The Origins of Gene Editing: Why Manipulating Genes is Nothing New

The Origins of Gene Editing: Why Manipulating Genes is Nothing New

Dr. André Choulika, CEO of gene editing company Cellectis, discusses how humanity has been manipulating genes for millennia without realizing it

  • 14 september 2017

We, humans, have committed an Original Sin. But the transgression did not occur in the Garden of Eden. Our Original Sin actually transpired approximately 11,000 years ago with the domestication of plants and animals. Humanity has been manipulating genes for millennia without realizing it, and that is our Sin of Origin.

Eighteen thousand years ago, hunter-gatherers roamed the land and fed themselves like any other animal, without tampering with genetics. Ten thousand years later, with the advent of settlements and cultivation, farmers and shepherds began selecting more reliable species to improve the yields of plants and animals. They manipulated the genetics of cultivated species to ensure the prosperity and growth of humankind.

These early breeders selected clones with specific traits to fit their needs, such as food, transportation, defense and even pets. Over centuries, laborious breeding efforts made it possible for humans to secure steady provisions for their basic needs, mitigating – even eliminating – the daily struggle for survival. The success of these environmental manipulations ultimately led humans to organize into settled communities and invent civilization.

But what do geneticists do to nature to serve civilization? They clone.

For example, over thousands of years, fruit from grapevines was bred to human taste, resulting in the now well-known grape varieties of Cabernet Sauvignon, Chardonnay, Pinot Noir, etc. The same process of selection was applied to cows, dogs, horses and roses. Over time, improvements in technology, along with increased agricultural yields and relative stability, mitigated food shortages, famine and disease. Population growth exploded.

Then, Gregor J. Mendel, founder of the modern science of genetics, articulated the laws of inheritance in plant hybridization and cross-breeding as the basis of gene segregation, and the Industrial Revolution exploded. Advancements in chemistry followed with the discovery of radioactivity, which led to new technologies that offer the capability for humans to intervene more directly in genetic selection.

With the population growing rapidly, an urgent need arose to advance the evolution of species, with the goal of streamlining food production and increasing agricultural yields. Efforts focused on accelerating the evolution of crops, such as wheat, barley and corn, by using mutagenic chemicals and radioactive rays.

In 1953, James Watson and Francis Crick determined the chemical structure of DNA, unveiling the molecular basis of heredity. Watson and Crick demonstrated that DNA is composed of chains of four chemicals: Adenine (A), Cytosine (C), Guanine (G) and Thymine (T), arranged in a double helix polymer, the molecule that makes up genes and chromosomes. The discovery of the molecular structure and mechanics of DNA revolutionized the sciences and has since become the center of interest for geneticists, the modern-day descendants of ancient breeders and hybridizers.

In 1972, Paul Berg successfully inserted a fragment of viral DNA into bacterial DNA. This unprecedented event dramatically changed the perspective of humans and allowed them to meddle with genes at the molecular level, opening up new horizons for applications of genetic modification. By introducing the DNA of one species into that of another, Berg had created the first recombinant DNA. He introduced this recombinant DNA into a bacterium, and then a miracle happened: the recombinant gene lived and replicated.

This breakthrough marked a turning point in history, and from that point in time, Berg’s technique was applied with successful results to plant cells, yeasts, mammalian cells and even human embryonic stem cells. The procedure was then performed on the embryos of flies, frogs, mice and other lab animals. Later, the procedure was applied to pets like fish and micro-pigs and livestock, such as the hornless cow.

Nature without human influence exists no more, as people everywhere reshape the natural world to their own uses and images. Now, after manipulating the DNA of all species, we are starting to manipulate our own DNA and suddenly find ourselves standing at the edge of a new frontier.

A half-century ago, the acreage of recombinant plants on Earth totaled zero. Today, over 50 percent of the plants that are grown on Earth are modified in some way with recombinant DNA. Recombinant DNA has powered the biotechnology revolution that has become, within the last 40 years, the principle driver of growth in the pharmaceutical industry, creating more powerful, precise drugs and turning them into a market that’s worth over $500 billion.

Now, recombinant DNA is getting into the DNA of humans. In the early 2000s, the first gene therapy trial led to the treatment of children who suffered from inborn severe combined immunodeficiencies using recombinant DNA.

Three thousand years ago, the average human life expectancy at birth was 20 to 30 years – a dismayingly short life span largely due to child mortality, famine and disease. Today, the average life expectancy in Western countries is around 80+ years, and the current admitted forecast for the coming decades is that human life expectancy will grow to over 100 years. Humans will soon become the mammals with the longest life expectancy, and the quest of mankind continues to be the fight against death and the ticking clock of biological destiny.

So what’s next? Today, we are entering a new era—the era of gene editing and synthetic biology.

Dr. André Choulika is the chairman and CEO of Cellectis. He received his Ph.D. in molecular virology from the University of Paris VI (Pierre et Marie Curie) and completed a research fellowship in the Harvard Medical School Department of Genetics. Later, while working in the Division of Molecular Medicine at Boston Children’s Hospital, Dr. Choulika developed the first approaches to meganuclease-based human gene therapy. 

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