Technological convergence in drug discovery and other endeavors

You would think that the Wright brothers’ historic flight from Kitty Hawk on December 17, 1903 had little to do with chemistry. And yet it did. The engine they used came from an aluminum mold; since then aluminum has been a crucial ingredient in lightweight flying machines. The aluminum mold would not have been possible had industrial chemists like Charles Hall and Paul Héroult not developed processes like the Hall-Héroult process for refining the metal from its ore, bauxite. More elementally, the gasoline fueling the flight was the result of a refining process invented more than fifty years earlier by a Yale chemist named Benjamin Silliman. There was a fairly straight line from the Bayer and Silliman processes to Kitty Hawk.

The story of the Wright brothers’ powered flight illustrates the critical phenomenon of technological convergence that underlies all major technological developments in world history. Simply put, technological convergence refers to the fact that several enabling technologies have to come together in order for a specific overarching technology to work. And yet what’s often seen is only the technology that benefits, not the technology that enables.

We see technological convergence everywhere. Just to take a few of the most important innovations of the last two hundred years or so: The computer would not have been possible without the twin inventions of the transistor and silicon purification. MRI would not have been possible without the development of sophisticated software to deconvolute magnetic resonance signals and powerful magnets to observe those signals in the first place. There are other important global inventions that we take for granted - factory farming, made-to-order houses, fiber optics, even new tools like machine learning - none of which would have materialized had it not been for ancillary technologies which had to reach maturation.

Recognizing technological convergence is important, both because it helps us appreciate how much has to happen before a particular technology can embed itself in people’s everyday lives, and because it can help us potentially recognize multiple threads of innovation that could potentially converge in the future - a risky but important vision that can help innovators and businessmen stay ahead of the curve. One important point to note: by no means does technological convergence itself help innovations rise to the top – political and social factors can be as or more crucial – but this convergence is often necessary even if not sufficient.

It’s interesting to think of technological convergence in my own field of drug development. Let’s look at a few innovations, both more recent as well as older, that illustrate the phenomenon. Take a well-established technology like high-throughput screening (HTS). HTS came on the scene about thirty years ago, and since then has contributed significantly to the discovery of new medicines. What made the efficient screening of tens of thousands of compounds possible? Several convergent developments: recombinant DNA technology for obtaining reasonable quantities of pure proteins for screening, robotic techniques and automation for testing these compounds quickly at well-defined concentrations in multiple wells or plates, spectroscopic techniques like FRET for determining the feasibility of the end results, and graphing and visualization software for mapping the results and quickly judging if they made sense. These are just a few developments: in addition, there are techniques within these techniques that were also critical. For instance, recombinant DNA depended on methods for viral transfection, for splicing and ligation and for sequencing, and robotic automation depended on microelectronic control systems and materials for smooth manipulation of robotic moving parts. Thus, not only is technology convergent but it also piggybacks, with one piece of technology building on another to produce a whole that is more than the sum of its parts, aiding in the success of a technology it wasn’t primarily designed for.

Below is a table of just a few other primary drug discovery technologies that could not have been possible without ancillary convergent technologies.

Primary technology	Convergent enabling technologies
Combinatorial chemistry	LCMS for purification, organic synthesis methodology, hardware (solid phase beads, plastic, tubes, glassware) for separation and bookkeeping.
Molecular modeling	Computing power (CPUs, GPUs), visualization software, crystal structures and databases (PDB, CSD etc.)
Directed evolution/phage display	Recombinant DNA technology, hardware (solid phase supports), buffer chemistry for elution.
DNA-encoded libraries	PCR, DNA sequencing technology (Illumina etc.), hardware (solid phase beads, micropipettes etc.), informatics software for deconvolution of results.
NMR	Cryogenics, magnet production, software.

I have deliberately included NMR spectroscopy in the last row. A modern day organic chemist’s work would be unthinkable without this technique. It of course depends crucially on the availability of high-field magnets and the cryogenics techniques that keep the magnet cold by immersion in liquid helium, but it also depends fundamentally on the physics of nuclear magnets worked out by Isidor Rabi, Edward Purcell, Richard Ernst and others. Since this post is about technology I won’t say anything further about science, but it should be obvious that every major technology rests on a foundation of pure science which has to be developed for decades before it can be applied, often with no clear goal in mind. Sometimes the application can be very quick, however. For instance, it’s not an accident that solid phase supports appear in three of the five innovations listed above. Bruce Merrifield won the Nobel Prize in chemistry for his development of solid-phase peptide synthesis in 1984, and a little more than thirty years later, that development has impacted many enabling drug development techniques.

There are two interesting conclusions that emerge from considering technological convergence. The first is the depressing conclusion that if ancillary technologies haven’t kept pace, then even the most brilliant innovative idea would get nowhere. Even the most perspicacious inventor won’t be able to make a dent in the technology universe, simply because the rest of technology hasn’t kept up with him. A good example is the early spate of mobile phones appearing in the early 90s which didn’t go anywhere. Not only were they too expensive, but they simply weren’t ready for prime time because the wide availability of broadband internet, touchscreens and advanced battery technology was non-existent. Similarly, the iPhone and iPod took off not just because of Steve Jobs’ sales skills and their sleek GUI, but because broadband internet, mp3s (both legal and pirated) and advanced lithium ion batteries were now available for mass production. In fact, the iPod and the iPhone showcase convergent technologies in another interesting way; their sales skyrocketed because of the iTunes Music Store and the iPhone App store. As the story goes, Jobs was not sold on the app store idea for a long time because he characteristically wanted to keep iPhone apps exclusive. It was only flagging initial sales combined with insistent prodding from the iPhone team that changed his mind. In this case, therefore, the true convergent technology was not really battery chemistry or the accelerometer in the phone but a simple software innovation and a website.

The more positive conclusion to be drawn from the story of convergent technology is to keep track of ancillary enabling technologies if you want to stay ahead of the curve. In case of the iPod, Jobs seems to have had the patience to wait before USB, battery and internet technologies became mature enough for Apple to release the device; in spite of being the third or fourth mp3 player on the market, the iPod virtually took over in a few years. What this means for innovators and technologists is that they should keep an eye out on the ‘fringe’, on seemingly minor details of their idea that might have a crucial impact on its development or lack thereof. If you try to launch an innovative product before the ancillary technologies have caught up, you won’t achieve convergence and the product might well be doomed.

Of course, groundbreaking ancillary technologies are often obvious only in retrospect and are unexpected when they appear – Xerox’s mouse and GUI come to mind – but that does not mean they are invisible. One reason John D. Rockefeller became so spectacularly successful and wealthy is because he looked around the corner and saw not one but three key technologies: oil drilling, oil transportation and oil refining. Similarly, Edison’s success owed, in part, to the fact that he was an all-rounder, developing everything from electrical circuits to the right materials for bulb filaments; chemistry, electricity, mechanical engineering – all found a home in Edison’s lab. Thus, while it’s not guaranteed, one formula for noting the presence or absence of technological convergence is to cast a wide net, to work the field as well as its corners, to spend serious time exploring even the small parts that are expected to contribute to the whole. Recognizing technological convergence requires a can-do attitude and the enthusiasm to look everywhere for every possible lead.

At the very least, being cognizant of convergent technologies can prevent us from wasting time and effort; for instance, combinatorial chemistry went nowhere at the beginning because HTS was not developed. Molecular modeling went nowhere because sampling and scoring weren’t well developed. Genome sequencing by itself went nowhere because simply having a list of genes rang hollow until the technologies for interrogating their protein products and functions weren’t equally efficient. Developing your technology in a silo, no matter how promising it looks by itself, can be a failing effort if not fortified with other developing technology which you should be on the lookout for.

Technology, like life on earth, is part of an ecosystem. Even breakthrough technology does not develop in a vacuum. Without convergence between different innovations, every piece of technology would be stillborn. Without the aluminum, without the refined petroleum, the Wright Flyer would have lain still in the sands of the Outer Banks.