Emile Zuckerkandl, 1922-2013

Pauling and Zuckerkandl in Japan, 1986.

We close out our posting schedule for the year on a melancholy note with this remembrance of the life of Emile Zuckerkandl, who passed away on November 9th at the age of 91.

Zuckerkandl was born in Vienna, Austria on July 4, 1922. His family was of Jewish descent and active in the scientific, artistic, and political culture of the time. His father, Frederick, was a biochemist and his mother, Gertrude, was a portrait and landscape artist whose father, Wilhelm Stekel, was an anatomist. His paternal grandfather, Emil Zuckerkandl, was also an anatomist – one of great prominence – whose wife, Berta, was a journalist and art critic. Berta also hosted salons in Vienna attended by all manner of literary, musical and artistic figures.  She likewise used her position to speak out against Nazi occupation and militarization, a stance that forced the Zuckerkandls to flee from Austria into France in 1938 and to later to Algiers.

The family’s flight from Vienna briefly disrupted educational pursuits for Emile, who was attending high school at the time. He finished school in Paris before going to university in Algiers where he studied medicine. While there – as he would relate in a 1996 interview with Gregory Morgan at the Dibner Institute – “I came to understand that it was biology that I was interested in, more than medicine.” He was soon expelled however, a victim of the Vichy’s anti-Jewish laws that extended to colonial Algiers. By this point, the only schooling still available to him was at the music conservatory, where he studied piano.

Emile and Berta Zuckerkandl, ca. 1930. Image courtesy of the Austrian National Library.

While the family had escaped the dangers of residence in Austria and France, Emile’s outspoken grandmother was still not completely safe and so she sought to go to the United States. During this time, Albert Einstein took an interest in the young Zuckerkandl and helped him to obtain a scholarship to study in the U.S. The Zuckerkandls ultimately did not need to come to the United States as the Nazis were soon defeated, thus rendering France safe for the family once again. Nonetheless, Emile spent one year at the Sorbonne in Paris before taking advantage of the scholarship that Einstein had helped him to obtain.

Once stateside, Zuckerkandl attended the University of Illinois where, in 1947, he obtained a master’s degree in physiology, spending summers researching at the Marine Laboratory at Woods Hole in Massachusetts. He returned to the Sorbonne afterwards and earned his PhD in biology. Following that, he spent ten years at the Roscoff Biological Station in western France – the country’s largest marine laboratory – where he carried out biochemical research.

---

Emile and Jane Zuckerkandl, October 1970. Image courtesy of the Esther M. Lederberg Collection.

In 1958, while in Paris, Zuckerkandl arranged to meet with Linus Pauling. The two had been introduced through Alfred Stern, an Austria-born professor of philosophy at Caltech and a friend of the Zuckerkandl family. The following year Pauling recommended Zuckerkandl for a post-doc position at Caltech, stressing his relationship with Stern as well as with Charles Metz, who had received his PhD in biology from Caltech and was the brother of Emile’s wife, Jane.

Buoyed by Pauling’s initial recommendation and continued support, Zuckerkandl spent the next five years at Caltech. While there, Zuckerkandl propelled important work on what would become known as the molecular clock. The project was spurred by a suggestion that Pauling made to Zuckerkandl; that he compare the hemoglobin protein sequences of humans and gorillas to trace their evolutionary development. As Zuckerkandl told Morgan, “When Dr. Pauling made this suggestion to me, I was not too happy,” as he wished to continue his own line of research. But “later I understood how right Dr. Pauling was… At first I did not know how lucky I was!” Indeed, the molecular clock and molecular evolution would form the foundation of much of Zuckerkandl’s scientific career.

In 1961 Zuckerkandl, on Pauling’s recommendation, began working in Walter A. Schroeder’s lab, one of the few in the world researching protein sequences at that time. Zuckerkandl proposed that Schroeder coauthor the publication of his evolution work, but Schroeder refused due to his own creationist views. Pauling came to the rescue by suggesting that he coauthor with Zuckerkandl instead, but stipulated that they “should say something outrageous” since the piece was slated to appear in a prominent collection honoring the birth of Albert Szent-Györgyi.

The result was a classic 1962 paper, “Molecular Disease, Evolution and Genetic Heterogeneity,” in which Zuckerkandl and Pauling first postulated the idea of the molecular clock. As Zuckerkandl told Giacomo Bernardi in 2012, Pauling was more focused on his peace work at the time and his involvement with the paper was relatively tangential. Burdened by a crush of other obligations, Zuckerkandl’s coauthor agreed that he would “make some changes that would be moderate, and then the paper would come out as I conceived it.”

Morgan described the basics of the paper and its impact in a 2001 essay.

The molecular clock hypothesis, as it came to be known, proposed that the rate of evolution in a given protein molecule is approximately constant over time. More specifically, it proposed that the time elapsed since the last common ancestor of two proteins would be roughly proportional to the number of amino acid differences between their sequences. The molecular clock, therefore, would not be a metronomic clock – that is, its ‘ticks and tocks’ would not be uniform – but would instead be a clock based upon random mutation events. In practice, a molecular clock would allow biologists to date the branching points of evolutionary trees.

The molecular clock hypothesis, while rarely cited among Pauling’s most important discoveries, has proven to be very influential. The UC Berkeley biologist Alan Wilson claimed that the molecular clock is the most significant result of research in molecular evolution. In his book Patterns of Evolution, Roger Lewin describes the molecular clock as ‘one of the simplest and most powerful concepts in the field of evolution.’ Francis Crick, co-discoverer of the structure of DNA, called the molecular clock a very important idea that turned out to be much truer than most thought when it was proposed.

---

For the remainder of his time in Pasadena, Zuckerkandl continued to develop his ideas, and in this was assisted in the laboratory by his wife, Jane. Yet he was also eager to return to France, fueled in part by continued uncertainty surrounding his funding at Caltech. Pauling tried to help by recommending Zuckerkandl for a position in the anthropology department at the University of California – San Diego and by bringing back to Zuckerkandl contact information for scientists in Europe. Upon returning to Europe for a conference in 1962, Zuckerkandl wrote to Pauling, “It was as exciting, after three years of life in California, to rediscover Europe as it had been to first discover America.” Soon afterwards, he obtained a position at a new research facility in Montpellier, France – the only hitch was that he needed to wait three years for it to be built. In the meantime, Zuckerkandl expressed worry to Pauling that his work on gorilla hemoglobin would soon “be out of date” because of the interruption posed by his return to France.

Once Zuckerkandl and his research materials had finally arrived in Montpellier in 1965, new problems arose. He told Pauling, “I did not foresee the particular kind of obstacles that I find in my way. Bureaucracy is taking over the direction of our laboratory.” (In a 1971 letter, when asking how Pauling had been such a “great fighter” for peace and science, Zuckerkandl concluded that it could only have been because Pauling had “not tried to found a research department in France.”)  This manner of struggle proved a defining feature of Zuckerkandl’s years at Montpellier and it was not long before he and Pauling began seeking out avenues to reunite, both through short visits and Zuckerkandl’s standing invitation for Pauling to come to Montpellier as a visiting researcher. A bright spot occurred in 1970 as Zuckerkandl was offered the editorship of the new Journal of Molecular Evolution by Conrad Springer.

Zuckerkandl with Ewan Cameron, New Years Day, 1979. Image courtesy of the Esther M. Lederberg Collection.

Zuckerkandl eventually decided to leave France and return to the United States. In 1975 Pauling offered Zuckerkandl lab space at the Linus Pauling Institute of Science and Medicine, but by then he was already at Woods Hole where he hoped details might get resolved at his old position and he could return to Montpellier. A bit later, when Zuckerkandl decided to take Pauling up on his offer, Pauling had to turn him down due to the Institute’s mounting financial problems. Zuckerkandl stayed at Woods Hole and had assumed a visiting professorship at the University of Delaware when, in 1976, Pauling offered him a year-long non-resident fellowship.

---

LPISM Newsletter, 1977.

Zuckerkandl quickly moved up the ranks at the Institute. At the end of his fellowship, Pauling recommended that he be sponsored for a two year visa and become Vice Director of the organization. By 1979 Zuckerkandl held the additional positions of Vice President and Research Professor, assuming responsibility for carrying out his own work on vitamin C and cancer while also helping Pauling with administrative duties. By the end of the year, Zuckerkandl was taking on even greater administrative responsibilities from Pauling, including budgeting, fund raising, and finding a new home for the Institute.

During this period, Zuckerkandl’s management skills came to the fore. He immediately set out to establish priorities for research, setting a “cutting off point” in time after which any new projects would be “provisionally abandoned.” He also dealt with the storm of controversy caused by the firing of Institute President Art Robinson and Robinson’s statement in Barron’s that high doses of ascorbate led to tumor development in mice. (In a memo to Pauling, Zuckerkandl noted that “the data do not appear to authorize Art’s statement’s” which were most likely based on a “scatter of the experimental points” and nothing more definite.)

The following year, Zuckerkandl was made President and Director of the Institute. Funding continued to be a problem, with each advance seemingly countered by a setback. Typically, at about the same time that the Institute agreed to pay a settlement to Robinson, Zuckerkandl also oversaw the opening of the Armand Hammer Cancer Research Center, with support from its namesake. In 1985, to show his dedication to the Institute, Zuckerkandl deferred a raise that he had been offered until it could be afforded.

However, in 1992 Zuckerkandl’s contract was not renewed. By then the Institute was in a dire financial position and needed to make some very difficult decisions concerning staffing and programs. Nonetheless, Zuckerkandl remained in the building through a lease agreement between LPISM and his new Institute of Molecular Medicine. He also invited many LPISM staff, some of whom had also been laid off, to join him in his fledgling enterprise.

---

Emile Zuckerkandl, 1993.

When not managing a research institute, Zuckerkandl continued to produce work on molecular evolution. In 1997 and 2007, continuing a career-long debate over the relationship between molecular evolution and natural selection, Zuckerkandl addressed molecular diseases and “junk DNA” to argue against the neutral theory of molecular evolution. Beginning in the late 1960s, Motoo Kimura, Jack King, Thomas Jukes, and others had used the molecular clock idea to suggest that evolutionary change occurs not because of natural selection, but due to neutral random mutations and allele drift. Zuckerkandl disagreed, arguing that natural selection and the molecular clock were compatible.

Zuckerkandl not only argued against what he saw as misapplications of his own ideas, but also against broader cultural attacks on science. Beginning in the late 1980s, he began to speak out against creationists, telling Pauling in a 1991 memo that “since in this country they seriously threaten education and culture, a response to them needs to be made.”  As Zuckerkandl saw it, the threat was not only cultural but also involved the health of humanity and of the Earth. In a 1991 draft titled “Genetic and Esthetic Winter,” which he shared with Pauling, Zuckerkandl proposed the need for more control of population growth to curb human impact on the environment, an imperative that he saw as being impeded partly by religious beliefs.

Zuckerkandl also turned his gaze toward enemies within the academy, attacking the application of social constructivism to science. In a 2000 paper, he argued that while scientific discoveries may be socially determined, the “mature” results that lead to practical applications, especially in technology and medicine, is “evidence for independence” of science from similar influences.

But Zuckerkandl did not maintain a strict scientism. In “Genetic and Esthetic Winter,” he described the resilience of science, but also its limitations. When speaking about threats to environmental stability, he stated,

In this situation, curiously, scientific culture is perhaps the least threatened province of culture. Yet knowing and knowhow are not enough. Perceiving and feeling cannot be replaced by engineering. We can’t be satisfied with preparing a future in which the environment will be enriching only for the vocation of engineers.

Zuckerkandl’s health steadily deteriorated as he advanced in age. Over time, a troublesome back proved to be especially problematic. He died on November 9, 2013 in Palo Alto, California, the victim of a brain tumor.