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The American geneticist and entrepreneur Craig Venter has announced that his team has succeeded in assembling an artificial genome from scratch and inserted it into the cell,which then took on the characteristics of the transferred genome and passed these on to its progeny.
Prof John Ward, Professor of Molecular Microbiology, University College London, said:
“This latest paper in Science builds on a series of previous high profile papers from this group and will probably be seen in the future as marking the point where Synthetic Biology came of age. The methods used in this work were in those previous papers and other groups will have already been using them to build complex, long DNA molecules. In the current work Craig Venter’s group finally manage to put the assembled genome back into a Mycoplasma host cell and create a synthetic genome that works inside a new host cell or ‘chassis’ as these bacterial hosts have become to be called in Synthetic Biology.
“It will be the start of many future applications where we might see cells built to make biofuels from sunlight and CO2 or clean up toxic waste or oil spills. New vaccines and diagnostics will also be the targets in the near future. The technology could be seen as incremental and several of the steps have been in the scientific literature for a while. But it does herald the start of the next age in society where the 21st Century will host the Biological Revolution.”
Sir Leszek Borysiewicz, Chief Executive of the Medical Research Council, said:
“The Medical Research Council commends Dr Venter’s achievement. To create a synthetic genome and then successfully combine it with an existing cell is a major technological triumph. This announcement holds up as a landmark in our ability to manipulate cells and offers great potential for the future; we are thrilled to see that the world is excited by the opportunities biological research can offer. It is vital, however, that we understand what has been accomplished here: by creating a synthetic genome, Dr Venter’s work is comparable to writing original software for a computer, but the process of creating ‘synthetic life’ or the ‘hardware’ of a cell remains a much greater challenge.”
Prof Sir Ian Wilmut, Director of the University of Edinburgh’s Centre for Regenerative Medicine, said:
“The authors have shown a great technical ability to modify an organism by introducing an entire genome in this way. This is an interesting step forward in our ability to breed organisms with specific and desirable abilities.
“Human beings have selected organisms with desirable abilities for our own use for many years. In this way yeasts have been modified to make them more suitable for beer, wine or bread production. In time this new research may make it possible to extend the range of purposes for which we are able to breed organisms dramatically and in ways that we cannot yet imagine.”
Dr Mark Downs, CEO, Society of Biology, said:
“This is a landmark in biological research. In the long term, it has the potential to bring many new business opportunities. The UK leads the world in many areas of life science research, and is well-placed to take up the opportunities that this exciting development offers.”
Prof Dek Woolfson, University of Bristol and Principal Investigator, BBSRC Synthetic Components Network, said:
“Craig Venter’s step forward is to show that genomes – the stuff that programmes natural cells and organisms – can be made chemically in the lab and then transplanted and ‘booted up’ in another cellular host. This could eventually allow the genes for the synthesis of drugs or biofuels to be smuggled into bacterial or yeast cells, which could then be made to produce these useful products. This is one end of synthetic biology that might be termed ‘genome engineering’.
“Other groups, including those in the UK, are working at understanding how we might design and engineer biological systems at the more-basic molecular level; e.g., can we make miniature motors out of proteins and other molecules from first principles? This is a very exciting time for the emerging field of Synthetic Biology, and the UK has a key role to play in it.
“The aim of Synthetic Biology is to design and engineer new biological building blocks that allow the reliable and predictable construction of biological or biologically inspired systems. In turn, these systems could be used to produce new biomaterials, biofuels, or drugs more cheaply, efficiently and in environmentally friendly ways.”
Prof David Delpy, Chief Executive of the Engineering and Physical Sciences Research Council (EPSRC), said:
“This latest announcement demonstrates the crucial role that engineering, chemistry, physics and maths play in driving forward developments in synthetic biology and that the range of UK research activities that we are supporting in this area will contribute to the advancement of this new technology.
“In synthetic biology we have a whole set of new possibilities to move from hypothesis to reality in areas as diverse as disease diagnosis, vaccines, fuel production or neutralising contaminants such as oil spills.
“EPSRC, together with BBSRC, have been mindful of the concerns that the public may have over what is a relatively new area of research, and from the outset have encouraged our researchers in the synthetic biology networks to actively consider the ethics of their work and discuss it with the public.”
Prof Julian Savulescu, Uehiro Chair in Practical Ethics and Uehiro Centre Director, University of Oxford, said:
“Venter is creaking open the most profound door in humanity’s history, potentially peeking into its destiny. He is not merely copying life artificially as Wilmut did or modifying it radically by genetic engineering. He is going towards the role of a god: creating artificial life that could never have existed naturally. Creating life from the ground up using basic building blocks. At the moment it is basic bacteria just capable of replicating. This is a step towards something much more controversial: creation of living beings with capacities and natures that could never have naturally evolved. The potential is in the far future, but real and significant: dealing with pollution, new energy sources, new forms of communication. But the risks are also unparalleled. We need new standards of safety evaluation for this kind of radical research and protections from military or terrorist misuse and abuse. These could be used in the future to make the most powerful bioweapons imaginable. The challenge is to eat the fruit without the worm.”
Dr Gos Micklem, Department of Genetics at the University of Cambridge, said:
“This is undoubtedly a landmark paper. The group has been building towards this step and, from their earlier published work, are leaders at synthesising and re-assembling large segments of DNA. There is already a wealth of simple, cheap, powerful and mature techniques for genetically engineering a range of organisms. Therefore, for the time being, this approach is unlikely to supplant existing methods for genetic engineering. DNA synthesis is rapidly becoming cheaper and so this could change, but not soon.
“The technique could potentially come into its own if one wanted to introduce a large number of changes into an existing genome. However making a system that works predictably after introducing a large number of changes is one of the design challenges of the young field of synthetic biology: in the general case it is a challenge that is unlikely to be solved soon.”
Prof Paul Freemont, Co-Director of the EPSRC Centre for Synthetic Biology at Imperial College London, said:
“The paper published in Science today by Craig Venter and colleagues is a landmark study that represents a major advance in synthetic biology. Venter and colleagues have for the first time demonstrated that a single genome of around 1 million base pairs can be chemically synthesised and assembled correctly and transplanted into a recipient cell. The step change advance, which has alluded them in previous publications, is that they have now demonstrated that the transplanted synthetic DNA can be ‘booted up’ to operate the functions of the new recipient cell in terms of replication and growth. Although the recipient cell is not man-made but is another natural cell, what Venter’s team have shown is that after transplantation and multiple cell divisions the recipient cell take son the characteristics or phenotype of the newly transplanted genome. (This is like taking a Mac computer operating systems and installing it onto a PC and the PC becoming a Mac computer.)
“This is a remarkable advance as it now provides a ‘proof of concept’ that we can chemically synthesise and assemble full genomes and transplant them into recipient cells, which after selection contain only the synthetic genome, and after rounds of cell division become a new and one might argue synthetic cell. The applications of this enabling technology are enormous and one might argue this is a key step in the industrialisation of synthetic biology leading to a new era of biotechnology.
“Of course one also needs to be cautious, as it is not clear if this approach will work for larger and more complex genomes or for transplantation in different bacterial cells. However, this is a landmark step in our abilities to manufacture man-made cells for man-made purposes.”
Additional information from Professor Freemont: In detail the paper describes the chemical synthesis and assembly of the 1.08Mbp genome of Mycoplasmamycoides. This organism is a small bacteria and lives as a parasite in cattle and goats. Mycoplasma lack cell walls, have no discernable shape and are the smallest (0.1 µM) known free-living life forms and are most likely to have evolved from Gram-positive bacteria. They are present in both animal and plant kingdoms and act as colonisers. The choice of Mycoplasma by the Venter group for genome synthesis and transplantation is based on the small size of the genome and for the mycoides species has a reasonably fast growth rate. The difficulties they report in terms of getting the synthetic genome booted up were due to a single base pair mutation in an essential gene (dnaA) which they noted after several attempts. Correcting this mutation allowed the synthetic genome to work properly, although its not clear how the mutation occurred – whether in the synthesis or assembly step. The transplantation process involves using an antibiotic selection process where the newly transplanted genomes infer resistance to the transplanted cell to live in the presence of a lethal antibiotic.
Prof Richard Kitney OBE, Co-Director of the EPSRC Centre for Synthetic Biology at Imperial College London & Fellow of the Royal Academy of Engineering, said:
“An important aspect of the paper is that the original natural genome was sequenced and the sequence sent in alphanumeric form to a company call Blue Heron near Seattle. They then synthesised the sequence in 1000 bp cassettes and sent back the biological material to Venter et al, who reconstructed the entire genome and checked for errors. The synthesised genome was then placed in a different natural cell and replication took place. After 2 or 3 generations the second cell population took on the characteristics of the first population (i.e. a different bacterium). The paper has major implications for the harnessing of biology for industrial purposes.”
Prof Douglas Kell, Chief Executive of the UK Biotechnology and Biological Sciences Research Council (BBSRC), said:
“The ability to do all of the steps of protein synthesis from genome to product in order to make something that has a useful application is an important step in developing the potential of synthetic biology.
“Synthetic biology is a relatively new field and within the global research community, including in the UK, there is some truly avant-garde science happening. Together with EPSRC and Sciencewise-ERC, BBSRC has recently been exploring the range of perspectives of the UK public on synthetic biology to ensure that the cutting edge research that is carried out in this field is supported by policies that reflect the views, concerns and aspirations of the people who fund it – the UK taxpayers.
“As we become technically better at doing synthetic biology, the potential applications open up. Mainly, what it will allow us to do is harness useful biological processes so that we can make the sorts of products that are difficult to synthesise with traditional chemistry and physics.”