It’s easy to forget in this super-sized world just how incredibly detailed and complex our planet is. Even the tiniest bacterial cell is a “veritable microminiaturized factory containing thousands of exquisitely designed pieces of intricate molecular machinery, made up altogether of 100 thousand million atoms, far more complicated than any machine built by man and absolutely without parallel in the non-living world”! [1]
The numbers continue to boggle: 100 million proteins of 20,000 different types in every living cell; the human genome is 3.5 billion letters long; the length of DNA in the human body, if uncoiled and stretched out would measure 20 trillion metres!
With these fathomless numbers in mind, it is impressive to think that we have begun to be able to design biological systems and living organisms – artificial life. In this new science known as Synthetic Biology which builds on molecular biology, engineering principles are being combined with gene sequencing and synthesis. In 2007 the American Journal of Tropical Medicine and Hygiene a study was published reporting how a collaboration of scientists had succeeded in making semi-synthetic artemisinin, a drug used for the treatment of malaria [2]. The motivation was the cost of the naturally occurring drug. Artemisinin is found naturally in the wormwood plant but is costly to chemically synthesise or harvest. So with funding from the Bill and Melinda Gates Foundation (the average cost of producing a new medicine is $800m [3]) a team from One World Health, Berkeley Center for Synthetic Biology and Amyris Biotechnologies set about trying to reproduce it in the lab.
By elucidating the metabolic pathway in the wormwood plant [Artemisia Annua] and identifying the genes required to make artemisinic acid, they then inserted this pathway into microorganisms and optimized the resulting microbial strains for commercial production of the precursor acid through fermentation. Although genetically engineered microorganisms have been used to produce recombinant protein compounds such as vitamins and antibiotics through industrial fermentation for years, this collaboration has pioneered the production of small molecule drugs. Prof Jay Keasling was at the centre of this achievement and described the bacterial factory process as ‘how to engineer a cell to do the kinds of chemistries that you want it to do’ [4].
Synthetic Biology is a nascent science, but it was named by the highly regarded Massachusets Institute of Technology [MIT] in 2005 as one of its top 10 emerging technologies, such is the potential of the subject [5]. And with its aims of producing entirely artificial molecules and cells, the ethical and policy ramifications are huge.
As if to prove the point, Professor Eckard Wimmer of Stoney Brook University, NY, managed to synthesize the polio virus in his lab in 2002 [6]. It was the first time a virus [which are not considered ‘live’ but which can self-replicate] had been created artificially. As a scientific achievement this was significant, but as Dr Wimmer pointed out himself, the fact that they had done this using only a genetic blueprint from the Internet as a guide and mail-order, tailor-made genetic sequences from a laboratory supply service to assemble the deadly virus, was shocking.
"One has to be aware that humans can recreate a virus," Wimmer said, "even if you think it's not around anymore…Now people have to take it seriously. Progress in biomedical research has its benefits and it has its down side. There is a danger inherent to progress in sciences. This is a new reality, a new consideration." [7]
So while true artificial life is still a synthetic biologist’s dream, we already have the reality of in one laboratory a life saving component of a much needed medication being engineered while in another the spectre of biochemists re-creating deadly viruses. The uncontrolled release of the latter by bioterrorists is a real danger of which both scientists and governments are aware, but no policy consensus has been reached.
Another ethical dilemma which has been raised is that of patenting. The writer Michael Crichton, having researched and written his novel ‘Next’, ended his book with several conclusions as a result of his future-gene-world-gazing. One of these was the outlawing of genetic patents. There are already 3 million gene patents [8] filed with the US Patent Office by companies wanting to claim the intellectual property rights of their genetic sequence ‘discovery’. Crichton argues that because genes are facts of nature, a gene patent becomes an ‘undeserved monopoly’ which inhibits creation and productivity, hurt patient care and suppress research. This was ably demonstrated by the delay of research into SARS [9], [10], due to three simultaneous patent claims being filed. If a patent is granted for a gene sequence that turns out to be fundamental to the discovery of a cancer vaccine, will the whole world be held to ransom for the 20 year patent duration?
But no matter how far off it is, the biggest ethical concern is the creation of artificial life itself. Most of us have long been familiar with other life forms through popular and diverse science fiction books and films. However the fiction of artificial life is fading. We are not at the point of having to put Turing’s Test to the test [where a machine is considered alive when it fools a person into thinking, based on its conversational skills, that it is human] as we are not talking about artificial cells demonstrating intelligence. But we are being faced with an unparalleled situation. With all the evidence of irreducible complexity and an ever expanding universe pointing to a creative source for all matter, should we be dabbling in the province of God?
Despite some saying that Craig Ventor, who is a leading pioneer in genomic research and who has made progress in the formation of a synthetic bacterial genome [11], means that ‘God has competition’, the reality is that Ventor is simply ‘photocopying’ the original blueprint. No new living organism is being created if all we are doing is ‘cut and pasting’. However we do need to be asking ‘why’ and ‘what happens’ if the new arrangement turns out to be catastrophic to the environment. The production of a rare and costly substance to save lives is noble, but why are we pursuing the creation of unpredictable microorganisms? If it’s been known for years that we can now produce deadly viruses in a test tube, what is being done to combat this? The repercussions of inaction could be momentous. The challenge is for leaders to introduce a societal debate on the ethics and purpose of Synthetic Biology and urgent discussions about necessary regulatory framework.
At 2020health.org we are involved the work of engaging with scientists and politicians in order to consider and debate the policy implications of all emerging technologies for health including Synthetic Biology. This is no mean task, not only due to scope and convergence of technologies, but also because it is a global concern. Nevertheless, we will be publishing the first of our reports in January 2009.
Julia Manning
Director
Julia@2020health.org
2020health.org is a centre-right think tank for health and social care. We want to change the way health is delivered by promoting real partnership between patients, professionals, government and the private sector to achieve the highest quality and productivity in care.
[1] Evolution – A Theory on Crisis p250, Quoted by John C. Lennox in God’s Undertaker has science buried God?
[2] http://www.ajtmh.org/cgi/content/abstract/77/6_Suppl/198 [accessed 9.9.08] Microbially Derived Artemisinin: A Biotechnology Solution to the Global Problem of Access to Affordable Antimalarial Drugs
[3] DiMasi JA, Hansen RW, Grabowski HG, 2003. The price ofinnovation: new estimates of drug development costs. J Health Econ 22: 151–185.
[4] http://www.technologyreview.com/read_article.aspx?ch=infotech&sc=&id=14407&pg=7 [accessed 9.9.08]
[5] Ibid iv
[6] http://www.sciencemag.org/cgi/content/short/320/5884/1784 [accessed 9.9.08] Virus Attenuation by Genome-Scale Changes in Codon Pair Bias
[7] http://www.geocities.com/giantfideli/cellnews_dangerous_virus_made_from_mail-order_kits.html [accessed 9.9.08]
[8] http://www.ornl.gov/sci/techresources/Human_Genome/elsi/patents.shtml [accessed 9.9.08]
[9] http://genomebiology.com/researchnews/default.asp?arx_id=gb-spotlight-20030512-01 [accessed 9.9.08]
[10] Preemptive SARS patents Bulletin of the World Health Organization
Print ISSN 0042-9686 Managing severe acute respiratory syndrome (SARS) intellectual property rights: the possible role of patent poolinghttp://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862005000900017&nrm=iso&tlng=pt [accessed 9.9.08]
[11] http://www.jcvi.org/cms/research/groups/microbial-environmental-genomics/ [accessed 9.9.08]
