The human body relies on a vast array of proteins to perform its intricate functions, from regulating metabolism to fighting off infections. These complex biological molecules are fundamental to health, and a deficiency or malfunction in even one can lead to significant health challenges. Biotechnology has significantly advanced the ability to produce these human proteins outside the body, offering new solutions for medical treatments.
The Landmark Achievement: Recombinant Human Insulin
Before modern biotechnology, individuals with diabetes relied on insulin extracted from animal pancreases. While life-saving, these animal-derived insulins often caused allergic reactions and were difficult to obtain in sufficient quantities. A consistent, safe, and abundant supply of human insulin was pressing.
A scientific breakthrough occurred in 1978 when recombinant human insulin was first prepared by David Goeddel and his colleagues at Genentech. This marked a paradigm shift, as it was the first human protein successfully produced on a large scale using bacterial transformation. The process involved synthesizing the two chains of human insulin, A and B, separately and then combining them.
Genentech partnered with Eli Lilly to commercialize recombinant DNA insulin. In 1982, Humulin, the first insulin utilizing recombinant DNA technology, became commercially available. This innovation revolutionized diabetes treatment, providing a purer form of the hormone that was less likely to cause adverse reactions and could be produced in much larger quantities.
The Science Behind Production: Bacterial Transformation
Bacterial transformation relies on introducing foreign DNA into bacteria. The process begins by isolating the human gene for the desired protein. For instance, to produce insulin, the gene encoding human insulin is extracted from human cells.
The isolated human gene is then inserted into a bacterial plasmid, a small, circular piece of DNA. Restriction enzymes, or “molecular scissors,” cut open the plasmid for gene insertion. The newly formed plasmid, now containing the human gene, is known as recombinant DNA.
Next, this recombinant plasmid is introduced into bacterial cells, typically Escherichia coli (E. coli). Bacteria are treated to make their cell membranes receptive to external DNA uptake. Once inside, the bacteria’s cellular machinery reads the human gene and produces the protein. These transformed bacteria are then cultured in large quantities, becoming tiny factories that continuously produce the human protein.
Expanding the Therapeutic Horizon: Other Recombinant Proteins
Human insulin’s success paved the way for bacterial production of many other therapeutic proteins. This technology has broadened significantly, demonstrating versatility in addressing various medical conditions. Approximately 30% of approved therapeutic proteins are currently produced using E. coli as a host organism.
Human growth hormone (hGH) is another example, produced to treat growth deficiencies. Before recombinant technology, hGH was extracted from human cadaver pituitary glands, posing supply limitations and safety concerns. Recombinant hGH provides a safe and abundant supply for patients requiring this hormone.
Clotting factors, like Factor VIII, are produced recombinantly to treat hemophilia, a disorder where blood does not clot properly. Erythropoietin (EPO), a hormone stimulating red blood cell production, is also manufactured to treat anemia, particularly in patients with kidney disease. Recombinant proteins are also used in monoclonal antibodies for targeted cancer and autoimmune therapies, and as antigens in vaccines for diseases like hepatitis B.
Transforming Medicine and Beyond
Bacterial transformation has profoundly impacted medicine. This technology has revolutionized disease treatment by ensuring a stable, safe supply of therapeutic proteins. Patients now benefit from treatments less likely to provoke allergic reactions than older, animal-derived alternatives.
Large-scale bacterial production has made these life-saving treatments more accessible and, in many cases, more affordable. Beyond therapeutic use, recombinant proteins are instrumental in drug discovery, serving as targets for new medications and diagnostic agents.
This biotechnological advancement continues to evolve, with research focused on improving production efficiency and expanding the range of reliably produced proteins. Bacterial transformation’s foundational principles have opened doors for advancements in vaccine development and novel therapeutics. This technology represents a significant leap forward in addressing global health challenges.