The Challenge of Biotech
By Paul B Little
In 1990 I saw a film in the career department of my school that was simply called "Pharmaceutical". It was a true piece of propaganda that I could not possible see through at the time. Men (and some women) in white lab coats drew chemical structures on the board and 'designed' the next new great drug. "Let's just try putting a phenyl group here." This is the biggest single driving quotation that I recall. There was simplicity in those few words. It seemed so trivial; all I need to do was learn to draw chemical structures and make bold suggestions and the world will be mine! Of course, from one end to the other it is nonsense. Chemistry is not as easily tamed as a humble white board. The word "just" is so misplaced when one considers the implications on a molecular level. How is it possible to persuade 6.022 x 10 (with 17 0s behind) molecules (we often work on the millimolar scale) to dance to one's tune? You cannot is the answer, they are not thought driven and they do not have what it takes to be persuaded. They follow the energy and do what chaos dictates: you get a mess, is what I am saying.
It took another eight years of chemistry training to be fully cognizant of the fact that molecules are more like cats than like dogs. You cannot train them, but you can make it seem like they are doing what you want by making the conditions right so that what they want is what you want, or will accept! So "just" putting a phenyl group there can be a very lengthy exercise and need not ever actually happen!
Let us describe now the pharmaceutical development process: imagine for a minute that you are a molecule and you are eaten by a human, what do you see and where do you go? Imagine that you are supposed to make your way to a single receptor that sits on a particular cell type in a specific organ and you are to do one job, get out, do not get caught. It all sounds very 'Mission Impossible' and somehow it is. The human body is a magnificently complex place and there are huge challenges for Doctor Molecule wherever he goes. The good Doctor can get stuck in fat, or never make it out of the stomach, be chewed up by the liver or rapidly sent out to the bladder. Of course the other side to the story is Mister Chemical. All drugs are chemicals, all life is organized chemistry, but for the sake of this metaphor Mister Chemical could attack the body, or disrupt it balance, do more harm than good and even kill the body if enough friends are present. The pharmaceutical development process is the long road from the lab bench to the bed side where hundreds of studies are undertaken to assess the good qualities of Doctor Molecule and the bad qualities of Mister Chemical. If the balance is right and there is separation between the good side and the darker impulses then clinical trials begin and the lucky few will get permission to be marketed.
This few, this lucky few, this pharmacopeia is the result of a huge effort. It is estimated that 95-97 % of all projects will end in failure, 80% or more of all medicinal chemists (the cat herders) will never work on a project that leads to a marketed drug. Some time ago it was often quoted that 10000 compounds were synthesized for each drug that is marketed. That number had grown substantially since the development of new synthetic techniques. Try to imagine 10000 struggles to "just" put a phenyl group there. Try to consider the huge amount of data that is published each day that goes into the hundreds of scientific journals covering every aspect of this crazy world. All of the data combined is used to make the best possible guesses as to which phenyl group should go where and what disease should be treated in which way. It is a mind boggling pit of insanity to dive into and expect that one will succeed.
So why do we do it? The answer is the same as the lottery: to win, because the rewards of success greatly outweigh the insanity of the small chance of attaining that success. For some of us it is also the "because it is there" drive to do something unusual and to potentially make a big difference in people's lives.
The biotech industry is the modern answer to the problem of this insanity, insofar as biotech is meant to mean small, highly focused companies with a very small number of projects. The point being that the individual drive of the people to make the individual projects a success is supposed to develop them faster, give them a higher chance of success or to fail faster and be cheaper doing so.
Why do I do this insane job of biotech? The answer is because I can. Somehow the last dozen years in this industry have given me the skills to understand that working for five to ten years on a project that can fail tomorrow is fine. The uncertainty is substantial, but when it works the benefits are enormous. Biotech is a business, and the only business I know that has to invest so much money, for so long without any certainty at all of any form of success. Which success stories should I quote to end this piece, to show that biotech has a benefit through the madness: it could be many: insulin for diabetics, cancer therapies that increase life expectancy, treatments for HIV infection, a whole pharmacopeia of remedies that I hope that you will never need but is designed to be there in case you do.
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