Creating Life from Four Bottles of Chemicals?

THE publication of a claim that scientists have created “life” from “four bottles of chemicals” in the American journal, Science, has attracted considerable attention. Reactions have been varied, with one commentator even hailing it as “one of the most important scientific achievements in the history of mankind”. Others have been more muted and many researchers in the field of biotechnology have questioned whether it is appropriate to claim that “life” had actually been “created” in a laboratory. Many other reactions have come in from religious groups decrying “man’s attempt to play God” and from those raising concerns that the release of “synthetic” organisms pose a threat to nature.

CRAIG VENTER: BIO-ENTERPRENEUR ICON

Perhaps the publicity around the claim would have been less extragavant if at the centre of it there was not a person called Craig Venter. A larger than life figure in the field of biotechnology, Craig Venter has been described by one commentator as a “bio-enterpreneur icon”. It is an accurate description, for Venter is better known as an enterpreneur working in the field of science, rather than as a person working at the cutting edge of science. So, while analysing the very important claim that Venter makes, his persona and past history needs to be factored in.

In 2001, Venter was in the centre of another widely reported event – the mapping of the human genome. The unveiling of the map of the human genome was greeted with the accolades that it deserved. But, for the first time in the history of science, the details of such a pathbreaking event was published separately by two different sets of scientists in two different journals! The two sets of scientists represent, respectively, the public funded Human Genome project, and a private company called Celera Genomics. Celera Genomics was a company that Craig Venter had started in 1996. The former published its results in the journal Nature, and the latter in the journal Science (the same, incidentally that has now published Venter’s recent work!).

The story of the human genome project provides us clues about how Craig Venter sees science and its utility. He left the premier public funded research institute in the US — the National Institute of Health (NIH) — in 1991 because he wanted the institute to patent individual genes that were then being discovered, in the early days of the human genome project. His biggest opponent at that time was James Watson, part of the Watson and Crick duo who first explained the structure of DNA – the basic building block of life that makes up the genome of any living organism. Watson is famously know to have said at that time that the patenting scheme was “sheer lunacy” and that “virtually any monkey” could do what Venter’s group was doing. In 2001, the public funded Human Genome project (in which many countries including India collaborated) published its data at the same time that Celera Genomics did. Many commented that this had saved science from a huge disaster — because if Craig Venter had been the first to publish he would have made sure that the information available through the decoding of the human genome would have been locked in by thousands on thousands of privately held Patents.

WAS LIFE REALLY CREATED?

Let us fast forward to 2010 and examine what Craig Venter and his team have achieved. Venter claims that his team has created life from four bottles of chemicals. Let us try to understand what was actually done. Venter’s team first analysed the entire genome of a single-cell bacterium called Mycoplasma mycoide. This was a huge exercise, which took about 15 years, cost $40 million and required 25 researchers to accomplish. The genome is the portion of any living cell (bacteria are single celled organism but complex organisms such as humans are made up of by millions of cells with specialised functions) that contains the code that tells the cell how it should function. The code is written into the genome by millions of permutations and combinations of four basic sugar molecules – in bacteria these sugar molecules are adenine, guanine, cytosine and thymine. In the case of the Mycoplasma mycoidegenome that Venter’s team worked with, over a million bits of code (1.08 million bits to be exact) in the bacterium’s genome was recorded in a computer. Exact copies of each bit of code was then synthesised artificially and assembled together by techniques that are now available. To differentiate the genome from a naturally existing one, “watermarks” were added – a few sequences that do not have any useful code written into them but were a form of signature added by the team to stamp their ownership over the synthetic genome. The final step involved the transplanting of the synthetic Mycoplasma mycoides genome into recipient cells of a related bacteria (Mycoplasma capricolum). To ensure that the recipient cell did not reject the newly inserted genome a gene responsible for producing a “restriction” enzyme in the recipient cell had to be inactivated. To put it in Venter’s own words, “on March 26, the synthetic genome was “booted up” — and it worked! The new bacterium started doing what bacteria do best – i.e. it started replicating and making copies of its own self.

Can we say that Craig Venter’s team actually “created” life? If we cut through the hype of newspaper reports, the answer is no. What the team of scientists did was not insubstantial, but they definitely did not create life. They diligently copied millions of instructions in an existing bacterium and then inserted these instructions into another existing cell. There should be no hesitation in accepting that it was a huge computational exercise. But it was just that and no more. The team blindly copied the code without any means to know what each bit of code actually meant. It was like making an exact copy of the Mona Lisa on a different canvas, without the copier being able to claim that he had been transformed into Leonardo Da Vinci. For while the copier could claim to have made an exact copy, unlike Da Vinci he would still not have acquired the knowledge of how each brush stroke would blend into the next. In other words, he would not know how to make another masterpiece on his own. The same is true for Venter’s team. If they do not have an existing genome to copy from, they cannot create another synthetic genome.

The above does not imply that sometime in the future we shall not have the knowledge and the technique to really create life from first principles. What it does, however, show is how far away we still are from being able to do so. For, in order to do so, we would need to know exactly what each of the over a million codes in the genome does. Only then can we create the bits, knowing their functions, and then assembling them to create an artificial organism whose functions and characteristics we would have defined. Remember that here we are discussing the synthesis of the most primitive one-celled form of life. Imagine how much more complex it would be to attempt to synthesise multi-celled living beings which can each have millions of cells, each with millions of buts of code. Hence it is mere speculation to infer that Venter’s accomplishments would lead to the synthesis of a wide range of useful products such as bacteria to tackle oil spills or to produce medicines.

In some ways recombinant technologies used to create genetically modified organisms (GMOs), where the genetic code of useful characteristics of one organism are identified and then inserted into another organism, is much nearer to the process of creating an entire new organism. Today this technology is still very primitive, and we are barely able to use it to identify, extract and insert one or a few (among millions) characteristics.

UTILITY OF & CONTROL OVER SCIENCE

Let us turn to the real issues that need to be addressed in the wake of what Venter’s team has accomplished. There have been the usual “knee jerk” reactions about the need to stop “messing” with nature and the need to restrict research in areas about the consequences of which we do not know enough. Such doomsday prophecies have two problems. While we have started “messing” with nature at the cellular level only recently, we have been doing so for the last hundreds of thousand of years – ever since the human species left the trees and started changing nature to suit its needs. Settled agriculture, urbanisation, industrialisation, etc., have been changing much of nature as it existed for centuries and more. Yes, we are reaping the consequences of some of our actions – as best evident from the looming climate crisis. But does the answer to that lie in our going back to living in the wild and foraging for roots and berries? We would argue that the answer lies, rather, in increasing our knowledge about nature, so that we are better able to decide how much we can extract from nature and still keep the planet habitable and able to provide to every inhabitant of the planet what she or he needs. Further, if all that we do in science was to be predictable, we would not be doing science! Which does not mean science should not have boundaries. But such boundaries need to be negotiated between the concern that we need to know more and that we should not use this knowledge to create something that can cause irreparable harm.

Of more immediate concern, as regards the feat achieved by Venter’s team, relates to how the knowledge that has accrued will be used and controlled. The use or misuse of knowledge can have boundaries only if it is open to public scrutiny and not bottled up in private hands through secretive means. This is of particular importance given Venter’s earlier track record of wanting to create knowledge monopolies through patents. It is incorrect to characterise what Venter’s team has done as an invention. Nothing new has been created. Rather, we have seen the demonstration – albeit at a hitherto unknown grand scale – of how we have the technique available to copy one of nature’s products. Athena Andreadis, Associate Professor of Cell Biology at the University of Massachusetts Medical School, writing in the Huffington Post, puts Venter’s work in clear perspective when she says: “The Venter work is not a discovery, let alone a paradigm shift. It’s a technological advance and even then not of technique but only of scale. The experiment is merely an extension of a well-known principle that every biology lab uses routinely: namely, that bacterial genomes can be modified almost at will (barring a few indispensable regions) and in such ways as to turn the bacteria into potent mini-factories for specific proteins. The Venter bacterium is actually pedestrian because it carries an exact duplicate of a naturally occurring genome. Its only artificial aspects are the molecular “flags” that its makers included in the synthesis to mark the artificial genome for further tracking – standard operating procedure in all such modifications”.

But such labeling of his work is unlikely to deter Craig Venter from using the opportunity to fence off large areas of research through applications for broad patents. This is already being talked about. John Sulston, chair of the University of Manchester’s Institute for Science, Ethics and Innovation, said to the BBC recently: “I’ve read through some of these patents and the claims are very, very broad indeed… I hope very much these patents won’t be accepted because they would bring genetic engineering under the control of the J Craig Venter Institute. They would have a monopoly on a whole range of techniques.” John Sulston is someone who would know well what he is talking about, having previously worked on the human genome project and having been a bitter opponent of Craig Venter’s attempt to patent the work related to the mapping of the human genome in 2001.

So, while we continue to wait for humans to break one of the final frontiers of science – creation of life – we need also to be vigilant of the smaller skirmishes that threaten our ability to widen the boundaries of knowledge that deepen our understanding of the world around us.