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Man-Made DNA has booted up a cell for the first time

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Postby sandra » Mon May 24, 2010 12:08 am

Man-made DNA has booted up a cell for the first time.

In a feat that is the culmination of two and a half years of tests and adjustments, researchers at the J. Craig Venter Institute inserted artificial genetic material — chemically printed, synthesized and assembled — into cells that were then able to grow naturally.

“We all had a very good feeling that it was going to work this time,” said Venter Institute synthetic biologist Daniel Gibson, co-author of the study published May 20 in Science. “But we were cautiously optimistic because we had so many letdowns following the previous experiments.”

On a Friday in March, scientists inserted over 1 million base pairs of synthetic DNA into Mycoplasma capricolum cells before leaving for the weekend. When they returned on Monday, their cells had bloomed into colonies.


“When we look at life forms, we see fixed entities,” said J. Craig Venter, president of the Institute, in a recent podcast. “But this shows in fact how dynamic they are. They change from second to second. And that life is basically the result of an information process. Our genetic code is our software.”

Coaxing the software to power a cell proved harder than expected.

After the Venter Institute announced in early 2008 that it had assembled a synthetic Mycoplasma genitalium genome, the assumption was that it would be running cells in no time. But this particular cell type, despite its minimal size, was not an ideal research partner. One problem was speed.

“We had to deal with the fact that M. genitalium had an extremely slow growth rate,” Gibson said. “For every experiment that was done, it took more than a month to get results.”

Moreover, transplanting the code into recipient cells was failing. So researchers cut their losses and called in a substitute, opting for the larger, speedier and less finicky Mycoplasma mycoides. The choice was a good one.

“Over the last five years the field has seen a 100-fold increase in the length of genetic material wholly constructed from raw chemicals,” said synthetic biologist Drew Endy of Stanford University. “This is over six doublings in the max length of a genome that can be constructed.”

Plunging costs of synthesis allowed a leap past the 1 million base-pair mark, from code to assembly. “Imagine doubling the diameter of a silicon wafer that can be manufactured that much, going from 1 cm to 1 meter [fabrications] in just five years,” Endy said. “That would have been an incredible achievement.”

“They rebuilt a natural sequence and they put in some poetry,” said University of California at San Francisco synthetic biologist Chris Voigt. “They recreated some quotes in the genome sequence as watermarks.”

It’s an impressive trick, no doubt, but replicating a natural genome with a little panache is also the limit of our present design capabilities.

Researchers, for instance, figure yeast can handle the assembly of 2 million base pairs, but they’re not sure about more. And an energy-producing cyanobacteria that sequesters carbon, Gibson says, is still several years off.

The ultimate goal, of course, is a brand-new genome from the ground up. Now, Voigt said, “what do you do with all that design capacity?”



Read More http://www.wired.com/wiredscience/2010/ ... z0opj1uGNy
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Postby Aquatank » Mon May 24, 2010 8:44 am

I'm still not sure if this is a good thing or bad thing. I am of the opinion that the RCC is throwing bricks in glass houses by preaching morality about it at the moment though.

The bad point is possible unstoppable hazardous organisms in the future. Possibly controlled by a multinational company with patents on everything and a low low liability limit of less less than $80million for any disaster.

The good point is the ability (in another 2000 years or so) to re-seed life anywhere or Anytime in the future from scratch without DNA breakdown. I'm looking at this as Noahs Ark/Titan AE of sorts. If we humans destroy just about everything in our tenedency towards war this might be part the mechanism that rescues life on this planet afterwards.

This is not counting any megalomaniacal daydreams of mine :) Bwah ha ha Bwah ha ha ha ha ha ha ha ha :)
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Postby sandra » Tue May 25, 2010 11:29 am

"Synthetic genomics combines methods for the chemical synthesis of DNA with computational techniques to design it. These methods allow scientists and engineers to construct genetic material that would be impossible or impractical to produce using more conventional biotechnological approaches. For example, using synthetic genomics it is possible to design and assemble chromosomes, genes and gene pathways, and even whole genomes.

Scientists foresee many potential positive applications including new pharmaceuticals, biologically produced (“green”) fuels, and the possibility of rapidly generating vaccines against emerging microbial diseases.

However, as with many technologies, there is the potential for misuse and accidents. Finding ways to mitigate possible nefarious uses and to prevent accidents in the laboratories of legitimate users so that positive uses are not undercut is an important concern of scientists, governments, and a large variety of stakeholders.

This report is the result of a 20-month examination of the safety and security concerns posed by this new technology. Including the authors, a core group of 18 individuals with a wide range of expertise undertook three tasks: assess the current state of the technology, identify potential risks and benefits to society, and formulate options for its governance. The report discusses options that would help to enhance biosecurity, foster laboratory safety, and protect the communities and environment outside of laboratories. Three sets of options apply respectively to commercial firms that supply DNA; the oversight or regulation of DNA synthesizers and reagent used in synthesis; and the legitimate users of the technologies, such as university researchers."
http://www.jcvi.org/cms/research/projec ... /overview/

First Self-Replicating Synthetic Bacterial Cell

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.

The JCVI scientists envision that the knowledge gained by constructing this first self-replicating synthetic cell, coupled with decreasing costs for DNA synthesis, will give rise to wider use of this powerful technology. This will undoubtedly lead to the development of many important applications and products including biofuels, vaccines, pharmaceuticals, clean water and food products. The group continues to drive and support ethical discussion and review to ensure a positive outcome for society.

Funding for this research came from Synthetic Genomics Inc., a company co-founded by Drs. Venter and Smith.

http://www.jcvi.org/cms/press/press-rel ... esearcher/

*****One of Venters main focus has been on biofuels, a complete redesign of the entire industry etc but there are a couple other big cometitors and patent applications are flying. Its not a comforting feeling that synthetic sefrepllicating cells will be in the hands of Universities for research studies, and I think no matter what, there will be much more room for bioerror and bioterror. That was a good point Aquatank, after much destruction synthtics have the ability to restore, seeding new life forms etc/ plant life etc. although that makes me think about 'history repeats itself', have we already done that? We are always believing some other types of beings have reseeded life here on earth. Who is to say we are not those beings, and getting ready to do it again. ;)
“Living backwards!” Alice repeated in great
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“—but there’s one great advantage in it, that one’s
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Postby Aquatank » Tue May 25, 2010 8:56 pm

Interesting reversal question, I was thinking the samething while reading Clive Cussler's Medusa the other day. It mentioned in passing an old hypothesis (i remember it from about a decade ago) that perhaps viruses where alien lifeforms, but the reversal is also a good question what if the non-viruses are the real aliens. I'm of the opinion we all came from the same primordial soup, and that it isn't history repeating itself. Humankind is one of the biggest stressors of natural selection and evolution known, we've been meddling in nature sionce we first started horticulture than agriculture and have been breeding animals. In the end creating life from scratch is just another bit of meddling. But what we do with that meddling is what really matters, in most cases we meddle in a good way like when someone kept breeding grass with bigger seeds until it became corn, or how we took precusor bovines and made them into relatively docile dairy cattle, or how we breed dogs for certain traits to aid us in different tasks, its when we screw up and do something for stupid reasons that things get out of control, humans do that quite a bit too.

Lately my mind has been on metallic hydrogen fuel, but at the same time my head is going "ouch that'd be nasty thing if it got weaponized". The same applies in biochemistry, and we have to step back and wonder how much Mary Shelley was right in her concern about such things in science while she herself was pushing social limits in the same way. Its a tricky thing coming up with an invention and hoping sdomeone doesn't abuse it.
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Postby rath » Sat May 29, 2010 11:59 pm

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Postby CodeBlack » Mon Jun 07, 2010 5:49 pm

I don't think people realize just how big this is. As an invention it is bigger than movable type, bigger than the light bulb, bigger than the airplane, bigger than integrated circuits. If they are able to actually start designing new lifeforms then the sky is the limit. You can cure diseases, pick traits in children, build specialized "humans" for specific tasks. If you aren't amazed and scared you should be.

I think its not too likely that a new virus will wipe out the human race but its not beyond possibility. But Mother Nature has been cooking viruses for billions of years and she hasn't wiped us out yet. I doubt Man will do any better. But you could kill millions by accident.

And you could make current humans obsolete. Who would hire a human that gets tired after 8 hours of work when you can build a pseudo-human that works round the clock? Forget steroids, all sports records will be broken. And on and on...

Not to get too religious, cause I know that turns some people off, but this was predicted thousands of years ago in Gnostic scripture. I don't even know where to begin quoting. I have mentioned it a good number of times on this and the old BV. People didn't comprehend what I was talking about but this is it. You should hear the things they knew thousands of years ago! And without any science at all. How possible? Obviously someone told them.

Just a few quick quotes:

"When you strip yourselves of the flesh, then you will enter the kingdom." -JC

"No man enters the kingdom in the flesh." -JC

"Do not ask what your garment will be, it will be provided for you." -JC again

"It is easier for a camel to pass through the eye of a needle than it is for a rich man to enter the kingdom." -JC
Why? Because wealth isn't what makes it possible to get there. You must be transformed in order to reach that place. And we will never reach that level of technology if we don't choose to give up the flesh (and its "sins").

"For it is difficult even for me to reach." -guess who? JC

No, this "heaven" is not some magical, ethereal place. It is real. And genetic engineering will be the stairway to it. First comes the "8th and the 9th".
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Postby Aquatank » Mon Jun 07, 2010 7:40 pm

Do have any idea what kind madness you are talking about unleashing Codeblack? Do you have any idea the kinds of lifeforms I would create if I got a hold of such power. :twisted: You should quake in unimaginable horror at meerest inkling of thoughts of the exotic lifeforms I would create :shock: . And I should know I've been dreaming up these global takeover schemes a looooong time :lol: . Although to be honest, lately I've been thinking Earth makes a better penal colony than a utopia :oops: .
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Postby CodeBlack » Tue Jun 08, 2010 5:17 pm

Well, Aqua, you and the Taliban are the types of people this technology should be shielded from, but, I seriously doubt any such shielding will be possible, long term. The technology will get out. You've taken the most negative and cynical line. However, I did say that people should be scared. This isn't the usual invention. It may take some time for people to figure that out.

Aqua, how do you feel about the things that governments did during the 20th century, like biological warfare and experiments performed on unsuspecting civilians? What about the military claiming in the 1950's that they didn't understand the effects of radiation from nuclear testing, when it was common scientific knowledge that radiation from nuclear weapons was deadly and long lasting?

If any "shielding' was going to happen it would be the government doing it, but we can't trust governments. They have proven they can't be trusted.
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Postby Aquatank » Wed Jun 09, 2010 7:03 am

I accidentally posted this in Alternative Futures:
I see my shock tactic worked. Lumping me in the same category as the Taliban is an ideological and theological contradiction, but it does bring up the point I was getting at. That is when messing with the building blocks of life especially in creating a new lifeform the process is inherently prejudiced and racist. That is the creator determines through pre judgement what is wanted and then eschews any other variants the lifeform could take, in some cases actually killing organisms that fail to meet the creators qualifications.

On top of that just using such a thing for an ARK still brings up the same matter regarding genocide, in this case I don't just mean humans I mean every biological would have to fit the creators utopian vision or be tossed aside to suffer whatever Earth's fate was.

We all know the day is coming when we can create life from scratch, but its a matter of "should we?". What stops a person from robbing another person from mugging someone if they are broke, what stops a person from murdering another person out of anger, what holds our hands from doing wrong, when we know in our minds we could. Its our own refusal our own judgements based on innumerable different and sometimes contradictory moral codes the world has and our own emotions. For the vast part of the world these are what keep us in check, and though you don't trust governments they to are held in check to a certain dgree as well by the people that them up. So our answer comes down to the vast majority of this will be on the up and up, but its what escapes that becomes our problem because it will escape and be abused. Not all our Monsters will be nice, and some of our idealistic Victor Frankensteins will find themselves turning into Victor Helios. Our dinosaurs will escape our amusement parks and someone will try to weaponize them. But as we know if the problem cannot be contained properly then it will become an endemic problem like narcotics and war.


Codeblacks response was this
C'mon, you're saying god is a racist because he created the life that inhabits this universe? The universe is a collection of physical laws. Before the universe there was infinite entropy (infinite choices). The universe as we know it began with a moment of extremely low entropy, perhaps zero, and very few choices, perhaps only one. All that there is exists because of this. God does not kill off life that doesn't measure up. The universe is filled with circumstances of limited access to resources and those species that adapt, survive, those that don't, don't.

The universe is unstable and in constant change so we have to adapt to those changing conditions. And our latest adaptation is creating new lifeforms to serve our needs. And in keeping with the topic of this thread, one of those things will be energy. You should be happy. You can't get any greener than biology.

And your last paragraph... governments are doing all those things now, nobody stopping them either.
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Postby Aquatank » Wed Jun 09, 2010 8:07 am

Codeblack
I'm sure somepeople won't agree with me on this but there are two different possibilities in answering whether God is Racist or not.

1) and I tend to hold to this is: No, God is not racist because the system that was set up works independently of God (for the most part) and hence biologicals develop on their own through the freedom of evolution and chance. Less interference means less chance of divine prejudged selection. I admit there is divine interference: Eesa, Muhammad, Budha, Angels & Gods showing up to help or hinder. But very little in the way direct selection of species reproducing, its more like having a whole lot of puppies and giving each love and affection when they need it or when they just look so darn cute.

2) Most creationist views put things somewhere on the Great Chain Of Being That is God then Angels then Humans (some might say then Man then Woman) then Higher Biological Life forms then Lower Biological Life forms Then Plants Then Viruses etc. If Such a chain of being exists then yes it is favoritism and inherently racist.

And Yes the universe is a constant state of flux, but nature can deal with flux without our human interference creating new life forms from scratch. Natural designs are superior and using her designs in traditional crossbreeding methods works better then meddling by inserting transgenic or artificial genes. Example: GM crops actually have lower yields ( http://www.independent.co.uk/environmen ... 12179.html ) than their traditional bred counterparts but GM is pushed on farmers like a drug, furthermore some GM have side affects such a poisoning beneficial insects (Example: "Transgenic pollen harms monarch larvae" Nature, Vol 399, No 6733, p 214, May 20, 1999) We already use genetics to create things like glow in the dark monkeys http://www.dailymail.co.uk/sciencetech/ ... ebate.html and multi eyed flies http://www.time.com/time/magazine/artic ... 51,00.html and then there are normal organism escapes like the Gambian Pouch Rat in the Florida Keys and Pigs & Boasr in America causing alien invasive species problems, what happens when the wrong GMO or scratch built organism escapes?

As much as we can complain about governments they are a necessary evil where humanity is concerned, without the social consensus that forms such administrations there is only trouble for all as humans will run amuck because without social consensus there are no group moral rules or standards to hold to own each individuals. Example: without a strong social order piracy tends to rise in coastal regions and gang activities increase on city streets. The only way to stop a government from misbehaving is to keep in constant check through mass social pressure to obey certain norms. To that end is why there is such an outcry against genetic modification, and why the worlds masses have virtually banned human cloning and why they will probablty rally against scratch built organisms.

Being the scamp I am, I see plenty of good things that can be done and will be done using these technologies but I also know the inherent risk is huge, such as what if Ebola became water born and could survive outside a host organism only to become more virulent inside a host. What If humanity created the humanoid equivelent of a Cape Bee and they escaped giving birth without mates constantly increasing our planets population too quickly. As much as I like technology and believe me I do I also see us planting the seeds of our own extinction, we need to be far more choosy over what is really needed to survive and what is just a want.
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