Nadrian (Ned) Seeman is widely credited with being the first person to recognize that DNA can be used to design and build programmable nanostructures and nanomachines. With this new way of thinking about self-assembly, he helped to turn chemistry into an information science. He has died aged 75.
Seeman was born in Chicago, Illinois, in 1945. A self-professed ‘Sputnik kid’, his passion for science was ignited by his high-school biology teacher. As a medical undergraduate at the University of Chicago, he was delighted to discover that professors did more than just teach. “I had no idea that I could spend most of my day having fun by doing research and also get paid to do it,” he wrote in an autobiographical note on receiving a Kavli Prize in Nanoscience in 2010.
Although by his own admission not a diligent student, he stayed at Chicago to take a doctorate in biochemistry, before switching to crystallography at the University of Pittsburgh in Pennsylvania. As a postdoctoral researcher, he worked with pioneer of DNA chemistry Alexander Rich at the Massachusetts Institute of Technology in Cambridge. He then joined the biology department of the State University of New York at Albany in 1977. He was disparaging about his time there. “The only thing worse than looking for a job was finding this one,” he wrote.
Ostensibly still a crystallographer, he bent his attentions in a new direction while at Albany. The turning point came when a postdoc asked him to build a model of a forked, double-stranded DNA structure called a Holliday junction, which can occur naturally.
The possibilities opened up by these structures dawned on him one day as he sat in the Albany campus bar recalling the image Depth by Dutch graphic artist M. C. Escher. In the 1955 print, rocket-like fish with horizontal and vertical fins touch ends in a 3D array. Seeman’s epiphany was that the branched units of the Holliday junction could assemble themselves into an orderly structure in a similar way, through interactions at the tips. If these tips were short single-stranded sections of DNA, their ends would stick to other complementary DNA sequences.
Seeman’s 1982 paper1 outlining the idea of making lattices from DNA junctions got, he recalled, zero reaction. Because he was using DNA, a common response to his work was ‘where’s the biology?’ To which Seeman would reply that he was exploiting an aspect of DNA that to the best of his knowledge is not used by biology. People took more notice when, in 1991, he and his graduate student Junghuei Chen synthesized a DNA molecule shaped like the edges of a cube2. Working in the chemistry department at New York University in New York City, where Seeman spent the rest of his career, they used three-armed Holliday junctions as the vertices.
The resulting report2 was initially regarded as something of a curiosity, but Seeman went on to produce more ambitious architectures and functions. In collaboration with Erik Winfree at the California Institute of Technology (Caltech) in Pasadena, and others, he began to think about assembly in algorithmic terms: programming DNA components through their sequences to link up in a manner governed by specific interaction rules. After Winfree, Seeman and their collaborators reported 2D DNA arrays3 in 1998, they and others created DNA ‘tiles’ that self-assemble into a connected mosaic following an algorithm, thereby conducting a kind of computation4.
The architecture of structured DNA
The architecture of structured DNA
From the late 1990s onwards, many other laboratories took up the challenge of what came to be called DNA nanotechnology. This pleased Seeman. “We don’t have to have all the ideas any more, and we don’t have to make all the mistakes,” he said in an interview.
One goal of DNA nanotechnology is to use the nanostructures as a scaffold, for example to arrange into regular arrays molecules that are hard to crystallize alone. Another goal is to use these biocompatible materials for drug delivery and tissue engineering.
Paul Rothemund at Caltech developed this programmable approach to make ‘DNA origami’, in which instructions for more or less any shape could be built into the folding strands5. Seeman and others made assembly reversible using short, single strands that can unzip, allowing DNA nanostructures to be fashioned into dynamic nanomachines.
Seeman was renowned for his blunt way with words and dry, self-deprecating wit. He has been described as a singular character — at once gruff and caring, vulgar and articulate, stubborn and visionary. Winfree told me, “I feel it’s no accident that DNA nanotechnology sprang forth from someone who took almost a perverse pleasure in thinking differently.”
Seeman’s many honours and awards included the American Chemical Society’s Nichols Medal in 2008. His real legacy, however, is to have launched a field of startling originality, the full potential of which has yet to be felt. “DNA nanotechnology has taken on a life of its own since Ned’s original vision,” Rothemund wrote6 in 2006. “We look forward to a new ‘DNA world’ in which an all-DNA ‘bacterium’ wriggles, reproduces and computes.”