World conquest at 39 cents a base

Pssst. Want to conquer the world? I can tell you how and it will only cost you 39 cents a base.

But first some background.

Recombinant DNA launched the Biotechnology revolution in the 1970’s. There were three key methods. The first involved making many copies of DNA by placing small portions of a DNA molecule in plasmids (small bits of circular DNA that live inside of bacteria). Since the plasmids duplicate themselves inside the bacteria and the bacteria reproduce themselves at tremendous rates, the artificial DNA introduced by a scientist would get copied many times. It could then be purified away from the bacteria and used in many ways. The second key technology was the use of restriction enzymes. Since only small segments of DNA could be manipulated, it was necessary to chop up the original DNA into pieces. Restriction enzymes recognise and cut DNA at specific sequences. Thus, specific segments of DNA could be obtained by cutting the original DNA with the appropriate restriction enzymes. The third key technology was the ligase. This enzyme allowed investigators to recombine different segments of DNA in many ways. This final step allowed scientists to create DNA molecules that had never existed before. For example, the gene that makes a jellyfish glow green at night could be attached to a mammalian promoter (a gene “on” switch) to study what causes genes to be expressed under different conditions.

The scientists who developed these techniques immediately realised their power – and potential danger. They all agreed to immediately halt experiments until a set of standards could be determined to allow the safe use of the new technology. The Asilomar Conference on Recombinant DNA was held in 1975. At this meeting, a set of principles was developed to ensure the safe use of recombinant DNA. Work was then resumed, and the Biotechnology boom began. Many benefits to mankind resulted from the development of this technology. Among these include safer forms of insulin for diabetics.

The next major biotechnology breakthrough was the discovery of PCR. This technique allowed investigators to duplicate DNA in a machine, called a thermocycler, rather than relying on plasmids and bacteria. Although PCR was far more convenient than previous methods, it did not introduce any major changes in terms of what sort of genes could be created.

The most recent biotechnological development is gene synthesis, and this is a world-changer, for good or evil. There is no clear date when we can say that this technology was invented. As far back as the 1970s, it was possible to chemically synthesise oligonucleotides, short (10 – 30 bases) bits of DNA. These were useful as tools, for example as PCR primers, but would not be considered genes. Over time, the technology for synthesising longer and longer stretches of nucleotides evolved. This has involved a variety of different techniques. Until recently, use of such techniques has required considerable and specialised skills. Today, however, there are a plethora of companies which will produce genes thousands of bases long to your exact specifications, for 39 cents a base. What a deal!

How can you use this service?

Here is some promotional material from one company involved in DNA synthesis (DNA 2.0):

Unlike nature, any sequence you can imagine is available with a synthetic gene. Synthetic genes provide an immediate and easy path from virtual sequences to physical DNA, offering a cost-effective way for research that wouldn’t be possible or feasible relying on existing DNA sequences.

What this means is that we are no longer limited to recombining DNA from nature. If we can think it, we can make it. I have been using recombinant DNA and PCR for decades, and I still can’t believe that de novo gene synthesis has become possible in my lifetime. This technology is almost certain to result in better understanding and treatments for many diseases.

And, unfortunately, it is also likely to be used for great evil.

You see, anyone with access to this technology can now resuscitate any virus for which the sequence has been made public (which includes smallpox and the 1918 flu virus). In addition, entirely new viruses with new properties can be created for a pittance. And no-one need know that the virus was created in a laboratory. The viruses created in this way will look and act like totally natural viruses. There will be no way to distinguish them. Although it was possible to use recombinant DNA technology to create artificial viruses, these were readily identifiable by the presence of restriction sites (the sequences used by restriction enzymes). Gene synthesis leaves no such telltale clue.

I am not the only one to be concerned about the potential misuse of gene synthesis. On May 11, 1995, J. Craig Venter (one of the pioneers of genome sequencing and synthetic genes) warned Congress of the potential for misuse of this technology (S. Hrg. 109-131, Twenty-First Century Biological Threats). Although there have been some attempts to regulate this technology, these are on the order of attempting to close the barn door after the horse is out: the government is requesting that companies that make genes let them know if anyone orders smallpox. Well, OK, that’s probably a good idea. However, the machines and associated technology are not controlled by American companies. Most of the gene synthesis companies are not located in the US. In fact, lots of them are in China. We should consider the possibility that the Chinese government has a different idea about what should or should not be done with this technology than the US government does.

What could a government with this technology do? Well, they could make, and test, an influenza virus with whatever properties they wanted. They could study all of the different flu viruses known to man and combine sequences however they wished. They could create new sequences never seen before in any flu virus. They could create a mild strain. They could create a severe strain. They could create strains susceptible to Tamiflu. They could create strains resistant to Tamiflu. They could release some or all of these strains in whatever combination they wanted, whenever they wanted, wherever they wanted. And no-one could prove it. No fingerprints.

If you want to conquer the world, you can do it for 39 cents a base. I just told you how.

References:

Smith et al. (2003) Generating a synthetic genome by whole genome assembly: φX174 bacteriophage from synthetic oligonucleotides. Proceedings of the National Academy of Sciences 100: 15440-15445.

Wimmer (2006) The test-tube synthesis of a chemical called poliovirus: The simple synthesis of a virus has far-reaching societal implications. EMBO Rep. 7(SI): S3–S9.

Chemical and Biological Weapons – China Special Weapons. Federation of American Scientists.