Barclay Kamb, 1931-2011

Barclay Kamb, 1994.

“I have just read an article about time by Hsü in PNAS.  I have not been able to understand it all.  However, he thanks you, so perhaps sometime when you come to the ranch you can explain his ideas to me.”

-Linus Pauling, letter to Barclay Kamb, December 3, 1992.

Geologist and former Caltech Vice President and Provost W. Barclay Kamb died on April 21 at the age of 79.  Caltech has published a nice remembrance of Kamb, which is available here.

Kamb, a member of the National Academy of Sciences, was a particularly distinguished scholar of the Antarctic who made many significant breakthroughs in his studies of the structure of ice and the nature of glaciers.  His influence on polar studies is evident in many ways; glacial researchers today make use of the Kamb-Engelhardt Hot Water Drill, to list one example, and an Antarctic ice stream was, in 2003, named the Kamb Ice Stream in his honor.

Barclay Kamb was also Linus Pauling’s son-in-law, and it is through this prism that we share a bit more about his life.


Kamb, a San Jose native who then went by the surname of Ray, entered Caltech at the age of 16 in 1948.  He completed his physics degree in 1952 and went on to obtain a Ph. D. in geology in 1956.  It was during his graduate years that Kamb caught the eye of Linus Pauling – Kamb’s doctoral adviser, under whom he was investigating the structure of zunyite – who thought very highly of the young scholar.  So highly, in fact, that he and Ava Helen began hatching a plan.  Biographer Tom Hager writes

From the moment [Linda Pauling] arrived [home from a trip to Europe], they threw her together as often as as long as possible with a favorite graduate student of Pauling’s, a handsome and brilliant young geologist named Barclay Kamb.  By the summer of 1957, Linda had settled down:  She was living at home, making money by assisting [Robert] Corey at Caltech, and occasionally cooking dinner for Kamb, who was, Pauling was happy to note, ‘hanging around our house quite a bit.’  The matchmaking worked.  On a beautiful day in September 1957, Pauling walked across the front lawn of his Sierra Madre home with Linda on his arm, in front of two hundred guests, and delivered her to Barclay Kamb – now a Caltech assistant professor of geology – for the purpose of marriage.

Linda and Barclay Kamb, 1957.

Pauling and Kamb quickly developed a very close relationship that was further cemented by their shared passion for scientific inquiry.  In 1990 Pauling nominated Kamb for the M. J. Buerger Award in crystallography, and in his nomination letter he quipped

He is recognized as having extraordinary ability.  When I get stuck on a problem, I go to him for help.  He is my son-in-law, so he finds it difficult to turn down my appeal.

Indeed, in reviewing their lengthy correspondence, it is overwhelmingly evident that science was a frequent topic of conversation between Pauling and his son-in-law.  The duo published seven papers together, on topics ranging from the effects of strontium-90 on mice, to the structure of lithiophorite to resonating valence bonds in hyperelectronic metals.  And in their letters, countless additional topics are explored from melting points in metals to an investigation of pseudobrookite.

Linda and Barclay Kamb, 1963.

In addition to his scientific acumen, Pauling admired Kamb’s writing skills – “Your ability at writing in a clear manner is so unusual that it would be a terrible waste if you did not write some good books,” Pauling opined in 1961 – and on multiple occasions enlisted his aid in the revision of both of his legendary texts General Chemistry and College Chemistry.  Many years later, in 2001, Kamb would serve as lead editor for the two volume set, Linus Pauling: Selected Scientific Papers.

Amusingly to the contemporary reader, Pauling also commandeered his son-in-law’s services – and title – for the more pedestrian task of fighting the construction of a trail that the Forest Service planned to build near his property.  “Perhaps you could write to him,” Pauling requested, “signing your letter as Professor of Geology and Geophysics, and saying that you have observed this trail in its relation to the beach 300-foot stretch along the cliff…where there is an absence of shrubbery that would prevent rocks from falling onto the trail.”

We leave it to Tom Hager to describe the fallout from a different and much more important cliff-related incident – during which Linus, at age 59, famously spent the night trapped on a ledge overlooking the Pacific Ocean – that once again served as evidence of the close relationship between Pauling and Kamb.

When they found him at noon the next day, Pauling was emotionally shaken and physically exhausted.  But he swallowed all that – almost as a matter of habit…

On Monday morning, less than twenty-four hours after his rescue, Pauling walked into his office at Caltech.  The news of his disappearance had been carried nationwide on the news wires, and everyone in his research group had been worried.  Now they festooned his office door with a large ‘Welcome Back, Dr. Pauling’ banner, and one of the secretaries baked a cake decorated with a little toy man on a cliff and a mermaid in the water below.  There was a small cheer when he arrived.  Pauling looked at the cake, then, without a word to anyone, walked into his private office and shut the door.  The little crowd that had gathered to greet him was stunned.  A moment later, a sheet of notepaper was pushed under the door; it was a request from Pauling to cancel his class and all other appointments.

No one knew quite what to do.  Pauling’s son-in-law, Barclay Kamb, was as close to him as anyone; he was called in, and the situation was explained to him.  Kamb knocked softly on Pauling’s door, then went inside to talk to him.  Something was seriously wrong.  Pauling seemed aware of his surroundings but unable to say a word.  Kamb decided to take him home.

Pauling did not say a word all the way back to his house and remained mute as Ava Helen put him to bed.  The trauma of the cliff episode had put him in a state of shock… When Linda visited with his new grandchildren, he began to cry.  It was the first time anyone had seen him emotionally vulnerable, in anything less than full control.

While Barclay was a great asset to Linus in many respects, it is clear that the father-in-law often served a similar role.  For one, it is worth noting that the Kamb family accepted Linus and Ava Helen’s invitation to move into the original Pauling family home in Pasadena once Linus left Caltech in favor of a position in Santa Barbara. The correspondence also indicates that Pauling acted as watch dog for Kamb in at least one instance, writing to express his indignation to an author of a paper on high-pressure ice forms who had neglected to adequately cite Kamb’s original research in the field. (The offender responded apologetically and issued a correction.)

In the main, it is clear that Linus Pauling’s overriding feeling toward Barclay Kamb was one of pride.  He was fond, for instance, of recounting a New Yorker article on flooding in southern California that referred to Kamb as “the smartest man in the world.”

Pauling family photograph, 1976.

And the fondness was clearly mutual, as perhaps best summarized by a handwritten letter penned by Kamb from his station at “Outstream Bravo” camp in Antarctica.  The letter is dated December 22, 1993, a point in time when Pauling was quite ill with the cancer that would claim his life eight months later.  In what Kamb conceivably could have regarded as a final communication with his father-in-law, he wrote with affection.

Here I am in the far south (latitude 83.5° S) doing my field work on the Antarctic Ice Sheet, but wishing I could be at home with Linda and able to come to visit you.  At times there is excitement and exhilaration here, and it is rewarding to me scientifically, but there is also a lot of plain hard work and a somewhat dreary existence.

One thing that I greatly miss during these long trips to Antarctica is the chance to discuss scientific subjects with you, which I so much enjoy when Linda and I come to visit.  This goes back many, many years, of course, and has been a great inspiration for me, and especially rewarding when we were able to produce joint papers as a result.  You have given me much good scientific (and other!) advice over the years, and I greatly appreciate it.  Particularly valuable to me was your suggestion that I work on the structure of the ice phases, which was a gold mine of interesting science.

…I am counting the days until I can get this job here done and come home to Linda, and I hope very soon after that we can come up to visit you.  I look forward to it very much…

Linda and Barclay Kamb with Lucile, Linus and Pauline Pauling, 1986.


For more insight into Barclay Kamb’s life and character, see this biographical text from “Welcome Barclay…Thank You Gene,” a Caltech Division of Geological and Planetary Sciences event marking Kamb’s assumption of the Division Chairmanship in October 1972.

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William Lipscomb, 1919-2011

Bill Lipscomb speaking at the 1995 Pauling memorial symposium, Oregon State University.

When I was growing up and learning science and all through my undergraduate days, I thought the worst thing you could possibly do is publish something that is wrong. It turns out that’s not right. Linus taught me that. It is much worse to work on something that is dull.

– Bill Lipscomb, November 1991.

William N. Lipscomb, Jr. a Nobel laureate with close ties to Linus Pauling, died last month at the age of 91. Several obituaries and remembrances are available online, published by sources as diverse as Chemical & Engineering News, National Public Radio and Harvard University, where he worked for over fifty years.

Born in Cleveland, Ohio and raised in Kentucky, Lipscomb conducted his undergraduate work at the University of Kentucky, which he attended on a music scholarship. In his own words,

I read Dushman’s Quantum Mechanics in my spare time and completed requirements for majors in both Chemistry and Physics. An appointment to graduate study in Physics at Caltech, at $20 per month, allowed me to refuse Northwestern’s offer of $150 as research assistant, and also allowed me to come to terms with a nice letter from Harold Urey rejecting my application to Columbia University.

Lipscomb initially planned to study quantum mechanics at Caltech under the direction of William V. Houston. His path changed, however, upon his first encounters with Linus Pauling.  Lipscomb recalled

I would sit in seminars and Linus Pauling would make comments afterwards, and they were comments that I was thinking about too, pretty much the same, and I decided to switch to chemistry after my first semester. And I went in to see him and he was a little surprised and looked at my record and said very good record, except there was a C in economics. He says, ‘I got an A in economics.’ And I said, ‘yeah, but I didn’t go to the classes at all.’

As a graduate student working under Pauling, Lipscomb conducted research on structural chemistry and also participated in the Institute’s vast program of scientific war work. Following the completion of his time in Pasadena, Lipscomb moved on to the University of Minnesota, where he began investigations into the structure and property of boranes – a program of research which would eventually lead to Lipscomb’s receipt of the 1976 Nobel Prize for Chemistry.

It turns out that there was a strong Pauling connection to this research as well. A New York Times feature following the Nobel announcement put it this way.

When William N. Lipscomb was a graduate student at the California Institute of Technology, he heard a professor propose a theory of chemical bonding in certain boron compounds. Something about the theory did not seem right, and he set out to prove his professor wrong. In so doing, he won the 1976 Nobel Prize in Chemistry.

The professor was Linus Pauling, a Nobel laureate and a strong influence on the career of Dr. Lipscomb. In fact, he used a research technique taught him by Dr. Pauling to identify and study the structure of boranes, the complex compounds combining the element boron with hydrogen.

Time magazine described Lipscomb’s breakthrough in these terms.

He discovered that boranes…were bonded differently from other chemicals. That discovery led to his finding that borane molecules were polyhedral, or many sided, and to a new understanding of how a host of new chemical compounds could be constructed.

Pauling was quite fond of Lipscomb and often wrote glowing recommendations on his behalf. A 1950 letter describes Lipscomb as “thoroughly competent” and “extraordinarily likable.” A year later Pauling upped the ante a bit, using the phrase “one of the most able physical chemists in the country” blessed with “an unusually fine personality.” By 1952 Lipscomb was “one of the leading crystal structure workers in the country – he may be the best one of his age,” and by 1979 Pauling had given his full support to Lipscomb’s nomination for the National Medal of Science.


Lipscomb at a Stanford University symposium honoring Linus Pauling, March 1994.

Lipscomb is as many faceted as his molecules; he is a tennis buff, plays a clarinet in local chamber orchestras, and is a genuine Kentucky colonel. His own concern about his Nobel: ‘I’m afraid everyone will think I’m finished, but I still have so much more to do.’

Time magazine, November 1976.

The Oregon State University Libraries Special Collections contain a number of resources related to Lipscomb, including a large correspondence file with Pauling and a lengthy interview conducted by Thomas Hager for use in his Pauling biography, Force of Nature. Lipscomb also spoke at the Pauling memorial symposium hosted by OSU in early 1995. Below are Lipscomb’s thoughts on a number of Pauling-related topics, as extracted from these resources.

On their working relationship

I was always doing some outlandish thing, and he would correct me, but that is the way it worked with Linus; he would come in once every two months, or three months, and ask what you have been doing, and suddenly he would toss up five ideas that you haven’t thought of, that would keep you busy for the next five months. And he’d leave you alone, which was the best thing in the world for me. Being left alone, and left with good ideas.

On Pauling the teacher

One of the most interesting things about those five years [1941-1946], is that Linus continued to lecture and gave only one course. It was his chemical bond course, and you could listen to it year after year, because every year, the lectures were different…. The first third of the lecture someone off the street could understand. The next third was what every graduate student could understand, and the last third was the research socket, which was new…. Also on seminars, when he would listen to a seminar, he would wait until everybody was finished asking questions. Then he would ask the best questions of anybody. A marvelous teaching method but, I regarded him as one of the finest teachers in the world.

On Vitamin C

You have to remember that sometimes Linus exaggerates his case. And if he takes twenty grams of vitamin C, well, I believe him, I take three; something like that. I think that is a good way to put it. Dorothy Hodgkin said that the best indication that Linus’s vitamin therapy…is right is his age and activity. I mean you can’t disbelieve that.

[But] one case doesn’t prove anything. He has one good solid point going for him, and that is most mammals don’t make…vitamin C – for 5 million years [they] didn’t need it because they ate so much fruit, and it is only in the last forty-thousand years since civilization that we really need it. And I think that the gene might have been lost much earlier in evolution if it hadn’t been needed. So, he translates what other animals make into humans and comes out with some large number of grams a day of vitamin C. He is probably right. There are hazards associated with it; I think that when people really look carefully, and they are beginning to look carefully, they will find that it won’t cure a common cold, and it won’t cure cancer, but it may help to alleviate symptoms, and help to scavenge free radicles that start cancer; it may be that statistically people will live longer than they have after taking some large dosage of vitamin C, provided they don’t generate kidney stones or gall. You know, you have to do some selection, or some careful testing before prescription.

On Pauling away from work

Pauling also was interested in reviewing books. He used to read review books, novels, things like that. We’d come in and he’d have a stack of books this high, and said he’d read them over the weekend. He is very, very good about reading. And he used to build chairs and furniture just as relaxation.

On Pauling the showman

At my request, Pauling visited the University of Minnesota in about 1952. In the middle of his lecture he stopped suddenly and began banging the doors of the lecture desk, asking, ‘Bill, don’t you have any structure models here?’ He found it:  a model of the new alpha-helix that he had placed there earlier in the day so that he could put on this moment of performance.

Pauling110

Linus Pauling. Lecturing at the Concepts of Chemical Bonding Seminar, Oslo University, Oslo, Norway. 1982.

Today marks the 110th anniversary of Linus Pauling’s birth, which occurred in Portland, Oregon on February 28, 1901. As has become tradition on the Pauling Blog, we are celebrating this occasion by looking back at Pauling’s life in increments of twenty-five years.

1911

At the tender age of ten, young Linus was already at a crossroads in his life. First and foremost, his father Herman had died of a perforated ulcer the previous summer, thus throwing the Pauling family into something akin to chaos. Herman was a pharmacist and businessman of middling success, and his death was a source of major financial concern for his widow Isabelle and their three children, Linus, Pauline (age 9) and Lucile (age 7). From this point on, Linus’s childhood was certainly informed, if not dominated, by the continual need to contribute to the household income. His mother’s only asset of consequence was the family home, which she boarded out on a regular basis in an attempt to make ends meet. But as time passed and Belle’s own health faded, her only son was frequently called upon to assist with the family finances, leading Linus to assume any number of odd jobs, from delivery boy to film projectionist to grocery clerk.

Young Linus, ca. 1910s.

It was at this same time that the boy’s interest in science was beginning to flower. The previous year Herman had written a letter to the Portland Oregonian newspaper indicating that his son was a “great reader” keenly interested in ancient history and the natural sciences. In 1911 Pauling’s scientific impulses continued to flourish in the form of an insect collection that he maintained and classified using books checked out from the Portland library. Not long after, as with many scientists of his generation, Linus would develop an interest in minerals and begin compiling a personal collection of classified stones that he found.

1936

By the age of thirty-five, Pauling had already established himself as among the world’s pre-eminent structural chemists and was well on his way to making a major impact in the biological sciences. In 1936 Pauling met Karl Landsteiner of the Rockefeller Institute, a Nobel laureate researcher best known at the time for having determined the existence of different blood types in human beings. In their initial meeting, Pauling and Landsteiner discussed Landsteiner’s program of research in immunology, a conversation that would lead to a fruitful collaboration between the two scientists. Importantly, his interactions with Landsteiner would lead Pauling to think about and publish important work on the specificity of serological reactions, in particular the relationship between antibodies and antigens in the human body.

Linus Pauling, 1936.

The year also bore witness to a major change at the California Institute of Technology: in June, Arthur Amos Noyes died. Noyes had served as chairman of the Caltech Chemistry Division for some twenty-seven years and was among the best known chemists of his era. His death ushered a power vacuum within the academic administration at Caltech, by then an emerging force in scientific research. Three of Pauling’s colleagues cautiously recommended to Caltech president Robert Millikan that Pauling be installed as interim chair of the department. Millikan agreed and offered the position to Pauling, but was met with refusal. At the time of the proposal,  Pauling was the object of some degree of criticism within the ranks at Caltech – certain of his peers felt him to be overly ambitious and even reckless in his pursuit of scientific advance – and the suggestion that Pauling assume division leadership was hardly unanimous. Millikan’s terms likewise did not meet with Pauling’s approval; in essence he felt that he would be burdened with more responsibility but would not gain in authority. The impasse would not last long however, as Pauling would eventually accept a new offer in April 1937 and begin a twenty-one year tenure as division chief.

1961

A busy year started off with a bang when the sixty-year-old Pauling was chosen alongside a cache of other U.S. scientists as “Men of the Year” by Time magazine. By this period in Pauling’s life his peace activism was a topic of international conversation and early in the year Linus and Ava Helen followed up their famous 1958 United Nations Bomb Test Petition with a second “Appeal to Stop the Spread of Nuclear Weapons,” issued in the wake of nuclear tests carried out by France. As a follow-up, the Paulings organized and attended a May conference held in Oslo Norway, at which the attendees (35 physical and biological scientists and 25 social scientists from around the world) issued the “Oslo Statement,” decrying nuclear proliferation and the continuation of nuclear tests.

Group photo of participants in the Oslo Conference, 1961.

While Pauling’s attentions during this period were increasingly drawn to his peace work, he did make time for innovative scientific research. Of particular note was his theory of anesthesia, published in July in the journal Science. Pauling’s idea was that anesthetic agents formed hydrate “cages” with properties similar to ice crystals. Owing to the nature of their molecular structure, these cages would impede electrical impulses in the brain, thus leading to unconsciousness. In a review article published one year later, the pharmacologist Chauncey Leake described the theory as “spectacular,” though for reasons that are still unclear it failed to gain traction with the larger scientific community.

1986

By age eighty-five, Pauling’s interests centered largely upon his continuing fascination with vitamin C. Having already published monographs focusing upon ascorbic acid’s capacity to ward of the common cold and the flu, Pauling was ready to put his thinking together into a general audience book that would discuss the path to happier and healthier lives. The result was How to Live Longer and Feel Better, a modest critical and commercial success that helped bolster the reputation and the finances of the struggling Linus Pauling Institute of Science and Medicine.

Pauling at 85.

Many of the recommendations that Pauling made in How to Live Longer… were fairly typical of most health promotion books: a sensible diet, regular exercise and no smoking. The major exception to this moderate approach was the famed author’s stance on vitamin supplementation. In biographer Thomas Hager‘s words

Pauling was now advising between 6 and 18 grams of vitamin C per day, plus 400-16,000 IU of vitamin E (40-160 times the RDA), 25,000 IU of vitamin A (five times the RDA), and one or two ‘super B’ tablets for the B vitamins, along with a basic mineral supplement.

This staunch belief in the value of megavitamins would stay with Pauling until his death eight years later, in August 1994.

Goodbye Cliff

Today marks the final day in the office for Clifford Mead, the only Head of Special Collections that Oregon State University has ever known. He is retiring after twenty-four years of service to OSU Libraries, a time during which the institution has experienced tremendous growth.

When Linus Pauling donated his papers to OSU in April 1986, there was no Special Collections unit in what was then known as the Kerr Library. Recognizing that this major new acquisition required its own department, the library soon hired Cliff from Keene State College in New Hampshire to oversee the monumental task of shepherding the Pauling Papers into usable form. Items flowed from at least four different locations to Corvallis (and to a warehouse in Albany, as the original Special Collections facility was not large enough to house the archive) and the staff went to work.

In the two decades that followed, the more than 4,400 linear feet of materials that comprise the Pauling collection have been arranged, described and made available, many of them in digital form. (Currently, fourteen online resources related to Pauling, including this blog, have been released by the OSU Libraries Special Collections.) At the same time, the department has added more than two dozen ancillary book and manuscript collections, most of which focus on the history of science and technology in the twentieth century.

Linus Pauling, Cliff Mead and members of the Special Collections student staff. 1987.

With Cliff’s retirement, the library loses its last employee who worked closely with Linus Pauling. So too will it lose a wealth of knowledge concerning the history of the book, for Cliff is surely among the region’s most capable evaluators of rare book collections. Cliff has headed the organization of three conferences of international import, overseen the awarding of six Pauling Legacy Awards and coordinated the month-long visits of five Resident Scholars. In twenty-four years, he has attended countless meetings, led innumerable tours and taught scores of classes, acting always as a knowledgeable and enthusiastic ambassador for Special Collections.

As an emeritus professor, Cliff plans, among other pursuits, to continue working on a book project of his own and to follow his beloved Yankees with the same energy that he has devoted to his professional work. To those of us on staff in Special Collections, he will remain a generous mentor, gracious colleague and loyal friend.

Oregon State University has released an official press release announcing Cliff’s retirement, the text of which is appended below. For those interested in watching Cliff in action, check out this ten-minute tour of our facility, recorded in 2008.


CORVALLIS, Ore. – Clifford Mead, an expert on the life of one of Oregon State University’s most celebrated alumni, Linus Pauling, and the man responsible for the growth of OSU Libraries’ world-class collections, is retiring after 24 years at the university.

Mead, who is head of Special Collections for OSU Libraries, will retire Jan. 1. His expertise in special collections administration has resulted in the development and growth of a collection that serves as a resource not only for the OSU community but for scholars from across the globe.

Mead has dedicated himself to making the OSU collections available to the public, explained Mary Jo Nye, the Horning Professor of Humanities and Professor of History emeritus.

Cliff Mead, Linus Pauling and biographer Thomas Hager on the OSU campus, March 1991.

“Cliff and his staff have pioneered online website communication of historically valuable documents, photographs, films, and other resources to the public,” Nye said. “He has been a real treasure at OSU whom countless visitors have found to be their engaging and omniscient guide in Special Collections.”

The focus of OSU Special Collections is on the Ava Helen and Linus Pauling Papers, with a broader emphasis on the history of 20th century science and technology. Mead has led the Special Collections’ development of digital resources, especially those that provide in-depth coverage of the life and work of Linus Pauling, the only recipient of two unshared Nobel Prizes.

“In addition to Professor Mead’s leadership in developing a truly innovative and world-renowned web presence for displaying the vast resources of the Special Collections department, he has provided exceptional opportunities for OSU students to have first-hand experience working with primary research materials,” said Karyle Butcher, former OSU University librarian and director of the OSU Press.

Cliff Mead with Warren Washington, 2010 recipient of the National Medal of Science.

Mead is recognized as the authority on the Ava Helen and Linus Pauling Papers. He has authored several publications, and most recently co-edited with OSU’s Chris Petersen, “The Pauling Catalogue: Ava Helen and Linus Pauling Papers at Oregon State University” (2006).

Mead received bachelor’s and master’s degrees from Syracuse University.

Paul Farber, an OSU distinguished professor emeritus, said Mead’s personality drove the collection.

“Cliff has that rare combination of intelligence, organization, personality, wit and humor that makes a university collection of papers and books into a Special Collection,” Farber said. “He has been at the center of creating this major asset at OSU, one that has large portions available online, and one that brings scholars from around the world to campus. He cannot be replaced, but he has built an institution that will persist.”

Larry Landis, OSU’s university archivist, will serve as interim director of Special Collections beginning Jan. 1. He has been at OSU since 1991.

Vitamin C, the Common Cold and Controversy

By Tom Hager

[Part 3 of 3. For the full text of this article, originally presented as a lecture sponsored by Oregon Health Sciences University, please see this page, available at http://thomashager.net]

Portuguese edition of Vitamin C and the Common Cold, a book that was translated into nine different languages.

Pauling’s reading of the literature convinced him that the more vitamin C you took, approaching megadose levels, the lower your chances of getting sick, and the less sick you got.  It was at this point that Pauling made what I consider to be a fundamental mistake. He decided to publish his ideas without peer review, in the form of a popular book.

He did not feel he could wait. He had, he thought, good evidence that a cheap, apparently safe, easily available nutrient could prevent at least an appreciable fraction of a population from suffering through an affliction that made millions of people miserable. And there might be even greater results. Pauling had read of small villages, snowbound in the winter, where no one got colds because there was no reservoir of respiratory viruses to pass around. When visitors arrived in the spring, they would bring colds with them, and everyone would suffer. What if, through the use of vitamin C, a great many more people strengthened their resistance to colds? The two hundred or so cold viruses rampant in the world would have many fewer places to replicate themselves. The spread of colds would lessen; the population of cold viruses would decrease. “If the incidence of colds could be reduced enough throughout the world,” Pauling thought, “the common cold would dis­appear, as smallpox has in the British Isles. I foresee the achievement of this goal, perhaps within a decade or two, for some parts of the world.” Vitamin C, properly and widely used, might mean the end of the common cold.

Packaging for commercial cold remedies pasted by Pauling into his research notebook, July 1970.

This, of course, would not only greatly lessen the amount of suffer­ing in the world; it would increase the fame of Linus Pauling. He was nearing seventy years of age. It had been nearly twenty years since he had captured international attention for his scientific work with proteins, and won the Nobel Prize for chemistry. His efforts had gone to politics in the years since, and none of his recent scientific work had had much impact. Science was moving on without him. He was becoming a historical figure.

Pauling did not feel like one. He was not ready for emeritus status, trotted out at honorary occasions, shunted aside while the young men made the discoveries. He was still strong, still smart, still a fighter. Or­thomolecular medicine was the newest of his grand plans, and no one had shown that his ideas about creating an optimal molecular environ­ment for the body and mind were wrong. The evidence he had uncov­ered about ascorbic acid and colds, evidence that showed human health could be improved by increasing the amount of vitamin C in the body, was the strongest indication yet that he was right. Bringing it to the public’s attention would not only be good for the public; it would be a striking example of the correctness of his general theory.

Pauling’s book Vitamin C and the Common Cold, written in his usual clear, well-organized, straightforward style, presented the results of his literature search. He discussed the findings of five controlled trials that supported his idea, several anecdotal instances of physicians who had treated colds with vitamin C, and evidence that ascorbic acid was safe in large doses. Pauling felt confident that a several-gram daily dose would do no more harm than to cause loose stools, that vitamin C was safe, especially compared with potentially toxic, commonly avail­able over-the-counter medications such as aspirin. The rest of the book was a summary of his orthomolecular thinking and Irwin Stone’s ideas about evolution. A good deal of space was devoted to the topic of bio­chemical individuality, which resulted in a wide personal variation in the need for vitamin C and other nutrients.

On November 18, 1970, prepublication galleys were released to the press, and an unprecedented public roller-coaster ride began. The next day, the New York Times quoted Pauling as saying that humans needed between 1 and 4 grams of vitamin C per day to achieve optimal health and prevent colds. Pauling also took the occasion to slam the medical establishment – from drug companies to medical journals and physicians – for attempting to quash the evidence in favor of ascorbic acid. Why would they do that? the reporter asked. Look at the cold-remedy industry, Pauling said: It was worth $50 million per year, and that bought a lot of advertising space in medical magazines.

This quickly alienated both physicians and the editors of medical journals, neither of whom liked the implication that profits were more important than health. The medical establishment felt it necessary to respond, and respond quickly, once they saw how Pauling’s idea took off.

The book sold wildly, and so did vitamin C.  Pauling’s timing, at least on the public side, was superb. The 1960s had seen a resurgence of interest in “natural” health based on a holistic attitude that said body, mind, and soul were one. Many streams fed into this alternative health movement: a back-to-the-land, organic-foods orientation; a fas­cination with yoga, acupuncture, meditation, and other Eastern health practices; the rediscovery of the lost Western arts of naturopathy and homeopathy. Pauling’s message about vitamin C resonated with mil­lions of people who were reacting against corporate, reductionistic, paternalistic medicine, with its reliance on drug therapy, with people taking a renewed responsibility for their own health and trying to do it naturally. It was delivered just as natural food stores were popping up on corners in every town in America, each one stocked with a section for herbal remedies, a rack for magazines on alternative health regi­mens, and plenty of shelf space for vitamins.

The publication of Pauling’s book triggered a nationwide run on vitamin C. Sales skyrocketed, doubling, tripling, quadrupling, within a week of its appearance. Druggists interviewed in newspapers across the nation told of people coming in to buy all the vitamin C they had. Wholesale stocks were depleted. “The demand for ascorbic acid has now reached the point where it is taxing production capacity,” said a drug company spokesman less than a month after Pauling’s book ap­peared, adding, “It wouldn’t pay to increase production capacity since we’re sure it’s just a passing fad.”

The reaction was swift. The physician-head of the Food and Drug Administration (FDA), Charles C. Edwards, announced to the press that the national run on vitamin C was “ridiculous” and that “there is no scientific evidence and never have been any meaningful studies in­dicating that vitamin C is capable of preventing or curing colds.” The FDA, Pauling found, had proposed in 1966 that no vitamin C tablets over 100 mg be available without a prescription, and he responded to Edwards with sarcasm. If the FDA had its way and he wanted to take 10 grams of vitamin C to fight off a cold without going to a physician for a prescription, Pauling said, he would have to take 100 tablets. “I think I would have as much trouble swallowing all these tablets as I would swallowing some of the statements made by the Food and Drug Ad­ministration in proposing these regulations,” he said.

The medical press was equally critical of Pauling. The American Journal of Public Health said that Pauling’s book was “little more than theoretical speculation.” The Journal of the American Medical Association said of Pauling’s book, “Here are found, not the guarded statements of a philosopher or scientist seeking truths, but the clear, incisive sentences of an advertiser with something to sell. . . . The many admirers of Linus Pauling will wish he had not written this book.” The Medical Letter launched the harshest attack yet, saying Pauling’s conclusions “are derived from uncontrolled or inadequately controlled clinical studies, and from personal experience” and pointing out that there was no good evidence that vitamin C was safe when taken over a long period of time in large doses.

The controversy over Pauling’s book arose from a simple fact: He had not made his case. The book was a combination of his interesting but unproven speculations about orthomolecular medicine and the human evolutionary need for ascorbic acid, coupled with a select handful of studies that indicated that vitamin C could prevent or ame­liorate colds in a fraction of a population. That might make an inter­esting conference paper, but it was little reason to advocate a wholesale change in the dietary habits of a nation. His critics pointed out that he had no clear theory of how vitamin C exerted it powers and that there was no good study – no study at all – establishing that the long-term ingestion of megadoses of vitamin C was safe. The current dogma in the medical profession was that vitamins were needed only in the small amounts provided by a well-balanced diet. Taking grams of vitamin C every day might cause everything from gastric upset to kid­ney stones, and who knew what else?

The way he had gone about publicizing his ideas, sidestepping the normal channels of scientific peer review to publish a popular book, also fueled criticism. He was behaving like a health faddist, not a scien­tist. In the eyes of most physicians – generally conservative about new therapies, disdainful of the holistic health movement, trained to be­lieve that vitamin C was needed only to prevent scurvy – Pauling looked like a nutritional quack, a vitamin pusher who was essentially prescribing without a license.

Typically, Pauling fought back. To pursue his ideas, in 1973 he cofounded (with Arthur Robinson, a young colleague who later moved to Oregon and this year ran for Congress) the Institute of Orthomolecular Medicine in Palo Alto, California.

He went on to publish more books, adding the flu as another disease vitamin C could fight, then Vitamin C and Cancer, and finally compiled all his ideas into How to Live Longer and Feel Better.

Anecdote published in Chemtech, September 1994.

Criticism from the medical community has never let up. A general belief still exists in most – although not all – of the medical community that Pauling went off his rocker.

However, despite what many physicians believe, the jury is still out. A significant amount of active biomedical research research continues to examine the effects of micronutrients on a variety of conditions. For instance the Linus Pauling Institute at Oregon State University (successor to Pauling’s Orthomolecular Institute) maintains a highly successful research program in 12 laboratories funded with millions of dollars of competitive grant funding. The Institute’s head, Balz Frei, believes that Pauling’s basic approach remains sound – but that his arguments with physicians might have caused as much damage to the study of nutritional science as they did good. In my own view, by putting personal controversy ahead of reasoned consensus both Pauling and his critics polarized the public into groups that still have trouble communicating with each other.

Pauling’s work helped give birth to today’s booming market in nutritional supplements. Vitamin C remains the world’s largest-selling supplement. A large number of advocates strongly believe that ingesting vitamins in amounts far above the RDA can help optimize human health, especially by preventing chronic disease. There is a growing understanding that the key in these studies – as Pauling pointed out long ago – is not to look for vitamins to act like pharmaceuticals, exerting significant effects at low doses, but more like nutrients, with less dramatic effects that accumulate at much higher doses.

Linus Pauling himself lived an active life well into his nineties, performing useful research until the end. He was taking many grams of Vitamin C every day.

Will the controversy he started ever end? Was he a genius, or a crank?

The Birth of Orthomolecular Medicine

By Tom Hager

[Part 2 of 3.  For the full text of this article, originally presented as a lecture sponsored by Oregon Health Sciences University, please see this page, available at http://thomashager.net]

Linus Pauling and Irwin Stone, 1977.

The concept of orthomolecular medicine was Pauling’s grand theory of human health.

His approach was chemical, and viewed the body as a vast laboratory buzzing with chemical reactions: enzyme-substrate reactions, energy-producing reactions, antibody-antigen reactions, the chemical interactions that resulted in genetic duplication, and electrochemical reactions in the brain and nerves. Health, in this view, resulted when the lab was well-run and reactions were moving ahead properly; disease resulted if the proper reactions were hindered or stopped. Optimal health could be achieved by perfecting reaction conditions and making sure that the body maintained the proper balance of chemicals (nutrients, catalysts, and products).

After thinking about this balance for years, he coined a term to describe it: orthomolecular, meaning “the right molecules in the right amounts.”

He first used the term in print in 1967 in relation to psychiatric therapy. He had by then become convinced that conditions such as schizophrenia could be treated with nutrients such as niacin (an approach developed by Abram Hoffer and Humphrey Osmond). However, his theory of orthomolecular psychiatry was either ignored or criticized by the medical community.

Then came Vitamin C.


 

In March 1966, in a speech Pauling gave after receiving the Carl Neuberg Medal – awarded for his work in integrating new medical and biological knowledge – he men­tioned to the audience that he wanted to live another fifteen or twenty years in order to see the wonderful new medical advances that would surely come. A few days later, he received a letter from Irwin Stone, a gregarious Staten Island biochemist he had met briefly at the Neuberg dinner.

Stone told him how much he appreciated his talk and then wrote that asking for twenty more years of life was asking for too little. Why not live another fifty years? It was possible, if Pauling listened to his ad­vice.

Letter from Irwin Stone to Linus Pauling, April 4, 1966. This is the communication that spurred Pauling's interest in vitamin C.

He then told him about vitamin C.

Irwin Stone had been interested in vitamin C since 1935, when he began publishing papers and taking out patents on the use of ascorbic acid, or ascorbate (both synonyms for vitamin C), as a food preserva­tive. Over the years his interest grew as he read a series of scattered re­ports from around the world indicating that ascorbate in large doses might have some effect on treating a variety of viral diseases as well as heart disease and cancer. Convinced of its health-giving power, Stone and his wife started taking up to 3 grams of the vitamin per day- many times the daily dose recommended by the government.

Stone felt better as a result, but it took a car crash to make him a true believer. In 1960 Stone and his wife, driving in South Dakota, both nearly died when they were hit head-on by a drunk driver. They not only survived the crash, however, Stone told Pauling, but healed with miraculous rapidity. This he attributed to the massive doses of vitamin C they took while in recovery.

He emerged from the hospital ready to convince others about the value of ascorbate. He began to read widely, noting that among mam­mals, only man, closely related primates, and guinea pigs were unable to synthesize their own vitamin C internally because they lacked an en­zyme critical in producing the vitamin. As a result, humans had to ob­tain it through their diet. If there was none available, the result was scurvy, the dreaded ailment that had killed thousands of sailors before a British physician discovered it could be prevented by providing lime juice or fresh oranges. The U.S. government had duly set the mini­mum daily requirement for vitamin C at a level just sufficient to pre­vent scurvy.

But Stone believed that it was not enough. Scurvy was not a simple nutritional deficiency, it was a genetic disease, the lethal end point of an inborn error of metabolism, the loss of an enzyme that robbed hu­mans of the ability to produce a needed substance. And it appeared from animal studies that simply preventing scurvy might not be enough to ensure optimal health. Only one good biochemical assess­ment of ascorbic acid production in another mammal had been done, on rats, and it indicated that on a weight-adjusted basis, a 150-pound adult human would need between 1.4 and 4 grams of vitamin C per day to match what rats produced to keep themselves healthy. Stone was convinced that taking less than this amount could cause what he called “chronic subclinical scurvy,” a weakened state in which people were more susceptible to a variety of diseases. In a paper he had writ­ten- and which had already been rejected by six medical journals – he concluded,

This genetic-disease concept provides the necessary rationale for the use of large doses of ascorbic acid in diseases other than scurvy and opens wide areas of clinical research, previously inadequately explored, for the therapeutic use of high levels of ascorbic acid in infectious diseases, collagen diseases, cardiovascular conditions, cancer and the aging process.

In other words, to Stone, giving someone enough vitamin C to pre­vent scurvy was like feeding them just enough to keep them from starv­ing. Full, robust health demanded more. He advised that Pauling start with about one and a half grams per day. It was especially good, Stone said, for preventing viral diseases like colds.

“I didn’t believe it,” Pauling later said jokingly of Stone’s letter. After all, Stone was no physician, nor was he a nutritionist exactly or a professional medical researcher.

Pauling's response to Stone's letter of April 4, 1966. Written in July 1966.

But Pauling was interested enough to try taking more vitamin C himself. He discovered that it helped him fight off the colds that had frequently afflicted him. He felt better. He took a little more. Then more.

But he told few people about it. He remained generally silent about ascorbic acid and its benefits through the late 1960s, limiting his few comments to ideas about how it might be used, along with other nutrients, in the treatment of schizo­phrenics. In late 1969, however, convinced by the theoretical argu­ments of Irwin Stone and impressed by his own success in preventing colds, Pauling began expanding his comments to include the subject of ascorbate and general health, noting in a speech he gave to physi­cians at the Mt. Sinai Medical School his success with the use of vita­min C as a cold preventive. His comments were reported in the newspapers.


Cartoon of Linus Pauling in the laboratory, by Sidney Harris. 1985.

That is how it began. Then, two things happened. First, he received a “very strongly worded” letter from Dr. Victor Herbert, a leading clinical nutritionist and a man who helped set the U.S. recommended daily allowances (RDAs) for vita­mins, who assailed Pauling for giving aid and comfort to the quacks who were bleeding the American public with unsupported claims about the benefits of vitamins. Where, Herbert asked, were the care­fully controlled clinical studies to prove that ascorbic acid had a real effect on colds?

Pauling was taken aback. He had not, in fact, carefully reviewed the literature on vitamin C, limiting his reading to a few of the cita­tions in Irwin Stone’s original papers. But now, “sufficiently irritated by this fellow Herbert,” he began a typically comprehensive tour of the scientific journals.

Second, a writer for Mademoiselle magazine contacted Pauling to get his comments on vitamin C for an article on its health benefits. Pauling offered the reporter the general observation that “optimal amounts of vitamin C will increase health and intelligence” and re­ferred readers to his paper on orthomolecular psychiatry. When the article appeared in November 1969, he found his statement rebutted by Frederick Stare, a professor of nutrition at Harvard, who said Paul­ing “is not an authority on nutrition” and that there was no evidence that increased C helped prevent the common cold; in fact, just the op­posite was true. A large-scale study done with five thousand students in Minnesota twenty years earlier, Stare said, had proven definitively that vitamin C had no effect on colds.

Stung, Pauling quickly tracked down the study and decided that Stare had gotten his facts wrong. The 1942 University of Minnesota study involved 363 student subjects who had been given either a placebo or some extra ascorbic acid over a period of twenty-eight weeks. It was true that the authors had concluded in their summary that there was no “important effect” of vitamin C on infec­tions of the upper respiratory tract. But when Pauling took a closer look at their data, he decided they were wrong. Despite what Pauling considered the very low dose of vitamin C given the students – an aver­age of 180 mg per day compared to the 3,000 mg Pauling was now tak­ing – the researchers had in fact seen an effect:  Subjects receiving the extra vitamin had 15 percent fewer colds, and the colds they got were 30 percent less severe than those receiving the placebo. Vitamin C was not a preventive or cure, but the results were, Pauling estimated, statis­tically significant.

It was confusing, especially when Pauling saw the same thing hap­pening in other reports he found on vitamin C and colds: Partial ef­fects were discounted. The physicians who ran the studies seemed to be looking for total cures, not an indication of an effect. The doses they used were low (150-250 mg was common in these early studies –  several times the current RDA but many times lower than what Pauling and Stone considered a protective dose), and the effects they looked for were too strong.

The problem, Pauling decided, was that the researchers were look­ing for vitamin C to act like a drug. In traditional drug testing, small differences in dosage could have tremendous effects, and overdoses were deadly. The tendency was to use relatively small amounts and look for big effects.

Pauling research notebook entry on Gunther Ritzel's 1961 study. Notes dated February 22, 1971.

But to Pauling, vitamin C was a nutrient, not a drug. When the medical researchers saw a small effect, he thought the logical next step should have been to follow up with larger doses. His literature search uncovered at least one study that showed what might happen if they did. In 1961 a Swiss researcher named Gunther Ritzel had given half of a group of 279 skiers 1,000 mg per day of vitamin C – more than five times the Minnesota dose – and the other half a placebo. Ritzel found that those skiers receiving ascorbic acid had 61 percent fewer days of illness from upper respiratory tract infections and a 65 percent decrease in the severity of their symptoms compared to the placebo group.

This, Pauling thought, was very strong evidence in favor of his ideas. Plot the dose of vitamin C along the bottom of a graph and the effects on colds up the side and you could draw a straight line from the Minnesota results (a small effect with small dose) to the Swiss findings (a larger effect with larger dose). He found a few other papers in which the results fit the pattern. True, some of the research he looked at showed no effect at all – most of these studies, Pauling estimated, were flawed because they used too low doses, too short duration, shoddy oversight, or improper blinding – but the important thing was that a small group of careful clinical studies existed that supported Pauling and Stone’s general theory of vitamin C and health: The more C you took, approaching megadose levels, the lower your chances of getting sick, and the less sick you got.

The Medical Research of Linus Pauling

By Tom Hager

[Ed Note:  In October 2010, Pauling biographer Tom Hager delivered a talk sponsored by the Oregon Health Sciences University which detailed and discussed the various contributions that Linus Pauling made to the medical sciences, including the controversy over his strong interest in orthomolecular medicine.   With the author’s permission, excerpts of this talk are being presented on the Pauling Blog over the next three posts.  The full text of Hager’s OHSU lecture is available here.  Those with an interest in learning more about Hager’s work, including his latest research on food issues and world hunger, are encouraged to visit his blog at http://thomashager.net.]

[Part 1 of 3]

Oil portrait of Linus Pauling, featuring a model of the alpha-helix in the foreground. 1951. Portrait by Leon Tadrick.

By 1939, at the age of 38, Linus Pauling was a full professor and head of the chemistry division at Caltech, as well as the father of four children (three sons, Linus, Jr., Peter, and Crellin; and a daughter, Linda).

He was also beginning to turn his considerable talents toward understanding the complicated molecules inside the human body. He started with proteins.

The Molecules of Life

Determining the structure of proteins at this time was a gigantic problem. Most were difficult to purify, easily degraded, and hard to characterize. Proteins appeared to be not only gigantic, comprising hundreds or thousands of atoms – much too large to solve directly with x-ray crystallography – but also relatively fragile, losing their function (denaturing) after even slight heating or mechanical disturbance. No one at the time was even sure that they were distinct molecules – one popular theory held that proteins formed amorphous colloids, gels that did not lend themselves to molecular study.

Studying them at the molecular level seemed an impossible task with the tools available in the late 1930s. But Pauling took on the challenge. He started with the building blocks of proteins, the amino acids, and directed his growing lab team toward pinning down their precise structures. Then he set himself to figuring out how they formed protein molecules, often building models out of wood, wire, and paper.

He based his approach in part on the ideas of the German biochemist Emil Fischer. Like Fischer, Pauling came to believe that proteins were long molecular chains of amino acids linked end-to-end. Working with Alfred Mirsky in the mid-1930s, Pauling discovered that the denaturing of proteins resulted from breaking weak bonds, called hydrogen bonds, that pinned these chains into specific shapes. Between the early 1930s and early 1950s he made a string of important discoveries about hemoglobin, antibodies (including the most sophisticated work at the time into the structural relationship between antibody and antigen), enzymes, and other proteins.

Foldable paper model of the alpha-helix protein structure published in the Japanese journal Chemical Field, 1954.

In May 1951, he put everything he knew into a celebrated series of seven papers detailing the structures of a number of proteins at the level of individual atoms, including the structure of the single most important basic form of protein, the alpha helix (a hydrogen-bonded helical chain that is a structural component of almost every protein). It was an astounding breakthrough, and it opened the door for an understanding of biology at the molecular level. Within two years, Watson and Crick had used his approach to decipher the structure of DNA.

Biological Specificity

But structure was not everything. Pauling realized that life resulted not from individual molecules, but from the interactions between them. How did organisms make offspring that carried their specific characteristics? How did enzymes recognize and bind precisely to specific substrate molecules? How did antibodies recognize and bind to specific antigens? How did proteins, these flexible, delicate, complex molecules, have the exquisite ability to recognize and interact with target molecules?

It all fell under the heading of biological specificity at the molecular level. Pauling directed much of his attention here during through the 1940s, performing a great deal of careful work on the binding of antigens to antibodies.

Drawings of antibodies and antigens made by Linus Pauling in the 1940s.

His findings were surprising. Pauling demonstrated that the precise binding of antigen to antibody was accomplished not by typical chemical means – that is, through covalent or ionic bonds — but solely through shape. Antibodies recognized and bound to antigens because one fit the other, as a glove fits a hand. Their shapes were complementary. When the fit was tight, the surfaces of antibody and antigen came into very close contact, making possible the formation of many weak links that operated at close quarters and were considered relatively unimportant in traditional chemistry — van der Waals’ forces, hydrogen bonds, and so forth. To work, the fit had to be incredibly precise. Even a single atom out of place could significantly affect the binding.

Having demonstrated the importance of complementary structure with antibodies, Pauling extended his idea to other biological systems, including the interaction of enzymes with substrates, odors with olfactory receptors, and to the possibility of complementary structure in genes.

Pauling’s idea that biological specificity was due in great part to complementary “fitting” of large molecules to one another proved to be essential in the development of molecular biology. His research now formed a coherent arc, from his early work on the chemical bond as a determinant of molecular structure, through the structures of large molecules (first inorganic substances, then biomolecules), to the interactions between large biomolecules.

He carried out much of this research during World War II, when he also worked on synthetic plasma substitutes and a fruitless search for ways to produce artificial antibodies.

He had already earned a place among the nation’s leading researchers in the medical applications of chemistry. But his greatest triumph was still to come.

Sickle-Cell Anemia

Toward the end of World War II, Pauling’s reputation was great enough to earn him an invitation to join a national committee that was brainstorming the best structures for postwar medical research. This committee’s work led to the foundation of the National Institutes of Health.

Pauling was the only non-physician asked to join the committee.

At a dinner with other members one night, talk turned to a rare blood disorder called sickle-cell anemia. One of his dinner companions described how red blood cells in the victims were twisted into sickle shapes instead of discs. The distortion appeared to hinder the blood cells’ transport through capillaries, resulting in joint pain, blood clots, and death. The disease primarily affected Africans and African Americans. What caught Pauling’s attention most, however, was one odd fact: Sickled cells appeared most often in venous blood, rather than in the more oxygenated blood found in the arteries.

Pastel drawing of sickled Hemoglobin cells, 1964. Drawing by Roger Hayward.

He thought about this during the next few days. From his previous work with blood, he knew that red cells were little more than bags stuffed with hemoglobin. He had also shown that hemoglobin changed its shape slightly when it was oxygenated. If the red cells were changing shape, perhaps it was because the hemoglobin was altered in some way. What if the hemoglobin molecules in sickle-cell patients were changed in some way that made them clump, stick to one another, as antigens stick to antibodies? Perhaps something had changed that made the hemoglobin molecules complementary in shape. Perhaps adding oxygen reduced the stickiness by changing the molecules’ shape.

He presented his ideas as a research problem to Harvey Itano, a young physician who was then working on his Ph.D. in Pauling’s laboratory. Itano, later joined by postdoctoral fellow John Singer, worked for a year trying to see if sickle-cell hemoglobin was shaped differently from normal hemoglobin. They found no detectable differences in any of the tests they devised. But they kept at it. Finally, in 1949, using an exquisitely sensitive new technique called electrophoresis that separated molecules by their electric charge, they found their answer: Sickle-cell hemoglobin carried more positive charges on its surface.

This was an astounding discovery. A slight change in the electrical charge of a single type of molecule in the body could spell the difference between life and death. Never before had the cause of a disease been traced to a molecule. This discovery – to which Pauling attached the memorable title “molecular disease” – received widespread attention. Itano and Singer’s followup work demonstrated the pattern of inheritance for the disease, firmly wedding molecular medicine to genetics.

Medical Chemistry

It was a great triumph – there was talk of a Nobel Prize in Medicine or Physiology for Pauling – and it led Pauling to make greater efforts in the medical field. He encouraged M.D./Ph.D. candidates, hired physicians to work in his laboratory, and began focusing his own research on medical problems, including developing a new theory of anesthesia.

He was ahead of his time. An example of what the atmosphere was like: Pauling noted that as he went around in the late 1940s seeking funds for a comprehensive marriage of biology and chemistry to attack medical problems, people at funding agencies were telling him that they found the term “medical chemistry” to be “a disturbing description.”

In the late 1950s, Pauling extended his concept of molecular disease to the brain. After reading about phenylketonuria (PKU) – a condition in which a mental defect can be caused by the body’s inability to metabolize an amino acid, phenylalanine, leading to a buildup of that substance and others in the blood and urine – Pauling theorized that the problem might be caused by a defect in an enzyme needed to break down phenylalanine. PKU, in other words, might be another molecular disease. Now interested in the possibility that there might exist a range of molecular mental defects, Pauling visited a local mental hospital, saw other patients whose diseases seemed hereditary, and decided to seek support for an investigation into the molecular basis of mental disease. The Ford Foundation in 1956 awarded him $450,000 for five years’ work – a vindication of Pauling’s approach and a tribute to his reputation. The grant, however, yielded little in the way of immediate results, with much of the funding going toward testing his (ultimately found to be mistaken) theory of anesthesia.

The long-term results were more significant. Pauling’s immersion in the field, thanks to the Ford grant, led him to read widely in psychiatry and general health, always on the lookout for another molecular disease that might lend itself to new therapy. By the mid-1960s he was coalescing his findings into another overarching theory, this one combining much of what he knew about chemistry and health. He called his new idea “orthomolecular” medicine.