Transcriber: Eszter Cselényi Reviewer: Denise RQ
I want to tell you a little bit about my work in hacking cancer.
Cancer is a genetic disease.
The cells program corrupts,
basically, the cell starts to grow, you get a freckle,
maybe a mole, maybe a benign tumor.
In some cases, the cell can spread through the body,
and it can act as seeds planting cancers all through the body
and when that happens, it can become life threatening.
And seen in this way, cancer is actually like an infection,
not with a microbe, not with a virus, but with your own cells gone rogue.
A 100 years ago,
we were actually more worried about microbial infections.
Surgery, contamination, we could get a bacterial infection,
it could overwhelm our bodies very quickly, produce sepsis, then we die.
That changed when this molecule was discovered; this is penicillin.
Penicillin attacks microbes specifically, killing them.
It doesn't hurt ourselves very much.
Penicillin and its chemical cousins revolutionized medicine.
All of a sudden, diseases that would kill us,
sepsis that would kill us,
almost overnight were cured.
Today, we don't even get a day off of work if we get an infection.
In contrast, cancer treatments, chemotherapies,
systemic therapies for the body are more like carpet bombs,
these are not targeted therapies.
This is broad spectrum killing of all fast growing cells.
And there is a lot of collateral damage.
The pale, weak, hairless stereotype of the cancer patient,
that's actually from the treatment, not the cancer.
More modern medicines do precisely target weaknesses in the cancer cell;
molecular pathways, certain proteins.
Drugs like Herceptin, drugs like Gleevec target this cancer cell very specifically.
But sometimes the targets don't exist in a particular cancer.
The drugs are also quite expensive, but if the targets are there,
and the drug is available, like penicillin,
it can be a wonder cure.
We need more of these targeted medicines.
They are revolutionizing oncology.
But there is a problem.
We are not going to get them.
Drug development is a very long process,
it takes up to 15 years, sometimes longer.
It's a pipeline starting with discovery, going through pre-clinical work,
validating the targets, working in animals,
and then there is a series of phase clinical trials:
figure out dosing, determine safety, figure out whether it actually works,
and then scale it up so that you can get the statistics.
It's expensive.
It's risky.
Here is the graph of the number of drugs produced
per billion dollars of R&D invested for the last 60 years,
and you'll see that the slope of this graph is negative.
More money goes into the drug development system,
less drugs come out.
This isn't just a linear decrease, it's an exponential decrease,
it's the reverse of Moore's law
which means we are not going to get cancer drugs
any faster, better, or cheaper, any time soon.
This is a fundamental problem with the system: how do we change it?
The business of drug development isn't really all that hard to figure out.
It's actually a lot like the Hollywood movie studio.
Hollywood movie studios go around the world,
they find interesting projects, they polish them,
they get them pass the censors, then they crank up sales and marketing,
and deliver it to the consumers.
They like blockbusters, they want big hits.
Cancer drugs are essentially the summer blockbusters of the pharma world.
Long lineups of people, very low expectations, easy money.
Last year, about 13 billion dollars worth of cancer drugs were sold.
The targeted cancer drug is more like an indie film:
very, very niche audience.
It really doesn't work with the blockbuster model.
It just doesn't.
And the thing is, an indie art-film is cheap.
It doesn't really matter whether you're making a drug
for a 1,000 people or a million,
it's about the same cost to develop the drug.
And the smaller the market, the higher the price.
The higher the price, the harder it is to get insurance companies to pay for it,
the harder it is for anyone to pay for it out of pocket.
So the reality is the best cancer drugs
really end up helping the fewest people.
Ironically, big pharma is actually struggling to survive as well
because it's costing them more and more each year to make drugs.
They're not getting the outputs,
their business model is in fact running out of gas.
My thesis is simple:
to beat cancer, we need to make more targeted drugs.
And to do that, we have to fix drug development.
How do we do that?
I've worked for the big pharma companies, I know them inside and out.
It's a problem.
Remember, this is not one particular company,
this is not one particular country and its regulatory models,
or its IP structure.
This is a global industry that has never been able to produce efficiencies.
It's fundamentally flawed.
So knowing that,
I though, well, how do we change this?
How do we fix this?
This has been going on
for longer then most of us have been alive.
I'm kind of an oppositional kind a guy,
I see people running this way,
I'm going to go and take a look at what they are running from.
- I can't live in dangerous places -
but the reality is, I had to just start with a blank slate.
And I figured: "Why not look at exactly the opposite
of what all the other companies are doing in pharma?"
And I kind of sketched out this little plan:
OK, while they make blockbusters, what if we only made targeted drugs?
They're closed in proprietary, why don't we be open?
They're for profit, let's be non-profit.
They want to do mass market drugs,
why don't we make drugs for just one person at a time?
And that little framework created in me
the idea for a really radical, different type of drug company.
And it kind of stuck in my brain,
I realized I actually want to go and try and build that sucker.
A few years later I incorporated something called the Pink Army Cooperative.
It's kind of a silly name,
but it's really the idea that you really have to do raise an army.
The most important word here is cooperative.
A co-op is a community that incorporates a business for a shared need.
This was the first, open, democratic, people-owned drug company in the world.
The first co-op.
And I start messaging about it just to find out what did people think.
Was it crazy?
No, I had a mission for this particular drug company:
to make best cancer drugs possible, as fast as possible,
and give them away for free.
People thought I was a little nuts.
But when you think about it, back in 1996,
just giving away free email accounts was kind of crazy,
but that's exactly what a little company, called Hotmail did.
They gave out tens of millions of e-mail accounts,
sold themselves a couple of years later for 400 million dollars,
and today, everybody has free e-mail.
More than that, companies like Google, Facebook, Twitter, and others
provide most of their services to consumers for free.
These are high-tech businesses.
I figured, there must be a way to do this with pharma.
So, the company was meant to be provocative, but not crazy,
and I had an ace up my sleeve: synthetic biology.
I'm a genetic engineer, synthetic biology is in my blood.
If you don't know what synthetic biology is
it's basically this:
it's genetic engineering done with digital tools.
That's it.
It makes it faster, better, and cheaper to do genetic engineering,
than you can imagine.
You don't really need a lab, you need a laptop.
You do all your genetic design on computer,
and then there is this brilliant machine called a synthesizer
that prints out the DNA.
You put that DNA into a cell, you can make it do damn near anything:
fuels, drugs, enzymes, biochemicals.
It's an amazing tool.
And the cool thing is,
it's the same tool as all the big companies use, except that it's cheap.
It's so affordable, it's really available for anyone.
And the cost of doing this type of digital genetic engineering is falling,
the printing of DNA has been falling exponentially in price
for as long as I've been tracking it.
Today, it's about 10 cents a base pair.
To give you some idea, to print out a thousand base pairs
is about a size of a single gene.
Back in 2000, it would have cost me about 12,000 US dollars.
Today it's a 100 dollars,
it's dropping in price quickly.
Every other drug company on the planet has access to this technology,
every other drug company has computers, they have smart people, they have robots.
Why aren't they able to accelerate drug development?
I realized the the most disruptive thing about Pink Army was
that it said it would make drugs for one person at a time,
that's the disruptive part.
It makes the logical sense to go after cancer one person at a time
because no two cancers are the same.
It's your rogue cells, not someone else's.
Every single one is different.
But the idea of making drugs for one person at a time,
puts the person front and center in the drug development process,
not profit, not anything else, not a big scientific paper.
It only requires super small scale manufacturing,
perhaps only a single dose.
It really simplifies the testing
as you're not trying to test on everybody's cells,
you are trying to test on one person's cancer cells.
But the real kicker is
you don't need phased clinical trials when you're making drugs for one person,
you can't do it.
All you can do is test on that one person's cells,
so that saves almost a decade of work.
It completely shaves half a billion dollars off the process,
and it lowers the risk-benefit analysis,
it reduces it to one person.
I'm not saying it's unregulated,
I'm just saying it's really simplified.
The problem is I need to figure out
what drug I could actually make with synthetic biology
that would work for cancer.
I had no idea.
But one day, a colleague put a paper on my desk
describing something called oncolytic virus.
I've never heard of it.
What's an oncolytic virus?
And it turns out it's exactly what it sounds like,
it's a cancer-breaking virus,
and I thought that was so cool.
Here is the basic idea: viruses infect human cells, we know that,
but there're some really, really weak viruses out there.
They're so weak, if they infect a normal cell, the cell shuts it down,
it can't replicate.
But it turns out the cancer cells are broken,
so they have weak and viral defenses,
and you can always find a virus, a weak one,
that can start to grow in the cancer cell,
and it produces lots and lots of virus, it breaks the cell open,
kills the cancer cell,
and it releases more virus particles which go on to infect the cancer.
I thought this was so cool
because you're actually using cancer cells to make the drug that kills them.
So I fell in love with oncolytic viruses, I fell in love with them,
and I thought: "Awesome! How can I make them synthetically?"
(Laughter)
Because then I can tune them for one individual.
A decade ago, in 2003, Craig Venter
and his Nobel prize winning colleague, Ham Smith,
made the second synthetic virus in the world.
It's a bacteriophage, it only kills E. coli.
It's harmless to humans.
And the process looks like this,
and it's a little complicated, so I just walk you through it.
You design the DNA of the genome,
you print out the DNA of the genome,
and you boot it up, and test it.
And the thing I want you to pay attention to
is that it took two weeks to do it a decade ago.
Of course, you know, Craig Venter and a Nobel prize winner.
I started to champion synthetic virology,
I wanted to be able to do this fast and cheap,
and the process just looks like this:
design on computer, print out the DNA, drop it into a tube of cell lysate,
inside that tube you make viruses you can purify them.
Cancer fighting viruses!
And the testing is simple. You only test it on the patient's cells.
If it kills the patient's cells, and it doesn't hurt normal ones,
it's a success,
otherwise you go back to the designboard.
I work with a company called Autodesk,
they make software for design and engineering,
usually for buildings, planes, cars, stuff like that,
but I got them interested:
"What if you design things for living systems?
Is that interesting?" And they said, "Yeah."
So for the last couple of years we've got a Bio-Nano Programmable Matter Group
and I've been focusing on viral engineering.
The software is actually kind of easy.
The tricky thing is, you have to be able to go and print it,
so I've been waiting for the printer technologies to catch up.
You've all seen 3D printing. I've 3D-printed viruses.
They're actually kind a cool.
This is my colleague Jackie Quinn, using a file by my friend Aaron Berliner,
and you can actually hold the file of this virus in your hand.
You realize it's a molecular jigsaw puzzle,
a little key that fits into a lock, and it's beautiful.
This is what you get when you order the genome
from one of these print companies.
It just comes in a tube.
And last month, I booted up Autodesk's first synthetic life form.
Wherever you see a spot on this plate, that's where a virus's infected an E.coli,
and started to grow killing E.coli cells.
It's kind of an antibiotic.
Now, it's not a cancer fighting virus in any way, it's completely harmless,
but this is a software company,
now being able to make a life form.
A life form that started as a file on my laptop.
The cool thing is just by doing that one file, that one program,
you can do research and development.
Using the same process, change the file, and now you can make a cancer drug,
and you can make it specific for an individual
because we are getting all that sequence data.
Change the file again, now you can make an antibiotic.
Change the file again, now you can do a diagnostic.
Get the idea?
Change the file again, you can start doing nano-materials.
There is so much flexibility to this process,
it's basically a molecular 3D printer.
Here is where I am today.
I'm starting to ramp-up this work in cell culture
being able to take cancer cells and normal cells,
take their DNA, take that information,
and turn it into an auto-design program for cancer drugs.
That's super cool.
That's going to take me probably the rest of the year,
but then I want to start doing this in dogs
because dogs get treated with the same, crappy drugs they give humans.
And when their hair falls out, you can't council them.
This could be the biggest advance in K9 oncology in decades.
But what I really want to be able to do is to show that from the animal studies
using these tools, we can start to work with humans,
that have run out of options in their conventional cancer therapies.
This doesn't take forever.
If you make the process work for just one person,
you can scale it for a billion people.
It doesn't take long.
All these technologies, the computers, the printers,
every component of this pathway can be miniaturized and automated.
Here is an example.
I see - it had been built into a pen.
It's essentially a pharma company in a pen:
it can receive WiFi signals for the design,
and it's got a little on-chip DNA synthesizer,
it can produce the drug right in the pen,
purify it, and make it prepared for injection.
Give me an inhaler, too. It really doesn't matter.
The point is you can send these pens out all around the world,
and they are inert until you upload the design.
And that design could be FDA proved and regulated.
This changes the business model of biotech.
It's not the blockbuster model, it looks more like Netflix:
all the personalized cancer drugs you want for one low price.
It also is an opportunity to bring together the R&D community
because right now they're on opposite sides.
Pink Army is the first open drug company:
Researcher, drug developer, patient; I don't care.
It's a new model.
I've come to believe in the power of us for solving these types of problems.
People, when they work together, have taken down the telephone systems,
they've built the operating systems that are the foundations of the web,
they've changed the way we fund the projects.
The power of us is unbelievable.
And I know it will work for pharma.
So how do we beat cancer?
It's simple.
We do it together.
We start today.
And we simply don't stop until we've won.
Thank you.
(Applause)