I'm not going to cover all

Biotechnology and health and a focus on one thing that makes the whole thing go in and it makes
us go and that's DNA. So I think we have to

focus down to the core of what's happening and look at the basic properties of the
molecule but it's going to take us into the future.

First of all. You have to think about the future in terms of what we can do with DNA and
how much we can get, how we can read it, how we can synthesize it. It's almost a new version

if you can think about a commercial metaphor DNA as a commodity at this point. It cost
about 20 million dollars to sequence a whole human genome at this point and that is changing very
very quickly. So we're on target and there's a stated goal of getting down to sequencing
an entire
human genome for a thousand dollars. This is not achieved yet but I think it will be achievable. In
In addition to reading the information in the DNA, it's possible that we will be able to synthesize our own DNA quite
cheaply. Right now you can have of segments of DNA up to several thousand bases sequence
quite easily

from more than fifty different commercial vendors.

Now I won't give a lot of biology but basically DNA is a recipe for human being and any other organism
on the planet and the central dogma is the DNA is there to make messenger RNAs and
messenger RNAs make proteins and proteins make the cells in your body work. So because of
the central dogma we'll see that all these subsequent molecules the RNA and the proteins will also


become commodities. The obligatory Morris lost light. Thank you Ralph for setting me up on this. So
the chart that you just saw is the lavender one. This is kind of combination of your competition in communication chart
and it does the look like there is a little steeper one. I borrowed this slide from George Church whose added on some
new tracks for this different kind of of exponential growth in synthesis you see
on the blue. This is the ability to make these molecules and we weren't able to make them
very well fora number years and then suddenly we suddenly this is taken off
dramatically and we're up to an enormous amount, and I'll tell you a little about a project to
synthesize an entire 5,000,000 base genome

Ecoli. Analysis similarily taken off. The units to different for each one of these things. So you have to look at
the relative growth rate. So in terms of sequencing that's also taken off and the latest
technologies you see in light green seems to be the most radically excellarating technologies. So
yes we do have a Morris Law for these for a synthesis and sequencing of DNA as well.

The new commercial sequencing technologies are very exciting. One of the ones that got most of the
attention recently is the technology by the company 454. It's shown a little bit here on
the right.

They read a hundred bases of DNA at a shot. They can do 200,000 reads in one run on a
micro or a nano device. They sequence the entire genome of a bacterium mico plasma
gentalium published this.

Another company, Selecsa, is promising a slightly different technology that
will also be able to sequence something like the size of the human genome in a few
months at a cost estimated at a hundred thousand dollars. So you can already see the dramatic drop from 20
million down very quickly and this is the beginning. There and many other companies that aregetting in
on it. It is a very exciting area now sequencing DNA.

There is George Churche's switching over to synthesizing so the field of synthesizing DNA is
part of a larger enterprise which is called synthetic biology. This is a radical concept. The concept that
we can actually get in and make biology in the lab is a new and very exciting and will
be a dramatic development. And this is so slight that I borrowed from George Church again
about his project and I'm not going to go through all the details but how you make a five million base pair
genome in the lab from scratch? You start synthesizing very short pieces. The pieces on the
very left upper side are just fifty base pairs of DNA. You overlap them. You synthesize an emorous amounts of DNA
and parallel you the overlap and when you overlap two pieces it's twice as long, and when you overlap 2 of those,
it's four times as long and gradually you build up to where you have a whole genome. I won't go through all the
details but if you switch from in vitro to in vevo, at the end, the bacteria themselves are making
the new genomes for you. It's a fascinating and exciting technology.

So there two big names right now in biology and health care. If you look down at the very basic
research that supporting all of these revolutions, the two big buzz words are systems biology and
synthetic biology which I just mentioned biology. Now systems biology is about thinking about the whole entity of the
biological organism to sell as a system. Traditionally, we've looked at it one gene or one protein at a
time but it's actually the system that makes it work and thinking about it and thinking about like an
electrical engineer would think about a whole system is a new and radically important idea. But I
claim that biologists always wanted to understand the system. They just haven't had the tools. So
systems biology to me is just quote unquote good biology. Synthetic biology is actually something
radically new but nevertheless system biology being so important we need to
understand what's the driver for that and the driver for systems biology is again technology and it's
technology not just to read the DNA but to interrogate the cell as it is doing its thing. Basically
wanted to be able to understand how to grow cells, that's the stem cell technology. How to modify cells, the
transgenics. We want to understand how to modify the behavior of the individual genes
within cells that's RNA interference or RNAI. We want to be able to measure all the expressions of the genes
at once. And that's expression ships. You want to be able to measure the differences in the DNA all at once
in a massively parallel way. That's SNIP single nucleai type polymorphism. These are the little
differences between people. We want to measure how the proteins are binding to the
DNA. There's a technological inaudible participation. And every time you notice I've said ONCHIP
so companies like Aqumetrics which are leaders in the area of high throughput
high technology of biology are able to put down to

and incredibly precise array of measurements down on a chip just like in the
semiconductor industry. So using photo lithography you can get down to one micron feature size. You can put
millions of experiments essentially all on one chip. That is creating a massively parallel
interrogation also the informatics and mathematical models that come with this are incredibly important.
I'm just going to go into, I don't have the fancy chip pictures to show you but I wanted to show you
one thing about RNAI this is a very very exciting technology and I'm not going to go through the whole pathway
but basically you can introduce a message into the cell that causes it to change the way it's behaving. Now that's
what a drug does which is exciting. A drug is nothing more than way to tell your body don't make so
much of this protein or make more this other thing. And that they're very hard to come by
because you have it lot of chemical work to understand how to make a small
molecule that would get out get that message and each one seems to be a different, that's why the pharmaceutical
company, the pharmaceutical businesses is a little bit slow to be able to produce a new
drug, it takes an enormous amount of investment because if each one is kind of a one off thing. This is an amazing
technology which is still far from being applicable to human health but has a great potential wehre you can
type in the sequence of the gene one to change and if there was a delivery mechanism, go ahead and then change
the activity of that gene.

So.

I want to switch to why DNA is so exciting. DNA

what's the the foundation for why DNA is so exciting and the foundation
is because the foundation of of understanding DNA is actually evolution. So where do we
get all the DNA on this planet?

It all came from evolution and so the theory the understanding of DNA involve inevitably
molecular evolution.

Evolution is the theoretical foundation of biology. It underlies the understanding of the differences between
people and that will allow us to do personal medicine. It's the key in our battle against inherited
diseases also infectious diseases. Known understanding the genomes of the infectious agents and it can be
used to reveal the functional elements in our genome itself and I'll

give you a quick tour of some of the

Things that we've discovered in the human genome.

Here's how you