Life's Greatest Secret (41 page)

At the beginning of 2015, a protein called Rqc2p was discovered that actually gets involved in ribosomal protein synthesis, and recruits tRNA molecules to add two kinds of amino acid – alanine and threonine – to the end of a protein chain when synthesis gets stalled.
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By adding a number of these two amino acids in what seems to be a random order, Rqc2p appears to mark the protein (or perhaps the ribosome) for imminent destruction by the cell’s house-keeping machinery. The order of the two amino acids does not seem to be important, and they are not added in any consistent sequence, so, strictly speaking, this example does not contradict Crick’s hypothesis that a protein cannot determine the amino acid sequence of another protein. However, it represents a step towards that possibility. Other odd examples may yet be discovered – as Crick emphasised in 1970, our knowledge is still far too incomplete for us to assert that our current understanding is completely correct. It explains what we have so far discovered, but we may find there are further surprises.

For some philosophers of science, the role of chaperones and the potential existence of information outside the genetic code undermines Crick’s 1957 assumption that protein folding is a spontaneous, self-directed phenomenon. Some even argue that proteins are an agency of heredity, opening the door to the inheritance of acquired characteristics.
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These are very much minority views among philosophers – and even more so among scientists. The role of chaperones is simply what their metaphorical name suggests: they protect and facilitate interactions that lead to three-dimensional protein structure; they do not actively guide and structure them. And even if it eventually turns out that some proteins do directly form the three-dimensional structure of certain proteins (as with prions), the wealth of existing data about protein synthesis indicates that these will be minor curiosities, exceptions that prove the rule.
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Some readers – and in particular any philosophers out there – may be uneasy with the way in which findings that do not conform to the central dogma seem to have been dismissed as exceptions or the products of pathology, thereby apparently leaving the fundamental argument intact when in reality it has been severely weakened. Apart from the fact that none of these examples provides evidence for the transfer of information from protein → DNA, this relaxed attitude, which I share with the vast majority of biologists, underlines a difference between general statements or hypotheses in biology and axioms or laws in mathematics or physics. A single example of a particle travelling faster than light would require a great deal of work by theoretical physicists in order to reshape our understanding of the Universe. In contrast, a solid example of information flowing directly from protein → DNA would not cause a radical revision of our concepts of how genetics and evolution work, unless it was discovered that such transfers take place systematically and on a wide scale.

Were such an example to be discovered, that part of the central dogma would no longer be true, and it is possible that new technologies would become available for manipulating organisms. But virtually all of our existing results and experimental protocols would almost certainly emerge unscathed, because they have been shown to function perfectly well in the absence of such an additional mode of information transfer. The challenge would be for scientists to put the new exception into the existing framework, explaining it in the historical and evolutionary context of the central dogma. If that were not possible, then a radically new explanation would be necessary, and the central dogma would be relegated to the status of an abandoned fruitful hypothesis, an idea that led to successful and informative experimental work, but which was ultimately shown to be wrong.

This would not constitute some kind of moral or philosophical victory for the epigenetic revolutionaries: the reason that scientists accept the central dogma is not because it is a dogma but because the evidence supports it. If new evidence were to arise, then, as the French phrase puts it:
Il n’y a que les imbéciles qui ne changent pas d’avis
– only fools do not change their mind.

* ‘Epigenetics’ sounds much more exciting than ‘gene regulation’, which is no doubt why the term is increasingly being used.

–     FOURTEEN     –

In 2010, the molecular geneticist and entrepreneur Craig Venter hit the headlines. In an article published in
Science,
his group claimed they had created the world’s first synthetic organism.
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More than a decade earlier, Venter’s group began to study the bacterium
Mycoplasma mycoides,
which causes lung disease in ruminants. Over years of painstaking work, they succeeded in creating a synthetic version of the
M. mycoides
genome, having disarmed various pathogenic genes. They then introduced the synthetic DNA chromosome – over a million base-pairs long – into a cell of a related species from which the genomic DNA had been removed. Once installed in its new host, the
M. mycoides
genome was able to function successfully, controlling the cell and reproducing. A new life-form had appeared, created through the work of scientists.

This feat had two important limitations. First, the cell they used was not empty: it contained all the natural cellular machinery, such as ribosomes, metabolites and enzymes, needed for the synthetic DNA to make the new organism function. These vital ingredients had not been touched by Venter’s group. Second, the DNA they introduced into that cell had not been written from scratch; it was copied from the genome of an existing organism. Despite all the human ingenuity involved, the success of the project relied fundamentally on work that had already been done over hundreds of millions of years by natural selection in creating the cell and its contents and in encoding the genome.

Nevertheless, in typical entrepreneurial fashion, the researchers from the J. Craig Venter Institute stamped their ownership on the new bacterium – called
Mycoplasma mycoides
JCVI-syn1.0 – in the shape of genetic watermarks. Using a complex code made up of combinations of letters from the genetic code, the Venter group hid several identifying marks in the DNA sequence of their creation. These included three quotations (one from
A Portrait of the Artist as a Young Man
was briefly the subject of a humourless legal action by the James Joyce estate), the names of forty-six people who were involved in the work, and an address to which e-mails could be sent by anyone able to crack the code. The first correct solution was received a little more than three hours after the watermark sequence went on line.
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In a 2012 lecture in Dublin to commemorate Schrödinger’s
What is Life?,
Venter suggested that he could use his technique to teleport life-forms from the surface of Mars. He proposed sending a robot to the Red Planet that could sequence Martian DNA (assuming that Martians contain DNA) and then transmit the sequence back to Earth. We could then reassemble the Martian in a laboratory, using the technique employed to create
Mycoplasma mycoides
JCVI-syn1.0.
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The idea of transmitting Martians caused some excitement in the press (‘Geneticist aims to teleport Mars life back to Earth’, said
The Boston Globe
) even though Venter did not even invent the idea of teleporting genes – Norbert Wiener first proposed this method for transmitting an organism through the ether in his 1950 book
The Human Use of Human Beings.

As Venter points out, recreating a Martian in a maximum-containment facility on Earth would be safer than bringing it hurtling back through the atmosphere, with the potential of a crash and the pollution of the planet. There are some difficulties, however. If there were life on Mars, it would be very surprising if a Martian genome were able to pop into an Earthling cell and just start working – the cellular context would almost certainly be utterly different from that required by the Martian DNA. In the extremely unlikely event that a Martian was found, that it was based on DNA and that it could kickstart itself into life in an Earthling cell, recreating it on Earth would show that the Earthling and Martian branches of life shared a common ancestor. The most probable explanation would be that the Martian microbe came from Earth, blasted into space on a lump of rock after a meteorite strike and eventually plummeting onto the Red Planet. If there is life on Mars that is truly Martian, it seems highly unlikely it is similar to Earth life. There is no reason to imagine that DNA is the only possible informational molecule; in fact, our deep evolutionary past, and the ingenuity of today’s scientists, both show that is not the case.

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Biotechnology is not a recent development. For thousands of years, humanity has used the power of microbes to produce two foodstuffs that are seen as an essential part of everyday life for much of the planet: bread and beer. Both rely on harnessing the respiratory mechanisms of yeast to produce carbon dioxide (which makes bread rise) and alcohol (which makes beer intoxicating). What was initially a blind process has been utterly transformed over the past four decades, as modern biotechnology has exploited our ability to manipulate the genetic code to create organisms containing new genes, including genes from other species.
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New terms have been coined – biotechnology, genetic engineering, synthetic biology – but they all ultimately describe the use of genetic manipulation to alter living organisms.
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Many drugs, including hormones, are now produced by harnessing the power of genetic engineering, involving the insertion of the relevant gene into a microbe that then churns out the desired material. Some examples are frankly bizarre, such as the goats that express a spider gene for producing silk, and excrete the stuff in their milk.
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If the spider-goats can produce sufficient quantities of the strong and flexible silk, new products such as stab-proof jackets could be created. Looking to the future, research groups around the world are trying to address the two central problems facing our species – energy and food supplies – by manipulating cells to produce fuel and meat.

Over the past couple of decades, genetically modified (GM) plants have become widespread in agriculture, in particular in the US. In 2014, 94 per cent of US soybean crops were GM, as were 93 per cent of corn crops, 95 per cent of sugar beet crops and 96 per cent of cotton.
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Some of these crops are pest-resistant because they have been engineered to produce a natural insecticide that is normally produced by the soil bacterium
Bacillus thuringiensis
(these are therefore known as
Bt
crops). Other crops are herbicide-resistant and enable farmers to increase yield by reducing the need to leave space for weeding – more plants can be grown per acre.

The best-known GM crop is the Roundup Ready soybean, produced by the agrichemical company Monsanto, which resists Monsanto’s own brand of herbicide, Roundup. Despite the very real benefits of these crops in terms of higher productivity, the increased use of herbicides reinforces the bleak monoculture of much of modern industrial farming, reducing biodiversity in the immediate vicinity of the farm. Herbicides can also pollute local water sources, with unintended consequences for wildlife, in particular for amphibians.
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The safety and reliability of GM technology is not at issue here; it is the aims and consequences of its use that need to be addressed.

When GM food crops were first introduced into the UK, the tabloid press described them as ‘Frankenfood’, and there was widespread hostility to scientific trials of new GM crops, including direct action by activists who trashed the fields. Health fears relating to the consumption of GM food have been widespread but are entirely unjustified: there is no evidence that consumption of GM organisms will do you any harm at all. Vague unease about ‘manipulating nature’ is similarly mistaken – all the food we eat has been genetically manipulated over thousands of years through artificial selection by our ancestors. The difference is simply one of method: artificial selection of our foodstuffs is merely slower and generally less effective than direct genetic manipulation.

Even the widespread feeling that there is something unnatural about transferring genes from one species to another is unfounded. Exchange of genes between species – known as horizontal gene transfer – occurs quite readily in microbes, and sometimes in animals and plants. Very specific adaptations have appeared through horizontal gene transfer. For example, the pea aphid is the only animal in the world that can synthesise red pigments known as carotenoids (all other animals have to acquire these compounds from the environment, by eating plants). The aphid gained this ability by incorporating genes from a fungus into its genome; when, how and why this happened is unknown, but it demonstrates that horizontal gene transfer, a form of inadvertent natural genetic engineering, can also explain some adaptations of multicellular organisms.
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