Synthetic Life and New Humankind
XNA is synthetic DNA that's stronger than the real thing
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.
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 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xeno prefix to indicate that one of the ingredients typically found in the building blocks that make up RNA and DNA has been replaced by something different from what we find in nature — something "alien," if you will.
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.
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 HNA system we've developed," explains Pinheiro, is "robust enough for meaningful information to be stored, replicated and evolved."
A Step Toward Novel Lifeforms
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 Science.
Top image via Shutterstock; XNA moieties via Science; all other images via Wikimedia Commons
How Artificial Chromosomes Could Transform Humanity
Normally, an extra pair of chromosomes would be considered dangerous. But what if we could design our own? According to biologists, we could create custom-built chromosomes to fix a variety of health problems, and even give us new abilities. Here’s how a 24th pair of chromosomes could change our biologies forever.
But before we get into artificial human chromosomes (AHCs), let’s quickly review what chromosomes are in the first place.
Packages of Genetic Material
Different components of chromosomes are turned on and off in different contexts and in various parts of the body. There are anywhere from around 250 million bases on some chromosomes, down to about 50 million on others.
We humans have 23 pairs, for a total of 46. These structures are very tightly organized windings of DNA that become encoiled in a complicated way and allow for division each time a cell divides, so that each cell has the same complement of genetics.
Sometimes, an added chromosome can be problematic. An extra chromosome 21 leads to trisomy, also known as Down syndrome. XXYY syndrome happens when males have an extra X and Y chromosome, leading to developmental delays, extra height, and learning disabilities.
Now With Added Function!
But adding extra chromosomes artificially won’t necessarily be a bad thing. And in fact, they could be quite advantageous. When inserted during the in vitro fertilization (IVF) stage, they could serve as remarkable and flexible platform for the insertion of genetics.
What’s more, he explains, physicians will be able to control the various elements of the genetic sequences. We’ll be able to turn them on or off, or even accelerate their expression. Certain chromosomes may be put in place to serve as a backup, or to function at a specific stage of a person’s life (such as during elderly years when existing genetics isn’t up to the task).
Stock says we could add an additional pair, bumping our total up to 24. Or, if we wanted to deploy them in discrete and tidy packages — which would contribute greatly to their flexibility — we could just keep adding pair after pair after pair. In fact, the technology to do this could come sooner rather than later, with chromosomes containing a mere 10 to 20 megabases.
“Ideally, if you were to create an extra chromosome, rather than putting extra genetic material and inserting it into an existing chromosome — where it might be put into a random spot or put into something else that’s going on — you have a very controlled environment,” he told io9. “You can create these things, duplicate them independently, and put them in different organisms. It’s a very controlled process.”
And in fact, this is already being done. The prospect got off the ground back in 1997 after John Harrington and Huntington Willard developed a technique for doing so. Bacterial artificial chromosomes are used in labs all the time, as are yeast ACs (called YACs). Biologists have even created ACs in mice. We’re currently at the nascent stage of human artificial chromosomes.
Stock says that we’ll be able to put some new genetic material into a chromosome and not have to turn it on until the individual is an adult. As a result, we won’t be tampering with the very sensitive arena of human development — something that would prove to be far more difficult to manage in a fully mature adult.
AHCs could also give humans new capacities altogether. Stock speculates about a range of futuristic enhancements, including the ability to see ultraviolet light, or navigation in the dark by a system of sonar similar to that employed by bats.
Therapy or Enhancement?
I asked Dr. Stock if this could be considered a therapy or an enhancement. “Well, I’d call this a therapeutic enhancement,” he replied. “But ultimately it’s a matter of perspective.”
Indeed, some people might consider a super-juiced immune system that's triggered later in life as an enhancement. Same for chromosomal interventions that could extend a person’s lifespan. Others, on the other hand, might simply say it's just a different way of doing therapy.
“But it also depends on whether or not someone is on the lower or upper area of performance of a specific category,” he added. “If you have diminished function, then they’re likely to be considered enhancements.”
One important thing to remember about enhancement, says Stock, is that it’s going to be tough. Unlike the repairing of health problems, which tend to be simpler, enhancement will elevate performance, which could result in unintended and unforeseen consequences. “That will require us to get everything right,” he says.
Stock points to the controversial realm of IQ and cognitive enhancement.
If somebody is functioning with an IQ of 70 — which is a couple of standard deviations below average — that may be the result of some very specific developmental problems that occurred, or some other underlying issue that’s relatively easy to repair. That person, if it’s caught early enough, might end up having an average IQ — which would most certainly seem like an enhancement to them.
But if a person has an IQ of 160, which is way out in terms of normal function, we’d be hard pressed to enhance their performance without having some subtle, or not so subtle secondary consequences that would be very difficult to gauge.
“For example, super-bright people often have quirks in their personality that, depending on your viewpoint, is either a positive a negative,” adds Stock.
Altering Our ‘Genetic Heritage’?
Stock says that the limited enthusiasm behind AHCs is due to a number of other viable interventions that could basically do the same thing.
“Naturally, we’re going to do what’s the safest and most effective thing.”
He points to embryonic genetic screening and drug treatments. Or even using assistive devices, like mobile phones, to ‘enhance’ our memories.
“All our tight associations with technology make us functional cyborgs, in which case we’re really and truly enhancing ourselves — so there are only a very few applications in which there aren’t easier paths when compared to genetic enhancement.”
Stock also notes the potential for somatic engineering, in which the existing cells of adults can be modified by injecting short genetic sequences.
“But technologically it’s much easier in the embryo,” he says. “With artificial human chromosomes, they’re automatically present in every cell in the body, and it can be set up in ways in which it can be turned on and off locally, like taking a specific drug that triggers it.”
This is a very important issue, he adds, because it makes the entire system failsafe.
I asked Stock about the ethical concerns related to the potentially permanent modification of the human germ line.
“Yeah, the general tone of the discussion is, ‘How could you possibly do that!? You’re altering our genetic heritage, and you’re altering genetics in humans — because once you get into our genetics then it’ll be passed on to the next generation!’”
But Stock thinks this represents a fairly limited view of technology.
“The fear that future generations won’t be able to remove it, inactivate it, make it non-heritable, or replace it with something better seems to me to be a rather tortured scenario,” he says.
But looking at advanced technologies, and then representing the context of them as being stationary and very limited, doesn’t make a lot of sense to Stock. What’s more, these technologies will be tested in animal subjects. And in fact, an artificial human chromosome has already been injected in mice.
“My suspicion is that we wouldn’t be reproducing naturally once we’re in that state,” says Stock, “because there’s so much more that we’ll be able to do 25 years from now. And we’re definitely going to want the next generation of artificial chromosomes. These things tend to move very quickly.”
As for a timetable, Stock expects to see the first artificial human chromosome put to use in about a generation from now, perhaps in 20 years.
“Bioengineers tend to underestimate the complexity of human biology,” he says. “These developments often come at a slower pace than we imagine. But they’re inexorable.”
Image: Creations/Shutterstock; Alila Medical Images/Shutterstock; Tehelka.
From io9 @ http://io9.com/5903221/meet-xna-the-first-synthetic-dna-that-evolves-like-the-real-thing and http://io9.com/how-artificial-chromosomes-could-transform-humanity-754993569
For more information about synthetic life see http://nexusilluminati.blogspot.com/search/labelsynthetic%20life /
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