Everything You Should Know About CRISPR — And Where to Learn More
A primer on gene editing for the rest of us
A few months ago, someone in my Facebook news feed shared an article with a title along the lines of, “You won’t believe what scientists are doing with CRISPR.” My first thought was, “What is CRISPR?”
After a bit of research, I realized just how difficult it is to get up to speed on subjects outside my area of expertise (software and startups). What are the best introductory explainers — print, video, and audio? Who are the most important thought leaders, operators, or researchers? After 30+ hours of research, I’ve learned so much, but I also wasted a lot of time filtering out low-quality derivative content.
After spending so much time researching CRISPR, I thought I’d save everyone else the time, write a summary of why I think it’s a big deal, and then curate some of the best content on the subject I found.
If people find this valuable, I’ll deep dive on another subject, and I’d love to hear what topics you’d like to learn about.
Table of Contents
The Super Duper High Level Summary
Once I finally got a grip on CRISPR, I had a revelation. Sometimes I ask myself, “What technology will we invent that could possibly change the world as much as the Internet?”
After all of my research, I’m convinced that CRISPR has the potential to do just that.
CRISPR is a term often used to refer to new methods used to edit DNA (that’s the chemical that makes up all your genes, which in sum is your unique genome) to a level of precision akin to using a microscopic scalpel.
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Not a scientist? Me either. In normal speak, CRISPR is what scientists call small (short) patterns (repeats) of DNA that occur in spaced out groups (clustered regularly interspaced) that are the same spelled backwards and forwards (palindromic). You will frequently see CRISPR appended like this “CRISPR-Cas9” or “CRISPR-Cpf1.” Cas9 and Cpf1 are proteins that can be used with these sections of DNA to edit them¹ ².
Using CRISPR to edit DNA is so cheap that a graduate student with access to a lab can get started for $75. Using these methods, scientists in labs have already edited genomes in mice that changed their fur from black to white³, in tomatoes that slow down rot⁴, and again in mice that reversed blindness causing mutations⁵.
Scientific consensus appears to hold that CRISPR is going to be huge⁶ ⁷. While CRISPR could be used to cure a wide ranging variety of diseases, some fear it could be used to create super humans or lead to accidental biological disaster.
How would that work?
Well, scientists are currently throwing around wild ideas for the application of CRISPR such as “making your bones so hard they’ll break a surgical drill” and genetically sterilizing mosquitos in order to prevent the spread of Malaria and Zika⁸ ⁹. While a world without Malaria and Zika might sound nice, keep in mind that we don’t know what kind of effect that might have on the biosphere.
Not only that, but some of these “ideas” have millions of dollars in funding from The Bill and Melinda Gates Foundation and numerous venture capital funds. After an initial pass, I found 15 companies that, according to data from Mattermark, have raised more than $1 billion dollars in aggregate.
But wait, there’s more.
Chinese scientists have already attempted two experiments on human embryos. Editing the DNA of human embryos is particularly controversial, because, if the DNA is edited as intended, then offspring of the edited human could inherit those traits.
In this case, the embryos could not have been brought to full term¹⁰, and the experiments were essentially failures. The second of the two proved to the scientific community that editing human DNA that can be passed on via reproduction via a methodology a “gene drive” is much more complicated than changing the fur color in mice¹¹.
Editing the human genome terrifies a lot of people. It raises endless ethical questions, and conjures up memories of 1997’s Gattaca. Before you break out your pitchfork though, know that “we are already preselecting humans based on medical conditions,” as a 1999 study suggested 92% of pregnancies where Down Syndrome was detected were being terminated in Europe¹².
Finally, much of the media coverage of CRISPR centers around a patent dispute between two groups of scientists, who have since founded companies, who filed CRISPR-Cas9 patents within months of each other.
To keep it simple, Jennifer Doudna of The University of California Berkeley and Founder of Intellia Therapeutics sits on one side. On the other, Feng Zhang of The Broad Institute of Harvard and M.I.T. and Founder of Editas Medicine.
The media loves a good patent dispute, but The New Yorker reported the following in 2015:
“Zhang was awarded the patent, but the University of California has requested an official reassessment, and a ruling has not yet been issued. Both he and Doudna described the suit to me as “a distraction” that they wished would go away. Both pledged to release all intellectual property to researchers without charge (and they have).”
My Take on the Present & Future of CRISPR
I think it’s absolutely bonkers that, in the majority of the media coverage I found via a significant amount of Googling (this is how most people learn), only one article mentioned this. One. I even talked to a venture capitalist at a well-known firm who had dismissed CRISPR as a potential area to invest in because of the patent dispute. Now that he knows the IP is most likely going to be given away for free, I believe he’ll be taking a second look.
After all my research, I can’t help but get the feeling that while it’s still early for CRISPR, this is one of those developments that’s going to change our lives a lot. I wasn’t even born yet when cell phones were as big as mustache guy over here to the left, but I’d bet that while people got excited about cell phones in the 80’s, very few people could imagine that Motorola big grey brick phones would lead to iPhones that could monitor our blood pressure, hold a map of the world, and turn our lights on and off.
To me, CRISPR is the beginning of a new age of tools biologists will use to manipulate our DNA. I would not be surprised at all if we see a disease cured by scientists using CRISPR by 2020. Whether it’s 2020, 2030, or 2040 though, what matters is that once the precision to eliminate or cure one disease is reached, it will be a watershed moment that enables us to eliminate or cure a many of them.
The ability to edit DNA opens up a lot of ethical questions, and we should take the time to discuss these over the dinner table. Would you make the call to edit your child’s DNA to prevent them from suffering from a disease? What about changing their DNA to have a specific eye color? It’s a slippery slope, but I’m pretty damned sure that someone will make the decision to do both.
I believe that day is going to come in our lifetimes, but even if you don’t, what if it does?
Where to Start Learning about CRISPR
After hours and hours of reading about CRISPR, these are the articles, videos, and podcasts I found to be the most helpful to get started. There are a large number of pieces that go deeper, and an even larger number that repeat what’s covered in what I’ve curated here. For as many of each content type I listed here, I chose not to include 2–3x others.
Under each section, content is sorted from longest [30m] to shortest [4m] time to consume. Each section has a link to a form with a 👉 to help me improve this on an ongoing basis, so if I’ve missed something or made a mistake, let me know! Pieces with a 💥 are my favorite.
💥 [31m] 11.16.15 “The Gene Hackers”
Michael Specter of The New Yorker shares a wondrously comprehensive analysis of the state of CRISPR. He introduces Feng Zhang, one of many scientists credited with pioneering the use of CRISPR to edit genomes, outlines current and future applications of the technology, acknowledges how CRISPR’s story is only starting, and helps us understand how genome editing has evolved over time. Perhaps most interestingly, Michael provides a perspective on the patent dispute over CRISPR not seen in many other publications and even quotes both the Doudna camp and the Zhang camp saying they plan to give away the IP to researchers. Specter’s article is also one of the few posts I came across that mentions use of Cpf1, a protein Zhang says is “smaller and easier to program than Cas9.” Specter addresses the ethical concerns in impressive detail to cap off my personal favorite post. It’s a year old, and the science is advancing quickly, but this is a great place to start.
[22m] 03.05.15 “Engineering the Perfect Baby”
Antonio Regalado of MIT Technology Review sounds the alarm about CRISPR’s potential to lead to designer babies a la Gattaca. Regalado dives deeper into germ-line editing than any other writer I’ve discovered, and draws particular attention to those rebuking the scientific party line and experimenting with it like George Church and another Boston startup, OvaScience. He draws attention to future applications of CRISPR such as human enhancements like, “making your bones so hard they’ll break a surgical drill.” Regalado’s post is characterized by a foreboding tone, but it is important to note that it came before research was released by Chinese scientists indicating that editing of the human genome in embryos will be far more challenging than initially thought. “Engineering the Perfect Baby”
[20m] 08.01.15 “The Genesis Engine”
Amy Maxmen of WIRED writes the best historical record of CRISPR’s origin I’ve come across, starting with the 1975 Asilomar Conference on the ethics of genome editing. Amy also draws attention to big companies and venture capital’s interest in companies related to CRISPR while also highlighting applications from food to editing mosquitos genome. Finally, she offers a much less chilling look at CRISPR than Antonio Regalado’s “Engineering the Perfect Baby,” and even shows us a much more cautious side of George Church in “The Genesis Engine”
[14m] 04.13.16 “The Extinction Invention”
Antonio Regalado of MIT Technology Review calls attention to the use of CRISPR to modify the genome of mosquitos via a technique called a “gene drive,” which would lead to genome modifications being passed onto affected mosquitos’ offspring. Regalado points out that The Gates Foundation has poured $44M into a project called “Target Malaria,” and the foundation is now convinced that gene drive utilization is the key to wiping out Malaria. While that sounds nice, Regalado also points out the risks with questions like, “what country, agency, or individual has the right to change nature in ways that could affect the entire globe?”
Gina Kolata of The New York Times dives into the intimidating Chinese study which used CRISPR to edit the germline of human embryos. Kolata helps us understand how the results of the study show us that the technology is not ready to be applied to human embryos, supporting Doudna’s call for a moratorium on doing so.
Sharon Begley of PBS announces the first approval for use of CRISPR in human subjects in a study designed to attack cancer cells.
[30m] 06.09.16 “Panorama on CRISPR”
BBC One — Panorama released the most recent piece of high-quality content I’ve been able to find on CRISPR. It includes interviews with key scientists and explores active experiments in more depth on screen than anything else I’ve been able to find.
💥 [17m] 04.10.16 “Genetic Engineering Will Change Everything Forever”
Kurzgesagt — In a Nutshell produced a beautiful, easy-to-understand animated overview of CRISPR, its potential applications and ethical dilemmas, and compares the state of genetic engineering to the state of computing in the 1980’s.
[16m] 11.12.15 “How CRISPR lets us edit our DNA”
Jennifer Doudna of The University of California Berkeley and Intellia Therapeutics presents at TED and explains how CRISPR can be used to engineer genomes and calls for a global pause in any clinical application of the CRISPR technology in human embryos.
[10m] 10.24.16 “What you need to know about CRISPR”
Ellen Jorgensen of Genspace speaks at TED emphasizes that the CRISPR technology is moving much faster than the regulatory mechanisms that govern it, digs into the myths and realities around CRISPR, and lays out open questions related to CRISPR.
[8m] 02.18.16 “What is CRISPR?”
Paul Andersen of Bozeman Science gets slightly more technical than the prior to videos as he explains how CRISPR works.
[7m] 10.08.16 CRISPR-Cas9 (“Mr. Sandman” Parody)
Tim Blais of acapellascience performs a hilarious a capella explanation of CRISPR.
[5m] 11.05.14 “Genome Editing with CRISPR-Cas9”
The McGovern Institute for Brain Research at M.I.T. walks us through how CRISPR works in a short, true to form animation.
💥 [33m] 06.06.15 Radiolab “Antibodies Part 1: CRISPR”
“I am waiting for someone to say CRISPR doesn’t work in species X, and I have not heard that.” — Science writer Carl Zimmer
[33m] 2016 Radiolab “Donation and Mutation”
[4m] 11.02.16 Morning Edition “Science Rewards Eureka Moments, Except When It Doesn’t”
[5m] 09.22.16 Morning Edition “Breaking Taboo, Swedish Scientist Seeks To Edit DNA Of Healthy Human Embryos”
[3m] 04.15.16 All Things Considered “Will Genetically ‘Edited’ Food Be Regulated? The Case Of The Mushroom”
[6m] 12.28.15 All Things Considered “Gene Editing Tool Hailed As A Breakthrough, And It Really Is One”
[4m] 04.15.16 All Things Considered “Scientists Debate How Far To Go In Editing Human Genes”
[4m] 11.05.15 Morning Edition “Powerful ‘Gene Drive’ Can Quickly Change An Entire Species”
People & Publications
If the individual is on Twitter, I’ve linked to their account. If not, I’ve linked to an account associated with them.
Jennifer Doudna & Emmanuelle Charpentier — Jennifer & Emmanuelle filed the first patent to use CRISPR-Cas9. Neither of them are active on Twitter, but both regularly appear in video & audio interviews all over the web. Jennifer co-founded Intellia Therapeutics, and Emmanuelle founded Crispr Therapeutics, both big players in the space.
Feng Zhang & George Church — Feng and George have collaborated at M.I.T. and Harvard. Feng filed the second patent to use CRISPR-Cas9, but his got approved first because his lawyer expedited the filing (smart). The two went on to found Editas Medicine.
Companies to Watch
Below are 16 companies each experimenting with CRISPR. According to Mattermark (full disclosure, I co-founded Mattermark) data they have raised more than $1B in aggregate.
Editas Medicine (NASDAQ:EDIT)
Intellia Therapeutics (NASDAQ:NTLA)
Crispr Therapeutics (NASDAQ:CRSP)
Sangamo BioSciences (NASDAQ: SGMO)
bluebird bio (NASDAQ:BLUE)
Horizon Discovery (LON:HZD)