Pulling on DNA’s bootstraps

Fifty years after the discovery of the structure of DNA, a new use has been found for the very molecule of life – as fuel for a molecular computer.

Ehud Shapiro of the Weizmann Institute of Science has, for many years, been working on developing the information technology inherent in DNA to power complex calculations. In the longer term, measured in decades, we might find autonomous, programmable molecular computers in vivo, sensing biochemical anomalies, consulting their programmed medical knowledge and synthesizing the appropriate drug molecules in response, Shapiro told Spotlight.

Ehud Shapiro

Ehud Shapiro

DNA provides one of the most compact and efficient digital information systems known. With just four basic building blocks it can represent the ingredients and blueprint for making a microscopic algae or an elephant in a molecule-sized space. A decade ago, researchers such as Leonard Adleman of the University of Southern California began to find ways to make laboratory-scale DNA manipulation solve mathematical puzzles, such as the travelling salesman problem. More recently, Shapiro demonstrated that a molecular-scale system that exploits the processing power of enzymes could carry out calculations without human intervention.

However, as with any electronic device, these molecular computers need a power supply. Obviously, connecting up a conventional power source, would be one option but Shapiro working with Yaakov Benenson, Rivka Adar, Tamar Paz-Elizur, and Zvi Livneh wanted a more frugal solution. They have now found that the single DNA molecule that encodes the input to the computation can provide all the power requirements too. In terms of speed and size, DNA computers may eventually surpass conventional computers that use silicon microchips.

DNA. Source: Proceedings of the National Academy of Sciences

DNA. (Source: Proceedings of the National Academy of Sciences)

Previously, the researchers had used the well-known energy molecule of living things – ATP, or adenosine triphosphate, as chemical energy for their DNA computers. In the new approach they have designed out this independent power supply so that the DNA input molecule spontaneously releases energy for the computational operations to take place. In each computational step, two complementary DNA molecules – an input molecule and a software molecule – spontaneously bond together. The software molecule then directs a DNA-cleaving enzyme to cut a piece of the input molecule. The enzyme, FokI, breaks two bonds in the DNA double helix, releasing the energy stored in these bonds as heat, sufficient to trigger the next step in the computation.

The Guinness seal of approval

The Guinness seal of approval

The computer itself is similar to the earlier system devised by the team. It is a special case of a Turing machine, a two-state, two-symbol finite automaton. It can answer simple questions about binary strings, which are encoded as DNA strings, such as Does a binary string of a’s and b’s contain an even number of a’s? or Is the length of the string even or odd?

This may seem trivial but such logical operations are at the heart of the computational process allowing much more sophisticated questions to be asked by linking many individual devices. Ultimately such computers could provide biological data analysis in vitro, without the need to convert the information to electronic format (i.e. sequence the DNA), Shapiro told us.

Astoundingly, a single teaspoon of Shapiro’s computer soup might contain 15000 trillion DNA computers, together performing 330 trillion operations per second with what he says is 99.9% accuracy per computation step. The overall process produces just 25 millionths of a Watt of waste energy. Shapiro’s work was recently awarded the Guinness World Record as the world’s smallest biological computing device.

Further reading

Proc Natl Acad Sci (USA), 2003, 100, (5), 2191-2196
http://www.pnas.org/cgi/doi/10.1073/pnas.0535624100

DOI: 10.1073/pnas.0535624100

Ehud Shapiro
http://www.wisdom.weizmann.ac.il/~udi/

Suggested searches

Molecular computers

DNA and chips

The secret ingredient in a future biological computer is to add a little DNA. But, making hybrid devices from a silicon chip and a strand of genetic material means mixing hard-wired microelectronics technology with the softer world of molecular biology.

Now, chemists at the University of Newcastle upon Tyne have come up with a solution that could lead to new lab-on-a-chip devices and biological sensors for use in medicine and environmental analysis. It might even one day allow biology to compute or provide an interface between electronic devices and living things.

Ben Horrocks

Ben Horrocks

Newcastle chemists Benjamin Horrocks and Andrew Houlton and their colleagues have devised a way to automate the solid-phase synthesis of DNA on a semiconductor chip. They believe their method could readily be adapted to the conventional fabrication techniques of photolithography used in the microelectronics industry to pattern the microscopic transistors and circuitry on a computer chip.

The team recently reported how it has found a way to attach a DNA sequence of just seventeen nucleotides to a silicon surface modified with organic molecules. The key to unlocking hybrid DNA chips lies in the team’s use of bifunctional organic molecules. At one end the molecule has the right chemistry to allow it to be attached to an oxide-free silicon surface. The other end of the molecule has a functional chemical group on which a DNA strand can be grown using an automated DNA synthesizer of the kind found in biotech laboratories the world over.

Andrew Houlton

Andrew Houlton

The team is working with two aims in mind – first, the development of chemical sensors and secondly the synthesis of DNA on silicon surfaces for nanoscale molecular architecture. This addresses the projected reduction in the size of electronic components which by 2015 are predicted to be of the order of nanometres (i.e. built from molecules), explains Houlton.

Gel electrophoresis reveals DNA is attached to the silicon

Gel electrophoresis reveals DNA is attached to the silicon

Previous endeavours in this area have generally used glass in preference to silicon wafers and those that have focused on silicon have applied organic molecules to an oxidised surface rather than the naked silicon chip. The Newcastle team has now confirmed that it is possible to cover the surface of a silicon chip with DNA strands. Moreover, the 17-base DNA strands can be coupled with the complementary DNA strand making the familiar DNA double helix. From the nanodevice perspective the importance of the team’s work lies in their ability to pattern the surface of the silicon rather than simply randomly deposit DNA strands. Patterning using the printing and etching techniques of microelectronics fabrication means they can tightly control the arrangement of the DNA on the surface and so produce what might one day become molecular circuitry.

A DNA-patterned silicon surface

A DNA-patterned silicon surface

Sequential modification of a silicon surface with DNA

Sequential modification of a silicon surface with DNA

Further reading

Angew. Chem. Int. Ed., 41, 615 (2002)
http://www3.interscience.wiley.com/cgi-bin/abstract/90512278/ABSTRACT

DOI: 10.1002/1521-3773(20020215)41:4<615::AID-ANIE615>3.0.CO;2-Y

Benjamin Horrocks
http://www.ncl.ac.uk/chemistry/staff/profile/b.r.horrocks

Andrew Houlton
http://www.ncl.ac.uk/chemistry/staff/profile/andrew.houlton

Suggested searches

Molecular Electronics
Nanotechnology