Please enjoy this excerpt from our recently revised book, The Biotech Primer: An Insider’s Guide to the Science Driving the Biopharma Industry. This book explains the science behind the industry in an accessible manner, providing the foundation needed to understand today’s advanced therapies.
Decoding the Master Plan
At the dawn of the 21st century, the Human Genome Project had just been completed. This revolutionary undertaking—determining the exact size, sequence, and location of genes within the human genome, or the full complement of DNA in each of our cells—is one of biology’s greatest achievements. For the first time, researchers possessed the complete human blueprint. Ideally, they could now pinpoint the source of countless diseases. This ushered in what many, including the European Commission and the National Academy of Sciences, have referred to as the Century of Biology. Since then, the ability to quickly and economically sequence the human genome has increased exponentially.
DNA is the blueprint of this Century of Biology. Found in all living cells, DNA is the genetic material that stores and transfers information. In this chapter, we look deep inside the cell and examine the molecule upon which the entire biotechnology industry rests, starting with key discoveries and the scientists behind them.
In the 1850s, an Austrian monk named Gregor Mendel performed breeding experiments with pea plants. He observed that certain genetic characteristics were passed down from one generation to the next in specific ratios. Because he was the first to analyze the inheritance of traits systematically, many consider Mendel the father of genetics. Mendel’s contributions are even more impressive because though he didn’t know about DNA, he predicted its existence. He called what we know now as DNA “particles of inheritance” which he suspected were responsible for passing traits from generation to generation.
Almost a century later, in 1944, scientists identified DNA as the “particles of inheritance.” The race was then on to determine its structure. Eventually, the research team of James Watson and Francis Crick solved this scientific puzzle in 1953. The structure that Crick and Watson conceived was a double helix. An X-ray image captured by English chemist Rosalind Franklin revealed that DNA was helical. Sadly, Franklin died before receiving full credit for her critical contribution. Scientists had proposed many other possible configurations, including a triple helix. However, only the double helix model fit the evidence of base pairing provided by Erwin Chargoff.
The last sentence of Watson and Crick’s Nature paper that described the double helix structure, made a critical point: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” This suggestion would have profound implications for the as-yet-unrealized field of biotechnology.
Life’s Building Blocks
The full name for DNA is deoxyribonucleic acid. It’s a long molecule made up of repeating subunits called nucleotides. Each nucleotide consists of three parts:
- A sugar molecule called deoxyribose the “D” part of DNA. This molecule has five carbon atoms that form a ring structure.
- A phosphate molecule attached to the fifth carbon atom in the ring. This gives DNA weak acidic properties and is the “A” in DNA.
- A molecule called a base attached to the first carbon atom in the ring. There are four bases: adenine (A), cytosine (C), guanine (G), and thymine (T).
The prefix “deoxy” means “without oxygen.” It refers to the lack of an oxygen molecule at a particular spot in the sugar molecule. “Ribo” stands for ribose, which describes the particular sugar. All organisms use the same bases—A, C, G and T, and the same sugar and phosphate molecules. In other words, the nucleotide building blocks for the genetic material of all forms of life are identical.
Putting It All Together
Nucleotides are linked to form a long chain. During DNA synthesis, a cellular enzyme called DNA polymerase links the phosphate group of one nucleotide to the sugar group of another. This forms what is often referred to as the sugar-phosphate backbone.
But how do nucleotide chains form a double helix structure? An early experiment by Chargoff revealed some striking patterns. He noticed that within a DNA molecule, the number of Cs is always the same as the number of Gs. Similarly, the number of Ts is always exactly the same as the number of As. This led to the conclusion that DNA is composed of paired strands: Cs on one strand are matched to Gs on the other, and As on one strand are matched to Ts on the other. The pairing of Cs to Gs and As to Ts between strands is accomplished by chemical bonds. Their geometry, determined by the particular shapes of the nucleotides themselves, gives DNA its iconic shape.
These four tiny bases—A, C, G, and T—come together to form the blueprint of life. Understanding this blueprint has enabled all of the incredible advances we’re now experiencing within biopharma, including full genome sequencing, gene therapy, and genome editing.
Where do cells get the nucleotide building blocks to make DNA? The food we eat, such as chicken, fish, fruits, and vegetables, are made of cells. Animal and plant cells contain DNA made of the same constituent parts as ours. The DNA you consume in your salad or salmon is broken down into the nucleotides we need. Our cells can also synthesize the four nucleotides de novo, meaning “from the beginning,” using atoms from proteins, sugars, and fats that we consume.
Immunotherapy, Cell Therapy, and Gene Therapy Oh My!
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Emily Burke, PhD has worked in biopharma for 20 years, gaining science writing experience at The Scripps Research Institute and Ionis Pharmaceuticals. As a Ph.D. molecular biologist, she is passionate about advancing the public’s understanding of science. In addition to being a self-proclaimed “science geek,” she is regularly asked to speak at international scientific meetings. When not teaching and writing the WEEKLY for Biotech Primer, Dr. Burke swims with her swim club and performs regularly on the improv circuit in San Diego.