Robert Frederick Loeb (1895-1973), who was chairman of the department of medicine at Columbia University, New York, from 1947 to 1960, came from an academic family; his father was the German born Jacques Loeb, a noted professor of physiology. Robert Loeb was a consummate general physician who could remember virtually every patient he had ever treated. He was revered by many as a great teacher although some deplored his teaching by humiliation and intimidation.
Robert LoebLoeb’s chief research interest was in electrolyte physiology. He noticed that the clinical picture in patients with advanced Addison’s disease was similar to that seen in salt depletion and dehydration. When he removed the adrenals from dogs a similar circulatory collapse ensued accompanied by a massive increase in the excretion of salt in the urine. This led him to suggest treatment with sodium chloride. He also postulated that the adrenals produced a salt retaining hormone, later identified as aldosterone.
Diabetes was, according to Clifton Meador, who worked with him, Loeb’s favourite disease because,
'it was what a medical disease ought to be: Some chemical (insulin) is missing from the body. The missing chemical has been discovered through rigorous scientific investigation. The absence of the chemical causes severe abnormalities in the chemistry of the body (elevated blood sugar levels and also keto-acidosis). When this missing substance (insulin) is given to the patient, all deranged physiology is corrected. For [him this] epitomized man’s triumph over nature .'
His most important research with his colleague and lifelong friend Dana Atchley (1892-1982) was on the electrolyte disturbances in diabetic ketoacidosis. In the 1930s the mortality of this complication was up to 50% and rational use of fluids and insulin was hampered by the fact that the time course of it's development was not clear and neither was it known which aspects were due to deranged carbohydrate metabolism and which to acidosis. The idea, according to Atchley, was to deprive patients of insulin and follow them closely. He remembered that,
'A 19 year old youth was studied over a baseline of 12 days; previously his diabetes had always been brittle but, in hospital when diet and exercise were kept constant, he remained sugar free without hypoglycaemia. After insulin was stopped, he became obviously ill at the end of the fourth day with epigastric pain, headache, nausea, restlessness and prostration. By midnight, after he had vomited three times, he was given an infusion of 1000ml normal saline and 40 units of insulin with 10 units every hour for the next 17 hours.’
The changes during the development of acidosis were summarised as follows:
‘Upon the withdrawal of insulin, there occurred a rapid loss of body weight and water, the average daily urine excretion increasing by about 1100cc. The urine pH became fixed at 5.4 and the NH3 and titratable acid increased rapidly and progressively after the first twenty-four hours. There was a change from a daily positive inorganic base balance of 29.5 meq. The loss of K was even greater than that of the base fraction. Na + Mg and both began to be excreted in large amounts before any striking drop occurred in the blood bicarbonate level and twenty four hours before any significant increase in NH3 excretion occurred…..the glucose excretion during the acidosis period exceeded the carbohydrate intake and was approximately equivalent to the carbohydrate of the diet plus 58 per cent of the ingested protein.’
Within 18 hours of restarting insulin he was symptom free and the electrolyte changes were striking and the reverse of those after insulin withdrawal. The second patient who had only had diabetes for one year had similar but less acute changes. He withstood insulin withdrawal for 11 days without developing ketosis. This serendipitous difference made it possible to distinguish between the effects of osmotic diuresis and ketosis.
Loeb was also a pioneer in the treatment of ketoacidosis. According to Clifton Meador,
'The medical service had a special six-bed metabolic unit for patients with diabetes mellitus and other intriguing metabolic problems, especially those with diabetic ketoacidosis or Addisonian crisis. I believe Loeb’s service at the time held the world’s record for consecutive diabetic coma patients (well over 70) with no deaths. This was phenomenal given that the death rate was easily 10 percent or more in most people’s hands. Dr. Loeb found success by standardizing the treatment of acidosis to a finely tuned protocol (at a time when protocols were unheard of). We recorded time from the moment the patient hit the front door of the emergency service until the patient got the first insulin injection and the first intravenous fluids. The mean time that elapsed from appearance of the patient to the injection of insulin was very short — a matter of minutes — and it was always the first bit of data Dr. Loeb wanted to know.'
Loeb became famous throughout the world as editor of Cecil and Loeb’s textbook of medicine, widely regarded as the successor to Osler’s classic Practice of Medicine. The first edition was edited by Russell Cecil (1881-1965) but Loeb joined him in 1947 and wrote many of the articles himself. That on diabetes was so comprehensive and well written that it only needed minimal revision for years after his retirement.
Loeb was also famous for his aphorisms such as,
- Diabetes care is most effective when the patient becomes the doctor, and the doctor becomes the consultant.
- If what you’re doing is working, keep doing it!
- There is no such thing as a dull patient, only a dull physician.
- The first duty of the physician is to keep the patient out of the hands of the surgeons.
- Do unto others as you would have done to yourself if you were that patient in that bed at that time.
- The Bible says seek and you shall find. Seek not and you won’t find a damn thing.
An excellent appraisal of Robert F Loeb can also be accessed at: http://download.thelancet.com/pdfs/journals/lancet/PIIS014067361261438X.pdf
^ Loeb.R.F. Effect of sodium chloride in treatment of a patient with Addison’s disease. Proc Soc Exp Biol Med 1932-3;30:808.
^ Meador, Clifton K. Twentieth Century Men in Medicine: personal reflections. iuniverse.com 2007. pp. 32-51.
^ Atchley DW, Loeb RF, Richards DW, Benedict EM, Driscoll ME. On diabetic acidosis. A detailed study of electrolyte balances following the withdrawal and reestablishment of insulin therapy. J Clin Invest 1933;12:297-326.
^ Bearn A. Robert Frederick Loeb (1895-1973) Biog Mem Nat Acad Sci 1978; 49: 149-183.