1960s In April 1956,
Hereditas published the discovery by
cytogeneticists Joe Hin Tjio and
Albert Levan at
Lund University in
Sweden that the normal number of chromosomes in
diploid human cells was 46—not 48, as had been believed for the preceding thirty years. In the wake of the establishment of the normal number of human chromosomes, 47,XYY was the last of the common sex chromosome aneuploidies to be discovered, two years after the discoveries of
47,XXY,
45,X and
47,XXX in 1959. Even the much less common
48,XXYY had been discovered in 1960, a year before 47,XYY. Screening for those
X chromosome aneuploidies was possible before the advent of human chromosome analysis by noting the presence or absence of "female" sex chromatin bodies (
Barr bodies) in the
nuclei of
interphase cells in
buccal smears, a technique developed a decade
before the first reported sex chromosome aneuploidy. An analogous technique to screen for Y-chromosome aneuploidies by noting supernumerary "male" sex chromatin bodies was not developed until 1970, a decade
after the first reported male sex chromosome aneuploidy. The first published report of a man with a 47,XYY karyotype was by the American cytogeneticist
Avery Sandberg and his colleagues at
Roswell Park Comprehensive Cancer Center (then known as Roswell Park Memorial Institute) in
Buffalo, New York in 1961. It was an incidental finding in a normal 44-year-old, 6 ft. [183 cm] tall man of average intelligence who was karyotyped because he had a daughter with
Down syndrome. Only a dozen isolated 47,XYY cases were reported in the medical literature in the four years following the first report by Sandberg. The XYY syndrome, if named after the discoverer, should rightly be termed Sandberg syndrome and not Jacobs syndrome although the British cytogeneticist
Patricia Jacobs did indeed contribute meaningfully to medical knowledge of XYY. In December 1965 and March 1966,
Nature and
The Lancet published the first preliminary reports by Jacobs and her colleagues at the
MRC Human Genetics Unit at
Western General Hospital in
Edinburgh of a chromosome survey of 315 male patients at
State Hospital in
Carstairs,
Lanarkshire—
Scotland's only special security hospital for
developmentally disabled people —that found nine patients, ages 17 to 36, averaging almost 6 ft. in height (avg. 5'11", range: 5'7" to 6'2"), had a 47,XYY karyotype, and mischaracterized them as aggressive and violent criminals. Over the next decade, almost all published XYY studies were on height-selected, institutionalized XYY males. Telfer found five tall, developmentally disabled XYY boys and men in hospitals and penal institutions in
Pennsylvania, and since four of the five had at least moderate facial
acne, reached the erroneous conclusion that acne was a defining characteristic of XYY males. In April 1968,
The New York Times—using Telfer as a main source—introduced the XYY genetic condition to the general public in a three-part series on consecutive days that began with a Sunday front-page story about the planned use of the condition as a mitigating factor in two murder trials in
Paris and
Melbourne—and falsely reported that Richard Speck was an XYY male and that the condition would be used in an appeal of his murder conviction. The series was echoed the following week by articles—again using Telfer as a main source—in
Time and
Newsweek, and six months later in
The New York Times Magazine. In December 1968, the
Journal of Medical Genetics published the first XYY review article—by Willam Michael Court Brown (1918–1969), director of the MRC Human Genetics Unit—which reported that he had found no overrepresentation of XYY males in nationwide chromosome surveys of prisons and hospitals for developmentally disabled and mentally ill people in Scotland, and concluded that studies confined to institutionalized XYY males may be guilty of
selection bias, and that long-term
longitudinal prospective studies of newborn XYY boys were needed. In June 1969, the
National Institute of Mental Health (NIMH) Center for Studies of Crime and Delinquency held a two-day XYY conference in
Chevy Chase, Maryland. In December 1969, with a grant from the NIMH Center for Studies of Crime and Delinquency, cytogeneticist Digamber Borgaonkar at
Johns Hopkins Hospital began a chromosome survey of (predominantly African-American) boys ages 8 to 18 in all
Maryland institutions for delinquent, neglected, or mentally ill juveniles, which was suspended from February–May 1970 due to an
American Civil Liberties Union (ACLU) lawsuit regarding the study's lack of
informed consent. In the late 1960s and early 1970s, screening of consecutive newborns for sex chromosome abnormalities was undertaken at seven centers worldwide: in
Denver (Jan 1964–1974),
Edinburgh (Apr 1967–Jun 1979),
New Haven (Oct 1967–Sep 1968),
Toronto (Oct 1967–Sep 1971),
Aarhus (Oct 1969–Jan 1974, Oct 1980–Jan 1989),
Winnipeg (Feb 1970–Sep 1973), and
Boston (Apr 1970–Nov 1974). The Boston study, led by
Harvard Medical School child psychiatrist Stanley Walzer at
Children's Hospital, was unique among the seven newborn screening studies in that it only screened newborn
boys (non-private-ward newborn boys at the
Boston Hospital for Women) and was funded in part by grants from the NIMH Center for Studies of Crime and Delinquency. The Edinburgh study was led by
Shirley Ratcliffe who focused her career on it and published the results in 1999.
1970s In December 1969, Lore Zech at the
Karolinska Institute in Stockholm first reported intense
fluorescence of the
A T-rich distal half of the long arm of the Y chromosome in the nuclei of
metaphase cells treated with
quinacrine mustard. In April 1970, Peter Pearson and
Martin Bobrow at the
MRC Population Genetics Unit in
Oxford and Canino Vosa at the
University of Oxford reported fluorescent "male" sex chromatin bodies in the nuclei of interphase cells in buccal smears treated with quinacrine dihydrochloride, which could be used to screen for Y chromosome aneuploidies like 47,XYY. In December 1970, at the annual meeting of the
American Association for the Advancement of Science (AAAS), its retiring president, geneticist
H. Bentley Glass, cheered by the legalization of abortion in
New York, envisioned a future where pregnant women would be required by the government to abort XYY "sex deviants". Mischaracterization of the XYY genetic condition was quickly incorporated into high school biology textbooks and medical school psychiatry textbooks, where misinformation still persists decades later. In August 1976,
Science published a
retrospective cohort study by
Educational Testing Service psychologist
Herman Witkin and colleagues that screened the tallest 16% of men (over 184 cm (6'0") in height) born in
Copenhagen from 1944 to 1947 for XXY and XYY karyotypes, and found an increased rate of minor criminal convictions for property crimes among sixteen XXY and twelve XYY men may be related to the lower intelligence of those with criminal convictions, but found no evidence that XXY or XYY men were inclined to be aggressive or violent.
1980s and later The
March of Dimes sponsored five international conferences in June 1974, November 1977, May 1981, June 1984, and June 1989 and published articles from the conferences in book form in 1979, 1982, 1986, and 1991 from seven longitudinal
prospective cohort studies on the development of over 300 children and young adults with sex chromosome abnormalities identified in the screening of almost 200,000 consecutive births in hospitals in Denver, Edinburgh, New Haven, Toronto, Aarhus, Winnipeg, and Boston from 1964 to 1975. These seven studies—the only unbiased studies of unselected individuals with sex chromosome abnormalities—have replaced the older, biased studies of institutionalized individuals in understanding the development of individuals with sex chromosome abnormalities. In May 1997,
Nature Genetics published the discovery by Ercole Rao and colleagues of the X/Y chromosome
pseudoautosomal region (PAR1)
SHOX gene,
haploinsufficiency of which leads to short stature in
Turner syndrome (45,X). It was subsequently postulated that the increased gene dosage of three SHOX genes leads to tall stature in the sex chromosome trisomies 47,XXX, 47,XXY, and 47,XYY. In June 2002, the
American Journal of Medical Genetics published results from a longitudinal prospective cohort Denver Family Development Study led by pediatrician and geneticist Arthur Robinson, which found that in fourteen
prenatally diagnosed 47,XYY boys (from high
socioeconomic status families), IQ scores available for six boys ranged from 100 to 147 with a mean of 120. For the eleven of fourteen boys with siblings, in nine instances their siblings were stronger academically, but in one case the subject was performing equal to, and in another case superior to, his siblings. ==Society and culture==