The Future Is Being Written in DNA: Inspiring the Next 20 Years of Discovery in Synthetic Biology

Emily, thank you very much. I am very, very excited to be here. I love iGEM. I think it's incredible, and at Twist we try to be here to help you. In my view, you are Batman and we are Robin. We're really your assistant. Obviously, DNA is very important and DNA is changing the world. What we do at Twist is, once you have a sequence, we've built the technology to put it into a tube. We have the digital-to-real-life converter. With that, there are a lot of things that can be done. In my talk today, the first part will be about the tools that we have, and the second part will be more about what can be done with them. But as a preview, I feel very strongly that everything can be impacted for the better with DNA. DNA is kind of like a hammer, and everything looks like a nail. The hundreds of iGEM teams are working in some of those great applications. As I mentioned, at Twist we write DNA, and we've built a technology to really push forward the state of DNA synthesis. On the left, I'm showing how DNA and genes used to be made. People use a 96-well plate, and the chemistry of writing DNA is very well known, published in 1982, and optimized over thousands of years of grad student. I put in my four years. But you can now buy a bottle of A, a bottle of C, a bottle of G, a bottle of T, and you combine them and you get any DNA sequence you want. The problem with a 96-well plate is the throughput in my view is too low and the cost is too high. So what we've done at Twist is we have developed a silicon chip which is the same size as a 96-well plate, but instead of making 96 oligos, we can make 1 million oligos on the silicon chip. Those million oligos are clustered in 10,000 clusters of 100 oligos. Then we can do molecular biology in each of those clusters such that we can assemble oligos into higher-size DNA. To give you a sense of dimension, each of our million oligos is made on a dimension of 50 microns, which is the size of one hair. It's extremely packed. Then we use the same chip to make all the orders for all the researchers at the same time on the same chip. We've also built a very sophisticated software infrastructure to track all of that work. The miniaturization really gives us something unique: more scale, lower cost, and more speed. To illustrate the benefit of miniaturization, we engaged outside firms to measure the carbon emissions it takes to make one gene. On the right, you can see that with a standard 96-well plate, making one gene is the equivalent of driving a car for 59 miles. But with a miniaturized approach, making one gene is the equivalent of driving a car for 0.92 miles. If you get one gene a day from Twist, you save your commute away. That really exemplifies the benefit of the technology beyond just the miniaturization. We're also working on improving the products. One of the things we work very hard on is quality. Not only do we make genes, those genes can be nonclonal as fragments or they can be clonal. We also make oligo pools, from 100 oligos to a million oligos. That's very powerful in CRISPR experiments if you want to do genome-wide experiments to associate a phenotype with a genotype. We also can make very precise libraries for enzyme engineering or antibody engineering. We are also going to the protein area. A lot of customers were getting DNA from us and then expressing a protein as IgG, and now we also can ship IgG. We'll do the expression for you. The first investment is in quality. In the bottom right, we are showing the percent of perfect clones as you increase the length of a gene fragment, which is nonclonal. You can see that even at 1,800 bases, more than 50% of the clones you pick are perfect. There's also another dimension which is speed. A lot of what you do is around the design-build-test-learn cycle. The faster you can get the DNA, the faster you can get to the learning part. On the right, you can see data from our production site where you can get gene fragments in 3 days average, and 90% of fragments ship in 4 days. Another investment is around clonal genes, now your gene in your vector, where the turnaround time is about 10 days. However, in the next few weeks we'll launch an express offering where you can get a clonal gene in 5 days. It's your gene in your vector in 5 days, it's very inexpensive, clonal, perfect, and you can order one or a thousand or 10,000. It's really scalable with very little carbon emissions. Some applications beyond assembling genetic circuits: a lot of our customers take DNA to express IgG, so now you can get IgG in 10 days. You've heard about RNA now being a very important new modality for therapy. You can get to mRNA in 2 days. As researchers develop RNA vaccines for cancer, even personalized vaccines, this is a very powerful tool. Lastly, in terms of tools we're developing, our oligo pools used to be up to 300 base pairs, which was powerful because you could get two guide RNAs together into an oligo. Now we are expanding our oligo pool offering where we can go all the way to 450 base pairs. For those of you who have synthesized your own oligos, you may know that the last 100 bases are the hardest part. With 400 base pair oligos, you can encode a full heavy chain or light chain in one shot. We think that will accelerate work for antibody discovery. With that, I'll switch to our effort to support iGEM. We are very excited that last year, 120 teams used fragments and oligo pools from Twist. We calculated that over the last few months, we shipped more than half a billion bases to iGEM teams. That's an absolutely massive amount of DNA, and we're very excited with what you have done with it. In the last part of the talk, I'll speak about some applications that I think could be transformative for the world. You as iGEMers have had an impact, and as you go into your careers you will have a huge impact. There are really three big problems we have to fix. We'll fix them thanks to the massive amount of brainpower in this room. The first problem is pollution. We are living a lifestyle that relies a lot on plastic, relies on fossil fuels that are extracted. We use those materials for a fleeting moment and then they go into dumpsters to live for a very long time. A lot of what you do in iGEM can impact this problem. The second problem we have to face is hunger, especially as climate change continues to accelerate. We need to adapt plants to different weather, different pests, different diseases. There is a lot we can do to ensure the world is fed. The last area is diagnostics and the eradication of diseases. Thanks to synthetic biology and the brainpower of all of you, I think collectively we will be able to decrease human suffering. In the next few slides, I have five slides till the end of my talk. I have a few questions that I'm asking iGEM to help with. The first is back to feeding the world. Can we grow food where people are? Right now food is grown in fields, and even if we enhance yield and decrease fertilizer or pesticides, you still have to transport them. I think there is an opportunity to grow food where people are, like nutritious rice in an apartment. Someone from iGEM will solve this problem. The second question is, can you adjust food, make kale taste good? I like kale but not everybody does. Not only can you bring nutrition, but can you bring delight in the food we consume? The next question is back to pollution. We live in an economy based on plastic. My vision is we can move to an economy based on protein. Our bodies are made of protein, and you can engineer protein to have whatever physical properties you want: elastic, hard, soft, transparent, flexible. Even though the last 100 years has been the century of plastic, I think the next 100 years we have an opportunity to make it the century of protein. That means a world that is more sustainable and also richer in more materials. The teams and people of iGEM, as they grow into careers in industry and academia, will have an opportunity to make this happen, so we don't need to pump oil from the ground anymore. We'll have to look at carbon as a system. Carbon is responsible for global climate change, but carbon is not the problem. The problem is that the carbon is in the wrong place, in the atmosphere instead of helping us make materials. There is a lot of work we can do to redirect and make sure carbon is used in a circular economy. If we do that right, we'll be able to lower the temperature of the planet to where it needs to be. Someone in this room will do that. Skipping this slide in the interest of time, something else that I think someone in this room is going to do is make cancer a chronic disease. It's long overdue. We have the example with AIDS. AIDS used to be a death sentence, and now as the virus evolves, sequencing is used to see how the virus is evolving, and different drugs and cocktails are used to keep the virus under control. The same thing can happen with cancer. Cancer doesn't have to be a death sentence. As cancer is treated and recurs, if we can develop personalized cancer treatment based on the power of synthetic biology, I think someone in this room will make it a chronic disease. That would have a huge impact on humanity. In the same area of disease, there's also a big issue with rare genetic diseases. These diseases are quite rare, so there is not a lot of investment in fixing them. But there are amazing examples, like the recent CAR-T cell treatment that is a massive improvement in quality of life. I think if we use the power of synthetic biology, we'll be able to find a treatment for all of those genetic diseases one by one. My last example in disease: we saw what happened in a pandemic with COVID. Through the tools of synthetic biology, we'll be able to leverage the amazing computing power and cameras on our iPhones to diagnose and detect infectious diseases faster in the future. So there are so many things that can be done. The world is in great need of your imagination, which you've shown in your iGEM teams. As you grow into more adults like we just heard, we can really use your imagination and what you can impact on the world. I really encourage you to try to find yourself among the greats. I'm sure many of you will be on that picture when I come back 5 or 10 years from now. I know you can do it. The world needs it, and the world deserves it. With that, I really ask you to think about what part you will play. When you decide what kind of Batman you're going to be, then come to Twist and we'll be your Robin to help you get there. Thank you very much, I'm looking forward to this day. Thank you.