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Dissing the scientists

I’ve written before about how science in this country has been murdered to within an inch of its life. This topic deserved more attention in the past and now that the viral apocalypse is upon us, it’s time we scientists had a louder voice. No one has been listening to us.

The Washington Post has a front page article about the problems developing a coronavirus vaccine and the impossible timeline Trump and Alex Azar expect to meet.

This paragraph makes me extremely nervous:

I would prefer to see the FDA at more arms’ length,” Lurie said. “I think it’s appropriate for the FDA to engage with manufacturers with vaccine candidates to explain what they will need so reviews can be expedited. But I think it’s a bad look for the FDA to be in the same room with a project that emphasizes speed.”

That remark deserves its own post. Trust me, we should all be horrified by that attitude if for no other reason than it feels like yet another attempt to deregulate.

Moving on.

Before I talk about how hard it will be to create a coronavirus vaccine, I’d like to remind everyone that we’ve been dealing with HIV for more than 30 years and we still don’t have an effective vaccine. That’s in large part due to the specific cells that HIV attacks- T cells. T cells are a critical part of the immune system. They need to be trained to recognize the virus protein on the surface of our cells. That’s basically how vaccines work. Your body is taught to recognize self from non-self. So if the virus you are trying to vaccinate against goes after a major component of the immune system, you’re going to have problems getting those rapidly diminishing T cells to do their job. If you do a thought experiment on that, it’s actually pretty depressing. Let’s just say that an HIV vaccine is probably going to be very difficult to create even 30 years later.

The way we keep HIV in check is through small molecule drugs like aspartyl protease inhibitors. I used to work in the area of small molecule drug discovery. There used to be a lot of medium sized pharma R&D companies strewn along the length of the Northeast Corridor that did small moleculr research. We used to work in many therapeutic areas such as antibiotics, to cardiovascular, central nervous system, women’s health as well as cancer.

In the 2000s, many of those drugs went off patent. With the loss of so many blockbusters, the industry laid off hundreds of thousands of career scientists, shuttered labs and switched to biologicals that didn’t have as many patent issues. Also, the portfolios switched to cancer and orphan diseases because they could be fast tracked and if there were awful side effects, well, desperate patients aren’t likely to sue. They’ll put up with a lower safety profile to eke out a few more months.

I just have to insert here that although chemo can be harsh, it’s not nearly as bad as it was 23 years ago. Some of that has to do with the drug cocktails we use these days that are effective and less likely to make you feel sick. Some of it has to do with a class of small molecule drugs called kinase inhibitors that are just hitting the market now. That’s what I used to work on.

Biologicals are great and show amazing promise. But they are just one weapon in the arsenal. Well, they used to be one weapon. With the destruction of the small molecule drug industry in the last 20 years, research has shifted disproportionally to biologicals.

Ah, you say, but don’t you want the most up to date science and technology? Yes. We do. But that doesn’t mean we have to abandon one avenue of discovery in order to chase profits. Someone should have been studying the effects of the patent cliff on medicine. Ok, the scientists who lost jobs can write papers on it now but there’s no mystery about this. No one gave a fuck about scientists. If you say “pharma” your mind immediately turns towards the shareholders who are making obscene profits on your misery. And I completely understand that. But it was our collective inability to distinguish between the financiers and greedy executives from the researchers that allowed the feeding frenzy on small molecule research to go on without any checks. And this is why we are partly in trouble right now.

Because people like myself were forced to find second careers at vastly lowered salaries. We had to shelve our knowledge, experience, skills and continuous training and are now sitting on the sidelines watching this catastrophe unfold, pretty much helpless to do anything about it.

Instead of working in IT in an entry level job, which is fine, I should be using my years of computational chemistry and structural biology experience to sift through millions and millions of possible drug compounds looking for hits against the coronavirus protein targets. BiFF should be writing code for combinatorial library generation and analysis. We should be working with med chemists, biologists, pharmacologists and animal model researchers to evaluate lead molecules. Some of us were at the height of our abilities and had just hit our zone when we were laid off.

The industry has been fragmented. The experienced lab rats were sidelined or shunted to small startups where they faced lay offs every couple of years as early discovery stage staff had to be let go due to lack of funding.

Anyway, I’ve gone over this before in many posts that most of you ignored because It was just not important at the time. Now it’s important.

Because there are two paths that I can see to getting coronavirus under control. 1.) A vaccine. 2.) Drug therapy, either biological or small molecule.

Vaccines can be tricky. They need to show efficacy, we need to know for how long they’ll be effective, we need to evaluate safety and we need to know about unintended consequences like triggering autoimmune responses. This takes time. It could take a couple of years or decades or maybe never.

I can see where Trump et al thought that whipping up a coronavirus vaccine was going to be as easy as making a flu vaccine. There’s a new one every year. We can track sequence mutation in publicly available databases. Piece of cake! But the influenza protein targets are well known. Flu vaccine production has been around for a long time. We know what we’re doing.

The ridiculous timeline that Trump proposes shows his profound ignorance of science in general. I really wish he’d just shut up. Every time he opens his mouth on the subject is infuriating. He makes it sound as if the long timeline is due to scientists not appreciating the urgency. They’re all sitting around on their elitist asses and if someone like Trump just applied right amount of pressure, whipping and humiliation, they would come down from their ivory towers and get to fucking work to save his bacon by Election Day. You can bet if there’s not a vaccine by then, it will be all the scientists’ fault.

Nevermind the years of neglect, underfunding of the NIH, lack of preparation or foresight on the part of Trump’s administration. Forget that the small molecule industry hit the patent cliff hard under Obama but was allowed to be picked to death by financiers, vulture capitalists and chided by smug Silicon Valley types who can’t understand why methods of innovation of man made products can’t operate just as well in incompletely understood natural systems.

We see through a glass darkly. That is the problem. Science on the level that Trump is demanding is not possible. Sure, we can have a Manhattan project. It’s still going to take time. It’s going to take drug therapy in case the vaccine stalls.

We are not data operators or factory workers whose productivity can be optimized. We could work our bodies to exhaustion, you could chain us to our hoods, make us work 18 hours a day. You’d be surprised at how much some of us find that scenario attractive. Science is the ultimate intrinsic reward system. It’s intoxicating and addicting when you’re onto something. But to be thorough, careful, rigorous, and to uphold our own natural instincts to share information, truthfully, not slanting data to fulfill some loyalty oath, goes against almost everything Trump stands for. And, no, big monetary rewards to single individuals as incentive does not make discovery go faster. This kind of work depends on collaborating with each other. Jack Welch type work structures are counterproductive.

I have no doubt that American scientists can accomplish what may look miraculous. I honestly believe that because our culture is so open, optimistic and non-hierarchical that we pay less of a cost to try things out and innovate. We do this better than any nation in the world.

But we can’t do it without the “means of production”. We can’t do it if we’re sidelined and sacrificed for shareholder value. And we can’t do it with criminally incompetent and stupid presidents breathing down our necks and throwing hissy fits because he has no fucking clue what he’s dealing with.