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.

Dr. Pauling’s Chiral Aliens

[A guest post expanding on Pauling’s idea for a science fiction novel. Post authored by the blog’s East Coast Bureau Chief, Dr. John LeavittNerac, Inc., Tolland, CT.]

Pauling lecturing with the "fish model" (foreground) that he used to demonstrate chirality, ca. 1960s.

Pauling lecturing with the “fish model” (foreground) that he used to demonstrate chirality, ca. 1960s.

In basic chemistry we have something called “chirality” which refers to a molecule with two possible non-superimposable configurations. One way to picture this is to look at your hands and place one on top of the other (not palm to palm) – your left and right hands are essentially the same shape but their shape is reversed. At the molecular level we can use one of the main building blocks of all proteins and all life – the amino acid alanine, depicted in the image below – to examine handedness.

alanine enantiomers

The diagram shows the arrangement of atoms of two alanine molecules, both of which exist in nature, arranged so that they are mirror images. They are the same molecules but if you turn the one on the right around so that it is facing in the same direction as the one on the left, the R (a single carbon atom in alanine with three bonded hydrogen atoms) on this alanine molecule faces toward the palm of the hand and the COOH moiety (a carboxyl group) and the NH2 moiety (an amino group) face outward away from the palm.

No matter how you rotate the alanine on the right, you can’t get the three moieties attached to the central carbon to line up in the same position as the alanine on the left. Likewise, you can’t get those hands to super-impose each other no matter how much you twist and turn them. So the alanine on the left is called L-alanine (levo- for the direction the molecule rotates photons) and the alanine on the right is called D-alanine (dextro- for the direction the molecule rotates photons). They are called “enantiomers,” or chiral forms, of alanine, and both exist in nature with identical chemical properties except for the way that they rotate polarized light.

There are twenty natural amino acids comprising the building blocks of all proteins. Of these twenty, only glycine is symmetrical around a central carbon atom and therefore glycine has no enantiomers. The other nineteen can exist in the L- and D-conformation.

Funny thing though, only the L-enantiomer is used to make proteins by the protein synthetic machinery of all life-forms, from single-cell organisms up to humans. It’s quite easy to understand why one enantiomer is used in life over random use of either enantiomer. In explaining this, note the pictures below, which show the three-dimensional globular structure of human beta-actin on the left and, on the right, the architectural arrangement of this actin in the cytoplasm of a cell.


The protein composed of 374 amino acids has an intricate folding pattern with coils which would not be possible if both amino acid enantiomers for the nineteen amino acids were randomly incorporated into the protein. This three-dimensional structure has to be preserved in order for actin to perform its dynamic architectural function inside living cells, as shown in the picture on the right. The coils are possible because the amino acids are all L-amino acids and glycine is neutral; otherwise the protein would behave like a wet noodle. The precise structure of the actin protein determines its function, which has been preserved and conserved since the beginning of all eukaryotic life-forms (that is, cells with a cytoplasm and a nucleus). Understanding the atomic forces that fold proteins in a unique shape is part of the reason why Linus Pauling received the Nobel Prize for Chemistry in 1954.

Aside from those who closely follow this blog, it is not well known that Linus Pauling was an avid reader of science fiction. In a 1992 interview with biographer Thomas Hager, he described his motivation to write a science fiction novel. The story line was to be the discovery of a human-like race from another planet that had evolved to use only D-amino acids (D-humans) rather than the L-isoform (L-humans). He explained that he never got around to writing this novel because the real science he was doing took all of his time.

If our L-humans met up with those D-humans, what consequences would there be? Well, what we would see in D-humans are people virtually indistinguishable from ourselves – barring, of course, the possibility that these extraterrestrials evolved out of some unearthly environmental niche. However, no mating, blood, or tissue sharing would be possible between these two races.

To explain this, consider the experience you have had when you accidently put your hand in the wrong glove. As you know, this doesn’t work well. All protein interactions and reactions catalyzed by enzymes require a direct fit to work. Substrates of enzymes have to fit precisely into the catalytic active site of the enzyme, like your hand fitting into the correct glove. Since L-humans have a different chirality from D-humans, nothing would fit or be transferrable, because of asymmetric incompatibility between L- and D- macromolecules. Even the food on our planet would not likely be nutritious for D-humans because all living things on Earth are L-organisms. In D-lifeforms, the actin coils would coil in the opposite direction and the DNA double helix would have to spiral in the opposite direction as well; otherwise the analogous D-proteins would not bind or fit on the chromosomal DNA.


It seems reasonable that D-humans might be found on other planets if you consider how life got started. By a quirk of nature on Earth, L-amino acids got a head start and self-assembled into peptides (small proteins) when this essential process for life as we know it got started. The assembly of only one enantiomer isoform into a peptide may have been favored thermodynamically over co-random assembly of L- and D-isoforms. This essential process evolved into a well-organized, membrane-protected and energy-driven protein synthetic machinery in single cell organisms like bacteria. Today, humans have essentially the same protein synthetic machinery that evolved in primordial bacteria and all life-forms on Earth have the same genetic code.

There are two essential enzymes that work together to catalyze protein synthesis in all living cells. One enzyme, called aminocacyl-tRNA synthetase, binds the amino acid to a transfer RNA molecule (there is one of these enzymes and a specific tRNA for each of the twenty amino acids). The second enzyme, peptidyl transferase, catalyzes the formation of a peptide bond linking two amino acids at the start of a chain and does this over and over again until the full length protein is synthesized and folded into its functional conformation. These two essential enzymes do not recognize the D-isoforms of the nineteen asymmetric amino acids. Thus, our chiral L-specificity has been preserved since the beginning of life.

I can’t think of any reason why the D-amino acids would not support life, but it has to be one isoform or the other, not both. Apparently Pauling felt the same way. Should it ever come to pass, D-humans will be interesting to meet and they will be equally interested to meet us, hopefully without mutual disappointment.

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 Coast Guard 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.

Caltech, Cambridge and Coiled-Coils

Coiled-coil illustration from Pauling and Corey's Nature publication of January 10, 1953.

Coiled-coil illustration from Pauling and Corey’s Nature publication of January 10, 1953.

Within the overarching saga of the race for DNA between Linus Pauling’s Caltech lab and Sir William Lawrence Bragg‘s Cambridge lab, the Cavendish, there existed a small yet interesting story of controversy and intrigue: the case of the coiled-coils.

In August 1952, Linus Pauling visited England during the final leg of a larger European tour largely devoted to touting his important new discovery, the alpha helix. Lecturing about his proposed protein structure inevitably led to Pauling’s visiting all of the major centers for research in England that were focusing on proteins. One of these centers was the Department of Physics at Cambridge University – the Cavendish – directed by Bragg, a Nobel laureate and Pauling’s long-time scientific rival. While visiting the Cavendish, Pauling also met with a non-traditional graduate student with whom he had communicated only a few times, via letter. This student was Francis Crick, the British scientist who, together with his American colleague James Watson, would go on discover the double-helical structure of DNA the following year.

Francis Crick, 1955.

One afternoon during Pauling’s visit, Crick and Pauling shared a taxi cab as they traveled around the premises of Cambridge.  During this jaunt, the two discussed several topics of mutual interest, including Pauling’s alpha helix. Eventually this conversation turned to an examination as to why Pauling’s model of the alpha helix lacked the 5.1 angstrom repeating turn (all helices, by definition, twist) found in x-rays of keratin, a fibrous protein structure that makes up the outer layer of human skin. Pauling’s model predicted a turn every 5.4 angstroms. This mystery had remained a thorn in Pauling’s model since his publication of the alpha helix a year prior.

During their cab ride, Crick is reputed to have asked Pauling about the possibility that alpha helices are coiled around one another. Pauling, according to a letter recounting the event, replied that he had, and that this reply marked the end of the discussion of coiled-coils between the two scientists. Crick, however, claimed in a later letter that the conversation was longer and more detailed. Whether or not the conversation was brief or of greater length, this was the beginning of a controversy.

His tour completed, Pauling returned to Caltech and renewed work on the angstrom reflection problem dogging the alpha helix. He and Robert Corey, the biochemist with whom Pauling and Herman Branson had collaborated to develop the alpha helix, soon found that if two to seven alpha helices were wound “like a piece of yarn around a finger, into a sort of coiled-coil” the resulting structure would match the 5.1 angstrom reflection found in x-rays of keratin. This addition to the alpha helix hypothesis built upon an undated idea of Pauling’s that was written down in a travel journal that he kept during the European tour. The notes describe a structure that Pauling named “AB6” – six alpha helices (B6) coiled around a seventh (A).

Pauling’s first notes on what would later be described as “coiled-coils.”

Meanwhile, back at Cambridge, Peter Pauling – one of Linus and Ava Helen’s three sons – was working at the Cavendish as a graduate student alongside Crick and Watson, having arrived the same summer as his father. Peter told Crick – who was also working on “coiled-coils” of the alpha helix – of his father’s research in Pasadena. This news undoubtedly felt to Crick like Linus Pauling had built upon the ideas that Crick brought up in their conversation.

In a rush to be published first, Crick hurriedly finished his research and dashed off a note to the journal Nature in October 1952, only to discover that Pauling’s own manuscript had arrived just a few days before. However, in a surprise twist, Crick’s manuscript was published first, likely due to two factors: 1. Crick’s paper was shorter, and 2. it was sent with a cover letter from Max Perutz, a supporter of Crick and part of Bragg’s Cavendish team, requesting high-speed publication.

The following month, Pauling wrote a letter to Jerry Donohue, a former Caltech doctoral student who had worked with Pauling since the 1940s and was, at the time, working at the Cavendish on a Guggenheim Fellowship. The communication was in reply to a letter that Donohue had written to Pauling reporting on Crick’s Nature submission.  In his reply Pauling explained that he remembered the conversation with Crick involving the alpha helix during the past summer. Cognizant of the controversy brewing over the provenance of the coiled-coil idea, Pauling specifically wrote that the conversation with Crick was brief.

A few months later, in March 1953, Pauling wrote a similar letter to Max Perutz, this one containing more detail on the matter. Pauling mentions in the letter that he had thought of Crick’s suggestion prior to their conversation, but had not fully fleshed it out; a claim perhaps supported by Pauling’s travel journal.

Pauling to Perutz, March 29, 1953.

Francis Crick was given a copy of Pauling’s letter to Perutz. In response, Crick recalled the taxi cab conversation as having been longer than Pauling remembered, and more in depth on the subject of the coiled-coils, thus leading him to the assumption that Pauling had built upon his ideas. This would have been fine, Crick wrote, had Pauling simply informed Crick so that the two scientists could publish simultaneously, giving credit where credit was due as well as bolstering each other’s work.

Crick to Pauling, April 14, 1953.

Crick did admit that Pauling’s paper was more detailed and thorough than was his own, and also came to different conclusions on key points. These factors were enough for both Caltech and the Cavendish to declare that Pauling and Crick had generated their ideas on coiled-coils independent of one other, if simultaneously.

Wrinch’s Legacy

Dorothy Wrinch. Image courtesy of the Sophia Smith Collection, Smith College.

[Part 4 of 4]

After her marriage to Otto C. Glaser in late August 1941, Dorothy Wrinch found herself in a happy, stable space and her work blossomed. She spent the 1940s researching the ways in which scientists could use mathematics to interpret x-ray crystallographic data and she wrote prolifically, eventually authoring 192 publications over the course of her career. In addition, she continued teaching at Amherst, Smith, and Mount Holyoke Colleges, where she was popular with her students and found her institutional status rising over time.

However, one detail that did not change was her attitude towards cyclols. She continued to insist that her model of protein structures was the correct one and was buoyed when, in the early 1950s, it became apparent that Linus Pauling and J.D. Bernal had also been off with their hypotheses. Both also admitted that they had missed the boat regarding the importance of the double helix and other issues relating to DNA. For her part, Wrinch insisted that “any day now” her cyclol model would be vindicated as the key to the secret of life.

In the midst of all this, Otto Glaser sadly died of nephritis – a kidney inflammation that also befell Pauling – on February 8, 1951. Mourning the loss of her husband of ten years, Wrinch moved into faculty housing at Smith College and eventually resumed her correspondence with Eric H. Neville, an old friend from the late 1930s. Neville’s wife had died during the 1940s and, have been reacquainted, Neville asked Wrinch to marry him. She refused, reasoning that she’d already been married twice and that was enough for her.

The year 1954 proved to be one of partial triumph when cyclols were discovered to exist in nature – specifically in ergot alkaloids. Ergots are parasitic fungi that are used as a starting base for numerous pharmaceuticals. Upon hearing the news, Wrinch declared that she had been correct all along, and that this revelation proved it. As she wrote to Marjorie Senechal, a student of hers who later wrote a biography of Wrinch

First they said my structure couldn’t exist. Then when it was found in nature they said it couldn’t be synthesized in a laboratory. Then when it was synthesized, they said it wasn’t important anyway.

In this, she was overstating her position. While Wrinch had indeed been correct that hexagonal cyclols do exist in nature, much of the remainder her hypothesis had been wrong, including the large “hollow-cage structure” that she claimed was built by cyclols. Regardless, Wrinch redoubled her efforts and in 1960 and 1965 wrote two books that were “meant to be the culmination of her [work].” The scientific community largely disregarded these books, treating them as continuing defenses of an outdated idea.

Wrinch retired in 1971 and moved to Woods Hole, Massachusetts, where she remained close with her daughter. In building her career, Pam had become rather notable in her own right. She had earned a Ph. D in international relations from Yale in 1954, one of the first women to do so. She later married a Cambridge publisher and became a fairly well-known lecturer on political science. Tragically, Pam was killed in a fire in late 1975. Wrinch, who was already weakened by advancing age, was completely heartbroken by the loss of her daughter. She died ten weeks later on February 11, 1976, aged 81.

Suffice it to say that the legacy of Dorothy Wrinch is a complicated one. Most would agree that Wrinch was an interesting, unusual, controversial, and polarizing figure in twentieth century science. She made numerous contributions to her field and overcame immense hurdles along the way, but the importance of her story is often buried behind the charged feelings surrounding her incorrect cyclols hypotheses.

To those with a lay interest in the history of science, she is not especially well-known. With the exception of Marjorie Senechal’s 2012 biography, I Died for Beauty: Dorothy Wrinch and the Cultures of Science, Wrinch is only infrequently mentioned in books, generally works on early biology or Linus Pauling or texts focusing on women scientists. It is clear, though, that she made an impact on her contemporaries, both positive and negative.

On the plus side, one notes commentary such as that issued in 1980 by Carolyn Cohen, professor of biology at Brandeis University, who wrote.

Dorothy Wrinch’s life centered on [the vital importance of proteins] and she influenced many, including Joseph Needham in England and, in America, Ross Harrison, the great embryologist at Yale, and Irving Langmuir, the physical chemist. I believe that her influence has been vastly underestimated.

On the other end of the spectrum lies biochemist Charles Tanford, who called Wrinch’s “despised” cyclol theory

the most forgettable of all the fruits of the 1930s’ harvest, not really worth more than a footnote…a theory built on nothing, no training, no relevant skills.

More examples from both camps are available to those who look. But perhaps Nobel Laureate Dorothy Hodgkin – a friend of both Wrinch and Pauling – pegged the essence of Wrinch’s story best when she said

I like to think of her as she was when first I knew her, gay, enthusiastic and adventurous, courageous in the face of much misfortune, and very kind.

What seems clear is that Dorothy Wrinch allowed her rhetoric to overwhelm the impact of her work, and that this caused her great harm both within the profession and ultimately within her life.

Pauling v. Wrinch

“Report on the work of Dr. Dorothy Wrinch.” Written by Linus Pauling and submitted to the Rockefeller Institute. March 31, 1938.

[Part 3 of 4]

Dorothy Wrinch’s 1937 American tour brought her, and her highly controversial cyclol hypothesis, into the public consciousness. She attracted a lot of attention, but mistook that attention for firm support. Thus buoyed, she began making outsized claims as to the importance of her theory and, more importantly, false claims that it had already been scientifically proven. Wrinch’s rhetoric caused many of her friends and colleagues to distance themselves from her and her ideas. And when Pauling ultimately agreed to meet with Wrinch in Ithaca, New York, the gloves came off: Pauling slammed her ideas as plainly ridiculous, more fancy than fact.

The critical reaction to Wrinch’s ideas soon built into an onslaught. When she returned to the U.K., a group of British x-ray crystallographers argued that her suggestions were false. While Wrinch claimed that x-ray crystallography proved her theory, these scientists pointed out that, to the contrary, crystallographic results actively disproved her cyclols.

Stateside, Linus Pauling and Carl Niemann officially got in on the act with their publication of “The Structure of Proteins” in the July 1939 issue of the Journal of the American Chemical Society. In it, the authors declared that Wrinch’s cyclol cage was so thermodynamically unstable that it couldn’t even be produced in a lab intentionally, let alone be found in nature. From the article:

[We] draw the rigorous conclusion that the cyclol structure cannot be of primary importance for proteins; if it occurs at all…not more than about three percent of the amino acid residues could possess this configuration. [emphasis theirs]

Wrinch, who was looking for work in the U.S., was forced to respond to Pauling’s article with one of her own. In it she publicly questioned his competency and stated that “opponents of the cyclol hypothesis have felt compelled to fall back upon arguments which are specious (due to errors in logic), and upon experiments which are irrelevant…or incompetent to decide the issue.” (Although it wouldn’t be known until 1952, the last part of her accusation was correct – Pauling’s hypothesis was also partially inaccurate.) In an effort to keep the peace, JACS refused to publish her rebuttal until Pauling had been given a chance to review it. Once done, Pauling and Niemann wrote another response to Wrinch’s piece – one equally acidic as Wrinch’s – rebutting her response point-by-point, just as “The Structure of Proteins” had done to cyclol theory.

Their battle, played out in the pages of newspapers and among the referees of major scientific journals, was defined by vitriol for it duration. Wrinch would attack Pauling, even going after his earlier theories on chemical bond resonance; Pauling would respond, calling Wrinch’s theories unworthy of serious scientific debate. At one point, 13-year old Pam, Dorothy’s daughter, wrote a letter to Pauling, which suggested

Your attacks on my mother have been made rather too frequently. If you both think each other is wrong, it is best to prove it instead of writing disagreeable things about each other in papers. I think it would be best to have it out and see which one of you is really right.

As time passed, evidence continued to grow that Wrinch’s cylol theory was wrong. Nonetheless, she continued to defend the work with vigor. In her 1987 book on women in science, historian Pnina Abir-am wrote that Wrinch developed a “lifelong obsessive defense of her theory and refusal to follow the shifting scientific frontier.” Additionally, her counterattacks on Pauling were full of shaky logic and bad science, which reduced her credibility far more than it reduced his.

Wrinch gathered little support in the scientific community by going after Pauling, by then known to many as a major scientific figure. Frustrated, her ego again got the best of her, and she accused her colleagues of being “cowards” who were too scared of Pauling to see the truth of her theories. This strategy bore little fruit and the remainder of her support had largely vanished by the end of 1939.  By 1941 Pauling had emerged victorious and Wrinch was largely ostracized from the scientific community.

An uncommonly vitriolic letter from Pauling to David Harker concerning his role in the Wrinch affair. July 6, 1940.

Victory aside, Pauling did not cloak himself in glory with his actions. In the estimation of Pauling biographer Thomas Hager, the saga managed to “illuminate less appealing sides of Pauling’s character,” his strong-arm tactics “a demonstration of his new power.” Clearly a rising star within the scientific world, Pauling’s

prestige and acclaim brought out negative factors in his personality that became more evident as his power grew: a tendency toward self-righteousness, a desire to control situations and frame debates, and a willingness to silence those with aberrant ideas.

The aftermath of the drama found Wrinch in a severely compromised position. For starters, the Rockefeller Foundation terminated Wrinch’s fellowship, rendering her without funding as a result of her having failed to find more solid support for the cyclol theory in the five years allocated to her.

Wrinch spent the years 1939–1941 searching for jobs in the US and Canada. She lamented to her close friend, Otto Charles Glaser: “I am notoriously poor at institutions about people.” Glaser was a frequent correspondent and a big supporter of her work. Finally, in 1941, Glaser engineered a deal for Wrinch and she was offered a position as a joint visiting research professor at Amherst, Smith, and Mount Holyoke Colleges.

Not long after she had moved to her new position in western Massachusetts, a mutual friend approached Wrinch and told her that Glaser was wildly in love with her. Wrinch was caught completely off guard by this news and was even more surprised when, shortly afterward, Glaser proposed to her. Wrinch asked for time to think about it before answering; she was still a bit nervous, seeing as how her first marriage had been so unhappy and ended poorly.

As she deliberated, Wrinch drew up a table of pros and cons on the topic of marrying Glaser, using terms including “net losses” and “net gains” in her contemplation. She asked Pam what she thought and her daughter told her to be careful, since her first marriage had been so awful. But on the same token, Pam thought, Glaser was a good man and Dorothy was clearly close to him. Ultimately Wrinch and Glaser were married on August 20, 1941, in the Marine Biological Laboratory in Woods Hole, Massachusetts. The wedding was a private affair, but still highly photographed and publicized. The couple permanently settled down in Massachusetts. As always, Dorothy was dedicated to maintaining her career, marriage, and her motherhood.

As published in the New York Times, August 21, 1941.

As published in the New York Times, August 21, 1941.

Wrinch’s Cyclols

Dorothy Wrinch holding a model of a cylcol, 1938. (Associated Press photograph)

Dorothy Wrinch holding a model of a cylcol, 1938. (Associated Press photograph)

[Part 2 of 4]

The late 1920s were, overall, a good time for Dorothy Wrinch. By 1929 she had published forty-two papers on mathematics, physics, and the philosophy of science. She was a rising star, among the most educated women in the United Kingdom, the first woman to receive a Doctorate of Science from Oxford. Additionally, and most importantly for her, her daughter Pamela had been born in 1928; Wrinch loved Pam more than anybody else in the world.

The decade ended on a bad note though, as Wrinch’s husband, John William Nicholson, was institutionalized in 1930, the result of a mental breakdown brought about by his persistent alcoholism. The couple separated at that time, though Dorothy was not legally granted a divorce until 1938. This put Wrinch in an even more awkward social position than had already been the case: she was now a single, professional, unsupported, and unaccompanied mother in the very conservative world of British academia. Wrinch left Oxford shortly after the separation and the same year published a book, The Retreat from Parenthood, written under the pseudonym of Jean Ayling.

The book discussed the problems that women face, especially those women trying to focus on both their careers and their children simultaneously. The book also prescribed remedies for these problems in the forms of radical and utopian revampings of labor laws, housing design, and child care. Controversially, she also proposed the creation of a Child Rearing Services, envisioned as a government-run program where career-minded parents could effectively leave their children with a professionally trained surrogate family for up to months at a time. The Retreat from Parenthood likewise strongly advocated for the usage of eugenics to improve Britain’s gene pool. While support for eugenics was a fairly common position at the time, stances of this sort have since become extremely taboo in light of atrocities committed by the Nazis under the banner of racial purification.

Starting in late 1930, Wrinch actively sought to broaden her research horizons. She received numerous fellowships, and spent the years 1931-1934 studying in Vienna, Paris, London, Prague, Leiden, and Berlin, all the while visiting various laboratories and universities. This was a chaotic time in Europe, and upheavals wracked the continent, seeing the rise of Nazi Germany and support of fascist movements in numerous other countries. Wrinch was not overly concerned by these turns of events, and while staying in Vienna in 1931, wrote of her optimism that the upheavals marked a “straight road to a final breakup of the present system and where we will then find a new system which is neither Fascism nor Bolshevismus???”

Beginning in 1931, Wrinch began to think about how she could apply her mathematical knowledge to the biological sciences, specifically regarding the functions of chromosomes and the structure of proteins. In the summer of 1932, she helped found the Theoretical Biology Club, which argued that mathematics, physics, chemistry, biology, and philosophy could explain everything in life. And in 1934 Wrinch published her first paper on proteins, an article in Nature titled “Chromosome behavior in terms of protein patterns.” The Rockefeller Foundation was impressed by her work and, in 1935, awarded her a five-year research fellowship to support her efforts in applying mathematics to biology. Wrinch came to the US that same year to begin the fellowship.

The year 1936 would forever change Wrinch’s life and her legacy; it was the year that she first proposed her theory on the structure of proteins. She called her hypothetical structures “cyclols” and presented the idea to the British Association for the Advancement of Science in 1937. Wrinch believed that proteins were formed into a sort of large hollow cage, made up of small hexagonal sheets of amino acids – the cyclols. This hypothesis made news – an article written at the time by the Associated Press labeled her “Woman Einstein” – and quickly garnered her a certain measure of celebrity, in which she reveled.  Energized, Wrinch took a tour of the US in 1937, and used this trip to spread information about her ideas. Unfortunately Wrinch, in the words of Pnina Abir-am

mistook her American reception, marred by curiosity of her persona as an attractive female theoretician, for scientific confidence in her model.

Even though her hypothesis did generate scientific interest, she greatly overestimated the extent to which it was supported within the community. She loved being in the spotlight, developed an inflated ego and began likewise exaggerating the importance of her hypothesis. Most egregiously, she stopped referring to her idea as a hypothesis and began referring to it as “a proven theory with predictive power.” This stance served to quickly upset many scientists who could see that the evidence did not support her claims and worked to alienate her from many of her friends in the British and American scientific communities. Even those who had helped her with the work distanced themselves at this time. Dorothy Crowfoot Hodgkin, who would receive the 1964 Nobel Prize in Chemistry for her research on vitamin B12, later said in an interview

[J.D. Bernal and I] were friends of hers, and had helped to develop her theories, but we did not believe in them, and that was our trouble.

Wrinch’s theory had catapulted her into both the spotlight and the crosshairs of the scientific community. But the end of the 1930s would prove to be a trial by fire of her ideas, and the attack would be led by another up and coming star of the scientific community: Linus Pauling.

Dorothy Wrinch: The Early Years

Dorothy Wrinch, 1940. (Cold Springs Harbor Laboratory Archives photo)

Dorothy Wrinch, 1940. (Cold Springs Harbor Laboratory Archives photo)

[Part 1 of 4]

Dorothy Maud Wrinch was a mathematician and biochemical theorist who, like many famous scientists, was an extremely complex individual. She became most well-known for her incorrect hypothesis on the structure of proteins and the vicious battle over that hypothesis that ensued between her and Linus Pauling. To a degree, Wrinch’s fame faded along with her incorrect theory, but her story is highly intriguing and we aim to explore it in detail over the next four posts.

(For much more on the life of Wrinch see the biography I Died for Beauty: Dorothy Wrinch and the Cultures of Science, by Marjorie Senechal, Oxford University Press: 2012.)

Dorothy Wrinch was born in Argentina on September 12, 1894, the daughter of Hugh Edward Hart Wrinch and Ada Minnie Souter. Her parents were English citizens, at the time living in Rosario, Argentina, where Hugh was working for a British firm that employed him as a mechanical engineer. Once the project in Rosario was completed, the Wrinch family returned to London and Hugh found a job at a waterworks in the London suburbs, at which point Dorothy began attending the nearby Surbiton High School.

Hugh loved mathematics and succeeded in fostering a similar sensibility in Dorothy. In 1913 she received an internship to Girton College, a women’s college at Cambridge University. While there, she began to study math and philosophy, and in her first year was introduced to the famous and controversial philosopher, logician, mathematician, historian and social critic, Bertrand Russell (who would later become a close friend of Pauling’s). In her sophomore year, she began to study mathematical logic under the direction of Russell and quickly became enamored with him. She excelled in her studies, earning numerous awards and honors as the highest ranked woman in her class, and ultimately graduated with extremely high marks.

In 1918 Wrinch began teaching algebra, trigonometry, calculus, and solid geometry to honors students at University College, London. By then she had become deeply infatuated with Russell. She spent huge amounts of free time with him and his social circle, and absorbed many feminist and socialist beliefs from the group. Russell was arrested in 1918 for his active opposition to World War I; specifically, for delivering a speech where he encouraged the United States to ignore Britain and remain neutral. While he was in prison, Wrinch visited him regularly, wrote him numerous letters and often brought him books. In one of her letters to him, she described herself as his disciple, and talked of how proud she was to be an intimate friend of his.

This intimacy abruptly ended in 1919 when Russell began a romantic relationship with Dora Black, a famous feminist, socialist, and proponent of free love. Wrinch felt humiliated, and many of her writings from that time period revolve around issues of trust and betrayal. Wrinch was a self-described manic depressive, and took Russell’s actions very personally and quite badly.

Bertrand Russell and Linus Pauling, 1953.

Nonetheless, Wrinch continued teaching at University College, and while doing so she earned a Master of Science degree in 1920, and returned to Girton College with a research fellowship in 1921. She rounded off her upper education and earned a Doctorate of Science in 1922. She was prolific, writing over a dozen papers about the philosophy of science.

The year 1922 was important for Wrinch in more ways than one: in addition to obtaining a doctorate, she also was married to John William Nicholson, the director of studies in physics and math at Oxford. The documentary record suggests that Wrinch and Nicholson met and became engaged rather quickly.

Wrinch also moved to Oxford in 1922 and became a part-time tutor and lecturer in mathematics at Lady Margaret Hall, a women’s college at Oxford. Once established, she branched out, lecturing at Oxford’s five women’s colleges on a per-term basis. Despite her track record of success, she encountered difficulties at Oxford, as its math and science community was tightly bound and very traditional. In this environment, Wrinch found many factors going against her: she was a married woman who also focused on her career; though married she retained her maiden name; she came from a modest social background; she was a feminist and very progressive socially; and she was new to Oxford.

Wrinch’s situation improved when she received an appointment as full-time mathematics lecturer for three years, making her the first woman to obtain such a position at Oxford. Her position also meant that male students would attend her lectures which was almost unheard of – female lecturers generally lectured to exclusively female audiences.

Her life was changed forever in 1928 with the birth of her daughter Pamela. Pam truly was the single greatest happiness and love of Wrinch’s life, as is instantly apparent by reading letters where Pam is described. Unfailiingly, Wrinch uses nothing but the most glowing of terms of endearment to describe her daughter.

As the 1920s drew to a close, Wrinch found herself a new mother, a scientific pioneer and a social radical. As she looked ahead, she charted a path that would make herself stand out even more: in an age where most British women would focus on career or marriage and motherhood, Wrinch decided that she would do all three.

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.’