Synthetic Biology: The leap from life-sciences to engineering

To read, edit, write, and rewrite forms of life is now possible, even for high school students, at home! (Representative Image)

By S Ramadorai, Raman Srinivasan & S Shivaramakrishna

While I (Ramadorai) have spent much of my professional life in the software industry, for almost a decade now, I am trying to learn and understand recent developments in the field of biology with the help of a few younger colleagues. School textbooks taught us that, in 1953, Watson and Crick “decoded life,” deciphering DNA as a 3-D double helix.

We now understand the DNA as the source code of life and know that it contains biological information and carries the genetic instructions for the development of all life. This Nobel Prize winning discovery of the double helix marked the shift in biology from a descriptive discipline to an analytical science. In the decades since, biologists have made a Kantian leap to a synthetic techno-science. The development of novel techniques like PCR (Polymerase Chain Reaction) to amplify tiny segments of DNA in 1983-84 have led to greater comprehension of the language of life. The grammar of genetic composition is now quite well understood. Biology is well on its way to becoming an established engineering discipline and engineers are driving this transformation. And like engineers elsewhere, they too are designing, building and testing new forms of things, biological. They are also putting together a new discipline.

Some 70 years ago, Alan Turing, the legendary British computer pioneer did path-breaking work, among other topics, on the formation of biological patterns. More recently, influential computer engineers began to view DNA as a storage medium for programmes executed by living cells. However, the leading edge of engineerable biology is of relatively recent origin—dating back to only early 2000—and is called synthetic biology. This is a field, inspired by the original Greek word “synthesis” that means “to assemble”, and is focussed on putting together biological components in order to better understand biological systems. Synthetic biology seems to have made exponential progress in the last two decades and it makes even a hardware engineer looking at the field from a critical distance, envious.

I (Ramadorai) propose a series of brief essays introducing the reader to this fast moving world of synthetic biology. Just as the 20th century was shaped by nuclear physics and semiconductor physics, the 21st century is already being defined by a new biology, a biology inspired and designed by best practices in engineering. Today, we can not only decode biology, but edit it, and furthermore synthesize it. To read, edit, write, and rewrite forms of life is now possible, even for high school students, at home!

Curiously enough, the first synthetic biology lab was nucleated right in the middle of the AI Lab at Tech Square of the Massachusetts Institute of Technology, in the mid-1990s by a MIT hardware engineer, Tom Knight. As a young high school student, Knight had been mentored by professor Marvin Minsky, founder of the MIT AI lab and later as a researcher, Knight worked on the early internet and also helped build the first LISP machine. A pioneer in early chip design, Knight anticipated the eventual physical limitations of semiconductors and turned to biology for building a future-proof Post-Moore’s Law world.

In the mid-1960s, around the time Gordon Moore published his article outlining what became known as Moore’s Law, early commercial semiconductor chips were manufactured using 50 micrometer or 50,000 nanometre lithography process whereas now your mobile phone might have a chip made with 5 nm process. Some far-sighted engineers like Tom Knight and science administrators in the US began to be concerned about Moore’s Law encountering physical limits. For example, in a 5 nm chip, there are typically about 175 million transistors per square millimetre.

In such a chip, the distance between two transistors is typically 5 nm, and a single transistor itself is barely 10-12 atoms thick. One approach to transcend the physical limitations of semiconductor physics was to explore biological alternatives. We know that biological cells process information efficiently. A single cell consumes just one trillionth of a Watt. Could one design and construct biological circuits using principles similar to the design of electronic circuits? Might biological processes be used to manufacture new types of devices? Could data be stored on DNA for thousands of years and retrieved in the distant future? Could one make novel materials through biology? Can biology reboot computing?

In 1996, Tom Knight ran a summer study programme for DARPA, conceptualising biological computing and manufacturing. He articulated the need to apply well-established engineering practices, such as the design-build-test cycle and the use of standardised parts. The argument was that the ability to put together biological forms with well-defined modular components would bring much needed engineering rigour to biology. The summer study was soon followed by DARPA funding Knight’s first synthetic biology lab within the MIT AI lab. It was staffed entirely by non-biologists and lacked several of the customary appurtenances of a bio-chemistry lab such as fume hoods, autoclaves or the usual means for disposal of hazardous waste!

Nevertheless, many computer science colleagues looked with askance at test tubes filled with bacteria and various incubators placed alongside computers. In any case, well-established engineers and computer scientists began hacking biological structures and processes with an engineering mindset and computational toolsets. Standard tech design principles like abstraction, encapsulation, modularisation, standardisation, and decoupling began to be imported into the making of this new biology. The great hacking of biology had begun.

Knight attracted other like-minded engineers to the revolution in biology at MIT. Some, like Randy Rettberg, joined from the industry. Rettberg was an expert in VLSI design and had worked at Sun before joining MIT to invent synthetic biology. Drew Endy was an intellectual serial-migrant, moving from “structural engineering to environmental engineering to chemical engineering, to genetics to cell biology, to biology to biological engineering.” Gerald Sussman, professor of electrical engineering at MIT and the author of the familiar Structure and Interpretation of Computer Programs, was yet another polymath engineer who played a key role in the early days of synthetic biology at MIT. These engineers engineering a new biology were strangers to biology, but in under 10 years, the field had made enormous progress, and Nature celebrated its birth with a cover story in November 2005 titled “Synthetic Biology: Life is what we make it.”

On its cover Nature prominently displayed a comic strip titled “Adventures in Synthetic Biology” and in its introduction, as if to highlight the fun aspects of this new science, it led with the story of a living biological camera made with the common E. Coli that could take pictures. A biological film of the engineered bacteria served as a photographic film as well, the editors of Nature pointed out. They declared that “this technology allows biological components, circuits and potentially replicating organisms to be developed from scratch, possibly based on different genetic codes from those found in the wild.”

This special issue devoted to synthetic biology had invited contributions from several pioneers. George Church, professor at Harvard, and amongst the most imaginative synthetic biologists, articulated the need for a strong culture of safety and risk assessment, and stakeholder dialogues in this emerging discipline. He wrote, “The developing field of ‘synthetic biology’ could be seen as yet another expression of scientific hubris. It has potential benefits, such as the development of low-cost drugs or the production of chemicals and energy by engineered bacteria. But it also carries risks: manufactured bioweapons and dangerous organisms could be created, deliberately or by accident.”

Church emphasised the need for more outreach. And in his programmatic essay, Drew Endy called for “vibrant, open research communities.” Outreach and open research have been, indeed, two key characteristics of this new field. One manifestation of this commitment to openness and inclusion has been the extraordinary success of the annual global student competition called iGEM. From a handful of teams in 2004 to over 350 teams from 60+ countries last year, the iGEM has become the incubator for young synthetic biologists. And more importantly, in the last 25 years, several significant start-up incubators in synthetic biology have successfully adapted the tech incubator model and given birth to many synbio unicorns.

Today, you can buy synthetic biology products on the market, even in India. For example, if you are a diabetic and take Sitagliptin, it is a drug manufactured using synthetic biology. In the upcoming essays, we will highlight several commercial applications of synthetic biology.

“What I cannot create, I do not understand.”
— Richard Feynman (The last message on his blackboard.)

Ramadorai is former vice-chairman, TCS, and Srinivasan and Shivaramakrishna are both with TCS