Angela Belcher is a materials scientist who makes things with viruses. She is now using them to attack cancer
“IT’S getting a little challenging,” says Angela Belcher. “I feel I am having to make choices now, which I never really wanted to.” But there are only so many hours in the day and she already combines multiple academic disciplines into a repertoire of research that spans an ambition to drive an electric car powered by a virus battery to building better touch-screens for digital devices and lately to giving surgeons new tools to detect and potentially treat minute traces of cancer.
There is more, but as eclectic as her work seems, it is united by a single intriguing idea. Evolution is a great problem solver and over millions of years has produced creatures of incredible breadth and complexity that can survive in the changing world around them. So why not copy the way nature innovates, speed it up and use it to help solve some of the problems researchers are presently working on. And that, in essence, is what Dr Belcher and her colleagues at the Massachusetts Institute of Technology (MIT) do. They rapidly evolve genetically engineered organisms to manufacture new materials and devices.
From the ocean
It began in the 1990s with an abalone shell, the sturdy home of a mollusc with a beautifully decorated mother-of-pearl interior. Dr Belcher was researching her PhD at the University of California, Santa Barbara, and was studying how abalones build their shells. The molluscs produce proteins which combine with ions of calcium and carbonate in seawater. This provides the material for them to make two types of crystals, which they assemble into layers to create an immensely strong composite structure.
Angela Belcher, 2013 winner of the Lemelson-MIT Prize Video: Lemelson-MIT
As she looked out of the window one day while wondering about this, her gaze drifted to a periodic table of elements stuck on the wall. If an abalone has within its DNA the ability to code for the proteins needed to gather the materials to construct a shell, would it be possible to tinker with the DNA sequences in other creatures to gather some of the elements on the periodic table? In particular, Dr Belcher asked herself, could creatures build semiconductors like those used in electronic circuits?
The idea might seem far fetched, but Dr Belcher thought that
the reason it had not happened before could be that nature had never been given the opportunity to try. Sea creatures once had soft bodies but started to build shells and bones
500m years ago in a geological period known as the
Cambrian. That could have been in response to increasing levels of minerals in the ocean. “
It took them 50m years to get good at it,” says Dr Belcher. “
Students in a research lab are not that patient.”
So the process would need to be speeded up.
The leap from evolutionary biology to semiconductors came naturally to Dr Belcher. She did her bachelor’s degree in creative studies and was allowed to combine different sciences. This highly multidisciplinary approach continued with her three PhD supervisors being experts in molecular biology, chemistry and physics. But it caused a bit of a problem with her first grant proposal in 1999, on becoming a professor at the University of Texas, Austin. The project was to find bacteriophages (a type of virus that infects bacteria, not people) that could be genetically engineered to bind to inorganic materials that they would not normally have an affinity for—in particular, semiconductors. If that was possible, then the viruses might be used as a template to grow and assemble electronic circuits, much like an abalone constructs its shell. It was, said one reviewer of her proposal, an “insane” idea.
Nevertheless, Dr Belcher stuck with her research and eventually was funded by the US Army. (Though interested in promoting basic science, the army likes to keep a look-out for potential breakthroughs in electronics which might benefit the increasing amount of technological kit it now uses.) In a paper published in 2000 in Nature, Dr Belcher demonstrated that her idea did indeed work. In 2002 she joined MIT and further scientific papers followed in collaboration with a number of her colleagues. Some of those papers explored making the components of a battery using viruses.
The technique begins by genetically modifying the somewhat basic DNA of a bacteriophage. This can be done to produce small but multiple changes in a billion or so viruses. All these variants, huge in number but individually tiny enough to be contained in a droplet of liquid, are then exposed to the material which the researchers are interested in manufacturing. Any viruses that show an affinity towards the material by attaching to it are gathered up. There may be only one or two in a billion, but when these candidates are used to infect a bacteria, millions of copies with identical DNA are made. The process can then be repeated to refine the characteristics. It is akin to high-speed natural selection. With further genetic modification and by changing the growth conditions, the selected viruses are used to bind with specific materials and assemble battery components.
Having found viruses happy to attach to nanowires of cobalt oxide, the researchers were able to produce a negative anode, one of the two main functioning parts of a battery.
Making a positively charged cathode, the other important bit, was more difficult because for a battery to work well the cathode needs to be highly conductive. Nevertheless, Dr Belcher and her colleagues succeeded in getting some viruses to attach to
carbon nanotubes, which are very good at conducting electrons. This resulted in a suitable cathode.
It was then possible to assemble virus-made components into a small cell battery capable of lighting up an LED. This work was published in
Science in
2009, to wide acclaim. Even Barack Obama was given a demonstration of the battery in action.
 |
| Angela Belcher with Virus Battery. Photo: BBC |
Viral motoring
What Dr Belcher would really like to do, however, is to scale the process up so that one day it is possible to produce a virus battery powerful enough to run an electric car. With a paper in Nature Communications in November 2013, that day moved a step closer. The MIT team demonstrated how to use viruses to make a lightweight lithium-air battery, which the researchers think could have an energy density more than twice that of the best lithium-ion cells, the type which are currently used in most electric cars, as well as myriad portable electronic devices. But there is still a long way to go before such a battery could be put into commercial use.
“I think it is very appealing that you can grow environmentally friendly battery parts”
Many still find the idea strange. “I am sometimes told: ‘what are you doing using a virus to make a battery? These things don’t go together,’” says Dr Belcher. Yet, as she points out, biological processes tend to be non-toxic, low-energy ways to make things, and result in little waste, unlike many conventional manufacturing processes in which batteries are made with noxious materials in energy-intensive factories. “I think it is very appealing that you can grow environmentally friendly battery parts,” she adds.
When scaled up for commercial use, the viruses may take a back seat. This is the case with some of Dr Belcher’s projects which are already in the shops. In 2002, along with
Evelyn Hu, a materials scientist then with the University of California, Santa Barbara, Dr Belcher co-founded
Cambrios.
This is a Silicon Valley company which makes transparent silver nanowires for use in touch screens. The nanowires are contained in inks which can be spread across the screen to provide a grid that produces an electrical signal when touched. The production process itself does not use viruses, but is based on techniques employed by them.
A number of companies are now using Cambrios’s technology in the screens of their smartphones, tablets and televisions. In December 2013 3M, a giant American maker of numerous innovative products, said it would employ Cambrios’s nanowire ink in a film that can be used to make giant, flexible touchscreens.
 |
| Image from Silura Technologies |
Siluria Technologies, another Californian company, was co-founded by Dr Belcher in 2007.
It uses viruses to produce templates for materials that work as catalysts to stimulate novel chemical reactions. Siluria is developing
a catalytic process to turn methane, the principal component of natural gas, into petrol (gasoline) for cars. America now has an abundance of natural gas, thanks to the hydraulic fracturing, or “fracking”, of underground rocks.
Siluria is building a demonstration plant near Houston to scale up the process and prove its commercial potential.
Siluria Process
How our process fits into industry, and how our catalyst materials are produced and continuously improved.
Siluria's scalable OCM process technology is designed to produce drop-in fuels and chemicals from a virtually endless supply of methane. Our catalyst materials make this process technology possible.
At the heart of Siluria's catalyst-development workflow are unique nano-structures inspired by nature. We have combined three highly innovative technologies to create our growing family of commercially viable OCM catalysts.
* Materials are 100% compatible with existing recycling infrastructure.
The same basic virus toolkit is now being used by Dr Belcher and her colleagues in the medical field. Dr Belcher is a member of two MIT faculties: materials science and engineering, and biological engineering. In 2010 she added a third by joining MIT’s Koch Institute for Integrative Cancer Research. She was nervous about this: “Working on cancer is so important. I didn’t want to take up space and not contribute and make a difference.” But she attended tutorials and became more confident by considering cancer as yet another material to work with. Although it is early days, the work looks promising.
The plan is to produce a medical probe which can be used to locate extremely small tumours. One way this is being tried is to get genetically engineered viruses to latch onto carbon nanotubes which glow under light from a laser. These viruses carrying the tubes would be injected into the body, and with light shining on the skin, be capable of glowing up to 10cm or so inside the body. The glow can be detected with a specialised camera.
To get these beacon viruses into the right places, the researchers engineer them to have a second affinity, one that makes them bind to certain kinds of cancer cells. They would then find any tumours, attach to them and glow.
The technique is still experimental and is being tried out in the laboratory on cellular models of ovarian cancer, which can be difficult for surgeons to detect when the tumours are tiny. There is a lot to do, but, says Dr Belcher, “I know we can find very small tumours and that should allow surgeons to remove them.”
It also raises an obvious question: if the viruses can find tumours and light them up could they also carry with them some kind of lethal weapon? Not surprisingly, that possibility is being explored, with attempts to engineer cancer-seeking viruses that can carry both an imaging material and a chemotherapy agent.
Dr Belcher’s idea of evolving organisms to help build novel materials and new devices is starting to look like a technique with a large number of potential applications. Already she has to be able to switch from discussing with one group of her colleagues the complexities of binding materials to cancer cells, to debating with others how to clean up industrial wastewater with genetically engineered yeasts (her work is not confined to tinkering with the DNA of viruses). “There are so many areas we would like to be involved in, but we can’t do them all,” Dr Belcher laments. The trouble is, her idea born from an abalone shell seems bound to turn up even more problems which are waiting to be solved.
