The End of Industrial Productivity?

A long time ago when I was a fledgling student studying college physics and chemistry, I ventured into the haunting, dark recesses of our library which housed science classics. As I browsed through those classic volumes by Kelvin, Einstein, Raleigh and Medawar and as the dust gathered on to my clothes, I saw a 1930s book titled "Electronics" by Bill Shockley, the Bill Shockley of the legendary Bell Labs who had played a key part in the invention of the transistor. As I eagerly opened the pages of the book in a cloud of dust, I was surprised to see equations covering the pages. Almost no diagrams of circuits and components found in modern electronic texts, but reams and reams of quantum mechanics detailing calculations of current density and electron transport. It was then that I realised that that singular device, the transistor, had its conceptual roots in fundamental physics. Without quantum mechanics and the basic physics of electron flow the transistor may never have been possible. The experience drove home a fundamental point for me; without the roots of basic research that nourish and inspire, there are no fruits of applications possible.

Sadly, the same Bell Labs which exemplified all that basic research stood for and which for a long time was the greatest industrial basic research laboratory in the world, is now getting divorced from its roots. An article in Nature documents the sad case of the once scientific giant whose basic physics research team has dwindled to four scientists, an extremely sad state of affairs. The division that generated six Nobel Prizes for basic and breakthrough research has now shrunk to basically non-existence. Unfortunately similar trends are seen elsewhere. The consequences for future technology cannot be anything but dire. In the last fifty years almost every one of the technological innovations that we take for granted, including the computer, laser, transistor and digital memory to name a few have come from research in basic science. Nobel Prizes have been gathered in the dozens by scientists who worked on these discoveries. Where Bell Labs scientists won Nobels for the laser and the transistor, IBM researchers in a grand encore performance won two Nobels in the 1980s- one for the invention of the Scanning Tunneling Microscope (STM) and one for high-temperature superconductors. Most recently it was academic scientists who won the Nobel for discovering Giant Magnetoresistance, the phenomenon that powers our iPods and computers.

This trend is hardly surprising however. As companies move increasingly towards satisfying the bottom line for the next quarter and pleasing shareholders, they are having scant patience and even more scant funding for basic research. While product development may diversify in the short term, it's like water flowing over a long distance which is slowly cut off at the source; while the flow of water will persist and even appear normal for some time, it is undoubtedly going to shut down after a while. With their current policies of downsizing even applied departments, let alone ones doing basic research, companies are headed for a downfall in new product innovation in the long term. And when I mean "new", I don't mean just another version of Windows or another MP3 player. I am talking about the kind of innovation that leads to a paradigm shift, an outburst of raw data resulting from a single discovery that drives ideas, applications and services for many future decades. Transistors, lasers and STMs all revolutionized the practice of science and technology.

Such innovation can be possible only if we go back to the roots of technology. After all, every technological invention that we are aware of is ultimately based on the laws of physics and chemistry. It is only by exploring these laws that we can discover new applications for them. Consider organic semiconductors and quantum computing that will promise untold increases in computer power that will overcome Moore's Law, or number theory and quantum entanglement that will allow for foolproof data encryption. If the history of basic industrial research has taught us anything, it is that only by pushing the frontiers of the fundamental laws of science can one achieve windfalls of industrial innovation. And yet it is precisely this kind of research that industry is ignoring, at its own and our great peril.

Sadly, science is not like cocaine, promising instant rewards. It treads a risky path, strewn with blind alleys and failures. And yet treading this path is an essential series of steps to achieve the few gems scattered on it. Only in the uncertainty of scientific discovery lies great opportunity. But companies, whether they are hardware developers or pharmaceutical innovators, want the gems without having to vet the stones. Pipe dreams. The greatest entrepreneurs of our time, Warren Buffet and Bill Gates, became who they are by engaging in a philosophy of investment. Invest now, reap the rewards tomorrow. Industry seems to have forgotten this essential philosophy of promising productivity. If this trend continues for long, the verdant branches of the tree that we see today, already divorced from their roots, will wither away to nothingness. And Bell Labs will be the star at the top that first toppled.

P.S. Excimer fumes too

Water and Amyloid Self-Assembly

One of the most significant, interesting and yet poorly understood effect in chemistry and biology is the hydrophobic effect. An important manifestation of its role in biology is invoked by the picture of two parallel hydrophobic plates with water between them that are slowly brought close to each other. At a certain distance called the 'dewetting distance', dewetting is observed and the water suddenly gets expelled out from them. Since nature abhors the resulting vacuum, the two hydrophobic surfaces collapse and 'stick' to each other.

Bruce Berne and his colleagues at Columbia had hypothesized that such dewetting could be observed in biological systems. A remarkable dewetting transition in the protein mellitin and in other proteins in the PDB provided evidence. Now they and others investigate such possible roles of water in the formation of amyloid by molecular dynamics simulations. They focus on the central core peptide of the Alzheimer's Aß (1-42) peptide consisting of the 16-22 region. Since one of my projects involves investigation of the self-assembly of this segment, it is of particular interest to me. This oligopeptide is interesting because it seemingly is the smallest stretch of the bigger parent that also forms the characteristic cross-beta sheet structure of amyloid. Importantly, it is also soluble which means it is more amenable to structural characterization compared to the bigger peptide.

Berne's group investigates the role that water plays between two sheets of 16-22 consisting of nine peptides each. The MD simulations were run for 1 ns, a typical time for such systems. The dewetting critical distance was found to be 12.8 A. Compare this with the classic repeat distance between amyloid beta-sheets which is 9.9 A. Basically two types of phenomena were observed depending on different trajectories and conditions; dewetting, which means that water expulsion was followed by hydrophobic 'collapse', and the simultaneous occurence of expulsion and collapse. The latter phenomena can be interpreted as a kind of 'lubrication' effect that water has been hypothesized to play in the folding of proteins. They haven't been able to put a finger on which is the phenomenon in the 'real' system, but it at least seems plausible that dewetting could be observed in such systems. In the cases where dewetting is not the driving force for assembly, they dissect the interaction energies of different amino acid residues that contribute to the total energy, and find that the Phe-Phe energy contributes to the most.

From a methodological standpoint, the investigation is complicated by the fact that, as in other such studies, the results seem to depend on the methods used. This is a common characteristic of modeling and theoretical investigations. In this case, turning off the protein-water Van der Waals forces causes dewetting in every instant, perhaps not a surprising conclusion since there is now no attraction at all between the water and protein. Also, turning off the electrostatic forces caused no changes, which means that electrostatic attraction plays a small role in the system. Again probably not too surprising. A third observation is that the choice between the two phenomena depends on rather small changes in temperature.

The interpretations are also rendered ambiguous by the fact that amyloid surfaces and indeed most 'hydrophobic' protein surfaces are a poor approximation to two parallel hydrophobic plates. It should be noted that the attractive energy of interaction between two flat plates separated by a distance R is inversely proportional to the square of R. Compare this with the case of two spheres of radius R whose classical Van der Waals attractive energy is proportional to the sixth power of R. That means that in the case of the plates the attraction falls off much more slowly which can lead to significant dispersion forces even at relatively long separation.

This paper, while not leading to very novel or practical results, sheds light through detailed investigation of the possible role water can play between amyloid sheets. It again demonstrates the important effect that choice of methods and parameters can have on observations.

Krone, M.G., Hua, L., Soto, P., Zhou, R., Berne, B.J., Shea, J. (2008). Role of Water in Mediating the Assembly of Alzheimer Amyloid Aß (16-22) Protofilaments. Journal of the American Chemical Society, 130(33), 11066-11072. DOI: 10.1021/ja8017303

I exist

But I had to inevitably be away. I will reemerge very soon. Put it in the bank.