Henry Frankenstein: Look! It's moving. It's alive. It's alive... It's alive, it's moving, it's alive, it's alive, it's alive, it's alive, IT'S ALIVE!
Victor Moritz: Henry - In the name of God!
Henry Frankenstein: Oh, in the name of God! Now I know what it feels like to be God!
Henry Frankenstein: The brain you stole, Fritz. Think of it. The brain of a dead man waiting to live again in a body I made with my own hands!
Dr. Henry Frankenstein: The neck's broken. The brain is useless. We must find another brain.
Henry Frankenstein: Dangerous? Poor old Waldman. Have you never wanted to do anything that was dangerous? Where should we be if no one tried to find out what lies beyond? Have your never wanted to look beyond the clouds and the stars, or to know what causes the trees to bud? And what changes the darkness into light? But if you talk like that, people call you crazy. Well, if I could discover just one of these things, what eternity is, for example, I wouldn't care if they did think I was crazy.
Doctor Waldman: You have created a monster, and it will destroy you!
Artificial life is only months away, says biologist Craig Venter. “Artificial life will be created within four months, a controversial scientist has predicted. Craig Venter, who led a private project to sequence the human genome, told The Times that his team had cleared a critical hurdle to creating man-made organisms in a laboratory.
“Assuming we don’t make any errors, I think it should work and we should have the first synthetic species by the end of the year,” he said.
Well, Dr. Frankensteen, I mean Dr. Venter, just how close are you to creating artificial life?
The answer is: not very. And for Dr. Venter, as the Beatles wrote, “I get by with a little help from my friends”.
Not to disparage Dr. Venter’s accomplishments, but let’s just see what he’s talking about.
In 2007, Dr. Venter succeeded in replacing the genome of the bacteria Mycoplasma capricolum with that of a closely related species Mycoplasma mycoides, thereby changing one species into another. Not a trivial feat, but the virtually naked donor chromosome from Mycoplasma mycoides (almost pure DNA) was introduced into a whole Mycoplasma capricolum cell containing all of the cellular machinery (e.g. proteins, enzymes etc and a cell membrane). The Mycoplasma mycoides genome was then selected in the recipient Mycoplasma capricolum cells by virtue of an antibiotic resistance gene present on the donor chromosome which allowed for the selection and segregation of cells containing the Mycoplasma mycoides chromosome.
Using a series of specific primers in PCR amplification (Polymerase Chain Reaction), genomic sequencing and Southern blot analysis to verify only the presence of Mycoplasma mycoides DNA, the research group concluded that “the above results were all consistent with the hypothesis that we have successfully introduced M. mycoides LC genomes into M. capricolum followed by subsequent loss of the capricolum genome during antibiotic selection”.
However, as the authors acknowledge “We cannot rule out the possibility that small regions of the donor genomes recombined with identical regions of M. capricolum recipient cell genome; however, those regions would be very small.” Because both genomes are initially present immediately following the introduction of the donor DNA during the transplant process, any shared identical stretches of DNA can lead to homologous recombination. Therefore the creation of hybrid genomes must be considered in appropriate cases.
The bottom line here is that the cell membrane (and components) and cellular machinery of M. capricolum were required for this significant advance of species change.
Subsequently, Dr. Venter’s group succeeded in synthesizing the genome of Mycoplasma genitalium by introducing short synthetic fragments of the genome into the bacterium Escherichia coli for amplification and assembly into larger DNA sequences followed by a final genome amplification and assembly step in the yeast Saccharomyces cerevisiae. The use of short identifier sequences in intergenic regions (regions between genes) called watermarks allowed for rapid tracking of the designed sequence.
The resultant genome was confirmed to be that of the original designed Mycoplasma genitalium by shotgun DNA sequencing. Dr. Venter’s group relied on biological organisms to produce the complete genome which had originally been synthesized as independent, short synthetic DNA fragments.
Dr. Venter presumably aims to then replace the genome of a recipient cell with that of Mycoplasma genitalium, using a similar genome transplant process as used for the replacement of the M. capricolum genome.
If Dr. Venter’s claims that “Artificial life is only months away”, rests solely on the premise that DNA is the sole requirement for artificial life (“software creates the hardware” of life), he is ignoring the initial required contribution of the cell membrane/components and the intracellular machinery.
If Dr. Venter is referring to the synthesized M. genitalium genome as the guiding blueprint for artificial life, it must be pointed out though, that the designed genome is simply “a 582,970–base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection.” This is a nature designed genome.
The minimal genome essential for M. genitalium’s, or any organism’s, viability has not yet been established, Dr. Venter claims artificial life is only months away. I repeat, it is not yet known how many and what genes are required to form a minimal genome.
The purist would maintain that not until all of the required minimal components for life have been identified, isolated and assembled into a viable organism can the creation of artificial life said to have been achieved. Dr. Venter would say that this is a new artificial organism (assuming changes were incorporated into the synthesized genome) and that the software (artificially synthesized DNA) created the hardware; i.e., subsequently all other cellular components which are replaced during subsequent cell divisions.
However, any required epigenetic factors (changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence), would have been initially supplied by the recipient cell’s environment.
Furthermore, the time investment and financial cost of assembling large stretches of DNA by starting with short oligonucleotides to produce a genome is questionable. The conventional approaches of using DNA delivery systems such as viral vectors and/or directed recombination methods offer many advantages over whole genome replacement strategies.
If whole genome or chromosome replacements are desired, synthesized DNA stretches such as genes can be added to sequenced, cloned fragments of biological origin using current methods and then used in replacement strategies.
And lest we forget, a chemically synthesized somatostatin gene that produced somatostatin in E. coli was constructed at Genentech in 1977. The synthesis of somatostatin represented the first synthesis of a functional polypeptide product from a gene of chemically synthesized origin. Soon after this landmark achievement, a synthetic insulin gene was constructed at Genentech in 1978 and used to produce insulin in E. coli and a synthetic human insulin gene shown to produce insulin in yeast in 1983 Gene. 1983 Oct.; 24(2-3):289-97.
Dr. Venter’s work, while being a technical tour de force, is an extension of work accomplished thirty-two years ago.
None the less, Dr. Venter’s approach offers the ability to create a defined, manipulable platform to investigate designed systems. Using Dr. Venter’s or more conventional methods, the obvious targets of medical investigations, ecological applications etc., will pale before the inevitable queries of creating colonial life, tissues and finally complex organisms.