The Future of Small Molecules

First, a potential-rambling-post warning. Normally, I like to cogitate on a post for a while before writing, forming something akin to a beginning, middle and end. But in this case, i am not quite sure of the structure. I’m going to just write and see where it leads. Hopefully somewhere interesting.

The initial spark for this post came from a suggestion from a coworker. He showed me an article about a man who had received a bone marrow transplant which had effectively cured him of AIDS. The donor is one of those few that is naturally resistant to HIV and the bone marrow transplant effectively passed on this resistance as the patient’s CD4 cells were free of disease. When the transplant was done, it was posited that this might happen, but now, 3 years later, the patient has no detectable sign of HIV in his system.

We are not about to give every AIDS patient a bone marrow transplant, but the goal of actually curing AIDS is beguiling. The drugs available for HIV have been an unqualified success for the pharmaceutical industry, but all of them suppress the virus, not eradicate it. This is a difficult task due to the nature of the virus, as it inserts its genetic code into the DNA of the host cell, so you can’t kill the virus completely without killing all the cells that carry its genetic information. Some progress toward a vaccine has been made, and it starts to beg the question – how much longer will people pay for the pills? How much will things like bone marrow transplants and vaccines hurt pharma profits?

There has generally been a progression of the standard of care for diseases. Perhaps there was once none but rest and prayer, then some vile concoction that might kill or cure. Slowly the quality of the drug got better and things moved on. That is happening in AIDS now, a disease we did not even know about until 30 years ago. With AIDS in particular, the ability to treat the poorest people in the world has long been a problem, with some companies donating or reducing prices for those parts of the world that cannot afford the regimen of pills that people take here in the USA. What I got to thinking about is this: how much more can small molecule drugs do for human health?

Coincidentally, as I was pondering this, everyone’s favorite pharma blogger Derek Lowe posts on the Failure of Modern Medicine. He highlights an article on the Atlantic about this subject and how Alternate Medicine is growing due to regular medicine not meeting our needs. And Matthew Herper at Forbes posted a counterpoint, saying there has been progress in the chronic illnesses like heart disease and cancer, it is just very difficult. Which is true.

The further truth though is that we live much longer than we used to and the main causes of death are what people used to call “old age”, the body slowly breaking down. There are treatments for cancer, cholesterol lowering agents for heart disease. They do some good. But how much more good can they do? Are we not reaching a point where the cost of living a few more months is such a burden on the rest of society that it hardly seems worth it? Or maybe the way forward now is not with small molecules, which can never really be truly without side effects, the work now becoming the domain of the biologic, with the pharmaceuticals we already have doing what good work they already do.

I don’t really have an answer. There are certainly some disease areas where some kind of therapy is needed – recent announcements about successful candidates in HCV show that there are areas that still need some kind of improved therapy and medicinal chemists will have a role to play in that. And maybe there is some advance in the world of cancer therapy that will open up whole new possibilities for medicinal chemistry.

I just can’t help wondering if there is not that much more to find.


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