Prophets of Technology: The Biotech Visionaries

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0:44And even change you. I literally feel like I'm a different person. Yes. Do you feel that way? Ideas worth spreading. From TED and NPR. I'm Manoush Zomorodi. This is the final episode in our three-part series with the prophets of technology. We've been talking to the inventors and scientists who've predicted and shaped the digital world we live in today. About what they've gotten right and wrong and where they think we're headed next. In part one, we talked to tech pioneer Ray Kurzweil and the original influencer Stuart Brand. In part two, Microsoft AI's Mustafa Suleiman and MIT psychologist Sherry Turkle gave us very different takes on AI and chatbots and the intensifying emotional relationship we'll have with our technology.

1:40Today, we're exploring a new chapter for the human body, as we enter an era where the boundaries between biology and technology are blurring, from our genes to the merging of the brain and devices. We begin with the story of a Nobel Prize winner, and an acronym that you have likely heard a lot over the past few years. CRISPR, or Clustered Regularly Interspersed Short Palindromic Repeats. Wow. Impressive. Did I get it? Okay, thank you. You did. Thank you. I have been working on that. I'm really glad you came up with the acronym. Well, I didn't, but the field did. Yeah. This is biochemist Jennifer Doudna.

2:20Around 2011, Jennifer started collaborating with a French professor named Emmanuel Charpentier. And they began studying CRISPR, a phenomenon that naturally occurs in bacteria. Correct. It's an adaptive immune system that bacteria employ to protect themselves from viral infection. And we began studying an enzyme, a protein called CRISPR-Cas9, which could be incredibly useful for detecting RNA and DNA molecules and for cutting them up. She and Emanuel found that this CRISPR-Cas9 molecule destroys viruses by cutting up their DNA and altering their genome. Their discovery was huge. And this led to a breakthrough, really a finding that this system could be harnessed as a tool, as a technology for manipulating DNA sequences in a programmable fashion.

3:21And it was through that work that we realized that this system could, in fact, be deployed as a genome editing tool. Meaning they could use CRISPR-Cas9 to target and alter specific genes. It was basically immediately clear that this was an extraordinary breakthrough technology. Do you remember what it looked like when you sort of connected the dots? Were you like, whoa, I have to sit down or I need a whiskey? Like what went through your mind on a purely human emotional level? Well, a great little vignette that comes to mind was an evening in those days when I was, you know, I had just come home from the lab and, you know, we had just gotten the data that showed how this worked.

4:09And I was at home. I was, you know, I was cooking spaghetti in my kitchen for my young son. And I just suddenly burst out laughing because I thought, this is so crazy, you know, that we started working on this thing. Didn't really know where it was going. And it certainly wasn't a popular area of science at the time. Most people had never heard of CRISPR. And yet we had uncovered this just absolutely extraordinary molecule whose chemistry was going to probably change the world. Jennifer Doudna and Emmanuelle Charpentier's work earned them the Nobel Prize in Chemistry in 2020. And now CRISPR is starting to deliver on its big medical promises.

4:55In late 2023, the FDA approved the first-ever CRISPR-based treatment for sickle cell disease. It works by tweaking a patient's own stem cells so that their body starts making healthier blood. More recently, doctors at Children's Hospital of Philadelphia used a CRISPR treatment on a baby born with a rare metabolic disorder, delivering the gene fix directly to his liver, making him the first person to get customized genetic therapy. Researchers are also testing CRISPR as a one-time fix for high cholesterol by editing a single gene linked to heart disease. After years of hope, CRISPR is getting out of the lab and into real lives.

5:36Victoria Gray, she was actually the first U.S. patient to receive a CRISPR-based therapy for her sickle cell disease. And she's showing that this type of approach can actually work quite well in terms of treating a disease at its source. And I think that's really what CRISPR offers is that kind of a cure really for genetic disease. But I think one has to think about the fact that, you know, what we're talking about here is effectively changing evolution. You know, it's changing us at our core and going back to the instruction manual that makes us who we are and making changes there. When we talk about it in the context of a disease like sickle cell disease that is so debilitating, it certainly seems like this might be something that some families might want to consider eventually, especially if the technology is vetted carefully and shown to be safe.

6:39But I think the broader issue really is equity, access to technologies, who decides about something like that, something as profound as that, who pays for it, who has access to it. I think it gets complicated quickly. Yeah, I mean, it goes from stopping a fatal disease to maybe optimizing for IQ or even, you know, being thin and tall and having a particular eye color, I suppose. I mean, in a most extreme case, you could imagine that someday couples, you know, go to an in vitro fertilization clinic and they receive a menu, right? And they can decide what types of traits they want for their children.

7:26Yeah, you actually brought that up back in 2015 in your TED Talk. Imagine that we could try to engineer humans that have enhanced properties, such as stronger bones or less susceptibility to cardiovascular disease, or even to have properties that we would consider maybe to be desirable, designer humans, if you will. Right now, the genetic information to understand what types of genes would give rise to these traits are mostly not known. but it's important to know that the CRISPR technology gives us a tool to make such changes once that knowledge becomes available. This raises a number of ethical questions that we have to carefully consider, and this is why I and my colleagues have called for a global pause in any clinical application of the CRISPR technology in human embryos to give us time to really consider all of the various implications of doing so.

8:26In 2015, Jennifer called for an international moratorium on applying CRISPR to human embryos, at least until the scientific community considered all the ethical implications of gene editing. But not everyone stuck to a moratorium. Overnight, an astonishing claim. A scientist in China saying he created the world's first genetically engineered babies. A line has been crossed that should not have been crossed. It's very disturbing. It's inappropriate. Oh, this is huge. That was definitely a motivation at that time was to call to the attention of everyone to just be aware that this technology does have the potential to create these very profound kinds of changes in human beings.

9:13What happened next was that there was an announcement in 2018, which actually happened at the second international summit on the topic of human genome editing, of a project in China in which two embryos had been edited using CRISPR and then were implanted to create a pregnancy that resulted in the birth of twin girls with edits to their DNA. And do you remember what your reaction was after he presented his research? Well, it was pretty horrifying. You know, it was just kind of shocking to see the way that the work had been performed. Just really an example of unethical behavior on the part of a scientist, you know, just rushing forward with something before it had been tested to be safe.

10:03and also without properly understanding how to explain and consent with patients, you know, to explain to them what was actually happening to the embryos that they were using in the study. And so I think it really did galvanize the international community to realize that this type of work really shouldn't be happening right now. And there has been a concerted effort on the part of not only scientific organizations, but also by the World Health Organization and the United Nations to get involved in this conversation. Okay, so you've got governments and NGOs talking. But of course, there's the other party that we're not talking about yet, which is private enterprise.

10:50There are a lot of companies who are hoping to make money off of this technology. You've started several companies that are developing CRISPR-Cas9 treatments. But should we be worried? Because companies are not always known for taking the moral high ground, right? You're right that I think this is always something that needs vigilance. One has to, you know, you can't relax. You have to remember, you know, there's always the risks that go along with a technology like this. But companies play an incredibly important role in all of this because generally this is not something that academic labs have the funding or the resources to do.

11:26And that's where companies come in. So how do you balance your business interests with your ethics? I think it begins at the beginning. You have to start with creating a culture in your team that focuses on ethical use of the technology and the benefit that can be created by developing it in the context of the company. I've been proud of the teams that I've been involved with as a founder, that I think in each case, these are people who I like, I trust. I think we have aligned values, core values, in terms of both doing excellent science and doing it with an eye towards ethics and appropriate use of a powerful tool.

12:12Those capabilities will advance, you know, the kinds of things that have only been dreamt of in biological systems to a point where we can actually achieve them. Imagine that someone gets a diagnosis for something. Maybe it's even pre-diagnosis. It's they get their DNA sequenced and the result comes back that they have susceptibility to Alzheimer's disease in the future. Imagine in the future it's possible to use a technology like CRISPR to change those genetics so that that person is no longer has that susceptibility. That would be extraordinary if we get to that point. Will we get there in 30 years?

12:55I don't know, but I think it's entirely possible that we will. That's biochemist Jennifer Doudna. You can see her TED Talks at TED.com. In a minute, we'll turn from the body to the mind and the people predicting what will come next for how we think. It's the TED Radio Hour from NPR and part three of our special series, The Prophets of Technology. We'll be right back.

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15:32We're talking to the inventors and scientists who have predicted and shaped the digital world we live in today. And asking them where they think we're headed next. Today we are focusing on the human body. Right now, it's not unusual for someone with heart problems to get a pacemaker, or someone with hearing problems to get a cochlear implant. But what if it becomes totally normal for someone with physical limitations to get an implant in their brain? There is a race going on to develop neural implants, or as they're called, brain-computer interfaces, BCIs. The Wall Street Journal estimates that fewer than 100 people with paralysis have had one of these devices permanently implanted.

16:19But many clinical trials are ongoing, and the companies jockeying to get ahead each have their own approach to putting technology inside the brain. One of the least invasive approaches comes from vascular neurosurgeon Tom Oxley. And I'm the founding CEO of Synchron, a brain-computer interface company. Tom's company makes the Stentroad, a brain implant to help people with neurological diseases who can't move their bodies or speak. So this technology is a way to put almost what is a microphone right on top of the brain and bypassing the inability of the body to transmit out your intention or your will to move.

17:05In 2020, they started testing their device in people, including a man named Philip O 'Keefe. Philip was the second participant in our first in-human study of our implantable brain-computer interface. He lives in Melbourne, Australia. And Philip has ALS, or motor neuron disease. and he was facing a progressing loss of control of his body as the ALS progressed. So if your muscles stop working but your brain is still working, you can in a sense become trapped inside your head. Basically, the technology decodes what part of the body the brain is trying to activate and then sends out a signal that makes a cursor move or a computer mouse click.

17:57Yeah, so you're able to directly manipulate a mouse or a keyboard by thinking about trying to move, even though your body is no longer moving. Almost like a Bluetooth mouse directly controlled out of the brain that can work on any system. Philip started off doing simple tasks using his BCI, like sending an email and browsing the web. But after a year, he wanted to take things to the next level. So he sent out a tweet. The first tweet said, hello world. That was what it meant to him. He was saying hello back to the world because he'd gone quiet, he'd gone dark and he was back. And that's really what this technology is about.

18:39Philip O 'Keefe can't use his fingers to type like UI, but thanks to a tiny brain implant, he was able to send the following tweets. Here's Tom Oxley on the TED stage. Hello world. Short tweet. Monumental progress. No need for keystrokes or voices. I created this tweet just by thinking it. My hope is that I pave the way for people to be able to tweet through thoughts. Phil, now you might be thinking there are some people out there who should not be allowed to tweet directly from their brain. I agree. But for people with paralysis and disability, this technology can be life-changing. They will fill up brain signals up on the screen.

19:20They're connected to their computers via Bluetooth the device is fully internalized, invisible to the outside world, and they learn to control the keyboard with clicks directly coming from their brain. Now, BCIs conjure up images of science fiction like the Matrix with a cable jacked up into your brain through a hole in your skull, but I'm here to show you that the future can be much more elegant than that. Do you remember the first time that you heard about brain-computer interfaces? Because people have been trying to do this for a while, right? The first report of a human implant was in 2006 by Lee Hochberg and colleagues in Nature.

20:02And I was immediately besotted with the idea that this was going to be a transformational technology. I went into medicine because I loved the brain. It was this mystery and romanticism about what the brain was, how it worked, how it generated consciousness. And then you realize that there's not many things that you can do for neurological disease. You can't reverse the death of neurons. You can't replace neurons. And I realized that this is a field in medicine, which is sort of behind the other areas of medicine and ability to treat conditions. And it struck me that the ability to directly interface with the brain was going to change that.

20:45Because up until then, what scientists have been trying to do, they had to go directly like drill a hole and put a device in people's brain. Is that what the challenge was? Yeah. The breakthrough early research device is a series of needles that sit on a base and those needles get pushed into the brain tissue and they are able to record information out of the brain. There's an issue with putting a needle into the brain, and that is that it can cause an inflammation reaction. The brain does not like to be invaded. The brain has an immune response which is different to the rest of the body. You can put a tattoo under your skin and it will not cause a huge inflammatory reaction, but you can't do that necessarily on the brain.

21:30So my concept was, well, how do we avoid putting something directly into the brain? What's the next closest we could do? and the idea that we had was let's try and solve getting these sensors into the blood vessels and it can stay there for a lifetime. The blood vessels are the natural highways into the brain. These are hollow tubes that connect every corner of the brain. The largest vein at the top there is right next to the motor cortex, the exact part of the brain that we want to connect to to restore control to the outside world. Now, we already know how to travel through the blood vessels.

22:12If anyone here today has had a heart attack, there's a pretty good chance you've had a stent. A stent is a metal scaffold delivered through a catheter, which opens up like a flower into the blood vessel. Millions of stents are delivered each year, not in the OR, but in the cath lab or catheter laboratory. It's now common in the cath lab to navigate up into the brain through the blood vessels. But what's really amazing about this is that for BCIs, we already know that devices can be left inside a blood vessel, cells grow over it, incorporate it into the wall like a tattoo under the skin, and we're protected from that immune reaction.

22:55so you've basically built a brain computer interface into a stent um and you place it not just in the brain but in the brain's blood vessels right yeah it's extraordinary uh can you take me through that process the procedure involves putting a catheter into the jugular vein in the neck then slipped up inside the skull through a little pre-existing hole that the jugular vein goes up. So it's kind of going up the drain pipes of the brain. So you carry your way up through those pipes all the way up into the brain until you sit on the blood vessel that's sitting right on top of the motor cortex. And what we had to solve was how do you put sensors?

23:41How do you build an electronic circuit onto that stent? So then that device opens up, it sits in the blood vessel, it's connected to a cable, that cable exits that point in the neck and the jugular, and it plugs into a device in the chest that sends the information from the brain wirelessly out of the body. So if you were to look at the patient with the device in, you wouldn't know that it was there. Okay. So once the stent has been put in, do you just think something and out it comes onto the keyboard? Do you have to train the patient in order to use their mind effectively to communicate through technology?

24:21The patients do undergo training. What's interesting is that we are born in bodies where there's a part of the brain attached to a muscle and that's all that part of the brain does. So if you make a fist right now, there's a very particular part of your brain that's firing to do that. But once you digitize that, you can apply what used to be a particular movement, like, say, closing a fist or putting up your finger or bending your elbow, and the patient will realize that that performs a particular task on the computer. And then in a different mode of action, it does a different thing. So probably a good example is thinking if you've ever played a video game with a Nintendo controller or a PlayStation controller.

25:09When you first start playing a new game, you have to look down on the buttons. and the button might jump or fire or do something in the game. But in a different game, it'll serve a different purpose. So in each different game, you have to learn what your fingers are doing when they hit the button. And for the first couple of attempts, you'll be watching your fingers, but then eventually you'll stop looking because you'll just know what it does and you'll stop thinking about it. So it's the same concept. We have a belief that the first brain-computer interface should be very easy to use. It should be robust.

25:43It should require very little training. You shouldn't have to spend weeks or months learning how to use it. And it should work as soon as you turn it on. Synchron recently announced a collaboration with Apple to build devices for people who can't use their hands. And while controlling our tech with our minds is probably still years away, the concept doesn't sound quite as far-fetched as it once did. One of the most famous people who's in this brain-computer interface field is, of course, Elon Musk. And he has laid out a vision where people control all kinds of things with their minds. Virtual reality games, but also way more than that.

26:24He's talking about the brain fusing with artificial intelligence. Are you thinking of those things, too, where it's not just for people who have medical issues, but for anyone who wants to enhance their mind? I watch Netflix and I read science fiction novels and I can see that there's a likely outcome where this technology progresses into humans being able to control things in a way which wasn't previously possible. The thing is that we're talking on a very long timescale and I think it's important for people to remember that this technology is critical for people who have lost the ability to engage in the world.

27:08So I just worry that the conversation goes into a hundred year out timeframe and we start looking at all the possibilities of how this could go wrong and we forget why actually we're doing this right now and who is it for. I'm not dismissing the ethical considerations for where this goes. I've seen Black Mirror, and I think the answer to that is let's confine the problem right now to what is needed to really help people and lay down a really strict regulatory framework about remaining in that domain. I mean, that's the thing, right? It's a Venn diagram of medical device and Silicon Valley utopian, maybe out there futurism.

27:51And I mean, your company, it's a for-profit company. You've taken venture capital and presumably your investors would like you to move as fast as you possibly can with this and scale it. So I guess I'm wondering when do the ethical considerations, like when does that conversation start? Because we've seen it start way too late with so many other technologies in the past. I mean, you're right. The conversation has started for us. We have an ethical charter. We have a group that's set up. We have internal conversations about this a lot. We're talking with the FDA and we've been in close contact with them and continue to discuss these issues in an ongoing basis.

28:32I think the community's taking it very seriously. The kind of Venn diagram into the tech utopia, I think our investors are investing because they see that there is a huge unmet need in the medical domain for paralysis. Now, I mean, one other thing that I'd probably add to it is if I was to think ahead about what it might look like into that tipping point and who would be the people in the consumer world that would start to do this, the corollary I think about is LASIK surgery. LASIK surgery started 30 years ago, and it's a laser on your eyeball, and it makes you see better. This is a procedure that's a day procedure, you have to go into a hospital, you have to see a physician, it's regulated by FDA, but if your visual disturbance is only mild, you can still go and do that and you can take on the risk and benefit to get that done.

29:23I think BCI might go in that direction. I'm not saying next year, this is probably like on a 15-year horizon, but once the technology is demonstrated to be safe and effective and it's in a day procedure and it's invisible to the outside world, there probably will be a portion of society who think, well, I would like to be able to engage in systems without having to touch anything, so I don't have to hold my phone. I can see that as a possibility. In the future, I'm really excited about the breakthroughs BCI could deliver to other conditions like epilepsy, depression, and dementia. But beyond that, what is this going to mean for humanity?