“The safest road to hell is the gradual one—the gentle slope, soft underfoot, without sudden turnings, without milestones, without signposts.”

- C.S. Lewis

“The more you seek the uncomfortable, the more comfortable you will become” 

- Conor McGregor 

"Never wrestle with a pig because if you do you'll both get dirty but the pig will enjoy it"

- Charlie Munger

A. Your Blueprint

Remember the old debate: Nature vs Nurture.

What do you think is more important Nature (your DNA) or Nurture (your environment) in determining your characteristics, abilities, even outcomes?

This is the topic of Professor Robert Plomin’s work and his book: Blueprint. He is a behavioral geneticist at King’s College London and has done some ground breaking work in behavioral genetics.

To start, how would you fill out the table below. Take a minute and jot some numbers down on paper.

Heritability is how much of the differences between individuals can be explained by their inherited DNA differences.

Now compare your notes above to this. These are the average ratings across 5,000 adults and the results of genetic research:

It turns out that we no longer see any reliably measured personal trait that is not heritable to some degree.

To be clear on this: the 70 per cent heritability for weight means that 70 per cent of the differences between people in their weight can be attributed to differences in their inherited DNA sequence.

The other 30 per cent could be due to systematic environmental factors, such as diet and exercise, or unsystematic – random – environmental factors.

Genetically, we are 99% the same, so genetics is the study of the influence of the 1% of our DNA sequence that differs between us (which is still 30 million rungs in the DNA sequence that has 3bn base pairs). 

Key ideas to take away:

A. Heritability is not due to one or even several genes. It is the product of thousands of tiny differences of extremely small effect, taken together. This set of differences can be brought together in a ‘polygenic score’ that draws in analysis of thousands of SNPs (pronounced as “snips” - single-nucleotide polymorphism – a change in one of the 3 billion pairs in the DNA double helix).

B. The Nature of Nurture (aka Parents Matter, But They Don’t Make A Difference): Parents who value reading, and read to their kids, often have kids that enjoy reading. This is not because the parents read to their kids (it is correlated with that, not caused by it). It is primarily an inherited feature – bookishness is approximately 50% heritable. Parents do not create kids except at a genetic level.

Your genes determine how you perceive things and what environments you are attracted to, parents who enjoy and value reading will likely have kids who also enjoy reading and being read too. That also means that two siblings with 50% DNA overlap will do differently in the same environment, but the good news is that children are great at making their environment, regardless of their parents, but you do have to listen.

C. The Genie Is Out of the Bottle and Our Future is DNA. Because we can predict better we can now do better at prevention. For example, we can identify through genetic testing, those at elevated risk of coronary heart disease and offer them advice on preventative behaviour. The UK health system, through the NHS, has a vested interest in prevention (unlike the private US system which thrives on performing procedures). Although the early focus has tended to be on rare, single gene disorders, the big advances in health will come when polygenic scores are able to predict common disorders in the population. Predictive power undermines the current risk-pooling insurance system, which will need to be totally rethought.

What does it mean for society? Our understanding of freewill is at stake: to what extent are we in control of our own destinies and those of our kids? In the future, people may have the ability to screen out partners based on their genetic profiles/polygenic scores. What will this mean and how will policy and regulators respond?

He underscores that despite his findings, we should not be too fatalistic: much of what happens to us in life is due to chance, a chance meeting, a random decision. We do not live in a fully deterministic world.

The Times reviewed the book in 2018.

If you want to dive deeper into the world of DNA and what it could mean for our future, check out Hacking Darwin by Jamie Metzl, covered recently on our post on the Future of Life.

And Walter Isaacson has just written a book on CRISPR and Jen Doudna (one of the founders alongside Emmanuelle Charpentier of CRISPR, they both won the Nobel Prize for Chemistry last year).

Water Isaacson was on the Tim Ferris podcast discussing why he choose to write about Gene Editing now given prior books on Steve Jobs, Ben Franklin, Einstein, Leonardo da Vinci.

B. The Other Side Of The Fourth Turning

By now many of you have read William Strauss and Neil Howe’s Fourth Turning about the cycles of history.

Here’s a wikipedia link and here is our discussion from May.

Suffice it to say history moves in cycles of High, Awakening, Unraveling and Crises.

Which begs the question, what comes next for us?

William Gibson said:

The future is already here — it's just not very evenly distributed.

I’ve been looking for people and ideas who can show a glimpse of this potential future.

One of the people I have found with an interesting vision is Balaji Srinivasan. Balaji was formerly the CTO of Coinbase and General Partner at Andreessen Horowitz. He was also the cofounder of Earn.com (acquired by Coinbase), Counsyl (acquired by Myriad), Teleport (acquired by Topia), and Coin Center.

He was recently on the Hidden Forces podcast, which I recommend subscribing to.

A bunch of big ideas to think about:

A. Sovereign Cities. For now Silicon Valley is focused on the idea of The Sovereign Individual (must read book recommended by Peter Thiel) with the focus on self-ownership but the future will see the rise of network state and a move from a sovereign individual to sovereign cities and towns. As we have seen, technology gives more and more control to smaller and smaller groups. How does this and cryptocurrencies pressure what we know as the current model of the state.

B. Internet 3.0. So much of Internet 1.0 and 2.0 has just been a digital version of the physical - he has this paper, scanner, digital framework.

Take online education as an example we have moved down these models:

Paper: Physical Universities

Scan the Paper: Coursera or Udacity

Digital: Businesses really made for the internet from the ground up

In his mind, going forward businesses will be digital first. What ever is working, whatever is premium will then become physical if its really going somewhere.

C. Is the US a country without alignment? Balaji asks, what do we have in common anymore? What is the idea that aligns us as a country? Do we need a common enemy to stick together as a country? Everyone says America is a country of immigrants, but then they forget that immigrants can also go somewhere else. They don’t need to keep coming to the US.

C. A Few Things Worth Checking Out:

1. My two man crushes were on The Invest Like the Best Podcast: Josh Wolfe and Tony Thomas of Lux Capital - The Past, Present, and Future of Defence.

On the subject of national security, I’m interviewing Shawn Henry, President of CrowdStrike and 25 years at the FBI in two weeks on behalf of Pi Capital, to discuss cybersecurity and what we can do to protect ourselves. Email if you’d like to join.

2. The Master Investor held a great conference last week on the Agrarian Revolution, and the opportunities in Alternative Proteins. We covered the Future of Food in November.

3. Here is some surprisingly good insight from Bill Ackman on the math and logic behind the explosion of SPACs (Bill is obviously objective on this topic because he raised $4B in the largest SPAC launch of 2020).

4. Bain Capital released their seminal Global Private Equity Report.

It is not the critic who counts; not the man who points out how the strong man stumbles, or where the doer of deeds could have done them better. The credit belongs to the man who is actually in the arena, whose face is marred by dust and sweat and blood; who strives valiantly; who errs, who comes short again and again, because there is no effort without error and shortcoming; but who does actually strive to do the deeds; who knows great enthusiasms, the great devotions; who spends himself in a worthy cause; who at the best knows in the end the triumph of high achievement, and who at the worst, if he fails, at least fails while daring greatly, so that his place shall never be with those cold and timid souls who neither know victory nor defeat. 

- Theodore Roosevelt, April 1910