The Biological Future of Theoretical Physics Cur.s Callan Princeton University The very success of theore.cal physics in elucidang the structure of maer at the smallest scales, and of the universe at the largest scales, has made the future course of this discipline uncertain. At the same .me, the new ability of biological experiment to produce massive data is creang an urgent need for mathemacal frameworks in biology of the kind theore.cal physics has tradi.onally provided for physical science. These overlapping “crises” offer a golden opportunity for both disciplines to collaborate. I will expand on this theme, and sketch some specific examples of how theore.cal physicists are taking up this challenge. Who am I and why am I here? (w. apologies to Adm. Stockdale!) • I used to be a theore.cal par.cle physicist .. wri.ng papers like these: – Worldsheet Approach to Hetero.c Solitons and Instantons – Brane Dynamics from the Born-Infeld Acon – D-Brane Approach to Black Hole Quantum Mechanics. • But about ten years ago I started wri.ng papers like this: – Precise physical models of protein-DNA interac.on from high-throughput data – Informaon capacity of gene.c regulatory elements – Quan.fying selec.on in immune receptor repertoires • I am occasionally asked why I did this .. why did I “switch” to biology? – Not really because of any dissasfac.on with “main stream” theore.cal physics – Rather that pioneering biophysics colleagues (Bialek, Leibler) showed me that biology poses fascinang ques.ons for theory, and that the .me is ripe to aack them. • On reflec.on, though, it seems to me that biology and theore.cal physics have both come to a “crisis” that offers opportuni.es for both subjects. – My purpose tonight is to explain what I mean by this and to give you some concrete no.on of what theore.cal physicists are doing to respond. – I am here for the “Quan.tave Immunology” program (largely populated by theore.cal physicists) … my talk may explain why KITP is hos.ng such an event! Theore.cal Physics is Hugely Ambi.ous! It comprehends a lot. But some things escape its net: It describes how It describes the our universe behavior of inanimate came from the maer everywhere in Big Bang. our universe Thanks to NASA for the image The primary task of theoretical physics • To discover the fundamental, mathemacally expressed, Laws of Nature … as well as the “stuff” that obeys those laws .. in our universe (?). • These laws are valid within broad domains of phenomena and are in some sense “simple”; o^en fit handily on a postcard in shorthand form. • They were discovered in steps over recent centuries: – Newtonian mechanics & the gravitaonal force law (1670s) – Maxwell’s equaons of e&M (1860s) (and special relavity) – einstein’s general relavity (gravity as dynamical geometry) (1910s) – Quantum mechanics of electrons, atoms and molecules (1920s) – Quantum field theory and the Standard Model of everything (1970s) – “Big Bang” cosmology and a theory of the origin of our universe (2000s) • The culminaon of this development, the outcome of an explosion of discovery over the last 50 years, is the Standard Model of our world. – It is a precise mathemacal theory whose scope is … everything. – Some modesty is of course in order, but a victory lap or two is jus.fied. The Standard Model Consensus Fi^y years ago, there was no agreement on the fundamental nature of maer, on the physical theory governing that maer, or how the universe worked. Over .me, a “picture” and “theory” of maer and the universe came together (on two tracks): The par.cle physics track: A specific quantum field theory of the strong, weak and electromagne.c interac.ons between three “generaons” of point-like quarks and leptons; forces mediated by “gauge” gluons, photons, and the W/Z, with a Higgs boson doing symmetry breaking and mass generaon. Some 21 parameters (that could have been different) completely define the whole thing. Total agreement with many and varied experiments. The search for “cons.tuents” could stop here! The cosmology track: The recession of the galaxies suggests a “Big Bang” origin for the universe. The exploraon of its thermal “aerglow” (cosmic microwave background now at 2.75 K) revealed how the universe was cons.tuted in its earliest seconds of existence. Two surprises came out: the maer of par.cle physics is there, but is a minority player in the energy census: “dark maer” and “dark energy” dominate, but seem to act on the world only via gravity. This explains many puzzles of astronomy and also how today’s universe coalesced from the Big Bang The Standard Model of particle physics We have a very specific quantum field theory of how these point par.cle cons.tuents interact. The quarks are not seen directly: they are “confined”, combining in triples to make neutrons, protons etc. Our ability to calculate specific results from in this theory is limited, but good enough to convince us of its accuracy. Graphic credit: Par.cle Data Group The Standard Model of cosmology We can see photons emi7ed back to here Density ripples start to grow about here BIG BANG!!! A remark on the method of modern physics Millions of data points in ….. A few model parameters out! In cosmology/par.cle physics we do not directly measure the “hidden variables” of interest. Given an underlying, simple, model for how they affect the noisy data sets we do measure, we use stas.cal inference to “see through the noise” into the underlying physical parameters. This is a nearly universal method in modern physical science. One of my messages is that biology is now entering this era. Massive resources were deployed to get here The WMAP satellite The LHC accelerator at CeRN The CMS detector at the LHC This consensus picture is the outcome of an enormous effort (intellectual, experimental, sociological, financial) carried out over a period of 50 years. This sustained effort to answer what amounts to a ques.on of “natural philosophy” is remarkable .. and a credit to the human race. Where does theoretical physics go from here? • There are loose ends, but the historic program has succeeded so well that it has put its own con.nuaon into serious ques.on! • On the conceptual side, we seem to be at a turning point: – Once you are down to point par.cle cons.tuents of maer, you can’t really “explain” them in terms of more fundamental en..es: Is the game over? – There could be more massive point cons.tuents that even the LHC can’t see (and neutrino masses and dark maer point that way … obscurely). – Going deeper, in the light of string theory, we can see a natural reduc.onist limit point at the Planck scale .. way beyond direct experimental reach. • On the experimental side, exploring the relevant energy scales is increasingly costly, and surely approaching societal limits – The LHC is speaking; we hope for surprises, but we may “only” get a comple.on of the Standard Model, not a view of deeper physical law. – Looking beyond the Standard Model, or into inflaon, the future experimental projects are in the 1010 euro class … will taxpayers support them? – And, in the long run, theory without experiment is not sustainable. • So, life is going to be hard for fundamental theory from here on … Not impossible, to be sure, but are there other paths to take? The “other agenda” of theoretical physics • Discovering the fundamental laws is the historic core mission of theore.cal physics .. but that’s not all theore.cal physicists do! • In addi.on, we want to explain phenomena that are not directly baked into the fundamental laws … we call them emergent phenomena. – e.g. show that superconduc.vity (a macroscopic quantum effect) follows from the Schrödinger equaon for many electrons moving in a host atomic lace. – Or prove “confinement”, namely that the quarks of QCD can never be seen outside the hadrons (neutrons and protons) of which they are cons.tuents. • Be7er yet, we want to predict unknown emergent phenomena (i.e. derive them from fundamental law) before their experimental discovery: – Our record on this is not good. The quan.zed Hall effect is a striking quantum effect and could have been predicted. But it wasn’t .. a failure of imaginaon? – It doesn’t happen o^en, but it is not impossible: cosmologists did an.cipate Big Bang phenomena like CMB. Topological insulators were also an.cipated. • Good news is that we have (so far) found that our fundamental laws are able to explain new “emergent” phenomena. Usually aer the fact … Life: the “emperor” of all emergent phenomena • There are phenomena of fundamental importance which are certainly described by the already-known fundamental laws … but whose derivaon from those Laws completely escapes us. • The chief of these is Life. There are good reasons why it is .me to bring the domain of living maer into the realm of predic.ve, mathemacal, science: – How “living maer” is governed by physical principles has always been a ques.on for theore.cal physics ... but inadequate data .ed our hands – The ongoing explosion of quan.tave biological data (hi-throughput sequencing, expression profiling, …) has created a totally new context for this issue – On the biology side, it is becoming clear that we need mathemacal frameworks (like we have in physics) to extract meaning from the growing mass of data. • Developing this kind of theory is what theore.cal physicists do .. and it is a major intellectual challenge, on a par with our quest for fundamental laws – A quick tour of the past, present and future of this enterprise will, I hope, give you a more concrete idea of what I am talking about • It used to be said that there is no theory in biology … the day may be coming when there is no biology without theory! The theoretical physics of Life: past Historical instances of using theore.cal principles to illuminate and make predic.ons about a broad class of biological phenomena include: • Schroedinger’s “What is Life?”: genes are carried by a polymer molecule – Basic quantum mechanics and the known rate of induc.on of mutaons by x- rays (Morgan, 1910) led him to the conclusion that genes had to be carried by a molecule.