Nature India | Indigenus

SciArt Scribbles: CRISPR and the smell of rain

Many scientists embrace the artistic medium to infuse new ideas into their scientific works. With science-art collaborations, both artists and scientists challenge their ways of thinking as well as the process of artistic and scientific inquiry. Can art hold a mirror to science? Can it help frame and answer uncomfortable questions about science: its practice and its impact on society? Do artistic practices inform science? In short, does art aid evidence?

Nature India’s blog series ‘SciArt Scribbles’ will try to answer some of these questions through the works of some brilliant Indian scientists and artists working at this novel intersection that offers limitless possibilities. You can follow this online conversation with #SciArtscribbles .

Mukund Thattai, a physicist practicing biology at the National Centre for Biological Sciences (NCBS), talks to us about bio-art and how some bio-artists from Bangalore are challenging scientists’ new-found power to edit life.

Mukund Thattai

Genetically enhanced humans have long been a staple of science fiction. He Jiankui’s announcement in November 2018 of the birth the world’s first genome-edited babies drew flak for flouting ethical norms governing the use of genome editing technologies. This wasn’t the first time scientists had used the DNA cutting-and-pasting tool known as CRISPR to modify genes in embryos. It was, however, the first time such embryos had been implanted and brought to term in their mothers’ womb. The modifications introduced into the twins’ genomes confer no medical benefit, and may even cause harm. It is an irreversible human tragedy: the baby girls, who never asked for this, will spend the rest of their lives as scientific specimens.

Nevertheless, genome editing is here to stay. Will we learn how to use this technology responsibly?

This is the central question that animates iGEM, the International Genetically Engineered Machines Competition. Inspired by the Massachusetts Institute of Technology (MIT) robotics competitions, iGEM looks at a future in which engineering and biology are indistinguishable. What would happen if we could build new types of cells?

I was at MIT in the early 2000s when iGEM was founded. Though I was doing a PhD in the physics department, I’d grown fascinated with biology. Across campus in the computer science department, Tom Knight and Drew Endy were thinking about how to bring notions of abstraction and design to biological engineering. In 2003, they threw out an inspiring challenge to MIT undergrads: could they engineer bacteria that would blink like Christmas lights? The very next year, undergrads from five US universities tried their hand at engineering cells. In 2005, 13 undergrad teams from the US, Canada, the UK, and Switzerland participated in the first international iGEM at MIT, in what has now become an annual jamboree of creations for student teams from around the world.

Science with a dose of fantasy

iGEMmers think of cells as computers, running an operating system that provides basic functions such as the ability to replicate DNA, translate genes into proteins, and convert nutrients into energy. Designer genes are like applications running on top of the operating system. iGEM teams remix components known as BioBricks, an enormous collection of DNA-based “standard biological parts” that give cells new chemical and physical abilities. Over the years iGEM has featured applications that allow cells to keep time, store a digital bit of information, sense toxic chemicals, and carry out basic computations.

The ethos of iGEM, and indeed of the entire synthetic biology community, has always included a culture of openness, sharing, and excitement for science, coupled with rigorous engineering and ethical practice. In the early 2000s, iGEM embodied a bracing and idealistic vision of our biological future, with a dose of fantasy. At the time our actual ability to manipulate genomes was rather limited. With the advent of CRISPR, this has now changed.

From 2012 to 2014 He Jiankui was the leader of the Southern University of Science and Technology (SUSTC) iGEM team. In December 2018, the iGEM Foundation released this statement: “We are stunned and disappointed by Dr. He’s actions, particularly as a former iGEM team leader. Conducting human genome engineering – and further, doing so without proper research or backing from the broader scientific community – is a clear violation of iGEM’s standards as well as those of the scientific community at large. Had this project been proposed within the iGEM competition, it would have been disqualified for violating iGEM’s policies.”

The power of genome editing is rapidly outpacing our ability to predict its effects or regulate its practice. To deal with this monumental challenge, biologists will need to go far beyond the routine laboratory spaces in which they operate. They will need to partner with historians, social scientists, ethicists and artists. An energetic collective of bio-artists is leading the charge.

Making bacteria that evoke petrichor

In 2009, a group of art students from Bangalore stood before the iGEM judging panel describing an unusual summer project: to construct bacteria that would synthesise geosmin, the substance responsible for the evocative smell of the first monsoon rains. The team’s presentation documented their journey of discovery, as they learned the language and techniques of the life sciences and explored its cultural, ethical, and aesthetic implications. As one of their team leaders, I sat nervously in the back row. My nervousness evaporated when we received thunderous applause from a packed hall. One of the iGEM judges declared: “This changes the way I think about synthetic biology.”

Here’s a little back story to this extraordinary scene.

In 2004, I relocated from MIT to India to set up a synthetic biology lab at the NCBS in Bangalore. Reshma Shetty, an MIT graduate student working with Drew Endy, and I discussed how to put together an iGEM team from India. In the summer of 2006 I ran an open workshop called “A crash course in designer biological networks” to overwhelming response. We assembled an NCBS student team that brainstormed on the kinds of “genetic circuits” that could be built. We zeroed in on one old classic idea: teaching cells to blink. But then we confronted the messiness of biology: all the circuits we built expressed the right proteins and seemed to be correctly assembled, but did not do what they were supposed to.

The team went to MIT as the first from India, and competed with 31 others, only to report three negative results. These were later published in a paper which (to my great surprise) has actually been cited! (In 2012 Navneet Rai, a student guided by K.V. Venkatesh at IIT Bombay and me, finally succeeded in making blinking cells as part of his PhD research).

The iGEM atmosphere was electric, and each one of us came away with a lifelong memory of being present at the start of something big.

Next year, with help from a summer research fellows programme at Indian Academy of Sciences, I assembled a team of six undergraduate students from six Indian institutions. Our project was a proof of principle: “How to build and test a genetically engineered machine in six weeks”. 2008 saw a group of IIT Madras students mentored by their professor Guhan Jayaraman, raise funds with institute alumnus and biotech entrepreneur Shrikumar Suryanarayanan. The team was judged as having the “Best Foundational Advance” at iGEM 2008, and got a special prize for the “Best Engineered BioBrick device”. Many members of this team went on to co-found, with Suryanarayanan, the biotech company Sea6 Energy.

Later IIT Madras iGEM teams have also had great success: the 2011 team was awarded the “Best New BioBrick Part” for a light-induced pump, and in 2013 it received the award for “Best Human Practices”. Since iGEM 2009, which involved 100 teams from 25 countries, multiple teams from India have made consistent appearances each year. Credit for this goes to iGEM mentors across the country, and also to India’s Department of Biotechnology, which encourages and supports the teams through the Indian Biological Engineering Competition (iBEC).

Breaking boundaries

At iGEM 2009, we broke many boundaries.

I had just started working with Yashas Shetty from the Srishti Institute of Art, Design and Technology in Bangalore. Yashas combines art and technology, pushing the boundaries of synthesis and sensation. He wondered whether a living piece of art would be an appropriate iGEM project, something that could provoke and inspire people to think about biology. He then narrowed down the problem, asking: “Could we make a biological device that can influence human emotions?” Out of this was born the “Smell of Rain” project. Yashas and his students landed up in my lab, where they learned molecular biology under Navneet’s experienced stewardship, and formally signed up as iGEM contenders. Describing themselves as “outsiders” in a competition dominated by engineers and scientists, the very existence of the team was a unique experiment in art-science collaboration.

It marked the beginning of an unusual and fruitful collaboration between NCBS and Srishti, under the provocative name ArtScienceBangalore. Building on their “Smell of Rain” success, in 2010 the students imagined a “post-natural ecology” exploring the interactions of genetically-engineered bacteria and worms on a petri-dish, in collaboration with Sandhya Koushika and her student Sunaina Surana at NCBS.

In 2011 the team went even further with their project “Searching for the ubiquitous genetically engineered machine”. They imagined a far future in which bioengineered cells from iGEM covered the planet. How could we tell what was natural and what was artificial then, if we did not establish a baseline today? The students sampled ecosystems across the state of Karnataka, including urban, rural, and forest areas, and used a sensitive method called PCR to search for any evidence of BioBricks in the environment. They did not find any, implying that any future BioBricks in the wild must come from human activity. This foundational effort was awarded the “Best Human Practices Advance”, with the judges particularly praising the role of art-science engagement.

These ArtScienceBangalore projects have gone on to win honourable mentions at the prestigious Prix Ars Electronica prizes, and are currently displayed at the Science Gallery in Dublin.

Does science belong just to scientists?

The idea that artists should be taught molecular biology strikes some scientists as frivolous, and appears to others as dangerous. Is it a worthy use of genetic engineering to make bacteria that can evoke the smell of rain? Why should non-scientists – “outsiders” – be trusted with these hard-won powers? But by the same token, it is reasonable to ask why scientists should be trusted with these very powers.

Scientists and inventors have used genetic engineering to probe the inner workings of cells, as well as to create new medicines, cure diseases and improve crops. The combined benefit of these activities to humanity has been tremendous. In this backdop, cases like He Jiankui’s are an aberration. Nevertheless, the genome-edited baby controversy is a critical opportunity to move the conversation forward.

It is the responsibility of the scientific community to continually earn society’s trust. In this ongoing process, artists have a unique role as observers of the human condition. Bio-artists push the limits of what can be done using the tools of science. They do this to provoke, to make us uncomfortable, to make us think. They do this now, today, so we are forced to imagine and prepare for what might happen in the future.

[Mukund Thattai is at the Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Bangalore. He can be contacted at thattai@ncbs.res.in.]

Suggested reading:

SciArt scribbles: Bringing art and science together for greater good

SciArt scribbles: The mellifluous gene editor

SciArt scribbles: The molecule painter

SciArt scribbles: Coupling creation and analysis with collages

SciArt scribbles: Technology to aid dance

SciArt scribbles: Music to tackle PhD blues

SciArt scribbles: Playing science out

Artists on science: scientists on art

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