Making Nootropics that really work

Currently available nootropics don’t seem to increase IQ. In fact basically nothing increases IQ, despite many claims to the contrary. Instead nootropics like modafinil, adderal, coffein, nicotine, etc. improve focus or endurance or energy level. Consequently, the difference in productivity is quantitative not qualitative.

If we could increase IQ by, say, ten points, simply by popping a pill, it would make a tremendous difference not just on an individual level, but especially on a societal or global level.

To see what difference ten points would make, take a look at the Ashkenazim. Ashkenazim are the Eastern and Middle European Jews and they are massively over represented in all cognitively demanding fields. Their total number was probably never higher than 15 million. However, roughly half of all chess world champions have had Ashkenazi ancestry, as well as more than 20% of all nobel prize winners [1]. In some fields, like economics, more than 40% of all nobel prize winners are of Jewish ancestry.

To illustrate how unusual that is, please try to name 3 famous Belgian thinkers or scientists. Unless you are from Belgium yourself, you’ll probably come up empty handed. If you make the same experiment for Ashkenazim your only problem might be that you possibly don’t know that Einstein, Marx, Freud, Von Neumann, Feynmann, Kasparov, Bobby Fischer and many others were Jewish. The theory of relativity, the nuclear bomb and modern computer architectures are all result of Ashkenazi genius.

This massive intellectual over performance is to a large part the result of an IQ advantage of just ten points [2].

On a societal level an advantage of ten points corresponds to a doubling of the GDP per capita. For comparison: Globally it took 45 years for GDP per capita to double between 1969 and 2014 [3]. Gaining this additional boost would make a massive difference, likely enough to eliminate all remaining poverty.

We also seem to live in a time where several massive problems are on the horizon, and we can certainly use all the smarts we can get to have a chance to solve them.

To sum up: A cheap and side-effect free pill that enhances IQ by ten points would usher in a technological and scientific golden age, accompanied by massive economic growth.

So how did the Ashkenazim level up? Cochran and Harpending make a convincing case that Ashkenazim IQ rose during the last thousand years to its current heights, due to strong selection for white collar work acumen [4]. Remember, during the middle ages crafts and farming was largely forbidden for Jews, leaving different kinds of businesses as possible occupation. Financial success was strongly correlated with surviving number of children.

One strong indicator for this selection is a cluster of genetic diseases unusually common in Ashkenazim. These are, for example, the so-called sphingolipid storage diseases like Tay-Sachs or Gaucher’s disease. These diseases are caused by loss-of-function mutations in enzymes that break down sphingolipids in cells. If such an enzyme doesn’t do its job, sphingolipids accumulate and over time lead to different neurological disorders.

Also, genetic diseases connected to DNA-repair dysfunction and miscellaneous stuff like Torsion dystonia. The kicker is that all these diseases likely rose to their current high frequency as by-product of strong selection for intelligence. In Israel people with Gaucher’s disease are six times as likely to be engineers or scientists as other Ashkenazim. Torsion distonia sufferers have been shown to have an IQ elevated ten points above the already high Ashkenazi mean [5].

There is also in vitro evidence for increased dendritic growth under high sphingolipid concentration. So while a homozygous carrier of Tay-Sachs is doomed to an early death, a heterozygous carrier profits from higher sphingolipids concentrations in his neurons and consequently higher dendritic growth, while the one working gene copy is still enough to clear out enough sphingolipids to avoid detrimental symptoms.

A very similar argument of strong selection for IQ, albeit over a significantly shorter time span, was made for French Canadians by Peter Frost, on the basis of an overlapping but not identical cluster of genetic diseases [6]. Here we get a list including several genetically mediated vitamin D deficiencies. Apparently vitamin D limits neuronal growth, and if intelligence is evolutionary very high-return, rickets takes a backseat.

Additionally, there is this Scottish family, where all members with a certain mutation, sport a 20 point verbal IQ advantage over those members without the mutation [7]. Unfortunately, they also go blind in their early twenties.

So, these cases gives us a rather long list of proteins, whose inhibition is likely to increase IQ. To me this sounds like a perfect opportunity to design drugs to target these proteins. The potential IQ gains are very considerable.

Of course if you inhibit these proteins completely you will get a nasty disease. But these diseases are very slow acting, so you probably have plenty of time to go off the stuff once you develop symptoms. Also, given this long list, you could cycle through different drugs/proteins evading negative symptoms while keeping the IQ benefit.

There is the possibility that the effect is limited to embryo genesis or early childhood development.This would make drug testing highly problematic. But given that newborn’s brains are already stuffed with synapses anyway, this seems quite unlikely for the dendritic growth enhancing diseases. So this problem is likely limited to the vitamin D diseases and those might be less promising anyway.

But even if the probability of this research avenue resulting in a side-effect free drug, that enhances IQ by some ten points or so, is only 0.1%, and even if it costs a billion dollars to design and test these potential drugs, the expected return is still pretty overwhelming.

So let’s say monday SpaceX, tuesday Tesla, wednesday Boring Company, thursday Neuralink, friday Open AI, and instead of smoking pot with Joe Rogan on saturday, how about a drug designing startup on saturday, that might just save the world?

[1] https://en.wikipedia.org/wiki/List_of_Jewish_Nobel_laureates

[2] https://en.wikipedia.org/wiki/Ashkenazi_Jewish_intelligence

[3] https://data.worldbank.org/indicator/NY.GDP.PCAP.KD

[4] http://web.mit.edu/fustflum/documents/papers/AshkenaziIQ.jbiosocsci.pdf

[5] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(70)91848-9/fulltext

[6] https://www.researchgate.net/publication/256296499_Tay-Sachs_and_French_Canadians_A_Case_of_Gene-Culture_Co-evolution

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740882/

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