building biotechnology 4.0 · knowledge of biotechnology fundamentals, most metaphors fail. it is...

Fourth Edition

BuildingBiotechnologyBusiness • Regulations • Patents • Law • Policy • Science

Yali Friedman

Buildin

g Biotechn

ologyFriedm

an

Business & Economics / Industrial ManagementScience / Biotechnology

Praise for Previous Editions“The need for a comprehensive guide to understanding the inner workings of corporate biotechnology is very acute ... This book does much to fulfill that role.”Nature Biotechnology

“An impressive compendium of information for people getting started in the biotechnology industry.”BioExecutive International

“A very valuable, readable, clear, comprehensive and up to date guide of the biotechnology industry. Building Biotechnology is a must read for investors, reporters, directors and other laymen that wish to understand the fundamentals of the biotechnology business.”William A. Haseltine, Ph.D.Founder and former Chairman & CEO, Human Genome Sciences, Inc.

GREAT OPPORTUNITIES AWAIT those who have the technology, skills, and perseverance to bring new biotechnology products to market. Applications for biotechnology exist in industries as diverse as health care, food

production, manufacturing, mining, oil extraction and refining, environmental remediation, and information technology. To successfully realize the potential of biotechnology it is essential to understand the dynamic commercial, scientific, regulatory, legal, and political factors which shape and define the biotechnology industry.

Building Biotechnology paints a complete picture of the biotechnology industry by illustrating how the complex interactions of legal, political, regulatory, commercial factors drive the biotechnology industry and define its scope. This third edition expands significantly on the foundation laid by the prior two, updating case law and business cases in this dynamic industry, and adding more boxes, informative figures, and tables.

Most importantly, Building Biotechnology enables seasoned business professionals and entrepreneurial scientists alike to understand the drivers of biotechnology businesses and to apply their established skills for commercial success.

Logos PressAction from Knowlegewww.logos-press.com

Yali Friedman, Ph.D., is publisher and chief editor of the Journal of Commercial Biotechnology. He has strong exposure to biotechnology innovation through multiple projects, including the international innovation ranking which he developed for Scientific American’s Worldview, a global biotechnology perspective profiling biotechnology industries and innovation capacity in dozens of countries.

www.BuildingBiotechnology.com

http://www.BuildingBiotechnology.com

Yali

Typewritten Text

www.BuildingBiotechnology.com

Building BiotechnologyFourth Edition

by Yali Friedman, Ph.D.

Published in The United States of America by

Logos Press®, Washington, [email protected]

Copyright © 2014, Yali Friedman, Ph.D.Fourth edition

All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording or by any information storage and retrieval system, without written permission from the publisher, except for the inclusion of brief quotations in a review.

LEGO is a trademark of the LEGO Group, used here with special permission.

10 9 8 7 6 5 4 3 2 1

ISBN-13Hardcover: 978-1-934899-28-1Softcover: 978-1-934899-29-8

I

Contents

IntroductionIntroduction 3

The Development of Biotechnology 7Knowledge and Skills . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Commercialization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11Industry Trends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

ScienceIntroduction to Molecular Biology 19

Information Flow in Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . 19The Big Picture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Drug Development 29Biotechnology vs. Pharmaceutical Drug Development. . . . . . . . . . . . . . . . . 30The Five Basic Steps of Drug Development . . . . . . . . . . . . . . . . . . . . . . 32Qualities of a “Good” Drug . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

Tools and Techniques 41Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41Combinatorial Chemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44Gene Sequencing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45Functional Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46Microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49Manufacturing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52Nanotechnology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54Synthetic Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

Applications 57Green Biotechnology: Agriculture . . . . . . . . . . . . . . . . . . . . . . . . . . 58White Biotechnology: Industrial Processes and Bio-based Products . . . . . . . . . . 66Red Biotechnology: Medical Applications . . . . . . . . . . . . . . . . . . . . . . . 75

Laws, Regulations, and PoliticsIntellectual Property 91

Patents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92When Patents Expire . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99Patent Infringement, Challenge, and Exemptions . . . . . . . . . . . . . . . . . . . 101Patent Licensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109Trade Secrets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113Trademark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114Copyright . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116The Role of Intellectual Property in Biotechnology . . . . . . . . . . . . . . . . . . 116

II BUILDING BIOTECHNOLOGY

Regulation 119Food and Drug Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120Department of Agriculture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146Environmental Protection Agency . . . . . . . . . . . . . . . . . . . . . . . . . . 148Securities and Exchange Commission. . . . . . . . . . . . . . . . . . . . . . . . . 148

Policy 151Supporting Biotechnology Innovation . . . . . . . . . . . . . . . . . . . . . . . . 152Balancing Innovation Incentives with Economic Constraints . . . . . . . . . . . . . . 156

The Business of BiotechnologyBiotechnology Company Fundamentals 163

Company Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163Business Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166Team . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170Company Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

Finance 183Development Stages and Funding . . . . . . . . . . . . . . . . . . . . . . . . . . 184Equity Financing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187Public Markets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194Other Funding Sources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198Valuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

Research and Development 209R&D Stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211The cost of Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213R&D Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214Project Selection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220Outsourcing Innovation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223

Marketing 227Marketing as a Guide for R&D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227Market Structure and Marketing Environment. . . . . . . . . . . . . . . . . . . . . 235Reimbursement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242Marketing Planning and Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . 248

Licensing, Alliances, and Mergers 251Licensing and Outsourcing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252Alliance Partnerships. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259Mergers and Acquisitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267Selecting Partnership Options . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269

Managing Biotechnology 271Starting Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272Managing R&D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274Intellectual Property Protection . . . . . . . . . . . . . . . . . . . . . . . . . . . 278Management Changes with Growth . . . . . . . . . . . . . . . . . . . . . . . . . 279Dealing with Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280Communications and Public Relations . . . . . . . . . . . . . . . . . . . . . . . . 283

CONTENTS III

International Biotechnology 287Benchmarking Against the United States . . . . . . . . . . . . . . . . . . . . . . . 287Intellectual Property Protection . . . . . . . . . . . . . . . . . . . . . . . . . . . 290Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292Operations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294Finance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298

ConclusionBuilding Biotechnology 303

Business Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304First Steps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305Selecting Opportunities and Business Planning . . . . . . . . . . . . . . . . . . . . 307

Investing 315Caveat Emptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315Investing in Biotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325

Career Development 327Job Descriptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328Ph.D., MBA, or Both? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330

Final Words 333

AppendicesInternet Resources 337

News and Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337Investing and Competitive Intelligence . . . . . . . . . . . . . . . . . . . . . . . . 338Angel Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339Federal Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339Industry Organizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340

Annotated Bibliography 341Business . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341Intellectual Property and Regulation . . . . . . . . . . . . . . . . . . . . . . . . . 343Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344Science . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344

Glossary 347Science . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347Legal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352Regulatory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354Commercial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356

Index 361

19

Three

Introduction to Molecular Biology everything should be as simple as possible, but not simpler.Albert Einstein

Biotechnology research seeks to develop applications of molecular bi-ology. Many educational sources use analogies to recipe books or blue-prints to explain the role of DNA and genes in molecular biology. Leaning

on these analogies is not recommended. Ultimately, these analogies obscure the importance of topics such as regulation of gene expression, which is of funda-mental importance in understanding molecular biology. When applying one’s knowledge of biotechnology fundamentals, most metaphors fail. It is only by un-derstanding molecular biology and biotechnology applications that one can ap-preciate the applications and limitations of techniques used in molecular biology.

This chapter presents a brief, metaphor-free, introduction to molecular biol-ogy. Subsequent chapters describe the tools, techniques, and applications of bio-technology and provide greater details on the potential and limitations of mo-lecular biology.

InFoRmATIon FLow In moLeCuLAR BIoLogyTo understand the basis of most biotechnology applications, it is necessary to first understand the process by which information in genes leads to the formation of structural and functional proteins.

Proteins serve structural and functional roles that give individual cells—and by extension whole organisms—specific structures and functional characteristics.

Information Flow in molecular Biology

Genetic information is contained in DNA and leads to the formation of proteins through an intermediary called mRNA.

20 BUILDING BIOTECHNOLOGY

When many people think of proteins, they think of nutritious foods such as meat and beans. While animal muscle and plant seeds are excellent sources of dietary protein, proteins play a central role in all cell types and perform functional and structural roles (see Table 3-1). Examples of structural proteins include keratin, which makes skin waterproof, and myosin, which interacts with other proteins in muscles to make them flex.

DNA contains information that describes the construction of proteins. The process of protein synthesis is as follows:

1. DNA contains the information to produce proteins.2. Information encoded in DNA is transcribed into a molecule called messen-

ger RNA (mRNA)—effectively a “working copy” of the DNA sequence of a given gene.

3. mRNA is translated into proteins by the protein synthesis machinery, with the composition of the resulting protein corresponding to the original DNA instructions.

This basic mechanism is conserved in all life forms, from bacteria to humans. The implication of this common process that converts information in DNA into functional proteins is that similar techniques can be used to investigate and ma-nipulate all biological systems. Furthermore, it is possible to make human thera-peutic proteins, for example, in organisms as distantly related as bacteria.

Understanding the roles of DNA, RNA, and protein and their relationships to each other is essential to understanding molecular biology. While there are some specific exceptions (e.g., retroviruses and prions) to the order and direc-tion of information flow shown in Figure 3-1, these examples still fit within the general framework, and the majority of biological systems use the framework as presented.

dnAStorage of

genetic information

mRnA“Working copy” of a

gene

ProteinStructural and

functional roles

transcription translation

Figure 3-1 Simplified model of information flow in molecular biology

3 - INTRODUCTION TO MOLECULAR BIOLOGY 21

dnA: SToRIng And ReLAyIng InFoRmATIon

Deoxyribonucleic acid (DNA) is the primary source of genetic information in cells. Humans, plants, animals, and bacteria all contain DNA. DNA is physically passed from generation to generation, bestowing certain traits of parents to their children. The reason why children have physical characteristics from each of their parents—a child may have their mother’s eye color and father’s hair color—is be-cause they received half their DNA from each parent.

Each of our cells (with a few exceptions like red blood cells, eggs, and sperm) contain all the DNA required to code our genetic features. Genes are discrete sections of DNA that confer traits. Information in genes is relayed to the pro-tein synthesis machinery within cells where it dictates the production of proteins. The word “genome” refers to all the DNA in an organism. The human genome contains approximately 30,000 genes arrayed on 46 long stretches of DNA called chromosomes.

DNA is essentially composed of two intertwined strands that form a double helix. The two strands of DNA are said to be complementary because the sequence of one strand indicates the sequence of the opposite strand, like a photograph and

Figure 3-2 General scheme of gene expressionModified from National Human Genome Research Institute


its negative. Each strand is physically composed of four different chemical units called nucleotides, the sequence of which encodes the genetic information. These four chemical units, adenine, cytosine, guanine, and thymine, are often abbrevi-ated as A, C, G, and T, respectively. Just as the English language can be expressed in twenty-six letters, the genetic code is expressed in these four chemical units. A DNA “sequence” refers to the specific order of A’s, C’s, G’s, and T’s in a stretch of DNA.1

There are two essential components of genes: coding elements and regulatory elements. The coding elements of genes are first transcribed as mRNA, which is then translated into protein. The chemical sequence of A’s, C’s, G’s, and T’s in the coding region of a gene determines the composition and structure of the result-ing protein and, by extension, its function. Regulatory elements affect the rate at which genes are transcribed and translated, and may be interspersed within the coding sequence or outside of it. Regulatory elements also control the cell types within which specific genes are activated, and the timing and magnitude of gene expression. Gene regulation thereby allows individual proteins to be expressed only in certain cells at specific times and at specific rates.

Proper regulation of gene expression—the production of gene products—is essential. Under- or over-expression of genes can have deleterious effects. For ex-ample, many forms of cancer are caused by mis-regulation of gene expression that results in uncontrolled cell division. Curing these cancers may be a matter of cor-recting the misregulation. A potential solution for diseases resulting from low ex-pression of genes is to use gene therapy to introduce affected genes or regulatory elements to spur additional production. One of the challenges of gene therapy is developing methods to not only introduce genes into cells and enable their ex-pression, but which also regulate the expression of the introduced genes to ensure that they are not over-expressed. A solution for diseases caused by over-expressed genes is RNA interference, which is discussed in the section immediately below. This procedure prevents translation of mRNA, inhibiting protein production. RNA interference is described in further detail in Chapter 6.

mRnA: The meSSengeR

Messenger RNA (mRNA) is used to relay information from genes in DNA to the protein synthesis machinery. An additional feature of mRNA is that it can be de-stroyed once sufficient protein is produced, permitting an extra level of control of gene expression. RNA is also present in forms other than mRNA, some of which are described later in this chapter.

It is possible to affect expression of genes by targeting their mRNA with an-

1. To ‘experiment’ with DNA coding, visit the author’s DNA-o-gram generator at http://www.thinkBiotech.com/DNA-o-gram


tisense RNA or DNA—these nucleic acids can bind mRNA and inactivate it or target it for destruction. Unlike DNA, which is usually double-stranded, mRNA is single stranded. Nucleic acids (DNA or RNA) containing a sequence that can bind to a given mRNA will prevent translation by the protein synthesis machin-ery, inhibiting gene expression. The Flavr Savr tomato, a tomato engineered to have a long shelf life, was produced by introducing antisense RNA corresponding to mRNA for an enzyme involved in fruit spoilage. Inhibition of this gene delayed spoilage. In 1998 the FDA approved Isis Pharmaceuticals’ Vitravene, the first an-tisense drug, to treat cytomegalovirus-induced retinitis.

Figure 3-3 DNA: Chromosomes and genesModified from National Human Genome Research Institute


TRAnSLATIon: mAKIng PRoTeInS

Just as DNA and RNA are composed of linked nucleotides, proteins are comprised of chains of amino acid units. When mRNA is translated to produce a protein, the protein-synthesis machinery “reads” the nucleotides three at a time, assembling amino acid chains that correspond to the mRNA sequence. The basic elements of the protein-synthesis machinery are tRNA, a form of RNA that transfers amino acids to the protein-synthesis machinery in a way that enables them to be linked together, and ribosomes, which help form the chemical bonds that attach amino acids in a protein chain.

The three-nucleotide sequence elements on mRNA that code for individual amino acids are called codons. These are matched by “anti-codons” on tRNA to ensure that the appropriate amino acid is aligned with a given mRNA sequence. The 64 possible combinations of A, C, G, and T at each codon code for only 20 dif-ferent amino acids. This redundancy in the genetic code, permitting multiple co-dons to specify common amino acids, is considered a form of protection against DNA mutations and has applications in identifying foreign DNA from sources such as viruses which may use different “dialects” of the genetic code.

The chemical characteristics of amino acids in a protein cause it to fold into a defined 3-dimensional structure. A protein’s structure determines its function.

Boxhuman chromosomes and genetic trait inheritance

The human genome is composed of chromosomes. We get 23 chromosomes from our mother and 23 chromosomes from our father, constituting 23 pairs.

While 22 of the 23 chromosome pairs are similar in both men and women, the 23rd pair is quite different and determines the sex of an individual. For the 23rd pair of chromosomes, women have two X-chromosomes while men have one X- and one Y-chromosome. Because X-chromosomes contain more DNA than Y-chromosomes, they are physically larger than Y-chromosomes. Having too many or too few chromosomes can affect gene regulation and cause diseases. Down’s Syndrome, for example, occurs in individuals with three copies of chromosome 21.

The roles of X- and Y-chromosomes are important in understanding sex-linked diseases. Women do not have Y-chromosomes, so diseases that are caused by defective genes on the Y-chromosome can only occur in men. Additionally, men only have one X-chromosome, so mutations in genes on the X-chromosome are more likely to affect males, because the second X-chromosome in women can sometimes compensate for mutations on the first. Color blindness, caused by a mutation on the X-chromosome, is more common in men than in women for this reason.


So, since the DNA sequence of a gene dictates the sequence of amino acids in a protein, and the sequence of these acids in a protein determines its structure, one can deduce a protein sequence, and potentially its structure and function, from the gene sequence encoding it.

PRoTeInS And enzymeS

Proteins, the workhorses of cells, are responsible for the majority of structural features and functions in cells. Enzymes are proteins that perform functional roles as part of the cellular process. Different types of cells get their characteristics by expressing a specific array of genes, resulting in production of a complement of proteins that give each cell type its unique characteristics. Pancreatic cells, for example, produce the protein insulin to regulate blood sugar levels; neurons pro-duce neurotransmitters essential for brain function; and hemoglobin is made in blood cells, enabling them to carry oxygen. Examples of enzymes include prote-ases that break down proteins or enable digestion of food, and polymerases that assemble DNA and RNA. Some genes are expressed only in certain cell types whereas others are widely expressed. Examples of widely-expressed genes include those encoding proteins and enzymes involved in general cellular activities such

Figure 3-4 Protein translationModified from National Human Genome Research Institute


as DNA replication, mRNA translation, protein synthesis, energy production and maintenance of structural integrity.

Production of inappropriate proteins and mis-regulation of protein expres-sion are at the root of many diseases. As mentioned above, many cancers result from mis-regulation of gene expression that causes uncontrolled cell division.

Molecular biologists can transfer genes from humans and other animals into bacteria, yeast, and other organisms to confer the ability to produce specific pro-teins that may be extracted for therapeutic use. For example, Genentech produced its first drug by introducing the gene for human insulin into bacteria and ex-tracted the resulting protein to produce a treatment for human diabetes. Genes can also be transferred from one organism to another to confer new attributes. Pesticide-resistant crops have been produced by incorporating naturally-occur-ing pesticidal proteins into plants. Bacteria have also been modified to perform roles such as decomposing oil spills by adding genes encoding proteins with the ability to break down components of oil. Additional examples are described in Chapter 6.

OTHER FORMS OF RNATraditional molecular biology held that the primary role of RNA in cells was largely limited to housekeeping functions such as transferring information from DNA to the protein synthesis machinery (mRNA), transporting amino acids to be assembled into proteins (tRNA), and translating mRNA into protein (rRNA).

Sidney Altman and Thomas Cech shared the 1989 Nobel Prize in Chemistry for their discovery of catalytic properties of RNA. The ability to catalyze (increase the rate of) biochemical reactions had previously been thought to only exist in proteins. Altman and Cech found a role for RNA in the splicing of mRNA. Splic-ing enables modification of an mRNA sequencing, making it possible for a sin-

Table 3-1 Examples of protein and enzyme functionsenzyme FunctionAmylase Breaks down starches and other complex carbohydrates into basic sugarsCellulase Breaks down cellulose, found in the cell walls of plantsLipase Breaks down fatsProtease Breaks down proteinsProtein Function

Collagen Main protein in connective tissue; structural roles in skin, cartilage, teeth, bone, and other tissues

Keratin Makes skin waterproof and contributes to strength and flexibilityMyosin Muscle contraction


gle gene to give rise to several different proteins. The significance of Altman and Cech’s discovery was expanded more than a decade after they received the Nobel Prize. Following sequencing of the human genome it was discovered that the hu-man genome contained only a fraction of the genes previously thought necessary to produce the complete set of proteins comprising human biology. mRNA splic-ing helped explain how this small set of genes could produce the full complement of human proteins could largely be explained through mRNA splicing.

More recently myriad forms of RNA have been discovered, and diverse roles for RNA have also been elucidated (see Table 3-2). These discoveries indicate that controlling cellular activities is more complex than previously thought, suggest-ing that there are also more opportunities to influence cellular activities.

The BIg PICTuReGenes interact with the environment and with each other to confer traits. While the presence or absence of a gene can potentially confer a given trait, environ-mental factors also play a role. Our physical characteristics are a combination of genetic and environmental factors. A child with a hypothetical tallness gene, for instance, would not necessarily grow taller than a child without the gene; the child with the tallness gene would also require adequate nutrition to fuel the ex-tra growth (and the effect of the tallness gene may be limited or enhanced by the action of other genes). Rather than thinking of genes as determinants of physical characteristics, they should be regarded as potentials or predispositions for char-acteristics.

The ability to modify characteristics of cells is similarly limited by biological and physical constraints. Since some cells are rapidly replaced, induced changes will be quickly lost. Other cells are dormant, precluding their potential to express

Table 3-2 Selected RNA typesRnA type FunctionmRNA Messenger RNA. Contains a working copy of a gene sequence and is

read by the protein synthesis machinery to produce proteins.tRNA Transfer RNA. Transfers amino acids to the protein synthesis

machinery to produce proteins.rRNA Ribosomal RNA. Part of the protein synthesis machinery. Also useful

for determining evolutionary similarity between organisms.aRNA Antisense RNA. Used for gene regulation.siRNA Small Interfering RNA. Used for gene regulation.snRNA Small Nuclear RNA. Used to edit mRNA, regulate gene expression, and

maintain chromosome tips (telomeres).


modifications. Furthermore, biology is complicated. In fields such as industrial chemistry or

engineering, applications are developed from well-characterized principles. With biotechnology on the leading edge of molecular biology research, it can be dif-ficult or impossible to foretell the outcomes of manipulations and they can have unforeseen consequences. Because it is not possible to fully predict the outcome of these procedures, scientists must perform experiments, take observations, refine theories, and finally develop functional applications. This is why biotechnology research is so complex, time consuming, and fraught with unforeseen setbacks and disappointments.

About the Author

Yali Friedman, Ph.D., is founder of thinkBiotech and chief editor and publisher of the Journal of Commercial Biotechnology. His other books include Best Practices in Biotechnology Education and Best Practices in

Biotechnology Business Development. He serves on the science advisory board of Chakra Biotech, is an associate of the World Technology Network, and has also served as a judge for the Biotech Humanitarian Award, the Maryland Incubator Company of the Year Award, and the AUTM Venture Forum.

Dr. Friedman has strong exposure to leading issues in international biotech-nology. Since 2008 he has produced a global biotechnology innovation ranking for Scientific American’s Worldview, and has participated in biotechnology in-dustry development forums for international groups such as the APO and APEC, and for individual countries such as Japan, Canada, Germany, the Philippines, and Turkey.

Dr. Friedman taught biotechnology management at the National Institutes of Health for several years and continues to guest-lecture at other biotechnology education programs for students ranging from traditional MBA students, to mili-tary officers at National Defense University. He also writes and speaks on diverse topics such as biotechnology entrepreneurship and biopharmaceutical globaliza-tion.

Dr. Friedman has a long history in biotechnology media. He created the first blog on the business of biotechnology for a NY Times company, which was named to Forbes “Best of the Web.” His other projects include the Student Guide to DNA Based Computers, sponsored by FUJI Television, BiotechBlog.com, and DrugPatentWatch.com, a pharmaceutical industry competitive intelligence ser-vice based on a business plan that was awarded second place in the Panasci En-trepreneurial Awards Competition.

Dr. Friedman can be contacted at [email protected].

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