Midwives used to lick the forehead of infants they delivered, believing that if the newborn's skin tasted abnormally salty it was a bad omen—the baby would soon grow sickly and probably die.

Their predictions were generally accurate, for excessively salty sweat is a symptom of cystic fibrosis. Until recently, not much else was known about the deadly disease, even though doctors kept their patients alive longer by using antibiotics.

Genetics detectives often try to locate the gene for a specific trait by comparing the DNA of people who have the trait with that of close relatives who don't. Eventually, if they are lucky enough to examine the right DNA fragments, they zero in on the gene. Then they can deduce what protein the gene codes for and what flaw in the protein is responsible for the disease.

Using this approach, in 1982 Lap-Chee Tsui (pronounced "Choy") of Toronto's Hospital for Sick Children, who was an HHMI international research scholar, and his colleague Manuel Buchwald started looking for statistical links between CF and various genetic markers—recognizable variations in DNA. Tsui tested blood from many families whose children had CF, and, eventually, his collaboration with researchers in Copenhagen and Collaborative Research Inc., a biotechnology firm in Massachusetts, led to discovery of a marker on chromosome 7. Meanwhile, Raymond White, a pioneer in gene mapping who was then at the University of Utah's HHMI unit, and Robert Williamson of St. Mary's Hospital Medical School in London, also discovered close markers on chromosome 7. The key findings of the three teams, published together in November 1985, meant that the CF gene, which was inherited along with the markers, was also located somewhere on that chromosome.

Up to that point, looking for the CF gene had been much like trying to find a particular house without even knowing what continent it was on. Now researchers could narrow their search to an area equivalent to a particular country.

Finding the markers meant that parents who already had a child with CF and were expecting another child could be told with reasonable accuracy whether the fetus was destined to develop the disease.

Finding the gene was still a long way off, however. The researchers did not know what direction to take—was the gene to the left or right of the markers, or in between? Finding the answer would require DNA from a large number of families in whom some members had the disease while others did not.

Seven independent research teams which had been racing to find the CF gene realized none could do so large a study alone. They decided to pool their families (211 in all), their probes, and their data.

From the pooled knowledge, Jean-Marc Lalouel of the HHMI unit at Utah and White found that two of the markers flanked the gene. The search could then focus on a stretch of DNA equivalent to an interstate highway, but still long enough to hold perhaps 50 to 100 genes. It was far too great a distance for researchers to "walk" toward the gene.

— Maya Pines

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Eventually researchers found out which chromosome carries the defective gene and established the gene's general location between known markers.

Illustration: Karen Barnes — Stansbury Ronsaville Wood, Inc.

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