Science is discovery and discovery evolve. Few discoveries have elicited as much excitement in the scientific world in recent times as has CRISPR-the gene editing tool made popular by the year 2020 Nobel Prize winning female duo of Jennifer Doudna and Emmanuelle Charpentier. Doudna calls CRISPR the molecular scissors capable of cutting and pasting genetic material at precise points in the gene-carrying molecule DNA. Its discovery and development have revolutionised diverse fields in medicine and agriculture. From being an obscure bacterial defense mechanism, it has become a veritable groundbreaking technology.
CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats. It was first observed in the 1980s when an otherwise bacterial immune system used in fighting invading viruses was noticed to contain the DNA of viruses that previously infected bacteria. The DNA sequences were peculiar with repeated sequences and unique segments, hence the name.
When a virus attacked bacteria, the bacteria stored snippets of the invader’s DNA in their CRISPR region. When the virus attacked again, it was quickly recognised by its DNA and quickly neutralised and disposed of. Further research uncovered an associated enzyme called cas9 as CRISPR’s partner acting like a pair of molecular scissors cutting the viral DNA to disable it.
This is nature’s way of fighting viral diseases in bacteria- a form of artificial intelligence occurring naturally and developed over the ages. And this naturally occurring phenomenon has become the foundation for one of biology’s most powerful tools. As with all human endeavors, the benefits to mankind of such a naturally occurring immune system can be re-engineered and configured to suit humanity’s purpose. This was what Doudna and Charpentier did in 2012 and carted home the Nobel Prize in 2020.
This development quickly turned CRISPR into a versatile and affordable easy tool for tweaking DNA. Unlike older gene editing methods, CRISPR required minimal customisation and thereby threw open the field of genetic research. It allowed scientists to cut off genes in laboratory organisms like mice and fruit flies to study how these genes worked and accelerated discoveries in genetics, biology, and the neurosciences.
In agriculture, it engineered crops to withstand climate challenges. Hence, there emerged drought-resistant corn, fungus-resistant wheat and tomatoes with enhanced nutrients thereby assuring food security. Earlier, Genetically Modified Organisms, GMOs, as such foods were called were controversial and subjected to severe regulatory controls. CRISPR surmounted these obstacles because the plants it edited did not have foreign DNA. In medicine, though at prohibitive costs, CRISPR can correct the genetic mutations that cause such diseases as sickle cell anaemia and cystic fibrosis. In the field of oncology and retroviral disease like HIV, CRISPR can modify the patient’s immune system to better target cancer cells and cut off HIV DNA.
But controversy bedevils CRISPR. This is in germline editing. That is, instead of editing the somatic cells of fully formed organisms like human beings, germline editing is the manipulation and editing of germ cells like sperm and egg or the zygote arising from the fusion of the two at conception. This form of editing is heritable, capable of being passed to offspring and future generations.
The CRISPR system can only edit one cell at a time and work on the target genes in DNA and so for it to be beneficial to a patient like one with sickle cell disease, it must edit a red blood stem cell and pray that cell division multiplies this edited cell to make up at least two-thirds of the body’s total red cells for it to make any impact in the patient. Otherwise, a laborious and time-consuming editing of numerous cells must be undertaken.
At this moment, CRISPR has not attained the capacity to mass-edit cells. Hence in the United States where CRISPR technology has been approved for the treatment of sickle cell disease, it costs a whopping five million dollars. Now, sickle cell disease is caused by a single mutation in the DNA where adenine replaces thymine, and this mutation can be corrected at the embryonic level and save the newborn from this crippling and life-threatening disease.
The fear here is that germline editing will further stimulate and rekindle interest in the long-lost and humanly irritable field of eugenics which seeks to scientifically reverse Darwin’s theory of natural selection. And there is a case to prove this point. In 2018, there came a man from China, He Jiankui, or JK as he is popularly called. He engineered a set of twins and one other designed by omitting the gene that codes for the receptors of HIV.
This conferred on the babies the ability to resist HIV and this character will be passed on to their offspring down the line. When JK announced the birth of these babies, all hell broke loose. He was excommunicated and reviled by the scientific community and was jailed for three years for indirectly related charges. But JK likened himself to Robert Edwards, the pioneer of in-vitro fertilisation, IVF, who was vilified in 1978 when the first test-tube baby Louise Brown was born. Robert Edwards went on to win the Nobel Prize in 2010. JK believes that with time, the scientific community will realise the importance of his work and considers himself a pioneer of some sort in a field that can eliminated such life crippling and debilitating diseases like sickle cell disease, Huntington’s disease, Duchenne muscular dystrophy, cystic fibrosis, and other diseases that can be eliminated by genetic engineering.
He is convinced that in the not-so-distant future, humanity will come to terms with his experiments. JK is out of jail and his current address is the Wuchang University of Technology Wuhan, China where he is the Director of the Institute of Genetic Medicine. A laboratory in Wuhan is suspected of hiding the secrets of the corona virus that led to COVID-19 pandemic. While China is notorious for her severe surveillance programme, it allowed JK to operate freely.
The sequenced human genome has led to a better understanding of genetics, heredity and disease. We now know the genetic code for all the twenty amino acids that make up the proteins in the body. Genes that govern melanin production and hence skin pigmentation have been identified as has those that lessen or completely obliterate the sensation of pain. We know genes that can make someone tall or short and those that can make a person work effectively with less than four hours of sleep daily.
But the most frightful of the complications of gene editing is the introduction of genes that will not only harm the person but also affect future generations. And some characters are governed by multiple genes while some genes have multiple functions
CRISPR’s journey will be a long and tortuous one. The benefits of the system are wide and open. It can cure a host of genetic diseases, combat climate change by engineering carbon-capturing plants, create microorganisms that produce biofuels and biodegradable plastics and revive extinct species in plants and animals like the woolly mammoth.
On the other hand, eugenics will blossom in territories and constituencies with little or no regulatory restrictions and especially in dictatorial regimes and closed communities. The deletion, blocking or substitution of a gene causing a genetic disorder may also remove the protective effect of this gene in another area of the body.
In JK’s case, the edited gene, CCR5 is a naturally occurring gene in one percent of White Europeans. While JK’s editing conferred on the individuals the immunity to HIV, it removed the protective effect of the gene against the West Nile virus and the flu. Hence the babies are more susceptible to common infections. And as for the benefits or otherwise of this this simple, affordable, and easy-to-use technological advancement, only time will tell.
Dr Oberabor is medical director, Baker Clinic Warri and Olomoro.
