Artificial life

Artificial life

Patent pending

Move over Dolly. Synthia is on her way

 

YOU have to hand it to Craig Venter, he is not someone who thinks small. The latest adventure of the man who was the first to sequence the genome of a living organism (three weeks after his grant request to do so was rejected on the grounds it was impossible), the first to publish the genome of an identifiable human being (himself) and the first to conceive the idea of sequencing the genome of an entire ecosystem (and to enjoy a nice cruise across the Pacific Ocean in his yacht while he did so) is curiously reminiscent of the incident that made him a controversial figure in the first place. That was when, 16 years ago, he attempted to patent parts of several hundred genes—the first time anyone had tried to take out a patent on more than one gene at a time.

This time, he is proposing to patent not merely a few genes, but life itself. Not all of life, of course. At least, not yet. Rather, he has applied for a patent on the synthetic bacterium that he and his colleagues Clyde Hutchison and Hamilton Smith have been working on for the past few years.

The patent application itself was filed without fanfare some eight months ago. But it was only at the end of May that the slowly grinding bureaucracy of America’s patent office got round to publishing it. The central claim is to what Dr Venter calls the “minimal bacterial genome”. This is a list of the 381 genes he thinks are needed to keep an organism alive. The list has been assembled by taking the organism he first sequenced, Mycoplasma genitalium, and knocking out each of its 470 genes to see which ones it can manage without. The theory—and the claim made by the patent—is that by synthesising a string of DNA that has all 381 of these genes, and then putting it inside a “ghost cell” consisting of a cell membrane, along with the bits and pieces of molecular machinery that are needed to read genes and translate them into proteins, an artificial organism will have been created.

Given that the ghost cell will be an enucleated natural bacterium rather than a synthetic structure in its own right, the new bug will not be a completely man-made creature. Nevertheless, if the three researchers can pull it off, they will have achieved an impressive piece of genetic engineering—or, rather, of synthetic biology as this high end of the field is now usually called. And there is every reason to believe that they will be able to pull it off. In 2003 the same team, working then as now at Dr Venter’s research institute in Rockville, Maryland, were the first to produce a truly viable synthetic virus. And techniques have moved on since then.

The patent does not claim that an organism based on the minimal bacterial genome has yet been made—and it hasn’t. It is more a question of the Venter Institute getting its retaliations in first. Nevertheless, the mere filing of the patent has upset some people. Among the dischuffed is ETC Group, a Canadian bioethics organisation whose eagle-eyed spotters noticed the publication of patent 20070122826 last week. They have asked Dr Venter to withdraw the patent—and, on the assumption that he will not, have also asked the patent office to reject it on the grounds that it is contrary to public morality and safety.

ETC’s objections seem twofold, and also slightly contradictory. One objection is that the patent’s claims are too widely drawn. It attempts, for example, to reserve the right to any method of hydrogen or ethanol production that uses such an organism. (Dr Venter thinks synthetic biology is going to be important as a way of making fuels.) It also, bizarrely, claims an interest in the genes the three researchers have identified as non-essential, as well as the essential ones.

To the extent that sweeping claims may stifle innovation, these are certainly things that need to be considered. However, the more profound objection ETC has seems to be based on the idea that there are areas where mankind should not meddle. As Pat Mooney, the group’s boss, put it, “For the first time, God has competition.” No doubt Dr Venter, hardly famous as a shrinking violet, will be amused by the comparison.

ETC’s argument has some force. Synthetic biology is developing fast and it is easy to see it being used out of malice. That said, one of the advantages of a minimal genome is that the genes removed, while not essential for survival, are essential for robustness. A bug relying on such a genome could not possibly live in the wild if it accidentally escaped. Also, the biologists in the field are as concerned as anybody that the subject develops safely. They have been asking for regulation rather than resisting it, and have already established codes of conduct to try to stop the malicious synthesis of pathogens.

Nevertheless, ETC is hoping to provoke a debate. And to give people a name to hang on to in that debate it suggests nicknaming Mycoplasma laboratorium, as the application calls the putative invention, as “Synthia”. The organisation hopes this name will stick in the popular consciousness in the way that Ian Wilmutt’s cloned sheep Dolly did. Indeed, it is rather a good name. Given the affection that Dolly attracted once the shock of her existence had been absorbed, perhaps Dr Venter—himself no slouch at publicity—will adopt it.

 

Turkey’s Kurds

Turkey’s Kurds

Guns and votes

Pre-election tension is rising among the Kurds of Turkey’s south-east

 

A GOLD-PLATED pistol in one hand, worry beads in the other, Hazim Babat sits at the foot of the mountain range that separates Turkey from Iraq and contemplates war. He is the chieftain of the Babat clan, which is fighting alongside the Turkish armed forces against the Kurdistan Workers Party (PKK) separatist guerrillas.

For years the Babats hunted PKK militants in Iraq with the help of Peshmerga warriors from the Kurdistan Democratic Party (KDP) from northern Iraq, led by Massoud Barzani. “The PKK slaughtered our women, our babies, they are going to pay the price,” vows Mr Babat.

But times have changed and the Kurds are beginning to unite, wherever they live. Nowhere is this truer than in northern Iraq where, with American support, as many as 4m Kurds have come closer to achieving full-blown independence than ever before. Mr Barzani, who runs the Kurdish-controlled enclave, declares that the days of Kurdish fratricide are over. He refuses to let Turkish soldiers overrun his territory in order to attack the PKK. “Turkey’s real problem”, Mr Barzani opined recently, “is that the Kurds exist at all.”

Despite its repeated calls for cross-border action against the PKK, the army’s real target may be the quasi-independent Kurdish state in northern Iraq. The generals see an independent Kurdish state as an existential threat because it would stoke separatist passions among Turkey’s 14m-odd Kurds. They are “willing to prevent its emergence no matter the price”, asserts Ibrahim Guclu, a veteran Kurdish politician. “Yet the harder they push, the closer together they drive the Iraqi and Turkish Kurds,” he adds.

Mindful of America’s opposition and of Kurdish votes, Turkey’s mildly Islamist prime minister, Recep Tayyip Erdogan, has ruled out any incursion, at least before the general election on July 22nd. Yet Turkish forces continue to mass along the Iraqi border. The beefed-up army presence is palpable in Sirnak, one of three border provinces in which no-go “security zones” have been declared. Turkish soldiers in armoured personnel-carriers point guns at passers-by. Attack helicopters clatter overhead. In the regional capital of Diyarbakir, your correspondent counted no fewer than nine F-16 fighter jets screeching towards Sirnak within the space of 20 minutes. The PKK is hitting back, murdering soldiers and civilians alike.

Ayla Akat, a human-rights lawyer who is standing for election in Batman for the pro-Kurdish Democratic Turkey Party (DTP), concedes that the violence is fuelling anti-Kurdish feelings throughout Turkey. She points to the attempted lynching this month of two Kurdish seasonal workers in the western province of Sakarya. Yet if the government were to accept the PKK’s demands to ease restrictions on the Kurdish language, offer amnesty to PKK fighters and allow their leaders to seek asylum in Europe, “the Kurdish problem would be solved”, she says. “Is anyone talking about independence?”

In 2005, emboldened by the European Union’s decision to open membership talks, Mr Erdogan explored a possible deal that would accommodate the Iraqi Kurds too. But he was forced to back off under pressure from the army. In the same year Mr Erdogan became the first Turkish leader ever to admit that the state had made “mistakes” in dealing with the Kurds. His words cemented his Justice and Development (AK) Party, whose Islamic credentials play well with millions of pious Kurds, as the DTP’s main rival in the south-east.

“My people are going to vote for Erdogan because he wants the European Union, and EU membership is the panacea for separatism,” says Cemil Oter, a tribal leader who has lost 40 men to the PKK. But hopes of membership are fading as EU bigwigs, led by France’s new president, Nicolas Sarkozy, lobby against Turkish entry. EU-inspired reforms that helped to win Turkey its prized date for membership talks are being quietly rolled back.

The effects are being felt in Diyarbakir, where a local mayor and his entire council were barred from office last week for using Kurdish as well as Turkish to communicate with their constituents. Abdullah Demirbas had already annoyed the authorities by erecting a monument in memory of Ahmet Kaymaz, a Kurdish lorry driver, and his 12-year-old son, who were gunned down outside their home in the town of Kiziltepe in 2004 on the grounds that they were “terrorists”.

All four members of the special forces who were implicated in the killings were exonerated by a court in April, proving that “there is rarely justice for the Kurds”, says Tahir Elci, a lawyer who defended the Kaymaz family. Mr Elci is now facing up to three years in prison for criticising the court. Meanwhile, reports of torture have risen sharply, because new regulations allow detainees to be denied access to a lawyer during the first 24 hours of interrogation by police.

All these things help to swell PKK ranks. The trouble is that the rebels’ new tactics—setting off landmines and planting explosives—have caught the army off guard. Abdullah Gul, the Turkish foreign minister, revealed last week that security forces seized two tonnes of plastic explosives smuggled by the PKK from Iraq in 2006 alone. Mr Gul said that “making compromises over democracy in the name of fighting terrorism” was “a trap that should not be contemplated”. But with each Turkish soldier killed fighting the PKK, Turks’ enthusiasm for democracy, and for the EU, gets harder to preserve.

The RNA revolution

The RNA revolution

Biology’s Big Bang

What physics was to the 20th century, biology will be to the 21st—and RNA will be a vital part of it

 

NATURE is full of surprises. When atoms were first proved to exist (and that was a mere century ago), they were thought to be made only of electrons and protons. That explained a lot, but it did not quite square with other observations. Then, in 1932, James Chadwick discovered the neutron. Suddenly everything made sense—so much sense that it took only another 13 years to build an atomic bomb.

It is probably no exaggeration to say that biology is now undergoing its “neutron moment”. For more than half a century the fundamental story of living things has been a tale of the interplay between genes, in the form of DNA, and proteins, which the genes encode and which do the donkey work of keeping living organisms living. The past couple of years, however, have seen the rise and rise of a third type of molecule, called RNA.

The analogy is not perfect. Unlike the neutron, RNA has been known about for a long time. Until the past couple of years, however, its role had seemed restricted to fetching and carrying for DNA and proteins. Now RNA looks every bit as important as those two masters. It may, indeed, be the main regulator of what goes on in a cell—the cell’s operating system, to draw a computing analogy—as well as the author of many other activities (see article). As important, molecular biologists have gone from thinking that they know roughly what is going on in their subject to suddenly realising that they have barely a clue.

That might sound a step backwards; in fact, it is how science works. The analogy with physics is deeper than just that between RNA and the neutron. There is in biology at the moment a sense of barely contained expectations reminiscent of the physical sciences at the beginning of the 20th century. It is a feeling of advancing into the unknown, and that where this advance will lead is both exciting and mysterious.

Know thine enemy

As Samuel Goldwyn so wisely advised, never make predictions—especially about the future. But here is one: the analogy between 20th-century physics and 21st-century biology will continue, for both good and ill.

Physics gave two things to the 20th century. The most obvious gift was power over nature. That power was not always benign, as the atomic bomb showed. But if the 20th century was distinguished by anything from its predecessors, that distinctive feature was physical technology, from motor cars and aeroplanes to computers and the internet.

It is too early to be sure if the distinguishing feature of the 21st century will be biological technology, but there is a good chance that it will be. Simple genetic engineering is now routine; indeed, the first patent application for an artificial living organism has recently been filed (see article). Both the idea of such an organism and the idea that someone might own the rights to it would have been science fiction even a decade ago. And it is not merely that such things are now possible. The other driving force of technological change—necessity—is also there. Many of the big problems facing humanity are biological, or are susceptible to biological intervention. The question of how to deal with an ageing population is one example. Climate change, too, is intimately bound up with biology since it is the result of carbon dioxide going into the air faster than plants can remove it. And the risk of a new, lethal infection suddenly becoming pandemic as a result of modern transport links (see article) is as biological as it gets. Even the fact that such an infection might itself be the result of synthetic biology only emphasises the biological nature of future risks.

At the moment, policymakers have inadequate technological tools to deal with these questions. But it is not hard to imagine such tools. Ageing is directly biological. It probably cannot be stopped, but knowing how cells work—really knowing—will allow the process to be transformed for the better. At least part of the answer to climate change is fuel that grows, rather than fuel that is dug up. Only biotechnology can create that. And infections, pandemic or otherwise, are best dealt with by vaccines, which take a long time to develop. If cells were truly understood, that process might speed up to the point where the vaccine was ready in time to do something useful.

But physics gave the 20th century a more subtle boon than mere power. It also brought an understanding of the vastness of the universe and humanity’s insignificant place in it. It allowed people, in William Blake’s phrase, to hold infinity in the palm of a hand, and eternity in an hour.

Know thyself

Biology, though, does more than describe humanity’s place in the universe. It describes humanity itself. And here, surprisingly, the rise of RNA may be an important part of that description. Ever since the human-genome project was completed, it has puzzled biologists that animals, be they worms, flies or people, all seem to have about the same number of genes for proteins—around 20,000. Yet flies are more complex than worms, and people are more complex than either. Traditional genes are thus not as important as proponents of human nature had suspected nor as proponents of nurture had feared. Instead, the solution to the puzzle seems to lie in the RNA operating system of the cells. This gets bigger with each advance in complexity. And it is noticeably different in a human from that in the brain of a chimpanzee.

If RNA is controlling the complexity of the whole organism, that suggests the operating system of each cell is not only running the cell in question, but is linking up with those of the other cells when a creature is developing. To push the analogy, organs such as the brain are the result of a biological internet. If that is right, the search for the essence of humanity has been looking in the wrong genetic direction.

Of course, such results are speculative and primitive. But that is the point. Lord Rutherford, who proved that atoms exist, knew nothing of neutrons. Chadwick knew nothing of quarks, let alone supersymmetry. Modern biologists are equally ignorant. But eventually, the truth will out.

 

Taglio di tasse addio

TITO BOERI

Con l’intesa raggiunta al Consiglio dei ministri di ieri gli italiani possono dire addio alla speranza di un taglio delle tasse in questa legislatura. L’extra gettito è stato tutto impegnato per finanziare nuove spese, molte delle quali sono destinate a durare nel corso del tempo. Anzi, se l’extra gettito dovesse poi rivelarsi un dono effimero, si dovranno nuovamente aumentare le tasse. Si rassegnino i più giovani: la montagna del debito pubblico non si abbassa. Nonostante il contesto macroeconomico favorevole, che dovrebbe favorire una sensibile riduzione del debito pubblico, non ci sarà alcuna manovra nel 2008. E, a meno di sorprese nell’ultima fase della trattativa sulle pensioni, i lavoratori possono abituarsi fin d’ora all’idea che fra pochi mesi dovremo aprire un nuovo tavolo sulle pensioni per trattare dei veri problemi del nostro sistema previdenziale, una volta di più elusi, rinviati ai governi, politici e sindacalisti futuri. La miopia della politica economica italiana sta diventando talmente forte da impedire di mettere a fuoco i numeri della calcolatrice. Il negoziato interno alla maggioranza, forse ancora più serrato che quello coi sindacati, si è sbloccato, a quanto pare, a partire dai risultati dell’autotassazione di giugno. Come se si stesse discutendo di come coprire le spese del prossimo mese e non invece di scelte che riguarderanno lo Stato sociale, dunque la lotta alla povertà e il futuro previdenziale nei prossimi 50 anni. In virtù di risultati dell’autotassazione migliori del previsto, il governo anziché abbassare l’obiettivo sul rapporto deficit/Pil per fine anno, ha deciso di alzarlo dal 2,1 al 2,5 per cento. Questo significa permettere di finanziare, con maggiore deficit pubblico, l’aumento delle pensioni minime, l’allungamento della durata dei sussidi di disoccupazione ordinari, il rifinanziamento delle ferrovie e dell’Anas. Il tutto per circa 6 miliardi di euro. Non c’è in tutte queste misure alcuna organicità. Se si voleva contrastare la povertà, ad esempio, si poteva varare una seria riforma degli ammortizzatori sociali che coprisse contro questo rischio a tutte le età. Sarebbe costata di meno di questa serie confusa di interventi. Avendo alzato il deficit per il 2007, il governo adesso cercherà di vendere a Bruxelles un obiettivo per il 2008 al 2,2%. Come dire che nel 2008 i saldi saranno peggiori di quelli su cui ci eravamo impegnati fino ad oggi per il 2007. Difficile che Bruxelles accetti questo artificio contabile perché infrange non una ma due regole al tempo stesso. Queste impongono, da una parte, che tutto l’extra gettito vada a riduzione del deficit e, dall’altra, che ogni anno si proceda ad un aggiustamento strutturale di almeno lo 0,5% fino all’azzeramento del deficit. Sulle pensioni la partita è ancora aperta. La parola spetta ora ai sindacati. Nelle intenzioni del governo sembra che lo scalone verrà trasformato in due scalini. Nel 2008 si dovrebbe poter andare in pensione a 58 anni (anziché a 60 anni) e poi dal 2010 ci dovrebbe essere un inasprimento dei requisiti contributivi e anagrafici per avere una pensione piena. E’ un nuovo scardinamento della riforma varata nel 1996 che prevedeva solo requisiti anagrafici (dai 57 ai 65 anni) per l’andata in pensione. Le quote sono complicate da capire, penalizzano le donne che hanno carriere contributive più brevi e portano a risparmi di spesa minimi. Non si sa ancora come verranno finanziati i costi della rimozione dello scalone. Soprattutto non sembra in vista un accordo riguardo ai cosiddetti coefficienti di trasformazione, quelli che serviranno a calcolare l’importo delle pensioni nel nuovo sistema contributivo. Il problema vero delle nostre pensioni è proprio quello di attribuire regole certe a chi inizia oggi a lavorare, mettendolo al riparo dal rischio politico di nuovi cambiamenti dei criteri di calcolo delle pensioni magari a ridosso dell’andata in pensione, quando si ha meno tempo per premunirsi. L’operazione che andava fatta, che doveva essere fatta fin dal 2005 per applicare la riforma Dini del 2006, era proprio la revisione dei coefficienti di trasformazione. Si annuncia solo l’ennesimo rinvio. Ciò significa che milioni di famiglie rimarranno in ansia. Il tormentone sulle pensioni non è affatto finito. Ci sarà solo la tradizionale pausa estiva.