So, what exactly do you do for Evil McSinister Corporation?

Science magazine has an article on one of those ubiquitous, awkward situations that anyone who works for the chemical, pharmaceutical or biotech industry must find themselves in at least once or twice in their careers: having to explain to a suspicious and wary interlocutor why exactly they work for Evil McSinister Corporation that's responsible for so many of the World's Woes. The author of the article documents the experience of a scientist who works for Monsanto:

“It must be hard,” I thought, “having to preface every answer to ‘What do you do?’ with ‘So, uh, here’s the thing.’”

VanderKraats confirmed this suspicion when I spoke with him after the panel. He said that there are a lot of misconceptions about his employer, and that he’s had a few awkward conversations in which he’s had to basically explain that his job—developing algorithms to analyze data about phenotypes and genetics—is not tantamount to throwing baby bunnies into a wood chipper.

“I think we contribute positively to the world,” VanderKraats told me, “but sometimes I still hesitate a little to reveal that in a conversation, because you’re not really sure if the person on the other end is an opponent.”

The article actually touches on a very important ethical dilemma than many scientists face: what do you do when, along with some bonafide positive contributions that it's making to the economy and to society, your company is also clearly engaging in some activities that would make even the most ethically hardened soul cringe? News about DuPont, Pfizer and a host of other corporations during the last few years has not done much to bolster the public's faith in these entities. 

Tragically though, the real good that some of these organizations have done along with the sheer complexity and challenges of the research that they are engaging in are two themes that somehow don't seem to filter as much to the lay public. No matter how extensively you may philosophize about why drug discovery is hard, the two main questions which you get asked when you mention you do pharmaceutical research are almost always, "Why are drugs so damn expensive?" and "Why do drugs have so many damn side effects"? That latter question is usually a good cue to transition into a succinct explanation of the scientific challenges of drug discovery: how even the basic science of the process is still woefully under informed, how if we knew how to get rid of side effects, we would with every fiber in our being, how the sheer risk and attrition in drug development can kill a compound during the end game, even after it has jumped over every single obstacle, how drug hunters need to have an appetite for risk that surpasses MacArthur's. By this time though, you are hoping that the person grilling you has not moved on to the next target of his or her outrage.

There's no simple answer to this dilemma. But one of the pieces of wisdom that emerges from thinking more about the issue is that it's almost impossible to work for any institution that does not flirt with morally questionable practices. 

After all, nearly every employer is perceived as evil by someone. If you’re in the chemical industry, you’re poisoning the world. If you’re developing medicines, you’re a shill for Big Pharma. If you’re an engineer at an energy company, you hate pelicans. If you’re in academia, you’re sneering at the peasants from your ivory tower. NASA wastes taxpayer money. Meteorologists are always wrong. Every form of energy production sucks. Military scientists love war. Mathematicians are superfluous. None of our results can be replicated, we’re all drawing unsurprising conclusions, and none of us would allow moral concerns to interfere with results.

I’d like to think that scientists have an ethical obligation to ensure that our work does no harm. It’s a credo I stole from the medical students. But at the same time, we can’t be held responsible for every decision our employers make—especially because most of us have very little power at our places of employment.

Indeed. Institutions after all are run by human beings, and human beings are flawed, and some are downright evil. I think that up to a fairly large margin of error, you can't be held accountable for what some of these human beings in your organization are doing as long as you are not complicit in their actions or have no knowledge of their activities. Where one draws the lines in this regard is hard to pinpoint and is an individual decision, although the extremes as usual are easy to identify: if I worked for a company whose senior management regularly ate babies on live television I probably won't have qualms turning in my resignation right away. Similarly if an organization has a serial record of engaging in unethical financial or environmental behavior combined with a shockingly blatant disrespect for its employees' well-being, it wouldn't be hard to strike that organization off your potential employer list.

Anything between those two extremes is up for debate though, especially at the lower end of the scale. So what does one do when asked why his or her organization was recently indicted for poisoning the waters of that pristine river that flows through your town? I think the article has it right in that whatever the reply is, it needs to be honest and balanced. I would be the first one to admit that like other corporations, drug companies do sometimes engage in patently unethical practices. I would make sure to make it known that I strongly believe that those who encourage such practices should be prosecuted proportionately. But I also would equally emphasize the countless lives that have been saved by drugs, the incredible, often heartbreaking complexity of the basic science of drug discovery and in fact the great positive contribution of chemistry and related sciences as a whole to our modern way of life. Or I could just do a George Whitesides.

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 said by pharma scientists, which originally came from academia, 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 beendocking, 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 docking 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, and the paradigm in which force fields are developed, 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.