Pernicious Anaemia – a fatal disease with a long history

Pernicious anaemia is a form of megaloblastic anemia due to vitamin B₁₂ deficiency, caused by impaired absorption of vitamin B₁₂[1].

Figure 1 - example from Russell et al 1900

The first description of the disease comes from 1849, in which T. Addison describes a patients falling into lethargy (insidiously over a period of weeks or months) and dying of exhaustion. He does describe one person recovering by using copious amounts of brandy, but does not recommend this as a cure [2]. 

Biermer went on to describe a similar disease but with some patients exhibiting neurological symptoms in addition [3], and by the turn of the last century a condition had been described that could either manifest as a blood and wasting disease, a neurological disease, or both, and could not be attributed to syphilis [4].

Because of this history, the condition may also be referred to as Addison’s anemia, Biermer’s anemia, or Addison-Biermer’s anemia.

B12 deficiency may be the cause of pernicious anemia, a fatal disease of unknown etiology when it was first described in 1849. The cure was discovered by accident. George Whipple had been inducing anemia in dogs by bleeding them, and then conducting experiments in which he fed them various foods to observe which diets allowed them fastest recovery from the anemia produced.  For the dogs, ingesting large amounts of liver seemed to cure the anemia of blood loss most rapidly, and  Whipple hypothesized that liver ingestion be tried for pernicious anemia, an anemic disease of the time with no known cause or cure. He tried this and reported some signs of success in 1920. After a series of careful clinical studies George Minot and William Murphy set out to partly isolate the substance in liver which cured anemia in dogs, and found that it was iron. They found further that the partly isolated water-soluble liver-substance which cured pernicious anemia in humans was something else entirely different—and which had no effect at all on canines under the conditions used. The specific factor treatment for pernicious anemia, found in liver juice, had been found by this coincidence. These experiments were reported by Minot and Murphy in 1926 reprinted [5], marking the date of the first real progress with this disease, though for several years, patients were still required to eat large amounts of raw liver or to drink considerable amounts of liver juice.

In 1928, the chemist Edwin Cohn prepared a liver extract that was 50 to 100 times more potent than the natural liver products. The extract was the first workable treatment for the disease. For their initial work in pointing the way to a working treatment, Whipple, Minot, and Murphy shared the 1934 Nobel Prize in Physiology or Medicine (the above from [6]).

Citations

1.            Chanarin, I., The Megaloblastic Anaemias. 3rd ed. 1986, Oxford: Blackwell Scientific Publications.

2.            Addison, T., Anaemia: disease of the supra-renal capsules. London Medical Gazette 1849. 43: p. 517-518.

3.            Biermer, A., Über eine Form von progressiver perniciöser Anämie. Correspondenz-Blatt Schw. Ärzte., 1872. 2: p. 15-17.

4.            Russell, J.S.R., F.E. Batten, and J. Collier, Subacute Combined Degeneration of the Spinal Cord. Brain, 1900. 23: p. 39-110.

5.            Minot, G.R. and W.P. Murphy, Treatment of pernicious anemia by a special diet. 1926. Yale J Biol Med, 2001. 74(5): p. 341-53.

6.            Wikipedia. Vitamin B12. [web page] 2009  [cited 2009 2 Oct]; Description of Vitamin B12 (cobalamin) including description of discovery of cure for Pernicious anaemia and structure of B12]. Available from: http://en.wikipedia.org/wiki/Vitamin_B12.