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  • 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 diseaseslike

  • cancers, immune diseases, or psychiatric disordersremained 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 moleculesbiosociality.

  • 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 promiseof 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 fieldsincluding

  • 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 - … omicsthe 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 genesso changing anything means

  • making not one, but several stable edits.

  • And every edit increases the chances that something is changed elsewherean 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 thetechnology of the centuryand one of the most valuable suites of patents

  • on the planet: clustered regularly interspaced palindromic repeats.

  • Which justrolls 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.

  • WhoinventedCRISPR?

  • 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 microbiologistrg 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 babiesboth to make them healthier and to makedesigner

  • babies with specific traits like eye color or height.

  • Whichyeaheugenics 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.

  • Althoughneuroscientist 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 diagramfor 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.