2000 Edwin F. Ullman Award
Leonard Skeggs, PhD, will receive the Edwin F. Ullman Award at the Oak Ridge Conference, May 5–6, 2000. As part of the meeting, he will present an address that we anticipate with pleasure. Dr. Skeggs is best known among clinical chemists as the inventor of continuous flow analyzers (e.g., Auto Analyzer, SMA 12/60, and SMAC). He has provided us with the following biographical sketch, which will help clinical chemists to appreciate his broad range of interests and accomplishments:
I was born in Fremont, Ohio on June 9, 1918. My family moved to Youngstown, Ohio when I was 2 years old. Our home was in Boardman, a suburb south of Youngstown. I attended Boardman Grade School and High School where I met and dated my wife-to-be, Jean Hossel. My father was Executive Secretary of the Youngstown YMCA. One of the last things he did before his death in 1933 was to raise the money, hire the president and faculty, and obtain accreditation for a new 4-year college, Youngstown College, to be dedicated to the education of young men and women without consideration of race, color, or creed. This is now Youngstown State University with 14, 000 students.
After graduation from high school, I attended Youngstown College while living at home with my mother, brother David, and sister Betty. I graduated in 1940 with a BA degree in Chemistry.
That summer I entered the Biochemistry Department of the graduate school at Western Reserve University (now Case Western Reserve University). I soon obtained a fellowship at the Cleveland Clinic that paid $65 a month. I worked under Dr. Roy McCullagh on the purification of a hormone, inhibin, which he believed existed in the germinal epithelia of the testes. My contribution after nearly 2 years of work was to prove it to be nonexistent.
I was alone in the rat room of the Cleveland Clinic doing vaginal smears on female rats, which formed the basis of our assay for "inhibin", when news of the Japanese attack on Pearl Harbor came over the radio. That evening my wife proposed to me. We were married the following Saturday, which gave time for Jean to finish nurse’s training and for us to get our license.
We were both soon at work at Ben Venue Laboratories, which had a contract to dry human blood plasma for use in the battlefields. I was in charge of the drying process, and Jean headed a group of nurses who separated the plasma from the blood collected by the Red Cross from many willing volunteers.
Early in 1943, the blood drying had become routine, and I signed up for the Navy. I was to go to Officers Training School at Cornell in August. In the interim, I worked at SMA Laboratories on methods for purifying penicillin from crude cultures. It was a thrill when some of my very impure extracts were used to save lives at our university hospitals.
After Cornell, I was assigned to the USS Hovey, a World War I destroyer converted to minesweeping duty. I soon became the Gunnery Officer. We lost our ship in the Lingayen Gulf in the Philippines, hit by a Japanese aerial torpedo. I was then ordered to the USS Earle as Minesweeping Officer. I was discharged in January 1946.
I started back to graduate school without delay and soon began working on artificial kidneys with Jack Leonards, who headed the department at that time. We designed and built the first flat-plate dialyzer. After working with dogs, we used the kidney on a number of patients at the university hospitals and elsewhere. We also supplied the kidney to a number of others, including Scribner of the University of Washington, who first used the radial artery AV shunt.
After receiving my PhD in January 1948, I took a job at the VA Hospital that was under the professional control of Western Reserve Medical School. I was placed in charge of the Clinical Chemistry Lab with four technicians. I soon learned from control samples that the results were not very reliable and were often misleading. I spent many hours thinking how our chemistries could be automated. Just after I got back from lunch one day it suddenly occurred to me—why not do analyses in flowing streams? Later I told my boss, Joe Kahn, the pathologist in charge of all of the clinical labs, that I thought I knew how to automate chemistries. He insisted that I work on my idea and loaned me the money to proceed. Joe loaned me a total of $5000: $1500 was spent in building the machine, and $3500 went for legal expenses. Altogether, I built four different models.
At first I did blood urea nitrogen, then blood sugars. I was pleased that although my machines had mechanical problems, the results were very good, even from the very beginning. I spent nearly 3 years trying to find a manufacturer. I would have given up without Jean’s insistence that I keep trying. Finally, Technicon Company heard of my analyzer and asked me to bring it to them in New York. They took it on and spent nearly 3 years designing it for production. Introduced in 1956, it was an instant success.
Later I conceived of a machine that could do many analyses on single samples of serum and record the results on a chart in graphical form. This was incorporated into the SMA (Sequential Multiple Analyzer) 12/60, 12/30, and finally SMAC, which did 20 analyses on a sample every 20's. These machines were manufactured and sold to nearly every laboratory all over the world until the early 1990s.
I hadn’t been at the VA very long before I began doing research with my chief, Joe Kahn, on our favorite subject, hypertension. In this we were followers of Dr. Harry Goldblatt from Case Western Reserve University, who first produced the equivalent of human hypertension in dogs and other species by restricting the blood flow through the kidneys. Goldblatt believed that the kidney released a pressor substance, "renin", into the circulation and raised the blood pressure. Renin was known to exert its effect through a substance called angiotensin, which could be found in crude extracts of serum that had been incubated with crude renin from kidneys.
Our group, Joe Kahn and I, assisted by Walt Marsh, treated hypertensive dogs with our artificial kidney. We purified and concentrated 250-mL samples of the dialysate and demonstrated the presence of angiotensin by assay using the effect of the samples on the blood pressure of anesthetized rats.
We later assayed angiotensin in 250-mL samples of blood taken from hypertensive humans. This early work demonstrated to us that angiotensin was probably responsible for the increase in blood pressure in hypertension. From then until 1983 in the VA, and then until 1988 at the Department of Biochemistry at the Medical School, I was engaged in work on what is now known as the renin-angiotensin system. In this work, I was assisted at various times by a number of co-workers, most notably my good friend Joe Kahn, Kenneth Lentz, and Rick Dorer. Our major accomplishments were as follows:
demonstrating the existence of two forms of angiotensin;
isolation of angiotensin I in pure form;
partial purification and elucidation of the function of angiotensin-converting enzyme;
purification of angiotensin II;
elucidation of the amino acid composition and sequence of hypertension II and its biochemical relationship to angiotensin I;
purification of several forms of renin substrate from hog plasma;
discovering that the substrate for renin could be enzymatically degraded from a large protein to a polypeptide;
purification and synthesis of a tetradecapeptide substrate for renin; and
demonstrating the kinetics of the reaction of renin with nine synthetic peptides.
Taken together, these findings laid the groundwork for our present understanding of the renin-angiotensin system that is now known to increase blood pressure in the majority of humans with hypertension.
Inhibitors of the angiotensin-converting enzyme are now widely used to lower the blood pressure of patients with hypertension and to decrease the afterload on the hearts of patients with congestive heart failure and to prolong their lives.
Apart from the laboratory, I have invented an alarm (Jean named it the "Baby Buzzer") to alert you that your mare is about to give birth.
Since retirement, I have been involved, along with the late Dr. Mitsui Teraguchi, a marine biologist, with raising fish in a very densely populated tank. Still more recently, I was Chairman and am now Director of a small company that is developing a new battery to power bicycles, scooters, and eventually automobiles.
1966 Outstanding Contributions to Clinical Chemistry