We continue to madly work on The Book, with a brief trip to Vegas last weekend for The Amaz!ing Meeting. To keep the cocktail party lively in our absence, Alex Morgan, budding science writer extraordinaire, is back with a fascinating historical account demonstrating the efficacy of case-based reasoning.
In 1877 in the well-to-do London suburb of St. John’s Wood, a sixteen-month-old infant is dying. Georgie has cried for weeks, but now he doesn’t have the energy to cry. Too feeble to sit up, he won’t move at all, if he can help it. He can’t bear for anyone to touch his legs, which are covered with bruise-like spots. His face is ash white. His gums are inflamed and spongy. His breath smells like a corpse.
The pediatrician, Dr. Sumner, has prescribed chlorate of potash and quinine bark – strong general-purpose medications – and later syrup of iodide of iron and cod-liver oil. For the inflamed gums, he orders alum and glycerin applied locally. But Georgie’s condition only worsens. The swelling of the gums grows still more extensive, until the whole of the mucous membrane of the upper and lower jaw seems to be involved, and the bleeding becomes more profuse. Georgie begins to have spasms in his throat that cut off his breathing.
Children die in Victorian England. In the upper-class areas of Liverpool, according to an 1899 report, 136 out of 1000 newborns die before they reach the age of one. Working class districts maintain a rate of 274 infant deaths per 1000, and 509 slum children die for every 1000 born, all within the first year after birth. A very sick child like Georgie, not responding to treatment, unable to eat, having difficulty breathing, is expected to die. But he gets a lucky break.
His pediatrician asks Dr. Walter Cheadle from London’s Hospital for Sick Children to consider the case. An unusually shy man, Dr. Cheadle avoids the clubs and dinner parties of his social class, but he is appreciated by his students and patients for his courtesy and concern. Large and strong as a stevedore, he stands taller than most of his peers at medical meetings. His friend and disciple, Dr. John Poynton, remarks that his enormous hands seem to “obliterate” the children who are his patients, but they respond to his kindness and aren’t afraid of him.
Famous in college for his athletic ability, he interrupts his medical-school studies in 1863 to join an expedition to chart a land route across Canada. In 1865, he co-publishes a popular book about his experiences, which includes his encounters with “scurvy, smallpox, starvation, massacres and hair-breadth adventures.” The picture below is from this book (Cheadle is the bearded man on the left).
Perhaps surprisingly, after returning from these adventures, he settles down, completes his medical studies and establishes a practice in London. Although he sees all sorts of patients, he becomes well known as an expert on children’s diseases. He is also an early champion of women in medicine. A note published at the time of his death hints that his professional reputation is damaged because he addresses the needs of children and the advancement of woman. This note refers to the “wrath and indignation” of some of his colleagues, because he lectures at the London School of Medicine for Women.
Imagine the scene as Dr. Cheadle first comes to examine Georgie: The enormous shy doctor in his Victorian black frockcoat asks the mother some preliminary questions then examines his desperately ill patient. He needs only a moment. He’s seen all this before: the child’s weakness, the still open fontanelle, the enlarged ends of the long bones, the bruised legs, the stinking breath, the inflamed gums. His report on the case notes “dark-red, soft, and gelatinous masses [protruding] from the mouth between the lips, and [giving] the child the appearance of being engaged in sucking pieces of raw flesh.” Dr. Cheadle asks what the boy has been eating. Georgie’s mother says he was weaned after six months. She’s been giving him oatmeal and rusks (toast). A little mutton broth. She can’t think of anything else. Georgie’s been living for eight months on oatmeal and toast, and occasionally broth.
Dr. Cheadle’s mind reviews his cases, thousands, indexed by the obscure associations of his experience: malnutrition and scurvy on the expedition to Canada; histories and symptoms of all the hospital’s sick children, treatments and cures, and failures; reports from polar expeditions, from the Franco Prussian War, from the American Civil War, many thousands of documents; and theories, about climate, about diet, about microorganisms, about lifestyle, conflicting with each other, sometimes conflicting with the evidence.
A colleague of Dr. Cheadle’s writes of him in the note mentioned above: “His [is] not that type of mind which [weighs] laboriously the pros and cons in the diagnosis of a case, but from his ample experience he almost intuitively [arrives] at the probable explanation of the illness." A hundred years in Dr. Cheadle’s future, the way a clinician uses cases to create diagnoses and treatments will be called “case-based reasoning,” and it will be offered as a variant of the scientific method. But here and now in Georgie’s nursery in a Victorian London suburb, case-based reasoning happens merely in Dr. Cheadle’s mind: He knows what he is dealing with and what to do.
His diagnosis for Georgie: rickets and scurvy. They are both vitamin deficiency diseases. Children who don’t get enough vitamin D develop rickets; the child’s body can’t absorb calcium properly and the bones are softened, often deformed. Vitamin C deficiency leads to scurvy, a dissolving of the connective tissues, dreadfully mutilating and painful. Rickets is common in the children of Victorian England, but scurvy is unexpected. In Georgie’s case, it is at a particularly savage stage.
Although scurvy has been known for centuries as a disease of sailors, soldiers, explorers, and others adults cut off from fresh food supplies, Dr. Cheadle is among the first to document it in children. He encounters two other cases like Georgie’s a few months later and writes a paper about them that appears in The Lancet in 1878 (“Three Cases of Scurvy Supervening on Rickets in Young Children,” available online from Science Direct for a fee. "Georgie" is called "G.S." in this paper.). He describes the three cases in detail, distinguishing the symptoms of rickets and scurvy, noting their separate implications and treatments, coining the phrase “infantile scurvy” to further make his point that this isn’t simply a more severe form of rickets but two diseases at once.
Dr. Cheadle has never heard of vitamins. Their discovery is decades in the future. But he understands that diet is the issue here, although many colleagues disagree. Dr. Cheadle argues in his 1878 paper against the various other theories about scurvy, including that it is caused by humid and/or cold climates, excess salt in the diet, lack of exercise, and ptomaine poisoning. “There is, however, an invariable factor, without the presence of which all other casual and irregular factors are powerless to set up the disease. This essential factor, it has been proved over and over again, is the absence of certain elements in food. If the body is deprived of these elements, [scurvy] is produced. What these elements are has not yet been absolutely settled with scientific precision, but we know positively that they exist in fresh vegetables, in lime-juice, in milk, and in less considerable degree, perhaps, in some other fresh animal foods.”
Dr. Cheadle prescribes fresh food and fresh air for Georgie. Using only his “case knowledge” and without any theory to back him up, Dr. Cheadle’s recommendations are remarkably on target. He allows the cod liver oil to continue, since fish oil is known to help cure rickets, but he stops the drugs. He orders raw (unpasteurized) milk along with a tablespoon a day of minced raw meat sweetened with sugar, foods which contain some vitamin C and vitamin D. Pasteurizing kills the bacteria in milk but also destroys vitamin C. Dr. Cheadle seems to understand that being outside will also help the child recover. Humans generate their own vitamin D in response to sunlight. In the other cases discussed in his 1878 paper, he adds potatoes and fresh orange or lemon juice to his dietary recommendations, all foods rich in vitamin C.
Georgie gets better. Less than two months after Dr. Cheadle provides his diagnosis and his recommendations, the pediatrician writes him the good news: “The child is decidedly improving. Sponginess of the gums has completely disappeared, and he can sit up now without any inconvenience.” And in a follow-up letter, "Since you saw him the child has greatly improved. The fontanelle is all but closed; the swelling &c. of the gums have entirely disappeared … The spine is straighter and firmer, and he can sit upright, and even move about the floor, though not as yet able to stand. … He has more or less continued the diet you recommended, and I have now allowed his parents to take him to Margate to try the effect of salt-water bathing." Dr. Cheadle’s final comments on the case are: “I have since learnt that the child is running about thoroughly strong and well.”
According to a 2004 article in the Journal of Nutrition Science, “[t]he first scientific approach to [rickets] was made by McCollum and his co-workers [in 1914].” This article describes the discovery of the biochemistry of vitamin D, a story climaxing in the awarding of the Nobel prize in 1928. (Nobels were awarded in 1937 for work on vitamin C.) Thus, Dr. Cheadle’s use of “case-based reasoning” to cure patients is not “scientific” by the criteria of this article.
Case-based reasoning (CBR) was formulated in the 1980’s as a way to teach computers “learning by experience.” The key insight was that most human problem solvers do not use rules or theories to guide their thinking but rather decide what to do based on their past experiences. CBR’s approach to problem solving is to develop a database of cases as an ongoing community resource that can be organized and understood like a person’s experiential memory.
In a medical CBR system, clinicians search the archive for past cases to help solve a current case, then enter the newly solved case to enrich the archive. CBR searches by “similarity” rather than “exact matching,” in analogy with the qualitative way that humans associate one thing with another. A contribution of CBR to cognitive science is in formulating ways to capture this subtle human skill in computer algorithms. While scientists might be inspired to develop theories from a carefully maintained archive of cases, the cases need not be reduced to theory to make the knowledge they contain useful. The goals of “ treating patients” and “understanding disease” are not identical.
Dr. Cheadle cured Georgie without having a twentieth-century understanding of vitamins. Georgie would have been 52 in 1928 and 61 in 1937, when the significance of vitamins D and C were being Nobel-y acknowledged, respectively, but it was thanks to Dr. Cheadle’s case-based clinical knowledge that Georgie lived to be 2 in 1878.
Such harsh times. Remembering how rough it was years ago I have to feel blessed to have had my children in this time and with this technology.
Posted by: Technobabe | July 16, 2009 at 11:19 PM
I really enjoyed reading that, nicely written Alex!
Posted by: Captain Skellett | July 17, 2009 at 12:25 AM
Awesome post, thanks!
Posted by: Prem | July 17, 2009 at 07:08 AM
very interesting . Thanks!
Posted by: splendid | July 21, 2009 at 09:40 AM