Ross Thyer and Jared Ellefson, molecular biologists
Researchers from Scripps Institute in La Jolla, CA generated a lot of excitement in May of 2014 when they announced the creation of the first-ever organism to utilize “alien” DNA.1
This groundbreaking advance raises a number of significant questions:
- Should humans play God?
- Is this type of work safe? If these organisms escape the laboratory, will they cause environmental devastation of biblical proportions?
- If humans can create artificial life in the lab, does that mean there is nothing special about life?
- If humans can create artificial life in the lab, does that mean God is not necessary to explain the genesis of life?
- Does this breakthrough make evolutionary explanations for the origin of life more reasonable?
In spite of these very real concerns, this achievement heralds the development of important new technologies that hold the potential to positively transform the world. (For an illustration of how advances in synthetic biology can benefit humanity see: God’s Providence, Man’s Dominion, and Synthetic Biology.)
In my opinion, the Scripps Institute scientists’ impressive work is also exciting for another reason. It points to a powerful new line of argumentation for God’s existence and role in creating Earth’s first life. To appreciate why the creation of artificial life in the lab undermines the evolutionary explanation for life’s origin, yet supports a creation model, it is necessary to review some basics about DNA structure.
DNA has a “ladder-like” architecture formed from two chain-like molecules. The molecular chains align in an antiparallel fashion to form a DNA molecule. (The two strands are arranged parallel to one another with the starting point of one strand in the duplex, or double-stranded DNA, located next to the ending point of the other strand and vice versa.) Envision the backbone of the chains corresponding to the uprights of a ladder. Then, the side groups that extend from the backbone interact to form molecular “rungs.” Finally, the paired chains twist around each other to form the well-known DNA double helix.
A cell’s machinery forms DNA chains by linking together four different subunit molecules called nucleotides. The four nucleotides used to build DNA chains are adenosine, guanosine, cytidine and thymidine, famously abbreviated A, G, C, and T, respectively.
A special relationship exists between the nucleotide sequences of the two DNA strands. Biochemists say the DNA sequences of the two strands are complementary. When the DNA strands align, the adenine (A) side chains of one strand always pair with thymine (T) side chains from the other strand. Likewise, the guanine (G) side chains from one DNA strand always pair with cytosine (C) side chains from the other strand. Biochemists refer to these relationships as base-pairing rules. As a consequence, if scientists know the sequence of one DNA strand, they can readily determine the sequence of the other strand.
Credit: DNA Structure/Wikimedia/Creative Commons
Creating Artificial Base Pairs
Biochemists have studied the pairings between A and T, and G and C, respectively, and understand the physicochemical basis for these interactions. Based on this insight, they have developed several unnatural base pairs (UBPs) that serve as analogs to the naturally occurring ones (A:T and G:C). One UBP of particular interest forms between two compounds designated d5SICS and dNaM. Over the last few years, researchers have incorporated this UBP into synthetic pieces of DNA made in the laboratory. They have also shown that some of the enzymes used to replicate DNA in vivo, will make in vitro copies of synthetic DNA when the d5SICS:dNaM UBP is incorporated into its structure.
As a logical next step, researchers hoped to move from the test tube into the cell by determining if DNA with the d5SICS:dNaM UBP could be formed and retained in living systems.
The First Organism with “Alien” DNA
To test this idea, the team made a synthetic version of plasmid DNA with the UBP at a single position in the plasmid. (Plasmids are small circular pieces of DNA that can reside inside bacteria, independent of the bacterial chromosome.) Then, they induced the bacterium E. coli to incorporate the laboratory-made plasmid.
Next, scientists fed the bacterium d5SICS and dNaM from the growth media. The microbes took up these artificial compounds and used them to make copies of the plasmids with the UBP retained within the structure. Then, plasmids harboring the UBP were successfully partitioned into the daughter cells upon cell division. The researchers observed that plasmid DNA was copied and passed on to daughter cells from generation to generation for nearly a week.2
While this accomplishment (replacing only one base pair in plasmid DNA with a UBP and then claiming to have created an organism with alien DNA) hardly seems worthy of the headlines garnered, it still is an important milestone in synthetic biology. This breakthrough paves the way for more interesting possibilities. And yet as “meager” as this accomplishment might seem, it required enormous effort and ingenuity on the part of the researchers. As Ross Thyer and Jared Ellefson—two synthetic biologists from the University of Texas, Austin—state in a commentary on the work, “This feat was far from simple.” 3
In order to more fully appreciate the amount of effort this accomplishment required, consider the following steps researchers took to successfully engineer E. coli to harbor a single UBP in its plasmid DNA.
- For the plasmid DNA to retain the UBP through several generations of cell growth and division, the researchers had to ensure a continual supply of d5SICS and dNaM. None of the transporter proteins encoded in the E. coli genome could do the job. Therefore, researchers had to genetically engineer the E. coli strain so that it could transport d5SICS and dNaM into the cell from the growth media. They did this by incorporating a protein from algae (called a nucleotide triphosphate transporter [NTT]) into the microbe’s genome. The right NTT was identified only after trying eight candidate NTTs from a variety of biological sources.
- The team determined they needed to work with the triphosphate form of d5SICS and dNaM instead of the mono- or diphosphate forms. The cell’s machinery requires the triphosphate form of nucleotides during DNA replication. Normally, a cell converts mono- and diphosphate nucleotides into the triphosphate forms using proteins called nucleotide monophosphate kinases and nucleotide diphosphate kinases, respectively. Unfortunately, these enzymes in E. coli didn’t recognize the mono- and diphosphate forms of d5SICS and dNaM.
- A complication was discovered in the use of the triphosphate form of d5SICS and dNaM. The triphosphates of these unnatural nucleotides were unstable in the growth media. To increase the stability of the nucleotide analogs, the researchers had to add inorganic potassium phosphate to the growth media.
- Researchers also had to carefully locate the UBP in the plasmid DNA. Previous in vitro experiments showed that the protein DNA polymerase I could replicate synthetic DNA with the d5SICS and dNaM UBP incorporated into its structure. But the protein DNA polymerase III could not. Unfortunately most of the DNA in E. coli is replicated with DNA polymerase III. Still, a small region of the plasmid DNA is replicated by DNA polymerase I. The team carefully synthesized the plasmid DNA so that the UBP resided in the region of the plasmid replicated by DNA polymerase I.
The First Organisms with Artificial DNA and the Case for Design
As the steps demonstrate, the incorporation and in vivo maintenance of the UBP at a single position in the E. coli plasmid DNA required extraordinary effort on the part of highly trained and highly skilled researchers. But it isn’t just the amount of effort expended by the researchers that is most impressive to me as a biochemist. It is the researchers’ ingenuity—the clever strategy they employed. Their strategy was based on knowledge and understanding of biochemical systems accrued over several decades.
To put it simply, the creation of E. coli that makes use of “alien” DNA required the activity of intelligent agency.
While many in the scientific community maintain that life’s origin and history can be fully explained within the evolutionary paradigm, I am skeptical of this assertion because of the inability of the scientific community to explain the origin of life through evolutionary means (see Creating Life in the Lab) and the presence of elegant designs in biochemical systems (see The Cell’s Design). I think the scientific data overwhelmingly supports the idea that life’s origin and design stem from the work of a Creator.
This recent, brilliant work by the Scripps Institute team provides empirical support for a creation model. It demonstrates that turning “inanimate” matter into living systems and radically transforming living systems require intelligent agency.