Pauling and Perutz in the Golden Age of Protein Research

Max Perutz, 1987. Image Credit: Graham Wood.

Max Perutz, 1987. Image Credit: Graham Wood.

[Part 3 of our series celebrating the Perutz centenary.]

In 1939 Max Perutz’s girlfriend gave him a book token for Christmas. Working on finishing his dissertation on the structure of hemoglobin, Perutz used that token to purchase Linus Pauling’s recently published text, The Nature of the Chemical Bond.

In the obituary of Pauling that he wrote some fifty-five years later, Perutz described how the “book transformed the chemical flatland of my earlier textbooks into a world of three-dimensional structures” and “fortified my belief, already inspired by J. D. Bernal, that knowledge of three-dimensional structure is all-important and that the functions of living cells will never be understood without knowing the structures of the large molecules composing them.”  The purchase of Pauling’s book marked the beginning of a long, fruitful and sometimes contentious correspondence between the two men, working on separate continents but united by similar interests.

Not until 1946 did Perutz first write to Pauling, asking for assistance as he labored through his research on the structure of hemoglobin. The Cavendish Laboratory, where Perutz was located, did not have the latest equipment that was available to Pauling at Caltech. In particular, Perutz needed a Hollerith punch-card machine to carry out calculations of the three-dimensional Patterson-Fourier synthesis. Perutz knew that Pauling’s lab was already conducting calculations of this sort and that the work Perutz was doing “would have to be done sooner or later, if the molecular structure of the proteins is to be worked out.”

As such, Perutz hoped that someone in Pauling’s lab might do the calculations for him. Pauling was not moved enough by Perutz’s request to offer the labor of his own team, replying that enlisting someone do such work in a “routine way” could lead to confusion. Pauling did offer that Perutz come to Pasadena, or send a surrogate to do the work, if he could find the money. Perutz was unable to support such an undertaking and so ended that conversation.

Linus Pauling and Lord Alexander R. Todd. Cambridge, England. 1948.

Two years later, in 1948, Pauling was in England, enjoying a stint as George Eastman Professor at Oxford. It was during this time that he and Perutz met for the first time in person. Perutz described his first experiences of Pauling’s lectures, in which

he would reel off the top of his head atomic radii, interatomic distances and bond energies with the gusto of an organist playing a Bach fugue; afterwards he would look around for applause, as I had seen Bertrand Russell do after quoting one of his eloquent metaphors.

The two also found time to talk together about their own particular research projects.

Pauling’s work at Oxford touched directly on Perutz’s own program, in what would become a oft-noted story in twentieth century history of science. As Pauling lay in bed with a cold, he did not stop working, choosing to spend his time making planar peptide models with paper chains. From his paper folding exercises, Pauling, according to Perutz’s obituary, “found a satisfactory structure by folding them into a helix with 3.6 residues per turn.” (A story that Pauling relayed many times himself.) The structure would come to be known as the alpha helix.

After Pauling recovered from his illness, Perutz showed him his own model of a polypeptide chain which was part of his larger hemoglobin model and was similar to fibers described by William Astbury. To Perutz’s “disappointment, Pauling made no comment,” and gave no hint as to his own breakthrough, which he announced the next year in a “dramatic lecture.”  That later unveiling of the alpha helix gave rise to a famous Perutz anecdote, which later informed the title of a book of essays that Perutz published.

When I saw the alpha-helix and saw what a beautiful, elegant structure it was, I was thunderstruck and was furious with myself for not having built this, but on the other hand, I wondered, was it really right?

So I cycled home for lunch and was so preoccupied with the turmoil in my mind that I didn’t respond to anything. Then I had an idea, so I cycled back to the lab. I realized that I had a horse hair in a drawer. I set it up on the X-ray camera and gave it a two hour exposure, then took the film to the dark room with my heart in my mouth, wondering what it showed, and when I developed it, there was the 1.5 angstrom reflection which I had predicted and which excluded all structures other than the alpha-helix.

So on Monday morning I stormed into my professor’s office, into [William Lawrence] Bragg’s office and showed him this, and Bragg said, ‘Whatever made you think of that?’ And I said, ‘Because I was so furious with myself for having missed that beautiful structure.’ To which Bragg replied coldly, ‘I wish I had made you angry earlier.’


Once Pauling returned to Pasadena, he and Perutz fell into a minor quarrel. In December 1950, Perutz had heard that Pauling had been “annoyed” by Perutz and John Murdoch Mitchison’s paper, “State of Hæmoglobin in Sickle-Cell Anæmia,” which had been published in Nature that October. Pauling was upset that Perutz and Mitchison had suggested that crystallization caused cells to sickle without properly citing his own seminal work on the subject.

In a December letter, Perutz said he was “very disappointed” that Pauling was upset with the publication, not only because there was a reference to Pauling, et al. in its introductory paragraph, but “particularly because all the new experimental evidence we report seemed to fit in so beautifully with the basic ideas set out in” Pauling’s co-authored Science article, “Sickle Cell Anemia, a Molecular Disease,” published in November 1949. Perutz explained his position in more detail, noting,

There is perhaps a slight difference between our points of view. Whereas you regard the sickling as being due to an aggregation and partial alignment of hæmoglobin molecules by a lock and key mechanism, an interlocking of specific groups in neighbouring molecules, we regard the cause of the sickling as being simply a crystallization, due to abnormally low solubility of the reduced hæmoglobin. No specific interaction of the kind you mention need be involved in the second process, though it obviously may be…I am sorry that this misunderstanding between us should have arisen, particularly as I have spent much effort trying to convert unbelievers to your scheme.

Pauling waited until the following February to respond and explained his feeling that readers of Perutz’s article might conclude that Perutz was making an original proposal. Having made this statement, Pauling, in his own way, moved beyond the quarrel by telling Perutz about his more recent work showing that “hemoglobin is not crystallized in the sickle cells, but is only converted to the nematic [or liquid crystal] state.” The ice broken, Perutz quickly responded by inviting Pauling to take part in informal discussions about protein structure at the Cavendish Laboratory before an annual conference, to be held in Stockholm. Pauling, however, could not attend.

The next year, Pauling attempted to visit England, this time to speak at a conference about the alpha helix, but was delayed due to his passport renewal being denied on account of his political activities. Perutz wrote that Pauling’s “absence had a sadly damping effect on our meeting at the Royal Society, and it made the discussion rather one sided as there was no none to answer the various objections to the α-helix raised by the Astburites and Courtlauld people” since Pauling’s supporters were unprepared to defend Pauling’s position without him. Perutz was also keen to show Pauling his own progress, an eagerness that Pauling reciprocated. By July Pauling had cleared up his passport problems and was able to spend time in person discussing his and Perutz’s work.

By 1953 Perutz and Pauling were quarrelling again over proper citation, though this time it was Perutz suggesting that Pauling had not given Francis Crick enough credit regarding the coiling of alpha helixes. Pauling explained to Perutz that, while he was at Cambridge the previous summer, he had talked with Crick and John Kendrew at length. During that conversation, according to Pauling,

There was only brief discussion of α keratin at this time, and, if my memory is correct, only a few sentences were said about the coiled coil, as Crick calls it. We discussed the fact that the 5.15-Å meridional reflection offers some difficulties of explanations, and that also there seemed to be a discrepancy in the density of α keratin. The discussion was very brief. Then Mr. Crick asked me if I had ever thought of the possibility that the α helixes were twisted about one another. I answered that I had. So far as I can remember, nothing more was said on this point.

Pauling went on to emphasize that “the idea was not a new one to me then” and that his own description of it in Nature was different from Crick’s understanding. Perutz ceded this point, adding that Pauling’s differences with Crick “stimulated Crick to clarify his own” ideas on the coiling of alpha helixes. More generally, Perutz found that the competition that arose between the two labs as they worked on similar problems helped to push each forward, thus leading to positive advances.

The famous group photo of the Pasadena Conference on the Structure of Proteins, September 1953. Pauling stands front row, third from left. Perutz stands two rows behind Pauling. [Image credit: The Archives, California Institute of Technology]

That September, Perutz made his first visit to California in order to deliver a paper at the Pasadena Conference on the Structure of Proteins, at which were gathered all of the world’s major figures in the field, including Jim Watson and Francis Crick, newly famous for their double helical structure of DNA. Perutz told his wife, Gisela, that his paper was “well received.” Additionally, with all of the different perspectives presented, there was “an atmosphere of soberness, and a realization that no-one’s solution of the protein problem was complete, and every approach was still fraught with complications.” Perutz was also quite taken with the Paulings’ home and their hospitality, pointing out that Ava Helen had invited him “after one of the meetings for a swim in their garden.”

Correspondence between Perutz and Pauling dipped a bit after the conference, though Pauling did take a moment to congratulate Perutz on being elected to the Royal Society the following Spring. While the exchange was brief, it reflected the long relationship built up between the two over the preceding years and, in particular, a confluence of work that had boosted the esteem of both scientists.

Perutz had begun looking at the structure of wool proteins back in 1951, thinking that there might be similarities to hemoglobin. He became excited after finding Pauling’s work on alpha helixes in fibers, thinking that the structure might be present in wool as well. His initial studies resulted in disappointment, but after adjusting the angle at which he was taking his x-rays by 30 degrees, he compiled new data that confirmed Pauling’s alpha helix structure. After applying it to his own work on hemoglobin, Perutz told Pauling “the discovery of this reflexion in haemoglobin has been the most thrilling discovery of my life…there is no doubt that it is a universal feature at least of all fibers of the α type. Whether all crystalline proteins show it remains to be seen.” Not suprisingly, Pauling was also “very pleased” with this discovery.

This research opened the door for Perutz to be considered by the Royal Society. But it was his development of a technique for determining a three-dimensional view of structures derived from x-ray crystallography that assured his election. He did this be attaching mercury atoms to hemoglobin, which allowed him to figure out where the crest and trough of a given x-ray was in relation to the structure that appeared on the photos. Perutz later said that after he finished the work and published it in Nature at the end of 1959, he went skiing in the Alps, and by the time he returned he was famous, assuring his fellowship in the Royal Society.


The Continuing Voyages of the R/V Alpha Helix

Schematic of the R/V Alpha Helix, 1966.

Schematic of the R/V Alpha Helix, 1966.

[Part 2 of 2]

Built in 1965, the R/V Alpha Helix, named after the protein structure discovered by Linus Pauling, had proven itself – over the course of two years and two voyages totaling 34,110 miles – to be a versatile research vessel. The National Science Foundation (NSF), which owned and had sponsored the construction of the vessel, was pleased with the ship’s performance in the Pacific Ocean and in the Amazon River. So in early February 1968, they deployed her on her third voyage, this time to the Bering Sea.

Due to environmental hazards posed by the Bering Sea, the expedition there was smaller in time, distance traveled, cost and crew. The voyage lasted nine months, cost $574,000 ($3.8 million in 2013) and utilized fifty scientists from five nations. The mission’s typically eclectic goals were to study how animals survive in frigid environments; to determine why spawning salmon suffer from atherosclerosis; and to investigate the feasibility of building research labs on floating sea ice. The Alpha Helix performed admirably, though she lacked sufficient hull strength and engine power to safely break through all of the ice that she encountered and thus required escorting by the U.S.S. Northwind, a U.S. Navy icebreaker. Researchers from the University of Alaska, Fairbanks (UAF) reported on the vessel’s performance to their school, a report which heavily influenced the future design of the Alaska Region Research Vessel.

In the years that followed, the Alpha Helix continued to be sent on missions as often as was safe. She averaged one mission a year, each taking between nine and thirteen months. In 1969 she went on a $613,000 ($3.85 million in 2013) expedition to New Guinea to study mammals, birds, fishes, bioluminescence and heatless light produced by fireflies, fungi, and fish. The U.S., Australia, New Guinea, Indonesia, Malaysia, France, and Japan sent 66 researchers on the trip. The years 1970-1971 saw the Alpha Helix undertake a 25,000 mile expedition to the Galapagos Islands, Antarctica, and the Marshall Islands. In 1972 she went to the Solomon Islands, West Hebrides and the Western Caroline Islands.

After her 1972 mission, she was sent to dry-dock for retrofits and routine maintenance. The retrofits mostly involved upgrading her lab equipment to the most modern gear, work which required an appreciable investment of time. Not until mid-June 1976 did she launch on another voyage (See 3-14-14 update below) – a second trip to the Amazon River basin. This trip was more extensive than the first: it lasted a full year and required sailing upriver all the way to the headwaters of the Amazon, 2,500 miles inland. One hundred and twenty scientists from the U.S., Brazil, Columbia, Peru, Canada, Italy, Scotland, England, West Germany, Denmark, Norway, Chile, and Switzerland studied a diverse range of topics including the genetic structure of “primitive man” amongst Brazilian Indian groups; hemoglobin in fish and their ability to see; chemical characteristics of the Amazon River; the ability of certain Amazon fish to live on land; the resistance of various organisms to stress; and the toxic and medicinal properties of local flora. The expedition was extremely productive and also extremely hard on the vessel, which upon return to the U.S. was put in dry-dock again for about three more years.

In 1980 UAF sent a message to the NSF requesting a larger, more modern research vessel to replace their aging and cramped ship (only 80′ long), the R/V Acona. The NSF decided to replace the Acona with the Alpha Helix, and transferred her from Scripps Maritime to UAF. Upon arrival, she was immediately put into dry-dock again, where she underwent extensive retrofits. The focus of her labs was changed from mostly biological research to general oceanographic studies. And the ship’s equipment was modernized: the vessel received a strengthened hull for icebreaking, more cold-weather protection was added, and deep-sea oceanographic winches were installed below decks. All of these retrofits brought the Alpha Helix up to American Bureau of Shipping classification standards for a ship of her size.


The Alpha Helix remained busy and valuable in the employ of UAF.  One particular task of note was to provide “systematic description of the Alaska Coastal Current from British Columbia to where it empties into the Bering Sea at Unimak Pass.” This data was invaluable in predicting the path of the oil spill emanating from the Exxon Valdez disaster in 1989. She also spent extensive amounts of time studying wildlife and water in the Bering Sea, Arctic and Alaska regions. During one trip taken in the early 1990s, she traveled about 25,000 miles, slightly more than the circumference of the Earth. Despite this, UAF increasingly came to feel that the Alpha Helix was insufficient for their needs. Specifically, they felt that her size was a limiting factor and that the hull was not strong enough to carry out the heavy ice work that they required.

In 2004 UAF put the Alpha Helix in dry-dock indefinitely and thus concluded a period of great productivity. Between 1981-2004, the ship had averaged 151 sailing days per year, and logged 3,629 total days doing research. Of those, she spent 2,390 days (65.8%) in the Bering Sea and Arctic Ocean, 907 days (25%) in the Gulf of Alaska, 187 days (5.2%) in southern Alaskan waters, and 145 days (4%) in other locations. The massive amount of research that she facilitated was mostly funded by the NSF, which paid for 76.4% of the cost. The National Oceanic and Atmospheric Administration (NOAA) covered the second highest amount at 10.8%. The remaining 12.8% of her operational costs were funded by the Japan Agency for Marine-Earth Science and Technology (JAMSTEC), the Bureau of Ocean Energy Minerals Management Services (MMS), the Office of Naval Research (ONR), private sponsors, the North Pacific Marine Research Program (NPMRP), NASA, UAF, and the Alaskan state government.

The Alpha Helix was kept in dry-dock from 2004-2007, at which point she was sold by UAF to Stabbert Maritime, a family-run private company with a fleet of about 10 vessels. At the time of this writing, the company was owned by Mr. Daniel Stabbert. In a phone interview conducted in 2013, Stabbert spoke of his affection for the vessel.  He described her as “the SUV of the fleet…you could beat the [heck] out of her and she’d just keep running.” She is very fuel efficient, and the company gave her a bulbous bow to further increase fuel efficiency. They put on speed stabilizers and stern jet thrusters to further increase her stability in rough seas; they also removed one of the smaller machine shops and expanded the science team quarters and the lounge, so it can now carry a science staff of 21.

Between 2007-2010, the Alpha Helix was contracted by Stabbert Maritime for missions in the Bering Sea, Alaskan waters and the Arctic Ocean. She worked for various groups, mostly doing research on geology, fisheries and drill site surveys for Shell Co. and other oil companies. During this time, she was also contracted by the U.S. Navy to monitor noise levels on nuclear submarines undergoing degassing and repair operations; other contracts she performed for the Navy remain classified. In late 2010 she was sent to the Gulf of Mexico to assist with the cleanup required by the Deepwater Horizon oil spill. She remained in the area for a year to help monitor local fisheries. In 2012 the Alpha Helix was sent to Trinidad to conduct hydroscopic research and collect core samples.

Over the past few years, government research for funding has been decreasing, which makes running research vessels riskier for private companies. As such, Stabbert decided that he needed to upgrade his fleet to more multipurpose vessels, which the Alpha Helix most definitely is not. Therefore, despite his personal affinity for her, Mr. Stabbert sold the Alpha Helix to the University of Mexico City (UNAM) and it is now uncertain what the future holds for the ship. No matter what, the vessel has made regular contributions to science over past 48 years, and has affected the lives of hundreds of people who worked on or with it, often in ways that were unexpected: in our interview, Stabbert reported that he had been on a trip to Thailand during the 2012-2013 winter season, and had run into a banker whose father was one of the researchers on the second Amazon expedition.

The Alpha Helix has proven to be a rugged, fascinating, and incredibly useful vessel that has brought together generations of scientists from around the globe to collaborate in finding out how this amazing planet works. In furthering our understanding of the world around us, she has acted in a spirit that surely would have pleased Linus Pauling.

Update (2-12-14):

We were tickled to receive this message and photo today from JC Leñero of the CICESE research center, Ensenada, Mexico:

You may like to know that last year, we purchased the R/V Alpha Helix from the guys at Stabbert Maritime, in order to replace our smaller Research Vessel, the Francisco de Ulloa (28 meters LOA). As of today, Alpha Helix keeps her name (and, regarding the historical weight of bearing said name, we will not rename her), has her home port at Ensenada, Mexico, she flies the Mexican flag and is due to begin research operations again, hopefully in a few months, after some maintenance to her machinery is completed.


The B/O Alpha Helix, 2014.

Update (3-14-14):

A further update submitted by Tom Forhan, a former marine technician on the Alpha Helix.

Enjoyed reading about Dr. Pauling and the Alpha Helix, which I had never heard before. For the record, though, the ship did not waste any time between the refit in 1972 and the second Amazon expedition in 1976. Off the top of my head in 1973 it worked in both Baja California and then headed for research in Hawaii. The following year began a Pacific tour. After a stop in Australia, including work on bioluminescence around the Banda Sea in Indonesia, and an investigation of sea snakes in the Philippines. Heading back to North America the ship did research on salmon physiology in British Columbia, and in late 1975 or early 1976 headed down to the coast of Peru to participate in a multi-ship (including OSU’s research vessel) investigation in a program called CUEA, looking at El Nino. I believe OSU archives has some pictures of the Helix at sea during that time. After CUEA, the ship went through the canal and up the Amazon. My source here is my memory;I was a marine technician aboard the ship during those years.

The R/V Alpha Helix

The R/V Alpha Helix, 1966.

[Part 1 of 2]

It was early 1966 when Linus Pauling received a letter informing him that a new research vessel had just been constructed in Washington state. The reason this was notable to Pauling was the vessel’s name – it was called the R/V Alpha Helix, named after a secondary structure of proteins that Pauling had discovered.

The Alpha Helix was designed by L.R. Glosten and Associates, a naval architecture firm based in Seattle, Washington. It was built by the J.M. Martinac Shipbuilding Corporation in nearby Tacoma; construction began on September 9, 1964, and the keel was laid on December 9, 1964. The Alpha Helix is 133’ long, 31’ abeam, 14.5’ deep, and made with welded steel construction, transversely framed. She is powered by an 820-horsepower General Motors diesel engine, which drives a variable pitch propeller (for superior speed control) at 800 rpm and provides a top speed of 12.25 knots and a cruising speed of 11 knots. She carries a 29,250 gallon fuel tank, which at 9.5 knots gives her a range of 6,500 miles. The Alpha Helix also holds a second tank which contains 5,000 gallons of potable water.

She is a pure research vessel, and designed to be extremely compact and versatile; she has air-conditioning for tropical conditions and a reinforced hull strengthened for “moderate ice work” in arctic seas. On the port, aft side of the vessel, she has a cargo crane capable of lifting up to 5,310 lbs., which she needs, as in the hold she carries a jeep and a prefabricated 8×12′ shore laboratory. The Alpha Helix is also outfitted with mountings such that special work platforms can be fixed to the hull just above the waterline, running from bow to stern. She carries two skiffs and two workboats, measuring 17′ and 24′ long, respectively.

Despite her relatively small size, the Alpha Helix is designed to use space at maximum efficiency. At the time of her construction, she had space for a crew of 12 and a scientific party of 10. Additionally, she has ample room for research, including a library “with a large blackboard and acoustics suitable for conferences and chamber music.” But the heart of the vessel are her numerous research laboratories. She has a wet lab taking up 81 square feet, which at the time of construction could be chilled to 5° C. She also featured 457 square feet of dry labs, electrophysiological labs, optical labs, and a freeze lab that could be chilled to -20° C. These spaces required a significant quantity of specialized equipment which would be difficult to replace or repair during voyages, so she also has a full machine shop, equipped with lathes, drills, presses, welding equipment, and even a glass-blowing station. At the time of construction in late 1964, the Alpha Helix cost $1,272,021, roughly equivalent to $9.14 million in modern currency.

Invitation to the dedication of the R/V Alpha Helix, June 1966.

Invitation to the launching of the R/V Alpha Helix, June 1965.

The Alpha Helix was launched on June 29, 1965 in Tacoma, after which point she set out for San Diego, California. She was owned and had been funded in near entirety by the National Science Foundation (NSF), which had assigned her to work from the Scripps Institute of Oceanography, operated by UC San Diego.

The vessel was going to be dedicated at a large ceremony on March 11, 1966. At the same ceremony, the new Scripps Marine Facility and the R/V Thomas Washington were also slated for dedication. Dr. P.F. Scholander, a professor of Physiology and the director of Scripps’ Physiological Research Laboratory, wrote to Pauling and asked him to serve as the principal speaker at the event, due in no small part to the name of the Alpha Helix. Pauling wanted very badly to attend but was unable to do so as March 11 was the day that he was scheduled to be in New York City to begin his ill-fated libel lawsuit against The National Review, which had published two editorials that accused Pauling of being a communist, a “megaphone for Soviet policy…” and a traitor. Due to Pauling’s inability to attend, Prof. Scholander invited Dr. Robert W. Morse to be the principal speaker. Morse was a Navy veteran of World War II, the assistant secretary of the Navy for research and development, and the chairman of the Committee on Oceanography of the Federal Council for Science and Technology.

Shortly after the dedication, the Alpha Helix embarked upon its maiden voyage, an eight-month, 16,500 mile expedition named “Expedition Billabong” (an Australian term for a waterhole). James Faughn captained the vessel for the mission, which would extend to Australia’s Great Barrier Reef, with brief stops at the Cook Islands, American Samoa, and Hawaii upon the return to southern California. The entire mission was funded by the NSF, and its objectives were to study desalination of seawater by mangroves, electrophysiology of mollusks, symbiotic interactions in corals, and osmotic and cardiovascular behavior in dugong. During the course of the expedition, 44 scientists from 19 different institutions sailed on the Alpha Helix. Pauling wanted to serve as a researcher on the initial trip, but his lawsuit prevented it. Of the scientists on board, 22 hailed from the United States, while the remaining 20 came from Australia, New Zealand, England, Sweden, and Japan. The vessel performed her mission admirably and no modifications were made after the voyage.

After a few months of routine maintenance, the Alpha Helix departed in early February 1967, for her second voyage. This expedition lasted 11 months, and the destination was far up the Amazon River, deep into the jungle. The NSF sponsored this trip as well, which cost $600,000 (about $4.14 million in modern dollars). The Amazon trip was grander than the first voyage; the total distance traveled was 17,610 miles. And the time, distance, and cost of the trip were not the only increases: 82 researchers from the U.S., Brazil, England, Canada, Norway, West Germany, France, New Zealand, Sweden, Australia, Japan and the Soviet Union participated as well. The mission’s research goals were ambitious and exotic in equal measure. They included:

  • “the insect-free Rio Negro River”
  • singing habits of cicada
  • hallucinogenic snuff used by indigenous locals
  • sloths, electric eels, piranha and fresh-water dolphins
  • infrared sensing capabilities of the boa constrictor
  • the physiology of salt and water in animals
  • the potential of crude petroleum emanating from “smog” given off by certain jungle trees
  • respiratory mechanisms in indigenous fruits
  • the moisture secreting capabilities of trees
  • sap pressure in the “drowned forests of Brazil”
  • the metabolism of fish
  • respiration of Galapagos Island marine iguanas

Once again the expedition was a solid success and the Alpha Helix performed admirably. In fact, the mission ended up being more even informative than the scientists had originally anticipated, as on the way to the Amazon they discovered ten new species of deep-sea scorpion fish.

Very quickly the Alpha Helix had proven herself to be an excellent, compact and flexible research vessel. While the first two voyages had taken place in tropic climates, the NSF next had plans to try out her arctic capabilities. As 1968 began, crews loaded the vessel up for her next trip, to the Bering Sea and beyond.

Pauling and Proteins: The Final Five Publications

Linus Pauling showing a molecular model to a young boy. 1950s.

[Part 3 of 3]

On March 31, 1951, Linus Pauling and numerous associates published seven revolutionary papers in a single issue of the Proceedings of the National Academy of Science. The research had been funded by the Rockefeller Foundation and carried out at the Gates and Crellin Laboratories of Chemistry, at Caltech. The first two articles: “The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain” and “Atomic coordinates and structure factors for two helical configurations of polypeptide chains,” have been discussed by us in the two weeks prior to this one. The remaining five will be described here in much shorter detail, as they are technical in the extreme.

The third article was titled “The structure of synthetic polypeptides,” and was written by Pauling and Robert B. Corey. The article claimed that the gamma helix and alpha-helix protein structures had forms that were also assumed by synthetic polypeptides. The authors discussed how the fibers of synthetic polypeptides had been analyzed using x-ray and infrared spectroscopy, which allowed them to determine the shape of the synthetic structures. Other scientists had also proposed the shapes of such structures, but Pauling and Corey rejected their hypotheses, as the structures the other scientists had proposed would have been “inherently unstable.” They concluded that their structure was the superior idea, and that while other structures potentially existed, they would be extremely difficult to measure due to their size.

The fourth article was more crucial to the narrative of protein structure that Pauling and his collaborators were weaving. The title was self-explanatory, and somewhat less technical than the others: “The pleated sheet, a new layer configuration of polypeptide chains.” In it, Pauling discussed how it had been long-believed that polypeptide chains are fully stretched and bound to adjacent, lateral chains of protein. He proposed instead a new idea, the so-called “pleated sheet.” In his suggested structure, the chains formed planes and certain bonds were arranged perpendicular to the planes of the chain, instead of coincidental with them. As a result, the chains are staggered and scrunched, instead of stretched in long, parallel lines. The rest of the article was devoted to the mathematics that Pauling had used to develop and explain the shape.

Feathers – specifically the atomic structure of feathers – was the topic of the fifth article, titled “The structure of feather rachis keratin.” The piece was written once again by Pauling and Corey and it analyzed rachis – a term with many meanings, but in this context referring to the central shaft of a feather – and keratins, which are structural proteins. The authors wrote that x-ray analysis of feather rachis keratin had shown the patterns of the polypeptide chains to be extremely complex, and notably shorter than expected. The rest of the article was spent explaining how the concept of the pleated sheet was mathematically relevant to feather rachis keratin.

Second to last was an article called “The structure of hair, muscle, and related proteins,” written by Pauling and Corey. In it, the authors pointed out that it had been many years since R.O. Herzog and Willie Jancke, in 1926, had made important x-ray photos of hair, muscle, nerve and sinew. Pauling and Corey felt that these photos, though revolutionary, were no longer adequate. Yet despite this deficiency, few modern attempts had been made to take better photographs. Two scientists named Lotmar and Picken had tried in 1942, but Pauling felt that their pictures were likewise not detailed enough. The Caltech researchers determined that their lab had found enough data though, and proposed structures for hair, muscle and “related proteins.”

This article differed from the other six in that it had an addition dated April 10, 1951. Written by Verner Schomaker, the addition revealed that subsequent research had shown that, while its basic premise was correct, the argument outlined on the piece’s first two pages was in fact wrong, and that the rest of the article hoped to amend that. Pauling and Corey argued that relaxed muscle was configured as a sheet, while contracted muscle formed an alpha-helix. The sheet configuration was inherently unstable relative to the alpha-helix, which made it easy for the hydrogen bonds holding the muscle in a sheet to break. This breakage allowed the polypeptide chains to coil and in turn made the muscle contract. The mechanism to prevent a chain reaction that might result in the sheet ripping itself apart during contraction was not understood, though Pauling had some ideas for that as well. The rest of the article was spent analyzing the amounts of energy released in frog muscle contractions to provide hypothetical amounts of energy expenditure and size for contractions in human muscle.

Representation of the collagen-gelatin molecule. April – May 1951.

The final article was “The structure of fibrous proteins of the collagen-gelatin group.” In it, Pauling wrote of his particular fascination with the protein in question:

Collagen is a very interesting protein. It has well-defined mechanical properties (great strength, reversible extensibility through only a small range) that make it suited to the special purposes to which it is put in the animal body, as in tendon, bone, tusk, skin, the cornea of the eye, intestinal tissue, and probably rather extensively in reticular structures of cells.

Another intriguing feature of collagen-gelatin was that it provided similar x-ray photos regardless of the source. In his article, Pauling noted that twenty-six samples, ranging from demineralized mammoth tusk to sheep gut lining, were all photographed by a scientist named Richard Bear and each resulted in remarkably similar images. Pauling compared them to a photograph of raw kangaroo tendon taken by Corey and Ralph W. G. Wyckoff, which also provided a view of what appeared to be the same structure. Pauling wrapped up the article discussing how three molecular chains wrapped into a distorted coil, and how the correlations between collagen-gelatin proteins and hydrogen could affect the structure.

The proteins work published by Linus Pauling and his Caltech colleagues in 1951 shook the scientific community and only added to Pauling’s growing fame. However, as time passed, evidence began to mount that his proposals regarding the gamma helix, muscle, and feather rachis were, in fact, wrong. Additionally, J.D. Bernal‘s lab found that the alpha helix, while fitting Pauling’s structural model, actually played a much smaller role in globular proteins than Pauling had suggested. However, Pauling’s media savvy and undeniable charisma won the day, at least in the short term. And so it was that, in the fall of 1951, (quoting Thomas Hager)

the 5 million readers of Life opened their new issues to find an enormous photo of Pauling, a big grin on his face, pointing to his space-filling model of the alpha helix. The headline read, ‘Chemists Solve a Great Mystery.’

Pauling and Proteins: Helices in the Air

Mounted models of the gamma helix and alpha helix, as housed in the Special Collections & Archives Research Center, Oregon State University Libraries.

Mounted models of the gamma helix and alpha helix, as housed in the Special Collections & Archives Research Center, Oregon State University Libraries.

[Part 2 of 3]

Linus Pauling sent shock waves through the scientific community when he published seven articles relating to the structure and function of proteins in the April-May 1951 issue of the Proceedings of the National Academy of Sciences. The first article of this volley was titled “The structure of proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain.” The second article was written by Pauling and Robert B. Corey, and was called “Atomic Coordinates and Structure Factors for Two Helical Configurations of Polypeptide Chains.” This paper was much more technical than was the first, and introduced two new important models developed by the Pauling group: the Gamma-helix and the Alpha-helix.

The article began by explaining in great detail Pauling’s idea for what he called the Gamma-helix (γ-helix). The γ-helix was the name assigned to the 5.1-residue helical configuration that Pauling, Corey, and Herman Branson had described in the first PNAS proteins article. The main difference between the γ-helix and the other configurations that they had proposed was that the bond angle between the C-N-C connection had been changed from 123˚ to 120˚. The authors explained that this small adjustment in the bond angle resulted in a miniscule change in the interatomic distances between various hydrogen bonds, but that these changes were significant enough to notably affect the number of residues per turn present within the structure.


(It is worth noting that the unit used to measure the distance between molecules is the Angstrom (Å). One Å equals 10-10 m, or one ten-billionth of a meter. Considering the truly tiny sizes being measured, it is likewise worth noting that the changes between hydrogen bonds that Pauling was talking about were often measured in the thousandths of an Angstrom or ten-trillionths of a meter. One trillionth of a meter is known as a picometer.)

The article stressed that differences as small as 10 picometers could notably change bond angles, which would then change the number of residues per turn, thus dramatically affecting the shape of the helix. Next, the authors elaborated upon the likely arrangements of molecules within the helix due to symmetry or lack of symmetry in certain molecular bonds. Pauling and Corey further noted that they had used x-ray crystallography to validate their arguments and determine the crystal structures in question. From his earliest days as a scientist, Pauling had established himself as a major figure in x-ray crystallography, a technique by which an operator fires x-rays at a substance in question, then measures the way that the x-rays have deflected off of the substance. By analyzing these deflection patterns, researchers were then able to develop models of the shapes of molecular structures.

Once the γ-helix had been explained, the article moved on to discuss the Alpha-helix (α-helix). The group explained that the γ-helix and the α-helix were similar in terms of how the hydrogens bonded with other molecular groups, and how the residues fit under those configurations. They also detailed the exact interatomic distances between hydrogen and various other molecules in the structure, while pointing out that the distance between carbon and its other bonds determined the number of residues per turn. The number of turns, however, was variable; the smallest possible angle of 108.9˚ resulted in a residue of 3.6, while the largest possible angle of 110.8˚ resulted in a 3.67 residue.


William Lawrence Bragg, an internationally famous scientist and proteins researcher of great import, was impressed by the α-helix, though he felt his rival Pauling to be overly excited about it. The α-helix was not a complete protein, except in a few cases including fibers, hair, and horn.  The structure also did not explain the functioning of proteins. As such, Bragg felt the paper to be an important first step – no more, no less. The rest of the scientific community was more enthusiastic than was Bragg and his team. Pauling received a Nobel Prize in 1954 in Chemistry “for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances,” the α-helix being among the most famous of these “complex structures.” The National Science Foundation even named a research vessel The Alpha Helix in honor of the discovery.

Bragg was even less generous regarding the γ-helix. Though in his very carefully worded congratulatory letter to Pauling he did not say so, he felt the γ-helix to be far-fetched, perhaps existing only in Pauling’s imagination. While this was not the case, the γ-helix ultimately made less of an impact on the scientific community.

Regardless, the import of Pauling’s work was felt throughout the profession.  Though Francis Crick would write that the alpha helix did not give him and Jim Watson the idea that DNA was a double helix, he did suggest that “helices were in the air,” at the time “and you would have to be either obtuse or very obstinate not to think along helical lines.”

Linus Pauling and the Structure of Proteins: A Documentary History


Today is Linus Pauling’s birthday – he would have been 112 years old.  Every year on February 28th we try to do something special and this time around we’re pleased to announce a project about which we’re all very excited: the sixth in our series of Pauling documentary history websites.

Launched today, Linus Pauling and the Structure of Proteins is the both latest in the documentary history series and our first since 2010’s The Scientific War Work of Linus C. Pauling. (we’ve been a little busy these past few years)  Like Pauling’s program of proteins research, the new website is sprawling and multi-faceted.  It features well over 200 letters and manuscripts, as well as the usual array of photographs, papers, audio and video that users of our sites have come to expect.  A total of more than 400 primary source materials illustrate and provide depth to the site’s 45-page Narrative, which was written by Pauling biographer Thomas Hager.


Warren Weaver, 1967.

That narrative tells a remarkable story that was central to many of the twentieth century’s great breakthroughs in molecular biology.  Readers will, for example, learn much of Pauling’s many interactions with Warren Weaver and the Rockefeller Foundation, the organization whose interest in the “science of life” helped prompt Pauling away from his early successes on the structure of crystals in favor of investigations into biological topics.

So too will users learn about Pauling’s sometimes caustic confrontations with Dorothy Wrinch, whose cyclol theory of protein structure was a source of intense objection for Pauling and his colleague, Carl Niemann.  Speaking of colleagues, the website also delves into the fruitful collaboration enjoyed between Pauling and his Caltech co-worker, Robert Corey.  The controversy surrounding Pauling’s interactions with another associate, Herman Branson, are also explored on the proteins website.

Linus Pauling shaking hands with Peter Lehman in front of two models of the alpha-helix. 1950s.

Linus Pauling shaking hands with Peter Lehman in front of two models of the alpha-helix. 1950s.

Much is known about Pauling’s famously lost “race for DNA,” contested with Jim Watson, Francis Crick and a handful of others in the UK.  Less storied is the long running competition between Pauling’s laboratory and an array of British proteins researchers, waged several years before Watson and Crick’s breakthrough.  That triumph, the double helix, was inspired by Pauling’s alpha helix, discovered one day when Linus lay sick in bed, bored and restless as he fought off a cold. (This was before the vitamin C days, of course.)

Illustration of the antibody-antigen framework, 1948.

Illustration of the antibody-antigen framework, 1948.

Many more discoveries lie in waiting for those interested in the history of molecular biology: the invention of the ultracentrifuge by The Svedberg; Pauling’s long dalliance with a theory of antibodies; his hugely important concept of biological specificity; and the contested notion of coiled-coils, an episode that once again pit Pauling versus Francis Crick.

Linus Pauling and the Structure of Proteins constitutes a major addition to the Pauling canon. It is an enormously rich resource that will suit the needs of many types of researchers, students and educators. It is, in short, a fitting birthday present for history’s only recipient of two unshared Nobel Prizes.

Happy birthday, Dr. Pauling!


The Alpha Helix

Space-filling model of the alpha helix.

[The Paulings in England: Part 5 of 5]

It has been said that sometimes blessings come in disguise, and so it may be that we have the damp English spring to thank for the elucidation of the alpha-helix structure of alpha-keratin – a fundamental and ubiquitous secondary structure pattern found in many proteins.

Linus Pauling was plagued by sinusitis for much of his time in England, and for three days in March 1948 it had become severe enough to put him in bed (as he was fond of saying over the years, this was before his vitamin C days). After a day spent devouring mystery novels, Pauling asked Ava Helen if she would bring him some paper and his slide rule, at which point he started trying to figure out how polypeptide chains might fold up into a satisfactory protein structure.

Pauling’s canvas was just an ordinary 8 1/2 by 11 inch sheet of paper. His first step was to draw the correct bond angles and distances onto the sheet, as determined from previous x-ray crystallographic work on polypeptides. Next he folded the sheet along parallel lines into a sort of squared-off tube. Doing so allowed him to add in representations of hydrogen bonds, which the impromptu model suggested would form between amino acid residues and, as a result, hold the turns of the polypeptide together.

The model made sense and pretty quickly it was clear that Pauling had discovered something important.  As he later wrote, his folded creation “turned out to be the structure of hair and horn and fingernail, and also present in myoglobin and hemoglobin and other globular proteins, a structure called the alpha-helix .”

Reconstruction of the alpha-helix paper model. Drawn and folded by Linus Pauling, 1982.

Pauling kept this idea to himself until his return to the United States because something didn’t match up quite right with the current laboratory data. Specifically, the turns of Pauling’s helix didn’t mirror the 5.1 angstrom repeat found in all of William T. Astbury‘s x-ray patterns. Pauling’s structure came close, but made a turn every 5.4 angstroms, or every 3.7 amino acid residues.

After his return home, with the assistance of colleagues Robert Corey and Herman Branson, Pauling continued refining his alpha helix structure and developing others, including the beta sheet. Simultaneously, the Caltech group’s chief British rivals at the Cavendish Laboratory published a paper titled “Polypeptide Chain Configurations in Crystalline Proteins.” The paper promised more than it delivered though, and while it listed many possible structures, Pauling found none of them to be likely. The competition was still on.

Pauling was finally convinced to publish when he received word that a British chemical firm called Courtaulds had created a synthetic polypeptide chain that showed no sign of Astbury’s 5.1 angstrom reflection in x-ray diffraction images. This was enough evidence for Pauling to decide that the 5.1 angstrom repeat was, perhaps, not a vital component of all polypeptide chains.  And so it was that in April 1951 Pauling, Corey and Branson published “The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain,” in the Proceedings of the National Academy of Sciences.

After devouring the Pauling group’s results shortly after their publication, Max Perutz headed to the Cavendish lab at Cambridge to check the data himself. Having confirmed the structure in images of horsehair, porcupine quill, synthetic polypeptides, hemoglobin and, for good measure, some old protein films that had been tucked away, Perutz wrote to Pauling, “The fulfillment of this prediction and, finally, the discovery of this reflection in hemoglobin has been the most thrilling discovery of my life.” He then published an analysis of his own data, concluding, “The spacing at which this reflexion appears excludes all models except the 3.7 residue helix of Pauling, Corey and Branson, with which it is in complete accord.”

Video Link: Pauling Recounts His Discovery of the Alpha Helix

It wasn’t until a year later that the mystery of Astbury’s 5.1 angstrom reflection was finally solved. In 1952, on a visit to the Cavendish, Pauling met Francis Crick, the then-graduate student who would go on to play a huge part in the discovery of the structure of DNA. The two maintained similar interests and during a taxi ride around Cambridge found themselves discussing the matter of the alpha helix. “Have you thought about the possibility,” Crick asked Pauling, “that alpha helixes are coiled around one another?” Whether Pauling had or had not considered this possibility remains a point of contention, but Pauling remembered replying that he had, because he had been considering a number of higher-level schemes for his helixes, including some which wound around each other.

Regardless, Pauling returned to Caltech and both he and Crick set to work on the problem. With help from Corey, Pauling discovered a means by which the alpha helixes could wrap around each other in a coiled-coil to produce the problematic 5.1 angstrom found in Astbury’s pictures of natural keratin.  Crick, in the meantime, was conducting a very similar study.  Pauling and Crick, independent of one another, ultimately submitted the solution to this puzzle for publication within days of each other, and at first there was a bit of grumbling as to whom the credit should be awarded. Though Crick’s note was published first, the Cavendish camp eventually conceded that Pauling’s paper included considerably more detail of consequence, and it was finally settled that both scientists had independently come to the same general conclusion.

Pauling receiving his honorary degree from the University of Paris, 1948.

After Pauling’s two fruitful terms as Eastman Professor at Oxford were up in July, the family split their remaining time between travels in Amsterdam, Switzerland and Paris. Pauling rounded off the trip by receiving yet another honorary degree from the University of Paris, and on August 25, 1948, the Paulings set sail once more on the Queen Mary.

His eight months in Europe had been productive and enlightening, but Pauling was ready to return to Pasadena where he could share the myriad ideas he had generated and gathered during his time away from Caltech. As we have seen, he was especially eager to get back to work on proteins, writing shortly before his departure that “I have continued to work on my theory of metals, and have been doing nothing about proteins. However, I am looking forward to being back home, and to thinking about that subject again.”