Craig Venter: From Reading to Writing the Genomic Code

3 institutes, including the first carbon neutral research building at UCSD.

DNA is an analog molecule with a 4-base system.

In 1995 his team sequenced the first genome of a living species. Scaled it up to 3 billion letters of the haploid genome.

Had 300 $350 million machines for breaking down the process.

Just celebrated the 10th anniversary of the human genome.

What was a four-story building can now be reduced to something smaller than a podium. The new machine can do it in a few hours for 1 or 2 thousand dollars.

In 2007 they did the whole genome with 2 sets of chromosomes. Found that we differ from one another 10x more than we previously thought (between 1-3% different).

Teams at the institute are sampling global diversity, traveling the world to find unique genomes.

Much more diversity within Africa than comparing Africans to others outside.

We’re on the verge of being able to figure out whether traits come from mother or your father. Can isolate the genome of a sperm cell.

Compound Mutations

Variations on two sets of chromosomes comes through w much more complex view of what we inherit or how we inherit them.

Venter’s genome is online so he’s now been sent all diseases he’s likely to die of. Pharmaceutical companies are now starting to use genes to create treatments. It’s starting to become important to know what your genomes are.

Pharmaceutical comps were worried they wouldn’t make $$ with this,but they’ve found success financially as they jack up prices.

You have 200 trillion bacteria on your body, known as the microbiome. This includes 10 million unique genes and 10s of thousands of unique species, which affect almost everything.

What’s the metabolic potential of these genes?

Metabolomics: using mass spectrology to measure all the chemicals in your bloodstream. There are about 500 unique chemicals circulating in your bloodstream. Only about 50% are human. 30% are from outside contaminants.

In the middle fo figuring out what all these hjman chemicals do. This information is already being used by Nestle, General Foods, etc to design new foods for specific medical issues like diabetes.

We need at least 10,000 microbiomes, human genomes, etc to start figuring out what’s nature and what’s nurture. So far there’s not enough info to figure it out: Need large data sets and stats.

It’s also easy now to make stem cells. Venter’s cells have been reproduced in La Jolla.

Cell to cell relationship is far more important than we imagined. When you take cells out of the body, methalation is lost, massive mutations build up in genome. Stem cell therapy didn’t take this into account and is sounding less promising.

What is there with cell to cell contact that keeps genome under human regulation? Big challenge for genomics.

Also trying to use synthetic DNA approaches to reprogram stem cells to eliminate DNA errors. Doing it in vitro is an entirely different thing and very often successful.

Sometime in the future we will be able to make synthetic stem cells and use them for whatever we want.

In the air, they’ve been able to suck particles out. There was a massive amount of iron in the air in NY. Done sampling in SD indoors and outdoors.

Indoor NY: Mostly human DNA (slough cells at massive rate), surprising amount of rodent DNA, other animals, plants

Outdoor NY (at 22nd floor): Almost half is rodent DNA. Mostly mouse DNA. Outdoor was mostly rat.

Outdoor SD: Mostly microbes blowing off land, sea

Hospitals: loaded with virulent micro-organisms.

Also have all HEPA filters from intl space station: Gets pretty ripe up there pretty quickly. Filters are like a zoo of life.

Talking about designing unique microbiome to administer to people that will enhance their life and metabolism when they’re in space.

What is minimal life?

Mycoplasma genitalium is the smallest known.

How many genes are essential for life?

What’s the smallest number needed to run cell machinery?

Can we design and construct a minimal M. gneitalium cell?

• Would chemistry permit synthesizing of entire chromosomes?
• If we make a synthetic chromosome can we boot it up?

Two teams:

• Finding ways to correct all errors in DNA
• Decided to remake FiX genome
• Built a virus. This software builds its own hardware
• Knew they could build viruses and compile them to make an entire genome
• Used brewers yeast as homologous recombination system to assemble overlapping pieces in vivo
• Put 4 synthetic polar molecules into yeast to make their own synthetic chromosome, which was reported in 2008

Dan Gibson came up with a simpler method to create isothermal in citro recombination. “I don’t know what took you old guys so long.”

• Allows process to be automated
• Goal is to build self-learning robot to take all gene iterations and do combinatorial genomics.
• Make things: If it lives, great, if not, find genomic patterns.
• Can now make large pieces of DNA accurately.

How do you boot up a chromosome?

• Developed new tools to move them around.
• In 2007, swapped out software in a cell and completely converted one species to another. They changed ONLY the DNA software

Two species, roughly difference of us from mice. Inserted one set of DNA into existing DNA. Within fractions of a second, that gene starts to be read and proteins created. Those proteins/ chromosomes recognized a foreign chromosome and chewed it up.

Eventually, all cells of the former species were eliminated.

The lesson: You change the software, you change the species. 

Needed to figure out how to get DNA out of yeast.

• Add yeast centamere to eukaryotic chromosome. Didn’t work.
• 2 1/2 years later, they found that original bacterial cells had methalated the DNA

Scaled it up to make twice as large genome, but it didn’t work. Created biological debugging software to find single letter out of 1.1 million that had been deleted.

Then the cells worked.

Devised a new way to watermark DNA, put codes into genes, including quotes from Feynman, James Joyce.

Why do this? 

Science has a critical role in society. Because of population growth, we are 100% dependent on science for our future.

• Fuel=water=food
• Each person needs 5,000 liters in US
• 10 billion tons of animal feed
• 10 kg of feed produces 1 kg of beef
• U.S. uses 70% of fresh water for agriculture

Disruptive change is needed and synthetic life will be part of the solution

Ability to write genetic code gives them control over nature.

Designing new microbial fuel cells to turn waste into water and desalinize salty water

This is design genomics: All genes are design components of the future. Trying to design new species using CO2, sunlight that do what they want to. Designing new food types, new fuels. 

First genomic vaccine is coming on market just now in Europe to fight Hep B, flu and others.

Are able to create new vaccines for test viruses in under 10 hours, which they send to Novartis.

Designing new proteins that are most nutritious possible. Can change amino acid contents to adjust your body goals (more muscle?).

Wants to eliminate cows and chickens as source of food. Can now manufacture cows and chickens at much faster rate and much more efficiently than in the pasture.

Creating fish oil out of algae (Where do you think the fish got it from?)

Most farmed salmon is fed corn equivalent rather than algae, so you’re not really getting nutritional value of eggs.

Have 81 acre facility to scale up algae technologies.

Ethical Aspects of Creating New Life Forms

• Government, Sloan Foundation, Penn State have done governance studies.
• Heard from Pope and President in same day that they made their own genome. Vatican said they’d just changed one of the engines of life but that they could be good if done correctly. Privately, they told him they have no problem with what they’re doing as long as they don’t do it to people.
• There is a lot of potential to do harm with this technology if used wrong, but there’s also the potential to be one of the biggest planetary wealth generators.

Integration in his work

• Venter’s small institute has had good success due to his integration of all disciplines: physicists, ethicists, biologists, mathematicians, etc, etc.
• Had no trouble recruiting best scientists in the world to work on this. Most people want to work on things bigger than themselves with highly integrated teams.
• Setting big targets allows people to pull together and focus on.

Ty Carlson: When we talk of releasing ability to create new worlds, it’s extremely powerful and dangerous. How do we protect this?

Craig Venter: Not much has been done to protect it so far. It is a serious issue, but there are so many other really efficient ways to kill people. The folks really focused on doing harm seem to want to make a bang when they’re doing it. Much bigger risk is new emerging infections.

Doesn’t want to eliminate everything (tomatoes should be kept around) but bulk crops like corn, etc can be created 2x or more more efficiently.

Can take proteins making food, algae items, particles,

Peter Byck: How do you stop hackers from printing out all of your work in random places?

CV: We’re able to make vaccinations quickly, we can’t keep bad people from getting ahold of these things, but I’m not sure why others would want to do that.

Mark Anderson: It’s society’s responsibility to learn how to deal with these things, not scientists.