In This Issue
Fall Issue of The Bridge on the Convergence of Engineering and the Life Sciences
October 1, 2013 Volume 43 Issue 3

The Convergence of Engineering and the Life Sciences

Tuesday, September 24, 2013

Author: Phillip A. Sharp and Robert Langer

Editors' Note

Two entities converge when advances and time channel them to the same point. This is an appropriate way to characterize and address converging research in life sciences and engineering, computation, and physical sciences.

The story of convergence starts in 1953 when molecular biology originated in the discovery of the structure of DNA by Watson and Crick (see timeline in Figure 1). Some consider this event in life sciences equivalent to Newton’s discovery of the principles of physics 200 years earlier. The importance of this statement is that molecular investigations of DNA are very recent and full fruition of this breakthrough is likely to unfold for centuries.

Figure 1

The decade following Watson and Crick’s insight saw the elucidation of the genetic code, the process of information transfer from DNA to synthesis of protein, and regulation of gene expression. The ability to synthesize a gene, called genetic engineering, emerged from many pioneering sources in the 1970s and led to innovations such as biotechnology, the first major translation of Watson and Crick’s discovery into societal benefit, yielding both new disease treatments and the creation of jobs and wealth. Ultimately this ability to isolate and synthesize genes led to the genomic era in the 1990s.

Mapping the human genome defined biomedical science at the turn of this century, 50 years after Watson and Crick’s original report in Nature. The sequencing of the first genome took 20 years, and today it takes an hour, if not minutes. This and associated advances in complex genetics have fundamentally changed understanding of human evolution, cancer, and even mental disorders.

The “-omics” movement, developing alongside genomics, sparked, for example, transcriptomics, sequencing of the RNAs in cells; proteomics, determination of all the proteins in cells; and metabolomics, characterization of all the metabolites in cells. These are less precisely defined than the genome as an objective but are dramatically revealing the components of cells in real time.

A beneficial tangent of genomics is the rapid and inexpensive sequencing of DNA. Before long, the sequences of the genomes of plants and microorganisms and other life forms will reveal an almost unlimited set of new genes, many with novel functions, the permutations of which will enable new scientific processes, medical treatments, and even fuel sources. As we wrote in 2011, the next challenge in biomedical research will be to solve problems of highly complex and integrated biological systems (Sharp and Langer 2011). We pointed out that there is an increasing need to merge disciplines in different fields to address such problems.

Mapping the genome required a multidisciplinary approach. Interestingly, the initial proposal for the project came from the Department of Energy (DOE), with its expertise in supercomputing and in large direct projects. The decades-long effort was led by a combination of agencies including the National Institutes of Health and National Science Foundation in addition to the DOE.

The collaboration of these agencies is a good example of the benefits of an integrated approach to the life sciences. Taking advantage of the genomic revolution and evolving toward an astounding new world of possibility will also require the convergence of the life sciences with engineering, computation, and the physical sciences.

Researchers in these fields are ready for the convergence approach. The advances in life sciences over the past decades challenge the community to create an integrated model of cells and multicellular assemblies. For instance, determining the structure of large complexes at an atomic scale offers new targets for drugs and additional frontiers in chemical synthesis. This is the case with the recent discovery of methods to interconvert differentiated cell states, greatly enhancing the power of tissue engineering to some day enable the growth of replacement tissue and even complete organs. Advances at the interface of engineering and life sciences continue to unfold, including the synthesis of genetic material on a genomic scale that raises the expectation of designing cells for specific functions.

Advances in engineering at the nanoscale—dimensions smaller than cells (and on the same scale as many intracellular complexes)—mean that composites can be designed to control cells using their normal cell surface recognition and transport machinery. Similarly, micro- and nanofabrication can create separation technologies at the dimensions of cellular organelles or molecular complexes.

The principles of engineering are powerful for modeling, in a quantitative fashion, large amounts of data and predicting behavior of a system in the absence of a complete description. This insight is critical for life sciences since the combinatorial possibilities of interactions of the thousands of cellular components are too numerous to be fully characterized. In fact, the impact on life sciences of the development of information technology and storage cannot be overemphasized. Thanks in large part to advances in engineering and computational science, it is now possible to store and analyze data on an unprecedented scale, and this is changing all aspects of life sciences. For instance, modern information technology has made it feasible to analyze and share the enormous datasets needed to advance systems biology and integrate medical records with genomic information.

At the most fundamental level, life science is about the transfer of information between generations and, within cells, between DNA and other processes. It is inevitable that the above recent powerful advances will converge into new integrated approaches for investigation and innovation in the life sciences.

The convergence research model was described as the “third revolution” in life sciences in a 2011 white paper by a group of faculty at MIT (Sharp et al. 2011). Before this a similar theme emerged from a report by the National Research Council’s Board on Life Sciences, A New Biology for the 21st Century (NRC 2009). Both publications made a strong case for the promise of this integration and suggested steps that would be important in making it a reality. There are related reports from the National Academies (NRC 2011) as well as at least two ongoing efforts, one from NSF regarding the convergence of knowledge, technology, and society (Roco et al. 2013) and a forthcoming NRC workshop report on key challenges in the implementation of convergence. These efforts have not gone unnoticed; the president’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, led by the National Institutes of Health and Office of Science and Technology Policy, is a strong example of convergence in action.

Convergence continues to accelerate and, with that in mind, the Bridge asked us to edit an issue on this exciting area. Because convergence depends on the integration of life sciences and engineering, most of the articles in the following pages are coauthored by engineers and scientists.

Sarah Petrosko, Catherine Fromen, Evelyn Auyeung, Joe DeSimone, and Chad Mirkin provide an excellent summary of nanotechnology, focusing on two representative examples: spherical nucleic acids (SNAs), which were created in the Mirkin laboratory, and the PRINT (particle replication in nonwetting templates) manufacturing approach pioneered in the DeSimone laboratory. The authors examine novel diagnostic and therapeutic approaches of SNAs, and then explain the PRINT approach, which involves the creation of nanoparticles of virtually any shape for a variety of applications. The authors also cover challenges in nanomaterials and present an outlook for their future.

Arup Chakraborty and Mark Davis consider the sentinel of human health, the immune system. They outline a blueprint for a convergence of approaches from science, engineering, and clinical medicine to produce vaccines against highly mutating pathogens, therapies for autoimmune diseases and cancer, and ways to predict disease states. Progress toward these goals includes (1) the convergence of high-performance computing, physical theory, high-throughput sequencing, and clinical research to define virus vulnerabilities and human immune repertoires and to rationally engineer vaccines against scourges such as HIV; and (2) the use of novel instruments and nanoparticles for monitoring the human immune system to predict disease onset and learn how to manipulate it in order to design therapies.

Doug Lauffenburger and Kathy Giacomini explain the nexus of systems biology and systems pharmacology. As they point out, both require understanding of how complex biological entities function, and this knowledge results from integrating multiple molecular and cell-level components and properties through computational modeling to generate hypotheses and predictions. They explore examples of whole organ phenotyping methods and molecular mechanisms of drug interactions.

Cato Laurencin, George Daley, and Roshan James discuss regenerative engineering, focusing on the role of materials and novel approaches to control cell fate. They describe the scaffold (which is materials based), the cells (which are biology based), stem cell–biomaterial interactions, and the control of cell behavior by both genetic and materials manipulation. They elucidate the effects of the chemical choice of the materials on which the cells grow as well as the physical architecture of the surface, which provides spatial cues.

Stephen Quake surveys the area of microfabrication and its role in medicine, discussing advances in the development of microelectromechanical systems (MEMS), lithography, microcontact printing, and microfluidics. He also describes the application of microfluidics, in particular, to areas such as protein crystallography, cell and tissue culture, single-cell genomic analysis, bioanalytic chemistry, and nanoliter-scale synthetic chemistry.

In the final article, Jay Keasling and Craig Venter examine the new field of synthetic biology, which they define as the application of engineering principles and designs to biology. They review progress in health, such as the creation of new pharmaceuticals; progress in producing new fuels, such as the creation of advanced biofuels from sugar and algae; the formation of engineered bio-based chemicals; food and feed applications; and terrestrial crops. They also consider ethical, legal, and social implications of synthetic biology.

To our knowledge, this issue of the Bridge is the first time scientists and engineers have collaborated as coauthors in a series of articles in a single volume on convergence. We hope these articles will be helpful in educating scientists, engineers, policymakers, and the public on this very important “third revolution.”

References

NRC [National Research Council]. 2009. A New Biology for the 21st Century. Washington: National Academies Press.

NRC. 2011. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. Washington: National Academies Press.

Roco M, Bainbridge W, Tonn B, Whitesides G, eds. 2013. Convergence of Knowledge, Technology and Society: Beyond Convergence of Nano-Bio-Info-Cognitive Technologies. New York: Springer.

Sharp PA, Langer R. 2011. Promoting convergence in biomedical science. Science 333(6042):527.

Sharp PA, Cooney CL, Kastner MA, Lees J, Sasisekharan R, Yaffe MB, Bhatia SN, Jacks TE, Lauffenburger DA, Langer R, Hammond PT, Sur M. 2011. The Third Revolution: Convergence of Life Sciences, Physical Sciences, and Engineering. Washington: Massachusetts Institute of Technology. Available online at http://dc.mit.edu/sites/dc.mit.edu/files/MIT White Paper on Convergence.pdf.

Watson JD, Crick FHC. 1953. A structure for deoxyribose nucleic acid. Nature 171:737–738.

About the Author:Phillip A. Sharp is Institute Professor in the Department of Biology and Robert Langer is David H. Koch Institute Professor in the Department of Chemical Engineering, both members of the Koch Institute at the Massachusetts Institute of Technology.