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