Slaying the gatekeepers

Something a little different today.

I’ve been banging on about CRISPR and its world-changing potential all week. I suppose I would: I wrote a book which detailed CRISPR’s revolutionary potential pretty prominently.

I’ve told you several times that you can get a free copy of my book The Exponentialist, by using this link. If you haven’t done so yet, today I want to take a different tack and show you what you’re missing. I’ve prepared a short sample for you to read.

Disclaimer: I’m not sharing this with you for entirely altruistic reasons. Yes, I think understanding (and investing) in CRISPR is one of the most valuable things you can do with your time and money.

But I’m also pressed for time myself today. I’m in the final stages of writing a speech I have to deliver to a room full of publishers and financial experts on Monday morning. I need the time to prepare!

The speech, if you’re interested, is loosely titled “Slaying the Gatekeeper”. I’m going to talk about how elite institutions – the mainstream media, government, central banks, mainstream political parties – perpetuate “gated institutional narratives”.

My argument is that these institutions effectively create, push and guard a narrow set of viewpoints and ideas about the world. These narratives don’t necessarily have to correlate all that much with reality or with the values massive numbers of people hold. But the fact they’re advanced by cultural, economic or political “gatekeepers” gives them a power and a reach.

What’s important, though, is that the gatekeepers will go out of their way to marginalise competing ideas. They’ll be silenced. Ridiculed. Dismissed. De-platformed.

You can map this on to the social or political world, but I’m particularly interested in how it affects the financial world, which I’d argue is the holy land of the gated institutional narrative.

There’s a reason the self-appointed guardians of the financial system – the Bank of England, European Central Bank, International Monetary Fund, etc – don’t see major turning points coming. I’m talking about high-impact, seemingly low-probability events like the 2008 global financial crisis, the Greek crisis, the rise of disruptive technology cryptocurrencies, the dot-com boom, the fall of communism (I could go on, but the point is made).

The forces that shape these events can be understood and predicted. But not if you use the narrow set of models perpetuated by “the gatekeepers”. True understanding of radical change requires considering ideas and possibilities that have been entirely dismissed or marginalised.

Perhaps I’ll publish my entire argument on that front another day. The reason I bring it up right now is that I believe CRISPR plays into this idea perfectly.

There’s plenty of evidence of CRISPR’s revolutionary potential. But I already sense that anyone putting this evidence together and following it through to its logical conclusions – and reaching a world that is radically different to the one we live in today – would be marginalised as a “sensationalist” or a “crazy”.

I think that’s wrong. Look back on tech history and you see that people repeatedly underestimate the speed with which new breakthroughs can change the world. Twenty years ago companies like Amazon, Apple and Google were mere upstarts. Now they’re the richest, most powerful companies in the world.

I believe in the next 20 years we’ll see a new kind of company emerge, and then dominate, the world – one built around manipulating the living world using genetic editing. That in turn will shape people’s lives and the world around them.

Who needs God?

Of course, Angela’s future life and the announcement that Crick made in The Eagle all those years ago are inextricably linked. Without Watson and Crick’s discovery, the modern field of genetics would not exist.

Crick and Watson’s discovery laid the foundations. The Human Genome Project pushed our understanding even further. But it is a very recent breakthrough that has really unlocked the potential for genetics to change the world. That breakthrough is known as CRISPR/Cas9, or CRISPR for short. It stands for Clustered Regularly Interspaced Short Palindromic Repeats. And it enables us to do something no civilisation before us has ever had the ability to do – to edit the genetic makeup of living things and remake ourselves the way we want to be.

Crick and Watson’s discovery was akin to finding an instruction manual for the human body. Decoding the genome in 2000 allowed us to read the words inside. CRISPR allows us to rewrite the book altogether –cross out parts we don’t like, swap whole pages with those of another book, create an entirely new book if we like.

Actually, it does more than that.

It is sometimes easy to forget that DNA is “the secret”, to somewhat corrupt what Francis Crick said, “of all life”. It is not just humanity. Every plant, animal and most single celled organism on the planet is built using that same code. The ability to edit it means we’re not just able to remake ourselves – we’re able to remake the entire world. It gives us the power to create entirely new “synthetic” creatures, resurrect animals that have been extinct for thousands of years, wipe out entire species if we so choose.

The ability, in short, to play God.

That’s ground-breaking. But before we jump too far ahead, just consider the fact that trying to manipulate the genetic makeup of animals and plants is something that’s been going on for centuries. Cross-pollinating one plant with another in an attempt to achieve a desired characteristic – a colour, resistance to disease, size, etc. – is something we have evidence of, stretching all the way back to the agricultural revolution.

The difference now is that we know exactly which genes we want to target, and in CRISPR we have a tool with the precision to make that possible. It allows us to target and modify DNA with incredible accuracy. And it’s already become both saviour to some and pariah to others. According to a Vice story in April 2015:

Not only are scientists publishing reports on the technique at breakneck speed (at 370 mentions in research publications so far this year, that’s a rate of 20 papers a week), but it also seems that each piece of news that comes out about CRISPR/Cas9 is grander and juicier than the last.

In the past two weeks alone scientists have announced that they have used the new technology to inhibit Hepatitis C in human cells and to defy Mendel’s laws of inheritance, which have governed the field of genetics for over a century.

We’ll explore the uses of CRISPR – and there are hundreds – in a second. But first, given that CRISPR has the potential to have the single biggest impact on our lives and the world we live in over the next 20 years, I think it’s worth understanding how it works. And what better way to do that than to hear it directly from one of the scientists who helped develop it? We spoke to Harvard’s Professor George Church, credited as one of CRISPR’s co-developers. First off, metaphors about editing the pages in a book aside, how does CRISPR actually work?

In nature, it works to kill bacterial invading viruses by remembering previous invasions. It does that by keeping a little piece of the DNA from the [invading] virus, and then that makes it super-easy for it to reprogram a cutting machine, the CRISPR nuclease. That’s what it does in nature.

Slowly, people adapted it. As a technology, it became editing: changing from killing viruses to editing DNA very precisely – not just making a mess, as you might with killing, with cutting, but replacing DNA. That was announced in January 2013 by two groups, mine and one of my ex-post-docs, Feng Zhang, who was by that time an independent investigator at the Broad Institute.

Soon thereafter, it became evident that, unlike some technologies which are hard, this one was easy. There is no way you could have predicted that.

It’s easy to adapt to other organisms once you solve how to adapt it to humans, which is what we did first.

 Any method of gene editing has some similarity to previous genetic engineering tools in what it can be applied to. Those applications include agriculture – plants and animals and to some extent microorganisms like fungi. It can be used for curing genetic diseases. It can be used for fighting infections, just like its original use for cutting viruses. It already is in use for fighting leukaemia and HIV-Aids. I’m being broad here, talking about genome editing – not just CRISPR.

It can be used for xeno-transplantations – moving organs from pigs to humans – and making those pigs virus-resistant, or making a variety of things virus-resistant.

Finally, it can be used for gene drives, where you can engineer wild populations at low cost and high precision to fight diseases like malaria, dengue, Lyme disease and so on.

Gene therapy is a big category that includes classically and typically inserting new genes. Then you can use more precise gene editing to both remove and insert, and that’s where CRISPR comes in.

There are 2,000 gene therapies in clinical trials, and many of those are already curing people. It doesn’t mean they’ve been approved for general use.

They’re in the process of doing the gene therapy trials to get a fair number of people cured of, for example, blindness. There are some genetic causes of blindness that are curable by gene therapies. In most cases, you have to do it very early in life, like in young children – or else they’ll be able to cure them to the point where they can see light but they can’t interpret the light or stasis because their brains have developed too far.

There are other infectious agents like hepatitis viruses, blood diseases that cause hemolytic anemia – the list is long. There are thousands of genes that are so well understood that some of them can be addressed by genetic counselling. But once you have a child that has the disease, then you need to have some kind of cure or prevention for the development of downstream technologies.

There’s a lot of debate about what can – and what ethically should – be done about this. Like any truly revolutionary technology capable of changing the world in a radical way, gene editing has both enormous upside and serious potential downside. Bioethicist Françoise Baylis, a professor at Dalhousie University, says it’s “like any dual-use technology that can be used for good or evil. It can be the murder weapon, it can be the gavel the judge uses. So I don’t know that there’s any way to sort of control that.”

Best,


Nick O’Connor
Publisher, Southbank Investment Research

Category: Genetics and Biotechnology

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