NYU's Nadrian Seeman

May 4/11, 2005
Technology Research News Editor Eric Smalley carried out an email conversation with New York University chemistry professor Nadrian Seeman during the week of April 24, 2005 that touched on nanotechnology, politics and art.

Seeman was born in Chicago, earned a bachelor of science degree from the University of Chicago, and a doctorate from the University of Pittsburgh. He did postdoctoral work at Columbia University and the Massachusetts Institute of Technology.

Seeman's start in nanotechnology began when, after a frustrating macromolecular crystallization experiment in the fall of 1980, he moved on to the SUNY Albany campus pub, where he made the connection between his research and a drawing by M. C. Escher.

He has won the Sidhu Award, the Feynman Prize in Nanotechnology, the Tulip Award in DNA-based computation, and is a Fellow of the American Association for the Advancement of Science. He holds the Margaret and Herman Sokol Chair in chemistry at New York University.

His major research interests are nucleic acid structure, topology and nanotechnology: branched, knotted, and catenated DNA and RNA motifs, as they relate to genetic recombination, to DNA nanotechnology and to DNA-based computation.

TRN: What got you interested in science and technology?

Seeman: I thought science and technology were both neat, and that one could make a lasting contribution, maybe make a difference by working in the field. In addition, one could spend one's day having fun by solving problems and having creative ideas; in this, I was correct.

TRN: What are the important or significant trends you see in science and technology research?

Seeman: I'm not really aware of trends. I do what interests me, and I hope that others are also interested in it.

TRN: How different is DNA nanotechnology and DNA computing from DNA-based drug discovery, disease research and genetic engineering?

Seeman: DNA nanotechnology and DNA computing ultimately may have impact in the biological sciences, but they are fundamentally not biologically oriented enterprises. They both use the chemical properties of DNA that allow it to function so well as genetic material, but they are not related to genetics. DNA is just a molecule.

TRN: Tell me about the trends in research on the technological uses of DNA. What are the pluses and minuses of today's DNA technology research priorities? What do you see as the most urgent needs in these areas?

Seeman: DNA nanotechnology is still a field in its infancy, so it is in an era of "100 flowers blooming".

Many of us believe that DNA offers a powerful bottom-up method for the organization of nanoelectronic components.

I suggested 25 years ago that DNA could organize lattices to facilitate macromolecular crystallization, both for academic purposes and for drug discovery.

Nanorobotics is a coming area with many applications, from novel materials to nanotherapy. More government money needs to be directed to these efforts. Most of the practitioners in the area are scrambling for support. My sense is that the most urgent need is to develop high-resolution 3D periodic or pseudo-periodic arrays.

The most pressing technical problem is the lack of a convenient inexpensive method for purifying synthetic DNA strands of the lengths used (up to 150-mers) to chemical levels of purity.

TRN: How does DNA computing differ from silicon chips and also from other forms of nontraditional computing, and what could it be used for?

Seeman: DNA computing is designed for problems that can take advantage of the massively parallel nature of molecules. Its main contribution to DNA nanotechnology has been the notion of algorithmic assembly, owing to Erik Winfree, which advanced the field beyond simple periodicity.

TRN: Can DNA computing be applied to "traditional" number-crunching parallel-computing problems, or is it better suited to algorithmic self-assembly and controlling biomedical technologies like drug delivery systems?

Seeman: I am not a computer scientist, but I suspect it is not well suited to traditional problems. I certainly feel that it is better suited to algorithmic self-assembly and biologically-oriented applications. Many people would probably disagree with me.

TRN: What makes DNA particularly useful for nanotechnology, and what does it lack?

Seeman: It is important to realize that DNA is largely used in nanotechnology in branched motifs, which are easy to design, from both the perspectives of molecular architecture and sequence assignment.

It is possible to self-assemble these branched motifs into objects, periodic and aperiodic arrays and nanomechanical devices. It is possible to direct the assembly processes with high specificity using sticky ends and other cohesive interactions. This gives us an enormous range of structural possibilities, limited only by the imagination.

It is the molecule whose intermolecular interactions are best predictable, both regarding affinity and structure.

In addition, it is a stiff molecule, with a persistence length of 50 nanometers in normal conditions; it is convenient to make; there are commercially-available modifying enzymes; it is robust up to 90 degrees C; it is amenable to biotechnology methods; it has an externally readable code even when it is in the double helical form; it has functional groups every .34 nm along the helix axis where it can be derivatized; there are hundreds of derivatives of DNA with varied properties.

As for deficiencies, like any molecule, its overall physical properties may not be exactly suited to a particular application.

TRN: What do you mean by "structural purposes".

Seeman: I mean using 3D DNA lattices to act as a host lattice to scaffold guest biological macromolecules in periodic arrays for crystallographic structure determination.

TRN: Can you give me a brief explanation of sticky ends?

Seeman: If a double helix is made with strands that are not the same length, one strand will overhang one of the ends. This overhang, say 4 to 8 nucleotide units is called a 'sticky end'. If another double helical molecule has a complementary sticky end, the two double helices will cohere.

TRN: Where is DNA likely to show up first in terms of useful technology? How soon could this happen?

Seeman: I don't know. Perhaps in the applications of crystal self-assembly for structural purposes. Only a trillion or so unit cells are needed, so scale-up won't be a problem there.

TRN: What are you referring to with "a trillion or so unit cells"?

Seeman: A crystal only needs about 1012 unit cells to be large enough for diffraction purposes.

TRN: Nanotechnology is a broad, vague term encompassing the cutting edges of biochemistry, inorganic chemistry, materials science and electrical engineering. What does the term mean to you, and what of the many, well-hyped promises of nanotechnology do you see as plausible and which do you see as likely?

Seeman: My favorite one-line definition derives from Carlo Montemagno, "Nanotechnology is taking what you want and putting it where you want it and getting it to do what you want it to do, all on the nanometer scale." I think we'll be able to do that in many systems in the foreseeable future. The applications noted above are all plausible.

TRN: How do the technologies you're working on relate to business, culture, and social life?

Seeman: We are still at the prototype stage. They eventually will result in processes that are likely to be of commercial value.

I do not know how anything on which we are working will have cultural or social impact. They are not in a category different from any other incremental research.

TRN: What are the important social questions related to today's cutting-edge technologies in general?

Seeman: I see changes for now as being incremental, so there is unlikely to be any major social question. If one arises, the relationship between the technology and the public is something that should be decided by the people via their representatives in the government.

TRN: In terms of technology and anything affected by technology, what will be different about our world in five years? In 10? In 50? What will have surprised us in 10 years, in 50?

Seeman: I am a scientist, not a futurist. I don't make predictions.

TRN: What do you imagine you or your successor will be working on in 10 years? In 20 years?

Seeman: I expect to be working on more advanced versions of the things that our current research will have brought to fruition by then.

TRN: What's the most important piece of advice you can give to a child or to a college student who shows interest in science and technology?

Seeman: If you have a passion for it, do it!

Other than a few manipulations, the main thing you learn in graduate school is how to deal with the daily failure of doing research. You have to be able to deal with that. I feel it is important not to go to school to become an uneducated person who has earned a Ph.D. You have to develop into a person who appreciates not only the sciences, but also the humanities. My research program has derived as much from art as from science.

TRN: What are your thoughts on the state of conventional wisdom on science and technology?

Seeman: It is pretty poor. C.P. Snow's 'Two Cultures' are still existent.

People will in the future need to be able to make intelligent decisions about various technological issues. They will need to understand how the scientific process works, and how to recognize which views are legitimate, because they are supported by evidence, and which are not.

There have already been national issues where the public has been relatively undemanding of their representatives, who endorsed what I feel were inappropriate stances.

TRN: What are the current science-related issues in which science is downplayed, ignored or distorted?

Seeman: Star wars, stem cells.

TRN: What could be done to improve the pursuit of science and technology research in terms of business trends, politics, and/or social trends?

Seeman: The public ultimately pays for research. The public needs to be educated as to its value for society, and so that it will support the activity better than it is supported today.

TRN: What books that have some connection to science or technology have impressed you in some way, and why?

Seeman: Peter Medawar's 'Art of the Soluble' has a clear message for scientists: It is your job to solve problems, not merely to grapple with them.

Horace Freeland Judson's history of the first 20 years of molecular biology, 'The Eighth Day of Creation' demonstrates repeatedly how the prevailing wisdom was wrong, and that success was obtained only when people recognized the flaws in the assumptions that everyone made.

TRN: What is the message -- that scientists should avoid intractable problems? That they need to do more to answer the questions they address, and/or something else?

Seeman: That one should choose the questions that look to have solutions within one's scientific lifetime. They should be hard, but not just an intellectual exercise.

TRN: Is there a tension between the rigorous skepticism required by the scientific method and scientists' ability to question orthodoxy?

Seeman: No. They are the same thing. Belief in anything without empirical evidence is inimical to the pursuit of science. We all make implicit assumptions in doing our work, but we must be aware that we are doing this.

TRN: What other readings do you recommend that would bring about more interest and/or a better understanding of science and technology?

Seeman: The people who would read those books are already interested. The trick is to get uninterested people to read such books.

TRN: Sports, commerce, crime fighting and warfare are glamorized in our society. Can science be made sexy? What would it take?

Seeman: I don't know if sexiness is the way to sell science. Our educational system is pretty successful at stifling the natural curiosity with which we are all born. That would be a place to start.

TRN: Is there a particular image (or images) related to science or technology that you find particularly compelling or instructive? Why do you like it; why do you find it compelling or instructive?

Seeman: My program was founded when I realized that the fish in Escher's woodcut 'Depth' were like 6-arm nucleic acid branched junctions and that they were arranged like the molecules in a molecular crystal.

TRN: What are your interests outside of work, and how do they inform how you understand and think about of science and technology?

Seeman: I read, go to the theater, and go to art museums. I get lots of ideas from art. For example, Anselm Kiefer's [Osiris and Isis] suggests a great way to bundle nano-objects with DNA.

TRN: Osiris and Isis is a painting of what appears to be a stepped pyramid with ropes or vines running from top to bottom. Tell me what you're seeing as a way to bundle nano objects with DNA.

Seeman: There are lots of wires with things on their ends (presumably pieces of Osiris). The wires are held together in a bundle. The wires could be DNA.

TRN: What question would you like to be asked in an interview like this? What is the answer to that question?

Seeman: Would you do it again? Absolutely! Life in science has been pretty stressful and frustrating, but I can't imagine a better way to have spent mine.

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Page One

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View from the High Ground:
NYU's Nadrian Seeman

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