Ethics and synthetics

Synthetic biology is fast becoming the guinea pig for merging social and natural sciences.

It never takes long for discussions about synthetic biology to get onto Frankenstein. For a branch of science that merges engineering with biology, that's no surprise. The question is: which Frankenstein? Are we talking about James Whale's movie, with a monster assembled from body parts, or Mary Shelley's book, with a creature fashioned from inanimate material but imbued with life?

This might seem an unnecessary distinction - especially as synthetic biology as it currently stands can encompass both. For people working in the field, there is little distinction between the idea of engineering life using existing organisms and creating unseen forms of life that go beyond what evolution has ever come up with.

The real distinction lies in what happens after the creature breathes its first. The monster portrayed by Boris Karloff started off bad. Shelley's creature is far more ambiguous. When the creature first awakens, Victor Frankenstein runs from it: a reaction that the hideous-looking creation encounters many times. Shunned and abused, the creature slowly turns to murder and revenge.

At the opening of the Centre for Synthetic Biology and Innovation (CSynBI) at Imperial College in May, Frankenstein, for once, was displaced by a less familiar parable of technology gone awry. Lord Winston, who holds a professorship at the college, used footage from the 1920 silent movie 'Der Golem, wie er in die Welt kam' to illustrate a similar point.

A rabbi creates the clay giant to protect the Jews of 16th century Prague from persecution. The golem is at first helpful but turns on those it was meant to protect, setting fire to the ghetto.

Lord Winston said the movie showed two sides: "The good and the evil of synthetic biology or, if you like, the side-effects and consequences." He added that technology has picked up pace, which makes consequences harder to predict. "In the past 400 years, the human mind has gone exponential. Now, we can't see the arena that we're entering and we have no clear idea of where we are going."

He added: "Synthetic biology is a rather vague collection of areas and that will undoubtedly change in a way that we can't predict. That lack of predictability is probably the biggest crisis that we have for technology."

The centre at Imperial College will be the first in the UK to try to combine work by natural and social scientists, with staff from the London School of Economics' BIOS centre joining those from Imperial. It is not the first centre in the world to attempt to do this - SynBERC at the University of California at Berkeley was opened several years ago with social scientists on site.

Toxic organisms

Professor George Gaskell, pro-director of the LSE, described a possible scenario that harks back to the kind of unforeseen circumstances of 'Der Golem'. He called up the example of organisms designed to consume toxic waste. "Some would argue that such an application brings significant uncertainties. An organism that has not been through the mill of evolution, might it go on and become even more toxic?"

Lord Winston argued the idea of teaching ethics as part of science courses is currently an omission: "We don't teach physical scientists the ethics of science the way we do with medical scientists."

Piers Millett, political affairs officer for the United Nations' Biological Weapons Convention (BWC), uses the example of the Hippocratic oath as being a useful weapon in heading off pressure from governments and other groups on scientists to work on harmful technologies. Aware that the techniques needed to conduct synthetic biology research are inherently inexpensive, increasingly accessible and difficult to police, Millett believes that the best way to avoid biotechnology being used for harm lies in self reporting.

"Top-down control is not feasible. There are just too many biological facilities and it would be too expensive to do it," says Millett. "And when you throw synthetic biology into the mix, you go up by an order of magnitude. We are going to have to find better ways of working together. We have to create a self-sustained effort."

In speeches to biotechnologists, Millett cites attempts by the US government, reported in the early 1960s, to set up a special teaching school for medics that would not demand they swear by the Hippocratic oath. By not taking the oath, the government felt they would be more amenable to working on chemical-weapons projects.

Millett sees the self-restraining behaviour of scientists as crucial to maintaining biosecurity: "What can I do to ensure that my science is not misused by somebody else?"

Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, argues that synthetic biology is one area of research where there is no 'ethics lag', although pressure groups argue there is.

"The first paper on the ethics of synthetic biology appeared ten years ago. I know, I co-wrote it," says Caplan. "But there are things lumped under the ethics rubric that don't belong there."

Caplan draws a distinction between concerns over safety and unforeseen consequences, versus ethical and unethical behaviour. Other factors, some of which drove opposition to genetically modified crops, have more to do with ethics of economic policies than the science itself.

"We maybe should change patent policy, but that has nothing to do with the nature of the technology," Caplan argues, but he is keenly aware that there are some aspects of synthetic-biology research that may prove unpalatable to the public, particularly in the way that the research might challenge what it means to be alive. He is not alone.

Speaking at the BioSysBio conference in the spring, Julian Savulescu, director of practical ethics at the Uehiro Centre at the University of Oxford, said: "The ethical debate won't turn on the benefits but on the ethical concerns. The first concern is that the research might be used in malevolent ways. And the research may undermine the status of living things.

"We could inappropriately ascribe lower status to synthetic lifeforms. These are very difficult concerns. We have got to decide what constitutes moral status and then decide whether the entity has that status. A second, more dangerous possibility is that we ascribe greater value to synthetic lifeforms. For example, a chimpanzee may have lower status than a biocomputer."

Speaking at the CSynBI launch, Professor Evelyn Fox Keller of the Massachusetts Institute of Technology, pointed out how language might influence the status of synthetic organisms. "Synthetic implies inauthentic, false. It is giving us life but not as we know it: it is not biology but synthetic biology."

Scientists point out that the question of what life is from a philosophical perspective is outside their remit: they study simply what is. But Savulescu points to the traditional separation of natural science from social science and ethics as viable no longer and that there has to be some crossover. "There is a strong tradition in science in maintaining a separation between the ethics of research and the ethics of the research's use. I would challenge whether scientific isolationism is defensible.

"The claim is that scientists enjoy a right to investigate. Some scientific inquiry is justified by the intrinsic value of the knowledge it produces. This assumes that the value of knowledge is a trump value: that it trumps all other moral value."

Similarly, the "gunmaker's defence" cannot work, Savulescu claims. "Wrongs for which we are not responsible can still be relevant to the assessment of our conduct."

In reality, genetic engineering and synthetic biology are areas in which scientists have taken steps to consider what the outcomes of their research might be. It is hard to find a synthetic biology conference that does not address the risks of the technology if not all the ethical challenges.

"The challenge for regulators is how to minimise the malevolent use of synthetic biology. For philosophers, it is to ascertain the criteria for moral status and to determine how to weigh the risk of future wrongdoing against the benefits of pursuing research," says Savulescu. "For scientists, it is to get better at predicting how research will be used."

Most are not going to want to emulate Whale's Frankenstein, but it's harder to see whether it's possible to avoid Shelley's scenario or unleash a golem.

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