December 2010

Henry A. Lardy (1917—2010)

Henry Arnold Lardy, past president of the American Society for Biochemistry and Molecular Biology, died Aug. 4, 2010, from prostate cancer, a few days before his 93rd birthday.

Henry LardyHenry Arnold Lardy, one of our most respected biochemists and past president of the American Society for Biochemistry and Molecular Biology, was born Aug. 19, 1917. He died Aug. 4, 2010, from prostate cancer, a few days before his 93rd birthday. He was raised on a farm near Roslyn, S.D. After graduating from high school, Henry received permission from his father to attend one semester at South Dakota State University. Henry found acquisition of knowledge to be addictive and spent the rest of his life in its pursuit. In the fall of 1939, Henry and I started graduate studies at the University of Wisconsin-Madison. This launched our rewarding, lifelong friendship.

Henry’s outstanding qualifications already were evident. After receiving his doctoral degree in l943 and completing a year of postdoctoral study, he was recruited to the faculty of the Wisconsin biochemistry department. He later had a key role in the establishment of the well-recognized Enzyme Institute, and in 1966, he became a prestigious Vilas professor. Although he reached emeritus status in 1988, he continued his research until he was incapacitated by cancer this summer.

Known to associates as Hank, he mentored more than 60 graduate students and 100 postdoctoral fellows over the years. He had an unselfish interest in their training and welfare and deservedly gained their respect and affection. It is likely that more of his past colleagues regard him as one of their best friends than anyone else I know.

His group contributed importantly to a wide swath of enzymology and metabolism, in part because he wanted his students and associates to have their own problems and challenges. In 2005, the leading journal in his field – the Journal of Biological Chemistry – celebrated its centenary by reprinting a series of classics (1). They chose three of the approximately 150 papers Henry published in the JBC.

One of these papers reported the important finding that respiratory rate could be controlled by the availability of acceptors for a phosphate group from the ATP formed by respiration. This finding provided the basis for the measurement of oxygen uptake as a probe of respiratory control; 2,4-dinitrophenol stimulated oxygen uptake by uncoupling electron transport from ATP formation. Another of Henry’s JBC papers included the first demonstration that the formation of phosphopyruvate from ATP and pyruvate was metabolically reversible.

The third paper provided an explanation of an old problem: how glyceraldehyde inhibits glycolysis. The paper noted that the L-glyceraldehyde, but not the D form, was inhibitory. It also traced the inhibition to the L-sorbose 1-phosphate formed. This finding was explained by the structural similarity of the L-sorbose 1-phosphate and the glucose 6-phosphate, a product of the hexokinase reaction.

Henry’s other notable accomplishments included the characterization and crystallization of 10 phosphate-transferring enzymes, the demonstration that many antibiotics inhibit oxidative phosphorylation and the finding that biotin functions in the uptake of carbon dioxide. His introduction of an egg-yolk buffer for storage of spermatozoa (which was adopted widely) reflected his farm background. In addition to pioneering this technique, he became a leading contributor to the understanding of sperm metabolism.

Relatively early in his career, Henry was elected to the American Academy of Arts and Sciences, the National Academy of Science and the American Philosophical Society.

When invited to contribute a “Reflections” paper for a 2005 centenary issue of JBC (2), Henry chose the title “Happily at Work” in accordance with his status at the time. His introductory page ably summarizes the major contributions of his group. In this introduction, he notes, “No aspect of living processes is more awe-inspiring than the union of a microscopic spermatozoan with an egg of the same species to initiate a new life.”

Some personal aspects of Henry’s life warrant mention. Henry and I both have had happy, 70-year marriages. He will be warmly remembered by his charming wife Annrita and his many friends. The Lardys and the Boyers have enjoyed many activities and travels together, such as a month of bicycling in France. In 1963, the Lardys acquired a farm some 30 miles from their home in Madison, Wis. They built a welcoming house from trees on the property and made a pond for swimming as well as a tennis court. Many days have been passed in this attractive setting.

The field of biochemistry has been enriched remarkably by the contributions of Henry Lardy and his associates. He is one of the few intellectual giants of our profession. It is a pleasure to record this recognition of a job very well done.

Below, we offer reflections from several of Henry Lardy’s friends and colleagues.

Henry Lardy’s remarkably long and productive scientific career began before World War II. His earliest scientific publications, with his mentor Paul Phillips, explored conditions that prolonged the survival of bull sperm in vitro and thus their useful lifetime for the then-developing practice of artificial insemination in the dairy industry. Henry’s first publication in the Journal of Biological Chemistry (J. Biol. Chem. 138, 195 – 202) brought his pioneering prior work into the scientific mainstream. It would have pleased Henry greatly to learn that Robert Edwards was awarded the 2010 Nobel Prize in physiology and medicine for his discovery of the conditions that allowed human fertilization in vitro. For this logical extension of Henry’s early work and its translation to address human clinical infertility, Robert Edwards will be remembered as “the father of 4 million.” Henry could have claimed, justifiably and with a chuckle, that he was the father of many times that number of bovines.
Henry’s publications in sperm physiology continued into the 1980s. A succession of students and postdoctoral fellows were recruited and given free rein to explore sperm bioenergetics, metabolism and biochemistry. The supportive and exciting environment of his lab produced ground-breaking discoveries of the involvement of cAMP, Ca2+ and pH as regulatory signals in sperm. Henry’s interest in sperm continued into the 21st century. He took great satisfaction in seeing the reports of definitive evidence of required roles for the sperm-specific C-alpha-2 catalytic subunit of protein kinase A (Proc. Natl. Acad. Sci. U.S.A. 101, 13483) and for the sperm-specific Ca2+-selective ion channel protein CatSper1 (Nature 413, 603 and Proc. Natl. Acad. Sci. U.S.A. 98, 12527). He and I shared an appreciation of the significance of the recent discovery (Cell 140, 327) that sperm possess the Hv1 proton-selective ion channel protein that was first proposed in a 1983 paper from the Lardy lab (Proc. Natl. Acad. Sci. U.S.A. 80, 1327).

I will leave it to others to speak of Henry’s wide-ranging contributions in other areas but would like to leave you with a citation of Henry’s single-paragraph letter in Trends in Cell Biology (Trends Cell. Biol. 5, 416). The letter is an elegant and concise statement of the importance of the precise use of language and a sterling example of the principle.
– Donner F. Babcock, professor of physiology and biophysics, University of Washington

Henry Lardy was a man of great talent. He had talents for raising a family, research, dog training, hunting and many other areas. This is why he was president of both the American Golden Retriever Society and the American Society of Biological Chemistry. He also had a great talent for living and for communicating his enjoyment of life to others.

I knew Henry not only as a friend but also as a source for research knowledge and a hunting partner. It was a great privilege to hunt with him and to see him with his dogs. While hunting, we occasionally met other hunters, and he never asked, “How many have you shot?” Instead, he might say, “That is a nice Gordon; not many of them around here anymore.”

He gave much to us, and what he gave was very precious because it was composed of the rarest elements: true goodness, kindness, fairness, generosity, humor, tolerance and love of life.
– Leonard “Mike” Fahien, emeritus professor of pharmacology, University of Wisconsin School of Medicine and Public Health

I was accepted into Dr. Lardy’s laboratory at the Institute for Enzyme Research at the University of Wisconsin in July of 1974 to begin my third postdoctoral fellowship. At the time, Dr. Lardy had a group of about 25 or 30 people in his group. All were postdoctoral fellows or graduate students except for five staff members. Of course, virtually all of them were extremely bright, and I learned a lot from interacting with many of them. I do not know how Dr. Lardy could keep track of all of us, but it seemed he could always remember details about the personal lives of everyone in the group – our families and so forth. Almost every one of his trainees has gone on to an important career in academia or industry, in part because of his or her association with Dr. Lardy.
When I walked into the Enzyme Institute on my first day of work, I noticed that the walls were covered with numerous pictures that showed crystals of glycolytic and other metabolic enzymes that Dr. Lardy had purified and crystallized. I learned that Dr. Lardy was credited with major advances in the areas of gluconeogenesis, mitochondrial physiology and especially sperm metabolism. His work as a graduate student led to the preservation of sperm for artificial insemination, revolutionizing livestock breeding and the treatment of human infertility. He discerned the actions of many toxic antibiotics on mitochondrial respiration, including dinitrophenol, oligomycin, bonkrekic acid and A23187, as well as describing at least one mitochondrial redox shuttle.

Dr. Lardy trained more than 170 students and postdocs, and each one liked and respected him. Some referred to their time in his laboratory as the Camelot days. Over the years, I frequently consulted with Dr. Lardy for advice on scientific information not readily available in the recent scientific literature. Invariably, he would reach into a file and pull out a reprint of a paper he had  written years ago that would provide valuable leads to answer my questions. 

Dr. Lardy came to work in his laboratory almost every day until about two months before he passed away in August, just weeks before his 93rd birthday. He always was excited about his work and scientific ideas – most recently, synthesizing derivatives of DHEA. He had a tremendous knowledge of organic chemistry, which enabled him to perform complex syntheses of steroid compounds and also explains why he was able to bring so much insight to biological problems. His memory was still strong, and he was mentally sharp when I last visited him in late July.

Dr. Lardy had many outside interests. He enjoyed raising Arabian horses and loved dogs and could play a good game of tennis well into his late 70s. There was often a large dog lying under his desk in his office at the Enzyme Institute. He enjoyed his farm in the hills about 40 miles from Madison and, every fall, entertained students, postdocs, lab assistants and their families there for an afternoon of making apple cider and playing touch football and tennis.
– Michael J. MacDonald, professor of pediatrics, head of the pediatrics diabetes and endocrinology division and director of the Children’s Diabetes Center, University of Wisconsin School of Medicine and Public Health
As a freshly minted Ph.D. from a small pharmacology graduate program at State University of New York Upstate in Syracuse, N.Y., I was in awe of the University of Wisconsin-Madison and the opportunity to pursue postdoctoral study in Professor Henry Lardy’s section of the Institute for Enzyme Research. From the literature, I knew of the many accomplishments of Lardy’s laboratory in fields as diverse as oxidative phosphorylation, gluconeogenesis, lipogenesis, enzyme purification and kinetics. But I knew little of Henry Lardy the person.

In the fall of 1967, I began my fantastic six-year voyage in Hank Lardy’s laboratory. I quickly learned that my mentor was a kind, generous and humorous person; a rigorous and super enthusiastic scientist and someone who treated everyone he met with dignity and respect. Henry Lardy’s spirit permeated the laboratory and motivated all who were in his group. He made science fun, and his students and postdocs took positions in academia or industry across the globe, where they carry on traditions learned in Hank’s research group. Many, myself included, established the foundations and research areas of their future careers during time spent in Lardy’s laboratory. Hank was the kind of human being that we all try our best to be. Simply put, he was one of the finest people I have ever known. I, and all who knew him, will hold a special place for him in our hearts and memories forever.
– Peter W. Reed, emeritus faculty and graduate dean, Vanderbilt University

Dr. Henry A. Lardy forever will command my deepest appreciation, admiration, respect and thanks as my graduate advisor, educator, mentor and, most importantly, friend. He always was available to talk about anything that was on my mind, academic or otherwise.

After completing several years of active duty with the U.S. Navy, I was working part time, taking some refresher undergraduate classes at the University of Wisconsin-Madison and searching earnestly for a discipline in which to pursue a career. During that endeavor, which involved contact with several universities, I received a phone call from Dr. Lardy one evening in the fall of 1969. He invited me to join his group at the Enzyme Institute as a new graduate student in the department of biochemistry. Henry, as he did for many others, had taken the chance to reach out and give me what turned out to be an opportunity that altered the course of my life. Looking back, his call seems incredible, especially considering that I grew up on a farm in east central Wisconsin and attended a one-room country school for all eight elementary school years (the school had slightly more than 30 students in all eight grades, and we learned music via the “Wisconsin School of the Air” over the radio). That phone call launched a career for me in the emerging field of biotechnology that spanned over 30 years and that continues through consulting now that I have retired from Monsanto. For Henry’s faith in me and the opportunity to obtain my doctorate degree in his laboratory at the University of Wisconsin, I will be grateful forever. The years spent learning at the Enzyme Institute truly are memorable and provided an opportunity to meet many colleagues and collaborators.

Dr. Lardy aided and mentored many others in the same way he did me, including many from countries with governmental troubles and others who needed financial or other help. He furthered our educations and give us the chance to advance our careers in biochemistry. His laboratory was a mixed group filled with academic enthusiasm; it was fun to be a part of it all.

Dr. Lardy graciously invited students to his home when leaders in specific fields of biochemistry related to our research areas were visiting Madison. This was a wonderful and unique opportunity. I know that for many of us, being a part of Dr. Lardy’s group is a major highlight as we look back on careers that have since touched many different facets of biotechnology. Dr. Lardy reached many other people in ways that are hard to comprehend. All who had the great pleasure of knowing Dr. Lardy will miss him – a wonderful colleague, mentor and true friend.
– Larry A. Bentle, Evans, Ga.

His scientific breadth and depth by themselves would have made Henry a remarkable person, but their being coupled with his great passion and sense of fun made him a truly exceptional mentor.
– Gerald M. Carlson, chairman of the department of biochemistry and molecular biology, University of Kansas Medical Center

I was privileged to be a graduate student in Henry Lardy’s lab. He was the most important mentor and role model in my professional life, and he also modeled how to have a rich life outside of the laboratory.

He had wide-ranging interests in biochemistry, pursuing research in enzymology, metabolism and hormones. I understand that he continued to synthesize and study steroids in his last year of life.

To be in his laboratory was an immersion in multiculturalism, as he always had postdoctoral students from several continents.

Henry had a gift for focusing his complete attention on whatever task he was pursuing at the moment or whoever he was talking to about research or life outside the lab. It was a treat to discuss research with him, as he listened attentively to the work being described and always had a number of ideas for further work.
– David O. Lambeth, Chester Fritz distinguished professor of biochemistry and molecular biology, University of North Dakota School of Medicine and Health Sciences

I truly was saddened to learn of the death of Dr. Henry A. Lardy in August. I was very fortunate to spend two memorable postdoctoral years with Professor Lardy in the early 1960s. I still have many precious memories of those years, highlighted by discoveries with inorganic pyrophosphatase and cytosolic PEP carboxykinase.

My work with pyrophosphate metabolism in the Lardy laboratory led to our discovery of the biosynthetic functions of glucose 6-phosphatase. Later, work on gluconeogenesis and its regulation directed by Professor Lardy led to our discovery of the cytosolic isozyme of hepatic phosphoenolpyruvate carboxykinase and identification of its pivotal role in the regulation of gluconeogenesis.

Professor Lardy was a brilliant scientist, and he was a wonderful, kind and caring human being as well. Personally, I owe him a great deal both as a scientific mentor and as a role model.

Not only was my association with Henry Lardy pivotal to my entire professional career, but he also made truly great contributions to the development of the department of biochemistry at the University of North Dakota Medical School. No fewer than five Lardy postdocs and graduate students served as tenured faculty in that department during its formative years out here in the plains of North Dakota.

A giant has passed this way, and we are all better for having known him.
– Robert C. Nordlie, emeritus chairman, James J. Hill professor and William Eugene Cornatzer professor of biochemistry and molecular biology, University of North Dakota School of Medicine and Health Sciences

One of the precious highlights of my life was the opportunity to work for and learn from Professor Lardy. It was a joy to be part of the daily enthusiastic, exciting and stimulating environment that he created. At his memorial service, his children described his passion for planting and nurturing multitudes of trees. In much the same way, he planted and nurtured many young men and women who went on to share his exuberance for science and life with their own protégés. All of us in the scientific community acknowledge his creative insights and brilliance. At the same time, I believe that all of us who knew him also will acknowledge his gentleness, kindness, caring, humbleness, sincerity and great passion for life. To me, he was a dear friend who left the world a better place in many ways. I always shall miss him and remember him fondly.
– Paul D. Ray, emeritus professor and Chester Fritz distinguished professor, University of North Dakota School of Medicine and Health Sciences


1. Kresge, N., Simoni, R., and Hill, R. (2005) Henry Lardy’s Contributions to Understanding the Metabolic Pathway. J. Biol. Chem. 280, e17.
2. Lardy, H. (2002) Happily at Work. J. Biol. Chem. 278, 3499 – 3509.

Paul D. Boyer is a professor emeritus at the University of California, Los Angeles. He received the Nobel Prize in Chemistry in 1997.

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