Gene Therapy, DNA's Past, RNA's Future: Early History

This story is part of a series on the current progression in Regenerative Medicine. In 1999, I defined regenerative medicine as the collection of interventions that restore tissues and organs damaged by disease, injured by trauma, or worn by time to normal function. I include a full spectrum of chemical, gene, and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.

In this subseries, we focus specifically on gene therapies. We explore the current treatments and examine the advances poised to transform healthcare. Each article in this collection delves into a different aspect of gene therapy's role within the larger narrative of Regenerative Medicine. The first six stories will cover gene therapy's history and primary successes.

The period between the 1920s and 1950s was a time of significant progress and exciting discoveries in genetics and biomedicine. Groundbreaking advances in understanding inherited DNA and genes unlock the secrets of heredity and pave the way for future breakthroughs in medicine and biotechnology. These discoveries have significantly impacted our understanding of human evolution, genetic disorders, and the development of new therapies and treatments for various diseases.

What is Gene Therapy?

Gene therapy involves altering an individual's genetic makeup to cure genetic diseases. It is a technique that offers hope for millions of people suffering from debilitating genetic conditions. Interestingly, successful gene therapies often use RNA molecules to modify DNA rather than directly manipulating it. RNA acts as a messenger between DNA and the cell, which is crucial for gene expression.

The emergence of gene therapy was initiated by the revelation of the chemical configuration of DNA, which paved the road for a more profound comprehension of inherited traits. Identifying specific genes responsible for genetic disorders opened up novel opportunities for gene therapy research. Over the following decades, researchers developed inventive techniques to introduce therapeutic genes into patients' cells.

With the advent of new technologies such as CRISPR-Cas9, gene therapy has continued to evolve, offering new possibilities for treating genetic diseases. Despite the challenges, the incredible progress made in this field provides hope for a future where genetic disorders are a thing of the past.

The Roaring 20's

During the 1920s and 1930s, genetics researchers such as Thomas Morgan were at the forefront of discovering the genetic basis of inheritance. Morgan and his colleagues recognized that genetic information is carried on chromosomes, which led to significant breakthroughs in genetics. Still, the precise molecular mechanisms of development remained a mystery.

At this time, there was a major interest in understanding the molecules that orchestrate the development of organisms. Much speculation surrounded these elusive molecules, and researchers were eager to uncover their role in the complex development process. While the specific details of how genes functioned were not yet fully understood, the groundwork laid by early geneticists during this period paved the way for future discoveries in genetics.

1940s Milestones in Gene Therapy

In 1944, a series of experiments discovered the 'transforming principle' concept. These experiments revealed that DNA was the primary genetic material, contradicting the previous belief that proteins served this function. This breakthrough is sometimes called the "gene therapy of bacteria" since DNA is the transforming factor that could modify the physiology of a bacterial strain. The results of these experiments suggested that external DNA could alter an organism's traits, making it a groundbreaking discovery in genetics.

In the late 1940s, experiments were conducted on mice's genetic traits, marking the initial attempts at gene therapy. These early experiments laid the foundation for further research into gene therapy and brought the notion of genetic modification to the forefront of scientific research.

The only Nobel Prize for strictly mouse genetics was presented during this period. However, the realization that genes were made of DNA didn't happen at one single moment. Instead, a series of discoveries and work led to the acceptance, in the 1950s, of the understanding that genes in all organisms, not just bacteria and viruses, were made of DNA.

The 1950s: A Time of Discovery Continues

The previous discoveries of the 1920s to the 1940s led to substantial advances in genetics, including the 1953 discovery of the DNA double helix structure by James Watson, one of my PhD program mentors, and Francis Crick. The double helix structure of DNA was crucial in comprehending how genetic information is stored and transferred from one generation to the next. This discovery established the groundwork for decoding the triple nucleotide code, essentially life's language.

The "triplet" code is how DNA encodes the twenty amino acids that are the essential components of proteins. By decoding this code, one understands the genetic information that DNA holds. This can help one comprehend how genes function and contribute to developing traits and diseases.

This was a crucial time in genetics research, as identification of specific genes responsible for various inherited disorders was possible. Some notable discoveries during this period include the identification of the gene responsible for sickle cell anemia and the gene linked to cystic fibrosis.

One of the most notable discoveries following the primary understanding of gene DNA was that bacteria could transfer genetic material through conjugation. This finding played a significant role in comprehending how bacteria evolve and adjust to their surroundings. It led to observing another gene transfer mechanism in bacteria known as transduction, which laid the foundation for further research in bacterial genetics.

The discoveries made in the early days of genetic research set the foundation for a renaissance of gene therapy research. From the early 20th century until the 1940s, gene therapy progressed from a theoretical concept to a concrete scientific reality, leading to significant advancements in treating inherited diseases. These breakthroughs marked the beginning of a new era in genetic research, which would continue to flourish in the following decades.

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