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NKS and Cancer Ilan R. Kirsch, M.D. 23 April 2004 NKS 2004.

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Presentation on theme: "NKS and Cancer Ilan R. Kirsch, M.D. 23 April 2004 NKS 2004."— Presentation transcript:

1 NKS and Cancer Ilan R. Kirsch, M.D. 23 April 2004 NKS 2004

2 Ph.D. Physics Princeton (John Wheeler) subsequently M.D., Harvard Internal Medicine, Massachusetts General Hospital (MGH) Currently a distinguished Physician at MGH Background to dissenting opinion #1:

3 I know very, very little about this area. I am aware of Wolfram and, (…), my initial reaction was to think that it was an elaborate fantasy. Particle physicists like to say that the theory of complexity is the most exciting new thing in science in a generation, except that it has the one disadvantage of not existing (Steven Weinberg, New York Review of Books, October 24, 2002)

4 Asst. Prof. Computer Sciences - MIT subsequently M.D., Harvard Emergency medicine FDA Now an independent consultant Background to dissenting opinion #2:

5 Ed Fredkin is one of the 2 or 3 smartest people Ive ever met, and what Ive heard about Wolfram is consistent with his being equally clever. Still, I was skeptical about Fredkins stuff half my life ago, and Im skeptical about Wolframs stuff now. Unfortunately, getting into a discussion of this material is a little like talking about the predictions of Nostradamus, or about nonstandard theories of the assassination of John Kennedy. The skepticism is based on a simple meta-argument: The new theory, if it is correct, should be able to predict things we didnt already know, not just fit a model with many, many degrees of freedom to an arbitrary selection from the great body of old data.

6 There is something unique about theoretical physics, making me even more skeptical about extending the cellular-automata model to other areas. In physics, most people seem to believe that the reality is going to turn out to be simple (in the sense of having only a few different kinds of components), but weirder and weirder, perhaps to the point of incomprehensibility to humans. Maybe cellular automata will be useful here, as yet another (misleading, but not totally misleading) metaphor. On the other hand, in most other parts of science everyone seems to believe that the reality is going to stay complex, less and less weird as knowledge grows, but just too damn detailed. Im not sure that metaphors have ever been of very much value in such circumstances.

7 Cancer as a starting point for historical/philosophical inquiry Cancer as a basis for the study of growth and development Cancer as a basis for the study of evolution Cancer as a model of targeted therapy Cancer as a platform for the implementation of technology Cancer as a microcosm of health care concerns

8 Cancer is a genetic disease caused by genetic instability

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10 Adenoma Carcinoma Sequence Normal Early Intermediate Advanced Cancer Mucosa Adenoma Adenoma Adenoma 5-20 yrs5-15 yrs APC, bcl -2, c- myc, Hypomethylation, ß-catenin K-ras SMAD 2, SMAD 4 p53 MSH2,MLH1, MSH6,PMS1,PMS2 Adapted from Ilyas et al. Eur. J. Cancer 1999; 35:335-351 and Kelloff et al. Oncology 1996; 10:1471-1484

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12 The nature and essence of mutational events…

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14 SKOV-3

15 Karyotypic complexity Ploidy Numerical abnormalities Structural rearrangements

16 NCI60 panel of cancer cell lines

17 +3n +5n +4n +3n +2n Ploidy

18 Numerical abnormalities

19 NH correlates with the number of numerical aberrations in the cell line (r=0.53, P<0.01)

20 Structural rearrangements 1 rearranged chromosome – ACHN 45rearranged chromosomes – NCI-H322M

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22 Karyotypic complexity of the NCI-60 (organized by lineage)

23 Karyotypic complexity of the NCI-60 (organized from less to more)

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26 Todd Rowland - Wolfram Science

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28 Rule 250 with mutated cell (white to black) creating BBB configuration

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30 Cancer Risk is a Function of: inheritance and inherent physiology environmental influences randomness (fate)

31 Is cancer (and therefore all biology) predetermined?

32 Does a probabilistic model partially solve the problem or just reduce the problem from the level of a pattern of cells to the level of a single cell?

33 There is something unique about theoretical physics, making me even more skeptical about extending the cellular-automata model to other areas. In physics, most people seem to believe that the reality is going to turn out to be simple (in the sense of having only a few different kinds of components), but weirder and weirder, perhaps to the point of incomprehensibility to humans. Maybe cellular automata will be useful here, as yet another (misleading, but not totally misleading) metaphor. On the other hand, in most other parts of science everyone seems to believe that the reality is going to stay complex, less and less weird as knowledge grows, but just too damn detailed. Im not sure that metaphors have ever been of very much value in such circumstances.

34 Deep simplicity: Chaos, Complexity, and the Emergence of Life by John Gribben (biology is as fundamentally predictable as physics) The Fabric of the Cosmos Space, Time, and the Texture of Reality by Brian Greene (physics (e.g. quantum mechanics) is as fundamentally unpredictable as biology)


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