These are not the only questions I can think of but they are certainly some of my favorites.

1. Will we ever understand quantum mechanics?

Richard Feynman famously quipped that “I can safely say that nobody understands quantum mechanics”. The situation has not fundamentally changed since Feynman’s time, but the question has become even more pressing. This is because no other scientific theory presents such an enormous gap between successful prediction and deep understanding as quantum mechanics. Starting in the 1970s, some of the most bizarre implications of quantum theory – most prominently the “spooky” (in Einstein’s words) phenomenon of entanglement – have been verified by precise experiments. Last year’s Nobel Prize was awarded in part for using these strange properties to trap ions and atoms.

And yet we have no clue how any of the fundamental facts of quantum mechanics including wave-particle duality, entanglement, quantum tunneling or the double-slit experiment – that disarmingly simple setup which, in Feynman’s words, contains “the only mystery of quantum mechanics” – actually work. The quantum world continues to be a fairyland that defies common sense and where anything can happen. For decades most physicists have used quantum mechanics, but nobody has convincingly shown us where it comes from. Einstein may have gone against the grain of experiment but he was right in feeling a decided sense of unease regarding the reality which the weird quantum universe encapsulates. Narrate the parable of Schrodinger’s cat and you will be met with laughs and smirks, but the laughter cannot obliterate the deep anguish of physicists, a feeling that their most successful theory of nature is, at its deepest level, a hazy ball of mist.

Since the theory was first developed there have been dozens of alternative interpretations of what it all means, from the classical Copenhagen interpretation to the simple but mind-bending many-worlds interpretation of Hugh Everett. And yet we are no closer to teasing out a winner among these bold conjectures. Perhaps our only flaw is in trying to use ordinary common sense to grok what is fundamentally an otherworldly universe that does not lend itself to our frail minds. Perhaps we should continue to “shut up and calculate”, reap the tremendous agreement with experiment that the theory gives us and just stop bothering about what it all means. What we do know is that physicists and philosophers will keep on searching for the true reality underlying quantum mechanics, whether one exists or not.

2. Will we ever be able to detect single gravitons?

Gravitons are hypothetical elementary particles that mediate the force of gravity within the framework of quantum field theory. Their existence is necessary for forging a meld between quantum mechanics and Einstein’s general theory of relativity, a quest that has been going on for fifty years. This quest has produced reams of equations and elegant experiments with no definitive answer (it’s worth noting that the search for individual gravitons is different from the search for gravitational waves, a purely classical endeavor). LIGO and LISA are only two of the more ambitious projects designed toward this goal. Until now none of these experimental setups have been able to detect gravitational waves, but with individual gravitons it might be a completely different ball game.

Over the last few years Freeman Dyson, Tony Rothman and Stephen Bough among others have written papers demonstrating that it might be impossible to detect single gravitons if anything resembling realistic physics is taken into account. They have analyzed existing approaches and concluded that the scale of the experimental apparatus in these approaches might have to approach absurdly unrealistic limits if they are to successfully detect gravitons. Gravity thus might remain a statistical bulk property like temperature or pressure, irreducible to the properties of individual particles. If this is indeed true there might forever be an ‘iron curtain’ of ignorance erected between the quantum and classical worlds. It’s a possibility that is maddening, and one that should certainly keep any physicist with even a modest ambition of unifying the known forces of nature awake.

3. Will we ever understand emergence?

In 1972, Nobel Laureate and brilliant “curmudgeon” of physics Philip Anderson lit a firecracker and threw it into the basement of the temple of reductionist physics. In a Science article titled “More is Different” Anderson underscored how the difference between understanding the behavior of individual particles  – something that physics has wildly excelled at – and collections of particles is not just quantitatively different but qualitatively so. In his article Anderson was appealing to the universal phenomenon of emergence, a term that’s often loosely thrown around but which is very much real. Simply put, emergence refers to the fact that the behavior of groups of entities cannot be predicted from the behavior of the individual entities alone.

Emergent phenomena bestride our world, from the properties of metals to termite nests to flocks of starlings to the global economy. In one sense all of chemistry, biology and sociology is a hierarchical clustering of emergent behavior. Physics has failed to explain this central and deep mechanism in the workings of the natural world. In fact as Anderson has noted, physics cannot explain emergence even in its own narrow domain, for instance in the field of superconductivity. Eighty years ago Paul Dirac noted that the laws of physics as then understood could explain “most of physics and all of chemistry”. And yet we don’t understand how to make the logical leap from the behavior of a quark to the behavior of a strand of DNA composed of multitudes of quarks. Understanding emergent behavior may be the single most important goal for physicists if they want to understand how physics connects to other sciences and to the human world. Without a grasp of emergence physics will remain a narrowly understood and applied science, of scant use to other practitioners.

4. How will we keep particle physics alive?

This is a question which is as social as it is scientific, and yet it is one that should keep particle physicists worried and awake. Last year in the New York Review of Books, Steven Weinberg noted that the biggest discovery at the LHC might not be the Higgs boson but in fact would be something unexpected, something that really overturns our knowledge of the universe as enshrined in the Standard Model. To make this discovery we would probably need to go to even higher energies, which in turn would entail even bigger particle colliders likely costing tens of billions of dollars. What is worse is that it might be impossible to do these kinds of physics experiments using cheap equipment and small teams.

In the face of economic downturns, political gridlock and widespread public embrace of pseudoscience it will be a tremendously uphill battle for particle physicists to expect support for the next multibillion-dollar physics experiments. The long history of failed projects like the SSC and even successful ones like the Hubble Space Telescope demonstrates the careful coalition building, favorable economic forces and political wisdom that need to align for taking a Big Physics experiment all the way to success. When it’s all over it looks streamlined and obstacle-free, but the fact is that a single item demoted in Congress’s budget can kill such dreams. The lack of support for Big Physics projects in particle physics and the impossibility of practicing their trade on a smaller scale might mean that an entire generation of particle physicists is unable to pursue the biggest mysteries of their field. It’s a thought that should keep practitioners in the field very worried indeed.

5. Will physics help us understand the nature of consciousness?

This is a question that’s somewhat related to question 3 above but its profound significance makes it deserve separate discussion. Beyond understanding things like the origin of the universe, understanding the origin of the very consciousness that allows us to understand the origin of the universe is rightly regarded as the most important question in science. We are quite certainly a long way from even attempting to answer it, but neuroscience is a young and vibrant discipline full of exciting possibilities. The physics question about the brain which we want to answer is: Is there more or less direct evidence of the principles of quantum mechanics operating in the workings of the brain at multiple levels, from neurons to behavior. In one sense this question is asking what it exactly is that connects the micro world to the macro world, a line of investigation going back to the beginnings of science.

At least a few scientists have tried to make a dent in the question. A few years ago Roger Penrose and Stuart Hammerof proposed that the switching of protein assemblies called microtubules in the brain could be seen as a direct example of the entangled superposition of elementary particles. This provocative thesis however received a major blow from the work of Max Tegmark who demonstrated that at ordinary temperatures any kind of particle entanglement in the brain would undergo very rapid decoherence, a kind of averaging out that would essentially sever the entangled states-observable biochemical properties connection. But the question seems far from settled; other work has demonstrated links between superposition and important phenomena like photosynthesis and electron transfer in proteins. Perhaps one day we will be able to explain how memory forms at the molecular level because of entanglement. Or perhaps explaining consciousness will be inherently impossible, as some physicists like Edward Witten seem to think. Either way, there is no doubt that contemplating the connection between physics and consciousness is one of the foremost conundrums that physicists will keep dreaming about.