Bitter Pills to Swallow

Another long week has gone by and in truth there isn’t much I feel like wanting to talk about. My archaic chemistry approaches I discussed last week were somewhat successful so I guess there is that.
This week though I’ve come to a sad realisation that chemistry as I know it, chemistry that I love is well and truly on its way out. Investment continues to be cut and the EPSRC don’t seem to give a fuck. I would not be surprised to learn that they spend more time and effort funding equality and diversity in research than actual research. Funding is sparse and it’s all biology’s fault.
Errr, well not exactly.  Really it’s our own fault. We had it so good for so many years telling the world we were synthesising molecules “of biological importance” when really we were just trying to feed our egos. Can I make it in less steps then this guy? Can I get a better yield? Can I make my approach more scalable, etc etc.
This was well tolerated during the era of small drug molecules. Yes, we were dicks and just showing off but what we made were drug molecules that could make A) someone sick healthier but more importantly B) a pharmaceutical company and its shareholders a shit tonne of dollars.
So there was acceptance and funding and all was well.
Today however it’s a very different story. I’m sure even those who do not have back grounds in science have been exposed to it by now. Every other night I hear in the news about a new way of “supercharging” the immune system to fight cancer or flooding the body with antibodies and what not. So what happened to making molecules to treat disease?  The answer is simple. Cancer is a very complex disease. There are well over 300 different varieties of cancer to choose from. I remember in 2015 at one conference, a plucky chap from AstraZeneca stated how they had taken a 9nm (nanometer 10-9M) thick slice of someone’s pancreas. They were intrigued as this cancer had massively failed all conventional treatment as well as their last resort clinical trial drugs. What they found when they did some basic screening was in fact 17 (SEVEN effin TEEN!) different types of cancer on that one very small piece of tissue. There is just no way that one drug or a cocktail of a few can treat 17 different types of cancer. So now research focusses on antibody drug conjugates and monoclonal antibodies. Antibody drug conjugates are essentially monoclonal antibodies that have been chemically modified to deliver a payload of drug.
Monoclonal antibodies are used in medicine for targeting a cancer cell, essentially putting a big ass red flag on it for your body to “see” it and kill it. They also work by inducing apoptosis (cell death) but my bio knowledge isn’t up to scratch enough to explain how.
mab1Antibody drug conjugate (left) and a 3D printed one (right) that sits on my desk.

In 2016 out of the top 10 selling drugs, i.e. highest grossing pharma drugs, 7 work through biological pathways, 5 are monoclonal antibodies and only three are small molecules. Only 3 have been made by a purely chemical approach. Only 3 represent classic synthetic chemistry of yester year. Only 3 exist as a product of the type of chemistry I love.
Now if we all take a peek at the top 10 selling drugs of 2006. All of them are small molecules. All of them exist as a by-product of synthetic chemistry wizards performing miracles. All of them represent everything right with organic chemistry. They all justified funding psychotic egomaniacs hell bent on churning out molecules more efficiently than the competitors. It seems I was born just a tad too late to get aboard that chem hype train. Now these are overall drugs for a variety of different ailments. Let’s focus on cancer as that’s where a majority of the funding goes into. Again we see it dominated by monoclonal antibodies. And if you had a look at 2006 top ranking cancer therapeutics? You guessed it, small molecule city.
In the future if you and your neighbour both find out you have the same cancer in the same place, don’t expect to both be given the same treatment. Treatments will become more personalised and hopefully more effective too.
But as a direct result of improved more effective cancer treatments, pure synthetic chemistry has suffered. Maybe one day over next few years ill learn to embrace the new bio overlords. But currently I find it all a pill too bitter to swallow.
So now it is a trade-off. Do you do chemistry with bio stuff and say well at least its impactful and will get into a high impact journal, the lowest probably being Angew Chemie or do you go somewhere on a pure synthesis project and say well maybe the best I can realistically hope for is JACS but at least I’m doing what I love and nothing else? It isn’t even that simple. Friends of mine on synthesis degrees still have to subject their molecules to cell assays and bio stuff. Shoot. One guy I know started in July and hasn’t been in a chem lab yet. Spent all the time to date in a bio lab learning bio stuff. Twice as much stuff across 2 departments and on top of all that, they slashed 6k off his initial 14k stipend. Talk about cutting a guy’s legs off from under him. Such is the nature of chemistry PhD’s in 2016. All this to go on, and let’s be honest here, not have a real shot at academia and research (I include myself in that statement)
Writing this has been quite sad, it certainly hasn’t filled me up with 1980’s cocaine fuelled Hulk Hogan levels of enthusiasm…

“Fear has two meanings, Forget everything an run OR Face everything… and rise. The choice is yours.”
hh

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