The Modern Frankenstein - Making Life Anew?

A study first disclosed on March 27th 2014 discusses the results of a new experiment undertaken at New York university in which researchers created for the first time a synthetic chromosome from a eukaryotic organism - a common yeast. The chromosome represented a drastically altered form of the yeast genome as compared to the natural form of yeast though it contained the same essential genes, and despite this drastic alteration the authors stated that this de novo yeast grew just as well as its natural forbears. This marks the first time that an artificial chromosome of this size has been generated, and the implications both for scientific purposes and philosophical musings are profound, making it important that the public understand just what this chromosome is and what it is not. Some would claim that this is an example of scientists overreaching the natural bounds of the world and violating the sanctity of nature, while others no doubt have fears that this sort of technology could be used to generate new diseases or might be extended to human research. This article aims to give a brief rundown of what this new study has done, how it did it, and what it found out in the interest of educating the public about this new breakthrough.

Artifice and Life

Your genome is the essential genetic material that determines your most essential heritable traits, and is composed of the DNA that makes you who you are, at least at a molecular level. While our understanding of genetics and alternative DNA modifications may have advanced over the years (indeed, studies now suggest that certain information can be etched into your DNA even without altering the genetic code), your DNA is still essential to your life. Extensive DNA damage as might occur in someone exposed to a carcinogenic compound or harsh radiation leads to the death of many exposed cells, and can lead to cancer in surviving cells. In short, DNA is essential and any modification to it has the potential to modify your own personal identity at a cellular and molecular level. In all organisms, the genome is organized into units called chromosomes, which are organized segments of DNA that condense your genetic information in a compact form that allows it to fit within your cells. Humans have 23 chromosomes, while bacteria or yeast have only a single chromosome. Even though your genome will have unique mutations as compared to the person next to you, your chromosomes will still be structurally virtually identical and all of the same genes will be located in the same location. This ordered organization ensures that genetic information can be stored and transmitted in an orderly fashion which is essential for any species to survive, especially if that species reproduces sexually.

Ever since we as a species first understood that our DNA held something of a blueprint for life, there has been a question of whether life could be newly created simply by generating new DNA that would match such a life form. For decades now, scientists have been modifying the genomes of experimental organisms in the lab, from yeast to flies to mice. These mutations generally only targeted individual genes, never the entire genome, and indeed until recently the technology simply did not exist to generate enough DNA to make a de novo genome. That all changed when a team of scientists headed by Craig Venter produced the first synthetic life form in the laboratory several years ago. The organisms was a bacteria with a relatively simple genome belonging tentatively to the family Mycoplasma. Despite the relative simplicity of the bacterial genome, it still took $40 million and several years to produce this synthetic life form, and in the end it was still largely modified after existing Mycoplasma rather than being an entirely new organism. In this sense, it was not an entirely synthetic organism so much as it was a modified copy of an organism that already existed. This is no less of an accomplishment however, and to date no one has ever attempted to create an entirely new and unprecedented form of life, as doing so would prove very difficult without a more advanced understanding of genetics and of life in general.

As compared to a Mycoplasma, a yeast is a huge organism with a massively complex genome, even though relative to a human a yeast is itself an organism of extreme simplicity. Indeed, there is an economy of scale to these synthetic life form studies, and it still took the latest group of researchers seven years from the time they began producing their new life form to the release of the paper in the journal Science this week. While the technology to create an artificial yeast chromosome was believed to exist, it would have taken decades for a traditionally sized lab to do as each step required the synthesis of small fragments of DNA which had to them be amplified and linked together in a process that took weeks to generate individual genes. In order to speed up this project, the researchers at New York University formed a class for students interested in building a genome - students that are now authors on this prestigious Science paper. These students were each given segments of the yeast genome which they would learn to create and would subsequently synthesize. By massively expanding the number of workers on this project, the research team was able to decrease a decade's long process into an experiment that took a relatively small number of years (though it still required inordinate amounts of money).

As the new yeast was being synthesized, the researchers decided to modify the genome rather than directly copy that of the naturally occurring yeast. The researchers omitted certain elements from the yeast in order to ensure that it could not replicate outside of the lab, and they further removed certain parts of the genome that can spontaneously move around as they had the potential to disrupt their synthetic life form before it had a chance to thrive. They also chose to shuffle around the genes within the organism. Despite all of this shuffling and these gene deletions, they were able to successfully create a synthetic yeast chromosome, and the yeast carrying this chromosome were indeed able to survive and thrive just as well as their wild type counterparts in the laboratory conditions where they were provided with the nutrients for which they were (intentionally) genetically deficient. The experiment was a success, and as a result this new synthetic yeast represents the most complex synthetic chromosome ever created demonstrating the great potential that synthetic biology may hold for the future, though this potential is ominous for some who have ethical qualms about humans playing god over new forms of life.

The Ethical Quandary of Creating Life

From a scientific perspective, these efforts in synthetic biology are an unprecedented breakthrough. In the long term, people hope to be able to use these synthetic generation techniques for both research and practical purposes. For researchers, the ability to fully design the organism that they are studying would hold immense promise as it would create a much more controlled environment that would allow for more robust experimentation and better experimental results. If researchers wanted to study how a particular gene affected a particular cellular process that was normally controlled by many genes in a wild yeast, for example, then they could simply design a new yeast that lacks the interfering genes so that they could then study only the gene they were interested in. For more immediate practical use, synthetic bacteria might be engineered that have specific desirable activity. For example, if researchers were able to create a microbe that was able to metabolize petroleum or plastic then they would be able to use these new life forms to clean up oil spills or degrade the waste in landfills, which are currently issues that lack a readily available scientific solution.

Despite the great promise held by synthetic biology, there is resistance to this new form of science and this resistance tends to come in either (or both) of two main forms. The first such form is a broad ethical concern about the morality of creating life. These individuals feel that it is not acceptable for humans to “play god” in this manner, and that in doing so we are transgressing against the very nature of nature itself. This artifice takes away from the sanctity of life for these individuals, and as such it is difficult to justify these experiments to them. Indeed, if someone believes that these experiments are fundamentally wrong then it is unlikely that and amount of scientific evidence will be able to persuade them that synthetic biology is a powerful form of future technology. Indeed, this si something of an ethical gray area in the sense that it represents the first time that we as a species have ever had the power to newly create a life form. At present, of course, we can only create organisms that are closely based on the life forms they mimic as in the case of these Mycoplasma and yeast. Life simply serves as a template for artifice, as in the case of Frankenstein's creation. In the future, however, there si the potential that we will be able to create entirely new forms of life that do not currently exist in any shape or form on this Earth. It is perhaps this potential future power to generate genomes that do not mesh with those found in a natural world that people along these lines of objection find most horrifying. We would, in essence, be literally playing god by creating an entirely unique and new form of life.

For the immediate future there is no chance that researchers would be able to generate the genome of a complex multi celled life form like a lab mouse or a human. For one, our genomes are massive compared to the 300 thousand base pair yeast genome, and the DNA we carry is split among several chromosomes all of which would need to be individually created and inserted into an acceptable cell without any damaging errors. Secondly, we have many additional modifications to our DNA in the form of proteins and markers on the DNA itself that are essential to its normal storage and function, and at present we have no way to generate complexes of these proteins and markers with the DNA which would be necessary to create a synthetic mammal, whereas these are not issues in yeast or simpler life forms such as bacteria. Even if we could create new forms of life, of course, it is uncertain if this would ever be considered sufficiently ethical to attempt in any complex organism that is subject to rules regarding laboratory treatment and ethical research considerations. For the near future it is far more likely that scientists will continue with their more standard techniques of breeding mice with targeted gene mutations that enable researchers to address fairly specific questions, though they do not have the precision of a fully designed organism.

The second camp of individuals that are opposed to synthetic biology have certain more palpable and immediate concerns about the ability to create life. Specifically, they worry that this technology is so powerful that it could readily be misused by people with access to the right equipment in order to create dangerous forms of life. For example, with this technology it is likely that someone with access to the genetic sequences of Smallpox would be able to create the smallpox genome. If they were then able to get that genome to be expressed in a cell, they would be able to produce new particles of smallpox virus that would have the potential to devastate the human population. It is very unlikely that any rogue scientist or terrorist group would ever be able to obtain the millions of dollars, years of time, or expensive equipment necessary to undertake such a malicious activity. It is still technically a risk that could be realized by an ill meaning government, although at present there is no reason to believe that anyone is working on such a project. For these reasons, there is currently no released version of the smallpox genome even though the technology to sequence it is readily available.

Of course, it might not be necessary to have access to smallpox itself in order to create a new synthetic and lethal virus. Smallpox has several extant related viruses such as Cowpox (which is used as the smallpox vaccine) that could be used as a template to try to generate a new smallpox virus through genetic engineering. Even though these techniques are theoretically possible, there is no evidence to suggest that they could ever be conducted with success. Similarly there is no reason to believe that anyone is working on such a project or indeed that anyone would want to do something like this which would devastate the world's populations without mercy. There is nothing more to fear here than there is from terroristic organizations that try to weaponize diseases such as anthrax. Indeed, weaponizing diseases that already exist is far easier than trying to create new ones, and as such at present there is no significant threat of synthetic diseases become a weapon of choice for any group. It is also worth noting that the yeast in these experiments are not wholly synthetic - the chromosome still needs to be inserted into a cell in order to begin its replication. As such, we are not able to fully generate life at this point, we are just able to synthesize the genetic code that must be places into its vital shell in order to be useful.

Conclusion

In summary, this new breakthrough in synthetic biology is monumental in that it represents the first time a chromosome of a eukaryotic organism (that is, a cell that has a nucleus and other complex parts) has ever been generated synthetically. This has profound implications for the future of synthetic and genetic biology and will no doubt prove to be a powerful tool both in the lab and in society as a whole. Despite this promise, this is a technology that will always be controversial because at its core it involves a process that many find appalling - the creation of new forms of life. For some, this concern is ethical or moral with fears of our own self deification, and for these people there will be no readily available way to allay their concerns as they are of a philosophical rather than practical nature. For others, this is a question of safety and efficacy as there are concerns that synthetic organisms might be generated that could harm the human populace. These concerns are reasonable, however at present there is no significant risk as the cost and difficulty of carrying out such an impractical project would be immense and would discourage such activities. Instead, we should look to the future of synthetic biology with cautious optimism, in hopes that it will be able to generate organisms that have the potential to solve some of our biggest issues as a species without crossing some moral threshold regarding the sanctity of life.

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