Life but not Alive: Kate Adamala at TEDxBeaconStreet (Full Transcript)

Hey everyone, I would like to talk to you today about engineering biology. And we start with a cell.

If you look around the room. Look around. Everyone you see, yourself included, is made of cells, and yet, despite truly hundreds of years of research, we don’t know exactly how cells work and what are they made of. We do know that they are incredibly complex. We’ve sequenced a lot of different genomes and we made inventories of different proteins, but we don’t know exactly how every gene and every protein works.

We don’t even have a complete, chemical ingredient list of a cell. So, all of that makes studying and modifying biology really hard. It’s like working on an engine without the blueprints. So, engineers are used to dealing with problems like that. They take things apart and put it back together, reshuffling the parts.

Can we do something like that with a biological system? We can and we do. We build synthetic minimal cells. They are biological reactors that have some, but not all properties of a cell. They’re made of biological parts, but they are designed and put together in the lab, so we know exactly what’s inside them. Synthetic life is like life made of jigsaw puzzles, we can mix and match elements of different organisms to make a synthetic cell with a very specific purpose.

Now, why would we want to do that? Well, we work with synthetic cells for all the same reasons we do any biology research. We want to study life, to understand it better. We want to build new biological structures. We want to make better drugs, we want to study the history of life in the universe, and we want to be able to one day teleport biology. And for all of those applications, synthetic cells offer certain advantages over working with live cells.

For one, working with cells is time-consuming, expensive and really hard. Synthetic cells are much cheaper and easier to work with. Synthetic cells are not alive, so there is no bio-safety and bio-containment considerations, and experiments with synthetic cells are much faster to iterate, because those cells are made, you don’t have to wait for them to grow. So, if any of you have ever made beer, or cheese, or bread, you might think that convincing microorganisms to do things for us is really easy. Unfortunately, that is not the case, when what you want to make is not a natural product of a cell metabolism.

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And that’s actually a problem in bioengineering right now, the molecules we want to make end up killing the cells that made them. But you know what? You can’t kill something that’s not alive. So we can use synthetic cells to make compounds that would be really hard, if not impossible, to make in live cells, like different drugs, even cosmetic or perfume ingredients. In a way, synthetic cells are like biomolecular assembly lines. Purifying the product out of them is much easier, because there is none of this natural cell debris clinging to our products.

And simplicity and lack of random cell debris is also very good for studying biology. Synthetic cells are much less crowded than natural cells, and they’re made of a very specific set of components. So, if you want to study a particular disease or a certain metabolic pathway, you can make a synthetic cell that has just that and nothing else, and you can do your experiment without the interference from all the other biology going on in there. So, this is really useful when you want to study drugs. If you want to look how a new drug interacts with a certain disease pathway, or which of the existing drugs could be used for a novel mutation of a disease. You can do drug experiments in synthetic cells much easier, and this idea of simplicity being easier to study is actually very generalizable.

Because there is a big problem in modern biology with reproducibility of the results, and the main reason for that is that no two natural cells are ever alike. Even genetically identical cells can end up just a little bit different from each other, because of all of the mutations they accumulated during their lifetime. So if you do experiment with live cells, the signal you are measuring is just an approximation of a state of each and every one of the cells in your tube. But on the other hand, all of the synthetic cells made in one experiment are alike. There are no individual differences, so the signal we are measuring is very uniform.

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And again that comes in really handy when you want to study a change, influence of a new drug, or development of a disease. With synthetic cells, the signal we are measuring is an amplification of identical signals from identical cells, so every change shows up much stronger. And this cheaper and easier way of studying drugs allows us to finally start considering developing true personalized medicine applications. And this is really exciting because today we give different patients with the same disease, most of the time, the same drug, but people are different, so the same disease can be just a little bit different in every patient, and the reason we don’t develop personalized cures for every combination of a patient and his or her disease is because biomedical research is prohibitively expensive and takes a really long time, but with synthetic cells, being cheaper and easier to work with, you could imagine building personalized models of patient cells and setting up custom pipelines for drug development. This idea that synthetic cells are easier to make and they are so modular, also means that the information about building one can be digitized.

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