Aiming for the Nobel Prize
Curing with genetic mutations
By Sujata Devadas, October 2, 2015
A way to the solution
Mohamed S Alameri is an Emarati, who did his entire schooling in Arabic at Itihad Model School. He was introduced to genetics in 12th grade. Although embarassed for not being able to recall the teacher’s name at a moment’s notice, and high school genetics was not as much fun as in University, his interest for the subject took off in school. For his college degree, he chose to do an Honors specialization in Genetics from London, University of Western Ontario, where he switched to English as language of instruction. “So you can imagine what my first year was.” says Mohamed chuckling. “And yet here I am aiming for a Nobel prize in genetics.” he says, grinning
It was not so
It did not take much prompting for Mohamed to explain his intense love for genetics. “Broadly speaking,” he says, leaning forward to convey his excitement, “the basic laws of inheritance, transmission of genetic traits in plants and animals, is named after Gregor Mendel who experimented with garden peas. It is also called ‘classical genetics.’ I find it rather boring because it does not give us much control.”
“BUT molecular genetics studies the structure and function of genes within a molecule. That is fascinating because it is DNA that forms the basis of all genetic expression. You understand, of course, that if you change the base of something, and you improve it, what builds up on that base will be better.
As of now, that can be done in mammals.” declares Mohamed, his eyes bright with hope and aspiration to succeed with his mission.
I am fascinated. “You mean to say…they are now experimenting how to do this gene replacement in mammals such as mice and..?” following Mohamed’s train of thought. “ermm…ermm..mice is the ‘go to’ mammal ‘cos they are kinda close to…” Mohamed intervenes. “Have they done it in monkeys?” I interrupt him, boggle-minded by the widespread implications of it all. Monkeys, to my mind are even closer to homo sapiens. Mohamed frowns and hesitates, “I think they did.” he says politely. From then on, Mohamed explains the whole thing to me in the simplest language:
Engineering genetic mutations
The first method of editing genes adopted by molecular genetics was to create a virus carrying DNA with the desired specific element as part of its helix. This virus, is sent into the body to reach a cell, where it integrates its own DNA with that of the cell. Now the newly integrated part of the DNA helix, expresses itself as part of the system, degrading the earlier defective genetic element which manifested itself as a genetic disorder. However, the virus that carried the DNA into the body remains there, liable to cause unforeseen complications or risks to life.
Found by the Japanese
In 1987, Japanese biologists, Yoshizumi Ishino and colleagues of Osaka University discovered a weapon that many bacteria use to fight viruses! They detected a strange pattern of DNA sequences in a microbe found in the gut: 5 short repeating segments with identical sequences composed of 29 bases, separated by short non-repeating unique 'spacer' sequences composed of 32 bases. Rudd Jansen at Utrecht University named this pattern ‘CRISPR’, which, the Japanese scientists noticed were always accompanied by a collection of genes nearby: ‘Cas genes’, short for CRISPR-associated genes. The “spacer” RNA binds invading virus DNA of matching sequence, then the Cas enzyme attached to the loop cuts up the virus DNA. This bacterial system of defense can be harnessed to make precise changes to the DNA of mammals.
Moving beyond diagnosis
In October 2012, Dr. Feng Zhang reported the first successful programmable genome editing of mammalian cells using CRISPR-Cas9. Feng aims to extract DNA binding proteins naturally occurring in micro-organisms, and tweak them to bond with specific kinds of DNA sequences to solve neurological and psychiatric medical conditions in the years that unfold.
Curing the helpless
Mohamed’s concern is to use genome editing breakthroughs such as these to help children born with genetic disorders: Stuve–Wiedemann syndrome, beta-thalassemia or alpha-thalassemia occur in the Arab world because of high rates of inbreeding, consanguineous marriage, elevated birth rates and child bearing in older maternal age caused by gene mutations, as reported by CTGA.
Congenital malformations are the second leading cause of infant mortality in Bahrain, Kuwait, Oman and Qatar and are the leading cause of infant mortality (40.3%) in the United Arab Emirates. Thalassemia, for instance, is a genetic blood disorder that makes an abnormal form of haemoglobin, the protein in red blood cells that carries oxygen. It results in excessive damage of red blood cells, leading to anaemia. Thalassemia patients need regular blood transfusion. It is reported that 1 of 12 people in the UAE is a thalassemia carrier, caused by marriage within the family.
“We don’t cure anything. We diagnose” states Mohamed. His desire is to help children born like this. “The genetics field is getting broader and more specific everyday. Broader in the sense that one gene could provide us with a lot of information that has been unknown so far. On the other hand, it also gets more specific because one base element could have a huge effect on something tiny like a receptor in a cell or it could affect a whole organ. My goal now is to connect the dots between personal medicine and specific gene replacement(gene therapy). I believe this will be the future of medicine."
"Within the next 10 years, I hope to lead a research team that focuses on gene disorders that are common but not previously treated.”