Articles

The age of genetic wonder | Juan Enriquez

December 15, 2019


So let me with start with Roy Amara. Roy’s argument is that most new
technologies tend to be overestimated in their impact to begin with, and then they get underestimated
in the long term because we get used to them. These really are days
of miracle and wonder. You remember that wonderful
song by Paul Simon? There were two lines in it. So what was it that was considered
miraculous back then? Slowing down things — slow motion — and the long-distance call. Because, of course, you used
to get interrupted by operators who’d tell you, “Long distance calling.
Do you want to hang up?” And now we think nothing of calling
all over the world. Well, something similar may be happening with reading and programming life. But before I unpack that, let’s just talk about telescopes. Telescopes were overestimated
originally in their impact. This is one of Galileo’s early models. People thought it was just
going to ruin all religion. (Laughter) So we’re not paying that much
attention to telescopes. But, of course, telescopes launched
10 years ago, as you just heard, could take this Volkswagen,
fly it to the moon, and you could see the lights
on that Volkswagen light up on the moon. And that’s the kind of resolution power
that allowed you to see little specks of dust
floating around distant suns. Imagine for a second that this
was a sun a billion light years away, and you had a little speck of dust
that came in front of it. That’s what detecting
an exoplanet is like. And the cool thing is, the telescopes
that are now being launched would allow you to see
a single candle lit on the moon. And if you separated it by one plate, you could see two candles
separately at that distance. And that’s the kind
of resolution that you need to begin to image
that little speck of dust as it comes around the sun and see if it has a blue-green signature. And if it does have
a blue-green signature, it means that life
is common in the universe. The first time you ever see a blue-green
signature on a distant planet, it means there’s photosynthesis there, there’s water there, and the chances that you saw
the only other planet with photosynthesis are about zero. And that’s a calendar-changing event. There’s a before and after
we were alone in the universe: forget about the discovery
of whatever continent. So as you’re thinking about this, we’re now beginning
to be able to image most of the universe. And that is a time of miracle and wonder. And we kind of take that for granted. Something similar is happening in life. So we’re hearing about life
in these little bits and pieces. We hear about CRISPR,
and we hear about this technology, and we hear about this technology. But the bottom line on life
is that life turns out to be code. And life as code is a really
important concept because it means, just in the same way
as you can write a sentence in English or in French or Chinese, just in the same way
as you can copy a sentence, just in the same way
as you can edit a sentence, just in the same way
as you can print a sentence, you’re beginning to be able
to do that with life. It means that we’re beginning
to learn how to read this language. And this, of course, is the language
that is used by this orange. So how does this orange execute code? It doesn’t do it in ones and zeroes
like a computer does. It sits on a tree, and one day it does: plop! And that means: execute. AATCAAG: make me a little root. TCGACC: make me a little stem. GAC: make me some leaves.
AGC: make me some flowers. And then GCAA: make me some more oranges. If I edit a sentence in English
on a word processor, then what happens is you can go
from this word to that word. If I edit something in this orange and put in GCAAC, using CRISPR
or something else that you’ve heard of, then this orange becomes a lemon, or it becomes a grapefruit, or it becomes a tangerine. And if I edit one in a thousand letters, you become the person
sitting next to you today. Be more careful where you sit. (Laughter) What’s happening on this stuff
is it was really expensive to begin with. It was like long-distance calls. But the cost of this is dropping
50 percent faster than Moore’s law. The first $200 full genome
was announced yesterday by Veritas. And so as you’re looking at these systems, it doesn’t matter, it doesn’t matter,
it doesn’t matter, and then it does. So let me just give you
the map view of this stuff. This is a big discovery. There’s 23 chromosomes. Cool. Let’s now start using a telescope version,
but instead of using a telescope, let’s use a microscope to zoom in on the inferior of those chromosomes, which is the Y chromosome. It’s a third the size of the X.
It’s recessive and mutant. But hey, just a male. And as you’re looking at this stuff, here’s kind of a country view at a 400 base pair resolution level, and then you zoom in to 550,
and then you zoom in to 850, and you can begin to identify
more and more genes as you zoom in. Then you zoom in to the state level, and you can begin to tell
who’s got leukemia, how did they get leukemia,
what kind of leukemia do they have, what shifted from what place
to what place. And then you zoom in
to the Google street view level. So this is what happens
if you have colorectal cancer for a very specific patient
on the letter-by-letter resolution. So what we’re doing in this stuff
is we’re gathering information and just generating
enormous amounts of information. This is one of the largest
databases on the planet and it’s growing faster
than we can build computers to store it. You can create some incredible
maps with this stuff. You want to understand the plague
and why one plague is bubonic and the other one
is a different kind of plague and the other one
is a different kind of plague? Well, here’s a map of the plague. Some are absolutely deadly to humans, some are not. And note, by the way,
as you go to the bottom of this, how does it compare to tuberculosis? So this is the difference between
tuberculosis and various kinds of plagues, and you can play detective
with this stuff, because you can take
a very specific kind of cholera that affected Haiti, and you can look at
which country it came from, which region it came from, and probably which soldier took that
from that African country to Haiti. Zoom out. It’s not just zooming in. This is one of the coolest maps
ever done by human beings. What they’ve done is taken
all the genetic information they have about all the species, and they’ve put a tree of life
on a single page that you can zoom in and out of. So this is what came first,
how did it diversify, how did it branch, how large is that genome, on a single page. It’s kind of the universe
of life on Earth, and it’s being constantly
updated and completed. And so as you’re looking at this stuff, the really important change is
the old biology used to be reactive. You used to have a lot of biologists
that had microscopes, and they had magnifying glasses
and they were out observing animals. The new biology is proactive. You don’t just observe stuff,
you make stuff. And that’s a really big change because it allows us
to do things like this. And I know you’re really
excited by this picture. (Laughter) It only took us four years
and 40 million dollars to be able to take this picture. (Laughter) And what we did is we took the full gene code
out of a cell — not a gene, not two genes,
the full gene code out of a cell — built a completely new gene code, inserted it into the cell, figured out a way to have the cell
execute that code and built a completely new species. So this is the world’s first
synthetic life form. And so what do you do with this stuff? Well, this stuff is going
to change the world. Let me give you three short-term trends in terms of how it’s going
to change the world. The first is we’re going to see
a new industrial revolution. And I actually mean that literally. So in the same way as Switzerland
and Germany and Britain changed the world with machines
like the one you see in this lobby, created power — in the same way CERN
is changing the world, using new instruments
and our concept of the universe — programmable life forms
are also going to change the world because once you can program cells in the same way as you
program your computer chip, then you can make almost anything. So your computer chip
can produce photographs, can produce music, can produce film, can produce love letters,
can produce spreadsheets. It’s just ones and zeroes
flying through there. If you can flow ATCGs through cells, then this software makes its own hardware, which means it scales very quickly. No matter what happens, if you leave your cell phone
by your bedside, you will not have a billion
cell phones in the morning. But if you do that with living organisms, you can make this stuff
at a very large scale. One of the things you can do
is you can start producing close to carbon-neutral fuels on a commercial scale by 2025, which we’re doing with Exxon. But you can also substitute
for agricultural lands. Instead of having 100 hectares
to make oils or to make proteins, you can make it in these vats at 10 or 100 times
the productivity per hectare. Or you can store information,
or you can make all the world’s vaccines in those three vats. Or you can store most of the information
that’s held at CERN in those three vats. DNA is a really powerful
information storage device. Second turn: you’re beginning to see the rise
of theoretical biology. So, medical school departments are one
of the most conservative places on earth. The way they teach anatomy is similar
to the way they taught anatomy 100 years ago. “Welcome, student. Here’s your cadaver.” One of the things medical schools are
not good at is creating new departments, which is why this is so unusual. Isaac Kohane has now created a department
based on informatics, data, knowledge at Harvard Medical School. And in a sense,
what’s beginning to happen is biology is beginning to get enough data that it can begin to follow
the steps of physics, which used to be observational physics and experimental physicists, and then started creating
theoretical biology. Well, that’s what you’re beginning to see because you have so many medical records, because you have
so much data about people: you’ve got their genomes,
you’ve got their viromes, you’ve got their microbiomes. And as this information stacks, you can begin to make predictions. The third thing that’s happening
is this is coming to the consumer. So you, too, can get your genes sequenced. And this is beginning to create
companies like 23andMe, and companies like 23andMe
are going to be giving you more and more and more data, not just about your relatives, but about you and your body, and it’s going to compare stuff, and it’s going
to compare stuff across time, and these are going to become
very large databases. But it’s also beginning to affect
a series of other businesses in unexpected ways. Normally, when you advertise something,
you really don’t want the consumer to take your advertisement
into the bathroom to pee on. Unless, of course, if you’re IKEA. Because when you rip this
out of a magazine and you pee on it, it’ll turn blue if you’re pregnant. (Laughter) And they’ll give you
a discount on your crib. (Laughter) Right? So when I say consumer empowerment, and this is spreading beyond biotech, I actually really mean that. We’re now beginning to produce,
at Synthetic Genomics, desktop printers that allow you to design a cell, print a cell, execute the program on the cell. We can now print vaccines real time as an airplane takes off before it lands. We’re shipping 78
of these machines this year. This is not theoretical biology.
This is printing biology. Let me talk about two long-term trends that are coming at you
over a longer time period. The first one is, we’re starting
to redesign species. And you’ve heard about that, right? We’re redesigning trees.
We’re redesigning flowers. We’re redesigning yogurt, cheese, whatever else you want. And that, of course,
brings up the interesting question: How and when should we redesign humans? And a lot of us think,
“Oh no, we never want to redesign humans.” Unless, of course, if your child
has a Huntington’s gene and is condemned to death. Or, unless if you’re passing on
a cystic fibrosis gene, in which case, you don’t just want
to redesign yourself, you want to redesign your children
and their children. And these are complicated debates
and they’re going to happen in real time. I’ll give you one current example. One of the debates going on
at the National Academies today is you have the power to put
a gene drive into mosquitoes so that you will kill
all the malaria-carrying mosquitoes. Now, some people say, “That’s going to affect the environment
in an extreme way, don’t do it.” Other people say, “This is one of the things
that’s killing millions of people yearly. Who are you to tell me
that I can’t save the kids in my country?” And why is this debate so complicated? Because as soon as you
let this loose in Brazil or in Southern Florida — mosquitoes don’t respect walls. You’re making a decision for the world when you put a gene drive into the air. This wonderful man won a Nobel Prize, and after winning the Nobel Prize he’s been worrying about how did life get started on this planet and how likely is it
that it’s in other places? So what he’s been doing is going around
to this graduate students and saying to his graduate students, “Build me life but don’t use
any modern chemicals or instruments. Build me stuff that was here
three billion years ago. You can’t use lasers.
You can’t use this. You can’t use that.” He gave me a vial of what he’s built
about three weeks ago. What has he built? He’s built basically what looked like
soap bubbles that are made out of lipids. He’s built a precursor of RNA. He’s had the precursor of the RNA
be absorbed by the cell and then he’s had the cells divide. We may not be that far — call it a decade, maybe two decades — from generating life from scratch out of proto-communities. Second long-term trend: we’ve been living and are living
through the digital age — we’re starting to live through
the age of the genome and biology and CRISPR
and synthetic biology — and all of that is going to merge
into the age of the brain. So we’re getting to the point where
we can rebuild most of our body parts, in the same way as if you break a bone
or burn your skin, it regrows. We’re beginning to learn
how to regrow our tracheas or how to regrow our bladders. Both of those have been
implanted in humans. Tony Atala is working on
32 different organs. But the core is going to be this, because this is you
and the rest is just packaging. Nobody’s going to live beyond
120, 130, 140 years unless if we fix this. And that’s the most interesting challenge. That’s the next frontier, along with: “How common is life in the universe?” “Where did we come from?” and questions like that. Let me end this with
an apocryphal quote from Einstein. [You can live as if
everything is a miracle, or you can live as if
nothing is a miracle.] It’s your choice. You can focus on the bad,
you can focus on the scary, and certainly there’s
a lot of scary out there. But use 10 percent of your brain
to focus on that, or maybe 20 percent, or maybe 30 percent. But just remember, we really are living in an age
of miracle and wonder. We’re lucky to be alive today.
We’re lucky to see this stuff. We’re lucky to be able to interact
with folks like the folks who are building
all the stuff in this room. So thank you to all of you,
for all you do. (Applause)

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