Not all dial tones sound alike. So says Shai Shaham, who can tell instantly whether Ma Bell is humming in E or buzzing in D. Shaham, a UCSF postdoctoral fellow and pianist who has picked a career in science over one in music, has the ability to recognize or play a specific musical note without hearing a reference note. It is called perfect pitch. Hit a random piano key, and he can name the tone.

He can also pick up the pitch of nonmusical sounds, like the telephone or the refrigerator. No big deal, says Shaham, 28, who has had perfect musical note recall ability since he was a kid. But others marvel at this unusual talent, possessed by the likes of Mozart, Andre Previn, Ella Fitzgerald and Bobby McFerrin. Only an estimated one in 2,000 in the general population has this skill to hear and immediately discern specific sounds and vibrations. It is analogous to being able to view many brilliant hues when everyone else sees only primary colors.

Perfect pitch, however, is not rare in Shaham's family. His father had the talent, as do his sister, Orli, an accomplished pianist, and his younger brother, who happens to be Gil Shaham, a world-famous pianist. Is perfect pitch learned or inherited? And was it the result of the Shaham children's exposure to a music-filled environment and the opportunity they had to develop skills, or is it a trait written into their DNA?

It is a classic nature-versus-nurture question, and one that intrigues UCSF geneticists Jane Gitschier and Nelson Freimer. Both are music lovers, as well as successful scientists. Gitschier, who studies the molecular basis of inherited X chromosome-linked disorders, such as hemophilia, is a "coloratura" soprano. Freimer, a neuropsychiatrist whose laboratory is homing in on a gene for maniac-depressive illness, comes from a musical family and played clarinet in his younger days. Neither has perfect pitch.

Is perfect pitch an inherited ability? The family tree of a musician in the UCSF study suggests how the trait was passed on to her. Interestingly, neither her father nor brother who play musical instruments have perfect pitch. On her father's side, two of her uncles has perfect pitch, as did her grandfather.

Two years ago they discussed their fascination with those who do and, adding a new twist in their genetics research, they decided to explore an area not associated with a "disease gene" -- not one likely to arouse the controversy that genes associated with violence or sexual orientation do.

They hypothesize that having perfect pitch may be a matter of both genetics and environment. One perhaps inherits a predisposition for this talent, but it must be exercised early in life in order for it to be realized.

With the help of biomedical sciences graduate student Siamak Baharloo, a multi-skilled researcher who describes himself as "musically naive," they have composed a study which could lead to a major scientific score -- pinpointing a gene or set of genes for perfect pitch.

Surveys by Baharloo of students at such schools as the San Francisco Conservatory of Music, the Curtis Institute of Music in Philadelphia, and the Peabody Institute in Baltimore, support the theory that a mix of nature and early age nurturing produces the perfect pitch person. Of 620 music students questioned, 15 percent reported possessing perfect pitch. Almost half of those who began musical training before age 4 reported perfect pitch, as did nearly one-third of those who started music between the ages of 4 and 6 years. Only 2 per cent of those who started music training after age 12 reported perfect pitch. On the nature side, 48 percent of all who reported perfect pitch claimed to have a relative with the talent. In contrast, only 12 percent of non-perfect pitch subjects reported other family members with the skill.

Questionnaires do not prove theories, so the UCSF trio is conducting their own series of tests, which they hope will set them on the right course in their gene hunt. Baharloo has used a test, designed by otolaryngology postdoctoral fellow Paul Johnson, on some 40 individuals to prove their perfect pitch. Testing included producing 40 pure and piano tones, each lasting one second, and asking subjects to make an instantaneous identification of each tone.

The most critical task to date has been to recruit enough subjects and their family members into the study. If a gene plays a role in perfect pitch it is present in all who possess the trait, so DNA samples -- taken from the blood -- must be collected from all so that researchers can comb their chromosomes. A pattern of frequent markers in individuals with the trait signals a link to the same gene. Once the site of the gene is narrowed, they can use today's tools of modern molecular biology to pinpoint the target gene.

The study's potential stumbling block, and certainly the most time-consuming part, is securing an adequate number of samples to bring to the laboratory, says Gitschier. Some 35 people with perfect pitch have agreed to be part of the research, but the UCSF team needs 50 to 100 to make the study scientifically sound.

Shai Shaham, who started piano lessons at age 4 and plays only occasionally now that he spends most of his time studying yeast genetics in the UCSF laboratory of Ira Herskowitz, has agreed to participate in the study. He scored perfectly in the sound test and has had his blood drawn.

As a child he could not understand the fuss and fascination surrounding his perfect pitch ability. "I was just used to having it," he says. "For music, it does help, but other than that, there are not a lot of other practical uses for it." The UCSF study, however, has triggered his own curiosity whether or not his talent is indeed inherited. He also believes that the findings may offer some clues to understanding the biological mechanisms of memory and learning. For geneticists Gitschier and Freimer, locating a perfect pitch gene may open a whole new biological pathway. An individual's genetic make-up contributes greatly to the type of person he or she is, but environmental variables play a considerable role in determining his or her characteristics.

"This study may give us important clues to how genes and the environment interact to form us," says Freimer.

By Andy Evangelista
(This article also appears in the current UCSF Magazine.)

1st appeared - 6/09/97