Hum. Genet. 39, 257--259 (1977) © by Springer-Verlag 1977

Letters to the Editors

Scientific Method and the Philadelphia Chromosome Peter H. Fitzgerald Cancer Society of New Zealand, Cytogenetics Unit,Christchurch Hospital, Christchurch, New Zealand

Lately I had my attention drawn to the letter of Hecht and McCaw (1977) about my paper 'Evidence that chromosome band 22q12 is concerned with cell proliferation in chronic myeloid leukaemia' (Fitzgerald, 1976). They claim that the data in my paper 'do not prove in any way that the genetic information on chromosome 22 concerned with abnormal myeloid cell proliferation is contained in band 22q12.' That claim indicates a misconception of fundamental scientific methodology by its authors. Scientific method, as I understand it, does not attempt to prove anything, but rather establishes an hypothesis from the available data and then attempts to disprove that hypothesis. The production of new data contrary to the hypothesis causes its rejection, substitution, or modification. The continuation of this procedure will ultimately lead to the true facts of a situation, and this procedure is the only objective manner of doing so. An hypothesis that withstands a vigorous series of tests may become accepted, but not proven. This is a crude paraphrase of the scientific method formulated in 1934 by K. R. Popper in 'Logik der Forschung,' and available in a later annotated translation 'The Logic of Scientific Discovery' (Popper, 1959). Popper sees the method of science to be like a Darwinian method of selection. We produce theories and then eliminate them. The remainder are those not yet refuted--but not therefore true. My paper formulated the reasonable hypothesis that chromosome band 22ql 2 was concerned with cell proliferation in chronic myeloid leukaemia, and presented that hypothesis for the process of public disproof or falsification. There must be few of your readers who look for proof in a scientific presentation or who read scientific journals with the faith of elders consulting Holy Books. Hecht and McCaw specify two reasons for their claim. The first reason seems incomplete, but appears to imply that a mutation affecting erythromyeloid cells will necessarily be different in effect if it arises somatically than if it were present constitutionally. It may be relevant that a supposed constitutional Philadelphia chromosome was reported in a family of which several carrier members had chronic myel0id leukaemia (Weiner, 1965). Their second reason, a claim that no

258

P.H. Fitzgerald

case of chronic myeloid leukaemia involves an 11 ;22 rearrangement, is incorrect. Such a case was reported by Muldal et al. (1975). The great advantage of the scientific method outlined above is its objectivity, and new data of real importance to my hypothesis has already appeared in the literature. The hypothesis that chromosome band 22q12 was concerned with cell proliferation in chronic myeloid leukaemia was based on the finding that three adults without evidence of leukaemia or haematological disorder carried a 11 ;22 translocation with the breakpoint on chromosome 22 at the q12/13 band interface compared with the presumed breakpoint of Ph I at the 2 2 q l l / q 1 2 interface or in band 22q11. There are now reports of persons carrying 11;22 translocations with the breakpoint on chromosome 22 at the ql 1 band similar to the presumed breakpoint of the Ph 1 chromosome. Although these reports are concerned primarily with abnormality of chromosome 11 rather than 22, it appears that carriers of the balanced translocations were normal individuals without evidence of haematological disorder, although this point remains to be confirmed (Ayraud et al., 1976; Noel et al., 1976). Also, I know of other reports to appear shortly that describe breakpoints at 22ql 1 in translocations with other chromosomes, and balanced carriers are haematologicaUy normal. These new data clearly conflict with my argument and, consequently, the suggestion that band 22q12 is concerned with cell proliferation in chronic myeloid leukaemia is no longer a valid conclusion. Popper makes the analogy of scientific method to a man finding his way through a wood in the dark. He must venture--do something. His method is trial and error with the emphasis on error. If you don't make mistakes, then you learn nothing. My paper was an attempt to move in the very dark wood of the Philadelphia chromosome and chronic myeloid leukaemia. It has helped to underline what we don't know about this chromosome and has drawn attention to a method that may tell us more about it. Specifically, attention must now be given to the exact position of the breakpoint in the Philadelphia chromosome, a fundamental point which has not been satisfactorily determined. We should consider a reciprocal exchange with the breakpoint on chromosome 22 immediately below the centromere, with the whole of 22q translocated to 9q in exchange for part of 9q34 which constitutes the q arm of Ph 1 in the usual translocation. Recent banding results support such a reciprocal exchange (Buckton and O'Riordan, 1976). 'Erroneous conclusions' could have been drawn about the 'Christchurch chromosome' only by those with the same naive misconception of scientific method already described, or by those who failed to read more than the title of the original paper (Gunz et al., 1962). That paper noted chronic lymphocytic leukaemia (CLL) in two sibling carriers of the abnormal chromosome and also the presence of normal chromosomes in nine unrelated cases of CLL. Subsequent papers reported these significant findings: the abnormal chromosome was not present in other instances of familial CLL, nor in a considerably larger series of individual cases of CLL; a third sib and carrier of the abnormal chromosome developed CLL; the abnormal chromosome was identified as 22p-; and the development of acute plasma cell leukaemia was reported in one of the three original sibs with CLL (Fitzgerald et al., 1966; Fitzgerald and Hamer, 1969;

Scientific Method and the Philadelphia Chromosome

259

F i t z g e r a l d et al., 1973). These findings are sufficient to p r e v e n t e r r o n e o u s conclusions b y a n y discerning r e a d e r a n d to m a i n t a i n the p o s s i b i l i t y t h a t this c h r o m o s o m e m i g h t have special significance for the d e v e l o p m e n t o f l e u k a e m i a in this family. T h e d e c l a r a t i o n b y H e c h t a n d M c C a w that this p a r t i c u l a r 2 2 p - a b n o r m a l i t y is 'clearly r e c o g n i z a b l e as a n o r m a l p o l y m o r p h i c v a r i a t i o n o n a G s h o r t a r m ' m i g h t be correct, b u t m i g h t be a n equally ' e r r o n e o u s c o n c l u s i o n . ' Elsewhere we have been e x h o r t e d a g a i n s t the a d o p t i o n o f p o l a r views in situations where i n f o r m a t i o n is insufficient ( M c C a w et al., 1 9 7 5 ) - - g o o d advice its a u t h o r s m i g h t well consider. F o r t u n a t e l y , we can rely on s o u n d scientific m e t h o d to help us sort o u t the alternatives.

References Ayraud, N., Galiana, A., Lloyd, M., Deswarte, M.: Trisomie 11q(q23.1qter)par translocation maternelle t(11;22)(q23.1;ql I. 1). Une nouvelle observation. Ann. Genet. (Paris) 19, 65--68 (1976) Buckton, K. E., O'Riordan, M. L.: Easy identification of chromosome translocation involved in chronic myeloid leukaemia. Lancet 1976 II, 1404 Fitzgerald, P. H.: Evidence that chromosome band 22q12 is concerned with cell proliferation in chronic myeloid leukaemia. Hum. Genet. 33, 269--274 (1976) Fitzgerald, P. H., Crossen, P. E., Adams, A. C., Sharman, C. V., Gunz, F. W.: Chromosome studies in familial leukaemia. J. Med. Genet. 3, 96--100 (1966) Fitzgerald, P. H., Hamer, J. W.: Third case of chronic lymphocytic leukaemia in a carrier of the inherited Ch 1 chromosome. Br. Med. J. 1969 III, 752--754 Fitzgerald, P. H., Rastrick, J. M., Hamer, J. W.: Acute plasma cell leukaemia following chronic lymphatic leukaemia: transformation or two separate diseases? Br. J. Haematol. 25, 171--177 (1973) Gunz, F. W., Fitzgerald, P. H., Adams, A.: An abnormal chromosome in chronic lymphocytic leukaemia. Br. Med. J. 1962 II, 1097--1099 Hecht, F., McCaw, B. K.: The consequences of the Philadelphia chromosome rearrangement in chronic myeloid leukaemia. Hum. Genet. 36, 127--128 (1977) McCaw, B. K., Hecht, F., Harnden, D. G., Teplitz, R. L.: Somatic rearrangement of chromosome 14 in human lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 72, 2071--2075 (1975) Muldal, S., Mir, M. A., Freeman, C. B., Geary, C. G." A new translocation associated with the Ph 1 chromosome and an acute course of chronic granulocytic leukaemia. Br. J. Cancer 31, 364--368 (1975) Noel, B., Levy, M., Rethone, M. O.: Trisomie partielle du bras long du chromosome 11 par mals6gr6gation d'un translocation materneUe t(11 ;22)(q231 ;ql I 1). Ann. Genet. (Paris) 19, 137--139 (1976) Popper, K. R.: The logic of scientific discovery. London: Hutchinson 1959 Weiner, L.: A family with high incidence leukaemia and unique Ph ~ chromosome findings. Blood 26, 871 (1965) Received June 27, 1977

Scientific method and the Philadelphia chromosome.

Hum. Genet. 39, 257--259 (1977) © by Springer-Verlag 1977 Letters to the Editors Scientific Method and the Philadelphia Chromosome Peter H. Fitzgera...
191KB Sizes 0 Downloads 0 Views