Tag Archives: biology

Research labs are literally sucking the blood from their graduate students

I’m going for a “clickbait” vibe with this one, is it working?

When I was getting my degree, I heard a story that seemed too creepy to be real. There was a research lab studying the physiology of white blood cells, and as such they always needed new white blood cells to do experiments on. For most lab supplies, you buy from a company. But when you’re doing this many experiments, using this many white blood cells, that kind of purchasing will quickly break the bank. This lab didn’t buy blood, it took it.

The blood drives were done willingly, of course. Each grad student was studying white blood cells in their own way, and each one needed a plethora of cells to do their experiment. Each student was very willing to donate for the cause, if only because their own research would be impossible otherwise.

And it wasn’t even like this was dangerous. The lab was connected to a hospital, the blood draws were done by trained nurses, and charts were maintained so no one gave more blood than they should. Everything was supposedly safe, sound, by the book.

But still it never seemed enough. The story I got told was that *everyone* was being asked to give blood to the lab, pretty much nonstop. Spouses/SOs of the grad students, friends from other labs, undergrads interning over the summer, visiting professors who wanted to collaborate. The first thing this lab would ask when you stepped inside was “would you like to donate some blood?”

This kind of thing quickly can become coercive even if it’s theoretically all voluntary. Are you not a “team player” if you don’t donate as much as everyone else? Are interns warned about this part of the lab “culture” when interviewing? Does the professor donate just like the students?

Still, when this was told to me it seemed too strange to be true. I was certain the storyteller was making it up, or at the very least exaggerating heavily. The feeling was exacerbated since this was told to me at a bar, and it was a “friend of a friend” story, the teller didn’t see it for themself.

But I recently heard of this same kind of thing, in a different context. My co-worker studied convalescent plasma treatments during the COVID pandemic. For those who don’t know, people who recover from a viral infection have lots of antibodies in their blood that fight off the virus. You can take samples of their blood and give those antibodies to other patients, and the antibodies will help fight the infection. Early in the pandemic, this kind of treatment was all we had. But it wasn’t very effective and my co-worker was trying to study why.

When the vaccine came out, all the lab members got the vaccine and then immediately started donating blood. After vaccination, they had plenty of anti-COVID antibodies in their blood, and they could extract all those antibodies to study them. My co-worker said that his name and a few others were attached to a published paper, in part because of their work but also in part as thanks for their generous donations of blood. He pointed to a figure in the paper and named the exact person whose antibodies were used to make it.

I was kind of shocked.

Now, this all seems like it could be a breach of ethics, but I do know that there are some surprisingly lax restrictions on doing research so long as you’re doing research on yourself. There’s a famous story of two scientists drinking water infected with a specific bacteria in order to prove that it was that bacteria which caused ulcers. This would have been illegal had they wanted to infect *other people* for science, but it was legal to infect themselves.

There’s another story of someone who tried to give themselves bone cancer for science. This person also believed that a certain bone cancer was caused by infectious organisms, and he willingly injected himself with a potentially fatal disease to prove it. Fortunately he lived (bone cancer is NOT infectious), but this is again something that was only legal because he experimented on himself.

But still, those studies were all done half a century ago. In the 21st century, experimenting with your own body seems… unusual at the very least. I know blood can be safely extracted without issue, but like I said above I worry about the incentive structure of a lab where taking students’ blood for science is “normal.” You can quickly create a toxic culture of “give us your blood,” pressuring people to do things that they may not want to do, and perhaps making them give more than they really should.

So I’m quite of two minds about the idea of “research scientists giving blood for the lab’s research projects.” All for the cause of science, yes, but is this really ethical? And how much more work would it really have been to get other people’s blood instead? I just don’t think I could work in a lab like that, I’m not good with giving blood, I get terrible headaches after most blood draws, and I wouldn’t enjoy feeling pressured to give even more.

Is there any industry besides science where near-mandatory blood donations would even happen? MAYBE healthcare? But blood draws can cause lethargy, and we don’t want the EMTs or nurses to be tired on the job. Either way, it’s all a bit creepy, innit?

The need for data, the need for good data

Another stream of consciousness, this one will be a story that will make some people go “no shit sherlock,” but it’s a lesson I had to learn on my own, so here goes:

My work wants me to make plans for “professional development,” every year I should be gaining skills or insights that I didn’t have the year before.  Professional development is a whole topic on its own, but for now let’s just know that I pledged to try to integrate machine learning into some of my workflows for reasons.

Machine learning is what we used to call AI.  It’s not necessarily *generative* AI (like ChatGPT), I mean it can be, but it’s not necessarily so.

So for me, integrating machine learning wasn’t about asking ChatGPT to do all my work, rather it was about trying to write some code to take in Big Data and give me a testable hypothesis.  My data was the genetic sequences of many different viruses, and the hypotheses were: “can we predict which animal viruses might spill over and become human viruses?” and “can we predict traits of understudied viruses using the traits of their more well-studied cousins?”.

My problem was data.  

There is actually a LOT of genetic data out there in the internet.  You can search a number of repositories, NCBI is my favorite, and find a seemingly infinite number of genomes for different viruses.  Then you can download them, play around with them, and make machine learning algorithms with them.

But lots of data isn’t useful by itself.  Sure I know the sequences of a billion viruses, what does that get me?  It gets me the sequences of a billion viruses, nothing more nothing less.

What I really need is real-world data *about* those sequences.  For instance: which of these viruses are purely human viruses, purely animal viruses, or infect both humans AND animals?  What cell types does this virus infect?  How high is the untreated mortality rate if you catch it?  How does it enter the cell?

The real world data is “labels” in the language of machine learning, and while I had a ton of data I didn’t have much *labelled* data.  I can’t predict whether an animal virus might become a human virus if I don’t even know which viruses are human-only or animal-only.  I can’t predict traits about viruses if I don’t have any information about those traits.  I can do a lot of fancy math to categorize viruses based on their sequences, but without good labels for those viruses, my categories are meaningless.  I might as well be categorizing the viruses by their taste, for all the good it does me.

Data labels tell you everything that the data can’t, and without them the data can seem useless.  I can say 2 viruses are 99% identical, but what does that even mean?  Is it just two viruses that give you the sniffles and not much else?  Or does one cause hemorrhagic fever and the other causes encephalitis?  

I don’t know if that 1% difference is even important, if these viruses infect 2 different species of animals it’s probably very important.  But if these viruses infect the same animals using identical pathways and are totally identical in every way except for a tiny stretch of DNA, then that 1% is probably unimportant.

Your model is only as good as your data and your data is only as good as your labels.  The real work of machine learning isn’t finding data, it’s finding labelled data.  A lot of machine learning can be about finding tricks to get the data labelled, for instance ChatGPT was trained on things like Wikipedia and Reddit posts because we can be mostly sure those are written by humans.  Similarly if you find some database of viral genomes, and a *different* database of other viral traits (what they infect, their pathway, their mortality rate), then you can get good data and maybe an entire publication just by matching the genomes to their labels.

But the low-hanging fruit was picked a long time ago.  I’m trying to use public repositories, and if there was anything new to mine there then other data miners would have gotten to it first. I still want to somehow integrate machine learning just because I find coding so enjoyable, and it gives me something to do when I don’t want to put on gloves.  But clearly if I want to find anything useful, I have to either learn how to write code that will scrape other databases for their labels, create *my own data*, or maybe get interns to label the data for me as a summer project.  

Stay tuned to find out if I get any interns.

“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.

Gene drives and gingivitis bacteria

One piece of sci-fi technology that doesn’t get much talk these days is gene drives. When I was an up and coming biology student, these were the subject of every seminar, the case study of every class, and they were going to eliminate malaria worldwide.

Now though, you hardly hear a peep about them. And I don’t think, like some of my peers, that this is because anti-technology forces have cowed scientists and policy-makers into silence. I don’t see any evidence that gene drives are quietly succeeding in every test, or that they are being held back by Greenpeace or other anti-GMO groups.

I just think gene drives haven’t lived up to the hype.

Let me step back a bit: what *is* a gene drive? A gene drive is a way to manipulate the genes of an entire species. If you modify the genes of a single organism, when it reproduces only at most 50% of its progeny will have whatever modification you give it. Unless your modification confers a lot of evolutionary fitness to the organism, there is no way to make every one of the organism’s descendants have your modification.

But a gene drive can do just that. In fact, a gene drive can confer an evolutionary disadvantage to an organism, and you can still guarantee all of the organism’s decedents will have that gene. The biggest use-case for gene drives is mosquitoes. You can give mosquitoes a gene that prevents them from sucking human blood, but since this confers an evolutionary disadvantage, your gene won’t last many generations before evolution weeds it out.

But if you put your gene in a gene drive, you can in theory release a population of mosquitoes carrying this gene and ensure all of their decedents have the gene and thus won’t attack humans. In a few generations, a significant fraction of all mosquitoes will have this gene, thus preventing mosquito bites as well as a whole host of diseases mosquitoes bring.

Now this is a lot of genetic “playing God,” and I’m sure Greenpeace isn’t happy about it. But environmentalist backlash has never managed to stamp out 100% of genetic technology. CRISPR therapies and organisms are on the rise, GMO crops are still planted worldwide, environmentalists may hold back progress but they cannot stop it.

But talk about gene drives *has* slowed considerably and I think it’s because they just don’t work as advertised.

See, to be effective a gene drive requires an evolutionary contradiction: it must reduce an organism fitness but still be passed on to the progeny. Mosquitoes don’t just bite humans for fun, we are some of the most common large mammals in the world, and our blood is rich in nutrients. For mosquitoes, biting us is a necessity for life. So if you create a gene drive that knocks out this necessity, you are making the mosquitoes who carry your gene drive less evolutionarily fit.

And gene drives are not perfect. The gene they carry can mutate, and even if redundancy is built in, that only means more mutations will be necessary to overcome the gene drive. You can make it more and more improbable that mutations will occur, but you cannot prevent them forever. So when you introduce a gene drive, hoping that all the progeny will carry this gene that prevents mosquitoes biting humans, eventually one lucky mosquito will be born that is resistant to the gene drive’s effects. It will have an evolutionary advantage because it *will* bite humans, and so like antibiotic resistant bacteria, it will grow and multiply as the mosquitoes who still carry the gene drive are outcompeted and die off.

Antibiotics did not rid the world of bacteria, and gene drives cannot rid the world of mosquitoes. Evolution is not so easily overcome.

I tell this story in part to tell you another story. Social media was abuzz recently thanks to a guerilla marketing campaign for a bacteria that is supposed to cure tooth decay. The science can be read about here, but I was first alerted to this campaign by stories of an influencer who would supposedly receive the bacteria herself and then pledged to pass it on to others by kissing them. Bacteria can indeed be passed by kissing, by the way.

But like gene drives, this bacteria doesn’t seem to be workable in the context of evolution. Tooth decay happens because certain bacteria colonize our mouth and produce acidic byproducts which break down our enamel. Like mosquitoes, they do not do this just for fun. The bacteria do this because it is the most efficient way to get rid of their waste.

The genetically modified bacteria was supposed to not produce any acidic byproducts, and so if you colonized someone’s mouth with this good bacteria instead of the bad bacteria, their enamel would never be broken down by the acid. But this good bacteria cannot just live in harmony and contentment, life is a war for resources and this good bacteria will be fighting with one hand tied behind its back.

Any time you come into contact with the bad bacteria, it will likely outcompete the good bacteria because it’s more efficient to just dispose of your waste haphazardly than it is to wrap it in a nice, non-acidic bundle first. Very quickly the good bacteria will die off and once again be replaced by bad bacteria.

So I’m quite certain this little marketing campaign will quietly die once its shown the bacteria doesn’t really do anything. And since I’ve read that there aren’t even any peer reviewed studies backing up this work, I’m even more certain of its swift demise.

Biology has brought us wonders, and we have indeed removed certain disease scourges from our world. Smallpox, rinderpest, and hopefully polio very soon, it is possible to remove pests from our world. But it takes a lot more work than simply releasing some mosquitoes or kissing someone with the right bacteria. And that’s because evolution is working against you every step of the way.