Saturday, May 29, 2010

Creation of the First Synthetic Cell: Time to Applaud or Cry?

The news that genomic specialists had created the first synthetic cell – after $40 million and 15 years of research- struck many in the scientific world like the news of the first atomic bomb. However, in the non-science world you could hear a pin drop in terms of reactions.

Before going into the consequences, which I believe will be major, let’s consider the back ground.

First, the researchers (at least a team of 25 working at the J.Craig Ventner Institute) had to select a “target” microbe which they would fully analyze in terms of it genome, then re-engineer into a novel form. Their choice was the bacterium Mycoplasma mycoides.

Working with the bacterium meant first understanding the DNA sequence. In the diagram I show part of a DNA sequence for an unknown organism. This is the starting building block to work with.

DNA or deoxyribonucleic acid consists of two strands of what we call polynucleotides. In the case of DNA there are four bases: A (adenine), C (cytosine), G (guanine), and T (thymine) that are paired in two mutually exclusive ways[1]. That is, A always goes with T, while G always pairs with C. A sketch of this complementary base pairing – as depicted.

One possible explanation for the preferential pairing arrangement is the presence of multiple hydrogen bonds between bases. The arrangement itself is evidently crucial to the encoding of information. In this sense, the way the bases are arranged in DNA – forming various ‘messages’, is precisely analogous to the way this sentence encodes structured written information. Change the order of the letters in the words, the order of the words themselves – or both, and noise emerges.

On this basis DNA can be said to be an informational molecule. Also on this basis, as we shall see, if the information content alters – and can be replicated in its alteration, there is the possibility of molecular evolution. This is in fact the phase at which evolution commences, since it directly affects the instructions for protein synthesis.

In the case of Mycoplasma mycoides, more than one million letters of genetic instructions had to be parsed to obtain its genome.

Having this in hand, the real work could begin, entailing:

- deleting 4,000 letters, which removed the function of two genes

- Replacement of ten genes with ‘watermark’ sequences (each over 1,000 letters in length- which decoded disclose the names of people, famous quotes and a website url)

- All the DNA sequences were then partitioned into 1,100 separate pieces with each piece synthesized using 4 different bottles of the chemicals that comprise DNA.

- The synthesized sequences were designed so there was an 80-letter overlap, a precaution actually, that facilitated the assembly process.

- These overlapping DNA sequences for Mycoplasma mycoides were then added to fragments of yeast.

- Once embedded inside the yeast cell, the yeast automatically “recognized” the two DNA sequences with the same sequence and assembled them at the overlap regions.

- The new genome wasn’t assembled from all 1,100 pieces at once but in 3 stages of ascending couplings or merges: a) 1,000 letters to 10,000, b) 10,000 letters to 100,000 and c) 100,000 letters to complete the 1.08 million synthesized genome

The result marked the largest chemically synthesized genome ever assembled in the laboratory. Marvelously, on March 26 this year, the new “creature”, Mycoplasma mycoides JCV1-syn1.0 was “booted up” and became the first self-replicating cell created in a lab.

The authors noted (carefully) that the cytoplasm of the new cell is not synthetic, but rather the control mechanism – the controlling genome – is. This control is what provides the instructions for the new bacterium. The authors also point out, fairly and accurately, they did not “create life in a test tube” but rather transformed existing life into new life – albeit synthetic.

Now, here’s where skepticism enters: should humans even be playing around with the instructional genetics of bacteria? The authors, as usual for many genetic experiments (including those that seek to manufacture hybridomas, or mixed genetic life forms – like mice with human ears, or sheep with human eyes) justify it on the basis of some future possible benefits. In particular they cite (WSJ, May 26, p. A7) the increasing population and the lack of sufficient food, clean water etc.

But can a new synthetic bacteria solve such an immense problem? I seriously doubt it. What WILL solve it is the more widespread use of contraceptive technologies already available – like the pill, and diaphragm, as well as condoms. We need to employ any and every device to halt the unsustainable increase in human numbers beyond the carrying capacity – and adding to our global warming problems, as well as energy problems.

Beyond this, there is the risk, however small, that a new synthetic bacteria (or virus) can turn on its creators like a mini-Frankenstein. Could an innocuous bug like Mycoplasma mycoides then acquire vicious tendencies – like a new form of cholera? We don’t know, but do we want to find out? The specialists in genomics that put the synthetic bug together act and write as if they are privy to all the permutations and consequences of their monumental act, but are they? I argue we can never be certain – which is why ethical standards and regulations must be applied.

We don’t want to try to close the barn door after the cows escape if an unforeseen biological calamity emerges. Say along the lines of the horrific organism that decimated humans in the scfi film ‘Twelve Monkeys’!

[1] RNA has the same bases except for T (thymine) now replaced by U (uracil).

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