In the neutral zone: is there an ethical side to science?

"I promise to work for a better world, where science and technology are used in socially responsible ways. I will not use my education for any purpose intended to harm human beings or the environment. Throughout my career, I will consider the ethical implications of my work before I take action. While the demands placed upon me may be great, I sign this declaration because I recognize that individual responsibility is the first step on the path to peace."

The above is the text of a ‘Hippocratic Oath for Scientists’ proposed by the physicist and Nobel Peace Prize laureate Sir Joseph Rotblat in Science in 1999 (1). Rotblat, a British physicist who grew up in Poland and moved to England just before the Second World War, was originally part of the Manhattan Project that created the atom bomb. When in 1944 it became obvious that the Germans were themselves not capable of building such a device, Rotblat was the only member of the group – which included many of the finest physicists of the 20th century such as Niels Bohr and Richard Feynman – who decided he no longer wanted to be part of the creation of such a powerful weapon of mass destruction. Throughout the rest of his life, he advocated that scientists had the responsibility of protecting the environment and humankind and should be main players in the quest for world peace.

Rotblat did not see science as amoral; he felt that scientists had a clear responsibility to the public and if the results of certain lines of research could lead to adverse effects for humanity and the environment, scientists should decide against conducting those experiments. But many have argued that, while the misuse of scientific knowledge can certainly have dangerous consequences, the scientific process itself is, and has to be, ultimately neutral.

Arguably the strongest advocate for such a position is Lewis Wolpert, Emeritus Professor in Cell and Developmental Biology at University College London. In 2000, in a published exchange of letters (2) between Wolpert and the environmentalist and founder of The Ecologist, Edward Goldsmith, he argued that “it is the very nature of science that it is not possible to predict what will be discovered, or how these discoveries could be applied”, and suggests that one should not confuse knowledge gained by scientific research with the (technical) application that follows. While he also argues that “scientists have neither the right nor the skill to make ethical decisions about the application of their work”, he does suggest that scientists have a responsibility to provide the public with the tools to make informed decisions about the application of science: they should explain their research to the public, explore possible consequences – positive and negative – of their scientific results, and make sure that the research is trustworthy (3). This then would allow for informed debates amongst policy makers and the general public such that society as a whole would be involved in decisions as to how scientific progress is applied.

The debate about the ethical responsibilities of scientists came to the fore again in May this year when the controversial American scientist, Dr Craig Venter, announced that researchers at the J. Craig Venter Institute, a private organisation run by a board of which Dr Venter is President, had been able to create ‘synthetic life’ - a notion disputed by some scientists who say that rebooting a living cell with synthetic DNA is not equal to the creation of new life - by replicating DNA from a bacterial cell artificially and replacing the original DNA of the cell with the artificial DNA (4).

While the technical advancements of this study are largely undisputed, it has been the ethical questions surrounding this research that have caught the headlines. Some of the more controversial reactions to Venter’s research came from Professor Julian Savulescu of the Uehiro Centre for Practical Ethics, who is quoted in the Times Online saying that “Venter is creaking open the most profound door in humanity’s history, potentially peeking into its destiny”, and even goes on to say that “he [Craig Venter] is going towards the role of a God: creating artificial life that could never have existed naturally … the risks are also unparalleled. These could be used in the future to make the most powerful bioweapons imaginable.” David King, director of the Human Genetics Alert watchdog also criticised Venter for playing God: “what is really dangerous is these scientists’ ambitions for total and unrestrained control over nature.” Although these statements seem extreme and guided by emotion rather than reason, they do illustrate an important issue: that there is a discrepancy in understanding of scientific research between scientists and lay-audiences – even highly educated ones – that needs to be addressed.

This research has also grabbed the attention of environmentalist groups who are calling for a moratorium on the release of any synthetic life forms into the environment. They argue that artificial life forms may threaten existing wild life and could lead to hastened extinction, resulting in diminished biodiversity. At the UN Conventional on Biological Diversity held in Kenya at the end of May this year, the Action Group on Erosion, Technology and Concentration (ETC Group) - an international civil society organisation that researches the impact of new technologies on marginalised peoples and is based in Ottawa, Canada - helped formulate a ‘de facto moratorium’ on synthetic biology, which calls for a total ban on any experiment where artificial life forms are released into the wild (5). Environment ministers of the 193 member countries of the Biological Convention will meet in Japan later this year to decide whether to adopt such a moratorium.

Browsing through the popular media coverage, it might seem as if Rotblat would not have approved of Craig Venter’s experiments; however, as Venter himself has pointed out, the ability to create synthetic life allows us to start understanding the function of the fundamental components of life. This may ultimately lead to cures for genetic diseases, such as cystic fibrosis and Alzheimer’s disease by replacing damaged DNA with synthetic DNA that does not have mutations. The environment may benefit significantly too. Synthetic cells may be used to develop synthetic fuels that could address our need for fossil fuels and the large amount of carbon emission in our atmosphere. Such technologies therefore have huge potential for business; BP and Exxon Mobil are already large funders of Dr. Venter’s research.

To a young scientist, it might seem quite straightforward to sign up to Rotblat’s proposed oath, but what would it practically mean to adhere to this code? How do you decide where your personal responsibilities lie? Are you always aware the possible effects of your research? These are particularly difficult questions to answer, especially in a scientific world where high profile publications are ever more important as a token for research money. 

As Wolpert argues, scientific discovery is not necessarily predictable, and the suggestion that controversial results can be avoided by not carrying out such experiments seems naïve. Furthermore, while some findings may be used in harmful ways, often their benefits far outweigh their risks. For example, 14% of the world’s electricity needs (30% in the EU alone) are provided for by nuclear power (6,7). Thus, despite its major image problem, this positive use of nuclear fission is of vital importance in today’s society.

While the argument for the scientific process being neutral seems well founded, it is harder to conceive exactly how the application of science should happen democratically. There are only a few scientific minds in the current UK parliament. The crucial question is whether we would really want to leave decisions about the application of synthetic life or genetically modified crops up to politicians or groups of activists. Many comments on Venter’s study came from philosophers, and they could potentially play a pivotal role in democratising the application of scientific progress. In the current era, where major scientific discoveries follow each other in rapid succession, there is a need for ethicists to guide scientists and policy makers on how to use controversial results responsibly. This need is beginning to be widely acknowledged and has already led to the founding of numerous centres dealing with the ethical side of scientific discovery worldwide. Scientists could, or maybe even should, play a major role in this process by helping ethicists and policy makers understand the science behind discovery.

While it may seem that the media increasingly represents scientific advances as lead to increasing a threats to our existence, such fears are by no means new. An image of the “mad scientist”, tinkering with the natural world, can be seen as far back as Aristophanes’ comedy ‘The Clouds’. Mary Shelley’s famous 19th century novel ‘Frankenstein’ expressed the uneasy feelings many people might have about science. However, one has to bear in mind that controversial advances have always led to criticism and ethical questions, but equally, controversial advances in science as well as literature, art and society, has made our society the way it is today.

References
1.    Rotblat, J. A (1999). Hippocratic Oath for Scientists. Science 286: 1475
2.    Wolpert, L. and Goldsmith, E. (2000). Letter exchange: Is science neutral? The Ecologist 30 No. 3 (May).
3.    Wolpert, L. (1999). Is science dangerous? Nature 398: 281-282.
4.    Gibson, D.G., Glass, J.I., Lartigue, C. et al., (2010). Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science 329: 52-56.
5.    Etc Group (2010). Synthia is Alive … and Breeding: Panacea or Pandora's Box? http://www.etcgroup.org/en/node/5142
6.    International Energy Agency (2009). Key world energy statistics. http://www.iea.org/publications/free_new_Desc.asp?PUBS_ID=1199.
7.    European Commission (2009). Eurostat. http://epp.eurostat.ec.europa.eu/portal/page/portal/product_details/publication?p_product_code=KS-SF-09-055.

This article appeared in the Science and Society section of the Michaelmas Term issue of 'Phenotype', the termly science magazine from the Oxford University Biochemical Society. Here you can read the magazine its entirety.

Finally ...

I know - months have gone past without fresh words on this blog. I have not been entirely idle during this period, but few of my energies have been directed towards writing (evidently!).

Moreover, I have also recently been moonlighting online elsewhere and have just posted a piece on Science Oxford Online provoked by the pointless nature-nurture argument on a recent edition of The Today Programme following the announcement of a possible genetic component to ADHD (Attention Deficit Hyperactivity Disorder).

This comes as part of my increasing involvement with Science Oxford, a charitable organisation for the promotion of local science to the general public and also more generally to educate and inspire children and adults about science from across the globe.

For the younger generation, they provide what is called a "Discovery Zone", essentially a large, educative and interactive play pen, which provides seemingly hours of distraction and fun while also quietly demonstrating some of the laws of magnetism and gravity and the like.

While many adults also seem to gain as much enjoyment from these toys as their children, Science Oxford also organises events more specifically tailored to their age group on Thursday evenings. Over the past year, I have helped out at talks on topics ranging from sustainable farming to Alzheimer's disease via a celebration of the contribution of black scientists. They even allowed me an evening to consider how memory and identity interact. For those of you not in Oxford, many of the events are streamed and archived on the website and can be downloaded as video podcasts via iTunes (search for Science Oxford in the iTunes store). Their recent event on everything you always wanted to know about sex (whether or not you were afraid to ask) should be up there shortly and there will soon be talks on the universe and the atom (quite some change in scale!) along with a seasonal take on the science of fireworks.

But don't worry, Science Oxford has not entirely taken over my life and I shan't be forsaking this blog entirely.  I hope shortly to write about some of the science that has caught my eye over the summer months.  Without a 4 month delay this time, I promise.

Double blind & placebo controlled, but where are the statistics?

For those of you who missed this morning's The Today Programme on BBC Radio 4, listen here to a fragment where homoeopathy-sceptic Simon Singh and conservative MP David Tredinnick take opposing views on the healing powers of homoeopathic remedies. Based on a couple of studies published recently, Tredinnick feels it is worth re-opening the debate on whether or not the NHS should fund homoeopathic remedies; Simon Singh explains why this would be a mistake. The latter's description of a French homoeopathic flu medicine that contains one crushed and highly diluted duck that serves millions of people - and therefore earns the company who created the remedy millions of Euros - as the ultimate quack remedy is a wonderful and almost perfect put-down for the values of homoeopathy.

Reading between the lines

Whenever we compare human and animal behaviour, one major difference that always comes up is our ability to use words to communicate with our fellow human beings. We can use words to order food in a restaurant and chat about everything and nothing over coffee with our friends, and the act of talking has become so normal to us that we don't even give much thought as to how extraordinary speech really is. And now researchers have discovered that our use of language gives away more than just the literal meaning of the words: there are hidden clues about ourselves in our words, in the frequency with which we use certain words, in the number of different words there are in our personal vocabulary and in the richness of our sentences.

In 'Vanishing Words', a recent episode of my ever favourite science-based radio programme Radiolab, Jad and Robert talk about those hidden messages. Drs Ian Lancashire, Kelvin Lim and Serguei Pakhomov are all interested in how characteristics of our personal vocabulary may be an indication of our likelihood of developing memory related diseases such as Alzheimer's. Moving from analysis of the crime novels of Agatha Christie to a comparison of how the linguistic content of teenage essays by a group of nuns relates sixty years on to their cognitive function, these researchers have found surprising associations between the richness of our language and our later susceptibility to cognitive decline.

And more messages can be found in this blog post on the British Psychological Society's Research Digest blog. Dr Paul Rozin of the University of Pennsylvania showed in a study published in Cognition and Emotion that our existential feelings about positive and negative events are reflected in our language. Analysing the frequency of positive and negative words in our language, the researchers found a large prevalence of the former type of utterance, mirroring, they claim, the preponderance of positive events that occur.  Nonetheless, while negative words are comparably scarcer, they exist in greater variety, which the authors argue again is typical of how such events occur in our everyday environment.

Perhaps this latter is not so surprising.  Even at its most gossipy or mundane, language is partly a translation of our needs and desires, and partly a reflection of our environment.  Slips-of-the-tongue have endlessly been interpreted, not just as mistakes, but as windows onto our souls (see, for instance, the furore when Gordon Brown once accidentally said that he had "saved the world" rather than just the monetary crisis). Similarly, the past fifty years have seen fierce battles over Whorfian linguistic relativism, questioning how language affects thought, perception and behaviour.

All this does give the phrase 'reading between the lines' quite a different meaning!

Illuminating the brain's bright future

In the 1920s Felix the Cat had a brilliant idea and a light bulb appeared over his head; thus was created the signature of an epiphany. But recent advances in neuroscience leave you wondering whether in the future we will be more familiar with light bulbs actually driving our thoughts and inspiration rather than just being a visual metaphor. Gero Miesenböck, currently Waynflete Professor of Physiology at Oxford University, has been pioneering work that uses light to control brain cells, a field known as optogenetics.

Our brain consists of approximately 100 billion neurons that, as Miesenböck lyrically describes, form “an intricate tapestry”. To understand how neuronal signalling drives our behaviour, he says, we need to tease apart the disparate contributions that each of the different populations of neurons make to our behaviour. Nobel laureate Francis Crick remarked in a famous article in 1979 that one thing scientists have dreamed about is a tool that would allow them to selectively activate or turn off certain groups of cells while leaving others unaffected. Twenty years later, he suggested how this might be achieved: with light and molecular engineering. And this is precisely what optogenetics does.

To understand this technique we have to go back to the 1990s when German biologist Peter Hegemann discovered that green algae, commonly found in ponds, respond to light by wagging their tail. This behaviour was intriguing because algae are unicellular creatures without eyes. Hegemann discovered that when light photons hit the protein coils packed in the algae’s cell membrane, a chemical reaction creates a tiny gap in the membrane, causing an ionic current to be produced and the algae’s tail to wag. The protein that allows this reaction with light is called channelrhodopsin and is comparable to rhodopsins found in our own eyes.

Meanwhile, Miesenböck and his colleagues, working in New York and later at Yale, wondered whether they could exploit a similar mechanism to control brain cells. They took light sensitive proteins like the photoreceptors of our eyes, transplanted them into neurons and, by simply shining a light on them, the team was able to activate the modified neurons, a first step towards neuronal control.

To exploit the full power of this method, however, the researchers needed to discover a way just to excite or inhibit selected populations of cells, and with genetic engineering they were able to achieve this. By harnessing the cunning of viruses or by creating genetically-modified mice and flies, it was possible to make expression of the rhodopsin-encoding gene specific to particular neurons, meaning that only those neurons would become active when illuminated.

The road to success for optogenetics was not easy. The first difficult step was to find out whether they were able to transplant the rhodopsin-containing photoreceptors of flies to other cells in a culture and activate them with a flash of light. Once they succeeded in doing this, the second, even more complicated challenge was to move from changing neuronal activity in a cell culture to changing the behaviour of a living being, in Miesenböck’s case the fruit fly. The promise became initially clear when Susana Lima, Miesenböck’s PhD student at the time, showed him the first baby steps taken by a fruit fly on command of light. Within 5 years, they had learned how to remote control a fly.

The technique is now so advanced there is a large volume of work looking at how brain cells control behaviour. Last year in Cell, Miesenböck and his team exposed the learning mechanisms of a fly by creating false memories (1). They placed a fly in a narrow chamber, half of which smelled of an old tennis shoe, the other half of sweet fruit. By observing how much time the fly spent on either side, the researchers were able to work out which was the fly’s preferred smell. When this location was later paired with a memorable, aversive signal – a painful electrical shock – the fly learned to avoid this location and spend more time on the opposite side of the chamber. From previous research, Miesenböck knew which neurons were involved in learning to associate the shock with an odour and could therefore directly target this system with optogenetics. By activating these cells with light when the fly was in the location of its preferred smell, Miesenböck’s team was able to provoke identical avoidance behaviour even though no electric shock was given. Thus, the fly learned from an experience it never had.

Might we be able to use this technique to control our minds in the future? Miesenböck thinks that it will be a while before optogenetics can be used in humans: “You would have to express a foreign gene in a targeted fashion and this is where the show-stopper currently lies”. While using this technique in humans may be a long way off, he does believe that optogenetic research in flies might nonetheless directly aid our understanding of the human brain because biology is generally conserved. “Nature rarely invents the wheel twice”.

For now, Miesenböck thinks the field should focus on blurring the boundaries between work in whole organisms and fine-scale research in cell cultures. They could make use of the fact that tissue in a cell culture can be treated as if it was still part of a functioning brain by activating the cells with flashes of light – a use of optogenetics that is currently underappreciated. “There will be room for brain-free neurobiology, where optogenetics provides the interface to allow researchers to really talk to and feed artificial information into neuronal systems”.

Miesenböck also advocates using light “to enable scientists to drive nervous systems outside their normal operating limits, because this is often where mechanisms reveal themselves”. Miesenböck’s team used this approach to investigate the origin of sex differences in flies. While male and female fly brains are very similar, they nonetheless display sex-specific courting behaviours. The gene that controls male courting behaviour is expressed in a very small number of neurons in the abdominal ganglia of the fly. By specifically targeting these cells with optogenetics and shining light onto this circuitry, Miesenböck’s team was able to produce male courting behaviour in all the flies, even the females (2). Thus, they were able to show that females possess a bisexual brain containing a motor programme necessary for male courtship behaviour, but do not activate it because the neuronal commands required for the behaviour are absent.

With the ability to dissect neuronal functioning in the healthy brain, optogenetics might also hold potential to help understand the exact mechanisms that cause neurological and psychiatric diseases such as depression and schizophrenia and even help treat them. For example, Karl Deisseroth and his team at Stanford University in California published a study in Science last year that used optogenetics in rats to investigate directly how deep brain stimulation might alleviate symptoms of Parkinson’s Disease, something that had previously been poorly understood (3).

Thus, despite the difficulties in applying the method to humans, Miesenböck is hopeful: “With optogenetics we can really identify the players that are responsible for particular behaviour and that may give us knowledge for targets of more conventional treatment. Then conventional treatment can become more effective and cleaner.”

References:
1. Claridge-Chang et al., 2009. Writing memories with light-addressable reinforcement circuitry. Cell 139:405- 415.
2. Dylan Clyne & Miesenböck, 2008. Sex-Specific Control and Tuning of the Pattern Generator for Courtship Song in Drosophila. Cell 133:354-363.
3. Gradinaru et al., 2009. Optical deconstruction of parkinsonian neural circuitry. Science 324:354-359.

This article appeared in 'Phenotype'. Here you can read the magazine its entirety.

A shorter, related post can be found on my blog here.

Death rites or delusions?

Yesterday evening I watched ‘Fantastic Mr. Fox’, Wes Anderson’s interpretation of Roald Dahl’s story about the adventures of Mr. Fox and his family. The film juxtaposes wonderfully human and animal behaviour: relationships between the animals are as layered and complex as those of humans, while their dining habits are highly characteristic for animals - putting their faces in their plates and ripping the food to pieces. As well as being a delightful story, this film also touches upon an interesting and ever-present question: do animals have feelings in the same way as humans do?

One aspect of this issue was addressed in two arresting articles in the always-interesting scientific journal Current Biology, both of which received a lot of press last week. Both concerned the reactions of groups of chimpanzees, one wild and one captive, to the death of a member of their troop. When Pansy, a 50+ year old female chimp living in the Blair Drummond Safari and Adventure Park in Sterling was dying, the females of the troop groomed her and following her death, her daughter spent the night by her side on a platform where she would never normally stay. The images from the other article were no less affecting: a mother carrying her deceased infant for as long as 68 days after its death.


When reading such stories, it is hard not to think in terms of the chimps' grief or anguish and to consider these rituals as part of a mourning process, just as we might respond to the loss of a mother or child. There are reports of death rituals in birds too, but I doubt they would affect us in quite the same way as watching these wild, yet recognisably close creatures in an apparent state of mourning - chimps are genetically our closest ancestor and possess features that we cannot help but respond to.

But at what point does such empathy turn into anthropomorphism? This touches on an old question of how well we can start to describe how animals actually feel, even one as close to us as a chimp. The philosopher Thomas Nagel once raised this famously in his succinctly titled article "What is it like to be a bat?”. This general problem was also a prime driver in the behaviourist movement in experimental psychology where people such as B.F. Skinner, and more recently Howard Rachlin, have argued that there can only be observable inputs and outcomes - the animal responds to its environment partly as a sort of reflex – as internal emotions or motivations are just hypothetical constructs which we try to guess through an animal’s responses.

The particular interpretations of these two recent Current Biology articles are discussed in a lucid comment piece in the Guardian last Saturday by Ros Coward, pointing out a need for replicable research that measures tangible effects such as stress levels or the amount of time spent engaging in particular behaviours. These existential questions concerning what goes on in the minds of animals are approached almost from an entirely opposite angle across a few episodes of my favourite radio programme Radiolab, where the potential similarities between our minds and those of other mammals are explored (main episode: Animal Minds, Shorts: Fu Manchu and The shy baboon).

There is also another side to the anthropomorphism that is less remarked upon, which highlights something fundamental, perhaps unique, to being human: our incessant ability to find narrative.  In a fascinating study which builds on original research from the 1940s and was published in the journal Brain in 2002, a group lead by Uta Frith at UCL documented how people would ascribe intentions and emotions such as being happy or even seduction to abstract shapes moving around on a screen. Have a look at the coaxing, dancing and drifting shapes and see for yourself how easy it is to attach human emotion to these inanimate animated objects. Interestingly, this effect that was much less evident in adults with autism, which goes along with a prominent theory that autistic people lack an ability to ascribe mental states to others.

Do these results published in Current Biology mean that animals have the same feelings of fear and pain as we do? If so, does the only difference between them and us lie in the fact that we can put our feelings into words to explain them to others? And how ‘animal’ are we? Are we just as much responding to our environment in a reflex-like manner, but with the benefit of having an ability to narrate our actions, seemingly explaining them to ourselves and others?

Why does sleep deprivation alleviate symptoms of depression?

Here's a link to an interesting article in the New York Times about depression and sleep that surprised me. A couple of months ago the neighbours upstairs had a new baby. He cries a lot, day and night, and you would think that the sleepless nights his crying causes could easily make anyone depressed. Indeed, postpartum depression can be remarkably common, affecting anything between 5-25% of new mothers in the first few months after giving birth. But if anything, according to this article by Terry Sejnowski, a renowned computational neurobiologist, an entire night without sleep can actually lift symptoms of depression in such afflicted women. Unfortunately, this is no miracle cure. You cannot escape the lack of concentration, irritability and memory loss inevitable after a night without sleep, and even the shortest nap can break the spell. Exactly how sleep deprivation alleviates symptoms of depression is still a still largely unknown, but one avenue of research scientists are currently exploring focuses on general sleep patterns with a particular focus on the rapid eye-movement (REM) stages of sleep. A link between REM sleep and depression has already been made: a common antidepressants blocks REM sleep and people with a genetic predisposition for entering REM sleep very early on in their sleep cycle are at a larger risk of becoming depressed. Thus, while staying awake for one night may not actually, at least not in a longer term, cure or even treat depression effectively, the alleviating effects of staying awake may give scientists an interesting direction for research into depression.