Revealing Early Development of Life

We and try to help to make things that are unseen seen. We try to make things visible.
And that’s really important in biology because a lot of times you just don’t know when
you look in a microscope if molecularly what you think is going on is actually what’s
going on. And I think what we do is very important because we try to get closer and closer to
the idea of molecular level imaging.
For everything that we publish we try many things that don’t work. And that’s what
we should be doing. Always. So there’s a fair amount of failure. And a lot of times
we learn the most when things don’t work. You sort of have to develop a thick skin because
frankly, most of the stuff we try doesn’t work.
I use physics to invent, design, and build new kinds of microscopes to see things no
one has ever seen before. So my boss Hari was giving a talk at my university
and I saw an abstract of his talk and I thought I knew some things about optics and I was
pretty sure what he said in his abstract was impossible. So I went to his talk to tell
him that he was wrong. He was not wrong, I was very wrong. So at the end of the talk
I asked him for a job. And that’s how I ended up here.
For about a hundred years there was a belief more or less that there was a hard limit for
the sharpest image that an optical microscope could take. And then in the past decade or
so there have been a number of breakthroughs that show, no, that’s not really true, they
were assumptions.
One thing that we have invented recently is a microscope that provides double the resolution
of a conventional microscope you can buy and is also applicable in relatively thick samples
like embryos. This is sort of a new thing. Resolution doubling microscopes have existed
before but they only are good for single cells. We also think about microscopes that are better
at imaging specimens less invasively. So without damaging them. Every time you shine light
on something you perturb it a little bit and most microscopes out there today are sort
of unsuitable for long term imaging of let’s say embryos or other sensitive, live biological
specimens. So a good deal of what we think about is how to make microscopes better suited
to that study. An example of a more biological problem we’re
genuinely interested in is how the nervous system wires inside living organisms. Inside
a very simple organism like a worm. So if you want to ask the question, “how do all
the neurons come together to create a brain,” one method for answering that question is
to actually visualize it. But the data set for that problem doesn’t exist yet because
most microscopes that are available will fry the embryo in course of imaging all of these
different cells in time and in three dimensions. So one thing that we’re doing in collaboration
with groups at Yale and Sloan Kettering is we’re providing microscopes that actually
let you image samples for many hours, about fourteen hours, and noninvasively to see this
brain develop inside an intact organism. What we kind of hope is that by studying the
way the nervous systems forms inside the worm we’ll discover general rules about how neurons
seek out other neurons that would be applicable in higher order organisms like the fish, the
fly, or the human.
The future of our work, I think, will be—make a few general purpose tools, try to genuinely
pick a few workhorses of the field that everyone uses and make them slightly better. And then,
and we’ve already started to do this to some degree, go looking for specific problems
in biology, important problems, that are resistant to existing techniques and design specific
techniques to solve those exact problems. I hope that the kind of work that we do, the
approaches we develop, enable other people to go further than we can. The idea is that
whatever simple rules we might discover in the worm almost certainly are not going to
be exactly the way things are in the human, but one can imagine scaling these things up.