This year, scientists in the United States used a gene editing tool inside a human body to try to correct a gene carrying an inherited form of blindness, for the first time ever.
Conducted at the Oregon Health and Science University on March 4, the process involved injecting the microscopic tool into the eye of a volunteer, hoping to make him see.
It will take them a few weeks to find out whether it worked.Much excitement in medicine circles already exists, with doctors around the world terming it a ‘new era in medicine’, saying it makes editing the human DNA (deoxyribonucleic acid) much more effective.
If they find it successful and safe, it will be tried on 18 patients.However, after this incidence, people got more concerned about the use of the technology, with many questions arising regarding its mass utility, safety and long term physiological effects on the human body.
This explainer explores these concerns, detailing what gene editing means, methods and how potent it is to disrupt the future of medicine.
So, what is gene editing?
This medical innovation, also called genome editing or gene engineering, involves the use of biotechnological methods to alter the genetic makeup of animals or plants with the core aim of improving them.
This can be done by replacing, deleting or adding a DNA sequence to correct a genetic disorder or normalise internal or external body functions.Simply put, it is like using a pair of scissors to cut off unwanted base pairs of a DNA sequence.
Which tools or methods are used for the procedure?
Four methods exist. The earliest method involved the use of restriction enzymes in the 1970s.
These enzymes recognize specific patterns of nucleotide sequences and cut at a certain point, paving way for the insertion of new DNA material at that location.
However, this method has lost popularity in recent years, and is only used for cloning molecules.
Zinc Finger Nucleases (ZFNs) is the method that was developed in 1980s as medical researchers kept looking for a better, precise way of gene editing.They looked for an editing technique that could identify the DNA location they wanted to alter as off-target positions were dangerous.
ZFNs showed real hope in medicine and scientists used it to to disable CCR5 (chemokine receptor type 5) on human T-cells, a major receptor for HIV.
Following ZFN-mediated editing, scientists found autologous CD4+ T-cells were safe to use and were an exciting potential for HIV therapy. ZFNs have also been used to edit tumor-infiltrating lymphocytes.
A third method emerged in 2011, which was an improvement over ZFNs. Named Transcription Activator-Like Effector Nucleases (TALENs), the tool uses arrays of 33-35 amino acid repeats.These repeats possess single nucleotide recognition, thereby increasing targeting capabilities and specificity compared to ZFNs.
However, in 2012, scientists discovered the fastest and easiest method of genome editing derived from CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) -Cas9, a system that has long existed in bacteria to help them fight off invading viruses.
Cas9 is an enzyme which acts as a pair of ‘molecular scissors’ that can cut the two strands of DNA at a specific location in the genome so that bits of DNA can then be added or removed.
Discovered by Jennifer Doudna of the University of California Berkeley and Emmanuelle Charpentier of Umea University in Sweden, CRISPR-Cas9 has gained global popularity since then, and researchers believe that it is the next wave of revolution in medicine.
CRISPR-Cas9 was adapted from a naturally occurring genome editing system in bacteria. The bacteria captures snippets of DNA from invading viruses and uses them to create DNA segments known as CRISPR arrays.
The CRISPR arrays allow the bacteria to remember the viruses (or closely related ones). If the viruses attack again, the bacteria produces RNA segments from the CRISPR arrays to target the viruses’ DNA.
The bacteria then uses Cas9 or a similar enzyme to cut the DNA apart, which disables the virus.
What diseases can be controlled using CRISPR-Cas9?
It is being explored in research on a wide variety of diseases, including single-gene disorders such as cystic fibrosis, hemophilia and sickle cell disease.
It also holds promise for the treatment and prevention of more complex diseases such as cancer, heart disease, mental illness and HIV infection.
Tackling obesity and creating hornless cows are other uses.In 2015, CRISPR was used to edit human embryos at the Sun Yat-Sen University in Guangzhou, China.
Scientists have used it to reduce the severity of genetic deafness in mice, suggesting it could one day be used to treat the same type of hearing loss in humans.
They’ve created mushrooms that don’t brown easily and edited bone marrow cells in mice to treat sickle-cell anemia.
Optimistically, CRISPR might help us develop drought-tolerant crops and create powerful new antibiotics.It could one day even allow us to wipe out entire populations of malaria-spreading mosquitoes or resurrect once-extinct species like the passenger pigeon.
In 2017, it was reported scientists successfully used gene editing to completely extract HIV from a living organism, with repeated success across three different animal models.Gene editing techniques have also made superbugs kill themselves.
By adding antibiotic resistant gene sequences into bacteriophage viruses, self-destructive mechanisms are triggered which protect bacteria.Using CRISPR, researchers have edited out Huntington’s disease from mice, pushing the symptomatic progression of the condition into reverse.
How much does it cost?
It can take months to design a single, customized protein at a cost of more than Sh100,000 when using older gene editing tools.
With CRISPR, scientists can create a short RNA template in just a few days using free software and a DNA starter kit that costs USD65 plus shipping. Unlike protein-based technologies, the RNA in CRISPR can be reprogrammed to target multiple genes.
What are the health risks?
Ethical concerns arise when genome editing, using CRISPR-Cas9, is used to alter human genomes.Most of the changes introduced with genome editing are limited to somatic cells, which are cells other than egg and sperm cells.
These changes affect only certain tissues and are not passed from one generation to the next.
However, changes made to genes in egg or sperm cells (germline cells) or in the genes of an embryo could be passed to future generations.
Germline cell and embryo genome editing bring up a number of ethical challenges, including whether it would be permissible to use this technology to enhance normal human traits (such as height, skin colour, hair type or intelligence).
Scientists have recently learned that the approach to gene editing can inadvertently wipe out and rearrange large swaths of DNA in ways that may imperil human health.
That follows recent studies showing that CRISPR-edited cells can inadvertently trigger cancer.
That’s why many scientists argue that experiments in humans are premature, and the risks and uncertainties around CRISPR modification are extremely high.Although human embryo editing is relatively easy to achieve, it is difficult to get good results, with threat for lifelong health outcomes.
The body’s own immune system could thwart some efforts to develop gene therapies based on the trendy genome-editing tool called CRISPR-Cas9, according to a 2018 study.The report dims hopes that CRISPR–Cas9 could one day be used in people to correct mutations that cause diseases.
The body’s immune responses can sabotage a gene therapy — and pose a health risk to the person receiving the treatment. Antibodies against Cas9 can bind to the enzyme in the bloodstream, before it has had a chance to act.
And T cells that target Cas9 could destroy cells in which the protein is expressed, wiping out ‘corrected’ cells and potentially triggering a dangerous widespread attack on the body’s own tissues.
Based on these concerns about ethics and safety, germline cell and embryo genome editing are currently illegal in many countries.
Any legal ramifications so far?
Yes. On December 30, 2019, a court in China sentenced He Jiankui, a researcher, to three years in prison for carrying out ‘illegal medical practices.
He had shocked the global medical community when he claimed to have created the world’s first genetically edited babies – twin girls.
The court found him guilty of forging approval documents from ethics review boards to recruit couples in which the man had HIV and the woman did not.
Dr Jiankui defended himself that he was trying to prevent HIV infections in newborns, but that was concluded as an action of deceit.
World governments must show commitment to controlling how CRISPR is used.
Although it has the potential to redefine the future of medicine, a self regulation framework may not work, nor a moratorium: a self-imposed ban of a few years before anyone tries using the technology on the human germline again since the twin girl story.
Africa, which has not done any substantial research work in this field, needs to develop the right policies regarding the use of the technology in breeding and agriculture, to edit out crop diseases before considering trying the same on human bodies.
Kenya is slowly warming up to the technology, in a bid to catch up with the rest of the world, as Pwani University students are conducting research on enhanced shelf life for cassava using genome editing.
While the risks for gene editing in humans currently outweigh the benefits but that should not discourage more research into this field, since science has always proven a sustainable remedy to many diseases the human body is exposed to.