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Predictive hypotheses are ineffectual in resolving complex biochemical systems

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Abstract

Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin–proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of complex systems. As data-based accommodation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential.

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(adapted from Pardee et al. 1959)

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Notes

  1. Watson (1953), a March 12, 1953 letter to Delbrück: http://osulibrary.orst.edu/specialcollections/coll/pauling/dna/corr/corr432.1-watson-delbruck-19530312-03.html.

  2. Untitled and undated typescript of a talk that was probably delivered in 1957: Wellcome Library Archives; Closed stores Arch. & MSS PP/CRI/H2/24: Box 79; Ref. no. ebaf293b-7f02-46c8-a16f-c45333219e28.

  3. Gamow's July 8, 1953 handwritten letter to Watson and Crick; facsimile 1 in Watson (2001).

  4. Facsimile of Gamow’s October 22, 1953 letter to Linus Pauling; OSU Linus Pauling Web archive: http://osulibrary.orst.edu/specialcollections/coll/pauling/dna/corr/sci9.001.43-gamow-lp-19531022-01.html.

  5. An even earlier version of the Central Dogma was submitted by Boivin (1947): "We may at the most, catch a glimpse of a series of catalytic actions, which set out from primary directing centers (the desoxyribonucleic genes), proceed through secondary directing centers (the ribonucleic microsome-plasma-genes), and thence through tertiary directing centers (the enzymes), to determine finally the nature of the metabolic chains involved, and to condition, by this very means, all the characters of the cell in consideration."

  6. In: “A career begins at the National Institute of Health”; the second of six oral history interviews that Ruth Harris conducted with Nirenberg between September 1995 and January 1996: http://history.nih.gov/archives/downloads/Nirenberg%20oral%20history%20Chap%202%20-NIH%201957_1959.pdf.

  7. Facsimile of Watson’s December 11, 1954 letter to Crick in the NIH Profiles in Science Web site: http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/SCBBJN.

  8. Crick’s unpublished communication to the RNA Tie Club (1955): “On degenerate templates and the adaptor hypothesis”. Facsimile in the NIH Profiles in Science Web site: http://profiles.nlm.nih.gov/SC/B/B/G/F/_/scbbgf.pdf.

  9. According to Judson (1996, p. 323), Crick did not attend Volkin’s talk and only a year later he read its published form (Volkin and Astrachan, 1957). Judson also claimed that Crick and Brenner were familiar with the Volkin and Astrachan results when they came up with the idea of mRNA. Asked whether he was aware of the Oak Ridge findings, Jacob had said, “The question is what you mean, to be aware? To be aware is to have it on the front of consciousness, and clearly we were not, at this level, even if we knew” (Judson 1996, p. 414).

  10. The other ‘bombshell’ was Arthur Kornberg’s report of DNA synthesis in E. coli extracts.

  11. Brenner referred here to Volkin and Astrachan’s (1956, 1957) original notion that the unstable RNA was a precursor of phage DNA. Notably, however, he did not recall their later conclusion that the different kinetics of accumulation of radioactivity in phage RNA and DNA discounted precursor-product relationship between the two. He was also unaware of their later suggestion that the short-lived phage RNA molecules were templates for viral proteins (Volkin et al. 1958).

  12. Facsimile of Crick’s handwritten note, dated May 1960 in the NIH Profiles in Science Web site: http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/SCBBFZ.

  13. Facsimile of Crick’s May 10, 1960 letter to Kornberg, in the NIH Profiles in Science Web site: http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/SCBBGZ.

  14. Meselson’s videotaped testament: http://www.dnalc.org/view/15330-Messenger-RNA-Matthew-Meselson.html.

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The author is indebted to the two anonymous reviewers and to the editor for their insightful comments.

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    Michael Fry

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Fry, M. Predictive hypotheses are ineffectual in resolving complex biochemical systems. HPLS 40, 25 (2018). https://doi.org/10.1007/s40656-018-0192-3

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