THE END OF INDUSTRIAL PRODUCTIVITY

More than ten years ago when I was a fledgling student studying college physics and chemistry, I ventured into the haunting, dark recesses of the library at Fergusson College which housed science classics. Few were allowed to venture into this section for fear that they might 'contaminate' the persona of the tomes which were kept there, tomes which stood magnificently alone in their dust and termite covered glory.

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.

CHARITY BEGINS IN THE UNIVERSITY

I mentioned in the last post how the transition time between academic science---->industrial technology needs to be accelerated, and it struck me that there were so many things in the conference which were being talked about by pharma scientists, which originally came from academia. Ketki has also mentioned the increasing collaboration between academia and industry, and I cannot help but think of technologies that people in pharma currently rave about, all of which were developed in academic laboratories.

Consider the recent use of NMR spectroscopy in studying the interaction of drugs with proteins, a development that has really taken place in the last five to ten years. NMR is essentially an academic field which has been around for almost fifty years now, originally developed by physicists who worked on radar and the bomb, and then bequeathed to chemists. It is the humdrum tool that every chemist uses to determine the structure of molecules, and in the last twenty years it was also expanded into a powerful tool for studying biomolecules. What if pharma had actually gone to the doorstep of the NMR pioneers twenty years back, and asked them to develop NMR especially as a tool for drug discovery? What if pharma had funded a few students to focus on such an endeavor, and promised general funding for the lab? What if Kurt Wuthrich had been offered such a prospect in the early 90s? I don't think he would have been too averse to the idea. There could then have been substantial funding to specially focus on the application of NMR to drug-protein binding, and who knows, maybe we could have had NMR as a practical tool for drug discovery ten years ago, if not as sophisticated as it is now.

Or think of the recent computational advances used to study protein-ligand interaction. One of the most important advances in this area has been the protocol called docking, in which one calculates the interactions that a potential drug has with a target in the body, and then thinks of ways to improve those interactions based on the structure of the drug bound to the protein. These programs are not perfect, but they are getting better every day, and now are at a stage where they are realistically useful for many problems. These docking protocols are based on force fields, which are programs that calculate the energies and structures of molecules. The paradigm in which force fields are developed, called molecular mechanics, was developed by Norman Allinger at UGA, and then improved by many other academic scientists. Only one very effective force field was developed by an industrial scientist named Thomas Halgren at Merck. During the 80s and 90s, force fields were regularly used to calculate the energies of simple organic molecules. One can argue that at that point they simply lacked the sophistication to tackle problems in drug discovery. But what if pharmaceutical companies had then channeled millions of dollars into these academic laboratories for specifically trying to focus on adapting these force fields for drug-like molecules and biomolecules? It is very likely that academic scientists would have been more than eager to make use of those funding opportunities and dedicate some of their time to exploring this particular aspect of force fields. The knowledge from this specific application could have been used in a mutually beneficial and cyclic manner to improve basic characteristics of the force fields. And perhaps we could have had good docking programs based on force fields in the late 90s. Pharma could also fund computer scientists in academia to develop parallel processing platforms specifically for these applications, as much of the progress in the last ten years has been possible because of exponential rise in software and hardware technology.

There are many other such technologies; fabrication, microfluidics, single molecule spectroscopy, which can potentially revolutionize drug discovery. All these technologies are being pursued in universities at a basic level. As far as I know, pharma is not providing significant funding to universities for specifically trying to adapt these technologies to their benefit. There are of course a few very distinguished academic scientists who are focused on shortening the science--->technology timeframe; George Whitesides at Harvard and Robert Langer at MIT immediately come to mind. But not everybody is a Whitesides or Langer, both of whom have massive funding from every imaginable source. There are lesser known scientists in lesser known universities who may also be doing research that could be revolutionary for pharma. Whitesides recently agreed to license his lab's technologies to the company Nano-Terra. Nano-Terra would get the marketing rights, and Harvard would get the royalties. There are certainly a few such examples. But I don't know of many where pharma is pouring money into academic laboratories to accelerate the transformation of science into enabling technology.

In retrospect, it's actually not surprising that future technologies are being developed in universities. In fact it was almost always the case. Even now-ubiquitous industrial research tools like x-ray crystallography, sequencing, and nuclear technology were originally products of academic research. Their great utility immediately catapulted these technologies into industrial environs. But we are in a new age now, with the ability to suddenly solve many complex problems being manifested through our efforts and intellect. More than at any other time, we need to shorten the transition time between science and technology. For doing this, industry needs to draw up a checklist of promising academic scientists and labs who are doing promising research, and try to strike deals with them to channel their research acumen into specifically tweaking their pet projects to deliver tangible and practical results. There would of course be new problems that we would need to solve. But such an approach in general would be immensely and mutually satisfying, with pharma possibly getting products on their tables in five instead of ten years, and academia getting funded for doing this. It would keep pharma, professors, and their students reasonably happy. The transition time may not always be speeded up immensely. But in drug discovery, even saving five years can mean potentially saving millions of lives. And that's always a good cause isn't it.