This new science and its potential applications have excited many, while creating uncertainty and skepticism in others. Two of the features of biotechnology that might have contributed to the fear that some have of this science are the speed with which it has been adopted in many economic sectors in recent years and the unexpected way its applications have reached the market. Consider, for instance, the elapsed time between the invention of some products and their arrival on the market (Table 1-1). Whereas only 50 to 100 years ago a new invention used to take as long as 30 years to be available to the public, more recent inventions are marketed even before the public becomes aware of them. Note the case of television, which was invented in 1907, but didn't arrive on the public market until 1936. However, it only took 11 years to market biotechnological products after the first transgenic plants were developed. The shortened period of time might not be long enough for society to learn and become accustomed to transgenic products.

Society is basically made up of three subgroups: conservatives, who tend to be resistant to innovations; progressives, who are enthusiastic for new technologies; and moderates, who only adopt new technologies gradually. All three segments of society can be clearly distinguished when considering biotechnology.

As biotechnology started to draw attention from scientists and the public in the 1980s, most people felt unsure about the new science. Debate frequently centered on the possibility of biotechnology solving the problems facing human health and farm production. Unfortunately, the method and the speed by which biotechnology began reaching society seemed to threaten many who were already working to solve the challenges of human health and agriculture.

In many forums, people were debating whether biotechnology, an emergent science, would substitute for classical genetics, the science that has contributed to food production worldwide through improved varieties of corn, soybean, and apples, as well as new lines of swine, poultry, and other livestock. The arrival of biotechnology was unwelcome news to those who had already dedicated a great part of their professional lives to developing improved varieties through traditional techniques. The fear that in vitro studies would replace proven field and greenhouse techniques was a valid concern. Additionally, a lack of good marketing in introducing the new science and its products to society contributed to the apprehension toward biotechnology. Fortunately, debates on the threat of molecular breeding substituting for classical breeding are now an anachronism; today, the two sciences are seen as complementary.

Although microorganisms have been used for many years in the production of wine and bread, it was Robert Hooke's discovery of cells in a piece of cork in 1665 that opened the door to many discoveries and innovations in biology. About 10 years later, Anton van Leeuwenhoek built a microscope with an amplification power of 270X, allowing him to see microorganisms for the first time. The microscope opened the window to a new world previously invisible to man. In the mid-19th century, Matthias Schleiden and Theodore Schwann presented the theory that all living organisms possess cells.

New issues emerged with the new knowledge, causing some scientists to question why offspring tend to resemble their parents. It was in the middle of the 19th century that the monk Gregor Mendel, working in Brno of the Czech Republic, unveiled the secrets of heredity. Mendel noticed that traits of the garden pea plant, such as flower color, plant height, and seed shape, were consistently transferred from parents to offspring. An inquisitive man, Mendel made hundreds of crosses with different pea plants over many years. By recording the segregation of traits from thousands of plants, Mendel discovered that the traits segregated into predictable ratios, season after season. This indicated that discrete units of heredity were passed from generation to generation. These discoveries were presented in forums in the mid-1800s and compiled in Mendel's “Experiments in Plant Hybridization,” published in 1865. These discoveries were an important key to the emerging sciences of heredity and genetics. Interestingly, Mendel's work was largely ignored during his life. In fact, his research was virtually lost for 30 years, until three other scientists rediscovered Mendel's work. His simple experiments in the gardens of an Austrian monastery have provided the basis for innumerable further advancements in biology. Today, no genetics or biology class is able to adequately treat the historical aspects of biology without mentioning Gregor Mendel (Figure 1-1).

Figure 1-1. Gregor Mendel, considered the father of genetics.

By connecting a few more pieces of the puzzle of this emerging science, scientists in the first half of the 20th century were able to conclude that something inside of cells was responsible for heredity. After the addition of dyes for visualization of cells under the microscope, some structures that were stained in a distinct way were identified and called chromosomes (Figures 1-2 and 1-3). Researchers eventually learned that these structures carry the genes that code for the diversity of life.

Source: (b) © The Nobel Foundation.

Figure 1-2. (a) Human chromosomes and (b) Thomas H. Morgan, who identified the structures as carriers of genes, the basis of heredity.

Source: Courtesy of DOE Human Genome Program and the web site http://www.ornl.gov/hgmis.

Figure 1-3. DNA, gene, and chromosome, responsible for the likeness between parents and offspring.

Table 1-2 shows numbers of chromosomes and estimates of genome size and number of genes in different species.

In 1941, George Beadle and Edward Tatum (Figure 1-4) established the theory of “one gene, one enzyme,” which answered a question that had persisted in the scientific community for many years by explaining how genes are coded instructions for the construction of proteins. Although genes determine human stature, eye color, hair color, and other characteristics, they are not seen, but their products—proteins—are.

Source: © The Nobel Foundation.

Figure 1-4. Beadle (left) and Tatum, who postulated the theory of “one gene, one enzyme.”

In 1944, Oswald Avery identified DNA as the raw material that contains genes. Starting from that discovery, several research groups focused their studies on DNA, and the chemical composition was elucidated quickly. DNA is a molecule made of sugar, phosphate, and four nitrogenous bases: adenine, cytosine, guanine, and thiamine, identified by the initials A, C, G, and T, respectively. Later, scientists realized the four nitrogen bases, also known as nucleotides, were the alphabet of the genetic code.

The year 1953 marked a landmark for genetics, with the discovery of the helix-like structure of DNA, by two scientists working at Cambridge University in England: James Watson and Francis Crick, an American and a British scientist, respectively (Figure 1-5). Their work revolutionized genetics and accelerated the discoveries of the fine structure of DNA.

Source: (a) Adapted fromMapping Our Genes, the Genome Projects How Big, How Fast?, U.S. Congress, Office of Technology Assessment, OTA-BA-373 (Washington, DC: U.S. Government Printing Office, 1988. (b) and (c) © The Nobel Foundation.

Figure 1-5. (a) Complementary strand of DNA and scientists (b) Watson and (c) Crick.

The capability of DNA to code for all the processes of living organisms rests in the order of the genetic alphabet (A, C, G, and T) and is written in the chromosomes. Genes differ in size (number of letters or nucleotides) and sequence (order of the nucleotides). For instance, a gene can have the following sequence: ATGCCGTTAGACTGAAA. However, the question remained of how the sequence of letters translated into proteins and traits.

Cracking the genetic code was a puzzle that challenged geneticists: How could only four nucleotides code for the 20 different amino acids that constitute the thousands of proteins found in living organisms?

It was only in 1967 that Marshall Nirenberg and Har Gobind Khorana deciphered the genetic code. They concluded that DNA could be translated by the way the nucleotides (or bases) were organized in groups of three, later called codons (Figure 1-6 and Table 1-3). As there are four nucleotides (A, T, C, and G), there would be 64 different ways to arrange them into different codons. Considering that only 20 amino acids exist, the 64 different codons were more than enough to code for each amino acid. Actually, a single codon can represent many amino acids (Table 1-3).

Source: © The Nobel Foundation.

Figure 1-6. Nirenberg (above) and Khorana and the amino acids for which the genetic code was deciphered in 1967.

Alanine (Ala)

Arginine (Arg)

Asparagine (Asn)

Aspartic Acid (Asp)

Cystine (Cys)

Glutamic Acid (Glu)

Glutamine (Gln)

Glycine (Gly)

Histidine (His)

Isoleucine (Ile)

Leucine (Leu)

Lysine (Lys)

Methionine (Met)

Phenylalanine (Phe)

Proline (Pro)

Serine (Ser)

Threonine (Thr)

Tryptophan (Trp)

Tyrosine (Tyr)

Valine (Val)

The final products of gene translation, through the genetic code, are proteins. Proteins differ from each other based on the number, type, and order of the amino acids. Proteins can have structural function, such as the collagen and the elastin that are present in the skin, or proteins can carry out metabolic functions, as in the cases of hormones and enzymes.

Until some decades ago, DNA could only be visualized with an imaginative mind; now it can be seen, photographed (Figure 1-7), and even precisely manipulated. As the nature of DNA and genes began to be understood, many questions that existed in the minds of geneticists for many decades were replaced by more applied questions of how this technology could be applied to life. These questions transformed biotechnology from a science to an important business. In 2001, biotechnology generated revenues of more than $200 billion in the United States alone. Employment and investment opportunities are available as biotechnology releases new products, such as medicines and new crop varieties, and new services like gene therapies and genetic tests.

Figure 1-7. Human DNA can now be visualized and photographed.

Although DNA stores the genetic information for production of all proteins, it is the ribonucleic acid (RNA) that processes the coded message from the DNA. That is, RNA is more directly used to assemble the proteins by joining amino acids, according to the message coded in the DNA.

Protein production begins with transcription, in which a molecule of messenger RNA (mRNA) is synthesized, copying the message from the DNA. After transcription, mRNA goes to the cytoplasm, where its sequence is translated into the sequence of amino acids that produces the proteins.

The human body possesses more than 100,000 proteins, coded for by about 30,000 genes, according to estimates generated by the Human Genome Project. There are more proteins than genes because many proteins are modified from a single basic protein or are composed of many proteins. Some proteins also arise from different mechanisms of gene expression, a subject too involved to be addressed in this book.

Scientists are still far from identifying and characterizing all the proteins in the human body. However, incredible strides have been made to provide a foundation for protein research. This reaches to the source of proteins and ultimately the source of life. This foundation is laid by deciphering the entire genome sequence, or DNA (gene) sequence of an organism. Beginning with bacteria, microscopic worms, and yeast, scientists and computational biologists have expanded DNA sequence information to include certain animals and plants. The ultimate goal of DNA sequencing is the human genome. This genome sequence would allow the understanding of the basis of human life by identifying the order of DNA nucleotides. To accomplish this goal, many groups have come together to work on the Human Genome Project.

The sequencing of the human genome, which is finding the order of the more than 3 billion nucleotides (A, T, C, and G) in the human chromosomes, is being accomplished by two independent groups of scientists. The two versions of this sequence were published in the magazines Nature and Science in February 2001. One group, formerly led by Craig Venter, is Celera Genomics, of Rockville, Maryland, a company started in 1998. The other research group is the result of a consortium of public agencies with laboratories in several countries.

The sequence of the human genome carried out by the public sector, now led by Francis Collins, has a budget of more than $3 billion. The major sponsors were the U.S. Department of Energy and the National Institutes of Health (NIH), as well as the Wellcome Foundation of England. The current map covers about 95 percent of the human genome and has been found to be 99.96 percent accurate. This work has revealed, in a surprising way, that the human genome only has about 30,000 genes instead of 70,000 to 140,000, according to previous estimates. With a DNA sequence of over 3 billion base pairs (bp) and considering the average gene size of 3,000 bp, it is estimated that only 3 percent of the human genome actually codes for some protein. This means that about 97 percent of the human genome has seemingly no coding function; that is, most of the nucleotide sequences in human DNA do not code for genes. This nonfunctional portion of DNA has, for lack of a more accurate term, been called “junk DNA,” and its function and purpose have yet to be understood. More important, the data from the Human Genome Project has also revealed that each human being, independent of apparent differences, is about 99.9 percent identical to any other person.

With so much interest and emphasis on the Human Genome Project, what are the practical applications of the sequence of the human genome? The information will help in the early diagnosis of disease, an understanding of the predisposition to genetic diseases, and in genetic counseling, for example. For instance, the sequence of the human genome allows geneticists to understand why certain people have a predisposition to heart disease, and it will eventually lead to the development of new drugs specifically developed to combat the cause of disease and not the symptoms alone. Sequencing the genome will make available basic scientific knowledge for the development of gene therapies for incurable diseases, such as diabetes, muscular dystrophy, cystic fibrosis, Parkinson's disease, and Alzheimer's disease.

By the beginning of 2002, geneticists had already isolated about 13,000 human genes and learned about their functions, including those that code for eye color, circulatory proteins, and genes that when mutated cause a predisposition for developing breast cancer and prostate cancer. All this complex information is contained in each and every cell of the human body. If it were possible to stretch out the incredible amount of information contained in the DNA of all the chromosomes in a single human cell, it would reach about seven feet. If the DNA of all the cells of the human body were stretched out and aligned, it would be enough to cover the distance from Earth to the moon about 8,000 times. Incredible packaging mechanisms allow this information to be stored within each tiny cell.