Last time, we asked some big questions about
the future of computing and artificial intelligence.
Today, we’re going to ask about the life
sciences, medicine, and the brain.
Like what happens when medicine shifts from
treating illness to preventing it, and then
to a whole new terrain: enhancing life and
longevity?
What happens when life itself becomes a technology?
Something increasingly cheap and fast to redesign?
And why has mapping DNA been easier than mapping
our brains?
[Intro Music Plays]
When we last left medicine, giant companies
had commercialized pills that targeted specific
physiological systems.
And the human genome was decoded!
But the links between particular alleles,
or versions of genes, and specific diseases—like
cancers, immune diseases, or psychiatric disorders—remained
to be proven.
So in the 1990s, scientists began developing
cheaper, faster, more robust genetic tests
for well-known genes linked to disease.
This has given rise to a new way of associating
with each other, based on shared molecules—biosociality.
Nowadays, for example, many women with a family
history of breast cancer get tested to see
what version they have of two genes called
BRCA1 and BRCA2.
Communities have formed around people who
have the versions of these genes that make
someone much more likely
to develop breast or ovarian cancer later
in life.
There was a big fight over whether a private
company called Myriad Genetics
could patent the natural DNA tied to these
genes.
But the Supreme Court ruled in 2013 that they
couldn’t patent the natural DNA,
or anything invented by evolution.
Genetic testing has helped with the early
diagnosis of thousands of cases of cancer.
Some medical researchers have experimented
with genetic therapies.
These would involve replacing a region of
DNA giving rise to a disease with a doctor-designed
“therapeutic gene.”
Basically, patients’ genes get taken out,
changed, and put back in.
In 1990, the first genetic therapy temporarily
corrected an immune system disorder.
Other trials followed.
But in 1999, Jesse Gelsinger, a young man
with a rare genetic liver disease, died four
days after receiving a genetic therapy.
This had a chilling effect on the field for
years, although research continues.
Genetic therapies points toward an even bigger
promise—of personalized medicine.
We don’t have it yet, but many companies
are winning investors on the promise that
we will soon.
In this new regime, each patient will have
care tailored to her individual genome, and
more.
First, we need more basic science in human
genomics and several other fields—including
transcriptomics,
or how regions of DNA are copied into little
strands of RNA, and what effects those have.
Then there’s proteomics, or how proteins
fold together, which affects how they work.
Then there’s metabolomics, or how energy
moves around inside and outside of cells,
through fats, sugars, and acids.
Collectively, these are called - wait for
it - … omics—the total study of life at
the scale smaller than the cell.
But even with more information, engineering
life using twentieth-century technology
still meant painstakingly creating new synthetic
DNA parts and proteins by hand,
and testing over and over again to find the
rare successful result.
Plus, the vast majority of diseases are linked
to many genes—so changing anything means
making not one, but several stable edits.
And every edit increases the chances that
something is changed elsewhere—an off-target
effect.
Which is potentially really bad.
What was needed was a way to edit not single
regions of a genome, but many regions, with
less likelihood of off-target effects.
Enter the “technology of the century”
and one of the most valuable suites of patents
on the planet: clustered regularly interspaced
palindromic repeats.
Which just… rolls right off the tongue.
Hence why everyone calls this system CRISPR.
CRISPR isn’t free or one-hundred-percent
perfect.
But it’s the most efficient way to edit
genes right now, and it may revolutionize
medicine and agriculture.
Who “invented” CRISPR?
Our little buddies, bacteria!
And archaea, bacteria’s weird uncle.
Many microbes use CRISPR to keep a list of
viruses that can kill them by putting the
bad DNA in between repeated palindromes.
It’s sort of like a police directory of
prior arrests: when a virus enters the microbe’s
cell,
if it’s recognized as being on the list,
a CRISPR-associated protein cuts up the virus.
And the system is a good editor: it reads
for specific DNA sequences and only cuts these.
ThoughtBubble, show us more:
Spanish microbiologist Francisco Mojica first
published about this system in 1993.
But back then, he saw a bunch of repeated
segments of DNA with weird other DNA in between.
He didn’t know what it meant, and it wasn’t
major news.
But Mojica didn’t give up.
In 2003, after a long decade of clever bioinformatic
work,
Mojica realized that CRISPR must be an adaptive
immune system—
a way for microbes to protect themselves against
viruses.
But on its own, in nature, CRISPR didn’t
help humans.
In fact, when Mojica submitted his discovery
to the scientific journal, Nature, they rejected
it!
CRISPR had to be transformed into a tool.
There were lots of steps and scientists involved.
First, scientists had to move beyond finding
the palindromic repeats in different microbes
to understanding how the whole system worked:
what told the cutting protein where to cut?
How could the system be reprogrammed?
Swiss microbiologist Emmanuelle Charpentier
and German microbiologist Jörg Vogel
figured out that a special piece of nucleic
acid called a guide RNA tells the cutting
Cas9 protein to cut DNA at the right place.
Other scientists worked out how to move a
whole system that evolved in microbes into
the cells of mice and humans—
a whole system of genes, tracer RNAs, and
proteins.
In 2011,
Charpentier met American structural biologist
Jennifer Doudna,
and they decided to collaborate on studying
synthetic CRISPR systems, outside of microbes.
Meanwhile, in Cambridge, Massachusetts, Chinese-American
molecular biologist Feng Zhang
and synthetic biologist George Church worked
on putting CRISPR systems into mammalian cells.
For example, Zhang made mouse models of human
disease using CRISPR.
Within fewer than ten years, CRISPR had gone
from a cool immune system for microbes to
the hot new tool in biology.
Thanks, ThoughtBubble.
In the wake of transforming CRISPR from a
microbial trick into a tool for the future
of biology,
Doudna and Charpentier filed patents through
their universities, to work with their companies…
and so did Zhang and Church, for their companies.
These biologists are academics, but they are
also entrepreneurs.
So, why is CRISPR such a big deal?
Instead of part-by-part steps, each likely
to fail, CRISPR enables a whole solution to
be programmed at once.
It’s not super simple, but it’s simpler
than what came before.
Proposed applications include precision medicine
as well as a new Green Revolution:
imagine staple crops edited to put their own
nitrogen into the ground.
Or to breathe out less water, requiring less
irrigation.
Or to photosynthesize more efficiently.
Or make more of the nutrients humans want.
And if you can engineer an apple, you can
engineer a human!
This is reprogenetics, or engineering babies—both
to make them healthier and to make “designer”
babies with specific traits like eye color
or height.
Which—yeah—eugenics never dies.
But CRISPR isn’t the only promising development
in medicine.
Other researchers are working to understand
how environmental stimuli like the foods we
eat interact with genes via epigenetics,
or the regulation of which genes can be expressed.
Historian of science Hannah Landecker calls
to rethink human health as existing in a “metabolic
landscape.”
Another important area of research is microbiomics,
or the genomics of microbes.
The human gut only works because of the trillions
of bacteria that live inside it.
But, just as we don’t know everything about
the human genome,
we also don’t know everything about how
these microbes function, interact with each
other, and interact with different foods.
If scientists could understand these complex
relationships better, maybe technologists
could make foods that were also therapies.
…
Or maybe they could just remind us to eat
healthy foods!
With more genetic therapies and a better grasp
of epigenetics and microbiomics,
some scientists hope that humans will live
much longer.
In fact, longevity itself is a hot topic.
Finally, many life scientists are turning
to one of those epistemic objects the proved
remarkably stubborn for a long time: the brain.
Alongside mid-twentieth century work on DNA
and drugs, other researchers figured out a
lot about brain surgery…
But, at a basic level, the brain remained
mysterious.
It’s a collection of neurons, joined by
little gaps called synapses.
Brain signals cross the synapses through a
mixture of electricity and chemicals.
Thought, memory, and self are in there somewhere,
and we mostly know the physical regions of
the brain where they are.
Although… neuroscientist and tireless brain-mapper
George Paxinos confirmed a whole new brain
region,
the endorestiform nucleus, only in 2018!
Clearly, there’s room for ongoing research.
Technologies let scientists see the brain
in new ways.
Invented in the 1970s, magnetic resonance
imaging or MRI creates a non-invasive map
of the brain.
And functional MRI, or fMRI, first used in
1990, lets scientists see the blood moving
around inside.
But the dream for many researchers is a database:
the connectome, or total map of how neurons
are linked in the brain, a “wiring diagram”
for a brain.
The NIH, for example, launched Human Connectome
Project in 2009.
To date, scientists have mapped the connectome
of one animal, a worm, and are working on
the mouse retina.
Maybe brains are so complex that we still
don’t understand much about them.
But we can control them!
Think about neuroenhancement: what if there
was a drug that targeted specific brain regions
linked to logic problems, memory, or creativity?
In fact, what if there was a drug that affected
the very genes that code your brain?
What if the whole world was, say, on average,
five percent smarter?
Finally, what if the true power of the brain
came from being allowed to escape the limits
of the body?
A technology developed in the late 1990s called
a brain–computer interface or BCI enables
human brains to interact directly with computers.
BCIs can transform the lives of people suffering
from paralysis, for one.
What else might humans enable themselves to
do by directly connecting their brains and
computer systems?
To conclude, let’s come back to basics.
Regardless of how immediately revolutionary
or still-science-fictional the various life-control
technologies we’ve covered in this episode
are,
they have one thing in common: rich people
will get them way before poor people.
And old technologies won’t go away due to
new ones.
Science, in the sense of a set of methods
for understanding the natural world, doesn’t
tell us which technologies we should deploy,
where, or when.
This is the realm of ethics.
So even as some lucky consumers will begin
to enjoy medical regimes personalized to their
genomes,
many people don’t have access to healthcare
at all.
While access remains uneven, or stratified,
new groups may arise based on healthcare—
not genetics or other forms of biosociality.
As some epidemiologists have said: “zip
code is a better predictor of health than
genetic code.”
Next time—we’ll talk about the future
of the planet.
It’s time to tackle climate disruption,
the Anthropocene, and some deep questions
about what knowledge scientists should make.
Crash Course History of Science is filmed
in the Dr. Cheryl C. Kinney studio in Missoula,
Montana and it’s made with the help of all
this nice people and our animation team is
Thought Cafe.
Crash Course is a Complexly production.
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