Synthetic Biology

Can we discover how genomes are designed and how they function? Can we discover the minimal set of genes necessary for an organism to viably exist on earth? Can we design synthetic genomes to create organisms from scratch with specific purposes? Can we improve existing organisms to allow them to become even more useful to us? Can we resurrect extinct organisms? Tentative affirmative answers to such questions are beginning to arise from a new field, synthetic biology.

Clonings were early exercises. It has now become possible and even mundane to clone organisms from intact cells. Now the process is being extended to start with DNA itself together with a donor cell. Processes such as the Gibson method are now available to support industrial strength generation of DNA strands from component DNA segments.

‘Evolution machines’ are necessary to produce variation in DNA rapidly enough to do productive research. Harvard’s Multiplex Automated Genome Engineering (MAGE) device uses viral enzymes to facilitate homologous recombination in bacterial DNA. At Johns Hopkins, they use estrogen triggers inserted into yeast cells to scramble DNA. Such approaches to inducible evolution provide gene variation on demand.

New advances in computing, genetics, and synthetic chemistry are facilitating such research. By studying the many gene variants produced from evolution machines, an information base can be quickly assembled regarding dependencies in the genome, how the various parts relate to each other when supporting cell function. The ‘mistakes’ are as valuable as the ‘successes’ in identifying necessary conditions for cell viability.

Computer-generated synthetic chromosomes will be based on the information learned from random gene variation trials. Chromosome redesign has several objectives. First, it can enable us to eliminate any unneeded garbage DNA that accumulates over time in our chromosomes, a kind of evolutionary reset or normalization.  We can insert other DNA segments designed to assist in ‘instrumenting’ the chromosome, allowing external chemical monitoring and control. The yeast estrogen trigger above is an example of such synthetic chromosome design. We can also insert ‘improved’ genes to make ‘enhanced’ organisms more useful to our ecosystem’s needs

It will require substantial funding to get synthetic biology out of academia and into engineered solutions to our problems. Perhaps some good PR would help overcome public resistance to GMOs. How about a project to resurrect an extinct species? The movie Jurassic Park introduced us to the concept and made it immensely popular with the public. Science for the masses. It didn’t turn out so well in the film, but fact may prove less strange than fiction.

It will be a long, technology intensive process to achieve a de-extinction, defined by a viable organism. Major problems must be solved. How would we determine the criteria for species selection? The first selection would have to appeal to public sentiment to have any chance at funding. Cool factor must be evident. As far as benefit to man and the overall Earth ecology, that is not so important. It will be sold as a pilot project, a proof of concept and technology development platform. The benefits of synthetic biology to man will come from later, engineered-from scratch projects that cure disease, provide a stable climate, and heal the environment.

Once a show species is selected, defining the successful endpoint becomes an issue. Cloning from ancient reconstructed DNA is an inexact science; we have no complete genome to serve as a species model. We would hope to get close to the original, but how close is close enough? Once viability and ability to reproduce are demonstrated, it will be close. Then getting the behavior right will surely test our skills.

The next major issue is providing a supporting ecology. It has been observed that such a project is not really species resurrection, since we are likely creating a similar but new species that mimics the original. More truly, it is an ecosystem resurrection. Predicting how re-introduction will change the current ecology that others have come to depend on, modeling the effect to other organisms and their necessary resources, and calculating unintended social and biological costs, will test additional skills of biologists and ecologists.

One gene-splicing approach suggested is to genetically engineer offspring of an existing species that is genetically close to an extinct species. Thus the woolly mammoth could be created from its closest living relative, the existing Asian elephant, by inserting into the modern genome certain gene segments identified to reproduce specific traits of the extinct animal. For instance, fur and body fat could be added to enable tundra survival.

The argument against such a re-creation is that the Asian elephant is already headed for extinction. If we can’t keep them alive, what hope is there for a new elephantid species? In our hypothetical show case, though, it would be basically a proof of concept project with little expectation of an ongoing environmental project.

Beyond the science, we would do well to avoid other gotchas, the political roadblocks that have beset all re-wilding projects to date, the omnipresent problem of attracting funds in a zero-sum game. There will be resistance from conservationists who will challenge with the possibility that successful de-extinction will undermine our nascent conservationist mindset, substituting razzle-dazzle technology bandaids for conservative measures aimed at preventing future extinctions in the first place.

The passenger pigeon is another animal undergoing consideration for de-extinction. On the surface, it seems that neither pigeon nor mammoth is well-suited to our current ecosystem as they both require larger ranges than are readily available. It would be smart to get Russia on board since they may have the most available space.

Problems of bioethics, animal rights, patent law, biosecurity, and biosafety will need to be addressed in parallel. Already there are considerable attempts to limit synthetic biology to the laboratory alone, or even to prohibit it entirely. Sanity and reason alone will not prevail. Advocacy, marketing of benefits, corporate sponsors, and political capital will be required. Early courting of regulatory agencies such as the FDA and EPA would be productive.


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