It seems quite likely that future historians of science will divide biology into the pre- and post-genomic eras.
In one way, post-genomic biology—biology 2.0, if you like—has finally killed the idea of vitalism, the persistent belief that to explain how living things work, something more is needed than just an understanding of their physics and chemistry. True, no biologist has really believed in vitalism for more than a century. Nevertheless, the promise of genomics, that the parts list of a cell and, by extension, of a living organism, is finite and cataloguable, leaves no room for ghosts in the machine.
Viewed another way, though, biology 2.0 is actually neo-vitalistic. No one thinks that a computer is anything more than the sum of its continually changing physical states, yet those states can be abstracted into concepts and processed by a branch of learning that has come to be known as information science, independently of the shifting pattern of electrical charges inside the computer’s processor.
So it is with the new biology. The chemicals in a cell are the hardware. The information encoded in the DNA is the preloaded software. The interactions between the cellular chemicals are like the constantly changing states of processing and memory chips. Though understanding the genome has proved more complicated than expected, no discovery made so far suggests anything other than that all the information needed to make a cell is squirreled away in the DNA. Yet the whole is somehow greater than the sum of its parts.
Another take on the whole artificial/synthetic life story.
More on artificial or synthetic life: An ‘Edge’ Symposium with Richard Dawkins, PZ Myers, Daniel Dennett and others
ON “CREATION OF A BACTERIAL CELL CONTROLLED BY A CHEMICALLY SYNTHESIZED GENOME” BY VENTER ET AL” [5.20.10]
On May 20th, J. Craig Venter and his team at J.C Venter Institute announced the creation of a cell controlled by a synthetic genome in a paper published in SCIENCE. As science historian George Dyson points out, “from the point of view of technology, a code generated within a digital computer is now self-replicating as the genome of a line of living cells. From the point of view of biology, a code generated by a living organism has been translated into a digital representation for replication, editing, and transmission to other cells.”
This new development is all about operating on a large scale. “Reading the genetic code of a wide range of species,” the paper says, “has increased exponentially from these early studies. Our ability to rapidly digitize genomic information has increased by more than eight orders of magnitude over the past 25 years.” This is a big scaling up in our technological abilities. Physicist Freeman Dyson, commenting on the paper, notes that “the sequencing and synthesizing of DNA give us all the tools we need to create new forms of life.” But it remains to be seen how it will serve in practice.
One question is whether or not a DNA sequence alone is enough to generate a living creature. One way of reading the paper suggests this doesn’t seem to be the case because of the use of old microplasma cells into which the DNA was inserted — that this is not about “creating life” since the new life requires an existing living recipient cell. If this is the case, what is the chance of producing something de novo? The paper might appear to be about a somewhat banal technological feat. The new techniques build on existing capabilities. What else is being added, what is qualitatively new?
While it is correct to say that the individual cell was not created, a new line of cells (dare one say species?) was generated. This is new life that is self-propagating, i.e. “the cells with only the synthetic genome are self replicating and capable of logarithmic growth.”
[*Update: I guess I should say ‘probably one of the most important scientific stories of the century’. I am sure other things might happen, such as an asteriod-mediated extinction-level event, which will probably be more important.]
[**Update # 2: Others are less convinced: ‘IRISH SCIENTISTS have given a cold response to research released by geneticist Craig Venter, describing it as anything from a minor advance to a complete scientific folly.’]
[***Update #3: A nice Financial Times story (reg req): “Venter’s achievement would seem to extinguish the argument that life requires a special force or power to exist,” says Arthur Caplan, bioethics professor at the University of Pennsylvania. “This makes it one of the most important scientific achievements in the history of mankind.”]
[Update #4: story in The Scientist: Read more: 1st cell with synthetic genome: After a 15-year marathon, researchers have created the first cell controlled by a synthetic genome, reported online today at Science. The advance, a landmark in synthetic biology, could someday be used to engineer microbes for environmental or medical applications. “This is a very impressive piece,” said Jim Collins, a bioengineer at Boston University, who was not involved in the study. The research is a “methodological tour de force,” said Collins.]
A synthesized genome has been assembled, modified and implanted into a DNA-free bacterial shell to make a self-replicating Mycoplasma mycoides bacterium1. Here, Nature presents short extracts from eight comment pieces on what this achievement means for biotechnology, evolutionary biology, regulation and philosophy. The full-length comments are available to read here.
Some newspaper coverage:
The Irish Times (‘SCIENTISTS IN California have created a form of artificial life. They built a species of bacteria from scratch, opening the way for the development of made-to-order designer bugs able to produce fuel or valuable medicines.);
The New York Times (‘The genome pioneer J. Craig Venter has taken another step in his quest to create synthetic life, by synthesizing an entire bacterial genome and using it to take over a cell.’ previous NYT coverage).
The Economist (‘Craig Venter and Hamilton Smith, the two American biologists who unravelled the first DNA sequence of a living organism (a bacterium) in 1995, have made a bacterium that has an artificial genome—creating a living creature with no ancestor (see article). Pedants may quibble that only the DNA of the new beast was actually manufactured in a laboratory; the researchers had to use the shell of an existing bug to get that DNA to do its stuff. Nevertheless, a Rubicon has been crossed. It is now possible to conceive of a world in which new bacteria (and eventually, new animals and plants) are designed on a computer and then grown to order.’)
And the press release from the Craig Venter Institute (note the quotes from James Joyce and Richard Feynman):
First Self-Replicating, Synthetic Bacterial Cell Constructed by J. Craig Venter Institute Researchers
ROCKVILLE, MD and San Diego, CA (May 20, 2010)— Researchers at the J. Craig Venter Institute (JCVI), a not-for-profit genomic research organization, published results today describing the successful construction of the first self-replicating, synthetic bacterial cell. The team synthesized the 1.08 million base pair chromosome of a modified Mycoplasma mycoides genome. The synthetic cell is called Mycoplasma mycoides JCVI-syn1.0 and is the proof of principle that genomes can be designed in the computer, chemically made in the laboratory and transplanted into a recipient cell to produce a new self-replicating cell controlled only by the synthetic genome.
This research will be published by Daniel Gibson et al in the May 20th edition of Science Express and will appear in an upcoming print issue of Science.
“For nearly 15 years Ham Smith, Clyde Hutchison and the rest of our team have been working toward this publication today–the successful completion of our work to construct a bacterial cell that is fully controlled by a synthetic genome,” said J. Craig Venter, Ph.D., founder and president, JCVI and senior author on the paper. “We have been consumed by this research, but we have also been equally focused on addressing the societal implications of what we believe will be one of the most powerful technologies and industrial drivers for societal good. We look forward to continued review and dialogue about the important applications of this work to ensure that it is used for the benefit of all.”
According to Dr. Smith, “With this first synthetic bacterial cell and the new tools and technologies we developed to successfully complete this project, we now have the means to dissect the genetic instruction set of a bacterial cell to see and understand how it really works.”
To complete this final stage in the nearly 15 year process to construct and boot up a synthetic cell, JCVI scientists began with the accurate, digitized genome of the bacterium, M. mycoides. The team designed 1,078 specific cassettes of DNA that were 1,080 base pairs long. These cassettes were designed so that the ends of each DNA cassette overlapped each of its neighbors by 80bp. The cassettes were made according to JCVI’s specifications by the DNA synthesis company, Blue Heron Biotechnology.
The JCVI team employed a three stage process using their previously described yeast assembly system to build the genome using the 1,078 cassettes. The first stage involved taking 10 cassettes of DNA at a time to build 110, 10,000 bp segments. In the second stage, these 10,000 bp segments are taken 10 at a time to produce eleven, 100,000 bp segments. In the final step, all 11, 100 kb segments were assembled into the complete synthetic genome in yeast cells and grown as a yeast artificial chromosome.
The complete synthetic M. mycoides genome was isolated from the yeast cell and transplanted into Mycoplasma capricolum recipient cells that have had the genes for its restriction enzyme removed. The synthetic genome DNA was transcribed into messenger RNA, which in turn was translated into new proteins. The M. capricolum genome was either destroyed by M. mycoides restriction enzymes or was lost during cell replication. After two days viable M. mycoides cells, which contained only synthetic DNA, were clearly visible on petri dishes containing bacterial growth medium.
The initial synthesis of the synthetic genome did not result in any viable cells so the JCVI team developed an error correction method to test that each cassette they constructed was biologically functional. They did this by using a combination of 100 kb natural and synthetic segments of DNA to produce semi-synthetic genomes. This approach allowed for the testing of each synthetic segment in combination with 10 natural segments for their capacity to be transplanted and form new cells. Ten out of 11 synthetic fragments resulted in viable cells; therefore the team narrowed the issue down to a single 100 kb cassette. DNA sequencing revealed that a single base pair deletion in an essential gene was responsible for the unsuccessful transplants. Once this one base pair error was corrected, the first viable synthetic cell was produced.
Dr. Gibson stated, “To produce a synthetic cell, our group had to learn how to sequence, synthesize, and transplant genomes. Many hurdles had to be overcome, but we are now able to combine all of these steps to produce synthetic cells in the laboratory.” He added, “We can now begin working on our ultimate objective of synthesizing a minimal cell containing only the genes necessary to sustain life in its simplest form. This will help us better understand how cells work.”
This publication represents the construction of the largest synthetic molecule of a defined structure; the genome is almost double the size of the previous Mycoplasma genitalium synthesis. With this successful proof of principle, the group will now work on creating a minimal genome, which has been a goal since 1995. They will do this by whittling away at the synthetic genome and repeating transplantation experiments until no more genes can be disrupted and the genome is as small as possible. This minimal cell will be a platform for analyzing the function of every essential gene in a cell.
According to Dr. Hutchison, “To me the most remarkable thing about our synthetic cell is that its genome was designed in the computer and brought to life through chemical synthesis, without using any pieces of natural DNA. This involved developing many new and useful methods along the way. We have assembled an amazing group of scientists that have made this possible.”
As in the team’s 2008 publication in which they described the successful synthesis of the M. genitalium genome, they designed and inserted into the genome what they called watermarks. These are specifically designed segments of DNA that use the “alphabet” of genes and proteins that enable the researcher to spell out words and phrases. The watermarks are an essential means to prove that the genome is synthetic and not native, and to identify the laboratory of origin. Encoded in the watermarks is a new DNA code for writing words, sentences and numbers. In addition to the new code there is a web address to send emails to if you can successfully decode the new code, the names of 46 authors and other key contributors and three quotations: “TO LIVE, TO ERR, TO FALL, TO TRIUMPH, TO RECREATE LIFE OUT OF LIFE.” – JAMES JOYCE; “SEE THINGS NOT AS THEY ARE, BUT AS THEY MIGHT BE.”-A quote from the book, “American Prometheus”; “WHAT I CANNOT BUILD, I CANNOT UNDERSTAND.” – RICHARD FEYNMAN.