cgiles

IME, in academic biology, the answer is generally no. Personally, I do use, but it isn't a result of competition, but rather a desire to achieve the most I can for a goal I care about. I don't feel pressured in any way to make this decision; if anything, the pressure is slightly in the other direction.

The big trouble with it is that a drug -- any drug -- will alter your perception of the world such that it is difficult to know with absolute confidence whether you are taking the drug for purely rational reasons to further your personal goals...or not.

Amphetamines at least, based on my experience and reading of the literature, improve your ability to do huge amounts of light/easy work at the expense of "deep" thinking. This means that they would be most effective for people who are knee-deep in work that is too easy for them and need to get more throughput. Undergrad is exactly this -- tons of relatively easy work. Professional life is not; quality is in the long term valued over shitty quantity.

I hope your article won't be a complete hatchet job on white-collar drug use -- the reality is very complex. Humans in general, and white-collar workers in particular, are living in environments and doing things extremely different from what humans evolved for. Thus, some of us use drugs to tweak our biology to adapt to the situation. Assuming that these do in fact improve performance -- a very disputable assumption -- this would be a success story for human intelligence and adaptability.

> a handful of people binge drink to come down

Biologist here, and yep, that was the only real discernible downside to me. Especially when I was new to the drug (Adderall) and didn't know how to time the doses and therefore took them too late in the day, I would get a powerful urge to drink about 3-5 hours after the last dose to come down. However, if you dose early enough in the day you will come down naturally.

Besides the desire to "drink to come down", the other problem is that Adderall will make you feel clearer and more energetic for longer while drinking, making it easier to miss the warning signs that you are approaching (or have passed) the "too much" threshold.

I am not aware of stimulant use being very common among the people I work with, and you are absolutely right that it is easy to tell the symptoms.

Relevant article: https://www.nature.com/news/2008/080409/full/452674a.html

If ~20% of biologists (broadly speaking, and higher in younger cohorts) "have used" a drug to enhance performance, then the number regularly using must be lower, unless there is selection bias in this informal poll, and if there was I would suspect the bias would be towards an overestimate of use, as people interested in the question seem more likely to respond.

Overall, then, I would guess use in these fields is "semi-rare" (maybe 5-10% of the population are regular users).

Thanks for the links, I will check them out. An embarassing correction: the 450K is (as you well know) not a SNP array. Can you tell I've been doing more than my fair share of methylation stuff recently?

The fundamental problem I have with your reply, though, is that the authors were not really concerned with any particular SNP. They wanted to make statements about the group of ASD-related SNPs. Clearly it is infeasible to do most of the things you have suggested here with >100 SNPs. Given that, what do you suggest they should have done?

1 & 2: This is setting the bar rather high, no? I hate GWAS, but am surrounded by people who do them all the time. To show any kind of function for a SNP is hard, to do it in humans is very, very hard for something like this involving nervous system function, and to prove the difference in function is "adaptive" virtually impossible. The furthest people go, and fairly rarely, is to show an eQTL and spin some unconvincing tale about how the difference in expression might have some effect.

But array-based methods do have one advantage which is that the 450K for example is heavily concentrated in genes and promoters. So the variant, which indeed does not span just one nucleotide, does have at least putative functions, which are simply the known functions of the gene, although yes, you cannot say whether the variant itself is helpful, harmful, or null on the functions of the gene. It is at least a step up from people who come to me (bioinformatics) and ask me to use my divining rod to guess what their SNP 100Kbp from the nearest gene might do.

3. Putting it in an abstract is fairly desperate, I agree. But broadly speaking the way you know you aren't getting total nonsense is if a lot of related terms cluster towards the top. Which looks to be what they got. It looks a lot cleaner than most GOEA results I see.

Perhaps you could educate me on what would be proof of positive selection. Would it be at least convincing evidence, if not proof, if you showed that phenotype P is associated with variant V, and variant V is associated with positive traits X,Y,and Z after controlling for P (so you can rule out direct links between P and X/Y/Z which bypass V)? From what I have seen, investigations into functions of individual SNPs are almost invariably a waste of time ending in handwavy stories so I wonder if there is a better approach.

> if it were true, we would see all sorts of genetic correlations where one good trait systematically boosts a bad trait. This is almost never true

I see it as almost axiomatically true, but I think the difference is you are taking a narrow definition of what constitutes a "bad" trait. Examples:

- Immune system: protects us from microbes but contributes to atherosclerosis, autoimmunity, and age-associated chronic inflammation

- Mitochondria: Generates ATP but also oxidative stress

- Infant brain size: makes humans as smart as we are but increases maternal mortality

- Body mass/volume: gives greater protection against predation but increases energy requirements

- Intelligence & brain volume: improves on-the-fly adaptability but costs a lot of energy to run

In the most general case, any gain-of-function adaptation which adds a new protein/organelle/limb/etc has a built-in bad trait which is that it costs resources to produce, DNA to maintain, and also adds another potential point of failure. The equilibrium point between benefit and costs is where evolution will land.

So I would argue that the reason we have X IQ points or Y neurons is exactly the same reason we have Z mitochondria: any more and the costs would have exceeded the benefits in the ancestral environment. The fact that we can seemingly get more benefits than costs from increased intelligence now merely reflects the fact that our environment has changed.

Also, JBS Haldane wrote an anti-eugenics book many years ago which used exactly this sort of argument.