Biotech is about to change your world

0:00This message comes from AT &T. Staying connected matters. That's why AT &T has connectivity you can count on, or they'll proactively make it right. That's the AT &T &T guarantee. Terms and conditions apply. Visit AT &T.com. Guaranteed. for details. This is the TED Radio Hour. Each week, groundbreaking TED Talks. Our job now is to dream big. Delivered at TED conferences. To bring about the future we want to see. Around the world. To understand who we are. From those talks, we bring you speakers and ideas that will surprise you. You just don't know what you're going to find. Challenge you. We truly have to ask ourselves, like, why is it noteworthy?

0:43And 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. About 25 years ago, the first draft of the Human Genome Project was completed. We are here to celebrate the completion of the first survey. Then-President Bill Clinton, surrounded by scientists and world leaders, Most wondrous map ever produced by humankind. Praised the Breakthrough Project from the podium at the White House. But today's historic achievement is only a starting point. It took another 20 years to sequence the last 8%. But meanwhile, this genetic map of the human body has led to major breakthroughs in cancer treatments, prenatal testing, and our understanding of rare diseases.

1:42It's considered a massive scientific accomplishment. And today, researchers want to go even further. So in the Human Genome Project, we only had to handle that genome. But remember, one genome yields many, many, many different kinds of cells. This is computational biologist Aviv Regev. And so instead of just having to map this one static genome that kind of stays the same throughout the lifespan, when you look at cells, they actually change. My cells today are not the same as the cells that I had 20 years ago or 10 years ago or the ones that I will have in 10 or 20 years from now. Aviv is the co-founder of a project to map all of the types of cells in the human body.

2:33The project is called the Human Cell Atlas. She and researchers all over the world are cataloging how our cells change and interact. The goal is to use it to develop highly personalized medical treatments. One of the critical things we need to navigate in the human body is our diseases. For example, I need an address for a cell if I want to go and target it with a therapy. Biologists have tried to do this for a very long time, but there's about 37.2 trillion cells in an adult human body, and they do different things and behave in different ways. And there's 20 ,000 genes in the genome. And these genes combine to act in different ways that are not predict.

3:21If I know what happens about gene A and I know what happens with gene B, it doesn't mean that I can predict what will happen when I put A and B together. So when you start calculating the number of ways our cells and genome could combine, the possibilities are astronomical. Some of the numbers are larger than the numbers of atoms in the universe. So it's big. But now, thanks to artificial intelligence, scientists can identify all those cells and do these complex calculations. That shift can only happen with the AI. Aviv expects to complete the first draft of the atlas in the next year or so. And she says the old way of understanding cells in the human body compared to the human cell atlas will be like comparing a 15th century map of the world to Google Maps.

4:12In a Google Map, you also have many, many layers. So you can look at a Google Map, right, and choose the Earth view, and you see the real topography. Here are the hills, and this is where the water is. but you can also look at a Google map for traffic patterns. And when you have a map like that, you can choose that different level in order to learn the things that you need to know in order to take the right action. These are the things that we need. We often like to call them atlases because they help us navigate. It's the things we need in order to navigate the human body. If I want to develop a medicine that would only go to the place where something is broken and help that cell function, help that tissue, I need to know how to get there.

4:54If you have a map, you have the zip codes. And if you have the zip codes, you can get where you want to get. And if you can get where you want to get, you can deliver a very targeted, very specific therapy that spares the rest of the body and gets only where it needs to go in order to help us be better. Those are the kinds of things that you can do with a Google map, and it's very hard to do with a map from the 15th century. And now we have something that's constantly at higher and higher resolution, And so that is extremely rich information for us to navigate. From mapping every cell in the human body to engineering climate resilient crops, some of the biggest innovations happening right now are in biotechnology.

5:37And that is what we're bringing you today. Ideas and projects at the forefront of this new wave and how these breakthroughs are upending our approach to disease, climate change and our longevity. Back to computational biologist Aviv Regev. Aviv says developing new medications is one of the toughest things for scientists to do. But the human cell atlas makes it much easier. Here she is on the TED stage. Making new medicines is really, really hard. We need to generate the next medicine, and then we need to predict the right dose for the right patient. This is not just hard and takes a lot of time.

6:21It does. It takes about 10 years or more to develop a new medicine. But the vast majority of the time, it fails. 90 % of potential drugs fail in either preclinical research or in clinical trials. You can focus on the fact that it's not happening, but I prefer to think that there's something we can do. What might that be? Well, one of the greatest innovations of our generation are the great advances that have happened in machine learning and AI. They can transform the discovery of medicines. And so, in mid-2020, I moved to Genentech to solve this problem. And so, every day when I come to work, our patients' pictures look at me from our buildings.

7:07Like Renita here, who is a patient with HER2-positive breast cancer. And like Renita, there are millions and millions of patients who need better medicines. Now, we haven't been idle. For example, we have developed medicines across seven major disease areas, in oncology, in neurology, in rare blood disorders. We run currently 732 clinical trials. Last year alone, more than 14 million patients were treated with our medicines. These are successes, but they are successes in a field where the odds against success are 9 to 1. We absolutely have to do better than that. Explain to me what we can do now and what you see happening in the next 5, 10, 20 years.

7:55So first of all, we use the Human Cell Atlas every single day. We use it to research and discover medicines and to develop medicines. And this is because we ask these questions every day. Which cells in the body use this disease gene? Where could I go in order to target a disease cell, but not the healthy cells of the body? What are the unique characteristics of this patient? What happens to cells when we treat with drugs? One of the unique things that we still have to figure out is not just where are the cells, but also the answer to what would happen if I treat this patient? What would happen if I had a therapeutic that inhibits the activity of this gene or of that gene?

8:49And those are harder questions to answer. To answer them, Aviv and her colleagues consult the cell atlas, kind of like you or I might consult chat GPT. For example, researchers have been looking at a medication for lung disease that targets particular cells. She can ask the atlas if those same cells show up in other diseases too. We said, we already know that we have a medicine that targets a particular behavior in cells. In what other diseases might we see cells like these? And the answer that we got back was inflammatory bowel disease, ulcerative colitis and Crohn's disease. This was not something we expected at all.

9:35It wasn't the direction in which we were originally going to develop this therapeutic. But now we actually have a phase two clinical trial in patients based on this finding. That's the kind of stuff that a human cell atlas allows you to do. You describe it as a lab in a loop, right, that you're constantly learning and applying your learnings and trying out different sort of medications. Do you mind just walking us through how quickly that can move now that you have this information? Yeah. So in the lab in the loop, you do different kinds of interventions. You go and you poke and you prod cells in different ways.

10:15Then you feed that into an algorithm, actually into AI, and you let it build a model of what it thinks is going on. That model might not be necessarily correct, but it is going to make predictions for you. And based on those predictions, you're going to go back and do another experiment and go on and on and on like that. The one that will succeed are the ones that the algorithm learns that worked well. The one that didn't succeed also teach the algorithm about what didn't work well. It gets better. It makes a new set of predictions. And you iterate and iterate until it is giving you a good enough answer that you can start making an actual medicine from.

10:58And that brings us to the final step, which is the patient, the ultimate step for us. But there's many patients in the world, and they're not all the same. And we have to provide the right medicine to the right patient. and sometimes we have to personalize this medicine to the patient. A notable example of that is in cancer. Tumors are different. Every patient's tumor is different. They have a lot of mutations in them. Some of these mutations are entirely private to the patient. These mutations are very important. They are identified by our immune systems, by our T cells in the immune system. They see them in the same way that they see viruses and they kill the cancer cell.

11:39What if, just like a vaccine against a virus, we could devise a vaccine against cancer? That we target the immune cells against the cancer cells. But the mutations are private. We need to make the vaccine personalized. Here comes our lab in a loop. We take the patient's tumor, we sequence this, we identify the mutation, and we use a transformer model trained on previous data in order to identify those mutations that would trigger the immune system. We collect a collection of these mutations and we make them into a personalized cancer vaccine just for this patient. And as we treat the patient, we monitor their immune response.

12:18We use this information to improve the model for the benefit of all. I mean, we're talking about the advent, finally, of really personalized medicine. This is huge, right? Like cancer patients will be able to get a vaccine that nobody else will have. It will be formulated just for them. Yeah, highly personalized medicine that the cancer patient can receive after their diagnosis and that will trigger the immune system to control the, you know, microscopic tumor that might have remained in the patient's body and that you cannot remove by surgery, resection and so on. In a moment, Aviv shares how AI and the human cell atlas could go so far as to predict if someone will develop a disease and treat it before it even starts.

13:11On the show today, the new wave of biotechnology. I'm Manoush Zomorodi, and you're listening to the TED Radio Hour from NPR. We'll be right back.

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14:52That's why when it comes to managing your wealth, Schwab gives you more choices. You can invest and trade on your own. Plus, get advice and more comprehensive wealth solutions to help meet your unique needs. With award-winning service, low costs, and transparent advice, you can manage your wealth your way at Schwab. Visit schwab.com to learn more. It's the TED Radio Hour from NPR. I'm Manoush Zomorodi. On the show today, the new wave of biotechnology. And we were just talking to Aviv Regev, one of the founders of the Human Cell Atlas Project, a mapping of every type of human cell and how they interact with genes.

15:38Aviv is now working at Genentech, where she and other scientists are applying this new knowledge to create personalized medical treatments. Imagine a vaccine formulated just for you based on your genetic and cellular profile. But her other goal is to predict and prevent disease from developing in the first place. Can I ask you about the future of preventative care? One of the teams working on the Cell Atlas has produced a blueprint of how human skeletons form in utero. And one of them found that certain genes were activated in early bone cells that might be linked to an increased risk of developing hip arthritis as an adult.

16:26So I guess I'm wondering, you know, in the future, when your baby is born, will a doctor be saying, OK, well, based on what we know about your newborn, they have these sorts of proclivities towards these diseases. So make sure you get these vitamins and make sure you get this sort of vaccine at this point. You know, we won't even have to develop the diseases because we'll nip them in the bud because we know the blueprint. Yes, there are huge diagnostic and prognostic opportunities, not just when you already have disease, but also well ahead of them. And there is a lot to say about that. The first actually starts with human genetics, which is the ability to look at your genome and assess some of your risk.

17:09We already know that we can assess the risk for some really serious conditions, which are really driven by a single gene. For example, if you have a certain mutation in your BRCA1 gene, then your risk of breast cancer is substantially increased and it changes how your doctor will monitor you and how you will be cared for throughout your life. But now we can actually look across information from a lot of our genes combined together. This is actually something known as the polygenic risk score. And for certain diseases, you can start making these assessments for people who have especially substantially increased risk.

17:47And I think this would be fantastic because most of our focus has been on looking at disease after it already exists. This gives so many opportunities for preventative care. I guess, could you just paint a picture for us about how you think the field of medicine and biotechnology will be different for the patient in the long term, 20 years, 30 years, 40 years? What sort of mindset will we have as people when we think of how to treat illnesses that we're born with or develop over time? I think it's a great question. I'm not going to put a timeline on it, but I do think things will change substantially for patients.

18:32There are so many patients who are treated on medicines and then they don't bring them benefit. We believe that there would be a great reduction in that pattern. And that will come from being able to predict a lot better which patient will benefit from which medicine so that we can come in a much more fine way rather than with broad strokes. This understanding of the cells and their internal mechanisms opens up so many possibilities. There's also going to be earlier disease treatment and even preventative disease treatment that today is simply not possible. If you cannot predict that the disease will develop and you cannot provide treatment for it.

19:14But if you can, and you can understand the early, early mechanisms of what happens in that disease, then you can imagine providing this therapy for the patient. We're also going to see, I believe, therapies that are one and done more. More cure rather than continuous care. We're going to see this also with a much broader range of vaccines that can be used. Those are things that do not exist yet. And you can never tell exactly when they will exist, how impactful they would be. But it is really exciting prospects for us going forward. And while I talk about it in the future tense, this is what people are doing right now.

19:56And it's getting better every year. Actually, it's getting better every six months. It's actually a scientific breakthrough that is happening right now. That's Aviv Regev. She is the executive vice president and head of Research and Early Development at Genentech, and the co-founder of the Human Cell Atlas Project. You can see her full talk at TED.com. On the show today, how a new wave of biotechnology could change our lives, including what we eat. In the 1990s, genetically modified foods, or GMOs, hit the market. Scientists developed these crops to make them more resistant to weeds and insects, and to be more hardy so that farmers could yield more of them.

20:46But GMOs were controversial. Anti-GM activists stormed the field about a month ago. To be sure, humans have been crossbreeding plants for thousands of years. But to some, the idea of messing with the genes of organisms that they would eat sounded dangerous. There were worries that GMOs would cause allergies or antibiotic resistance or other long-term health effects. Today, concerns remain about cross-contamination with wild species or farmers relying on GMO seeds that can withstand herbicides and pesticides. The consensus on the whole, though, is that GMOs are just as safe as non-GMO foods to eat.

21:30Which is why you don't hear much about genetically modified food these days. That might be about to change because of CRISPR. The beauty is that this is a technology that can work on human cells. It can work on microorganisms, bacteria, and it can work on plants. This is Brad Ringguizen. He's a physical chemist and head of the Innovative Genomics Institute. Brad says the gene editing tool CRISPR could make it possible to feed the world's 8 billion people without destroying our planet in the process. I think when you hear CRISPR for climate, people sometimes sort of shake their head and they don't understand the impact that this amazing technology has to help stabilize food supply into the future.

22:19So I'm old enough to remember when GMO or genetically modified crops were introduced and there was in Europe especially a huge uproar about this idea of genetically changing plants, seeds, so that they are resistant to insects, to heat, all those sorts of things. How is CRISPR different than what's been used for the last three or so decades? So this is a really important question. And the good news is that CRISPR is a tremendously precise tool. I think people don't understand that nature itself produces genetic changes. And that's been occurring over generations and generations of all plants in the world.

23:09But GMOs specifically really have very uncontrolled genomic changes. They're changes throughout the entire genome. And oftentimes you're doing this in a way that is not very precise. Most of the food that we eat, at least in the United States for sure, are very high-yielding crops called hybrid crops. that several decades ago during the Green Revolution, people realized that you could actually cross two parents, two distinct, different genetically distinct parents, and the offspring actually have better traits, better yields, much, much higher yields than the parents did. And those are all just genetic changes that have resulted that dramatically increased yields.

23:59Well, the problem is, is that when those seeds from hybrid crops are planted the next generation, you see changes then in the genome of those seeds because the parents, some of the mix-up of genes that have occurred don't translate into that next generation. So people do not plant hybrid seeds into the next generation. So they have to go back to the seed suppliers and buy the seeds every single year. So if you enter CRISPR into this equation now, the beauty of CRISPR is that you can go into a very controlled location on the genome and make one very small change. In some cases, just at the base pair level, where you're really just making one very small change.

24:48You're maybe just turning off a gene. In many cases, you can actually have a disease-resistant crop, for instance, where you're just changing one gene. And that's a very precise way to make controlled changes. And at least in the United States and in countries like India and many countries in Africa and South and Central America, these changes that I was just talking about, if it's done with CRISPR, actually are not considered GMOs from a regulation standpoint. So there's actually a very fast-tracked way to be able to get these CRISPR products to market around the world. OK, so legally, the law understands the difference.

25:29I was reading about a barley trial that began in spring of 2024 in Switzerland where they were they're testing to see if CRISPR can increase barley grain yields. But, you know, in Switzerland, they are not GMO friendly. And so this this field is enclosed by an electric fence. It is patrolled by security and a guard dog. Yeah, I think there is a lot of misunderstanding and Europe is still one of the holdouts that they consider even crisper edits, those precise edits that I talked about that could occur in nature. Europe is one of the sole holdouts that still consider those a GMO and the regulatory aspect of that is very, very difficult in a place like Europe.

26:15But look, I've talked with the Danish ag minister. I've talked with Danish dairy farmers. And when I talk about CRISPR with the agricultural aspects in places like Germany and Denmark, the agricultural ministers are very much in support of this technology because they understand the climate implications and the greenhouse gas emissions and the threat to food security. And so they're pushing the European Union to make changes. And they want to make those changes in support of sustainability. There's just so much impact that you can have on the world to potentially feed billions of people using this technology to do it in a sustainable way.

27:02I became the executive director of the Innovative Genomics Institute, the IGI, in 2020. Here's Brad Ringgeisen on the TED stage. The same year that our founder, Jennifer Doudna, won the Nobel Prize in Chemistry for her pioneering work in CRISPR. That's right. Let's go, Jennifer.

27:22I was drawn to the IGI as a place where CRISPR could be applied to help improve the lives of nearly every person in the world, to help create a sustainable future. The work to improve food security is already underway. Our scientists at the IGI can already edit over 30 different crops. Rice, wheat, broccoli, sunflowers, tomatoes. We're even trying to develop crops that can persist against emerging pathogens by knocking out disease susceptibility genes. Or create drought-tolerant crops by reducing the number of pores that are on the water-losing pores on their leaves. We're even trying to save the banana and chocolate from emerging pathogens.

28:12So the idea is that you take a particular crop and you edit the genes so that they are more climate-friendly, so that they grow more heartily without using resources. Is it that simple? Yeah, well, I mean, nothing's ever simple in science. But yes, the concept is indeed that simple. And Jennifer and I have developed sort of a climate strategy at the IGI. And the first leg of that strategy is that we are looking at areas of the world that are on the front lines of climate change. So I just got back from a big trip to India where I met with a lot of agricultural scientists and government officials in India.

29:00Look, they have to feed nearly 1.4 billion people and they're seeing a tremendous threat to their food supply. They're seeing it from heat. They're seeing it from drought. They're seeing it from floods. They're seeing it from salinity as there's a storm. if you're growing food on the coastline, you now have to deal with ocean water that has contaminated your soils. And so what I learned in that trip to India was that it's becoming very much more difficult to predict what those threats to their food supply are going to be. There used to be traditional areas that were drought-prone, traditional areas that were flood-prone, and now what they're seeing is a very large degree of uncertainty.