Drew Endy

I truly believe that as the engineers learn how to construct cells, there will still be profound mysteries in biology and life that will lurk underneath.

Building cells from scratch is no longer a research project.

It's now an engineering project, which means we can plan to do it and anticipate deadlines.

And it's right in front of us.

Yeah, the question that motivates thinking about a cell as a building is, are cells intrinsically complicated?

Or do they just appear to be complicated because they're so darn tiny?

And so we can't see what's going on.

And so as a mental...

exercise, imagine taking a cell that might be a millionth of a meter across, a micron, super tiny, and now imagine making it magically a hundred meters long.

So we're going to scale up.

We're going to multiply the size of the cell by a factor of a hundred million with a magic wand.

You know, the cell's not this solid object.

It's an object comprised of smaller objects, molecules.

And so now we can, at this scale of a 100-meter cell, a building-sized cell—by the way, I would love for somebody to build a building that's a cell.

Yeah, totally.

Or like Roombas or whatever.

But so a protein inside this building-sized cell is going to be about as big as a basketball.

I love it.

And then the thing that makes proteins, the ribosome—

This molecular machine that makes proteins from genetic instructions, that's going to be about as tall as a person.

And then the DNA, the inside cells is DNA, the genome, the genetic instructions.

That DNA for our cell is going to go back and forth across the cell over a thousand times.

If the building's 100 meters long...

The DNA is going to be kilometers long, and it's going to be coiled up and wrapped up and packed inside the cell.

And then another thing that shows up is if you're inside a cell in this building, the building's going to be packed maybe 20% to 40% of stuff.

Wow.

It's like a hoarder of molecules.

Imagine a bookstore that's 50% full of books almost, and you could just barely move through it.

All right.

Now, there's one more wrinkle that blows my mind.

The molecules inside the cell are moving.

They're not fixed in one position, and they're moving spontaneously automatically.

because the molecules are free to move due to the energy of the system.

And so that protein that's a little basketball in this big building is moving so fast

it's able to go through the entire building within a second.

And so that's what's incredibly interesting to me when we start to think about how are these systems working?

How are these cells making other cells?

How are they alive?

If we could see it and follow it in real time, I'm 100% certain we could figure it out.

It's just that it's moving so fast and it's so darn tiny, we haven't been able to follow it exactly right yet.

Yeah, I'll give my version and then I beg Kate to chime in too.

I see there's three different factions or groups that were interested and are interested in the topic.

One are the folks who are interested in the origins of life.

where does life come from?

And so that tribe, if you will, or group has been working towards building cells for a very long time.

Then there's another group that's been taking natural cells and whittling them down to remove all the extra pieces they can and building synthetic genomes with just the stuff needed to keep it going and making a type of minimal synthetic cell starting from natural cells.

And that's been going on for a couple of decades.

And then over the last decade plus, the third group, the engineers are arriving.

And genetic engineering is 50 years old.

That starts by moving small numbers of genes around.

By 2010 or so, the people from that group are getting good enough that they can begin to put together 30 or 40 gene systems, making sophisticated biochemical pathways in natural cells.

There's a subtle point in what Kate's describing that's central to building cells from scratch, which is we're not constrained to any one natural cell.

So all of life on Earth in nature descends or derives from the life that's already here.

That's lineage, right?

We come from our parents and so on.

If you're minimizing a natural cell, you're operating within the context of lineage.

And if you wanted to understand it, you can take this top-down approach, as you say, which is to begin to remove pieces bit by bit and see if it's still alive.

I think of it as whittling or sculpting a block of marble.

You're removing everything that's not needed.

When Kate's talking about building a cell from scratch, we are not subject to that constraint because she gets to choose every block of DNA that goes into that system.

That's the bottom-up, exactly.

The way I think about it metaphorically is I imagine we're all part of this giant world called lineage land, right?

And if we leave that continent or world, go to a new world, you know, we just get to build new things.

Wow.

And it's a very subtle mental shift.

All of bioengineering right now is Edisonian.

This is not something that's decades into the future.

This is something that's a very active field making progress in real time.

Tinker and test, tinker and test.

We don't know when we go to make something happen, if it'll work or not, until we build it and test it.

Thanks for having us.