Cosmological inflation, water in proteins and JFK: The enigma of ignorance

I was immersed in the American Chemical Society's national meeting in Dallas this week, which meant that I could not catch more than wisps of the thrilling announcement from cosmology on Monday that could potentially confirm the prediction of inflation. If this turns out to be right it would indeed be a landmark discovery. My fellow Scientific American blogger John Horgan - who performs the valuable function of being the wet blanket of the network - prudently cautions us to wait for confirmation from the Planck satellite and from other groups before we definitively proclaim a new era in our understanding of the universe. As of now this does look like the real deal though, and physicists must be feeling on top the world. Especially Andrei Linde whose endearing reaction to a surprise announcement at his front door by a fellow physicist has been captured on video.

But as social media and the airwaves were abuzz with news of this potentially historic discovery, I was sitting in a session devoted to the behavior of water in biological systems, especially in and around proteins. Even now we have little understanding of the ghostly networks of water molecules surrounding molecules that allow them to interact with each other. We have some understanding of the thermodynamic variables that influence this interaction, but as of now we have to dissect these parameters individually on a case-by-case basis; this is still no general algorithm. Our lack of knowledge is hampered by both an overarching theoretical framework and computational obstacles. The water session was part of a larger one on drug design and discovery. The role of water in influencing the binding of drugs to proteins is only one of the unknowns that we struggle with; there are dozens of others factors – both known unknowns and unknown unknowns – which contribute to the behavior of drugs on a molecular level. We have made some promising advances, but there is clearly a long way to go.

Sitting in these talks, surrounded by physicists and chemists who were struggling to apply their primitive computational tools to drug design, my thoughts about water briefly juxtaposed with the experimental observation of cosmological inflation. And I could not help but think about the still gaping chasms that exist in our understanding of so many different fields.
Let’s put this in perspective: We have now obtained what is likely the first strong experimental evidence for cosmological inflation. This is a spectacular achievement of both experiment and theory. If true no doubt there will be much well deserved celebration, not to mention at least one well deserved Nobel Prize.

But meanwhile, we still cannot design a simple small organic molecule that will bind to a protein involved in a disease, be stable inside the body, show minimum side effects and cure or mitigate the effects of that disease. We are about as far away from this goal as physics was from discovering the Big Bang two hundred years ago, perhaps more. Our cancer drugs are still dirty and most of them cause terrible side effects; we just don’t have a good enough scientific understanding of drug behavior and the human body to minimize these effects. Our knowledge of neurological disorders like Alzheimer’s disease is even more backward. There we don’t even know what the exact causes are, let alone how we can mitigate them. We still waste billions of dollars in designing and testing new drugs in a staggering process of attrition that we would be ashamed of had we known something better. And as I mentioned in my series of posts on challenges in drug discovery, even something as simple as getting drugs past the cell membranes is still an unsolved problem on a general level. So is the general problem of figuring out the energy of binding between two arbitrary molecules. The process of designing medicines, both on a theoretical and an experimental level, is still a process of fits and starts, of Hail Mary passes and failed predictions, of groping and simply lucking out rather than proceeding toward a successful solution with a trajectory even resembling a smooth one. We are swimming in a vast sea of ignorance, floundering because we often simply don’t have enough information.

The fact remains that we may have now mapped the universe from its birth to the present but there are clearly areas of science where our knowledge is primitive, where we constantly fight against sheer ignorance, where we are no more than children playing with wooden toys. In part this is simply about what we call domains of expertise. There are parts of nature which can bend to our equations after intense effort, and yet there are other parts where those equations almost become pointless because we cannot solve them without significant approximations. The main culprit for this failure concerns the limitations of reductionism which we have discussed many times on this blog. Physics can solve the puzzle of inflation but not the conundrum of side effects because the latter is a product of a complicated emergent system, every level of which demands an understanding of fundamental rules at its own level. Physics is as powerless in designing drugs today  - or in understanding the brain for that matter - as it is successful in calculating the magnetic moment of the electron to ten decimal places. Such is the paradox of science; the same tools which allow us to understand the beginnings of the cosmos fail when applied to the well-being of one of its tiniest, most insignificant specks of matter.

Scientists around the world are calling the latest discovery “humbling”. But for me the finding is far more humbling because it illuminates the gap between what we know and how much more we still have to find out. This may well be a historic day for physics and astronomy, but there are other fields like chemistry, neuroscience and medicine where we are struggling even with seemingly elementary problems. As a whole science continues to march on into the great unknown and there remains an infinite regression of work to do. That’s what makes it our impossibly difficult companion, one whose company we will be confronted with for eternity. While we have reached new peaks in some scientific endeavors, we have barely started clearing the underbrush and squinting into the dark forest in others. It is this ignorance that keeps me from feeling too self-congratulatory as a member of the human species whenever a major discovery like this is announced. And it is this ignorance that makes our world an open world, a world without end.

A comparison, however, provided a silver lining to this feeling of lack of control. Catching a break in the day’s events I strolled down Houston Street after lunch. Almost fifty-one years ago a car drove down this street and then slowed down for the sharp left turn on Elm Street. At the intersection stood the Texas Book Depository. Three shots rang out, a young President’s life was snuffed out and the river of American history changed course forever. All because of the rash actions of a confused and deranged 23-year old former marine. Looking out of the sixth floor window I could see how a good marksman could easily take the shot. What really strikes you however is the perfect ordinariness of the location, a location made extraordinary in space and time because of a freak accident of history. It compels us to confront our utter helplessness in the face of history’s random acts. Oswald got lucky and left us floundering in the maelstrom of misfortune.
 
But a cosmic perspective may help to assuage our incomprehension and provide salve for our wounds. Carl Sagan once said that if you want to make an apple pie from scratch, you have to first invent the universe. That fateful bullet on November 22, 1963 was the result of an infinitude of events whose reality was energized into potential existence by the same inflation that we are now exploring through ground and space-based telescopes and the ingenuity of our scribblings. There is something reassuring in the fact that while we still do not understand the enigma of human thought and feeling that dictated the trajectory of that bullet, we can now at least understand where it all started. That has to count for something.