The Five DNA Discoveries That Changed Our World
Team Genomes takes a journey back in time and reveals the 5 biggest genomic discoveries to date.
In the year 2000, geneticist and physician Francis Collins said, “What more powerful form of study of mankind could there be than to read our own instruction book?” While this statement might now seem slightly naive (given that we’ve since learned reading our genetic code is far more complex than a simple instruction book) he was referring to the field of genomics. The area of research which allows us to explore the blueprint of our existence, unlocking secrets about human health, evolution, and biology.
With whole genome sequencing now more accessible and personalised medicine rapidly advancing, it’s crucial to acknowledge the key discoveries that have shaped genomics. Rather than covering them all, we’ll highlight the five most significant breakthroughs in this transformative field.
The Discovery of DNA Structure — James Watson and Francis Crick
Picture the scene: It’s 1953, and you’re enjoying a lively evening at your local pub, ‘The Eagle’ in Cambridge, when a gentleman bursts in, claiming he and his colleague have ‘discovered the secret to life.’ At the time, you might think he’s had one too many, but when Francis Crick made this claim alongside James Watson, it was about a groundbreaking discovery that remains crucial to science today.
That discovery was the structure of deoxyribonucleic acid, more commonly known as DNA. The significance of this breakthrough was formally recognised in 1962, when Watson, Crick, and Maurice Wilkins were awarded the Nobel Prize. They were the first scientists to create an accurate model of DNA, revealing the iconic double helix structure for the first time.
Their model aligned with Chargaff’s rules, which state that in any DNA sample, the amount of adenine (A) equals thymine (T), and guanine (G) equals cytosine (C). From this, the Watson-Crick base pairing rules were established: adenine pairs with thymine, and guanine pairs with cytosine. These base pairs are held together by hydrogen bonds in the DNA’s three-dimensional double helix structure.
It’s also crucial to acknowledge Rosalind Franklin’s significant role in this discovery, even though she did not receive the Nobel Prize (due to her passing in 1958). Her X-ray diffraction images of DNA were key to Watson and Crick confirming their theoretical model, although she was unaware that her data had been shared with them without her consent by Maurice Wilkins. Without her work, it’s possible that Watson and Crick might not have been the first to make this groundbreaking discovery.
You can read more about it here.
DNA Sequencing — Sanger sequencing and NGS
Transporting you to 1977, we have another key moment in molecular biology, led by a man who changed the way we understand DNA: Frederick Sanger. His technique, known as Sanger sequencing, became the foundation for modern DNA sequencing and is still used in some cases today.
Prior to this invention, determining the exact order of nucleotides in DNA was not only incredibly challenging but also highly time-consuming. Sanger’s method involves using molecules called dideoxynucleotides (ddNTPs) to terminate DNA replication at specific points, resulting in DNA fragments of varying lengths.
These fragments were labelled with radioactive markers and separated through a process known as gel electrophoresis. In this, the fragments move through a gel under an electric field, with smaller fragments migrating faster as they encounter less resistance.
By reading the radioactive tags attached to these fragments, scientists could determine the DNA sequence base by base with a high degree of accuracy. Today, fluorescent tags have replaced radioactive markers, making the process safer and easier to detect automatically.
For more than three decades, Sanger sequencing remained the gold standard, but with the rise of next-generation sequencing (NGS), we witnessed some big improvements in sequencing. NGS addressed the limitations of Sanger’s method, including the high cost and low throughput.
At Genomes, we utilise 30x sequencing with Dante Genomics and Nebula, allowing you to see your entire genome which was not possible until one of the discoveries discussed later in this blog.
You can see more about sanger sequencing here, and NGS sequencing here.
Gene Cloning — Dolly the Sheep
In 1996, the world was introduced to a major scientific achievement: Dolly the sheep. At first glance, she may have appeared to be an ordinary sheep, but Dolly was no ordinary animal — she was a clone.
More specifically, she was the first ever mammal cloned from an adult somatic cell (cell from the body which is not an egg or sperm cell) using a technique known as somatic cell nuclear transfer.
Dolly was such a huge step in science due to her existence challenging the belief many people had. That once an adult cell was specialised, it could only be used for the certain job it was specialised in (such as being a skin or liver cell). Dolly showed that an adult cell could be used to generate all the different types of cells in the body.
However, the creation of Dolly did not come without controversy. Many questioned the ethics of cloning and whether it posed a threat to society, especially if applied to humans. Religious institutions, such as the Vatican, also expressed strong opposition, with Pope John Paul II referring to the idea of cloning as dangerous experiments.
Despite these ethical concerns, Dolly’s creation led to significant scientific advancements, particularly in the field of regenerative medicine. Her cloning inspired the later discovery of induced pluripotent stem cells (iPSCs), which offer an ethical alternative to embryonic stem cells.
Today, Dolly’s body is preserved and on display at the National Museum of Scotland in Edinburgh, where she has resided since her death from an incurable lung tumour in 2003. You can read more about her here.
Sequencing the entire genome — The human genome project
The Human Genome Project was a huge international collaboration lasting from 1990 to 2003, with a budget of around $3 billion USD. It is often recognised as one of the greatest achievements in scientific history, with the main aim of generating the first complete sequence of the human genome.
To accomplish this ambitious goal, researchers had to refine and improve existing DNA sequencing methods. They built upon the Sanger Sequencing technique, enhancing it to handle the vast amount of data needed for the human genome.
PCR (polymerase chain reaction), a relatively new technology at the time, was vital to the project, enabling the amplification of small amounts of DNA to create a large enough sample for sequencing. Instead of using the traditional radioactive labels, researchers adopted fluorescent dyes to mark the DNA bases This not only made the process safer but also allowed for more efficient detection.
By 2003, the Human Genome Project had produced a sequence covering roughly 90% of the human genome. This was as complete as could be achieved with the technology available at the time. Notably, the sequence was a patchwork derived from the DNA of multiple individuals. Although most of the reference genome came from one anonymous donor, the rest was drawn from a mix of 19 others.
The discoveries and data produced from this project have laid the groundwork for the developments seen in genomics today. Since its completion, the field has progressed much faster than many had anticipated. Sequencing a human genome, which once took years, can now be done in a matter of hours. The cost has also dramatically decreased, making it far more accessible than it once was.
You can read more about the project here
Curing genetic diseases — CRISPR-cas9 and gene therapy
Gene therapy has been revolutionary for the treatment of many genetic disorders, working by altering the genetic material of a person. The basic idea of the therapy is that it corrects defective genes which are responsible for the disease, which could be by replacing it, turning it off or introducing a new gene. Among the many forms of gene therapy, CRISPR-Cas9 has emerged as the most promising.
Discovered in 2012 by Jennifer Doudna and Emmanuelle Charpentier, CRISPR-Cas9 was quickly recognised for its immense potential, eventually earning the Nobel Prize in Chemistry in 2020. This gene-editing technology, adapted from a bacterial immune system, allows scientists to precisely target, cut, and modify specific sections of DNA.
The mechanism involves a guide RNA that locates the desired DNA sequence, while the Cas9 protein makes precise cuts to enable the insertion, deletion, or correction of genetic material.
The impact of CRISPR-Cas9 is already being felt in medicine. In December 2023, the FDA approved Casgevy, the first CRISPR-Cas9-based treatment for sickle cell anaemia, marking a major breakthrough.
You can read more about CRISPR-cas9 here.
Summary
To summarise, genomics has profoundly transformed our understanding of life, health, and disease. From the discovery of DNA’s structure to the cutting-edge applications of CRISPR, each breakthrough has contributed to the rapidly advancing field of personalised medicine and genome sequencing.
By exploring these key moments in genomic history, we aim to highlight the immense progress that has shaped modern science and to provide context for the future innovations that are sure to come. Understanding these milestones not only helps us appreciate how far we’ve come but also prepares us for the exciting developments still on the horizon.
