Home' Technology Review : May June 2006 Contents Q&A
TECHNOLOGY REVIEW /
The genomic revolution is being
driven by advances in analytical
and computational techniques,
and George Church has been behind
many of them. Starting in the late
1970s, Church helped create the
tools, including early software and
protocols for DNA sequencing,
that eventually made possible the
Human Genome Project. These days,
Church, a professor of genetics at
the Harvard Medical School, and his
50-person lab are still nding ways
to synthesize and sequence DNA
faster and more cheaply. One of his
latest interests is synthetic biology,
in which researchers design and
synthesize biological "parts" that
they then incorporate into microbes
or cells. Some anticipated products
of synthetic biology: engineered cells
that produce novel types of phar-
maceuticals, redesigned biological
therapeutics that are more e ective
and safer, and biosensors that can be
built directly into cells.
TR: What is synthetic biology?
Church: Genetics turned into
genomics when you dealt with
the whole genome. Biology turns
into systems biology when you
deal either with the whole of the
cell or some fairly large part of it.
Genetic engineering tur ns into syn-
thetic biology when you use what
you learn from parts and the-
ory to engineer real systems.
How could synthetic biology help you
design more-effective drugs?
Some groups are making cells that
sense tumors and respond by pro-
ducing a toxin. Synthetic biology will
help you engineer the cell to home
in on the tumor, to recognize the
tumor, and, once it is con r med, to
start making a tumor-speci c dr ug.
You and your colleagues recently
developed a new way to synthesize
DNA. What are the benefits?
It s about reducing cost at a rea-
sonable accuracy. Right now the cost
of synthesizing a base [using conven-
tional technology] is about 10 cents.
That s the current street price for raw
oligonucleotides. For synthesizing
simple genes, it s more like $1.30 a
base. [Our method] can manufacture
oligonucleotides at .01 cent per base.
How will getting the cost down aid
It means you re willing to make
many more [genetic] constr ucts. Mak-
ing more constr ucts means you re
much more likely to make some-
thing that works or something useful.
The new method also allows you to
make longer stretches of DNA, right?
Longer stretches are certainly
enabled. The implications are that
we are getting closer to being able
to arbitrarily "program" the mil-
lions of base pairs in microbes or
billions of base pairs in plants and
animal genomes similar to the
way that we program computers.
There has been a lot of buzz about a
$1,000 personal genome.
That s sequencing. So we re o
Right. Now we re talking about
sequencing an individual s genome.
We might never get a perfect
$1,000 diploid genome [the six bil-
lion base pairs in a human s two sets
of chromosomes]. The question is,
what can we a ord and what do we
get for it? Think back to the begin-
ning of the computer industry. They
didn t say, "Oh, we re going to get you
a $1,000 supercomputer." No, they
said, "What can people a ord? And
what can we give them for it?" And
what they gave us was the likes of the
Apple II computer, and people started
writing software for it. Current per-
sonal computers cost about the same
but deliver more. The same thing
may happen with personal genomes.
So what are people likely to spend to
know their own genome?
I think what is a ordable---and
remember, this is a lifetime expense;
your personal genome will hope-
fully last you 80 years or more---is
$10,000. If I can save $100 on average
a year, it is a no-brainer. That s the
cost of a couple days of missed work,
or one diagnostic test that can be put
o due to low risk, or avoiding bad
choices on a year s worth of drugs.
Then the question is, how much of
a person s genome can we sequence
for $10,000? Seven thousand dol-
lars will buy you a million base pairs
of DNA [using conventional technol-
ogy], which is one-6,000th of your
diploid genome. Not very much.
Polony sequencing [a method
developed by Church and colleagues]
is about a hundred times less expen-
sive. So you can sequence about 1
percent of the genome [for $10,000].
That s not bad. You could focus on
likely places you re going to have
problems.We got a factor-of-ten
improvement in the last six months,
so if we could get another 10 per-
cent improvement in the next year,
that would give us 10 percent of the
genome. If we could pick 10 per-
cent of the genome for which we
have lifestyle, nutritional, or syn-
thetic solutions, that would be a good
deliverable for a $10,000 investment.
And it will just get better from there.
We jumped from synthesis to
I do that all the time. It may sound
like a wordplay, but it is actually a very
fundamental concept. There is almost
no synthesis that doesn t involve
sequencing, and vice versa. And that
is why I have really emphasized this
connection in my lab. They are very
Rewriting the genome
Links Archive March April 2006 September October 2006 Navigation Previous Page Next Page