An Engineering Introduction to Biotechnology

Excerpt

Biological discovery has accelerated tremendously in the decades preceding the twenty-first century and promises to continue. As the solid-state transistor enabled so much of the information revolution, a few fundamental contributions were critical to the life science revolution. Technologies such as polymerase chain reactions, restriction enzymes, and recombinant DNA have opened new scientific possibilities. A new vocabulary has been brought to life—genomics, proteomics, physiomics, etc. What may be missing from the public view is the dependence of these new biological approaches on principles and technologies from engineering and the physical sciences.

There have been several significant breakthroughs in biotechnology that require mentioning the scientists and inventors. This is not meant to be an exhaustive list, but rather a mini who's who of biotechnologists. 1865 Gregor Mendel is the parent of classic genetics. His experiments and observations of hybridizing pea plants were reported in 1865. 1944 Oswald Avery, Colin MacLeod, and Maclyn McCarty in the 1940s put DNA and inheritance together and called it the transforming principle. Before their research, proteins were believed to be the mechanisms for transference of inherited properties. 1953 James Watson and Francis Crick measured the structural form and other properties of the DNA double helix. 1958 Frederick Sanger developed the Sanger-sequencing approach and determined the structure of insulin, for which he was awarded the Nobel Prize in chemistry in 1958. 1973 Stanley Cohen and Herbert Boyer created ways to engineer the recombination of DNA in living organisms. The first results in 1971 used calcium chloride to make escherichia coli more permeable so it would accept a small circular ring of DNA known as a plasmid. Later results were used to create Genentech with businessman Robert Swanson (co-founder with Boyer), one of the first successful biotechnology companies. 1975 M. E. (Ed) Southern developed DNA fragment separation on an agarose gel, followed by blotting onto a membrane where sequence specific probes can be used for identification. This invention led to numerous other assays based on binding or hybridization. 1993 Kary Mullis invented the polymerase chain reaction, which can copy specific regions of DNA, and received a Nobel Prize in 1993.

Biology is usually presented differently than engineering and physical science. The physical sciences strongly promote a reductive approach that decomposes complex phenomena into simpler subsystems that can be incorporated into models. As an example, consider the high-energy physics community's pursuit of subatomic particles. The expectation is that models increase in accuracy with the goal of becoming predictive of the phenomena. Biology has been an observational science. The quantification and reduction of the complex phenomena observed in biology has not usually allowed a reductive approach. This can be a source of frustration for nonbiologists, who often conclude that the science is only a memorization activity with vocabulary and experimental anecdotes in place of models and predictive theories. One of the goals of this book is to present introductory biotechnology from the perspective of someone trained as a physical scientist.

This book is for technical professionals—engineers, physical scientists, and technical managers and marketers. The goal is to create the opportunity for these professionals to determine if their technologies and organizations have relevant application in the life sciences. The plan is to introduce the basic concepts of biology, emphasizing “omic” or “whole mass” approaches, describe large-scale applications such as DNA sequencing, and illustrate technical successes with a few case studies of bioinstrumentation. The subtitle might be “omic” technologies for “ohmic” engineers. We do not attempt to present the detailed biochemistry, safety, or ethical issues that are also important components of biotechnology. It is hoped that this approach will appeal to the reader, will facilitate new discoveries through the interaction of disciplines, and will enable follow-on reading of existing molecular biotechnology texts. The canonical reader of the book is an engineer who has not had biology or chemistry for a while. This book is offered as a “prep class” for more detailed books on biology and biotechnology. I hope this book fills the gap and makes texts like Molecular Biotechnology by Glick and Pasternak reachable.

There are many ways to define biotechnology. Sometimes biotechnology is considered to be the use of engineering principles in biology. Two examples are producing new enzymes for laundry detergent and brewing beer, constrained by safety, consumer appeal, and business considerations. Sometimes biotechnology is used to describe the technical or engineering part of a life science program. This might include instrumentation and software for applications that include drug discovery and DNA sequencing. One common interpretation is that biotechnology is synonymous with genetic engineering, where functions are added or removed by modifying the nucleic acids in an organism. In this book, biotechnology is any technique, technology or application that depends on or benefits from information obtained through the ability to extract, copy, modify, or reintroduce the nucleic acids of an organism.

Many people have enabled this writing endeavor and deserve acknowledgments. I am grateful to my family for their loving support and donating many nights and weekends required for this project. Thanks to the biologists at Lawrence Livermore National Laboratory who have encouraged me, especially T. Carrano, L. Ashworth, J. Felton, P. McCready, and L. Stubbs. I have enjoyed collaborating with many exceptional engineers, computer scientists, and physical scientists, including T. Slezak, J. Balch, and C. Davidson. Thanks to the staff at the SPIE for encouraging the short course on an introduction to genomics and then this writing endeavor.

A special thanks to Bahrad Sokhansanj, a Ph.D. candidate at the time of this writing, for his many contributions and discussions and for his enthusiastic pursuit of our joint projects. Our joint paper, “Genomic engineering: moving beyond DNA sequence to function” (Proceedings of IEEE, vol. 88, no. 12, pp. 1949–1971, Dec. 2000) was an excellent starting point for collecting the thoughts presented in this book and for revising the SPIE short course.

There were also several people who provided significant input on drafts of the manuscript—in particular, Janine Garnham, Beth Vitalis, and Tom Kuczmarski. A special thank you to Kathy Fitch for helping review every version of the manuscript.

I would also like to acknowledge the Public Health Image Library PHIL™ provided at the Centers for Disease Control (CDC) web site http://phil.cdc.gov/Phil. The CDC provided in the public domain the PHIL™ images used in this book. I have included the PHIL™ identification number and the source acknowledgement (organization and scientist) when available. Some of this work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48.

An additional dedication to the heroic people aboard UA93 on September 11, 2001 is appropriate. As one of many people in the Washington, DC area that day, thank you. May the knowledge derived from and the activities that follow this book honor your memory through applications beneficial to humanity.

J. Patrick Fitch

November 2001