Giants of the Past

Ralph Theodore Holman, 1918 to 2012

Holman_1.jpg Ralph Holman’s life story should be an inspiration to everyone. A depression era young man coming from a modest hard working family, who was a committed Christian and developed into a world class biochemist, is emblematic of the American dream.

Introduction

Ralph T. Holman grew up in Minnesota. His parents and grandparents were descended from Swedish Immigrants who settled there in the mid-1880s. Ralph’s father was employed as a street car conductor in Minneapolis and, during the great depression of the 1930s, struggled financially.

The Minnehaha Baptist Church, Sunday school, and Bible study encouraged a lifelong devotion to Christianity. By the time Ralph reached high school age he took a job at his church as a janitor with a salary of 3 dollars/month during summer and 5 dollars in winter. Thus, with little money, college seemed impossible, but his pastor with the Dean worked out a plan to allow him to attend Bethel Junior College. After graduation, he was able to attend and graduate from the University of Minnesota, when he was encouraged him to apply for a teaching assistant position at Rutgers University leading to a master’s degree. He was accepted and received his degree in biochemistry. His first publication “The sulfur balance of the non-laying, molting, and laying hen” resulted from his Master’s thesis. At Rutgers, the shy Ralph Holman met a young lady during a blind date by the name of Karla Calais. The couple were married in 1943 and their love for each other grew for over 60 years until her passing in 2003.

Ralph then returned to the University of Minnesota to continue his graduate work under Professor George Burr, who in 1929 had discovered essential fatty acids. After 2 years of work involving the growth of plants using labelled carbon dioxide, his research came to a halt when his supply of labelled carbon dioxide ran out. His topic was changed and he began his life’s work as a lipid chemist for which he was never sorry. He quickly began a new project resulting in 4 publications. After receiving the PhD in 1944, Ralph became an instructor in physiological chemistry at Minnesota. In 1946, he was awarded a National Research Fellowship in Stockholm where he worked with Professor Hugo Theorell at the Nobel institute. The collaborations proved to be fruitful and Holman was able to crystallize the enzyme lipoxidase, and determine its activity and amino acid composition. In 1947 he received a grant from the Scandinavian-American Foundation and took a fellowship under Professor Arne Tiselius who pioneered a new technique named displacement analysis. This too was fruitful and upon his return to the U.S.A. in 1948 he took an Associate Professor position at Texas A & M University and began to publish a series of 10 publications on displacement analysis of lipids.

In 1951, Holman returned to University of Minnesota and the Hormel Institute in Austin, Minnesota, remaining there for 5 years. He then took a position as a resident in the Biochemistry Department in Minneapolis. In 1959, he returned to the Hormel Institute. By the early 1960s, mass spectrometry entered the field of lipids and Holman was quick to realize its potential. By 1962, he had received an NIH grant and spent time in Professor Stenhagen’s lab at the University of Gothenberg to learn the technique. During the 1950s and 60s, he published a series of seminal papers on the metabolism of essential fatty acids with a number of students and post-doctoral fellows many of whom went on to have distinguished careers in lipid biochemistry

From 1975-1985 Holman was the director of the Hormel Institute and under his leadership the Institute grew in funding ($1.62 Million to $3.37 Million) in spite of cuts to research by government agencies. Publications increased from 779 to over 1100 from 1975-1985. In 1988, Ralph retired as Emeritus Professor of Biochemistry. During his long and productive career he published well over 425 papers with the most significant contributions being on the biochemistry of fatty acids and their roles in human nutrition. At the time, some believed the work applied to rats only. However his results were validated by others and, by 2000, twenty diseases had been linked to essential fatty acid deficiency in humans. Today this list has grown to about 50. This is the story of the man who pioneered the biochemistry of polyunsaturated fatty acids.

 

Holman’s Roots and Early Years.

The Holmen family emigrated from Sweden to the United States. Ralph’s paternal grandfather Alfred Johannson took the name Holmen when he arrived in Minnesota in 1886, but Ralph’s father Ted Holmen, the first to be born in America (1889), moved from Upsala to St. Paul, Minnesota, in 1908 and took a job as a street car conductor. Here he became a Holman. In 1915, Ted and May were married and son Ralph was born on March 4th, 1918 in Minneapolis.

Ralphs earliest memories of his mother came from her rocking him to sleep while singing lullabies. His favorite was the “Little dog under the wagon”, which a generation later she sang for Ralph’s son Teddy. Ralph’s faith began to develop at the age of 4 when Ted and May began to attend Minnehaha Baptist Chapel, which in 1922 it became an independent church; Ted and May were charter members. Ralph was baptized on his 12th birthday and joined the church on March 4th, 1930.

These were the hard depression years. Ralph took a job as janitor of the church in his senior year of high school. He was paid 3 dollars per month in summer and 5 dollars in winter, when making fires and shovelling snow were required duties. He was responsible for his 25 cent haircuts and other expenditures. By the end of the year he had saved 25 dollars. This was not enough for college but he took all the maths and science courses offered at Roosevelt High School. Ralph graduated in June 1935 20th in a class of 420 and was a National Honor Society scholar. In the summer of 1935, the Rev. Franklin Nelson his pastor, asked of Ralph’s future plans, aware that he lacked funds for University. Shortly thereafter Pastor Nelson came to his home bringing Professor Carlson, Dean of Bethel Junior College, who generously and charitably conceived a plan that enabled him to attend the college.

At Bethel, Professor of Chemistry Nordstrom handled Ralph’s registration and noted that his application stated he wanted to be a chemist. Nordstrom warned him it would not be easy, but he helped Ralph by giving him laboratory duties and advanced chemistry experiments. Nordstrom’s portrait hung in Holman’s office at the Hormel institute for many years after which it went to the Department of Chemistry at Bethel.

Although not mandatory, chapel services at Bethel were recommended and Ralph was a regular attendee because he always learned something. Bethel had one black student who Ralph befriended and made feel part of the group. Bethel’s inter-denomination vision was displayed when the entire student body walked en masse to the Hamline University Fieldhouse to hear the well known Methodist missionary F. Stanley Jones speak. Dean Carlson took Ralph to a downtown church to see and hear the famous black chemist and inventor Dr George Washington Carver of the Tuskegee Institute.

After graduation from Bethel, Ralph took a position as a paid lab assistant in the Biochemistry Department of the University of Minnesota as well pursuing a biochemistry major. Professor Ross Gortner inquired if Ralph’s plans included graduate school. Gortner told him of a half-time assistantship at Rutgers leading to a master’s degree, which he applied for and received in 1939. He began his graduate work and in 1941 received his M.Sc. degree. His thesis was published in the Journal of Nutrition. Ralph thought his best discovery at Rutgers was Karla Calais whom he married in 1943, with his old pastor from Minnehaha Baptist Church officiating the ceremony.

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Ralph and Karla Holman in 1991

Fast forwarding to October 1998, Ralph and wife Karla attended Bethel’s homecoming festival where Ralph received a Distinguished Alumnus Award. He gave a 15 minute sketch of his career after which he received a 5 minute standing ovation. He remarked that 61 years before he couldn’t imagine he would have the attention of a student body of over a thousand telling them about the Gospel according to omega–3 essential fatty acids! After the ceremony the Holmans were taken to look over the excavation for the new Chemistry laboratory scheduled to open in the fall of 1999. Above the door was a sign reading “The Bethel College Chemistry Laboratories are named in honor of 1937 graduate, Ralph Holman.” Holman remarked “life is full of nice surprises.”

 

Research Career

Upon returning to Minnesota Ralph began his PhD thesis work. Professor George Burr suggested he investigate glucose metabolism in plants. The project required heavy 13C-labeled carbon dioxide provided by the Physics Department. In August 1943, Ralph went to the physics lab for a bottle of CO2 only to find the room empty. The physicists were gone and no one knew of their whereabouts. After the war, it was learned they had been sent to join the Manhattan project where fissionable uranium was concentrated. George Burr suggested another thesis topic involving lipid oxidation. Ralph quickly began the new project which resulted in three publications in the Journal of the American Chemical Society. After receiving his doctorate in 1944, Ralph applied for a National Research Council Fellowship for study abroad. In 1945, he was awarded the Fellowship and worked for a year with Professor Hugo Theorell at the Medical Nobel Institute in Stockholm (in the land of his forefathers). Ralph succeeded in crystallizing the enzyme lipoxidase. This work resulted in six publications including co-authorships with the future Nobel Prize Winner Sune Bergstrom.

While in Stockholm, Ralph learned of a new analytical technique (displacement analysis) developed by Professor Tiselius (U. of Uppsala). Ralph applied for and was granted a stipend from The American Scandinavian foundation. Within 3 months he had applied the Tiselius method to separation of complex fatty acid mixtures. Displacement analysis involved placing organic molecules onto adsorbents and separation into zones of increasing affinity. Other workers had attempted to separate fatty acids by displacement with little success. Ralph believed that the problem could be solved with improved adsorbents. By treating charcoal with picric acid, Ralph was able to separate C1-C20 saturated fatty acids via displacement analysis, leading to a series of 10 publications.

In 1948, Ralph was offered a position as Associate Professor at Texas A & M University, where he spent three productive years. Ralph and Karla became parents to son Teddy, and the couple’s first car was purchased there. Ralph was most fortunate to have some excellent graduate students and it was here that his interest in fatty acid metabolism was rekindled. The initial work showed linoleic acid to be the precursor of a fatty acid with 4 double bonds and linolenic acid a precursor of acids with 5 or 6 double bonds in vital tissue lipids.

In 1951 Ralph had an opportunity to return to Minnesota and the Hormel Institute, founded by Jay Hormel (CEO Hormel Company, Austin, Minnesota), with a grant from the National Livestock and Meat Board. Prior to his arrival at the Hormel Institute, nutritional studies with animals had not been undertaken. However, within a short time a new wing was built for animal research with enough space and cages to house 100 rats at a time.

Soon he was able to begin his arachidonic acid work which had been started at Texas A & M. Widmer and Holman were the first to discover that linoleic acid fed to essential fatty acid (EFA) deficient rats was the precursor of arachidonic acid in tissues and that alpha-linolenic acid was the precursor of the penta- and hexaenoic fatty acids in tissues. Rats fed a fat-free diet produced the trienoic 20:3ω9 acid from oleic acid, and linoleic and linolenic acids corrected EFA deficiencies and stimulated growth. At the time, the mechanism was unclear and desaturases were unknown. Later, in 1960, Holman proposed the triene/tetraene ratio as an Index of EFA deficiency and status based on feeding studies, in which rats were given four diets - a fat-free diet, butterfat, cottonseed oil, and a blend of 80% butterfat/20% cottonseed oil. After 89 days, the rats were sacrificed and blood lipids (plasma, erythrocytes) and tissue lipids were taken for polyunsaturated fatty acid (PUFA) analysis. The control group showed severe EFA deficiency, the butter fat diets produced only mild symptoms and the cottonseed and butterfat diets showed no signs of EFA deficiency. The fatty acid patterns indicated a relationship to the content of linoleic acid in the diet. A plot of the percentage of trienoic acid in the endogenous PUFA versus dietary linoleate showed a break when the latter was about 1% of calories and a similar effect was observed with tetraenoic acids. Thus, the ratio of triene/tetraene of less than 0.4 indicates that the minimum requirements of linoleate (1% calories) had been met.

Holman_3.jpgIn subsequent studies, Holman and co-workers investigated dose levels of EFA on the composition of rat liver lipids. Diets of ethyl linoleate, ethyl arachidonate, and ethyl linolenate were tested and weight gain, fat deficiency and lipid compositions were determined. Dietary linoleate fed in excess of 1% of calories maintained good growth and cured EFA deficiency and the liver lipids showed conversion to 20:4 and 22:4 acids, while 20:3 acids decreased. Dietary arachidonate cured EFA deficiency three times more effectively than linoleate and a further conversion to 22:5ω6 was observed. Dietary linolenate was shown not to support weight gain as effectively as linoleate or arachidonate. With linolenate, EFA deficiency could not be cured completely. Thus biochemical changes in tissue fatty acids relative to diet were shown to be useful in determining EFA requirements from tissue analysis.

Gas chromatography, then a new technique, proved to be very useful in the study of dose levels of pure EFA in rat livers and their metabolic products. Dose response curves for dietary alpha-linolenic acid fed to rats showed that conversion to 22:6ω3 rose much more rapidly than the levels of the intermediate acids 20:5ω3 and 22:5ω3 suggesting that the 22:6ω3 is the most important structural acid of the three metabolic products. Further work confirmed that the same phenomenon occurs in erythrocytes, depot fat, brain, and heart tissues and showed that EFA deficiency affects all tissues. The gas chromatography studies showed that two cascades of fatty acids were involved in which the location of double bonds changed at each step of the cascade. The use of the abbreviated Geneva chemical nomenclature became very confusing and a new numbering system for double bond unsaturation was needed. Since biochemistry dictates that the terminal end remains unaltered, Ralph with his knowledge of the Bible (“I am the alpha and the omega”) proposed a numbering system counting from the terminal end of the fatty acid molecule (omega (ω) is the terminal letter of the Greek alphabet). Thus, the omega nomenclature was introduced in 1964 and is still widely used.

The omega-3 acids have become synonymous with nutritional benefits. When a local market hung a sign “Omega-3 are here”, Ralph was so excited he ran home to get his camera to record the event. He lived to the age of 94. When asked his secret to longevity, he replied that consumption of fish (rich in omega-3 acids) is “the Gospel I preach”. In later life, both Holmans had their omega-3 levels checked and learned they were much higher than most Minnesotans.

Ralph’s group showed that linoleic acid (18:2ω6) and alpha-linolenic acid (18:3ω6) are metabolized by the same microsomal enzyme systems by alternating desaturation and elongation steps (cascades) to make metabolic products with chain lengths up to 22 or more carbon atoms. These occur in both animal and human tissue lipids. Thus, linoleic and linolenic acids are the precursors of the two main families of essential fatty acids. The pathway for linoleic acid (18:2ω6) involves conversion to 18:3ω6. It can be followed by chain elongation to 20:3ω6 then desaturation to 20:4ω6 followed by another chain elongation to yield 22:4ω6 and eventually 22:5ω6. Linolenic acid follows a similar desaturation chain elongation sequence to produce 22:6ω3 as the final product.

Further work showed that when dietary 18:2ω6 was held constant, increasing the level of dietary 18:3ω3 suppressed ω6 products and conversely when 18:3ω3 was held constant increasing 18:2ω6 suppressed ω3 products. Based on these studies, Holman proposed a general hypothesis that all fatty acids of the ω3 and ω6 series can compete at all steps of the cascades since the same enzymes are involved in the required desaturation/elongation reactions. The importance of these findings was not recognized until some years later.

Much of Holman’s research focused on EFA deficiency in humans. It had been shown that an infant born with numerous medical problems fed a fat-free TPN diet (total parenteral nutrition) developed skin lesions after 3 months. Analysis of the plasma phospholipids showed that the infant was deficient in EFA and analysis of tissue lipids confirmed EFA deficiency. These findings provided evidence that plasma and tissue phospholipid profiles can be used as a measure of EFA deficiency in humans. During the same period an elderly lady was put on a fat-free diet and lesions appeared within a month. Lipid analyses at 1, 2, and 3 months indicated a severe (nearly complete) EFA deficiency. These cases showed that EFA deficiency can occur rapidly in both the young and old.

Holman also reported the first case of omega-3 deficiency in a six-year old girl who was the victim of an accidental gunshot wound. By 1982, the FDA approved the use of two TPN preparations with lipid emulsions, one of which contained soybean oil and the other safflower oil to provide EFA. The soy preparation contained 18:3ω3, whereas safflower oil is devoid of omega-3 acids but with a high content of 18:2ω6. Within 5 months on the safflower TPN diet, the girl exhibited numbness, tingling, weakness and the inability to walk. It was suspected that the safflower TPN was inducing omega-3 deficiency and this was confirmed by lipid analysis. After a switch to the soy oil-TPN, the neuropathy disappeared and lipid analysis confirmed that omega-3 deficiencies were restored to normal.

In addition to single case studies, Holman reported several larger ones including vegetarians in the U.S.A. and populations from foreign countries. 100 Healthy vegetarians from the University of Minnesota faculty and students were the control group while blood lipid data from 6 countries were compared. A plot of total ω3-PUFA versus total ω6-PUFA showed a correlation between the two acids. As ω3 acids increased the ω6 acids decreased. Although wide ranges of dietary acids support life it is interesting to note that countries where fish is consumed (Northern Sweden, Kerala, and Nigeria) had the highest omega-3 acid contents. American infants and the Minnesota group had the lowest omega-3 status.

Ralph reported a study in which the omega-3 acids of subjects with known diseases were compared to the above subjects and found that diseased humans had lower omega-3 values (similar to the Minnesota controls and infants). These observations were attributed to diets in which omega-3 acids are not provided since in many of our foods. Indeed, omega-3 oils such as soybean oil had been modified by hydrogenation to provide increased shelf life and functionality. At the time, some believed that EFA effects pertained to rats only. However, by 2000, 20 diseases had been linked to essential fatty acid deficiency in humans and, currently, 50 afflictions and diseases have been so linked.

An excellent review of his work up to 1998 can be found in - The slow discovery of the importance of ω3 essential fatty acids in human health. J. Nutr., 128, 427S-433S (1998) (jn.nutrition.org/content/128/2/427S.full).

 

The Hormel Institute

After a long and productive career of leading and conducting lipid research at the Hormel Institute Ralph moved into administration. In 1974, the Director Walter Lundberg requested medical leave until retirement. Eventually, Ralph was unanimously selected as Director by the Hormel Institute Board. Before accepting, he explained the conditions under which he would take the position. The directorship should be no longer a lifetime appointment with the change effective with him. Secondly, the board should fix the term of office at 5 years and a review of performance by faculty after 4 years, with reappointment depending upon satisfactory performance. Thirdly, he requested more interest and involvement from the Institute Board. The Board agreed and, after salary had been set, Holman accepted the invitation effective from July 1, 1975.

The 10 years of Ralph’s tenure as director were excellent ones despite funding cuts to research in general. From 1975-1985 Funding doubled from 1.6 to 3.4 million dollars and the Institute continued a high rate of publication. The governor of Minnesota paid them a visit and was so impressed that a further 550,000 dollars was appropriated. The electronics and computer departments were expanded and updated as well as the purchase of a state-of-the-art mass spectrometer and other important instrumentation. Highlights of the decade included the 50th anniversary of the Institute celebrated with a birthday cake enriched with omega-3 acids that Holman had baked himself. The Institute developed a program to assist small biotechnology start-up companies by providing space and a distance learning program.

The Hormel Institute was a Mecca for attracting post docs and visiting scientists. From 1951 until 1997, 85 persons came to study or work, 30 of whom came from outside the U.S.A. Three of the visiting scientist had received or would receive the prestigious AOCS Award in Lipid Chemistry

 

Editorial Duties - Honors - Awards

In early 1951, while still at Texas A & M University, Ralph was invited to contribute three chapters to an updated book first published in 1936 by Dr. Schoenfeld (The Chemistry of Fats). Ralph accepted and completed one chapter with two others in progress by the time he left Texas. Shortly after arriving at the Hormel Institute, he learned that Schoenfeld had died. Asked for his advice, Ralph suggested that the rapidly developing field of lipid research was ready for a series of volumes. Thus, the 33-year-old Holman become the editor together with Walter Lundberg and Thomas Malkin of “Progress in the Chemistry of Fats and other Lipids”. The first volume appeared in 1952 and, in 1962; the 6th volume was in preparation when Ralph became sole editor. Within a few years the Progress series evolved into a journal renamed “Progress in Lipid Research” to reflect other fatty materials. Volume 17 appeared in 1979 and was dedicated to Walter Lundberg, while another volume was dedicated to Stina and Einar Stenhagen. Holman remained editor through Volume 28 (1989) with assistance from Howard Sprecher and William Christie, former post-doctoral fellows from his lab; John Harwood (Cardiff, U.K.) replaced the latter with Volume 29 (1990). The journal is still going strong with Volume 53 appearing in 2014.

In addition to the Progress series, Ralph was the founding editor for the AOCS journal Lipids, and he served on the Editorial boards of the Journal of Nutrition, Excerpta Medica, the Journal of Parenteral and Enteral Nutrition and the Journal of Laboratory and Clinical Medicine. He also served on the advisory board of the CRC Press Handbook of Prostaglandins and Related Lipids.

The “Metabolic Conferences” began in 1956 when a group of top lipid biochemists met in various west coast cities. Among them were four Nobel laureates. From 1958 to 1987, Ralph attended nearly every meeting. In 1958, Harry Deuel, who had authored a three-volume set on lipids, passed away. From then on the conference was renamed the Deuel Conference in honor of his numerous contributions to lipid biochemistry. Ralph served on the program planning committee as well as chairing fund-raising efforts needed to support the conferences, which covered many lipid topics other than the essential fatty acids dear to his heart.

Ralph had tried to convince the conference that too much emphasis was being placed on lowering cholesterol levels rather than increasing omega-3 levels in the diet. Finally, in 1981, he got his wish as the theme centered around omega-3 acids; the essential fatty acids were now getting the attention they deserved!

1979 marked the Golden Anniversary of Burr’s discovery of essential fatty acids. In 1980, Holman organized the First International Congress on Essential Fatty Acids and Prostaglandins to be held in Minneapolis where Holman’s supervisor George Burr had discovered EFA some 50 years previously, and the proceedings were published in Progress in Lipid Research. The volume soon became the “Bible” of the field and remained so for several years. The second Conference was held in London (1985), where Ralph was part of the organizing committee, while the third (1992) was held in Adelaide, Australia with Ralph as the Honored Speaker.

1981 brought good news to Holman. In April, he received a call announcing his election to the National Academy of Sciences. Holman reacted by “you have to be kidding”, because he had never of thought of that possibility. In 1982, he and Karla traveled to Washington DC for the NAS meeting and were formally inducted by signing the large roster book holding the signatures of all NAS members.

Ralph travelled extensively abroad including trips to Sweden, Norway, Italy, England, Japan, Argentina, Mexico, New Zealand and Australia. Karla travelled to Sweden and Norway with him. The highlight was an invitation to attend the Nobel ceremony in Stockholm where Professor J.B. Sumner was honored for his pioneering enzyme work. He had succeeded in crystallizing the enzyme urease by using techniques that were rapidly adopted by others. He discussed the work on soybean lipoxidase with Ralph, who found him shy but cordial and friendly. In 1995, Ralph was a Guest speaker at the “Meat composition, nutrition and health Conference in Buenos Aires, Argentina.

Ralph was a regular attendee at AOCS Meetings and was heavily involved in the governance of the Society as a member of the Governing Board, as Secretary, Vice President and President in 1974. After his retirement in 1988, he attended few meetings, but the 2001 meeting was held in Minneapolis. Here he received the A.R. Baldwin distinguished Service Award for outstanding service to the Society. The last meeting he attended was held in Cincinnati where he was inducted as an AOCS Fellow. The Health and Nutrition Division of AOCS established an award in recognition of meritorious service and contributions to health and Nutrition, He was the first recipient in 2004, and it was renamed the Ralph Holman Award in subsequent years. A framed colour print of orchids (dear to his heart) was a momento of the Award as well as a 1000 dollar honorarium.

In 1959 the North Central Section of AOCS established the Alton E. Bailey Medal to commemorate Bailey’s contributions to fats and oils technology. The award is the oldest and one of the most prestigious honors given to a lipid chemist. Ralph along with Walter Lundberg and Orville Privett from the Hormel institute staff received this Award, together with several visiting scientists who had worked under Ralph’s guidance.

The AOCS award in Lipid Chemistry (renamed since) dates back to 1964 and its recipients include three Nobel laureates, which no other lipid award can claim, and currently carries a 10,000 dollar honorarium. Ralph received the award in 1979 for his pioneering work on essential fatty acids in human nutrition.

Ralph was a Fellow in the American Institute of Nutrition and recipient of the society’s Borden Award. The Italian Oil Chemists society awarded Ralph the Fachini Medal in recognition of his accomplishments on essential fatty acids. Other international honors include appointment as Foreign Academic Correspondent, Academy of Medical Sciences, Cordoba, Argentina. In addition to holding full professor appointments at the University of Minnesota and the Hormel Institute, Holman was an adjunct Professor at the Mayo Medical School from 1977-1990. After his retirement in1988 he became Emeritus Professor of Biochemistry (U. of Minnesota).

 

His Personal Life

Over his long career Holman had many friends and colleagues who impacted his life. Pastor Nelson at the Minnehaha Baptist Church along with Dean Carlson at Bethel College was instrumental in helping him attend college. Walter Lundberg (a post-doctoral fellow) was described as a brilliant scientist who mentored Holman as a graduate and was a valued colleague first at the University of Minnesota and later at the Hormel Institute. Ralph considered Professor George Burr his mentor and teacher. Burr had a number of careers including pioneering work in essential fatty acids and at the Hawaiian Sugar Planters Association, where he discovered that the initial photosynthetic product in sugarcane was malic acid not the expected pyruvic acid; he had the distinction of making major discoveries in both animal and plant biochemistry. He was described as a very accomplished, yet humble scientist and a true southern gentleman. Holman presented Burr and Lundberg copies of his doctoral thesis complete with their photos.

Karla Holman was the only woman Ralph ever dated and their meeting was the result of a blind date arranged by one of Karla’s friends. Karla had been warned that Ralph was very religious and the subject was to be avoided. Apparently this was not a problem and the married couple attended church service regularly for nearly 60 years and for over 50 of them as members of the First Congregational Church in Austin. After nearly 60 years of marriage, Karla developed serious health problems. Ralph cared for her as long as possible but eventually she was placed in a nursing facility. Every day for 3 years, Ralph spent afternoons at her bedside until she passed away in June 2003.

Dr. Ralph Holman was a truly unique individual having been blessed with a keen intellect, a love for his God, his family, students, associates, and his fellow man. He was possessed with a sense of humour and could laugh at himself and not take himself too seriously. He was a man of integrity, humble, and of a quiet gentle spirit. Moreover his personal life reflected a lifelong devotion to Christianity. Smoking, alcohol, cursing, and off-color jokes were to be avoided.

The Holmans lived in a small well-furnished home in Austin. His frugal lifestyle belied the fact that investments had brought relative wealth. Throughout his undergraduate studies he traveled by bicycle to and from school; the Holmans did not own a car until 1948. He loved Minnesota and built a log cabin on a lake near his in the north of the state, where he and his many colleagues and collaborators enjoyed pleasant weekends communing with nature. He had a particular fondness for orchids, and indeed was one of the few people permitted to grow the state flower - the Showy Lady Slipper orchid (Cypripedium reginae).

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The Holman cabin in northern Minnesota Showy Lady Slipper orchids in the Holman back garden in Austin

 

Epilogue

Ralph Theodore Holman died in August 2012 at the age of 94 from natural causes. At the time of his death he was living in the home that he and his wife Karla had shared for over 50 years before her passing in 2003. Ralph was not only an accomplished biochemist but a devoted father and husband, a man of integrity, and a role model for students and young scientists as well. Ralph was humble, and credited God for any success he had in his personal and professional life. All of his students and colleagues held him in the highest esteem and were the beneficiary of his friendship.

 

Selected Bibliography

1945 With Lundberg, W.O. and Burr, G. Spectrophotometric studies of the oxidation of fats II. The oxidation of dienoic fatty acids. J. Am. Chem. Soc., 67, 1386-1390.
1947 With Thoerell H. and Akeson, A. A note on the preparation of crystalline soybean lipoxidase. Arch. Biochem., 14, 250-252.
  Holman, R.T. Crystalline lipoxidase. II. Lipoxidase activity. Arch.Biochem., 15, 403-413.
1948 With Bergstrom, S. Lipoxidase and the autoxidation of unsaturated fatty acids. Adv. Enzmol., 8, 425-457.
1949 With Reikenhoff I. and Burr, G. Polyethenoid fatty acid metabolism. Effect of dietary fat on polyethenoid fatty acids of rat tissues. Arch. Biochem., 20, 331-340.
1950 With Taylor, T.S. Polyethenoid fatty acid metabolism. III: Arachidonate supplementation. Arch .Biochem., 29, 295-301.
  With Hagdahl, I. Displacement analysis of lipids III: Separation of normal saturated fatty acids from formic to behenic. J. Biol. Chem., 182, 421-427.
1951 Holman, R.T. Metabolism of linoleic and linolenic acids. Proc. Soc. Exp. Biol. Med., 76, 100-102.
1952 Holman, R.T. Chromatography of fatty acids and related substances. Prog. Chem. Fats other Lipids, 1, 104-126.
1953 Holman, R.T. Mode of action of lipoxidase. Trans. Am. Assoc. Cereal Chem., 11, 135-146.
1955 Holman, R.T. The nutritional significance of essential fatty acids. Food Nutr. News, 26, 1-4.
1956 Holman, R.T. The function of essential fatty acids. Sven. Kem. Tidskr., 68, 282-290.
  With Jorgensen, E.A. Effects of trans fatty acid isomers upon essential fatty deficiency in rats. Proc. Soc. Exp. Biol. Med., 93, 175-179.
1957 With Hill, E.G., Warmanen, E. and Hayes, H. Effects of essential fatty acid deficiency in young swine. Proc. Soc. Exp. Biol. Med., 95, 274-278.
1958 With Jorgensen, E.A. Essential fatty acid deficiency II. In adult rats. J. Nutr., 66, 245-259.
1960 Holman, R.T. Essential fatty acids in nutrition and metabolism. AHA Arch. Int. Med., 105, 33-381.
  Holman, R.T. The ratio of trienoic:tetraenoic acids in tissue lipids as a measure of essential fatty acid requirement. J. Nutr., 70, 405-410.
1963 With Mohrhauer, H. A hypothesis involving competitive inhibitions in the metabolism of polyunsaturated fatty acids. Acta Chim. Scand., 17, S84-S90.
  With Mohrhauer, H. Effect of linolenic acid upon the metabolism of linoleic acid. J. Nutr., 81, 67-74.
1964 Holman, R.T. Nutritional and metabolic interrelationships between fatty acids. Fed. Proc., 23, 1062-1067.
1975 With Andersson, B.A. and Christie, W.W. Mass spectrometric determination of positions of double bonds in polyunsaturated fatty acid pyrrolidides. Lipids, 10, 215-219.
1982 With Johnson, S.B. Linolenic acid deficiency in man. Nutr. Rev., 40, 144-147.
  With Johnson, S.B. Am. J. Clin. Nutr., 35, 617-623.
1985 With Johnson, S.B., Gordon, E., McClain, C. and Lowe, G. Abnormal polyunsaturated fatty acid patterns of serum lipids in alcoholism and cirrhosis: Arachidonic acid deficiency. Proc. Nat. Acad. Sci., 82, 1915-1818.
1990 With Phinney, S., Oden, D. and Johnson, R.S. Reduced arachidonate in serum phospholipids and cholesterol esters associated with vegetarian diets in humans. Am. J. Clin. Nutr., 51, 385-392.
1991 With Phinney, S.D., Davis P.G. and Johnson, S.B. Obesity and weight loss alter serum polyunsaturated fatty acid metabolism in humans. Am. J. Clin. Nutr., 53, 831-838.
1998 Holman, R.T. The slow discovery of the importance of ω3 essential fatty acids in human health. J. Nutr., 128, 427s-433s (jn.nutrition.org/content/128/2/427S.full).

This biography is based in part from his own personal memoirs and a personal relationship through the American Oil Chemists Society. Dr. Douglas Bibus was a Post-Doctoral Fellow at the Hormel Institute and has remained to continue essential fatty acid research. He credits Ralph with teaching science but just as importantly how to live life productively.

An additional memoir of Ralph T. Holman by the same authors has been published in (Biographical Memoirs of the National Academy of Sciences (2014)).