31In 2016, the UK’s HFEA (Human Fertilisation and Embryology Authority) became the first government agency to approve the genetic modification of human embryos using CRISPR/Cas9 technology.
Fast forward to 2024, and this same technology is now being used to treat diseases like HIV, as well as some of the most aggressive cancers, including glioblastoma and metastatic ovarian cancer. But what exactly is CRISPR? In simple terms, it’s a genome editing tool that nature invented for us. While it was first discovered in the 1980s, it wasn’t until decades later that scientists figured out how to apply it to humans. In this article, we’ll explain this groundbreaking discovery that could potentially change human biology — and maybe even lead to immortality.
It All Started with Salt Marshes and Archaebacteria
Back in the late 1980s, a graduate student named Francisco Mojica was studying archaebacteria, microorganisms that live in saltwater and saline soils near Alicante, Spain. These microorganisms had strange repeating patterns of DNA — 30 nucleotides long — separated by unusual segments that looked like blocks. At first, no one knew what these sequences were for, so it was assumed they were involved in regulation (a common explanation when scientists aren’t sure what something does). These repeating sequences were named CRISPR, which stands for Clustered Regularly Interspaced Palindromic Repeats.
Mojica didn’t give up on his research and found similar sequences in other types of microorganisms, suggesting that this wasn’t just a coincidence — it was a pattern and must serve some vital function. What exactly it was wasn’t clear until the 2000s, when researchers used a tool called BLAST (a comparative algorithm) to analyze the growing database of genetic sequences. This allowed them to finally identify that CRISPR sequences were common in certain bacteria and viruses. They discovered that CRISPR was a memory bank for bacteria, storing fragments of virus DNA. But how did bacteria use this memory, and why was it important? That remained a mystery.
The next key breakthrough came from microbiologist Philippe Horvath, who was studying lactic acid bacteria in sauerkraut fermentation. Bacteriophages, or viruses that attack bacteria, were a significant problem in the dairy industry because they destroyed the bacteria needed for fermentation, resulting in substantial losses. Horvath was looking for a way to make bacteria resistant to these viruses and, in doing so, stumbled upon CRISPR. He was the first to prove that bacteria use CRISPR to acquire DNA from viruses they’ve encountered, which makes them immune to future attacks from the same virus.
When a bacterial cell survives an encounter with a virus, it cuts the viral DNA into pieces and stores it within its own CRISPR sequence. This stored DNA is passed on to the next generation of bacteria, effectively granting them immunity to the virus their parent encountered. In other words, CRISPR acts as the immune system for bacteria. And if you’ve ever eaten yogurt or cheese, you’ve likely consumed bacteria containing CRISPR systems, which aid in the fermentation process.
The mechanism behind CRISPR is often described as “genetic scissors.” The Cas9 nuclease (a protein that works with CRISPR) acts as the scissors. It binds to a specific segment of viral DNA, makes a cut, and effectively prevents the virus from reproducing. This is how bacteria protect themselves, and scientists are now using this exact mechanism to edit human genes and combat diseases.
CRISPR/Cas9 in Genetic Engineering: Great Prospects and One Tiny Catch
You might already have a basic understanding of how CRISPR/Cas9, the natural bacterial tool, is used in genetic engineering. The idea of applying this system to directly cut human DNA was first proposed by scientists Emmanuelle Charpentier and Jennifer Doudna, who met at a conference in Costa Rica. They combined their research and shared their findings with Science magazine in 2012, an achievement that earned them the Nobel Prize. By the way, they became the first women to receive this honor without a male collaborator, and they did so only eight years after their landmark publication. According to their research, CRISPR/Cas9 can indeed be used to edit the DNA of any living organism, though initially, this was only possible in vitro.
Feng Zhang, a Chinese-American scientist from MIT, was the first to transfer CRISPR/Cas9 technology into living cells with nuclei. He successfully edited the human genome, as well as the genomes of mice, fruit flies, fish, and yeast — essentially, the lab’s model organisms.
So, why haven’t we edited the next generation of children or ourselves using CRISPR/Cas9 yet? The issue lies in the fact that DNA is a highly stable structure — perhaps the most stable one in existence. The oldest DNA on record is over 1.7 million years old, meaning that it is highly resistant to degradation. This makes it exceptionally resilient. When CRISPR/Cas9 “scissors” cut DNA, the cell immediately triggers a repair process. There are two potential outcomes:
- Homologous Recombination (HR): Most animals, including humans, have at least two copies of each chromosome. When a break occurs, the cell can repair it using the other copy. Scientists can trick the cell by providing a piece of DNA with the correct mutation (the one they want to insert). When the cell repairs the break, it integrates the desired change, and everything works as planned.
- Non-Homologous End Joining (NHEJ): In this case, the break in the DNA results in a fragment with no matching information. The gene stops working, and the DNA is effectively “broken.” This process is less desirable because it doesn’t repair the gene — it destroys it.
The goal for researchers is to induce homologous recombination — but that's no easy task. Most of the time, the cell opts for the second, less effective path, which leads to broken genes instead of properly repaired ones. While scientists have been able to break genes intentionally for years, they must focus on ensuring precise, beneficial repairs.
One of the major advantages of CRISPR reagents is their affordability. At just 10-20 euros, they’re thousands of times cheaper than previous gene-editing tools, making research faster and more scalable. This has spurred rapid development in the biotech industry. The main challenge now is perfecting the process of inducing DNA breaks without causing harmful damage.
Still, the progress made with CRISPR/Cas9 represents a monumental breakthrough in genetic science, potentially changing how we approach genetic diseases, medicine, and possibly even human biology.
Tomatoes, Piglets, and Bone Marrow: Where Gene Editing Can Be Applied
Did you know that pig organs are often transplanted into humans due to their biological compatibility? The problem, however, is that pig genomes contain dormant retroviruses that can activate in humans and pose serious health risks. Thanks to genome editing, scientists have developed a breed of pigs with inactivated viruses, making their organs safe for human transplant.
Gene editing has also made its mark in agriculture. CRISPR has been used to adjust the number of branches on tomato plants and their fruit size. As a result, researchers can now grow tomatoes with five branches from one cutting, which produces three times as many fruits. Gene editing has also led to innovations like blue strawberries, black tomatoes, and mini (peach-sized) watermelons. Even cows with gray spots instead of black are being bred for heat resistance in hot climates.
For many years, genetically modified products were banned in Europe due to concerns about their long-term consequences and potential effects on ecosystems (e.g., genetically modified cabbage affecting silkworm populations). The potential impact on human health was also uncertain. However, CRISPR technology has proven to be different because it introduces changes without leaving any trace. Essentially, CRISPR replaces traditional selective breeding, allowing plants to be created that are resistant to specific climates.
In humans, CRISPR holds great promise for treating genetic diseases such as diabetes, schizophrenia, or sickle cell anemia — conditions caused by genetic mutations present at birth. But there are scaling challenges. For example, to correct a mutation that causes diabetes, scientists would need to fix the entire pancreas. Since cells resist DNA alterations, the most feasible approach so far is to start with bone marrow and blood — cells that can be edited and multiplied in a test tube before being transplanted back into the patient. This method has been used to treat leukemia and HIV. In one experiment, a patient with both leukemia and HIV received bone marrow from a donor with a corrected CCR5 gene, effectively curing both conditions.
AN INTERESTING STORY
In 2018, Chinese scientist He Jiankui conducted an unauthorized experiment on human embryos from couples with HIV-infected fathers. Using CRISPR, he attempted to repair the CCR5 gene, and three healthy babies were born as a result. His goal was to create innate immunity to HIV in the embryos — something that naturally exists in about 3-4% of the world’s population. Unfortunately, his experiment failed, as HIV-infected couples with proper therapy can already have healthy children. He Jiankui was criticized for violating ethical standards and was sentenced to three years in prison. However, his experiment demonstrated the potential of CRISPR in creating healthy offspring from sick parents.
The ability to edit genes and DNA remains the holy grail of biotechnologists, doctors, and scientists. CRISPR/Cas9 is the closest we've come to realizing this dream. In the future, CRISPR/Cas9 could not only fix broken genes but also modify genes that predispose individuals to health risks or those that are considered "undesirable," such as traits like hair or eye color. It may even be used to increase muscle mass, contributing to athletic success. While this sounds like a futuristic utopia out of Brave New World, it’s too early to claim such a utopia is imminent. Challenges such as potential damage from DNA breaks, difficulty in delivering CRISPR/Cas9 to all necessary cells and organs, and the long-term consequences that may take decades to manifest still need to be addressed. But one thing is clear — what seems like science fiction today could very well become a reality in the future.
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