Better Hay Stacks

Andrew Myers

Dr. Andrew G. Myers has been researching new chemical sources for antibiotics, often without being funded. His approach:

  1. Start with a working drug.
  2. Adjust it to get something new.
  3. Test this new thing to see if it has desirable medical properties.

There are different ways to do this. You can start with a molecule that works, and treat it like a Christmas tree. New molecules can be made by adjusting the ornaments on the tree. This kind of chemistry is called "semisynthesis". Once a new molecule is made, you can test it to see if it can kill the target bacteria without causing toxic side effects in the patient.
Saskia_Bauemeister_Christmas Dr. Andrew Myers used this approach with the drug tetracycline, then founded a company called Tetraphase Pharmaceuticals.

Semisynthesis is hard. So, Dr. Myers has developed an easier way of building novel medications from old antibiotics. He has found a way to start with a molecule that works, then to adjust the deeper structures within it. This would be like making entirely different types of Christmas trees, like a palm tree, or an elm tree rather than using a standard evergreen. It is significantly more expressive than semisynthesis in its ability to make new and useful things which can be tested for their bacteria-killing properties. AlternativeChristmasTree

Dr. Andrew Myers followed this more expressive approach with the drug Erythromycin. He has found a way to use 9 industrially available chemicals and synthesize the base molecular class within the Erythromycin drug. These base classes are call macrolides.

The creation of an effective drug is like looking for a needle in a haystack. Dr. Myers is building better haystacks; he can make them much, much smaller, and full of lots of needles. His ability to generate new antibiotics of the macrolide class has been industrialized, in his founding of Macrolide Pharmaceuticals.

This company has already created a new drug which can defeat infections that are resistant to Vancomycin. Vancomycin, is like the previously mentioned colistin, in that it is a toxic, 'last resort', antibiotic that is used against infections that aren't killed by traditional antibiotics. So Dr. Myers can kill superbugs.

Why not go a step deeper, and find the things from which macrolides come from? Macrolides were first discovered in the bacteria called Saccharopolyspora Erythraea by the Philipino scientist, Abelardo B. Aguilar, in 1949.

Dr. Aguilar got very lucky when he found a bacteria that could be grown in agar, since even today 85-99% of bacteria and archaea cannot be grown on their own in a lab.

Abelardo B. Aguilar

Why not go a step deeper? It's hard to actually isolate bacteria for study and Dr. Myers is a chemist, not a biologist. He's not about to go digging into the ground looking for new bacteria sources of base class antibiotic chemicals. He has bitten off plenty to chew. His macrolide approach is extremely pragmatic, and from it, his company will likely discover new compounds that can treat pathogens that even the original Erythromycin could not treat.

Dr. Andrew Myers still has a colossal regulatory problem to solve. He can make a lot of drugs, but as far as the market is concerned, the FDA requires a company to spend 1-4 billion dollars and wait 12 years before they can sell their first pill. Macrolide Pharmaceuticals, following their better-hay-stacks approach, will probably get their costs lower than this and even break free of Eroom's law. But why would someone invest in a drug which will be made obsolete by evolution within a few years? Especially when the wholesale price of Erythromycin is currently $0.06 per pill.

Say it takes a billion dollars to pass regulatory approval. At $0.06 a pill, you will need to sell your drug 16 billion times to just break even. There aren't 16 billion people in the world.

But the interplay between biological evolution and the market will change these numbers favorably for Macrolide Pharmaceuticals.

There are two evolutionary effects taking place here. One, as some antibiotics are being made ineffective by evolution, this will drive up the price of the surviving antibiotics. This increases the price of your new drug. Two, if you make a new medication, it won't last that long because of the increased concentration of humans and its use in agriculture. This decreases the time over which you can profit from your drug.

The FDA is not structured to deal with these types of evolutionary issues. They didn't mean to create the perverse business incentives that their regulations have burdened us with. I have argued before that it is the ever-higher costs they have imposed on American society that is the driving force behind the next plague. There isn't any malicious intention behind it — it is an emergent political phenomenon.

We need to solve an easier problem, we need to move the FDA off the field of play.

If I were on the macrolide board of directors, I would recommend that we build these drug discovery platforms into infrastructure that could be purchased by hospitals. Each hospital would have the ability to generate their own proprietary antibiotics based on the Macrolide haystack.

To understand how this would work, imagine that you are a person who has contracted a superbug and you have been told that it will probably kill you. Now, a physician approaches you and says that they are developing experimental drugs that could save your life. There is a very high risk that it is toxic, but you are in a hospital and they have had good results with mice. The drug has not passed regulatory approval. Would you take it? I would.

Over time they would lose some patients, but they would quickly determine which candidate drugs are useful and grow their research in this direction. If they kept these formulas as trade secrets, they couldn't be over-prescribed, put into antibacterial soaps or fed to pigs in China. The only place that evolution could occur would be within the patients themselves.

The small haystack infrastructure provided by Macrolide Pharmaceuticals would mean that different hospitals would generate their own unique solutions. It would be unlikely that the same innovation would be discovered twice by two different institutions. Instead of personalized medicine, this would be hospital-centric medicine.

When the costs of antibiotics go up, and the business case suddenly starts to make sense, a hospital could monetize their working medication and begin the FDA approval process. Hopefully, this would make that hospital and Macrolide Pharmaceuticals a lot of money.

More importantly, when people start dying from plague there would be enough political pressure to force the FDA to fast track new antibiotics to the people who need them. The key would be to have those medicines invented in time.