Tag Archives: Craig Venter

Biological Transporter

Molecular-biology entrepreneur and genomics engineering pioneer, Craig Venter, is at it again. In his new book, Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life, Venter explains his grand ideas and the coming era of discovery.

From ars technica:

J Craig Venter has been a molecular-biology pioneer for two decades. After developing expressed sequence tags in the 90s, he led the private effort to map the human genome, publishing the results in 2001. In 2010, the J Craig Venter Institute manufactured the entire genome of a bacterium, creating the first synthetic organism.

Now Venter, author of Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life, explains the coming era of discovery.

Wired: In Life at the Speed of Light, you argue that humankind is entering a new phase of evolution. How so?

J Craig Venter: As the industrial age is drawing to a close, I think that we’re witnessing the dawn of the era of biological design. DNA, as digitized information, is accumulating in computer databases. Thanks to genetic engineering, and now the field of synthetic biology, we can manipulate DNA to an unprecedented extent, just as we can edit software in a computer. We can also transmit it as an electromagnetic wave at or near the speed of light and, via a “biological teleporter,” use it to recreate proteins, viruses, and living cells at another location, changing forever how we view life.

So you view DNA as the software of life?

All the information needed to make a living, self-replicating cell is locked up within the spirals of DNA’s double helix. As we read and interpret that software of life, we should be able to completely understand how cells work, then change and improve them by writing new cellular software.

The software defines the manufacture of proteins that can be viewed as its hardware, the robots and chemical machines that run a cell. The software is vital because the cell’s hardware wears out. Cells will die in minutes to days if they lack their genetic-information system. They will not evolve, they will not replicate, and they will not live.

Of all the experiments you have done over the past two decades involving the reading and manipulation of the software of life, which are the most important?

I do think the synthetic cell is my most important contribution. But if I were to select a single study, paper, or experimental result that has really influenced my understanding of life more than any other, I would choose one that my team published in 2007, in a paper with the title Genome Transplantation in Bacteria: Changing One Species to Another. The research that led to this paper in the journal Science not only shaped my view of the fundamentals of life but also laid the groundwork to create the first synthetic cell. Genome transplantation not only provided a way to carry out a striking transformation, converting one species into another, but would also help prove that DNA is the software of life.

What has happened since your announcement in 2010 that you created a synthetic cell, JCVI-syn1.0?

At the time, I said that the synthetic cell would give us a better understanding of the fundamentals of biology and how life works, help develop techniques and tools for vaccine and pharmaceutical development, enable development of biofuels and biochemicals, and help to create clean water, sources of food, textiles, bioremediation. Three years on that vision is being borne out.

Your book contains a dramatic account of the slog and setbacks that led to the creation of this first synthetic organism. What was your lowest point?

When we started out creating JCVI-syn1.0 in the lab, we had selected M. genitalium because of its extremely small genome. That decision we would come to really regret: in the laboratory, M. genitalium grows slowly. So whereas E. coli divides into daughter cells every 20 minutes, M. genitalium requires 12 hours to make a copy of itself. With logarithmic growth, it’s the difference between having an experimental result in 24 hours versus several weeks. It felt like we were working really hard to get nowhere at all. I changed the target to the M. mycoides genome. It’s twice as large as that of genitalium, but it grows much faster. In the end, that move made all the difference.

Some of your peers were blown away by the synthetic cell; others called it a technical tour de force. But there were also those who were underwhelmed because it was not “life from scratch.”

They haven’t thought much about what they are actually trying to say when they talk about “life from scratch.” How about baking a cake “from scratch”? You could buy one and then ice it at home. Or buy a cake mix, to which you add only eggs, water and oil. Or combining the individual ingredients, such as baking powder, sugar, salt, eggs, milk, shortening and so on. But I doubt that anyone would mean formulating his own baking powder by combining sodium, hydrogen, carbon, and oxygen to produce sodium bicarbonate, or producing homemade corn starch. If we apply the same strictures to creating life “from scratch,” it could mean producing all the necessary molecules, proteins, lipids, organelles, DNA, and so forth from basic chemicals or perhaps even from the fundamental elements carbon, hydrogen, oxygen, nitrogen, phosphate, iron, and so on.

There’s a parallel effort to create virtual life, which you go into in the book. How sophisticated are these models of cells in silico?

In the past year we have really seen how virtual cells can help us understand the real things. This work dates back to 1996 when Masaru Tomita and his students at the Laboratory for Bioinformatics at Keio started investigating the molecular biology of Mycoplasma genitalium—which we had sequenced in 1995—and by the end of that year had established the E-Cell Project. The most recent work on Mycoplasma genitalium has been done in America, by the systems biologist Markus W Covert, at Stanford University. His team used our genome data to create a virtual version of the bacterium that came remarkably close to its real-life counterpart.

You’ve discussed the ethics of synthetic organisms for a long time—where is the ethical argument today?

The Janus-like nature of innovation—its responsible use and so on—was evident at the very birth of human ingenuity, when humankind first discovered how to make fire on demand. (Do I use it burn down a rival’s settlement, or to keep warm?) Every few months, another meeting is held to discuss how powerful technology cuts both ways. It is crucial that we invest in underpinning technologies, science, education, and policy in order to ensure the safe and efficient development of synthetic biology. Opportunities for public debate and discussion on this topic must be sponsored, and the lay public must engage. But it is important not to lose sight of the amazing opportunities that this research presents. Synthetic biology can help address key challenges facing the planet and its population. Research in synthetic biology may lead to new things such as programmed cells that self-assemble at the sites of disease to repair damage.

What worries you more: bioterror or bioerror?

I am probably more concerned about an accidental slip. Synthetic biology increasingly relies on the skills of scientists who have little experience in biology, such as mathematicians and electrical engineers. The democratization of knowledge and the rise of “open-source biology;” the availability of kitchen-sink versions of key laboratory tools, such as the DNA-copying method PCR, make it easier for anyone—including those outside the usual networks of government, commercial, and university laboratories and the culture of responsible training and biosecurity—to play with the software of life.

Following the precautionary principle, should we abandon synthetic biology?

My greatest fear is not the abuse of technology, but that we will not use it at all, and turn our backs to an amazing opportunity at a time when we are over-populating our planet and changing environments forever.

You’re bullish about where this is headed.

I am—and a lot of that comes from seeing the next generation of synthetic biologists. We can get a view of what the future holds from a series of contests that culminate in a yearly event in Cambridge, Massachusetts—the International Genetically Engineered Machine (iGEM) competition. High-school and college students shuffle a standard set of DNA subroutines into something new. It gives me hope for the future.

You’ve been working to convert DNA into a digital signal that can be transmitted to a unit which then rebuilds an organism.

At Synthetic Genomics, Inc [which Venter founded with his long-term collaborator, the Nobel laureate Ham Smith], we can feed digital DNA code into a program that works out how to re-synthesize the sequence in the lab. This automates the process of designing overlapping pieces of DNA base-pairs, called oligonucleotides, adding watermarks, and then feeding them into the synthesizer. The synthesizer makes the oligonucleotides, which are pooled and assembled using what we call our Gibson-assembly robot (named after my talented colleague Dan Gibson). NASA has funded us to carry out experiments at its test site in the Mojave Desert. We will be using the JCVI mobile lab, which is equipped with soil-sampling, DNA-isolation and DNA sequencing equipment, to test the steps for autonomously isolating microbes from soil, sequencing their DNA and then transmitting the information to the cloud with what we call a “digitized-life-sending unit”. The receiving unit, where the transmitted DNA information can be downloaded and reproduced anew, has a number of names at present, including “digital biological converter,” “biological teleporter,” and—the preference of former US Wired editor-in-chief and CEO of 3D Robotics, Chris Anderson—”life replicator”.

Read the entire article here.

Image: J Craig Venter. Courtesy of Wikipedia.

Living Organism as Software

For the first time scientists have built a computer software model of an entire organism from its molecular building blocks. This allows the model to predict previously unobserved cellular biological processes and behaviors. While the organism in question is a simple bacterium, this represents another huge advance in computational biology.

[div class=attrib]From the New York Times:[end-div]

Scientists at Stanford University and the J. Craig Venter Institute have developed the first software simulation of an entire organism, a humble single-cell bacterium that lives in the human genital and respiratory tracts.

The scientists and other experts said the work was a giant step toward developing computerized laboratories that could carry out complete experiments without the need for traditional instruments.

For medical researchers and drug designers, cellular models will be able to supplant experiments during the early stages of screening for new compounds. And for molecular biologists, models that are of sufficient accuracy will yield new understanding of basic biological principles.

The simulation of the complete life cycle of the pathogen, Mycoplasma genitalium, was presented on Friday in the journal Cell. The scientists called it a “first draft” but added that the effort was the first time an entire organism had been modeled in such detail — in this case, all of its 525 genes.

“Where I think our work is different is that we explicitly include all of the genes and every known gene function,” the team’s leader, Markus W. Covert, an assistant professor of bioengineering at Stanford, wrote in an e-mail. “There’s no one else out there who has been able to include more than a handful of functions or more than, say, one-third of the genes.”

The simulation, which runs on a cluster of 128 computers, models the complete life span of the cell at the molecular level, charting the interactions of 28 categories of molecules — including DNA, RNA, proteins and small molecules known as metabolites that are generated by cell processes.

“The model presented by the authors is the first truly integrated effort to simulate the workings of a free-living microbe, and it should be commended for its audacity alone,” wrote the Columbia scientists Peter L. Freddolino and Saeed Tavazoie in a commentary that accompanied the article. “This is a tremendous task, involving the interpretation and integration of a massive amount of data.”

They called the simulation an important advance in the new field of computational biology, which has recently yielded such achievements as the creation of a synthetic life form — an entire bacterial genome created by a team led by the genome pioneer J. Craig Venter. The scientists used it to take over an existing cell.

For their computer simulation, the researchers had the advantage of extensive scientific literature on the bacterium. They were able to use data taken from more than 900 scientific papers to validate the accuracy of their software model.

Still, they said that the model of the simplest biological system was pushing the limits of their computers.

“Right now, running a simulation for a single cell to divide only one time takes around 10 hours and generates half a gigabyte of data,” Dr. Covert wrote. “I find this fact completely fascinating, because I don’t know that anyone has ever asked how much data a living thing truly holds. We often think of the DNA as the storage medium, but clearly there is more to it than that.”

In designing their model, the scientists chose an approach that parallels the design of modern software systems, known as object-oriented programming. Software designers organize their programs in modules, which communicate with one another by passing data and instructions back and forth.

Similarly, the simulated bacterium is a series of modules that mimic the different functions of the cell.

“The major modeling insight we had a few years ago was to break up the functionality of the cell into subgroups which we could model individually, each with its own mathematics, and then to integrate these sub-models together into a whole,” Dr. Covert said. “It turned out to be a very exciting idea.”

[div class=attrib]Read the entire article after the jump.[end-div]

[div class=attrib]Image: A Whole-Cell Computational Model Predicts Phenotype from Genotype. Courtesy of Cell / Elsevier Inc.[end-div]

J. Craig Venter

[div class=attrib]From Discover:[end-div]

J. Craig Venter keeps riding the cusp of each new wave in biology. When researchers started analyzing genes, he launched the Institute for Genomic Research (TIGR), decoding the genome of a bacterium for the first time in 1992. When the government announced its plan to map the human genome, he claimed he would do it first—and then he delivered results in 2001, years ahead of schedule. Armed with a deep understanding of how DNA works, Venter is now moving on to an even more extraordinary project. Starting with the stunning genetic diversity that exists in the wild, he is aiming to build custom-designed organisms that could produce clean energy, help feed the planet, and treat cancer. Venter has already transferred the genome of one species into the cell body of another. This past year he reached a major milestone, using the machinery of yeast to manufacture a genome from scratch. When he combines the steps—perhaps next year—he will have crafted a truly synthetic organism. Senior editor Pamela Weintraub discussed the implications of these efforts with Venter in DISCOVER’s editorial offices.

Here you are talking about constructing life, but you started out in deconstruction: charting the human genome, piece by piece.
Actually, I started out smaller, studying the adrenaline receptor. I was looking at one protein and its single gene for a decade. Then, in the late 1980s, I was drawn to the idea of the whole genome, and I stopped everything and switched my lab over. I had the first automatic DNA sequencer. It was the ultimate in reductionist biology—getting down to the genetic code, interpreting what it meant, including all 6 billion letters of my own genome. Only by understanding things at that level can we turn around and go the other way.

In your latest work you are trying to create “synthetic life.” What is that?
It’s a catchy phrase that people have begun using to replace “molecular biology.” The term has been overused, so we have defined a separate field that we call synthetic genomics—the digitization of biology using only DNA and RNA. You start by sequencing genomes and putting their digital code into a computer. Then you use the computer to take that information and design new life-forms.

How do you build a life-form? Throw in some mito­chondria here and some ribosomes there, surround ?it all with a membrane—?and voilà?
We started down that road, but now we are coming from the other end. We’re starting with the accomplishments of three and a half billion years of evolution by using what we call the software of life: DNA. Our software builds its own hardware. By writing new software, we can come up with totally new species. It would be as if once you put new software in your computer, somehow a whole new machine would materialize. We’re software engineers rather than construction workers.

[div class=attrib]More from theSource here[end-div]