Man makes life:

[underlankers.livejournal.com]

New research has brought us closer than ever to synthesizing entirely new forms of life. An international team of researchers has shown that artificial nucleic acids - called "XNAs" - can replicate and evolve, just like DNA and RNA.

We spoke to one of the researchers who made this breakthrough, to find out how it can affect everything from genetic research to the search for alien life.

The researchers, led by Philipp Holliger and Vitor Pinheiro, synthetic biologists at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, say their findings have major implications in everything from biotherapeutics, to exobiology, to research into the origins of genetic information itself. This represents a huge breakthrough in the field of synthetic biology.

The "X" Stands for "Xeno"

Every organism on Earth relies on the same genetic building blocks: the the information carried in DNA. But there is another class of genetic building block called "XNA" — a synthetic polymer that can carry the same information as DNA, but with a different assemblage of molecules.

The "X" in XNA stands for "xeno." Scientists use the xeno prefix to indicate that one of the ingredients typically found in the building blocks that make up RNA and DNA has been replaced by something different from what we find in nature — something "alien," if you will.

Strands of DNA and RNA are formed by stringing together long chains of molecules called nucleotides. A nucleotide is made up of three chemical components: a phosphate (labeled here in red), a five-carbon sugar group (labeled here in yellow, this can be either a deoxyribose sugar — which gives us the "D" in DNA — or a ribose sugar — hence the "R" in RNA), and one of five standard bases (adenine, guanine, cytosine, thymine or uracil, labeled in blue).

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The molecules that piece together to form the six XNAs investigated by Pinheiro and his colleagues (pictured here) are almost identical to those of DNA and RNA, with one exception: in XNA nucleotides, the deoxyribose and ribose sugar groups of DNA and RNA (corresponding to the middle nucleotide component, labeled yellow in the diagram above) have been replaced. Some of these replacement molecules contain four carbons atoms instead of the standard five. Others cram in as many as seven carbons. FANA (pictured top right) even contains a fluorine atom. These substitutions make XNAs functionally and structurally analogous to DNA and RNA, but they also make them alien, unnatural, artificial.

Information Storage vs Evolution

But scientists have been synthesizing XNA molecules for well over a decade. What makes the findings of Pinheiro and his colleagues so compelling isn't the XNA molecules themselves, it's what they've shown these alien molecules are capable of, namely: replication and evolution.

"Any polymer can store information," Pinheiro tells io9. What makes DNA and RNA unique, he says, "is that the information encoded in them [in the form of genes, for example] can be accessed and copied." Information that can be copied from one genetic polymer to another can be propagated; and genetic information that can be propagated is the basis for heredity — the passage of traits from parent to offspring.

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In DNA and RNA, replication is facilitated by molecules called polymerases. Using a crafty genetic engineering technique called compartmentalized self-tagging (or "CST"), Pinheiro's team designed special polymerases that could not only synthesize XNA from a DNA template, but actually copy XNA back into DNA. The result was a genetic system that allowed for the replication and propagation of genetic information.

A simplified analogy reveals the strengths and weaknesses of this novel genetic system: You can think of a DNA strand like a classmate's lecture notes. DNA polymerase is the pen that lets you copy these notes directly to a new sheet of paper. But let's say your friend's notes are written in the "language" of XNA. Ideally, your XNA-based genetic system would have a pen that could copy these notes directly to a new sheet of paper. What Pinheiro's team did was create two distinct classes of writing utensil — one pen that copies your friend's XNA-notes into DNA-notes, and a second pen that converts those DNA notes back into XNA-notes.

Is it the most efficient method of replication? No. But it gets the job done. What's more, it does all this copying to and from DNA with a high degree of accuracy (after all, what good is replication if the copy looks nothing like the original?). The researchers achieved a replication fidelity ranging from 95% in LNA to as high as 99.6% in CeNA — the kind of accuracy Pinheiro says is essential for evolution:

"The potential for evolution is closely tied with how much information is being replicated and the error in that process," he explains. "The more error-prone… a genetic system is, the less information can be feasibly evolved." A genetic system as accurate as theirs, on the other hand, should be capable of evolution.

The researchers put this claim to the test by showing that XNA strands made up of the HNA xeno-nucleotides like the one pictured here could evolve into specific sequences capable of binding target molecules (like an RNA molecule, or a protein) tightly and specifically. Researchers call this guided evolution, and they've been doing it with natural DNA for some time. The fact that it can also be accomplished in the lab with synthetic DNA indicates that such a system could, in theory, work in a living organism.

"The HNA system we've developed," explains Pinheiro, is "robust enough for meaningful information to be stored, replicated and evolved."

A Step Toward Novel Lifeforms

The implications of the team's findings are numerous and far-reaching. For one thing, the study sheds significant light on the origins of life itself. In the past, investigations into XNA have been largely driven by the question of whether simpler genetic systems may have existed before the emergence of RNA and DNA; the fact that these XNAs appear to be capable of evolution adds to an ever-growing body of evidence of a genetic system predating DNA and RNA both.

Practical and therapeutic applications abound, as well. "The methodologies [we've developed] are a major step forward in enabling the development of nucleic acid treatments," says Pinheiro. Natural nucleic acids [i.e. DNA and RNA] can be forced to evolve so that they bind tightly and specifically to specific molecular targets. The problem is that these nucleic acids are unsuitable for therapeutic use because they are rapidly broken down by enzymes called nucleases. As a result, these evolved nucleic acid treatments have a short lifespan and have a difficult time reaching their therapeutic targets.

To get around this, Pinheiro says medicinal chemistry is used to modify evolved DNA sequences in an attempt to create a functional molecule that can still bind to a therapeutic target but resist nuclease degradation. But doing this is tough:

"Overall, this leads to high cost and a high failure rate for potential therapies - there is still only a single licenced [nucleic acid-based] drug on the market (Macugen)."

But all six of the XNAs studied by Pinheiro and his team are stronger than regular DNA or RNA, in that they're more resistant to degradation by biological nucleases.

As a result, these molecules would need little or no adaptation for therapeutic (or diagnostic) use. "Since these molecules can now be selected directly on XNA, medicinal chemistry should no longer be limiting," says Pinheiro. You could select a suitable XNA for its biocompatibility and therapeutic potential, and not worry about having it rapidly degrade inside the body.

Pinheiro also says the outcome of the research could even have a strong impact on exobiology:

In my view, exobiology looks for life in regions it cannot physically visit. In that context, it searches for tell tale signs of life that can be remotely monitored but it has only life on Earth as examples to identify such suitable markers. Based on extant biology, DNA and RNA are good candidates for such a search. However, by showing that other nucleic acids can also store information, replicate and evolve, our research may force a rethink as to whether DNA and RNA are the most suitable tell tale signs of life.

Of course, nothing would call the indispensability of DNA- or RNA-based life into question more than the generation of an entirely synthetic, alternative life form, built from the ground up entirely by XNA. Such an organism would require XNA capable of driving its own replication, without the aid of any biological molecules. Pinheiro says that's still a ways off. "Even in its simplest setup... it would be very challenging to develop an XNA system within a cell." Such a system would require XNA capable of self-replication, and capable of undergoing evolution in a self-sustained manner.

That said, his team's work represents a major step in the right direction. As the molecular machinery designed to manipulate XNAs grows, so, too, will the capacity for synthetic genetic systems to stand and operate on their own.

The researchers' findings are published in today's issue of Science.
Top image via Shutterstock; XNA moieties via Science; all other images via Wikimedia Commons

The link to the arcticle:

http://io9.com/5903221/meet-xna-the-first-synthetic-dna-that-evolves-like-the-real-thing/

So now that it's possible to make synthetic DNA, what would the potential political ramifications be if people start making truly synthetic life? I'm not talking a clone of an animal that is implanted into and carried by another animal but a literally artificially engineered lifeform with everything from DNA upward being synthetic? IMHO the smallest ramifications here are that it would force a major shift in how life is defined, and that's just the most minor one.

I think another potential one here is whether or not artificial DNA might have applications in terms of a revival of legal bio-weapons research, as I'm not sure that the rules against biological warfare would necessarily cover an attempt to make something like that from XNA (and yes, it would be a very long time before this is possible, but still).

Your thoughts?

Comments

[policraticus.livejournal.com]

What could possibly go wrong?

[underlankers.livejournal.com]

Dammit, now that you've asked this I just know the world ends with the Andromeda Strain. ;P

[policraticus.livejournal.com]

That, at least, came from outer space.

This wound will be self inflicted. As usual.

[chron-job.livejournal.com]

I thought the Alpha Strain was local earth life, mutated by taking a ride on a satellite?

[policraticus.livejournal.com]

As I remember it, andromeda was a life form adapted for existence in interstellar space, converting energy to matter directly, without the use of organic chemistry. It was collected as part of a bioweapons search.

[jerseycajun.livejournal.com]

I was thinking more along the lines of Jurassic Park. Same author, at least.

[dexeron.livejournal.com]

Athiests: "SEE?! Abiogenesis! Life does not require some kind of creator to exist!"

Deists: "SEE?! Designed life! Life requires a creator to exist!"

[policraticus.livejournal.com]

It is pretty obvious who wins that argument. This Creator even comes with a NI number.

[yes-justice.livejournal.com]

Gawd we're that predictable!

[dexeron.livejournal.com]

To your actual question:

Maybe people with expertise in biology can speak to this, but the whole idea of how we adapt is that we have... well... adapted to coexistance with life as it is. That includes everything down to little viruses and bacteria. It's when we introduce unfamiliar things into that "balance" (such a stupid way to descrbe it, but I have nothing better to use) we have problems. Hence when a population that hasn't developed immunity to a certain disease encounters a population that has... and carries it.

I'm not saying that "creating life" is automatically turn into Captain Tripps form The Stand, but the same evolutionary processess that "created" the life we interact with on a daily basis are the same processess that have adapted us to be able to co-exist with them. We've seen the unintended (perhaps not) consequences when certain types of GM plants were introduced, and very easily spread into non GM fields. That's existing life that we've just modified (at first over long periods of time, now not so long.) How much more so with something completely unseen and unpredictable? We need to be damn cautious before allowing any form of artifically created life into the wild (and hell, that means even allowing it to interact in controlled situations in labs). If anything, I think any "bio-weapons" based on something like this would be far more terrifying, and should be that much more strongly opposed.

[yes-justice.livejournal.com]

We need to be damn cautious before allowing any form of artifically created life into the wild

And that's the rational argument against GMO's.

However, life is basically a war against death. All the things trying to kill us have a 100% success rate. I see this research as the first major step to forming a resistance to the enemy. Pick a side.

[meus-ovatio.livejournal.com]

There is nothing bad or unnatural about death.

[telemann.livejournal.com]

Bullshit.

[telemann.livejournal.com]

Yeah, last October up at Sleepy Hallow!

[telemann.livejournal.com]

Location is everything.

[chron-job.livejournal.com]

unnatural, I agree. 'Bad', this is a value judgement very dependent on context. For instance, MY death would be very bad indeed. Yours is your own business.

[meus-ovatio.livejournal.com]

No, your death would just be the natural operation of life as it has been for 5 billion years. It's ok man.

[luzribeiro.livejournal.com]

But, but, the Universe screams in pain every time something dies and there's a disturbance in the Force! A master Jedi once told me so.

[dexeron.livejournal.com]

The Jedi were all: "You can't unnaturally extend life! That's the dark side!"

Another reason the Sith were right.

[yes-justice.livejournal.com]

The universe is indifferent to mourning. Kinda like water doesn't care who it drowns.

[chron-job.livejournal.com]

Good and bad being subjectively assigned based on the values of the person doing the assignment, they don't necessarily map onto "natural" versus "unnatural".

An asteroid hitting the earth is utterly natural. But I would call the death and suffering that ensues as "bad". If you feel differently, that's the wondrous magic of subjective values.

[yes-justice.livejournal.com]

Death is no fun.



"Cambridge researcher Aubrey de Grey argues that aging is merely a disease -- and a curable one at that. Humans age in seven basic ways, he says, all of which can be averted."

[underlankers.livejournal.com]

Actually it's not for every organism. There are trees older than the oldest modern state, some older even than the entirety of human civilization. There is a species of jellyfish that is biologically immortal. And in any event humans killed off all the other cavemen and kept our non-talking cousins condemned to ultimate extinction at our hands in the forests because we have numbers and they did not. So life has always been cheap for any individual human. And in reality, death and life are not the absolute opposites people make them out to be.

[yes-justice.livejournal.com]

Actually it's not for every organism.

Agreed.

"Cambridge researcher Aubrey de Grey argues that aging is merely a disease -- and a curable one at that. Humans age in seven basic ways, he says, all of which can be averted."




And in any event humans killed off all the other cavemen and kept our non-talking cousins condemned to ultimate extinction at our hands in the forests because we have numbers and they did not. So life has always been cheap for any individual human

Not suggesting our track record isn't poor, just that there is a direction for improvement. Lowering a high birth rate and a making lower death rate?


And in reality, death and life are not the absolute opposites people make them out to be

Death is no fun.

[underlankers.livejournal.com]

Unfortunately a strict view of GMOs must include all existing food crops.

This is "natural" wheat:



And this is what makes bread:



Obviously one of these is somewhat different from the other. Humans have done just fine for the history of civilization with artificial organisms, so is it really that different going from new artificial ones from prior ones?

[dexeron.livejournal.com]

A valid point. Is there any different, though, between the kind of changes that can come about through natural breeding over time and changes that come about through much more intricate tinkering (that wouldn't actually come about through nature)? I mean, I'm not saying in terms of "good" vs "bad", but more in terms of the possibility of unintended consequences? Like... I don't SEE any reason why one should be more likely to cause that than the other, but that seems to be one of the big arguments against it. Is there an answer to that, or is it just a unfounded worry?

[chron-job.livejournal.com]

I see your point... just as introducing utterly new chemical substances (like, say, nylon) via chemical engineering, synthetic life that doesn't partake of the typical 'conventions' of the life which we have evolved along side might act in ways and produce things that we might have great difficulty adapting to.

But remember, Nylon-eating bacteria appeared only 40 years after the invention of nylon itself.

[yes-justice.livejournal.com]

Is there any different, though, between the kind of changes that can come about through natural breeding over time and changes that come about through much more intricate tinkering (that wouldn't actually come about through nature)?

In nature, there exists a parasitic brain worm that must breed inside the stomach of a cow. This parasite infects ants and forces them to climb atop a stalk of grass to ensure the parasite and ant will be eaten by a cow and the parasite can reproduce inside its stomach. The parasite takes over the ant just like a human drives a car.

That is some elaborate "tinkering" on the part of the parasite. It is akin to humans making tools out of the natural resources around them and using those tools to modify the growth of another organism (GMO's) to help us eat.


More on the ant:

[mahnmut.livejournal.com]

I'm not sure that the rules against biological warfare would necessarily cover an attempt

Rules change all the time.

[yes-justice.livejournal.com]

I think this kicks ass and I am in favor of it.

Creating life will help us understand how to combat death. Yes, there are tons of moral problems, but I assert they are a better quality set of problems than just being blind victims waiting to die mumbling helplessly to the sky ghosts for mercy. This is progress!

[telemann.livejournal.com]

Yep. Ditto that.

[eracerhead.livejournal.com]

It's only a matter of time. Prepare for it now or be miserable later.

[dv8nation.livejournal.com]

The only thing we really need to worry about here is furries. I've seen furries discussing if genetic engineering could be used to make real catgirls. Clearly, this must not be allowed to happen. Therefore, we must imprison all furries now so that science may continue to explore this new wonder in whatever direction will be the most cool.

[terminator44.livejournal.com]

Suffer not the furry to live.

[dv8nation.livejournal.com]

Damn right!

[meus-ovatio.livejournal.com]

You might want to cool your jets on this, if by "making new life" you mean "replacing a couple nucleotide molecular bonds with functionally equivalent molecules".

[chron-job.livejournal.com]

If it results in something novel, why the hair splitting? Was nylon a "new" chemical? It had never existed before, but it only has a few molecular differences from tons of other polymers.

[chron-job.livejournal.com]

No two things that are not exactly the same will "do" exactly the same thing in the real world. If they 'did' the same thing, we wouldn't be able to tell the difference.

Example: Silicon has 4 available bonds, like carbon does, so it is possible to replace some carbons in a polymer chain with silicon.

But the result is not "the same", since, silicon being bigger and heavier than carbon, the resulting polymer has different thermal properties. Knowing these different thermal properties might lead to a specific use that can be exploited, like say, engine oil that does not break down as quickly under thermal stress.

If XNA contains different elements, or different arrangements, than DNA, then it will behave differently in some way. This difference in behavior will have side effects, which might be put to positive use.

[meus-ovatio.livejournal.com]

Ok, or we'll just treat it like a polymer. lulz

[chron-job.livejournal.com]

See above response to belmincour

[the-rukh.livejournal.com]

Well I think by new he just means a new kind. I mean depending on your definition, we create new life all the time anyways either from having sex or simply when our body produces new cells anyways.

[meus-ovatio.livejournal.com]

Meh, I used to make DNA all the time with wooden balls. Take that!

[peamasii.livejournal.com]

Yes, it seems the scientists in this case are more concerned with being able to replicate chromosomes in an artificial medium than with creating a living organism from synthetics.

[peamasii.livejournal.com]

I would hope politics would adapt so that XNA people and DNA people can all get along, speak the same language, work, vote, have rights, have needs met, etc. Personally I don't see how it makes a difference whether a human being is made from natural DNA or artificial XNA, if they are conscious and breathing then they should be equal before the law. Whether life springs from a womb or from a lab makes no difference to the being who's living it.

[harry-beast.livejournal.com]

Great. Not only do we have to worry about increasingly advanced computers and robots turning on us, we now have the threat of genetically engineered superbeings kicking our asses. Thanks a lot, science!

[major-dallas.livejournal.com]

"All of this has happened before, and will happen again."

Skynet and Cylons, nice future to look forward to. Perhaps mankind isn't really ready yet, to play God... anymore than we do now...

[rimpala.livejournal.com]

Maybe it could one day bring us to cure a few diseases?