On the Scent: The Discovery of PKU
Dr. Asbjørn Følling, 1930, in a Colorado cabin laboratory. Følling was the first to identify the disease today known as phenylketonuria. (Willard R. Centerwall)
Through her kitchen window Borgny Egeland surveyed grey skies made luminous by a midday sun hanging low on the horizon. The distant sound of the town hall’s chimes might have lightened her spirits, but Borgny had reached her wit’s end.
Her first child, Liv, had been born a healthy, bright-eyed girl. A joy to Borgny and her husband, Harry, Liv was the child they dreamed of when the young couple started their family in late-1920s Oslo. But after three years little Liv had not learned even one word. The family physician reassured Borgny: ”Just give it time,” he said. So Borgny and Harry waited. In the meanwhile they welcomed their second child, a healthy son named Dag. But Dag began showing signs of developmental delay even more quickly than his sister. By 1934 six-year-old Liv could say only a few words and walked with spastic irregularity. At four, Dag could not speak and was unable to walk, eat, or drink on his own.
Borgny visited a number of medical specialists, herbalists, and even a psychic healer. Why, she asked, had her healthy babies gradually, inexorably fallen into profound mental disability? No one had an answer. Curiously, the children gave off a strong musty odor from their hair, skin, perspiration, and urine. Their asthmatic father could barely tolerate it.
As well as struggling with her children’s disabilities, Borgny was struggling against doctors’ dismissive views of “feeblemindedness.” Mentally disabled people were considered hopeless cases, suffering from a defect of the brain caused by bad genes and destined to be warehoused in mental institutions alongside patients with psychiatric disorders, epileptics, and others whose “bad brains” were beyond the help of modern medicine.
This attitude was about to change. A chance conversation connected Borgny’s husband to Asbjørn Følling, a doctor who had worked on high-altitude metabolism and physiology in the mountains of Colorado. His unusual dual background in chemistry and metabolic medicine would prove crucial: the disease he was about to discover would open up a new view of cognitive disability and inherited disease.
In 1934, as the frigid Oslo winter finally yielded to the coming of spring, Følling, professor of nutritional research at Oslo University Hospital, agreed to an appointment with Borgny, but with no expectation of being able to help her. “I examined the children mainly because I did not want to be hostile to the mother,” he later recalled. He performed a full physical examination and found nothing remarkable, except for their unmistakable “feeblemindedness.” Følling then examined the children’s urine, working from his own improvised laboratory in the attic of the medical ward. He checked the urine samples first visually and then chemically for acidity, pus, protein, and glucose. Protein or glucose in the urine would have suggested kidney malfunction, especially diabetes. But all the tests were negative. Except for the musty odor, the urine seemed perfectly normal.
Følling faced the same impasse that had confronted all the previous physicians, including his own colleagues at the Oslo hospital, who had thoroughly examined Dag on previous occasions. But unlike the others Følling tried another test: he added a few drops of acidified ferric chloride solution to each urine sample. This test, sometimes called Gerhardt’s test, was commonly used to detect diacetic acid (now typically called acetoacetic acid), which would have indicated complications of diabetes or possibly starvation. If diacetic acid is present in the urine, the sample turns a purple or burgundy color. But both children’s samples turned a deep green color, a reaction Følling had never seen before. A search of the literature told him that no one had seen this reaction before. Borgny’s children were excreting an unknown substance into their urine.
At his self-made laboratory bench Følling set out to identify the substance. After four weeks of trial and error he devised a way to extract, isolate, and purify the unknown material from the children’s urine. He found that his unknown readily reacted with oxygen in the air and so performed his experiments under an inert nitrogen atmosphere in the hunt for his chemical quarry. The spring was turning to summer when, two months and 22 liters of the children’s urine later, Følling concluded that the unknown substance was phenylpyruvic acid, a chemical not normally found in urine.