Talk given at annual lab Christmas luncheon, Dec. 2012.
In the last few decades, computerized automated equipment has completely changed how the clinical laboratory looks and operates. In a sense, we are leaving the age of alchemy. A large portion of my research involves a laboratory over a thousand years old, which the Persian physician al-Razi described in his alchemy manual the Kitab-al-asrar or Book of Secrets. I was impressed with how modern his procedures sounded—how he specified weights and measures, incubation time, temperature, even safety concerns. Not to mention the equipment he wrote about — flasks, sieves, glass funnels, ovens. But especially important to the alchemist was color change. Almost every procedure says to heat the mixture: “until it is black,” “red as blood,” or “white as snow.” How the laboratory depends on color change!
Picture yourself in 1968, just back from morning draws, lining up the test tubes for the first batch of glucose and BUNs, pipetting the reagents and the serum into the tubes, setting them in a heat block and setting a timer for each set. You start to prepare to do the electrolytes, the first timer goes off, and you put the test tubes in a rack and take them to your colorimeter or new Coleman Junior Spectrophotometer. You titrate the CO2 levels and observe the color change. Everything depends on color, heat, and timing. We ran our enzyme tests in a 37 degree heat block, stopwatch in hand. Oh how it broke our rhythm when a test was ordered that couldn’t be batched. The LE test, the ammonia, the fecal fat, the urine porphyrins with the Wood’s lamp. Taking the urine into the closet to see if it glows under black light, now that had a real alchemy feel to it.
These tests are relatively new, but one well-known test goes way back. Can you guess which one? The oldest continuously running laboratory test is urinalysis or uroscopy, which goes back to ancient times in Egypt, India, and the Byzantine Empire. As early as the 1850s, American hospitals did routine urinalysis on most admissions. (1) A study of hospitals in Pennsylvania and NY shows that over 80% of the patients admitted between 1900 and 1925 had a urinalysis on admission. It was not diagnostic and not charged separately, but it was rather a routine part of the history and physical that physicians carried out.(2) Chemical tests on urine were not routine, but they came out early. Fehling’s test for sugar in the urine was invented in 1849. In 1905 Otto Folin, a German scientist at Harvard, devised procedures to test urine for urea, ammonia, creatinine, and uric acid, based on methods used in German breweries. With chemistry and the microscope, urinalysis became more technical.
There was a long history of physicians looking at urine, but blood tests were a different matter. At first there was discussion over whether red blood cells needed to be counted or just estimated. And where and by whom? Some physicians felt that they could tell anemic blood from a drop on a white handkerchief. They also knew that when blood clotted it sometimes had a gray crust, which they called the buffy coat and associated with inflammation. It was later found to be made of white cells. But physicians didn’t have the time or feel the need to do quantitative blood analysis. Paul Ehrlich helped make blood testing part of pathology when he defined blood as a tissue and emphasized the diagnostic importance of microscopic examination of the cells. Tissues and microscopes were pathologist’s territory. In 1879 Ehrlich developed a stain to distinguish 5 kinds of white blood cells. Biernacki invented the sed rate in 1897. Wright’s stain was invented in 1902. (3) Serology and chemistry tests were developed next. The Wasserman test for syphilis came in 1906. By 1926 American hospitals were required to have a laboratory—a dedicated space for testing.
Let’s go back to 1962. My Todd and Sanford gives us a snapshot of the clinical laboratory at that time. Blood was usually drawn with a glass syringe. Vacutainers are mentioned, but not yet in common use. You use an oilstone to sharpen the needle and the book states that “Many laboratory workers now insist upon individual needles or lancets for each patient and sterilize them by autoclaving after each use.” Safety issues that are critical today were very different in 1962. Filling pipets is usually done by mouth unless the fluid being pipetted is toxic or offensive. Handwashing between patients is recommended to prevent spreading infection. (Disposable latex gloves were not invented until 1964.).(4) Mercury spills are handled almost as casually as in al Razi’s time– with a simple vacuum device you could make from a flask and rubber tubing. Why would you have spilled mercury? You may have been using a Van Slyke manometer to measure CO2 concentration.
But there were two impromptu suggestions that really got my attention in the 1962 Todd and Sanford:
First, a coagulation test: “The simplest and most effective way of finding out whether there is sufficient fibrinogen in the blood to form a clot is to draw some blood without an anticoagulant, place it in a test tube, and let it stand five or ten minutes. Then turn the tube over. If the blood stays in the tube, the fibrinogen is adequate; if it does not, clean up the mess.” (5)
Second, sweat chloride: There was no way to induce localized sweating. The sweat was collected in gauze sponges taped to the child’s back, after which you put him in a plastic bag tied at the neck for 15 to 60 minutes. After collection, you need to recover the sweat from the sponges, undiluted if possible. “Place the golf tee point down in a 15 ml conical centrifuge tube and place the sponges on top of the tee. Seal the tube with a rubber cap and centrifuge. The sweat will collect undiluted in the tip of the tube.” (6)
What about my personal favorite, Blood Bank? In 1962, donors were paid for giving blood. They were tested only for syphilis. No laboratory test was capable of detecting or ruling out the hepatitis virus, but donors who had a history of jaundice were rejected. Shelf life was 21 days.(7)
Fortunately, chemical tests for pregnancy were available in the 1960s, and it was no longer necessary to inject a frog and wait 24 hours. But there was no RhoGam in 1962. Todd and Sanford spend pages on how to work up HDNB (Hemolytic Disease of the Newborn). In fact RhoGam became available in 1968, the year I started training at Long Beach Memorial Hospital. The policy for all OB patients was to check their blood type and Rh, if they were Rh negative, we called their husband in and check his type, and then if he were positive, we would prepare RhoGam for her by testing it against her blood with a minor crossmatch. Many patients still had antibodies from previous pregnancies, and these we monitored with anti-D titers, and prepared to give the baby an exchange transfusion if indicated.
Things were still quite manual in 1968. Donor blood was collected in glass bottles. To make packed cells, you took a bottle of blood that was settled, prepped the top, and siphoned off the plasma under a hood—and yes they did order it stat. Departments like hematology, coag, and urinalysis had a series of work stations along a countertop. I’ll never forget our training in the urine lab, a small room lined on three sides with counters. All urines started on the left next to the door, where they were examined for color and appearance. They were moved down the countertop to the hydrometer station to check specific gravity. A portion was spun down for the microscopic analysis. We did have dipsticks for the chemistries. Techs in training spent a memorable week in the urine room.
I first started working at Mission Hospital in 1976. At that time there was no night shift, so we took turns being on call at night. You might get a call at home at 2 AM to do a stat urinalysis, and then if you went home you might get called back. I remember one night a physician stood and watched me do a blood glucose test on an ER patient. This involved hand pipetting reagents and serum plus setting up controls, incubation, and colorimeter testing. I was tired and nervous and very relieved when the controls came out on target.
I probably did the last Lee White clotting test ever sometime in the mid eighties. I had to find tubes, a rack, and a stop watch. Has anyone else done one recently?
Long Beach Memorial had an auto analyzer when I trained in the 1960s. It was a mechanical monster that took up half a room and required constant supervision. Today the analyzers are smart, compact, and sleek and use an amazingly small sample size. Hands-on weighing, measuring, pipetting, and incubating are still around, but vastly diminished. If I had started working in the lab 10 years ago, the Book of Secrets might have sounded quaint rather than familiar. For those who are still transitioning into this world of innovation, I would like to dedicate these words found in an accreditation manual: “Labs contain largely unsung heroes.”(8)
(1) Joel D. Howell, Technology in the Hospital (Baltimore: Johns Hopkins University Press, 1995), 70.
(2) Ibid., 76.
(3) Ibid., 174.
(4) Israel Davidson and Benjamen Wells, eds. Todd-Sanford Clinical Diagnosis by Laboratory Methods, 13th ed. (Philadelphia: W. B. Saunders Co., 1962), 62, 392, 830.
(5) Ibid., 440.
(6) Ibid., 592.
(7) Ibid., 833, 300.
(8) Sandra Wilson and Geoff Weir, Food and Drink Laboratory Accreditation: A Practical Approach (London: Chapman and Hall, 1995), 64.