However, Minot, Murphy, and Whipple received the joint Nobel Prize for discovering a cure for a previously fatal disease of unknown cause in 1934, becoming the first Americans to be awarded the Nobel Prize in Physiology and Medicine.It is not easy to eat uncooked liver, and extracts were developed as a concentrate of liver juice for intramuscular injection. In 1928, chemist  Edwin Cohn prepared an extract that was 50 to 100 times stronger than obtained from raw liver. This became part of the standard management of pernicious anemia until the 1950s. The active ingredient in the liver remained unknown until 1948. The anti-pernicious anemia factor was only isolated from the liver by Smith, Rex and others. The substance was cobalamin, which the discoverers called "vitamin B12". They showed that giving a few micrograms could prevent relapse in the disease. Dorothy Hodgkin and co-workers went on to use X-ray crystallography to elucidate the structure of cobalamin for which she, too, was awarded a Nobel Prize.Understanding of the pathogenesis of pernicious anaemia increased over subsequent decades. It had long been known that the disease was associated with defects in the gastrointestinal tract: patients had chronic gastritis and lack of acid secretion (achlorhydria). It is known that transport of physiological amounts of vitamin B12 depends on the combined actions of gastric, ileal and pancreatic components. The gastric moiety was discovered and named intrinsic factor by William Castle in 1930.
Untreated, it can lead to neurological complications, and in serious cases, death. It can take several years for pernicious anemia to appear, and the disease often goes unrecognized, as the body becomes used to feeling unwell. The onset may be vague and slow, as the same symptoms are often also present with anemia; in 81.1% of cases of cobalamin deficiency, pernicious anemia is not observed. Pernicious anemia may be present without a person experiencing symptoms at first, over time, feeling tired and weak, lightheadedness, dizziness, headaches, rapid or irregular heartbeat, breathlessness, glossitis (a sore red tongue), poor ability to exercise, low blood pressure, cold hands and feet, pale or yellow skin, easy bruising and bleeding, low-grade fevers, shakiness, cold sensitivity, chest pain, upset stomach, nausea, loss of appetite, heartburn, weight loss, diarrhea, constipation, severe joint pain, feeling abnormal sensations including tingling or numbness to the fingers and toes (pins and needles), and tinnitus, may occur.