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Part of the first layer of expertise.

Lot more risk of scientists focused on publication,

not regulation/risks.

I've seen really scary projects in biotech.

Nature has tried to tweak genetic code.

Maybe nature doesn't do it because, it would be like having 100 different internets. They would not talk to each other.

Be really careful about - not regulation, regulation - which would choke economy and drive opportunities elsewhere.
My work is cracking the failure of drug development.

Health is not on an exponential.

60 years of innovation.

Process is so complex with so many stakeholders.

Never been able to accelerate.

Regardless of how much money we put in.

To apply data we are collecting and move forward.

N1 medicine.

Each of us, there is no control for our complex lives.

We are getting sophisticated enough to evaluate those risks.

Make medicines for ourselves.
You want your own biotech company. Buy 1 share. You'll be a full member.

Grow like Linux.

- cooperative membership

Fascinating people.

Like open source, it can go into the corporate realm.
Derek: Pink army?

Just waiting for energies to stabilize.

I do want you to become members.
Santiago: How mitigate risks that make you afraid?
What makes you afraid is different from what makes me afraid.

If I had end stage cancer, I'd be in a different place.
\"You are here\" a new branch to this evolutionary tree.

This took 4 b years.

Synthia - always copy first before you start to

100 m years per calendar year.

May be much faster depending on tools and technologies.

You might have synthetic pets in 40 years? 20 years?

syn and methlyations.
Darwin did not see this coming.

That we'd start to forward engineer.

Natural selection does not apply to us anymore.
Can we make enzymes that make diamond.

or just expresss it in our skin.

Without those constraints - we can build the environments these creatures live in.

Homo evolutis.

We reimagine ourselves in this century.
That is something to think about.
Venter is teased about playing god.

I think it is a responsibility we have to take seriously.

Something spiritual about it as well.
It has to be about doing good things. Not profit.

We need to work together to do that.
These little bacteria growing on a plate will change the world.

It will make us happy.

And be a little weird (smiley face with three eyes).

12:30 [applause]
Q: Is lack of concern from DIY based on ...

A: All of the above. They are self-identified, coming to meetings.

Recreating all the equipment.
Q: Erez. Thank you for a wonderful visionary talk. Humanity genome will be about an Exobyte.

A: One copy. Dynamic genome analysis.

6x faster data generator than Moore's law.

Maybe we'll get an up-step.
Q: Erez: Drug mfg today is not new technology, needs a new system.

A: Yes.

Some countries have assisted suicide. Why do they need an FDA?

As we get more and more sensor technologies, more will become automatic.
Q: Sasha: As we translate genetic information into digital - is there a consistency?

Q: Gene ontologies quite early on. Pretty good structure. Other layers have different formats. Still in early days.


Doesn't have a business model yet.

May end up something like Apple app store.

Just pick up the seeds, instead of going to Home Depot.
Cross over may be food. As we start to do boutique food. You know the designs, health effects. More interest in the outputs of genetic engineering. Design also does the manufacturing.
Q: Tony: Synthia - how much do we understand.

A: Copying the gene is easy. We don't understand how it does all the replications. People are hacking that. We'll get first protocells.

Life is modular.

We are 100 T computers.

Have a good lunch and a great summer.
Salim: Stress over ignite?

Rationale for this. Never enough time to get them done in a proper way.

This is deliberate. A little bit stressful. We want to see these cracks, so when you in the real world, it is a lot more polished.

Will be around for feedback this evening.
Candice: Order?

Salim: Randomly.

== end
Afternoon pad:





Brad Templeton
NCS Core track
Slides: [Manuel Zaera]

All Our Ideas:
Kathryn will review later looking for any [ref] markers.

She will attempt to fill these in with references.
2:29 Lead in: Flight of the Conchords. \"The Humans are Dead\"

Binary solo:








2:31 \"In the know\" segment:
Brad: Our goal is to breakout. Come up with ideas nobody else has come up with.

This isour first attempt at this with our large group. We'll see what we can do.
Robotic transportation. Robots driving cars. Cars driving themselves.

Train systems already.

Heathrow - pod cars on dedicated track.

What about ordinary roads?

Studying this. Incredibly large numbers around cars.

Think about the future city. Mostly the first world city. But we have people from more chaotic cities.

Wired everywhere.

Gigabits of connectivity everywhere.


Sensors everywhere

Data about movement.

Reality could be very different from today.

In 20th century: suburbanization.

Could reverse or become worse.
Got excited about cars driving themselves. Discovered they are REAL.

May have visitor - hisroboticPrius drives him around town.

What is future about it is the legal, ethical battles.

Human beings are terrible drivers.

We kill 40,000 people every year. 1.2 m around the world.

Largest cause of death between childhood diseases and diseases of old age.

Cities session ended with a call for end of traffic accidents.
Transportation safety $230 Bn. Worldwide 2.5% of GDP 8 cents per mile.

Gas is above 8 cents per mile. This cost - your share of the cost of traffic accidents -- was highest.

We spend billions of hours behind the wheel.

Accidents due to inattention, drinking. Robots will NOT have inattention. Won't drink and drive.
60% of land in LA belongs to \"the automobile\"

25% of energy use goes into cars.

Building cars also takes energy.

Onething we replace quickly that we could do something about.
Artificialhorse intelligence. More like a bug. Not a lot of AI. Why people have already done it.
About 5 years ago, the military -

[clip showing how DARPA grand challenge #2 - humans could not keep up with robot driver]

Sponsored contest. Small teams, even individuals. Astounding results.

First contest, no one made it 7 miles.

Some of these went 150 miles.

[another vido - cars goes down ravine]

That was 2005. Main sensor broke and car still worked.
What does it mean for how we live? for safety? for our cities?
Third contest was to go on streets -

[video of self driving car with some rock guitar backing BOSS
Ubuntu LINUX.

Terabyte of storage.

Monitor to debug things.

Inertial system.

\"How does itkeep from running over dog?\" Laser.

\"Complicated?\" Started about a year and a half ago.

Maybe by 2020you will be able to buy this.

Get from place to place without having to worry about it.]
18 months to build a revolution with a small team.

Dangerous to predict when a technology will arrive.

I want to tell you that you can alreadybuy cars that automatically park themselves, keep fixed spacing, tells you what car is near -- for lane changes, spotting pedestrians, read road signs, find timing of stop lights, parking garage pillar avoidance. Can save 100,000s of lives

Elimiate importation of oil
: Ulitimate, non-killer app.

This is a way for softare to save the world.

Here is the autonomous Prius. Fisherman's Wharf to Oakland without touching the wheel.

Not science fiction.

Push button on cell phone.

Get car in seconds.

Arrive at elevator of building you are going to - without centralized intervention.
Ability to go in \"right vehicle for trip.\" SUV for skiing. More than one child: minivan.

Vast majority of trips are 1 person, short distance rips.

Energy efficnet. Greener than transit.

In BTUs (unit of energy used in US, not Britain),

People in car: 1.5 (the half person is in the trunk) 3400 BTU/passenger mile.

Buses use more - on average. Not all are full.

Results in US - not as good as Europe and Asia.

NYC system is only a bit better than cars.

Japan is twice as good.

Electric scooter is 10x as good.

Amazing to see

500-600 lbs of weight per passenger. Start and stopall the time.

Not able to compete with lightweight vehicles.
If robots could make us tolerate electric cars, that would be great.

If lighter, much more efficinet.

Movie, \"Who killed the electric car?\"
Long time to recharge. Hard to find place to charge.

What if we had people use standard batteries.

We CAN build theese vehicles. Harder to get people to use them.

This is a chance to apply Moore's Law to Transportation

Competing innovators vs 19 C

Compare: Early adopters vs municipal gov. admin.

Big infrastructures vs bottom-up growth with almost no new infrastructure
Individuals buy the cars - happens amorphously - ground swell - rather than a whole new network with planning and infrastructure - if you allow people to ride on the existing infrastructure - people can ride on that!
It begins in expensive vehicles

but what costs $10,000 today - will cost $100 in ten years
Down the road you will be able to buy a car, that if you are going to enter an accident, the safest thing will be to let go of the wheel and let the robotics take over.
one test - school of fish - do you succeed in touching the fish in a school? No! They manouver out of the way.
Steps along the way:

-existing technology

-safer car

-valet parking



-school of fish

-safety contest
Nice to have a race between humans and robots to see who can drive more safely.[Kind of a Turing test for robotic cars, in a sense.]
[video Valet car prototype] parking itself

Two small lasers, downloads maps, drives itself and parks. Technology available in labs. Available in the future.

some speed is slow enough to be safe

some special roads with decent speed

slow in the last mile...
Political issues:

must be legal

must not be over-regulated

juristictions will compete

Signapore, China, India, Israel, Japan possibly?

Children, the aged, the drunk?

No walking

Longer trips, Robo-RV, super-sprawl

Computer intrution, bugs
Sometimes when we are given an efficiency or benefit, we eat it up and exploit it. i.e. anti-locking brakes giving people a false sence of security and people taking undue risks.
There are already a great deal of computers in your car, and your life does depend on them but they are not as prevelant as what we are suggesting.

Cameras and sensors are everywhere...

Can we oder our robocar to do something illegal?

Will police have the power to redirect it?

WIll the police ever have the grounds to pull you over?

Will you have the freedom to tinker?

New traffic code: - Be safe - Don't unfairly impede others
Example. Tom Cruise in the film (Robocop?)
More downsides:

abuse of robocar avoidance

sourcing the electricity

Arrrgh! (pirates!)

Killbots (Military asks for this technology and built this for killing purposes. Land robots and air predator drones already exist)

Slow cars and empty vehicles moves

Disruption - economic and cultural - positive and negative






S.M.O.P (small matter of programming - ironic comment)

Software recalls
Police may want to control all the vehicles etc.
Engineering changes:

range not a factor

acceleration and speed not a factor

comfort i.e. syncronisation with the traffic lights, soft rides


different dafety constraints

small widths, single passenger or face-to-face, sleepers, RVs

consequence of the military developing this technology - they have made a committment 1/3 of all vehicles will be autonomous - air, land (and sea?) for delivery

If they are used only for cargo - these robots could change the nature of our cities via shopping for instance. i.e. pizza delivery or general shopping. Imagine being able to get anything in a short amount of time. How is that going to change urban design. Retail outlets? Our homes and activities? All of these things can be obtained on demand...

This is something that will be possible with delivery robots. e.g. Meals delivered by robots changing the economics of what we keep in the house, how we use our time etc.
How could this technology change at airports? Robots greeting you at arrival and delivers your luggage. Farms would change with this technology...
Parking and congestion

They do not park - they stand

Can stand in the driveway
Q: If it's using the reflection of the laser to determine the distance of the object why would a mirror make it not work?
Poor Man's teleporter

- Con
What are existing cities going to do?

What can a brand new city do?
Sketch/collage of talk:
[end of presentation]

All Our Ideas crowdsourced questions:

Please take 2 minutes to vote for suggestions.

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SkyTran: the future of transportation

Local company aims to build its 'SkyTran' at NASA Research Park
$295.54 EZIP 750 Front Suspension Long-Range Electric Scooter
Futuristic car design
Global market outlook for electrical scooters

(copy in Google docs: )
JCDecaux bicycle sharing

(copy at )
Electric tricycle $990 on EBay
Robot Rickshaw

- effective for elderly





Brad Templeton / Salim Ismail

NCS CL1 delle reti e dell'informazione
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Philip Low PhD, Founder of NeuroVigil Will speak on novel Neuromonitoring technology and computational biometrics.


II/ iBrain

III/ biomarkers

Andrew Kogelnik MD PhD (Founder of The Open Medicine Institute). The present and future of clinical diagnostics and medical informatics.


Keith Murphy, CEO of Organovo The future of 3-D Organ Printing


William Haseltine, PhD Chairman of Haseltine Global Health. Bill is a former Harvard prof, and a very significant figure in Biotech, including founding Human Genome Sciences with Craig Venter.

Dr Haseltine will speak on challenges and opportunities in developing/commercializing new technologies in healthcare & biotechnology.
=============== PRE-presentation notes
Erez has introduced a new SUMMARY Etherpad:

Please contribute.
Spreadsheet of all core Etherpads:
Link to full SU Etherpad index:
=============== End of PRE-presentation notes
2:36 Daniel: Intro
Philip Low: Have you had your blood pressure checked?

Your brain?

- Painting - George Seurat

Revolutionary painting. Put microscopic dots on canvas to make this painting.

We can understand the different figures.

If you take a few steps closer, we lose detail. Just a bunch of dots.

Why is this important.

- Spikes

Used to representing things in terms of dots in neuroscience.

When cell fires, we get dots. Repeat over and over.

Cell tends to fire at pretty much the same time.

Neurons are responding in reliable, reproduceable fashion.

More cells in our brains than stars in the Universe.


Heiroglyph of the brain.

Very hard to decode

Brain is not on or off. This is an analog signal.

How can we present it as something less abstruse.

REM sleep - around head near eyes that tell us about this sleep.

Can we do this [find patterns?] with the brain.
Three parts.


II. iBrain - sort of an iPod for the brain

III Biomarkers - what kind of biomarkers can we get non envasively and remotely (not in a clinic)

- Yearly Cost

$25K Alzheimers patient

- $100 B for Alz

$42 B for Schiz
Strong link between sleep and schizophrenia
- \"increased insomnia\"
Sleep apnea
Amount of sleep - we've lost 20% of our sleep.

1 in 6 say severe problem.

Half of all auto fatalities caused by people falling asleep

70 million Americans have a sleep disorder

4 million get sleep tests
why don't more people get tests? current system sucks


1 in 3 americans claim sleep is a problem

1 in 6 says it's a severe problem

1/3 of accidents on the road are due to falling asleep

1/2 of fataliites on the road are due to it


What is a sleep test?


EEG, blood pressure, oxygen saturation, heart beat, etc.

Takes about two hours to set up and by the end have about \"400 electrodes hanging from you\" - Luke
Electrode placement process:

rub skin with abrasive skin glue suction cups containing sensors then duct tape them

about 22 wires



So that's the way we record sleep in 2010

How do we treat sleep?

Have you heard of Haclion?


It was the ambien of late 80s early 90s

It made people nutz

Makes the problem worse


example: Woman killed her mother before her mother's 83rd birthday put the card in her hand and won a settlement against drug maker


Do you own an MRI?


Super Computer?


Cell phone?

Let's use cell phones for our studies


Going back to the study let's focus on a single channel

Let's do some analysis, from my work at Salk

I initially started on Birds, if you look at a bird brain it is very different than a mammalian brain

bundles of neurons that are highly specialized, very well pattern defined when bird is singing identical when they are sleeping

Invented a method to record and an algortihm to analyze


alanyzed rats, birds, lets do humans


usually don't see anything over 20 Hz even though we know the brain can do it, call above 20 Hz \"dark matter\"

normalizing data allows you to see higher frequencies with low amplitude relative to their low frequency high amplitude counterparts


Take all the labels and super impose them on the map


Who thinks REM is red? etc.

Red is Rem

White is sws

blue light sleep

yellow wakefullness


with german data the same trick works

interesting because it means we can go from 30 second snapshots to a single dot and we can create an entire map of sleep using clusters of those dots


Separation Clusters

how many groups? 4

3d graphs using: w filter, sws filter, rem filter, time filter, etc


we have great ways of looking at the info but still need a better way to test


so this is where the iBrain comes in


User friendly on off switch, easy electrodes, washable, secure, HIPAA compliant, 60+ hours of recording storage, USB or wall chargeeable, rechargeable 20+ hours of battery life

you get fairly clean EEGs


Go from big guy with all these wires and a graph to sleeping beauty with analyzing down in under a minute


Here is the team


here is the science board


business board


which parts of brain causes which sleep patterns?

thymus = sws

etc, etc, etc.

Chart: Frequency Separation over Time

What do you see on this chart?

Red dots have two levels


If we looks at just rem and remove all the colors

do you think this is automated or same subjects on two different nights


arruban dolls made when children with special powers die so the sibling can take care of him/her, special powers = twins


neither I am showing you twins



looking for partners around the world


X prize for a alzheimers diagnoses algorithms


get same sensor readings through shirt


\"We shall not cease from exploration, and the end of all our exploring will be to arrive where we started and know the place for the first time. \"

T. S. Eliot
I am only one of many, thank you
Q: Biggest task of using a single channel EEG?

A: Convincing people that all we need in most studies is a single channel EEG
Q: What are you doing with Pharma?

A: Take the drug and send the patient off to home to use drug and sleep sensors, we don't know what drug they are on and we look for changes in brain

we test before, during, after

Phase 1: look for safety of drug

Phase 2: look for efficacy of drug compared to controls
Q: Why were there studies with multiple channel EEG and not one?

A: It was thought that we needed multiple reading to understand patient was undergoing REM
Q: Compared to competitor[which one anyone]?

A: We are different, can't really talk about what they are doing, they are trying to show people their current brain patterns, we are creating a map of brain based on your sleep
Q: DB?

A: We want to build the biggest db for the brain

7606 Fay Avenue

La Jolla, CA 92037

T +1(858) 454-5134

F +1(858) 454-5164
530 University Avenue

Palo Alto, CA 94301

By Appointment Only
3:34 [Julielynn gets wired up and brain waves are displayed on iPhone]

Daniel: Thank Dr. Low.

Salim: Quick update. In DC. On the worst days to leave SU for the summer. Strategy US-AID $120 b budget. How do they structure themselves for the future.

By end - participated in grand dinner. Hillary Clinton gave a talk.

Standing at the grand podium - for 4 minutes talked about SU.
We are way ahead of everybody else.

How quickly can we have followups with you.

Pretty profound day and a half.
Great solutions come when you are playing with it.

Orthogonal turns.

Speed with which you can iterate with goal in mind is what gets you there.

Have fun with it.

Think of each of these lectures as fun, in a sense.

Talks off the main track.

Far out, outlier idea. How would I use this in synthetic biology.

Have peripheral talks, little clouds, something interesting will come of it.
Luke is here for a few days. Major pain in ass last year. Extraordinary.
Luke: Quick announcement. Sarah Jane Pell. TED Fellowship. Deadline Aug 20. Will talk late tonight, ad lib. Really good idea to have video on-line about you talking about your passion.

Friday night - record that.

Andrew Kogelnik
Where diagnostic testing

- Overview



Real World and Future

Often a void of data being returned to you.
- History

Ear to chest ... Koch, isolate microbes ... radiology

In last 50 years, have moved along.

Biotech DNA, messages

A lot has not translated well into clinical practice

1960s were first regular blood tests

PCR in 1980s. Now full genome sequencing.

(under 100 people)

Clinical medicine is not geared to figuring these things out.

Data / Physician -- gap -- how to leverage genome, testing like iBrain.

Would love to hook iBrain up to patients.
- Diagnosis and the Elephant.

X disease and here is the chromosome
-Sensitivity vs. Specificity

[ see also

Moving beyond sensitivity and

specificity: using likelihood ratios to

help interpret diagnostic tests ]

-ROC Curves


the study of classifying diseases

doesn't do much when we are at molecular level

- Blood Diagnostics

diagram of cell seperation tube (plasma, cellular band, gel, RBCs and granulocytes)

based on where you simple (blood vs tissue or much more granular than that) you may find different results

you have to make sure you are talking about the same thing hen you get down to that level (FISH)
- Convergence

- Examples. Biotech vs Clinical Medicine
-Dx Summary

treatments for ? and typhoid fever are very very different

and we can give them the right treatment on day one which could be life or death for these patients


You can find individual gene responses on this graph over time and type

See different responses in staff vs. viral infection


shortcuts this pathway

- Future of Diagnostics

where are we going with this?

is there a unique RNA or molecule for a particular disease

I may not be able to culture the specimen

It's possible to find molecular reaction to treatments
4:20 [applause]

Peter D: Singularity Ring Options

New developments

Kip will have ring sizer

8 like A

22 like B (with rocket)
4:38 Keith Murphy


Regenerative Medicine in Three Dimensions

Daniel: The last part of our medicine track.

Cutting edge work - coming to clinical reality
KM: Thanks Daniel.

I understand you have seen a lot of 3D printing.
Excited to talk about the biology part of that

cells need sterility so couldn't bring a demo

but I brought some slides:
- TIME magazine. Alexis Carrel.

Invented way to connect two blood vessels.

Joined with Charles Lindbergh

Developed large perfusion system

Lindbergh had material science background and developed the pump

Able to perfuse a chicken heart and keep it alive for multiple weeks

seen as engendering life, capturing the secrets of life

- The Early Years and Successful Skin Tissue Engineering

Organogenesis - Living Technology

Apligraf from Advanced Tissue Sciences - $100 m raised, then liquidated

Generation of life has proved much harder

we are at 2D tissue generation

Created skin successfully to give to patients but it is hard to do succesfully

Advanced Tissue Sciences is now out of business because they were too widespread in their ims and only had one skin product in one market

Then Organogenesis narrowed their focus but also went backrupt

You've got to have science matched with -- in medicine -- reimbursement.

Novartis - expert in getting paid.
- Engineering the Third Dimension Tissue Engineering

[book: Principles of Tissue Engineering] [ref]

[photo of mouse with ear growing out of its side - the ear-mouse]

2D is where we have had our successes but their have been a lot of attempts at 3D

printing construct in a 3D printing way then grow cells in that collagen structure
- Successful 3D Organ Generation

Grew a ear on a mouse with the idea of transplanting it to a human, for cosmetic purposes not functional
fRom an engineering point of view, build the structure, grow tissue on structure, add blood vessels so the cell don't die, erroding the support structure at the right rate, ...
Tengion via Anthony Atala developed a bladder-esque device made of smooth muscles, huge success, in phase 2, works in some patients not others but still a breakthrough even if it is still in 2D space
- Decellularization of Organs Shows Initial Promise

Another concept: instead of creating a scaffold structure, take something from the body and create the scaffold from that. This is called decellularization. Anthony [?]

Anthony Atala works on this a lot.

Doris Taylor at U. Minnesota

This has only been done in animals for obvious reasons. Strip organ of cells, usually with a basic solution that will wash away the cells. What you're left with is the collagen matrix.

You can actually get the cells you put on that structure to beat. The challenge is getting it to last long-term and be effective.
Another example - in the lung - published 4 or 5 weeks ago. She took a similar tack and used it on the lung. The time frame was very well documented - it lasted 45 minutes to 2 hours. This leads me to another big challenge in the field. You can create something 3D in cells, maybe even with a biofactory, but if you do that, how do you get the cells to remain alive? That's the role of the vascular system. One of the goals of this strategy is starting with that - one of the hardest things for anyone to do. You can put these cells back in the body, but they're outside the collagen matrix and blood vessels are on the inside, so they're starved of blood and die in about 2 hours.
With Organovo printing technology, we can make a 1cm cube of liver cells, but the cells in the middle will die in 2 hours.

we are not at the point where we can print an organ yet
- Inkjet technologies Developed by Thomas Boland at Clemson
One of the important things is to distinguish what we do - organovo - from inkjet. Inkjet is just taking a regular HP inkjet and find way to make the orifice work so the cells will spray out and stick to a surface. It can be as little as 1 cell at a time. Can be good for testing - 96-well plate, etc....

If I can print one layer of cells, and then another layer, and then a third, can I get to the point where I'm making a structure. You guys get that because you've been playing with the 3D printers.
They [who?] have re-engineered their HP printer so it has a 3rd axis stage. They're using a combination of collagen and cells to print their structures and get to 3 dimensions.
- Organovo Story - NovoGen Tissue Printing

Organovo has a similar technology to that, but we're trying to break through the traditional scaffold-based tissue engineering.
Tangent: I'm a chemical engineer by training. I was studying drug delivery at MIT. A Bob Langer technology, encapsulating proteins. Moved to Amgen, went to B-school, but I had the background in that tech and a real drive to be entrepreneurial. i went out and looked for a technology that could essentially do this - 10^9 - be really big. I had to good fortune to get introduced to [??] at Unive. Missouri. He didn't get the attention from the VCs there. I connected with him, he knew he wanted to get this commercial, but we formed a very good team. I'm coming from business, he's coming from the scientific side. I wanted to be back 20 years before, at the dawn of biotech. I was able to grow with that. Thinking about where that took me, it was obvious I wanted to be in regenerative medicine.
Tissue culture is so well-defined and commonly used that people have even forgotten what happens in tissue culture. They don't think about what's going on in the system. They say \"you can't culture liver cells. They don't grow in culture.\" I look at it from an entirely different perspective. They grow in the body. We're just not transferring the right abstraction to allow them to grow outside the body. The same thing is true of liver cells, eyelet cells. People say \"we can't do diabetes because you can't grow those cells outside the body to test them.\" But they're just not creating the right environment. Some time ago people said you couldn't make smooth muscle cells outside the body. Well, our EVP of R&D was responsible for a breakthrough in that field. She showed everything done in cell culture involved turning on the incubator, creating a temperature, CO2 environment, and you're done. Well, there's a key gas you're not thinking about, which is Oxygen. What's the composition of air? 79% Nitrogen, 20% Oxygen, and the rest is Argon.
What percent of oxygen is seen by the average cell in your body? In the blood flowing through the arteries, it's about 5-12%. Completely different from 20% in ambient air.
Many of us take anti-oxidants. Oxidative stress is one of the major causes of aging. So when you're sitting with these cell cultures in a high-oxygen environment, you're causing them to die faster.
That's the kind of breakthrough thinking we like to build at Organovo.
Let's talk about Novagen. It's not inkjet. From the earlier talk we saw Pointillism. Think about your TV,'s creating a 2D image out of tiny pixels of color. You can just do color by numbers and Serrat can just put those little tiny dots there. Organovo is doing that but instead of colors, cells. Make that 3D grid very small, so they're each comprised of just one cell type. You put those cells in those places - you're not done, but you're on the way. Our cartridge is filled with tiny spheres of cells. 100-500 microns in size. Thousands of cells. What is proprietary about what we do is making those cell aggregates. Intermediates that survive printing, but fuse into a greater structure. The way it works - what's the - uh - MakerBot. MakerBot prints two materials, positive and negative. We do the same. We print the cells as the positive, the negative is a gel that the cells have no affinity for. Then we wash away the gel. There's a gel head and a cell head.
In this picture, the tiny orange balls are cells. (They're not actually orange.) The grey is the gel material. We just lay these two down next to each other with high precision. It doesn't have to be hexagonal, but it tends to line up that way. You can actually imagine if you look at the bottom right, branched structures. That's important to solve that problem I was talking about before - vascularisation. To make this a real transformational tech, we need branch structures and blood vessels.
- NovoGen Bioprinting Explained


We take cells, and then recombine, in this one you'll see the cells are initially cylinders. The intermediate after printing...and then that's the finished product after incubation for 24 hours.
Essentially, what you saw is that in some cases we don't need to start with spheres. If you know you have a constant cross-section, may as well start with cylinders so you don't have to fuse in an extra direction.
- After Printing, Blood Vessels Are Matured in Bioreactors

What you have to do with this afterwards - the downstream challenges really start to cause us problems. You have to keep that tissue alive. And what environment do I have to put it in before it's ready to go in a body. As soon as it's fused, we need to start maturing it because it's not strong enough right away. The burst pressure is going to be 0 right away. At 24 hours, it's going to be 5 mmHg. So that's about 1/24 of the pressure we need. At day 4, it's 360 mmHg. In the body it's 1500 mmHg. What's going on in that interim that makes that happen? Connective tissue. If you take a picture of your body, if you think about what's inside, there's only two things fundamentally. Cells and collagen. There are different variations of collagen, we call them the extracellular matrix. Cells bind to those by tethers that they put out from the cell membrane. And where I'm talking about day 1, what's holding the cells together is those little tethers that stick to each other. It's kind of what happens when your hand sticks to leather or vinyl. The key is that collagen can grow over time, but you have to give the cells the right conditions to grow, in a bioreactor.
These are blood vessels being profused. We give it constant pulsation, at 60 HZ to 168 Hz. It will beat over time. That strengthens it. Largely we're training the muscle to be able to grow. it will strengthen in burst pressure and decrease in compliance. On the right you see the pumps.
- Successful bioprinting of branched cellular tube

I mentioned that one of the challenges is blood vessels in thicker and thicker tissue. This is something else we use the printer for. Here's that schematic - cells as spheres, another layer, and then a top layer, being printed out of spheres. In this case we want to make the branch structure, so not cylinders. it tapers down in diameter, because we're making a macrovasculature. We have made these already. But we haven't shown we can make those grow in tissue and make it work. We have a number of grants - DARPA, SBIR, NIH - but it needs more funding to really get it going.
Our goal is tissue on demand. The concept is, when a surgoen goes to do work inside the body, their palette is very small. They can only work with the tissues available from that body, or a cadaver in some cases. So there are things they can't even dream of doing. Bypass surgery is simply taking a blood vessel from your body, and using it to bypass an artery that's going to the heart. The reason they don't do it very often in your brain is because you don't have the right size blood vessel to work with. The vasculature is going to be the same diameter in some places, but you can't do it in the toes or the brain because you don't have the right size material. Would be solved by tissue on demand. You have a problem with your urinary tract, you want to reroute to a urinary bag, you have to take bowel tissue to do that. We could make a simple tube of smooth muscle, so you wouldn't do further harm in the body.
- NovoGen Bioprinting Techniques Are Also a Platform Technology for Creating More Complex Geometries

We think we can get to things like liver tissue. A kidney is a big filter. A liver is more like a bioactive sponge. Actually performing functions on toxins. A big bed of hepatocytes

That bed, with four different sets of vessels, the biliary system, two different venal systems and an arterial supply of blood. When you get to printing that you have to break it down into these tiny little grid spaces. When you think about printing at each level, you just take a cross section and print on that 2D layer. You can print a tube with a series of ellipses. The challenge is maturing it and making it work.
- Why Do Cells Fuse Together? Why Do Cells Hold Together?

I want to show you a bit of actual biochemistry in our process. The cells bind to the collagen proteins. They make the collagen themselves - that's at the core of our tech. You don't have to start with a foreign material and attach cells. First place the cells where they need to be, and then if you give them the right signals they know what to do. If you put them in a bioreactor they actually build which is what you need in a blood vessel.
That process starts with our cell aggregates, the building block of the bioprinter. As soon as two cells are put in close proximity, they start to bind through cell adhesion molecules. Then, they have some flowability{?} They're not completely bound. They move by normal tissue liquidity into the shape you wanted, and over time build more and more of these bonds and become a closely bound piece of tissue. Start with weak adhesion, and then build a lot of adhesion. The 3D structure build when these cells are close together causes the collagen to be built.
This happens in your body every day. 60% of your body is not the same as it was 180 days ago. Collagen included. Cells eat away collagen and build new collagen. We're just starting with none and getting to the point of having enough. (Bones work the same way too.)
- How Long will it take?

[bar chart showing Scaffold Based effort totally dominates 3D printing approach]

Success Timing is Entirely Dependent on Funding

Alliance for Regenerative Medicine

Biggest question we'll get in our field: How long will it take to actually create large organs? And this is where prizes come in. The concept we need to do somehting big as a society to make organs happen. We're a company, we have to be profit-oriented, and what we said we'd do is to be a platform to make the greater good happen. We want to provide our tech broadly. You have a choice, you can do the two things you can fund yourself, or create a platform for everyone, bring in people who know what you don't know, give the tools to the people who can work with them best, and make an iterative process.
What we're trying to do is use these bioprinters we've already created - very easy to use for a researcher - we can literally take them tomorrow to a university, if they have the cabinet where they make cells, it fits inside that same cabinet and they can print something within a week.
A ton of work for 20 years with the scaffold, a tiny bit with bioprinting. Early days here. We're working with groups like the Alliance for Regenerative Medicine to get more funding.
- Click and Print (TM) Technology

Automated calibration - makes things easy. Accuracy +/- 20 microns. Click and print technology: we'll need help from guys like you in the future - our skill set does not include cad-type data. Right now it's a very basic system where we just click this - the blue represents gel, the red and orange represent cell types. You can just click this in - about 60 clicks and then hit print and it will make the structure. But in terms of taking MRI, CT data, turn it into a CAD to make the tissue you want, we're gonna need a lot of help.
Our field, I feel, is one of the most in need of multi-talented people from all different perspectives. Theoretical physics, biophysics, anaesthesiology, developmental, zoology, cardiac profusionist, industrial automation, biochem. The only way we get to where we're going is blending all these together. That's I think the essence of what the Singularity is about.
So essentially, this is the printer in action - we couldn't bring it in [video]. It's printing a blood vessel. Let's take questions while this plays.
Q: Can you print a brain or a whole body one day?

A: The hardest thing to do is going to be brain. Axon grows very thin and can go for meters. It's going to be hard to print. However it can be done. There's a lot of things in the body you can contemplate making already. Nerves are the hardest. We've got a product that's essentially a nerve conduit. Can't print the axons, but we can print the structure that surround them and then the axons grow. In animals, to reconnect gaps in the periphery, this works. But in the brain it's a mass of neurons, and you're talking about placement of molecules, not cells.
Q: What are the next steps for other areas to focus on?

A: We try to keep things simple - allow the cells to remain alive. Work through the hierarchy - larger tubes, when you get to a certain wall thickness you need to build more blood vessels into the wall. Trachea, bowel - like a large tube - Our wall thicknesses are 500-600 microns. The next level is tubes like 4mm.
Q: What about the other direction? Stopping development? [For cancer?]

A: We're not smart enough - we can give people tools. Talk about testing antiangiogenesis {Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels.Angiogenesis is a normal and vital process in growth and development. However, it is also a fundamental step in the transition of tumors from a dormant state to a malignant one.}. Can take cells from all different phenotypes, create 10 different tumor types, show that it works on some but not on others, reduce cost of clinical trial. We'd like to sell them into cell biology in a broad sense. Diabetes research, cancer research works the same way.

Q: Chiara. Work in biotech. Really great. Nuclear fusion. 1 cubic centimeter.

A: What i was saying is that I could print it but it wouldn't live. The cells would die.

Q: Just using the profusion through the bioreactor?

A: So, eventually I think we can. But it's about making that branched vasculature first, and then allowing that - flowing through all the branches at once to make the tissue live. Needs to run through capillaries. If it's tissue it's so integrated you can't flow through. Once the cells are bound together, they're impenetrable to the flow. Let's talk more offline.
Q: Justin/Canada. Great stuff. Dozens if not hundreds of hapatocytes? What have you done for anatomy of liver to show different cell types.

A: We know the microarchitecture of the liver. We didn't do that but it's been done. What we rely on is inherent programming in the cells. Our strategy is to use some of the stuff - multipotent stem cells can become all of those different cells, if they're next to the right cell and have the right env't, they will do that. We can print a mixture of endothelial and smooth muscle cells, and we give that flow, they migrate to the lumen.[??] So they know what's going on.
Q: Extreme project by Stelart. Tissue engineered an ear, implanted into his arm. Wire it up so it functions and has hearing. Given extraordinary project? Can you imagine this technology way in the future?

A: I'm gonna back up a couple steps. Does anybody know Dogtown and Z-boys?

The guys in the 70s breakthroughs in skateboarding? When I saw that as an engineer, what struck me was the breakthroughs in making skateboards. The grip of the wheels, the ability to flex at the join. Tony Alva was a great skater but he wouldn't have been able to do that without the tech. I don't know the number of things that could be done with this. I fear the number of things that could be done with this - with cosmetic surgery these days, things could go really crazy.

In Belgium they took a cadaver trachea, placed it in the forearm in the patient, taper them off immunosuppressant drugs, and then they were able to implant that in the trachea. There are all sorts of things that people will be able to do. That's the Singularity, I can't see past it!
5:30 [applause]

Daniel: Thank you. New faces, in case anyone needs them.

Another un-ERB approved medical experiment.

Alex and Teguest and Emiliano and Emma Brooke

Aug 1 is cold turkey day.

Peter: Nice job Daniel.
William Haseltine

[ no slides ]
I thought I'd give a more personal story of what it's like to be involved in transforming fields. I created the first dep't of HIV/AIDS. Got the first significant funding for HIV/AIDS, both private and public. I might sound a little unmodest, but I think my work has laid the foundations for not the cure of AIDS but the control of AIDS. What was I thinking about and how did I proceed?
The first time I heard about AIDS it was called Gay-Related Immunodeficiency. I had two labs, one to support cancer therapy, and another which was following my passion, the possiblity that retrovirus caused human cancer. I had two things going on - one was how to treat cancer better (I think we made a big different to head and neck cancer, chance of survival went from 20% to 80% in 15 years. It was basically cooking, just trying different mixes of things) and at the same time I was working on a quest to see if this virus, a retrovirus, was involved in human disease. I built a very specialized lab, that was capable of working on human retroviruses, which did not exist at the time. We were fortunate that people were handing around money in great big chunks. We were one of 2-3 that applied. Before HIV appeared, we had a lab ready to work on it. As soon as retrovirus involved in human cancer - transmissible leukemia - I immediately began to work on it. What was it that made me think there might be a retrovirus for humans? It came from understanding the viruses in real detail, and a deep desire to make a difference in human health. I thought I should learn as much as I can about science. I looked at the natural world - and I saw in large animals retroviruses would go in, disappear, and then years later show up as cancer or immunodeficiency. I thought the way people were looking, in small animals, it was very different. The first virus that appeared and caused human disease was transmitted from mother to child, through milk, and through blood transfusion. A bit familiar if you know AIDS. When I first heard about AIDS I realized it was immunodeficiency.

[...]personal stories and medical interpretation. Bob Gallow, NIH scientist, involved in discovery of HIV/AIDS. Cattle viruses, sheep viruses. We hyptohesized that HIV was the cause of AIDS. The virus was independently discovered in France and US. And because I'd worked on HTLV1, the leukemia virus, I was in a great position to work on HIV/AIDS.Within six months of that work, ideas we had were being tested in humans. it was pheonomenal how fast that went. It was a systematic exploration of how you can use genomic information to inform drug delivery. Also, we were using the same technology to very quickly;...aids tests. They uses a whole mishmash, and we were able to give them very pure antigen. Able to have a very clear test.
In the early days one of the real problems was false positives. 1 in 300. I had friends who tested false positive. It was not a pretty picture. A couple was planning to move to the US, lived in England. She tested positive. She wasn't able to go with him to the US. It turned out to be a false positive, but it did lasting damage to the relationship.
Go back a little bit to what I was thinking about. I was convinced these viruses caused human disease, based on knowledge and intuition but not fact. It was a guess. The moment AIDS arrived I was there. But something else came from a whole different dimension. I was convinced this was the problem to work on. I transferred the leadership of cancel pharmacology to somebody else and turned my whole lab over to HIV. Why? I had read enough about human behavior, mostly in nonscientific literature...
Guns Germs and Steel

Diseases in human History

Plays by Gibson [or ?] ...books about the plague

I knew about these viruses and I could see very clearly that this disease would be the pandemic it would be today. It turns out it was not clear to very many other people. I integrated information about human behavior, literature, the arts, with science.
All the work I've done has never been directed by science itself. Colleagues, brilliant people, Nobel winners, were driven by science itself. Science presents questions, and you can go from there. I never took my direction from that source. I always took it from human health need. That's why I put myself in a hospital, not a university. That's what I was thinking, and when I looked at this virus, there was one other key piece of data. This virus is different from almost all other viruses. Why? This virus goes into your body, and has evolved to be able to live with every sort of immune assault. Any other kind of virus, the immune system goes in, it clears the virus, and you're either done or dead. That's why vaccines work. It's not a shield that prevents infection. You get infected but your immune system can shut it down. It's not a shield, it's a rapid response.
We made a couple measurements of AIDS patients. We'd never seen an immune reactions. People dying had off-the-charts responses to this virus. Both arms of the immune system - antibody and cell-mediated immunity. This virus was evading it. The 2nd Int'l AIDS conference in France, at the end I said, if you think you're going to find a vaccine using any tech we know today, you are wrong. I was literally booed off the stage. First time, last time. The whole community wanted to do what they did for polio. But it was a very simple observation. You just can't do better than what the body was doing, but the virus was evading it.
Once I had those facts - one very startling fact: you would think that if I told you your sex partner had a disease that if you had sex without protection you would die, you would use protection right? What do you think the fraction is? I worked with the Army - they personally counseled couples. \"The person you're having sex with has a lethal disease, you'll get it if you have sex, we can't treat it.\" The answer was 30% used protection. It turns out that in medicine the answer is always 30% of people do what you say they should do. And we saw all those other 70% got infected. You may be interested in a detail - whether anal sex is more of a vector than vaginal sex. No, it's about the same.


Putting all those facts together, I projected that by 2010 there would be 50 million people infected in the world. The answer turned out to be 35 million are thought to be infected now and 2.5 million are thought to be dead. How unpopular that projection was! There was a book sponsored by CDC called \"The Myth of Heterosexual AIDS\" basically designed to knock me and others out as experts. I was one of the only people who would speak publicly about this. Once, on Good Morning America, Jane Pauley was sitting there, and they like to surprise you with a different guest. This was a mother who had just taken her 5-year-old kid out of school. So I said to the mother, \"you have other kids?\" \"Yeah I have a 15-year old, 7-year-old.\" \"You should be worried about the 15-year-old who's going to have sex.\" But they didn't like that. The CDC and the HHS were controlled by the Mormons, and they just didn't like the idea that HIV was going to be a heterosexual problem.
[?} did a retrospective. There was only one story we really got wrong. The story of whether it would be a big problem. How did we make that mistake? \"We interviewed 20 scientists. 19 of them said it wouldn't be a problem. 1 of them said it would be a problem. We went with the majority opinion. Dr Hazeltine got it right.\" I wrote them back and said this is a lesson for all young scientists. Scientific truth is not determined by public opinion. Truth is not determined by the majority. If you think it's right, stick to it. If you have good reasons and a firm belief, you might be right. You make a big difference not only by your work [ but by your convictions ]
How do you build an institution? I went around to med school deans and said \"this is going to be a big problem.\" One said yes, most said no. Even the other nobel winning retrovirologists. They would say \"They're good for oncogenes, but they're never going to be an interesting subject.\" Joshua Lederberg said \"you're right. I'm not going to do anything about it, but if the population of New York knew anything they'd come down from Harlem and kill us all.\"
If you want to get science to move one way or another, you have to channel money there. Well, I knew all about how you mobilize money. I was on the boards of many groups - ACS, I'd been on study sections at NIH. What I realized is what we needed was an institution which is very much like the National Cancer Institute. We needed private foundations, high-profile spokespeople, a lot of gov't money...At the time two groups had started private foundations. One around Elizabeth Taylor, one around [?], they got together. I told them our mission should be to put together a special fund that would give people money to start new funds. We gave grants to almost any reputable scientist who said \"i want to have a post doc work on x y or z with respect to AIDS.\" Step 2 was money from the federal gov't. Many people here are probably NGO-oriented. That's a mistake.
Gov't can get things done in a huge way that private orgs can't. To institutionalize you want to change government policy. To give you two examples, the economic miracles in India and China were not caused by NGOs, they were caused by systematic change in gov't policy. Deng Xiaoping 30 years ago in China, and 20 years ago in India. Way more effective than all the NGOs combined.
So what we did with the program was to try to convince the gov't to spend more money. And there I was very fortunate. [Worked with the National Cancer Foundation.] Their whole philosophy was to use their small budget to write legislation. Created Kidney Institute, Cancer Institute, ... back in the days when you could pay Congressmen to do what you wanted. And that's what they did. We got their lobbyists, Elizabeth Taylor and I went to Congress, there needed to be a catalyst, I was on vacation and I read that Rock Hudson had gotten AIDS, and he was being treated in France with a drug that didn't work and someone chartered a 747 to fly him back. it made a big splash. So I immediately went to DC, worked with lobbysists, and in 6 weeks increased the budget from 1 mln to $320 mln for AIDS research.
Once you have that, $260mln of that came from health and $60mln came from military. The consequence was the breast cancer lobby got another $120mln from the military for their research. HIV/AIDS was seen as a male problem. All of a sudden it became worth working on - literally. The same people who pu-pued retroviruses became the major spokesmen of why HIV was important. Money is important, makes a big difference.
Today's budget is in excess of 2bln a year. The net result of that - the whole sort of public thing - I did the same with Princess Diana - holding an HIV baby - and also, by going to visit an HIV hospital - that made a global impression - worked with Valentino in Italy to do the same sort of thing. To serve as examples that HIV was something you could talk about and work with.
Back in the lab, we reduced every piece of the AIDS virus to a form that was easy for a drug company to assay. All the proteins. In the early days, the drug companies - the typical response would be, that's an interesting problem, but I don't have any budget.
The way we addressed that was also something I learned from cancer. We created these projects -triple size grants went to a uni prof if they had a pharma partner that they would give 2/3 of money to. I and other scientists would say \"we'll give you money if you start working on this problem.\" That is how almost all the drug companies got involved. The net result today is that there are probably more drugs for HIV than any other single disease - at least 50. And in combination, they can suppress the virus. It was extremely interesting science.
We had to invent a new vocabulary to describe it. It was exciting in terms of public heatlh, too. A few people made a really big difference. I have to say, we were really helped by the gay community. At first they were really hostile. It didn't happen to me, but people had blood poured on was a tough environment. In one sense it was funny, but if you have blood poured on you, it's not funny.
There were a lot of interesting stories, but from my point of view, it filled what I'd wanted to do in my career, which was to use science to make a difference to human health. I'm very pleased with the way it's worked out. We don't have a cure or a vaccine, and I think we are still decades away, but there is finally a glimmer of hope on how to control the infection. There is a program in Botswana, just now being put together. 7% of adults in Baltimore, Washington and Florida are positive - same pop as in West Africa[?]. If they're positive, treat them immediately. The virus load drops, and people become much less infectios. Combination of male circumcisicon which drops rates by 90% from men to women, combined with [?] has a real chance. That's how syphilis was controlled. Any guess on syphilis prevalance in 1910? 20% of adults in many parts of america had syphilis. It was controlled by test and treat. It's more difficult for HIV because it's a chronic treatment.
Probably most of you not fans of George W Bush. But probably going to save more lives than anyone else. How much has the US committed to spend to control AIDS in Africa? 60 billion dollars. And you go to many places in Africa, but there are probably about 3 million people being treated every day thanks to George W Bush. And it was his personal decision to do it, and he didn't want to take credit either, he just did it. Human beings are complex. He's probably the last person you would have thought to do that, but he did it. May have been Christian duty, who knows, but the fact is he did it.
In this particular region of Botswana, the political aspiration...the village leaders, the area leaders have all agreed that it's good to do. You can't make people test - not compulsory - but 30% are infected.
Emem: My own opinion is that it's discrimination *not* to test. If you go in to say there's a pain, the first thing they ask is \"when was your last menstrual period?\" The UN has written it down that it's a violation of human rights to ask for a test of HIV.
HIV was an exception in many ways. There were a lot of exceptions. It's fair to argue the ethics of some of those, but in many areas now there are certainly models for how you can effectively treat HIV. If there is a way to damp down the infection, we have learned from Africa what to do in Baltimore, Washington, and Miami. it's really informed the programs for those areas. There is a chance that disease can get controlled.
Next phase of my career. Probably most of you are here because you're restless. You have done one thing and you want to do something else. You're not career track types.
(gap - explained how he moved from HIV/Aids to the human genome)
What is the difference between a liver and a brain?

What are all these parts?

Use recombinant DNA techniques to revolutionize treatment.

Used to be find what was systematically wrong.




Now we are overwhelmed

Gene to function rather than function to gene, people thought we were nuts.
Blank pieces in HIV. Knew we could do it. Crank gene through standard procedure and figure out what it did.

Where is it

What does it make

Whole series of things we could do.

Convinced once we had a freezer full of genes.

Craig Venter - difficult person to deal with.

Very creative, really energetic. But we got a hell of a lot done.

There was a VC willing to back this.

You cannot believe everything they say.

This guy was to make money and have a good time.

We promised Venter $75 m.

This VC could only commit $15 m disposable to split between two organizations. I thought this was a tremendous idea.

On sabbatical.

Why should I do this?

My job was to go out and raise the rest of the money. At least $150 m.

Wally Sandrig[?] - whole thing as big picture to one guy.

Head of Sandoz.

Can't sell it one piece at a time. I'm not going to buy it, but that's what I'm going to do.

I will do it, pay $80 m, if I get to be CEO.

Somebody else got the job.

Post at SmithKline.

Brought $120 m.

Sold later - raised $300 m and split that.

So what did we do. Within year and half we had isolated all the messenger RNAs. 90% of what human has. Kept machines cranking.

We knew where they were.

As I envisioned, \"give us 5 cancer cells for X Y ans Z and there they were.\"

We were the villans.

First, it was private. And everybody here is open source.

We were raising money and couldn't be public.

Hand over on proprietary basis to SmithKline.

You could file patent.

Ground then shifted.

Needed to put data out if you wanted money.

Caused schizm

We paid off Venter - he then started work on total human genome.

Any time you have gov't and universities involved, everyone worries about money.

We had found humn genes for a fraction.

Who would pay to get all the junk in between.

When people get worried about 3 million dollars, they get nasty.

First, you create a new tool.

This time, we had opposition, so we had to do it a different way -- opposition in your mind.

We had to find drugs.

Two quick hits: Clone by Phone

?? at Johns Hopkins - inheritable cancer.

He'd narrowed it down to an enzyme. Do you have any in this class?

We consulted Oracle and we had 5.

Within a month we solved a problem people had been working on for many, many years.
Second story. Lipitor beater.

You can have low lipids and still get heart disease.

SKB - lpPLA2 - isolated protein, but could never get gene.

Could never go from protein to gene.

Within minutes of turning on our database, they had the gene.

We were able to bridge that gap. And we did it, and did it.

People are still writing about the failure of genomics.

If you are a young scientist today - you do it the way everybody said was nuts.

If you are raising money- raise as much as you can as fast as you can.

Dot com bubble - in one year I raised $2 bn.

We needed every nickel of it.

It took 16 years to get drug.

We want every option we can get.

Stock fell to 50 cents, from high of $100.

Announced drug for lupus - 50 cents to $30.

Hold on to your options.

\"Subducted options\" - one continent slipped under another.

Worked out because it was a good idea and we got people to back it.

Took advantage of fluctuations to raise lots of money.
Big problems. New venture.

Make discovery more efficient.
Let me say a couple of other things.

What is the dogma? Genomics is not necessarily genetics.

You'll hear about human variation.

Those who are in the field know that has been a spectacular failure.

Almost every gene you find contributes 1-2%.
Answer is 7%. 20 genes. Evolution has worked in such a way that any pool gives you a predisposition.

Even with MULTIPLE genes, it isn't working very well.
You heard a talk on diagnostics. Genetics diagnostics?

Did not use the word INHERITANCE.

I'm going to tell the difference between this tissue and that tissue.
There will be some examples where the inheritance determines the treatment.

Measure what the tissue is actually doing.

If 90% of breast cancer is not inherited, what is it?

I have a friend, daughter diagnosed. Right away, get fresh tissue and grow it.

Find out what protiens are there.

Look at microRNAs. Again expression.

Sequence to find how DNA is ALTERED.

That isn't inheritance.
30-40% heritability. In Science.

Breast cancer.

Marko: 2 studies.
All breast cancer, about 7%.

There are genes you can get 30%.
You do not know how the story will end.

When you do a real experiment you don't know what the outcome will be.

You try something. You do your best.

Doing something new now - health care services.

How do we get all these wonderful medicines to people.

Many people go without care.

Study systems that are applying affordable, in the context where they are, health care.

We are collecting best examples.

This idea - may or may not work - get enough good examples and scale them up. Get people to copy them. Models we have found.

Make best in India become the biggest.

Give very high quality health for about 20% of the cost for what we are doing now.

Mostly management. Number 2, technology.

Together we will be able to transform health services in all countries.

India is place for these experiments.
I am chairman of the board. Claudia.



international community - health care systems and delivery.

Number of names for it.
6:39 [applause]
Q: Justin/Canada: presence of biotech cos?

No one to pay doctors.

No financial structure.

On board of one world health [ref]

Off patent drug for lechmaniasis?? - no functioning system to get it to the people.

You've got to build a functioning health care system.

We, together with the Global Fund and others,

if you are a person at the end of the last road - you can be tested for AIDS.

Everyone who has a problem can be put into this network in Botswana.

Pockets like that all over Africa.

Expand for tuber

Fundmental programs - other than education - network of health care providers - from clinic to hospital.

Hold workshops try to find best examples.
Daniel: New tech. How quickly developed. Still takes 1, 2, 3 process with FDS?

You have someone here from the Pink army. That is an interesting way. Internet

Bean Foundation - patients ready and in place.

Internet will allow self-organize patient groups.

Lot of complicated issues. Coordinate pharma and government.

Internet will appreciably speed that up.

Big pharma is failing. Efficiency is dropping by 10x to 15x.

Catastrophic productivity decrease.

Has to be better way.

Were some ways to address that. We had a couple billion. CEO chickened out.

Now we can't pull the money together.

How to restructure the R&D process in the pharma industry.

6:46 [applause]

Daniel: Dinner now.

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=============== POST-presentation notes
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Tonight's pad:


Cost might be high due to level of purity we don't normally use.

How do you get 100% pure without high failure rate?
Points: more money needs to go to nanotech research.

3rd revolution - but when
Cost of this technology (in general) is high without nanotech.

In past century, we paid high environmental cost. Stopped PCB and dioxins. We learned it had a high price.

Related question: what is environmental cost of having to generate materials with ultra-high purity. 99.999% pure - hard to do.
If technologies already exist, why not in use?

Who will pay for this?


Being able to see individual molecules is important.

Being able to manipulate structures.
Important capability. Ability to monitor will be important.

Scanning microscope can be used to feel around.

Intersting idea - create holographic images.

IBM Almaden - high resolution molecular resonance imaging (MRI) - single atom level.

They've made remarkable progress.

Within several years, you should be able to \"see\" whole structure.

If techniques turn to be correct, we will be able to make remarkable progress.



Disruptive potential. Transform things. More than 100x stronger than steel.
A lot of capabilities that are nascent.

Large, complex structures: biology can do this now. We have a lot of biological capabilities advancing rapidly. Genome leads to designer bacteria. Lot of capabilities in non-biological world.

Need a bunch of capabilities together - in about 20 years. With a lot of hand waving.

Some time in the next few decades - depending on investment.



Large scale mfg.

Manufacturing food.
Basically provide low cost food production.
Chiara: most striking things for us.
Food production could be critical area. Portions of planet hungry / starving.

Material wants go away.

Concept that we will have material abundance - difficult to hear.

Pretty much for everyone on the planet. Including abundant supply.



Interested in food issue.

Solve distribution problem. How healthy?

All food modified with nanotech.
Basic question - synthetic food good for you all your life? Will be a lot of study on that.

You can cheat. Just provide good growing conditions for standard life - tomatos. If you have a properly controlled environment - humidity, sunlight, high CO2. Can provide at low cost.

Reduce acreage by an order of magnitude or more.

If food substance itself is out of bounds, you can still use nanotech.

Stick with natural stuff.
Salim: How many of you have conerns with GM foods?

First point: many modifications already. Dog breeding.

Strains or rice.

In our environment, millions of bacteria trying to kill you all the time.

Chance you will be hurt by something man made is low.



Already mentioned ideas.


Scale up, getting into market. Various applications


Downstream, not talked about, but once you incorporate nanomaterials, what will happen in the environment. Will we be able to control them. That whole ball of wax.
Implications of nanofactories. Workshop planned to discuss downside.

We want to arrange matters.

Unpleasant. Done pretty good job of getting benefits while avoiding downside.

Analogy. Fire is an advanced technology. Very dangerous. How do you deal with it.

Fire departments

Fire extinguishers.




Industrial processes.

We would not give it up, but have safeguards.


Cost of assembly.

How do you get atoms to bond correctly.
Temperature is not going to be a problem. You look at thermal noise.

Concerned about side reactions - undesired.

Simplest thing is to lower temperature.

Would need liquid nitrogen environment.

If you work harder, could find more tolerant systems.

Figure out what side reactions would be.

Room temp operation will be standard.
Another thing, not brought up. Very energy intensive processes. Many very wasteful of energy. As time goes by, there will be less energy intensive versions.

These things will not be that expensive.

If biology can do it, we ought be able to do something similar.

Probably a lot lower.


Implication - engineering one. Build things in an optimal way.

Will that be a natural progression of tools to build tools to build tools to build tools.

Will we continue in an optimal cost way?
Will have general purpose tools building more special purpose tools.

General tools will be atomically precise systems.

Mfg process itself will have assembly lines.

Short answer- most mfg systems will shift over.

Essentially a complete elimination - some will still use traditional techniques.

Molecular techniques may not be best - for example, ham and eggs.

May be simplest.

Probably bulk processes will continue to be used.

Computers will be all nano.



Walking army of nano bots.

Things in synthetic cells, cross over to true synthetic - cell looks more and more like molecular manufacture.
I don't know. Basically using biological mechanisms.

Barely to point where we can put in a synthetic genome. Will have extensive redesign of bacteria. Creative leaps. New avenues will open up. Can't see what will happen when money is applied here.

Dry ...

A lot of pressure to use designer bugs to build things.

Whether pressure will bridge gap, then we'll see very interesting designer bugs.

Otherwise, bugs will be over here. Nano independent developments. Perhaps a different track.

Bio systems will top out in performance.
Salim: 5 minute break. Survey - vote for break.



Second discussion.
Davidad: What are orbitals?

As electron numbers go up, structure becomes more interesting.

You can use those as you want as you are generating the electronic structure, superposition of multiple orbitals. Seems to work well for a variety of systems and approximate structurs.
Salim: Who has a good question.
: Diagram, as energy goes up. What about part of graph where it goes to infinity?

Two protons - fewer electrons between. End up with two positively charged protons looking at each other. Push them together. They get less and less happy.
Carlos: Learned attractive and repulsive. What about affinity and replicators?

So, what is relation between forces and replicators?

Classic von Neuman replicator has a tape. Uses that to execute a series of instrutions.

A biological device - DNA is monomere. Uses 4 bases. Held together by forces I was describing into polymere. That holds information of what is to be built.

Manufacturing device is also held together by forces.
Q: 5 principles. How much does that actually reflect reality. 99%

Yes. We cheat. If you have set of principles which describes some chunk, then confine self to that part of reality well described by the model I have. Design within the constraint of the model. Components will not be well described, but I will avoid those in my design.
One approach, have design rules - flexible enough to cover a lot of territory, but not too hard to wrap your head around.
Misses excited states.

Doesn't deal with computers. Which may use excited states.

We are not dealing with computations, we are manufacturing.

We can BUILD a computer.

Various aspects. We are ignoring a lot of stuff.

Deliberately chosen subset of a much larger domain.
Salim: How could you use nanotechnology to impact 1 bn people?



11:29 Third discussion.
More efficient batteries.


Make food.

Recycle everything.
Applies to all 5 projects.
Develop nanopumps.

Dmitry: with these structures, very sturdy - how to recycle? Problem?

What about processing composite materials?

Will we have a problem?
I would not anticipate any fundamental problems. If you want to take things apart.

Space is excellent idea.


Space Elevator

Upcycling - break down

Water - purification

Energy = more efficient solar panels

Food - synthetic
Yes. Excellent ideas.


Decrease dependence on imported oil

Upcycling - use elemental Carbon to build whatever hydrocarbon you want.
Obvious choice would be CO2 in air. Solar energy. Use to recombine Carbon into diamond or whatever you want. CO2 in atmosphere would drop.

: Create robotic super-antibodies. Maintenance workers. So we'd all be lot healthier.

Question - we build in macro way, not tearing down at molecular level. Would it take a lot more energy?
Answer depends. Breaking something - say diamond to something with carbon/oxygen bond. Should PRODUCE energy. CO2 + residue + energy output.

Others may require energy input. Depends on efficency.

We should be able to have thermodynamcally reversible processing.


Water idea. Collect dew on roof tops.

Water - never ending well.
Sounds good to me.

Removing water fromthe atmosphere - very possible.

Make deserts bloom. Be cautious. If you move a lot of water, you may shift weather patterns.

Obvious solution would be to pump water into the atmosphere. Rathe than building a caanal. Let the atmosphere carry water.
Salim: 2 minutes left. Developments 15-20 years out. What is next? (soon)

Getting nano factories working. Will take awhile.

Lot of interest in nano in broader sense.

Lot leading up to capabilites we are talking about.

Research on small structures.

Seeing people talking about drug delivery.

Seeing other developments.
Thank you Ralph.


5 minute break





David Bolinsky Video Presentation

\"David Bolinsky\" \>,

1:45pm \u2013 2:30pm
2:30 -- 5:30 pm
Medical Informatics

Chris Longhurst


Integrative Medicine

Rachel Schneyer


2:14 Buzz Aldrin

Massive changes in short period of time.

Compliment you on your great optimism.

Things in my business slowed down.

Came along at the right time, took advantage.

If not the way they needed to be, we changed them.

Share a variety of different outlooks from many different backgrounds

to make things better.

Recognized as seond leut in war. About your age. Began volunteering.

Quest for big picture. How could I make it a bit better.

Has stood me in pretty good stead.

Look at problems, approaches that might address something I knew something about.

That others weren't that familiar.

Kind of a twist to how you do that.

As a fighter piliot - you eliminate the variables as you can.

Eliminate the problems, then do something you can do something about.

Make corrections.

Typical guidance.

Open my mind to think here we've got different ways for going from one place to another.

Something that went from here to there.

Going to the moon.

There and back.

Operationally useful.

Whatever is doing that is a new entity.

Not that long.

Why not look at Mars. Not that complex.

Way to get to Mars and keep doing that again and again.

Orbital gymnastics. Maybe this might work.

Problem of Not Invented Here. Selling an idea that wasn't invented by someone else.


Decided to go to moon. Really big rocket or two Saturn V.

Send two.

The other one, once it gets there, does something else.

Every mission comes back with something that gets landing in the ocean.

Why not have a specialized interplanetary spacecraft.

Why not have it dock with an up and back system.

Orion will be interplanetary craft.

Comes back and aero-captures at the Earth.

After 30 years of landing on a runway, I don't think that was a mistake.

What is cheapest? Land in the ocean. Will we go back to that?

No, land on a runway.

Develop a spacecraft to do that, then sell it to other countries.

These feed into the unified space vision.

What does it unify?


Strategy / Security.

Make an overall policy.

Introduce ideas which have just kind of come along to me in the experience realm.

You are trying to do that in a very short period of time. Share with one another in a common task.

Probably going to be one of the opportunities in your life.

Wasn't I lucky to be part of that.

I really wish you well.


Back to work.
Daniel: So, that's a tough act to follow.

I've had a picture on my wall since I was 5.

He was on Apollo 11. Second man to walk on the moon.

Formulas for orbital mechanics.

An architect of that program.

Visioneering. 2-1/2 hours. 8 person panel of extraordinary folks.

40 min with David Bolinsky.


David: Thanks Daniel.

Best tool of bandwidth aggregation - your eyes.

More information than your eyes.

Much more than you could read in a lifetime.

Mass of information in medicine, technologies increasing exponentially.

Students will be just completely stoppered up.

Need to establish a \"California closet\"

How do you establish a visual vocabulary.

A commonly agreed on thing.

So ideas I am trying to get to you are not something really different.
Approached by Rick Sataba. Extraordinary futurist.

Head of MASH units.


Concerned that military was planning to cut non-spearpoint staff, including medics.

Meant greater peril.

Wanted to initiate program where all the technologies using robotics, AI, remote sensing, datastorage, would all be put into environment where soldiers would be followed by intelligent robots, monitor data from soldiers. Autonomously put soldier into robotic uint. Scan the soldier. Automatically do surgical stabilization and tranport. Very expensive.
Problem Rick was having. Years of planning. He had 5 minutes to explain it to Congress.

Big task. So what he asked us to do was to help take 90 seconds of 5 minutes that would show what successful program would look like in an urban combat environment.

[video we saw earlier - viewed through commander's heads up display]

Automatic intubation.

Automatic IV.

Lipstick cameras for remote monitoring.

So Rick was the first PI to get his approach funded.

Lot to be said for storytelling, how you envision the future.

Academically thorough, inject just enough honesty into your piece.

Not promising the world what you can't deliver.

When words fail, this is a great way to get your point across.

How many people \"got it\" with just words?
Interesting things with Health Care reform.

Situation where most physicians and personnel are oversubscribed.

Already hugely put upon. Now mandated to take on additional 50 million patients.

That is not going to work well.

How do we change medical school to quickly educate care givers.

People who understand




and upgrade system as a whole.

Visual interactive, immersive, active,

Change from show-me based to deeply immersed way.

Things they would find out piecemeal in traditional environment.
Inner life of the cell - Harvard.

So much information to know. Needs to be done differently.

Cinematic techniques. Give students a whole new way to learn.

This was not meant to be seen in public. Meant to show only to experimental study group.

SIGGRAPH submission. Electronic theatre. About a year after YouTube.

Seen now about 11 million times.

How we could change medical education.

Molecular and cellular motion and transport

[video we have seen before - piano music, animated colorful molecular or cellular structures. No text, just visuals. DNA generating proteins. Something squeezing between cell walls]

You can go to the biovisions website at Harvard to see the whole piece.

Piece we just finished a couple weeks ago. Kept some of the basic color themes. Made it a bit more ....

[video - violin music this time.]

This is not your father's Krebs cycle.

Because this is below the wavelength of light, we decided to use palette of coral reef.



[Video - ad for transgenic goat outputs]

2:46 [Video - stem cells]

One of the interesting things that comes up from having a visual vocabulary is it gets you into areas you would not expect.

[Video - Ad - Dove beauty bar]


Only way to get public research money and communicate to public health workers and get public to take charge of their own health is to communicate in a sophisticated way. Make them feel they are not being talked down to. Integrate astounding amounts of information. We need to communicate with these people and get a positive feedback loop.

I have other animations, that is a good introduction.

Thank you.


Q: Videos online?

A lot we are not allowed to show.


DARPA piece is only piece in 14 years that we were able to talk about.

Q: Cost?

That was about $90,000/min. Charged to client. Partly because of national broadcast rights.

Typically $35,000/min. Harvard stuff is harder. We use orbital velocity we get out of this stuff to compensate.

Q: Using ?

Different way of doing it. Realtive distance - stereo 3D takes really building a lot more things.

When we do things, we scale it to make is smaller. You eye compensates.

Stereo 3D is coming.

Q: Do you combine raw data?

Protein databank. Take atoms and skin it.

For some scenes up to 300,000 items on screen at once.

We use data when we can.

We are a story driven company.

Q: Great fan. Is there anything you can share as we move on our team projects, power of story telling?

Power of story telling - oldest human endeavor. Oldest \"human\" endeavor. How do you get it into their head. Align your thinking with their thinking. Add to the details. Do what a good committee does - come up with a new hybrid. For all of you who have new things to say, talk to other people. Get perspectives from other disciplines.

You are chimeric.

You are combining professions.

Someone in one alone would never come up with your solutions.

Storytelling is what sticks.
Sasha: Translation issue - maintaining integrity. Tricks to visualize, maintain rigor?
Two different questions. Telling story and making it stick is about giving someone something interesting. Introduce virus into heart and person starts to get sick. This molecule comes in to defeat the virus. This is how it fixes the problem: standard story telling arc.

Something is right, something messes it up, something fixes it.

Slippery slope with regard to facts.

FDA has to see backup research.

Not show questionable things. We try to be really good.

Can show things we can't talk about.

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