The Methods of Thomas Addis

Portrait of Thomas Addis by Marion C. Raulston, held in the Thomas Addis Papers, Lane Medical Library Special Collections, Stanford University.

[Part 3 of 5]

[In the beginning] I was all set on measuring things and was trying to be ‘scientific.’ But anyone who has patients and patience can scarcely help coming at last to see that experiments that don’t answer questions about patients are, for the doctor, pretty irrelevant.

-Thomas Addis

The result of a lifetime of work devoted to the study of kidney disease, Thomas Addis became the first true American nephrologist. In studying the urinary contents of both healthy individuals and individuals affected with Bright’s disease, Addis was able to develop a systematic treatment plan unlike any other proposal of the time. As a clinical investigator Addis provided for his patients what most other kidney specialists at the time could not – hope and options.

Throughout his career, Addis consciously integrated his laboratory research into his clinical practice by methodically “mixing patients with rats.” In his effort to thoroughly understand the kidney and its diseases, Addis followed a group of nephritics for over thirty years while also maintaining a colony of over 1,000 rats for in vivo experimentation. Addis refused to separate his clinical work from his laboratory studies, and even went so far as to see his patients in a small cubical in the corner of his laboratory.

From his laboratory experiments and clinical experiences, Addis developed a unique method for the treatment of nephritis. Based on the physical concepts of work and healing, Addis believed that in order for the kidneys to recover, the patient must allow the organs time to rest. In pursuit of a reduced renal workload, Addis prescribed a low protein, low sodium diet for his nephritic patients. This method appeared to have worked effectively for the treatment of many (but not all) of Addis’s patients and proved to be the answer for Pauling’s ailments.

Addis’s system for treating nephritic patients relied heavily upon a series of quantitative measurements that soon became known as the “Addis count” and the “Addis urea ratio.” The “Addis count” quantitatively determined the number of red blood cells, white blood cells and casts (clumps of red and white blood cells) excreted in the urine. The “Addis urea ratio” measured the concentration of urea in the urine. These two measurements, in addition to a measurement of the total urine output, were the basis for Addis’s assessment of a patient’s progress throughout treatment. Addis believed that these measurements provided insight into both the nature and extent of the disease.

When Pauling came to Addis in 1941 for assistance with his diagnosis of Bright’s Disease, Pauling was quickly impressed by Addis’s methodology. Beyond the measurements described above, Addis qualitatively examined the cells obtained from the urine sample and identified any deformations and abnormalities that he observed.

Although Addis relied heavily on his laboratory group, he took all of the measurements and conducted the sample analyses himself, adamantly insisting that in order for the work to have meaning, the physician must be responsible for all of such analyses.  Upon gathering sufficient data, Addis used his qualitative and quantitative findings, as well as his experience with his patients, to clinically reclassify Bright’s disease and develop tailor-made treatment plans.

While Addis’s treatment offered relief to many, his findings and conclusions were often criticized by the scientific community for lacking validity. These critiques stemmed from Addis’s refusal to use controls in his clinical studies. In a note written by Pauling about Addis, Pauling proclaimed, “The trouble with Addis – no controls!” Addis firmly believed that controls in his research would be unethical. His duty, he wrote, was “to treat each patient in the way that I think will do him the most good.”

Were Addis to have incorporated controls into his clinical research, he would have been forced to split his patients into two groups. This experimental design would have left half of his patients without the treatment that he, as their physician, believed to be most effective. Addis considered such methodology to be unacceptable. As such, because Addis refused to include controls in his research, the majority of the scientific community considered there to be significant limits to Addis’s contributions.