Wednesday, July 28, 2010

Synthetic Life and the Delicateness of Life

"It shows you how accurate it has to be, one letter out of a million..." ~ Dr. Craig Venter

Many of you heard about the very impressive step that Craig Venter and his team at the J. Craig Venter Institute have made in the quest to create artificial life. It was in the headlines about two months ago. If you did not hear about it, just do a Google search for "A step to artificial life: Manmade DNA powers cell" and a good number of results from many different news agencies will come up. I have wanted to write about this incredible scientific advance for a while but have not been able to find the time until now.

The above statement by Dr. Venter, I think, has great implications for the design debate going on in the scientific community (though he probably did not mean for it to). I will get into that, but first I would like to summarize what he and his team did because it is very impressive work that should be applauded for it has almost limitless potential for possible agricultural, commercial, biomedical, and environmental applications.

First things first: what did Venter and his team do? They truly have created a cell completely powered by synthetic DNA and it was an achievement he and his team have been working on for the past fifteen years. What did they do? For the details one would have to have read the paper that was published in the journal Science, so allow me to break it down for you as best I can.

Let me start with a basic overview. In this research they were working with two different kinds of bacteria, Mycoplasma mycoides (M. mycoides) and Mycoplasma capricolum (M. capricolum). They chose these bacteria because of their relatively small genome size (about one million genetic letters which is about 1,000 genes) and the rapid growth rate of M. capricolum (less time wasted growing bacteria). First, they sequenced the entire genome of M. mycoides. A genome consists of many DNA molecules and the DNA molecules are a collection of genetic letters (abbreviated A, G, C, and T), which hold the genetic information about the organism. Sequencing a genome means determining the order of all the genetic letters, thus creating the "blueprint" for the organism. Second, they synthesized/created a synthetic version of the M. mycoides genome starting with the four basic chemicals of DNA (corresponding to the genetic letters). Third, they implanted the synthetic M. mycoides genome into a M. capricolum bacterium. That genome replaced the host's native genome and took over the operation of the bacterium, essentially changing the M. capricolum bacterium into a (synthetic) M. mycoides bacterium.

Even though I only described three major steps, the process is not simple at all. Allow me elaborate on some of the difficult points.
  • Sequencing the entire genome of M. mycoides, even a small genome like this one, is very difficult. They had to take the genome and fragment it (separate it into chunks) and then take each fragment and further fragment them until the whole genome was broken down into its individual letters. (A recent advance in graphene could potentially speed up this process considerably.)
  • Synthesizing the genome is even more difficult. They essentially did the above process in reverse. They created small fragments (about 1,000 genetic letters) of the genome, took those fragments and put them together to make larger fragments, then took those larger fragments, and so forth until they had a complete genome. To do this they needed a very good strategy. They looked at the entire sequence (all one million letters), determined the best points to break it up into 1,000-letter fragments, made sure the fragments overlapped slightly (so they could piece them together), and then started creating the fragments and assembling them. To assemble the fragments they used yeast as a kind of "factory" to combine sets of ten 1,000-letter fragments into fragments of 10,000 genetic letters, then combine those 10,000-letter fragments into 100,000-letter fragments, and then, finally, combine those into the one million-letter genome. (Using the yeast as a "factory" is far more complicated than what I just explained because they had to incorporate DNA sequences that caused the yeast to recognize the DNA as its own and they had to do this without altering the M. mycoides genome. They also had to introduce DNA sequences to allow them to do quality control checks after every step to make sure each stage was executed without error.) This is an incredibly ingenious, complicated, and delicate strategy for synthesizing DNA sequences.
  • Their strategy for implanting the synthetic genome into a M. capricolum bacterium was equally ingenious and difficult. One of the big hurdles were enzymes known as restriction endonucleases (RE). These are enzymes found in bacteria and archaea that serve as a defense mechanism against the introduction foreign DNA into the cells of the organism (which is exactly what Venter's team was trying to do). These enzymes cleave to specific locations of the DNA helix and cut the DNA at those locations, destroying the foreign DNA. One might then ask, "What about the natural DNA in the host organism? Why is it not destroyed?" Well, natural DNA has a protection system against the RE called the methylase system. This system "methylates" the host's natural DNA by adding a modification enzyme to the RE cleavage sites, which protects it from the RE. In order to get around this, Venter's team developed a strain of M. capricolum with the RE disabled, thus making the M. capricolum susceptible to the (foreign) M. mycoides genome they needed to implant. Then, after implanting it, the synthetic M. mycoides genome produced its own RE that destroyed the host's M. capricolum genome, thus allowing the M. mycoides genome to take over the operation of the M. capricolum bacterium completely. This transformed the M. capricolum bacterium into a synthetic M. mycoides bacterium, which was able to grow into a whole colony of synthetic bacteria.
Even if you got lost in the above explanation, you probably are beginning to realize now how incredibly complicated and difficult this scientific advance was. It took dozens of scientists fifteen years to be able to get this far and there were many setbacks along the way. One setback, the one Venter was commenting on in the above quote, was the result of a mutation (a "typo") that altered one genetic letter out of the million-letter genome. This typo set them back several weeks and completely disabled their synthetic M. capricolum bacterium. The mutation of one genetic letter out of a million caused the organism to be unable to operate and die.
    What does mean for the design debate (I mentioned this in the very beginning of this post)? 
    1. This advancement shows how complicated and delicate life is and that the work of an incredibly intelligent mind (or a team of incredibly intelligent minds, in this case) is required in order for life to originate. It has shown empirically that to transform life (representing the evolutionary process) or to create life from scratch (representing the origins of life process) requires the intervention of an intelligent agent (if one genetic letter is wrong, as mentioned above, the whole genome is useless). Work like this does not eliminate a need for God; quite the opposite, for it demonstrates how precarious life is and that God is required for life. 
    2. This work also demonstrates life's minimum complexity and shows that, even in its lowest possible state, life is extremely complex (far more complex than any naturalistic evolutionary model can account for). 
    3. This work creates a completely new category of arguments for design in the universe. The already existing categories of arguments made by scientists that support design are the following: 1) inference to the best explanation, which basically looks at all the models that could account for life and seeks to show that the naturalistic evolutionary models are inferior in their explanation of the facts and 2) argument from design, which basically looks at the apparent design in the universe, notes the similarities to independent human designs, and then argues by analogy that life must be designed. This work introduces a third form of argumentation, which argues that we know now from empirical experience that the making of life requires intelligent ingenuity.
    From my Christian point of view this work is very exciting not only because is it just really cool science, not only because it opens up science to a not-too-far-off world of possible applications (bacteria that can create hydrogen for clean fuel, bacteria that can create cheap pharmaceuticals, or even bacteria that can consume oil), but also because it shows in a compelling way, I think, that life requires a Mind--Intelligent Designer--to exist and cannot be the result of random, natural processes. 

    By His Grace,
    Taylor

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