“I hate them, their antibodies are bull****”

I want to tell two stories today, they may mean nothing individually but I hope they’ll mean something together. Or they’ll mean nothing together, I don’t know. I’ve gotten really into personal fitness and am writing this in between sets of various exercises I can do in my own house.

The first story is from before the pandemic. I used to be a biochemist (still am, but I used to too). During that time I went to a lot of conferences and heard a lot of talks by the Latest and Greatest. One of the most fascinating talks was by a group out of Sweden who were preparing what they called a “cell atlas,” a complete map that could pinpoint the locations of every protein that would be in healthy human cells.

The science behind the cell atlas was pretty sweet. We know that the physical location of proteins in the body really matters, the proteins that transcribe DNA into RNA are only found in the nucleus because DNA itself is only found in the nucleus. Physical location is very important so that every protein in the body is doing only the job it’s assigned, and not either slacking off or accidentally doing something it isn’t supposed to. The first gives you a wasting disease and the latter may cause cancer.

So knowing the location of these proteins on a subcellular level is actually pretty important. But how can we even determine that? We can’t really zoom into a cells and walk around checking off proteins, can we?

The key was that this group was also really into making their own fluorescent antibodies. They could make antibodies for any human protein and then stick on a fluorescent tag that lights up under the right conditions. Then it was just a task of sticking the antibodies into cells and seeing which part lights up, that tells you where the protein is.

There was a bit more to it of course, I should do a post about how all this relates to Eve Online, but that was the gist of it: put antibodies in cells and see where the cell lights up. Use that to build an atlas of the subcellular locations of the human proteome.

It was some cool science and a nice talk. A few months later I was at another conference and the discussion came up of if conferences ever really have “good” talks or if scientists are incapable of anything above “serviceable.” I proffered the cell atlas talk as one I thought was actually “good,” it was good science explained well. The response I got from one professor stunned me: “oh I hate those people, their antibodies are bullshit.”

I don’t know how or why, but somehow this professor had decided that the in-house antibodies which underpinned the cell atlas project were all poorly made and inaccurate. That then undercut the validity of the entire project. I didn’t press further for this professor’s reasoning or evidence, I could tell he was a bit heated (and drunk) and left it at that. But while I never got any evidence against the cell atlas antibodies, I also never heard much in their favor. They seemed like a big project that just never got much recognition in the circles I ran in.

So was the cell atlas project a triumph of niche science, or a big scam? Well I don’t know, but it reminds me of another story.

As I said above, I’m much more into personal fitness these days. The Almighty Algorithm knows this, and so youtube serves me up a steady stream of fitness influencer content. I still stay away from anything that isn’t Mike Israetel or a few other “evidence based” youtubers, but even this small circle has served up its own helping of scientific slapfights.

In this case the slapfight is about “training to failure.” Most fitness influencers agree that you have to train hard if you want results. What exactly counts as “hard” though, that is where the controversy lies.

First of all, what is “training to failure?” Well unfortunately that too is controversial, because everyone has a different definition of what “failure” actually means. But generally, failure is when you are doing some exercise (a pushup, a pullup, a bench press) and you cannot complete the movement. Say you’ve done 5 pullups and you can’t do another, that’s “failure.”

Mike Israetel shows off example workouts of himself training hard, and he claims he’s training with “0 to 1 reps in reserve,” that’s a fancy way of saying he is training very near failure. If he does 5 pullups and claims he has 0 to 1 RIR (reps in reserve), then he is saying he could do AT MOST 1 more pullup, but he might actually fail if he even tried. He does this for almost every movement: bench presses, leg presses, squats, deadlifts, his claim of 0 to 1 RIR means he is doing the exercise until he can either no longer do it, or do it at most 1 more time before failure.

Failure itself is hard to measure, and sometimes you don’t know you’ll fail a move until you try. I once was doing pushups and just suddenly collapsed on my chest, not even knowing what happened. A quick assessment showed my shoulders gave out, and since pushups are supposed to be a chest exercise this implies I was doing them wrong, but that was a case where I clearly trained to failure since I tried to do the motion and failed.

But other fitness influencers have called Mike out on his 0 to 1 RIR claim, they think he isn’t training anywhere close to failure. The claims and counterclaims go back and forth, and unfortunately the namecalling does as well. I’ve kinda lost respect for the youtubers on all sides of this argument because of it.

But it gets back to the same point as the antibody story up above: a scientist is making a claim that they think is well-founded and backed by evidence, other scientists claim it’s all bullshit.

We think of science as very high minded and such, that science is conducted through solemn papers submitted to austere journals. I don’t think that’s ever been the case, science is conducted as much through catty bickering and backbiting as it is in the peer-reviewed literature. Scientists are still people, I’m sure a lot of us will be happy to take our cues from people we respect without spending the time to go diving into the literature. The literature is long and dense, and you may not even be the right kind of expert to evaluate it. So when someone you respect says a claim is bullshit, I’m sure a lot of people accept that and don’t pay the claim any additional mind.

So is the cell atlas actually good? Is Mike Israetel actually training to failure? I don’t know. I’m not the right kind of scientist to evaluate those claims. The catty backbiting has reduced my opinion of all the scientists involved in these controversies, although I understand that drunk scientists are only human and youtubers need to make a living through drama, so I try not to be too unkind to them.

Still, it’s a reminder that “the science” isn’t a thing that’s set in stone, and “scientists” are not all steely-eyed savants searching dispassionately for Truth. I don’t have any good recommendations from this unfortunately, the only thing I can think of is the bland “don’t believe scientists unquestioningly,” but that’s hardly novel. I guess just realize that scientists can disagree as childishly and churlishly as anyone else.