WALD, GEORGE

(b. New York, New York, 18 November 1906;

d. Cambridge, Massachusetts, 12 April 1997), biochemistry of vision, photoreception, retinol (vita-min A), color vision.

Wald made crucial contributions to the study of vision and, in so doing, provided a molecular basis for photoreception research in the twentieth century. In the early 1930s, Wald found a derivative of vitamin A in the retina of the eye. This allowed him to assign, for the first time, a functional role in the body for a fat-soluble vitamin. Wald went on to biochemically analyze the light-sensitive pigments that reside in the rods and cones of the eye. By the 1950s Wald and his colleagues had described, in molecular terms, how a visual pigment reacts to light. It is this light reaction that “triggers” the molecular events that lead to photoreceptor excitation and vision. In recognition of these fundamental discoveries, Wald was awarded the Nobel Prize in Physiology or Medicine in 1967.

Wald was a highly regarded teacher at Harvard University for forty-three years, retiring in 1977 as Higgins Professor of Biology. He taught biochemistry, photobiology, and an introductory biology course that earned him a 1966 citation in Time magazine as “one of the ten best teachers in the country” (unsigned article, 6 May 1966). A scientist of broad intellectual interests, Wald wrote and taught on topics ranging from the origin of life to the evolution of consciousness. From the mid-1960s until the time of his death, Wald devoted much of his time to social activism. He traveled widely and spoke out eloquently against the U.S. war in Vietnam, nuclear power and weaponry, and violations of human rights.

Early Years and Education. George Wald was the youngest of three children of immigrant parents. His father, Isaac Wald, a tailor, was from a village near Przemysl in what was then Austrian Poland. His mother, Ernestine Rosenmann, came from a village near Munich, Bavaria. Wald grew up in Brooklyn, New York, and attended Manual Training High School (now Brooklyn Technical High School). He showed aptitude and interest in mechanical things and science, especially electricity, from an early age. Wald also had a lively wit and flair for the dramatic, and he created a vaudeville act that he and a friend performed at local Jewish community centers.

The first member of his family to attend college, Wald received a bachelor of science degree from Washington Square College of New York University (NYU) in 1927. He had started at NYU as a prelaw student, but eventually decided “law was an artificial, manmade thing and I needed to be able to get into something more substantial, more organic” (Hubbard and Wald, 1999, p. 6). Wald switched to premed studies, but became disen-chanted with the idea of caring for patients and attracted to the pursuit of scientific research after reading Sinclair Lewis’s Arrowsmith. After NYU, Wald entered Columbia University as a graduate student in zoology.

In his first year at Columbia, Wald took a genetics course with Thomas H. Morgan, whose work to establish chromosomes as the carriers of genetic material would win him a Nobel Prize in 1932. But Wald was more taken with the biophysics professor he met his first year: Selig Hecht, a leader in the field of visual physiology and a man of vigorous personality and considerable culture. Wald joined Hecht’s laboratory as his graduate student and research assistant, and Hecht became for him a mentor, father figure, and lifelong role model. Hecht’s laboratory was, for Wald, a stimulating place where conversation was devoted each day not just to science but to topics in art, literature, music, and politics. Wald, when he later joined the faculty of Harvard University, would foster such an intellectually lively atmosphere in his own laboratory.

Hecht was engaged in analyzing photoreception (the detection, absorption, and use of light) in organisms ranging from the relatively simple Ciona (sea squirt) and Mya(soft-shell clam) to humans. Hecht investigated dark adaptation, brightness discrimination, the visual threshold, and other physiological aspects of vision. For his doctoral research, Wald studied visual acuity in the fruit fly Drosophila. To do so, Wald glued two microscope slides together to make a narrow glass track for the fly to walk in. He then projected stripes of various widths along the track and measured the limits of visual acuity in the dark-adapted fly, because when a fly saw two stripes merge into a continuum, it would stop dead. Wald enjoyed conceptualizing and even building his experimental apparatus, an interest that did not wane throughout his scientific career.

Hecht’s generalized theory of photoreception would guide Wald toward his postgraduate studies. Hecht in 1920 had postulated that a photosensitive substance S in the retina is decomposed by light into the precursor products P and A (light adaptation). In the dark, P and A combine to reform S (dark adaptation) (Hecht, 1920, p. 112). After completing his graduate work in 1932, Wald left Hecht’s laboratory “with a great desire to lay hands on the molecules for which these were symbols” (Wald, 1967a, p. 292). This desire led him to the laboratories of three different past or future Nobel Prize winners within the space of several months, supported by a fellowship from the U.S. National Research Council. Wald was accompanied by his wife, Frances Kingsley Wald, whom he married in 1931.

The Role of Vitamin A in the Retina. The first laboratory he went to visit was that of biochemist Otto Warburg in Berlin. Since the mid-1920s, Warburg had been using spectrophotometry to identify an enzyme (now called cytochrome oxidase) involved in cellular respiration. In spectrophotometry, light is passed through a solution of interest in order to differentiate the solution’s components by their characteristic pattern of absorbing some wavelengths and transmitting others. For this work, Warburg had received the Nobel Prize the year before Wald joined his laboratory.

Wald learned how to extract retinas in Warburg’s laboratory, and initially tried experiments on retinal respiration both in the dark and the light. But he was more interested in Hecht’s “S” substance. A light-sensitive pigment had been discovered in frog retinas in 1876 by Franz Boll. Boll and Willy Kühne, a professor of physiology at Heidelberg, soon after showed that the visual pigment is reddish-purple in dark-adapted retinas (visual purple) but when exposed to light it “bleaches” to a yellowish-orange color (visual yellow) and then fades over time to a colorless substance (visual white). Kühne also extracted visual purple (which Boll had named rhodopsin) into aqueous solution with bile salts and showed it was a protein.

In Warburg’s laboratory, Wald hypothesized that rhodopsin was a carotenoid pigment, akin to the pigments responsible for phototropism in plants (the tendency to be attracted to light). Reading the literature, Wald found that the carotenoids, when mixed with antimony chloride, turn bright blue. So Wald isolated some frog retinas, shook them with chloroform, and mixed the extract with an antimony chloride solution. The extracts turned blue and, when analyzed spectrophotometrically, showed an absorption band characteristic of vitamin A (at wavelength 320 nanometers). The “vitamins were still deeply mysterious, and at that time one hardly expected them to participate directly in physiological processes” (Wald, 1967a, p. 293). Yet when Wald read further, he found literature linking vitamin A deprivation to night blindness, an abnormal insensitivity to light. This condition could be cured by administering cod-liver oil, which was known to contain vitamin A.

After Wald found vitamin A in the eye, Warburg suggested he go to the laboratory of Paul Karrer, an organic chemist in Zürich, to confirm his result. Karrer had just described in 1930 and 1931 the structural formulas of b-carotene, a carotenoid found in plants that animals can convert to vitamin A, and of vitamin A itself. By showing that vitamin A is one-half of a carotene molecule with a hydrogen and a hydroxyl (OH) attached to the broken end, Karrer had given the first description of the chemical structure of any provitamin or vitamin. Wald and his wife collected thousands of eyes from sheep, pigs, and cattle at slaughterhouses. They then isolated the retinas and extracted them with fat solvents. With Karrer, they confirmed that the retinas yielded vitamin A (Wald, 1935).

The Discovery of Retinal. Wald then went to Heidelberg and the laboratory of Otto Meyerhof, a distinguished physiologist and an expert in muscle biochemistry. While there, Wald extracted three hundred frog retinas and analyzed them. It was then that he discovered a previously unknown yellow carotenoid, similar to vitamin A but with a different absorption spectrum, present in dark-adapted

retinas and in retinas bleached to the visual yellow stage. He named this substance retinene (now called retinal). As the visual yellow continued to fade to the visual white stage, the retinal disappeared and in its place, Wald found vitamin A. Wald had here succeeded in identifying some of the molecules in Hecht’s conception of the visual process. The visual pigment rhodopsin (S), which contains retinal bound to a protein, is decomposed by light into products P (a protein) and A (retinal). Retinal is then converted to vitamin A, and vitamin A somehow reconstitutes rhodopsin. (Retinal itself can also combine with protein to form rhodopsin.) Because some vitamin A is lost during this cycle, it must be replenished through dietary consumption of plant carotenoids (Wald, 1936a).

By that time, the summer of 1933, the Nazis had come to power in Germany and the National Research Council insisted that Wald, who was Jewish, must return to the United States. Wald continued his fellowship at the University of Chicago and, in 1934, he accepted a position as tutor in biochemical sciences at Harvard University. Wald would remain at Harvard for the rest of his academic career, becoming professor of biology in 1948 and retiring in 1977. Wald, also in 1934, began a long association with the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, where Selig Hecht had carried out his Mya and Ciona studies and had brought Wald as his student in 1929. Wald returned to Woods Hole almost every summer for the rest of his life, becoming an instructor in the MBL’s famous Physiology Course in 1947 and serving as a trustee of the laboratory for thirty-four years during the period 1948 to 1997.

In Woods Hole, Wald confirmed in several marine fishes the cycle of rhodopsin–retinal–vitamin A–rhodopsin that he had observed in the frog (Wald, 1936b). However, he was puzzled by an 1896 finding by two German biologists, Else Köttgen and Georg Abelsdorff, that the visual pigment of fishes was a darker purple than the rhodopsin of frogs and mammals. Looking into that, he discovered in freshwater fishes a new visual pigment, which he called porphyropsin, that engaged in a cycle like rhodopsin but in which different carotenoids took the place of retinal and vitamin A (Wald, 1939). Saltwater fishes, on the other hand, had rhodopsin. That raised the question: What visual pigment would be found in euryhaline fishes, which migrate back and forth between freshwater and saltwater? Wald determined that they possess either the visual system that goes with the fish’s spawning environment, or a mixture of both systems, with the one that goes with its spawning environment predominating (Wald, 1941). This intriguing result led Wald to larger questions on biochemical changes during vertebrate metamorphosis, the evolution of visual systems, and the origin of life. He took special pleasure in exploring these kinds of relationships for the rest of his life (Wald, 1957, 1958b, 1964b).

Thus far, Wald had studied the visual pigments found in the rods of the eye, which mediate vision in dim light. In the mid-1930s he set out to find a visual pigment in the cones, which are the receptors of daylight vision and color vision. From chicken retinas, which contain primarily cones, Wald extracted two photosensitive pigments: rhodopsin and a new, more violet one, which he called iodopsin (Wald, 1937). He was unable to separate the two pigments, though, so could not confirm whether iodopsin, like rhodopsin, yields retinal and vitamin A when bleached by light. Nor was he able to differentiate the proteins present in each pigment, as protein chemistry at this time was in its infancy. It was not until the mid-1950s that Wald and his coworkers were able to synthesize visual pigments and thereby show that iodopsin does, in fact, bleach to retinene and vitamin A. This implied that the rod and cone pigments differ only in the proteins—by then called opsins—with which the carotenoid combines (Wald, Brown, and Smith, 1955).

The Trigger of Vision. World War II interrupted Wald’s work on the chemistry of visual pigments, which distressed him. “Those who think that war stimulates scientific research are not scientists,” he wrote in a 1953 review article. War

may stimulate technology. All the organized projects, the money and material poured into them, the committees and conferences, succeed mainly in obscuring the fact that little of scientific importance is being accomplished. One of our problems is to keep these conditions from continuing throughout the peace. (Wald, 1953, p. 497)

During the war, Wald worked at Harvard under contract for the U.S. Army Board of Engineers and the Office of Naval Research, studying the limits of human vision in the infrared range as well as chromatic aberration of the human lens.

After the war, he resumed his study of visual pigments with a new group of graduate students. One was Ruth Hubbard, who would perform distinguished research and in 1973 become a tenured biology professor at Harvard. Wald’s first marriage ended in divorce, and he and Hubbard married in1958. Another person who played an important role in the laboratory was Paul K. Brown, who became Wald’s research assistant in 1946 and remained for more than forty years. Brown never finished college, but he had exceptional scientific skill and insight. He designed and built equipment for the laboratory, coauthored numerous papers, and lectured on vision in Harvard’s graduate course in photobiology.

Wald’s laboratory leaped forward in analyzing visual pigments after R. A. Morton and his colleagues in Liverpool, in 1946, showed that retinal is the aldehyde form of vitamin A. This enabled Wald’s group to obtain ample amounts of retinal by purchasing and oxidizing vitamin A.Afew years later, Hubbard and Wald described the enzymatic interconversion of retinal and vitaminA, and the following year Brown synthesized rhodopsin by simply mixing retinal and the opsin protein in the dark (Wald and Hubbard, 1949; Wald and Brown, 1950).

For Wald, the central question of his research was how the visual pigment acts in photoreception: how it interacts with light to trigger the neural excitation that leads to vision. Wald’s group was aware of a 1944 result by Leonard Zechmeister showing that light, along with an iodinecatalyst, can induce carotenoid molecules to assume different geometrical shapes, called cis-trans isomers. In the cis form of the isomer, the carotenoid molecule is bent around one or more of its carbon double bonds, while in the trans form, it is straight.

Hubbard showed that, when illuminated, retinal yielded rhodopsin when mixed with opsin, and it did so

with or without an iodine catalyst. This led Hubbard and Wald to express the rhodopsin visual cycle in terms of a cis-trans isomerization cycle. Rhodopsin, in the dark-adapted eye, contains retinal in a bent, cis form plus opsin. Upon the absorption of light, the cis-retinal straightens out to the all-trans form, which is then reduced to all- trans vitamin A. In order for rhodopsin to be resynthesized, as a first step the vitamin A must be re-isomerized from the all-trans form back to the bent, cis form (Wald and Hubbard, 1952).

Working with several organic chemists, Wald, Hubbard, and Brown then showed that only one cis shape of retinal—the 11-cis isomer—combines with opsin to form rhodopsin. This shape, the 11-cis isomer, is the precursor to all visual pigments. (They found that another isomer, the 9-cis isomer, can form a photosensitive pigment with opsin, which they called isorhodopsin, but this pigment is less light sensitive than rhodopsin and is not ordinarilyfound in the eye.)

By 1958, Hubbard and Allen Kropf had shown in Wald’s laboratory that the only action of light in vision is to isomerize the retinal from the 11-cis to the all-transconfiguration. All other changes are “dark” consequences of this one light reaction. The 11-cis- retinal thus is the chromophore in visual pigments: it is the molecule that absorbs light, which result in the molecular changes that eventually cause excitation of the photoreceptor cells (Hubbard and Kropf, 1958). This trigger of vision is found in all animals.

But exactly when and how does visual excitation occur? Wald’s group made important contributions to answering these questions. By bringing rhodopsin to very low temperatures and then warming it slowly in the dark, Wald and Toru Yoshizawa were able to identify several intermediate stages between the time the rhodopsin chromophore absorbs light and the time it is released as all-trans-retinal (Yoshizawa and Wald, 1963a). These intermediate stages represent conformational changes in the opsin, and one of these stages, metarhodopsin II, leads to excitation of the photoreceptor.

Wald also provided a prescient conceptual framework for how visual excitation might occur. Selig Hecht and coworkers had shown in the late 1930s that absorption of a single photon is enough to stimulate a rod, which implies that just one molecule of rhodopsin needs to be activated. How could this one isomerization trigger such a large response as light perception? Wald, in 1965, proposed that when a molecule of rhodopsin absorbs light, it sets off a cascade of enzymatic reactions, similar to what happens in blood clotting, that lead to excitation of the photoreceptor cells (Wald, 1965). As was shown by several laboratories in the mid-1980s, this is indeed what happens in th cyclic-GMP cascade of vision, as reported in Lubert Stryer’s 1986 article.

Color Vision and Social Activism. In the 1960s, Wald’s research focused on human color vision, a topic that had long intrigued him. It had been known for more than a century that normal color vision involves three independent variables. So, presumably, there would be three types of cones. Wald and Brown determined that there are, indeed, three types of cones in human and monkey retinas, with each type absorbing light predominantly in the red, blue, or green parts of the visible spectrum. Crucial to this wor was the design of a microspectrophotometer, which Brown built, that allowed them to measure the difference spectra (the changes in absorbance) of the visual pigment in single rods and cones. Brow and Wald went on to show that each of the three cone pigments has an 11-cis-retinal chromophore, and thus it must be differences in their opsins that tune the pigments to absorb different wavelengths of light (Wald and Brown, 1963b; Wald and Brown, 1964a; Wald, 1964b).

Wald’s laboratory made another contribution with the discovery, by John Dowling, that retinoic acid (an acid corresponding to vitamin A) can substitute for all functions of vitamin A in the body except as precursor to visual pigments (Wald and Dowling, 1960). Retinoic acid is now believed to play an important role in the development of many tissues.

Wald was elected to the National Academy of Sciences in 1950 and to the American Philosophical Society in 1958. In 1967 Wald was awarded the Nobel Prize for Physiology or Medicine in Stockholm, sharing the prize with two other vision researchers, Ragnar Granit and Keffer Hartline. The three had worked independently, although Hartline, too, had been active at the Marine Biological Laboratory in Woods Hole for nearly three decades.

Two years later, Wald’s life changed dramatically after he delivered a speech at the Massachusetts Institute of Technology called “A Generation in Search of a Future” (Wald, 1969). This speech, which criticized the U.S. war in Vietnam and the nation’s buildup of nuclear weapons, was published in periodicals around the world, and it propelled Wald into the limelight of social activism. Over the next twenty-five years he traveled extensively, using his great skill as a teacher to speak out on these issues as well as on human rights and the misuse of genetic engineering. Wald continued to teach his highly regarded introductory biology course, Natura Sciences 5: The Nature of Living Things, at Harvard until his retirement in 1977. But he largely stopped doing research after 1969, except for summer investigations in Woods Hole on lobster photoreception.

At age ninety, Wald died at his home of natural causes. He was survived by his wife, Ruth Hubbard, their two children, Elijah and Deborah, two children from his first marriage, Michael and David, nine grandchildren, and three great-grandchildren.

BIBLIOGRAPHY

The George Wald papers, 1927–1996, Harvard University archives, Harvard Depository hugfp143, Hollis no. 008421916, in 145 boxes, document the public life of George Wald, including his work as a scientist and his efforts as a prominent social activist. As such, the papers document the field of vision science and liberal American politics, especially the era of the late 1960s toearly 1970s. Also included are materials relating to Wald’s varied interests in the arts, sciences, and other aspects of culture. Chronologically, the papers cover Wald’s adult life;the earliest material dates from his college years. Material consists of many formats: correspondence, manuscripts, publications, notebooks, note cards, photographs, video, and audio tapes.

WORKS BY WALD

“Vitamin A in Eye Tissues.” Journal of General Physiology 18 (1935): 905–915.

“Carotenoids and the Visual Cycle.” Journal of General Physiology 19 (1936a):351–371.

“Pigments of the Retina: II. Sea Robin, Sea Bass and Scup.” Journal of General Physiology 20 (1936b): 45–56.

“Photo-labile Pigments of the Chicken Retina.” Nature 140 (1937): 545–546.

“The Porphyropsin Visual System.” Journal of General Physiology 22 (1939): 775–794.

“The Visual Systems of Euryhaline Fishes.” Journal of General Physiology 25 (1941): 235–245.

“Human Vision and the Spectrum.” Science 101 (1945): 653–658.

With Ruth Hubbard. “The Reduction of Retinene₁ to Vitamin A₁in Vitro.” Journal of General Physiology 32 (1949): 367–390.

With Paul K. Brown. “The Synthesis of Rhodopsin from Retinene₁.” Proceedings of the National Academy of Sciences of the United States of America 36 (1950): 84–92.

With Ruth Hubbard. “The Mechanism of Rhodopsin Synthesis.” Proceedings of the National Academy of Sciences of the United States of America 37 (1951): 69–79.

———. “Cis-trans Isomers of Vitamin A and Retinene in the Rhodopsin System.” Journal of General Physiology 36 (1952): 269–315.

“The Biochemistry of Vision.” Annual Review of Biochemistry 22 (1953): 497–526.

With Paul K. Brown and Patricia H. Smith. “Iodopsin.” Journal of General Physiology 38 (1955): 623–681.

“The Metamorphosis of Visual Systems in the Sea Lamprey.” Journal of General Physiology 40 (1957): 901–914.

With Paul K. Brown. “Human Rhodopsin.” Science 127 (1958a): 222–227.“

The Significance of Vertebrate Metamorphosis.” Science 128 (1958b): 1481–1490.

“Light and Life.” Scientific American 201 (October 1959):92–108.

With John E. Dowling. “The Biological Function of Vitamin A Acid.” Proceedings of the National Academy of Sciences of the United States of America 46 (1960): 587–608.

With Tõru Yoshizawa. “Pre-lumirhodopsin and the Bleaching of Visual Pigment.” Nature 197 (1963a): 1279–1286.

With Paul K. Brown. “Visual Pigments in Human and Monkey Retinas.” Nature 200 (1963b): 37–43.

———. “Visual Pigments in Single Rods and Cones of the Human Retina.” Science 144 (1964a): 45–52.

“The Receptors of Human Color Vision.” Science 145 (1964b): 1007–1017.

“The Origins of Life.” Proceedings of the National Academy of Sciences of the United States of America 52 (1964c): 595–611.

“Visual Excitation and Blood Clotting.” Science 150 (1965): 1028–1030.

“The Molecular Basis of Visual Excitation.” Nobel Lecture, 12 December 1967a. Available from http://www.nobelprize.org.

With Tõru Yoshizawa. “Photochemistry of Iodopsin.” Nature 214 (1967b): 566.

“A Generation in Search of a Future.” Speech given at the Massachusetts Institute of Technology, 1969. Available from http://www.elijahwald.com/generation.html.

“Life and Mind in the Universe.” International Journal of Quantum Chemistry 11 (1984): 1–15.

OTHER SOURCES

Dowling, John E. “George Wald.” Biographical Memoirs, vol. 78. Washington, DC: National Academy of Sciences, 2000. Available from http://www.nasonline.org. Dowling’s memoir, and the memorial talk by Ruth Hubbard and Elijah Wald cited below, are the two most complete and accurate accounts of Wald’s life and scientific contributions.

Hecht, Selig. “Human Retinal Adaptation.” Proceedings of the National Academy of Sciences of the United States of America 6 (1920): 112–115.

Hubbard, Ruth, and Allen Kropf. “The Action of Light on Rhodopsin.” Proceedings of the National Academy of Sciences of the United States of America 44 (1958): 130–139.

Hubbard, Ruth, and Elijah Wald. “George Wald Memorial Talk.” In Rhodopsins and Phototransduction. Novartis Foundation Symposium 224. Chichester, U.K.: Wiley, 1999.

Stryer, Lubert. “Cyclic-GMP Cascade of Vision.” Annual Review of Neuroscience 9 (1986): 87–119.

Diana E. Kenney

George Wald

The American biochemist George Wald (born 1906) discovered the role that vitamin A plays in vision and made many contributions to the knowledge of the biochemistry of vision. He won the Nobel Prize in medicine/physiology in 1967 and was a prominent activist in the movement against the Vietnam War and the nuclear arms race.

George Wald was born in Manhattan, NY, on November 18, 1906, the son of Ernestine Rosenmann, a Bavarian immigrant, and Isaac Wald, a Polish immigrant tailor. He was raised in Brooklyn, NY, and attended Brooklyn High School. He earned a bachelor of science degree in zoology at New York University.

Wald went to Columbia University to do graduate work, receiving a masters degree in 1928 and his Ph.D. in 1932. At Columbia he worked under Selig Hecht, one of the founders of biophysics and an expert in the physiology of vision. Hecht had great influence on Wald. In a memorial written after Hecht's death in 1947, Wald observed that "Hecht had a high sense of the social obligation of science. He thought it imperative that science be explained to the layman in terms that he could understand and could use in coming to his own decisions." Hecht wanted to abolish the military uses of atomic energy, and Wald came to similar beliefs.

Work on Vision

After completing his Ph.D., Wald was awarded a National Research Council Fellowship in Biology (1932-1934). He worked first in the laboratory of Otto Warburg in Berlin-Dahlem, Germany. There he first identified vitamin A as one of the major components of pigments in the retina and part of the process that turns light into sight. He completed the identification in the laboratory of Paul Karrer at the University of Zurich, Switzerland, the laboratory in which Vitamin A had just been isolated. Wald next worked in the laboratory of Otto Meyerhof at the Kaiser Wilhelm Institute in Heidelberg, Germany. There he discovered retinal (vitamin A aldehyde), a component of the visual cycle, in a batch of frogs imported from Hungary. Wald completed the second year of his fellowship at the University of Chicago (1933-1934).

In 1934 Wald was appointed a tutor in biochemical sciences at Harvard University, where he spent the rest of his academic career. He became instructor and tutor in biology (1935-1944), associate professor (1944-1948); professor (1948-1968), Higgins Professor of Biology (1968-1977), and Higgins Professor of Biology Emeritus (after 1977). He also was visiting professor of biochemistry at the University of California at Berkeley for the summer term in 1956. As his reputation grew, he frequently lectured to packed classrooms and his energetic style aroused students' interest in science.

In the late 1930s Wald discovered that the pigment of rhodopsin is the light-sensitive chemical in the rods, the cells in the retina responsible for night vision. He found rhodopsin was derived from opsin, a protein, and retinene, a modified form of Vitamin A.

For more than 20 years, Wald's research colleague was Paul K. Brown, who started out as his research assistant, then became a full-fledged collaborator. With Brown, Wald studied cones, the retinal cells responsible for color vision, and found that color blindness is caused by the absence of either of the pigments sensitive to red and yellow-green, two different forms of Vitamin A that exist in the same cone.

Wald married Frances Kingsley in 1931 and they had two sons, but they divorced. A former student, Ruth Hubbard, became Wald's second wife in 1958, and they had a son and a daughter. Hubbard joined Brown and Wald and formed a productive research team, "the nucleus of a laboratory that has been extraordinarily fruitful as the world's foremost center of visual-pigment biochemistry," according to John Dowling in Science (October 27, 1967).

Many Honors

In 1950 Wald was elected to the National Academy of Science and in 1958 to the American Philosophical Society. He was a fellow of the American Academy of Arts and Sciences in Boston and of the Optical Society of America. As a Guggenheim fellow, he spent a year in 1963-1964 at Cambridge University in England, where he was elected an Overseas fellow of Churchill College. He became an honorary member of the Cambridge Philosophical Society (1969).

Wald received many awards, including the Eli Lilly Award from the American Chemical Society (1939), the Lasker Award of the American Public Health Association (1953), the Proctor Medal of the Association for Research in Ophthalmology (1955), the Rumford Medal of the American Academy of Arts and Sciences (1959), the Ives Medal of the Optical Society of America (1966); and, with Hubbard, the Paul Karrer Medal of the University of Zurich (1967).

In December 1967 Wald was awarded the Nobel Prize in physiology/medicine, sharing the prize with Haldan Keffer Hartline and Ragnar Granit. Dowling noted: "No one has contributed more to our understanding of the visual pigments and their relation to vision than George Wald."

Political Activism

Six days after receiving the Nobel Prize, Wald exploited his new prestige by going before the city council of Cambridge, MA, to support a resolution placing a referendum on the Vietnam War on the city's ballot. A few years earlier, Wald had stunned an audience at New York University by denouncing the war while receiving an honorary degree. He also declared his support for anti-war presidential candidate Eugene McCarthy in 1968.

On March 4, 1969, Wald gave a talk at the Massachusetts Institute of Technology titled "A Generation in Search of a Future." It was part of a teach-in organized by radical students. The speech became famous and "upended his life and pitched him abruptly into the political world," according to an article by Richard Todd in the New York Times Magazine. Rejecting military uses of science and denouncing nuclear weapons, Wald said: "Our business is with life, not death." He called some political leaders "insane" and referred to American "war crimes" in Vietnam. The speech was widely reprinted and distributed.

In ensuing years, Wald poured his efforts into what he called "survival politics." He served as president of international tribunals on human rights issues in El Salvador, the Philippines, Afghanistan, Zaire, and Guatemala. In 1984, Wald was one of four Nobel Prize laureates who went to Nicaragua on a "peace ship" sent by the Norwegian government.

Wald's activism didn't halt the honors bestowed on him for his work in the field of vision. They included the T. Duckett Jones Memorial Award of the Whitney Foundation (1967), the Bradford Washburn Medal from the Boston Museum of Science (1968), the Max Berg Award (1969), the Joseph Priestley Award (1970), and honorary degrees from several universities.

Wald was also a collector of Rembrandt etchings and primitive art, particularly pre-Columbian pottery. Speaking of his interests in science, art and politics, Wald told the New York Times Magazine in 1969: "Nature is my religion, and it's enough for me. I stack it up against any man's. For its awesomeness, and for the sense of the sanctity of man that it provides."

Further Reading

A list of 183 publications by George Wald was printed in The Journal of the Optical Society of America 57 (November 1967). Wald's books include General Education in a Free Society (1945) and Visual Pigments and Photoreceptors: Review and Outlook (1974). Among notable articles by Wald are "Fitness in the Universe: Choices and Necessities," Origins of Life 5 (1974); and "Life and Mind in the Universe," International Journal of Quantum Chemistry. Quantum Biology Symposium 11 (1984). See also John E. Dowling, "News And Comment. Nobel Prize: Three Named for Medicine, Physiology Award. George Wald," Science (October 27, 1967), and "George Wald: The Man, the Speech," New York Times Magazine (August 17, 1969). □

WALD, George

(b. 18 November 1906 in New York City; d. 12 April 1997 in Cambridge, Massachusetts), biochemist, teacher, and political activist who won the 1967 Nobel Prize in physiology or medicine for his research on the role of vitamin A in vision and on the light-absorbing molecules in the retina.

Wald was the son of Isaac Wald, a Polish immigrant tailor, and Ernestine (Rosenmann) Wald, a housewife, who came from a small village in Bavaria. Shortly after his birth, the family moved from lower Manhattan to Brooklyn, where Wald attended Brooklyn Technical High School. The training he received there allowed him to modify and even build the scientific instruments later needed in his research. Wald did his undergraduate work at the Washington Square College of New York University, completing his B.S. in zoology in 1927. He then enrolled as a graduate student in zoology at Columbia University, earning an M.A. in 1928, and worked with Selig Hecht, who studied the physiology of vision.

Wald received a Ph.D. in 1932 and went to Europe on a National Research Council Fellowship in biology. He was accompanied on this trip by Frances Kingsley, whom he had married on 15 May 1931 and with whom he had two children; this marriage later ended in divorce in 1957. Wald did research in the laboratories of three noted European biochemists, beginning with Otto Warburg in Berlin. Working in Warburg's lab, Wald discovered that vitamin A plays a role in the functioning of the light-sensitive pigment rhodopsin, which is found in the retina of the eye. In Paul Karrer's lab at the University of Zurich, Wald confirmed the presence of vitamin A in the retinas of cattle, sheep, and pigs. At his third stop, Otto Meyerhof's laboratory at the Kaiser Wilhelm Institute in Heidelberg, Germany, Wald did research indicating that light splits rhodopsin into a protein called opsin and a molecule ultimately called retinal, a derivative of vitamin A. The reverse process occurs in the dark, thus regenerating rhodopsin. Wald discovered the biochemical explanation for the fact that when a person goes from a brightly lit room into a dark one, there is a temporary difficulty in seeing, called night blindness. The bright light splits rhodopsin into opsin and retinal. The pigment rhodopsin detects light in the cells of the retina, called rods. It takes a few moments to re-form the rhodopsin, thus making it possible to detect what little light there is in a darkened room.

After returning from Europe in 1934, Wald began his association with Harvard University in Cambridge, Massachusetts, ultimately becoming a professor of biology there in 1948. For the next forty years Wald continued to study the biochemistry of the visual pigments. He discovered that the cones, the cells that work in bright light and are responsible for color vision, also contain pigments with retinal attached to opsins. But the opsins of each of the three pigments in cones are different, and each responds to different wavelengths of light.

In 1958 two students arrived in Wald's laboratory who had a huge impact on the work done there in the 1960s. One was Paul K. Brown, who discovered how the cone pigments function and found that each form of color blindness is due to the absence of one of the three pigments. In the 1980s other researchers discovered the genes that determine the structure of the opsins in these pigments. The other student was Ruth Hubbard, who came as a graduate student and married Wald in 1958, while continuing to do research with him. They had two children. With Hubbard and Brown, Wald discovered that light causes a structural change in the retinal in rhodopsin. This change leads to the separation of the retinal from the opsin.

In 1965 Wald published a significant paper in the field of the biochemistry of visual systems. His research led him to speculate that a single photon or particle of light, initially splitting one rhodopsin molecule in a retina cell, could trigger a cascade of reactions that amplify the trigger, leading to the initiation of a nerve impulse going to the brain. He likened such a cascade or amplification process to that found in blood clotting. Wald's article stimulated research that established the validity of his view.

The 1960s were a busy time for Wald. In 1967 he was awarded the Nobel Prize in physiology or medicine for his research on visual pigments; he shared the prize with Ragnar Granit and Haldan Keffer Hartline. Also in the 1960s Wald became a political activist. The Vietnam War, which he opposed, initially stimulated his interest in civic matters. He was active in antinuclear causes and was supportive of the political uprisings in Nicaragua, the Philippines, Guatemala, and elsewhere. On 4 March 1969 Wald gave a speech at Harvard entitled "A Generation in Search of a Future," which attracted national attention to anti–Vietnam War sentiment and thereafter was referred to as "The Speech." After his retirement from Harvard in 1977, he devoted himself to political activism until the last two years of his life.

In addition to teaching his highly regarded biochemistry course, Wald began teaching a biology course for nonscience majors in 1960 and continued to do so until his retirement. In 1966 Time magazine cited him as one of the ten best college teachers in the United States. Wald was known as a brilliant lecturer, and his presentations on the origin of life and the evolution of the visual pigments were particularly popular. Wald's impact on the field of vision studies was immense. His work on the visual pigments took the study of vision down to the molecular level, describing how the molecular changes caused by light create electrical impulses that are sent to the brain. His 1967 Nobel Prize testified to the importance of these discoveries, and his work as a teacher and political activist indicated how science is not an isolated field but is tied intimately to the larger culture. Wald died of natural causes at his home in Cambridge at the age of ninety.

Wald's scientific papers, speeches, and correspondence are held by the Harvard University Archive. Biographies of Wald include "George Wald," in Modern Scientists and Engineers (1980); Marc Kusinitz, "George Wald," in Notable Twentieth-century Scientists (1995); and John E. Dowling, "George Wald," in Biographical Memoirs of the National Academy of Sciences (2000). See also "George Wald," New Yorker (1966); articles about Wald in Time (6 May 1966) and Science (27 Oct. 1967); and "George Wald: The Man, the Speech," New York Times Magazine (17 Aug. 1969). Obituaries are in the New York Times (14 Apr. 1997), Harvard University Gazette (17 Apr. 1997), and Time (28 Apr. 1997).

Maura C. Flannery

WALD, GEORGE

WALD, GEORGE (1906–1997), U.S. biologist and biochemist; Nobel Prize winner. Born in New York City, he received his B.Sc. in 1927 from New York University and his Ph.D. from Columbia University in 1934, where he developed his continuing interest in the biochemistry of vision. In 1934 he joined the Biological Sciences Department at Harvard University, where he rose to the rank of full professor in 1948. After discovering vitamin A in the retina, he showed that a derivative of this substance (retinene) is the primary lightsensitive pigment. Retinene is joined to specialized retinal proteins (opsins) in the visual pigments which abound in tiny structures of the retina called rods. Upon exposure to light, this attachment is broken as a result of chemical rearrangement of the retinene molecule, and ultimately vitamin A is produced. The significance of this fundamental biochemical cleavage pattern was enhanced by Wald's demonstration that it underlies the visual process in all organisms which possess a highly structured eye. Specific modifications of retinene and vitamin A characterize the lower vertebrates and provide biochemical insights into evolutionary relationships. He was the recipient of many honors and in 1967 was awarded the Nobel Prize for physiology and medicine. He wrote a widely acclaimed laboratory manual for general biology and co-authored General Education in a Free Society (1945). He was also active in the political arena and played a leading role in mobilizing opposition to U.S. involvement in the Vietnam war.

bibliography:

Current Biography Yearbook, 1968 (1969), 412–4.

[George H. Fried]