The design debate through the looking glass

Design through the Looking Glass

Evolution News & Views 

You don't have to hold an amino acid up to a mirror to see its mirror image. Amino acids (except for one, glycine) come in pairs, like gloves, on the real-world side of the looking glass. So do the sugars used in DNA and RNA; they are assigned a "handedness" based on conventional rules of describing their orientation in 3-D space. In all other physical respects, chemical and thermodynamic, they are identical in their activity. This makes them difficult to separate.

The phenomenon is known as chirality. The chiral "isoforms" are called enantiomers of each other. Left-handed enantiomers are preceded byL- (from Latin levo) as in L-alanine, while right-handed enantiomers are preceded by D- (fromdextro) as in D-ribose. A mixture of both hands is said to be racemic, or heterochiral. A pure mixture of one hand is called homochiral.

With only rare exceptions, all living things use just one "hand" of these molecular gloves: left-handed amino acids in proteins, and right-handed sugars in nucleic acids. How this came about has long been a mystery, as four Chinese scientists from Tsinghua University in Beijing explain in Nature Chemistry:

Despite biology's seemingly limitless diversity and the vastness of its territories that permeate into virtually every corner of the Earth, at the fundamental level of biochemistry, all known forms of life are narrowly defined by a single version of molecular machinery based on L-amino acids and D-ribose nucleic acids. Although rare examples of the use of D-amino acids, such as D-aspartic acid in animal brains, and L-sugars, such as L-arabinose in plants, do exist, the central dogma and most of the biological macromolecules have followed the homochirality established by life's earliest ancestors. Processes that led biology onto this particular chiral path have remained largely elusive, even though experimental evidence for breaking the mirror symmetry has been reported and many theoretical models have been proposed.[Emphasis added.]

As it stands, no experimental or theoretical model explains the origin of life's homochirality by natural processes. Some experimenters have produced a slight enantiomeric excess of one hand or the other, but usually with non-biological chemicals, and nothing approaching the purity of life's chiral molecules. Proteins and nucleic acids cannot work with mixed handedness. A single wrong-handed building block is enough to destroy DNA, RNA, and proteins. As we saw last year, checkpoints ensure that life's building blocks remain homochiral.

This purity of handedness baffles materialists, because their causal toolkit only includes natural law and chance. The probability of getting a single-handed polymer from racemic ingredients is comparable to getting a string of coin tosses coming up all heads. The longer the sequence, the more improbable it becomes -- quickly swamping the chance hypothesis. Yet as Wang et al. state, our knowledge of natural laws isn't helping solve the problem.

Recently, an in vitro selected catalytic RNA capable of incorporating nucleotides in a cross-chiral fashion without enantiomeric cross-inhibition was reported. The fact that no known laws of physics and chemistry preclude biology's use of either of the two chiral systems, mirror-image twins of one another, has led to an intriguing question as to whether a parallel mirror-image world of biology running on a chirally inverted version of molecular machinery could be found in the universe or be created in the laboratory.

Turning from origins to application, they describe their initial attempts to create mirror-image life:

We reasoned that towards synthesizing a mirror-image biological system, an imperative step would be to reconstitute a chirally inverted version of the central dogma of molecular biology with D-amino acid enzymes and L-ribose nucleic acids--although reconstituting a mirror-image, ribosome-based translation systemthrough the total synthesis of all the ribosomal RNA (rRNA) and protein building blocks is still beyond the current technology, the totalchemical synthesis of (small enough) mirror-image polymerases might be feasible. Here we set out to synthesize such a mirror-image polymerase and to test if two steps in the central dogma, the template-directed polymerization of DNA and the transcription into RNA, can be carried out in a synthetic mirror-image molecular system (Fig. 1a).

(For present purposes, we won't dispute the central dogma, although biologist Jonathan Wells has written extensively on its problems.)

These scientists did, in fact, succeed in getting some template-driven polymerization and transcription of opposite-handed amino acids. It was very slow, but it demonstrates that, in principle, life could exist in a mirror image of itself. Alice through the looking glass would appear identical to her mirror image, but would not be able to eat opposite-handed food!

Commenting on this work for Nature, Mark Peplow explains why synthetic mirror-image biomolecules have desirable properties:

In principle, looking-glass versions of these molecules should work together in the same way as normal ones -- but they might be resistant to attack by conventional viruses or enzymes that have not evolved in a looking-glass world.

That makes mirror-image biochemistry a potentially lucrative business. One company that hopes so is Noxxon Pharma in Berlin. It uses laborious chemical synthesis to make mirror-image forms of short strands of DNA or RNA called aptamers, which bind to therapeutic targets such as proteins in the body to block their activity. The firm has several mirror-aptamer candidates in human trials for diseases including cancer; the idea is that their efficacy might be improved because theyaren't degraded by the body's enzymes. A process to replicate mirror-image DNA could offer a much easier route to making the aptamers, says Sven Klussmann, Noxxon Pharma's chief scientific officer.

Wang et al. took the smallest known polymerase enzyme, just 174 amino acids long, and laboriously constructed a right-handed counterpart. They succeeded in getting it to extend a primer from 12 nucleotides to 18 nucleotides in 4 hours. Getting it to 52 nucleotides took 36 hours -- a "glacial pace," Peplow remarks. Nevertheless, it was an important discovery. Both the normal and mirror-image enzymes worked independently, without interference, when mixed in the same test tube.

The Design Inference

The researchers admit it would be a "daunting task" to build a mirror-image version of a ribosome where translation could take the left-handed RNA and translate it into a right-handed protein. Building a "looking glass cell" is a far-off dream. At this stage, though, we can draw some conclusions about chance and design.

Peplow confirms that homochirality remains a vexing problem. He surely would have said otherwise if a likely non-random cause were known.

In their research paper, the Tsinghua researchers also present their work as an effort to investigate why life's chirality is the way it is. This remains mysterious: it may simply be down to chance, or it could have been triggered by a fundamental asymmetry in nature.

But Steven Benner, at the Foundation for Applied Molecular Evolution in Alachua, Florida, says it's unlikely that creating a mirror form of biochemical life could shed any light on this question. Almost every physical process behaves identically when viewed in a mirror. The only known exceptions -- called 'parity violations' -- lie in the realm ofsubatomic physics. Such tiny differences would never show up in these biochemical experiments, says Benner.

Benner and Peplow just conceded that natural law cannot explain homochirality. To a materialist, that leaves chance. For a short polypeptide of 100 amino acids to have formed by chance would be ½ x ½ x ½ ... 100 times: 1 chance in 2100, which is approximately 1 in 1030. There aren't enough probabilistic resources to make this likely to happen in a primordial soup of racemic amino acids. But then, even if it did, homochiral DNA or RNA would have to form independently out of its own racemic building blocks. There's just no realistic chance of success in a materialistic world. Intelligence, by contrast, can easily select one hand over the other; consider how quickly an eight-year-old could sort a pile of coins into heads and tails.

Another conclusion from this paper is that homochirality as observed in life is contingent: i.e., it could exist in the opposite mirror-image form. There is no chemical or thermodynamic reason why proteins must be left-handed as opposed to right-handed, or why nucleic acids must be right-handed as opposed to left-handed. The experiments show that chemical reactions can proceed just as well in a mirror-image world. When a choice has been made one way to the exclusion of other possibilities, and it is beyond the reach of chance, it gives indication that intelligence has embedded information into the system.

Finally, these researchers demonstrate empirically how intelligence can embed information into a system. They purposefully selected building blocks of one hand to construct their polymerase. They had a goal, and a means of reaching it. If we rightly judge their work as a product of intelligent design -- as glacially slow as it was -- how much more the products of a cell that work rapidly and accurately, using machinery at a level of sophistication beyond our ability to imitate?

It's logical. If a system on the far side of the looking glass is intelligently designed, then the system on the near side is also intelligently designed. Only a fun-house mirror could distort that conclusion.