Information in Genetics and Developmental Biology: Comments on Maynard Smith Sahotra Sarkar Philosophy of Science, Vol. 67, No. 2 (Jun., 2000), 208-213. Stable URL hitp:/ links jstor-org/sii?sici=003 1-8248% 28200006%2967%3A2% 3C208%3 ATIGADB%3E2,0,CO%3B2-F Philosophy of Science is currently published by The University of Chicago Press. ‘Your use of the ISTOR archive indicates your acceptance of JSTOR’s Terms and Conditions of Use, available at hup:/www,jstororglabout/terms.hml. ISTOR’s Terms and Conditions of Use provides, in part, that unless you have obtained prior permission, you may not download an entire issue of a journal or multiple copies of articles, and you may use content in the JSTOR archive only for your personal, non-commercial use. Please contact the publisher regarding any further use ofthis work. Publisher contact information may be obtained at hupulwww.jstor.org/journals‘uepress html. Each copy of any part of @ JSTOR transmission must contain the same copyright notice that appears on the sereen or printed page of such transmission. STOR is an independent not-for-profit organization dedicated to creating and preserving a digital archive of scholarly journals. For more information regarding JSTOR, please contact jstor-info@umich edu hupswww jstor.org/ Fob 28 04:20:25 2004Information in Genetics and Developmental Biology: Comments on Maynard Smith’ Sahotra Sarkart Department of Philosophy, Univesity of Teas at Austin 1. Introduction, Maynard Smith notes that he provides a natural history and not a philosophical analysis of the use of concepts of information in contemporary biology. Just a natural history, however rich, would do litle to resolve the ongoing controversy about the role of these concepts in biology. None of the disputants deny that the biological use of these con- cepts is pervasive. The dispute is about whether these concepts—and the framework in which they are embedded—continue to be of explanatory value in contemporary biology. Fortunately, Maynard Smith does much more than provide a natural history: his contribution is also a sustained. attempt to justify many (though not all) of the uses of information in biology, ‘As in my earlier work which he criticizes (Sarkar 1996a, but see also Sarkar 1996b), I remain skeptical. But this skepticism should not be con- strued as being more radical than itis: there is considerable agreement between Maynard Smith's position and mine, particularly on the critical heuristic role played by the informational framework in molecular genetics in the 1960s. Moreover, I do not deny that the informational framework for molecular genetics has a certain perspicuity that its critics must explain and incorporate into their own putative alternatives. Finally, L agree with, his criticism of Mahner and Bunge (1997), My main purpose here is (i) to reintroduce certain distinetions that puts into perspective my original criticisms (§2) and (ii) to show why Maynard ‘Smith's attempt to escape these criticisms is not altogether persuasive ($3). ‘Received January 2000; revised February 2000. {Send requests for reprints to the author, Department of Philosophy, University of ‘Texas at Austin, Austin, TX 78712-1180, Phi fee 20. 28-21. 1014067000820 Copy yh Paleogene cen A ea oan 208INFORMATION IN GENETICS AND DEVELOPMENTAL BIOLOGY 209 Maynard Smith restricts his attention to developmental biology, evolution and genetics (though there isa passing reference to ethology). I will restrict attention to developmental biology and genetics since Maynard Smith's assessment of the role of information in evolutionary biology is no more positive than mine. 2. Preliminary Distinetions. The first distinetion that will be important is that between the heuristic use of a concept, rule, theory, or framework and-for want of a better term—a substantive use of the same. If some- thing plays a role in the construction of some scientific entity, that role is heuristic; it explicitly occurs in that entity, that role is substantive. Some- thing may have either a heuristic or a substantive role without having the other. For (scientific) realists this distinction is a qualitative one; for the type of instrumentalism that I endorse, itis a matter of degree: a good theory is simply a successful heuristic. Maynard Smith claims that infor- ‘mational concepts play both heuristic and substantive roles in genetics and, at present, at least a heuristic role in developmental biology. Contrary to what he believes about my position, I do not deny that these concepts played a useful heuristic role in genetics in the 19605; I only deny a sub- stantive role because the utility of that heuristic was soon lost. As §3 will indicate, twas primarily lost due to what Watson, Tooz, and Kurtz(1983) revealingly called the “unexpected complexity of eukaryotic geneties.” The second set of distinctions concerns three different concepts of in- formation that have historically been used in genetis: () eybemetic; i) communication-theoretic; and (ii) semantic. Cybernetic information is anything that produces feedback in self-regulating systems. Communi cation-theoretic information i (roughly) the entity measured by the log- arithm of the number of choices available during a communication pro- cess: it isa measure of disorder thatis isomorphic to entropy in equilibrium statistical mechanies. Semantic information will be discussed in §3 using concepts of specificity and semioticity. In a very important sense, cyber~ netic information has only a functional definition: itis defined by what it does, and this definition imposes no structural restriction on what bears that information. In contrast, the other two definitions impose some struc- tural constraints Whatever scientific interest eybernetics may once have had, it is no Jonger of anything but historical interest. Cybernetic information has litle relevance to contemporary genetics or developmental biology irrespective of whether, as Maynard Smith claims, Monod's (1971) ideas about gene regulation are central to developmental genetics. In our contemporary framework, Monod's analysis would be recast in terms of semantic infor- mation. Maynard Smith notes—as I did also (Sarkar 1996a, 6)—that, in spite of Kimura’s (1961) result connecting communication-theoretie in-210 SAHOTRA SARKAR formation to Haldane’s idea of a substitutional load, that concept has been a dead end in genetics and evolutionary theory. However, Schneider’s (e.g., 1988) use of that concept in the analysis of DNA sequences is prom- ising, especially in the context of the ongoing genome sequencing projects, and deserves at least to be mentioned, ‘What remains is semantic information, the concept we invoke to say, plausibly, () that DNA sequences contain information for producing pro- teins or, not very plausibly, (ii) that DNA sequences contain all the infor- mation for producing an organism. I do not believe that any of us has fully satisfactorily explicated this concept of information. §3 contains a tentative sketch—which remains incomplete for lack of space—of what such an explication should look like. It will show why claim (i) is plausible and claim (ii) is not. 3. Semantic Information. The first locution that has to be unpacked is “s contains information for 6.” For example, a DNA sequence contains in- formation for a protein. It seems to me that this requires the satisfaction of two eriteria @ differential specificity: isis diferent from’, then o must be different from a’. When we think of DNA and proteins this criterion seems to be trivially satisfied, but this turns out to be deceptive. There is one trivial ‘way in which this criterion is violated: the genetic code is degenerate. How ever, this s nitpicking. More importantly, noncoding regions of the DNA can vary without any effect on the final protein product. In eukaryotes, these noncoding regions occur within as well as between genes. [ have argued elsewhere (Sarkar 1996a, b) that because of this (and other com- plexities), a DNA sequence and the genetic eode cannot be used by then selves to predict protein sequences. Maynard Smith argues that this is misleading because biologists routinely make such predictions. The point | was making was that we need more than just a sequence and the code— for instance, the boundaries between coding and noncoding regions. These boundaries cannot always be identified by sequence alone and my original point remains correct. However, this does not prevent us from saying that some parts of the genomic DNA sequence carry information in the rele- ‘vant sense—but that is all we are left with (ii) semioricity: scan be viewed as a sign for o in the sense that the theory which provides the mechanisms by which s produces « allows that an different from s could have been the sign for &. DNA sequences are signs for proteins because (as far as we know) the genetic code isa frozen accident. The intuition here is that of arbitrariness (as Maynard Smith notes); the problem is that this eriterion seems to deny even the mild de- terminism invoked by criterion (). The underlying chemistry—unless quantum mechanies is involved in some way of which we have no idea—INFORMATION IN GENETICS AND DEVELOPMENTAL BIOLOGY 211 requires that a different RNA transcript at the ribosome produce a dif ferent protein. The point is that, in an important sense, the explanatory theory providing the mechanisms for translation does not preclude a di ferent genetic code. Some organisms have a (slightly) different genetic code (Fox 1987). Once we understand how s is a sign for 6, we can say that, if s produces a different o, there is a mistake. This, as Sterelny and Griffiths (1999, 104) argue, is a critical desideratum for the concept of information that we are trying to capture. It seems to me that an additional criterion of intentionality is unnecessary: semioticty already captures the sense in which s is about 6. Maynard Smith not only adopts intentionality as a separate criterion but tries to ground it entirely in natural selection. But this is hyper-selectionism: surely we should be able to say that some DNA. sequence contains information for a protein, or was mis-ranslated, and 0 on, irrespective of whether it was selected for, against, or is neutral The critical empirical fact, in our genetic context, is that semioticity of this sort is present in many other biological entities than DNA. To take just cone example: the (arbitrary) D-stereoisomerism of amino acid residues in some naturally occurring polypeptides (not synthesized on ribosomes) ‘make them information-carrers. A second locution we have to unpack is that “only s contains infor- mation for 6.” Afterall, what makes Maynard Smith's position interesting is the claim that only DNA contains biological information. To capture this locution, a third criterion must be added to the other two: ii) reverse differential specificity: if « is different from 0’, then s must be different from s', This is the criterion that was the target of much of ry earlier criticism. In eukaryotic genetics itis routinely violated. Take just one example: alternative splicing allows the generation of two different proteins from a single DNA sequence. There are many others. ‘The most serious problem with Maynard Smith's account is that it relies, only on criterion (i), including intentionality as an independent criterion. Consequently it does not escape from counter-examples that rely on the problem of satisfying criteria (i) and (ii). Moreover, even if only criterion (i) is used, examples such as D-stereoisomerism show that information does not reside only in DNA sequences. Consequently we cannot maintain both that there is a conceptually respectable concept of information in genetics and that the genomic DNA. is the sole purveyor of information. At least one of these two assumptions must be given up; my inclination is to abandon the latter. This has the ‘consequence that the Central Dogma turns out to be false, but it can be replaced by a palatable, and attractively less grandiose, claim that DNA. sequences specify protein sequences in a way that the latter do not specify the former. There is no need to bemoan the dissolution of the Central Dogma: it plays no cognitive role in contemporary biology.212 SAHOTRA SARKAR Maynard Smith (1965, 67; reiterated in §2 of the article in this issue) must bear some responsibility for the introduction ofa fallacious inference ‘that has often been used to suggest that the Central Dogma is central to biology, viz., that it explains the non-inheritance of acquited characters. Acquired characters are sometimes inherited (Landman 1991, Jablonka and Lamb 1995), usually not, depending on the mode of inheritance in the system. Maynard Smith (1990) has himself constructed elegant models ‘of epigenetic inheritance. The status of the Central Dogma, which is sup- posed to operate at the molecular substratum common to all biological systems, is independent of whether the system allows the inheritance of acquired characters. It follows ipso facto that the two issues are indepen- dent and neither ean be construed as a basis for the other. Turning, finally, 1o developmental biology, this is where Maynard Smith's contribution is potentially most significant. There are two separate claims involved: (that an informational framework is invading devel- ‘opmental biology just as it once did genetics: and (i) that the relevant information resides in the genomic DNA. What was said above argues against the second claim, but there is an additional point to be made. Maynard Smith's position is at least partly motivated by a desire to make a sharp distinction between nature and nurture, with the former being conflated with the genome. Ascribing information solely to the genomic DNA is supposed to underscore this distinction. This position is particu- Jarly surprising coming from Maynard Smith, since it denies a long tra- ition involving, among others, Hogben (1933) and Maynard Smith's ‘mentor, Haldane (1936, 1946), which emphasizes the interaction between, and relativity of, nature and nurture in phenogenesis. Leaving aside the point that information may reside in moieties other than DNA, itis far from clear why Maynard Smith feels that a sharp nature-nurture distine- tions necessary, or even helpful, n the pursuit ofa theory of development. Returning to the first claim, Maynard Smith’s contention is based on the example of the eyeless mutation in the mouse. The unmutated allele induces the formation of a compound eye ina fruitly leg, Maynard Smith interprets this induction as the allele sending a signal, “make an eye here ‘There are two problems with this: i) as Sterelny notes in his commentary, it is equally plausible to think that the unmutated allele receives infor- ‘mation from other alleles to make a compound eye. This hermeneutical relativity makes Maynard Smith's interpretation less than compelling; (even if we grant this interpretation, a few examples ofthis sort do not suflice to show that an informational framework makes sense of devel ‘opment. Maynard Smith’s position willbe shown to be correct if the prom- issory note can be cashed: if informational models eapture all—or atleast ‘most-—of the developmental data emerging from experiments. The Future will tell. However, given the continued failure to develop a comprehensiveINFORMATION IN GENETICS AND DEVELOPMENTAL BIOLOGY. 213 theory of eukaryotic gene regulation based on prokaryotic analogues, 1 remain pessimistic. While some recent advances suggest that eukaryotic -gene regulation can sometimes be profitably modeled similarly to prokary- otic (ee Ptashne 1992), the variety of the available developmental data seems to give little ground for optimism (see Gilbert 1997). REFERENCES. Fox, T.D. (1989), “Natural Variation inthe Genetic Code", Amma Review of Geneties 21 6-31 Gilbert, S:F. (1997, Developmental Biology, Sth ed, Sunderland: Sinauer. Haldane, 1, B.S. (1936), "Some Principles of Causal Analysis in Genetics”, Erkemnnis 6 6-357, —~" (1946), “The Iteration of Nature and Nurture", Annals of Eugenics 1: 197-208, Hoghen, L. (1938), Nanure and Nurture. New York: Norton. Jablonka, E-and M. J. Lamb (1995, Epigenetic Inheritance and Evolution. Oxford: Oxford University Pres Kimura, M. 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