Then, in 1953, a geneticist in Texas accidentally mixed the wrong liquid with HeLa and a few other cells, and it turned out to be a fortunate mistake. The chromosomes inside the cells swelled and spread out, and for the first time, scientists could see each of them clearly. —Rebecca Skloot, The Immortal Life of Henrietta Lacks
Okay, Ms. Skloot, no fair teasing a geneticist reader like that. Who was the scientist in Texas? What was the wrong liquid? How long did it take for the scientist to realize he had launched the entire field of cytogenetics with his mistake? This inquiring mind wants to know.
In 1950 researchers were fairly certain that the human chromosomal complement was 48. By 1959 researchers changed their minds and were publishing papers showing normal karyotypes of 46 chromosomes obtained from cells grown in culture from seven different tissue samples (1). By 1960 the Philadelphia chromosome associated with human chronic myeloid leukemia had been identified (2). Additionally, in 1959 at a Symposium on Cytology in Human Genetics, a keynote speaker was able to review progress made in the field of cytogenetics in understanding the genetic causes of developmental illnesses such as Down, Klinefelter’s and Turner’s syndromes (3). And, by 1962, physicians were publishing case studies of patients with chromosomal abnormalities, including one in which a 15:21 chromosome fusion could be detected and its inheritance traced through the familial pedigree (4). In 1959, science was predicting “a steady increase in our understanding of the relationship of chromosomal abnormalities to congenital disease, to neoplasia, and to general human biology (3).”
So what was the accident that helped the field of cytogenetics along? Well, it turns out that in 1952 a researcher by the name of T.C. Hsu who was working at the University of Texas was preparing cells grown in culture for fixation. His protocol required that the cells be washed in an isotonic saline solution before fixation; however, the cells were instead washed with a hypotonic “Tyrode” solution (5). When Hsu looked at his cells to observe the metaphase chromosomes, he found that the chromosomes were spread out so well on the slide they were very easy to count. At the same time another scientist, Arthur Hughes at Cambridge, was studying the effect hypotonic solutions on cells, and he shared his work with Hsu (5). By comparing the effects of the Tyrode solution on the cells Hsu’s lab was studying with the data Hughes had obtained, Hsu was able to determine the nature of the “mistake” that lead to the excellent chromosome preparations and is later quoted as having said:
it only shows that to achieve some discovery, sloppy technicians are occasionally helpful (5,6).
However, Hsu maintained that the normal human chromosomal component was 48, not 46. It wasn’t until his mistake of pretreating cultured cells with hypotonic solution was refined and combined with colchicine pretreatment and chromosome squashes that researchers Tjio and Levan proposed that 46 was the correct number of human chromosomes in normal cells (6,7). Later Hsu said he looked for 48 chromosomes in his cells and was biased toward that number (6).
So that’s the story, a technician uses the wrong solution, and a scientist sees human chromosomes more clearly than ever and he says “hmm…that’s funny”. So he does some detective work and finds the fortuitous mistake. But his biases about what he should be seeing cloud his vision, and he still counts 48 chromosomes at every opportunity. Other scientists build on his work, refine it, and they publish the surprising results that go against convention—46 human chromosomes. Then other scientists replicate their findings, and the convention is changed.
That’s how science works. One study is never the entire story. It’s iterative, with everyone building on everyone else’s work, standing on the shoulders of those who have come before and being prepared to learn from mistakes.
And, the conventional wisdom of the day? It’s always up for discussion.
- Tjio JH, & Puck TT (1958). THE SOMATIC CHOMOSOMES OF MAN. Proceedings of the National Academy of Sciences of the United States of America, 44 (12), 1229-37 PMID: 16590337
- BAIKIE AG, COURT-BROWN WM, BUCKTON KE, HARNDEN DG, JACOBS PA, & TOUGH IM (1960). A possible specific chromosome abnormality in human chronic myeloid leukaemia. Nature, 188, 1165-6 PMID: 13685929
- FORD CE (1960). Human cytogenetics: its present place and future possibilities. American journal of human genetics, 12, 104-17 PMID: 13823894
- PENROSE LS (1962). Some clinical aspects of human cytogenetics. Postgraduate medical journal, 38, 284-5 PMID: 14485139
- Hsu, T.C. (1952). Mammalian Chromosomes In Vitro: I The Karyotype of Man J. Heredity, 167-172
- Kottler MJ (1974). From 48 to 46: cytological technique, preconception, and the counting of human chromosomes. Bulletin of the history of medicine, 48 (4), 465-502 PMID: 4618149
- Tjio, J.H. and Levan, A. (1956). The Chromosome Number of Man Hereditas, 42 (January 26), 1-6
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I have been reading the same Henrietta Lacks story that is quoted above. While I am not a scientist, I had the same reaction to the quote and was interested to know the story related above.
Thank you for writing this blog.
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