In the last couple of years substantial progress has been made towards creating synthetic life. At the beginning of the century synthetic biologists identified a series of accomplishments they would need before synthetic life that would never occur naturally, would be possible. This year marks a point in time by which substantial progress has been made in all of the key areas they identified.
They knew as a first step, they might have to work with a natural living “shell” they could insert their synthetic creations into, counting on the life shell to continue living and sustaining its synthetic parts. This was viewed as a more practical target than trying to create brand new life in a laboratory. They knew they needed an inventory of synthetic parts that could be manufactured to order and mixed and matched to create a targeted life form. Probably hardest of all, they knew they had to create complex molecules, synthetic nucleotides, enzymes and proteins that were capable of retaining genetic information, replicating and allowing change and mutation over time. Only this would mimic the evolution of a natural living system.
In May of 2010, Craig Venter and his research team at the J. Craig Venter Institute announced the accomplishment of the first step or the creation of a laboratory produced synthetic bacterial cell. The researchers took two related mycoplasma species, M. mycoides subspecies Capri (GM12) as donor and M. capricolum subspecies capricolum (CK) as recipient to make their synthetic bacterial cell. These two bacterial species are forms of a microorganism parasite in ruminants, like cattle and goats, causing lung disease.
The team created in the laboratory a synthetic but faithful copy of the GM12 bacterial chromosome referred to as the donor and inserted it into a stripped down CK cell, which had selected genes removed and was identified as the recipient. This was the natural living shell referred to earlier. The CK cell accepted the transplanted chemically synthesized chromosome. The resulting bacterial cell was controlled by the synthetic GM12 chromosome and the accepting CK cell functioned as a GM12 cell. The team proclaimed they were first to synthesize, assemble, clone, and transplant a synthetically produced chromosome, creating a new cell controlled by the synthetic genome. Others would argue a similar achievement was accomplished some years earlier by Eckard Wimmer and a research team that chemically synthesized a complete viral genome that was used to regenerate a live polio virus.
Significant progress was made in creating an inventory of synthetic parts when a 2011 research team headed by Steven Benner, founder of the Westheimer Institute for Science and Technology, announced it had created two new molecules which could be slotted into DNA alongside a chromosome’s natural bases, adenine (A), guanine (G), cytosine (C), and thymine (T). An August 2011 article in the RSC Chemistry World stated “The new bases, dubbed ‘P’ and ‘Z,’ look similar to natural ones but have orthogonal hydrogen bonding patterns.” While this was not the first time unnatural nucleotides have been inserted into DNA, they typically are eliminated during replication by un-accepting copying enzymes. Benner’s team claims they have overcome this rejection. Benner says his group “have already obtained GACTZP DNA replication in artificial cells, and are working to introduce [it] into E. coli.”
Finally, in the search for a complex molecule that will mimic life by retaining genetic information, replicating and allowing change and mutation over time, a research team headed by Phillip Holliger at the UK Medical Research Council’s Laboratory of Molecular Biology reports they have created selected alternatives to or competitors with DNA. The team has developed six alternative polymers that they call xeno-nucleic acids (XNA). These XNAs differ from the familiar DNA in that the team has substituted different sugars for the deoxyribose (the D in DNA). Dr. Holliger explained, “We’ve been able to show that both heredity – information storage and propagation – and evolution, which are really two hallmarks of life, can be reproduced and implemented in alternative polymers other than DNA and RNA.”
A DNA strand is composed of three basic materials, sugars, phosphates and bases. An article appearing in discovermagazine.com explains these XNAs as follows, “DNA looks like a twisting ladder. Its sides are chains of a sugar called deoxyribose (the D in DNA), connected by phosphate groups. Each sugar is attached to one of four ‘bases’ – these form the rungs of the ladder, and are signified by the letters A, C, G and T.” Each of the six XNA’s has a slightly different molecule making up its sugar replacement. Like DNA “all the XNAs use the same bases and the same phosphate groups. Any of them could pair up with a complementary strand of DNA or RNA.”
The article further describes a key breakthrough by Vitor B. Pinheiro, a research team member, “Pinheiro created his XNAs by tweaking a natural enzyme called DNA polymerase, which copies DNA. It ‘reads’ a piece of DNA, grabs nearby bases, and assembles a matching strand….Here is the clever bit. DNA polymerase is normally very fussy about the bases it grabs. It only selects ones with a deoxyribose sugar so that it assembles DNA, rather than any other nucleic acid. But Pinheiro evolved the enzyme so it prefers to use the building blocks of his XNAs instead.” The replication is accomplished using these special polymerases (enzymes) that not only synthesize XNA from a DNA template but also copy XNA back into DNA. The copying to and from DNA is achieved with a high degree of accuracy which is a requirement that is essential to evolution.
Pinheiro cited yet another advantage researchers see with the new XNAs. The natural nucleic acids, DNA and RNA, can be made to evolve so they bind tightly to specific molecular targets. The problem is they are unstable because they are rapidly broken down by enzymes called nucleases which snip and degrade things in the body. The new XNAs because of their different chemical composition, should not be easily recognized by these enzymes. Their chemistry already makes them more stable and consequently more resistant to the enzymes. As an example, Pinheiro incubated one of them, HNA (with a five carbon sugar called anhydrohexitol), in an extremely acidic solution for an hour and the XNA molecule was unaffected. “DNA just would have been shredded,” said Pinheiro.
Gerald F. Joyce, a professor at The Scripps Research Institute, commented on the limitations of this research in an article in the April 20, 2012 issue of Science. He observed that the replication that was achieved was still dependent on the participation of DNA. He stated, “Finally, construction of genetic systems based on alternative chemical platforms may ultimately lead to the synthesis of novel forms of life. For that goal to be realized, the XNA must be able to catalyze its own replication, without the aid of any biological molecules, and thus be capable of undergoing Darwinian evolution in a self-sustained manner.”
What is of greatest concern about all of these developments is the repeated and continued involvement of life. None of the supposed accomplishments would have been possible without the flexibility of life processes and chromosomes. It could be argued this flexibility is one of the strengths of life’s genetics for it facilitates life’s ongoing evolution. Not only was the inherent malleability of natural chromosomes necessary for these changes to work but it is the absence of a “firewall” or barrier, in fact an actual attractiveness, between the resulting synthetic life properties and the rest of the gene pool that is the most troubling. Should any of these experiments expose life outside the laboratory environment to these altered elements there are very large risks the changes would be incorporated into the mainstream genetics of life. At the end of the aforementioned article in the April issue of Science, Dr. Joyce issues a telling admonition, “Synthetic biologists are beginning to frolic on the worlds of alternative genetics but must not tread into areas that have the potential to harm our biology.”
Background: In Beyond Animal, Ego and Time, Chapter 13: Protect Life Imperative – Synthetic Biology discusses the evolution of Synthetic Biology from genetic engineering. This dedicated chapter on Synthetic Biology identifies it as one of four looming global threats to the continuation of life on our planet.
Use the following links to obtain more information on these topics: