Introduction: Biotechnology — An Ever Expanding Toolbox for Medicine

LARA V. MARKS

University College London, UK Email: l.marks@ucl.ac.uk

1.1 INTRODUCTION

Biotechnology is intrinsic to medicine. Everywhere you look today, from medical research conducted in the laboratory through to the diagnosis and clinical treatment of a patient, biotechnology is pivotal to that process. Despite its importance, few non-scientists understand what biotechnology is, where it has come from or the many different functions it serves in everyday healthcare.

The term biotechnology was first coined in 1919 by Károly Ereky, a Hungarian agricultural engineer and economist. At its most basic level biotechnology refers to the controlled and deliberate manipulation of organisms and living cells to create products for the benefit of humans. In one form or another, humans have deployed biotechnology for thousands of years. Since prehistoric times, for example, they have used yeast to get bread dough to rise and to produce alcoholic drinks. Bacteria have also been added to milk for generations to make cheese and yoghurt. Animals and plants have also been selectively bred over many centuries to generate stronger and more productive offspring for multiple purposes. In more recent years, increasing knowledge about how to manipulate and control the functions of various cells and organisms, including their genes, has given birth to a burgeoning number of products and technologies for combating human disease.

Biotechnology is currently one of the hottest growth areas in medicine. Between 2001 and 2012 investment in medical biotechnology research rose globally from £6.7bn to £66bn. Such work is helping to determine the molecular causes of disease, to generate more accurate and faster diagnostic platforms and to develop drugs that are more precise in their target and personalised for individual patients.

Just how important biotechnology has become can be seen from the fact that by 2013 seven out of ten of the best selling drugs were biological products. Also known as biologics, such drugs replicate natural substances in our body, including enzymes, antibodies and hormones. They are made from a variety of natural resources — human, animal, and microorganism — and are usually manufactured using biotechnology techniques. Living entities, such as cells and tissues, also comprise biological products. Analysis in 2013 predicted that by 2018 biological drugs would account for a quarter of all drug spending worldwide and for more than 50 percent of the top selling drugs in the world. Such therapeutics include those that are manufactured in either animal cells or bacteria and make use of the body's natural immune system to fight disease.

1.2 MOLECULAR DISEASE AND DNA

Much of the application of biotechnology in medicine is directed towards addressing structural changes at the molecular level that cause disease. This rests on the premise that an illness can be driven by an abnormality or deficiency of a particular molecule. Such thinking can be traced back to the work of Linus Pauling and colleagues at the California Institute of Technology in the late 1940s. Importantly, they demonstrated that sickle-cell anaemia, an inherited blood disorder, was linked to an abnormal haemoglobin, the protein responsible for delivering oxygen to cells in the body. They proposed the hypothesis that a mistake in the protein was caused by a defective gene. Pauling would go on to win the Nobel Prize in Chemistry for this work in 1954. A gene is a distinct stretch of DNA (deoxyribonucleic acid) that carries the instructions needed to create proteins, specific molecules that are essential to the functioning of the body. Proteins not only do most of the work in cells they are also vital to the structure, function and regulation of the body's tissues and organs.

The concept that DNA could play a role in the disease process was highly novel for the time. DNA had been first discovered in the late nineteenth century, but remained little studied for many decades. In part this was due to the belief that DNA was an inert substance incapable of carrying genetic information because of its simple structure. Instead, proteins, which had a more complex structure, were assumed to act as genetic material. Attitudes to DNA began to shift as a result of some experiments by the physician and molecular biologist Oswald Avery and colleagues at the Rockefeller Institute in New York. In 1944 Avery showed that DNA could transform non-infectious bacteria associated with pneumonia into dangerous virulent forms. Avery's work ignited a new interest in DNA. It would take time, however, for scientists to agree that it was DNA, not proteins, that carried genetic information. Consensus finally emerged after experiments conducted by the geneticists Alfred Hershey and Martha Chase at Cold Spring Harbor in 1952.

By the 1950s a number of researchers had begun to investigate the structure of DNA in the hope that this would reveal how the molecule worked. The structure of DNA was finally cracked in 1953 as a result of the culmination of efforts by the biophysicists Rosalind Franklin, Maurice Wilkins and Ray Gosling, based at King's College London, and Francis Crick and James Watson based in the Cavendish Laboratory, Cambridge University. Their work showed DNA to be a long molecule made up of two strands coiled around each other in a spiral configuration called a double helix. Each strand was composed of four complementary nucleotides, chemical sub-units: adenine (A), cytosine (C), guanine (G) and thymine (T). The two strands were oriented in opposite directions so that adenines always joined thymines (A T) and cytosines were linked with guanines (C G). This structure helped each strand to reconstruct the other and facilitate the passing on of hereditary information.

Soon after this breakthrough, in 1955, Fred Sanger, a biochemist at the William Dunn Institute of Biochemistry, Cambridge University, unveiled the molecular composition of the first protein: insulin. This protein, Sanger showed, had a specific sequence of building blocks, known as amino acids. Sanger's finding was quickly seized upon by Crick, who by 1958 had developed a theory that the arrangement of nucleotides in DNA determined the sequence of amino acids in proteins and that this in turn regulated how a protein folded into its final shape....