May 20, 2010 might be a significant date someday.  The J. Craig Venter Institute (JCVI), a not-for-profit genomic research organization team’s paper was published online at Science Express. The paper describes the successful construction of the first self-replicating, synthetic bacterial cell.

The JCVI scientists envision the development of applications and products including biofuels, vaccines, pharmaceuticals, clean water and food products from the knowledge gained by constructing this first self-replicating synthetic cell. Along with decreasing costs for DNA synthesis, the genetic construction science should give rise to wider use of this powerful technology.

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. That’s just three seemingly simple steps.

Elements for Yeast Propagationa & Genomic Transplantation. Click image for more info.

To start, the 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 80 base pairs.

Then the team employed a three-stage process using a previously described yeast (Yeast was chosen because bacteria donor and recipient mycoplasmas share a common restriction system which yeast lacks.) 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 one hundred ten 10,000 base pair segments. In the second stage, these 10,000 base pair segments are taken 10 at a time to produce eleven, 100,000 base pair 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.

To finish, 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.

Of course the process is nowhere near so simple in practice.  The first attempt 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; allowing the team to narrow 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.

With a successful proof of principle in hand, the JCVI group is now working on creating a’ minimal genome’, that would be the smallest simplest genetic code that could live, 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.

Getting the minimal genome is likely more important than synthesizing a living self-replicating genome.

If not for leaking oil wells, wars, elections and other distracting events the JCVI milestone might have gotten more attention.  But the fog might be useful, as the ethical issues are sure to get rolling with a vengeance now that the life lives.

Mr. Venter said, “This is an important step we think, both scientifically and philosophically. It’s certainly changed my views of the definitions of life and how life works.”  Acknowledging the ethical discussion about synthetic biology research, Venter explained that his team asked for a bioethical review in the late 1990s and has participated in variety of discussions on the topic.

“I think this is the first incidence in science where the extensive bioethical review took place before the experiments were done. It’s part of an ongoing process that we’ve been driving, trying to make sure that the science proceeds in an ethical fashion, that we’re being thoughtful about what we do and looking forward to the implications to the future,” he said.

That’s a fine, intellectually forthcoming and forthright position.  But for all enthusiasts out there, keep in mind – the opposition will be based in fear, raw emotions, press spin, sound bites, and the rest of the destructiveness available in the PR toolbox.

As impressed as this writer is, the concern is there as well.  Genetically modified food and seed have been warred upon for years with lives lost and suffering measured in hundreds of millions of human life years with no ill effect ever found.

A new technology has been born, will society let it live and grow?

Update: J. Craig Venter and Daniel Gibson explain how their team created the first synthetic cell.


Comments

8 Comments so far

  1. knowledge is freedom on May 25, 2010 1:56 AM

    The article should have been titled as Synthia & Apollo and their Synthetic Life.

    Synthetic/Synthia/Cynthia

    http://www.urbandictionary.com­/define.php?term=Synthia

    Cynthia or “Synthia” was originally an epithet of the Greek goddess of the moon, Artemis, who was sometimes called “Cynthia” because, according to legend, the goddess was born on Mount Cynthus. Known also as a master of animals. Parallel Greek goddess to Roman goddess Diana. Daughter of Leto and twin sister of Apollo.

    Synthia & Apollyon are one in the same… The hermaphrodite beast of the book of Revelations as seen as Apollyon and the ‘scarlet whore’ named as Hel…

    All you have to do is study the Apollo/Athena, whom is Synthia/Artemis, angle in every story/issue/matter, and you will find the source of the evil. Because the beast named as Apollo/Athena is at the core of EVERY evil ever seen down through ALL the eons and ages… That evil can be seen when the connected names are completed… They touch every evil ever known…

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  3. College Grants on June 2, 2010 5:39 PM

    This is pretty mind blowing technology and with what I read in this post, I left wondering what harm this could bring if any. Its a little to complicated for me to digest in one bite.. but the subject is very interesting and Im sure to learn more about this technology and what it has in store for our future.

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