Harper's Illustrated Biochemistry

"This particular book has, also, personal significance, because it was recommended to me by another professor from Egypt. This was Ali Khalifa, who was the professor of biochemistry at the time. He taught us in the first and second years of medical school and happens, also, to be my late father-in-law. I met his daughter Abeer, my wife, at medical school in the first year. He was the one who, in his lectures, as we were studying biochemistry, recommended reading Harper’s to understand DNA and RNA and how they work, and how a gene gets transcribed to give a message that then becomes a protein. It was all very, very new at the time, we’re talking about the late 1980s. Reading those chapters was just fantastic, because you start getting closer to understanding how the cells in our body work. That book opened my appetite, hugely, to trying to understand gene function, and the importance of genetics in cancer, because it is known that cancer is essentially, at its heart, the perturbation of gene structure and gene function. It’s how every cell in our body works. Every cell in our body has DNA molecules, and DNA is arranged in chromosomes that are present in a structure called the nucleus. There are about three billion base pairs of nucleotides, the building blocks of DNA, and there are four nucleotides, A, C, T, and G. They are essentially written as a huge dictionary of life. It’s a long string of “text” that has encoded in it the message of what a protein should look like. Within that DNA, 2% to 5% gets changed into RNA, and is called the messenger RNA. That message then goes from the nucleus to the cytoplasm, and each of three nucleotides gives rise to one amino acid. “When I went to medical school, as a naïve first year medical student, I thought everything was known.” The bases (nucleotides) are the building structure of the DNA and the RNA. The amino acid is the building structure of the protein. So each of the three nucleotides will give one amino acid, and then one amino acid arranged after the other forms a protein. The proteins are things like globin, which is part of haemoglobin, which carries oxygen in our body. Or actin or keratin in our skin. Those proteins are the workhorses in our body. They do all the essential cell and body functions. You get perturbations of the gene, either a fault in the gene sequence, or part or all of the gene gets deleted from the code. Then, if that gene is playing an important function, that could lead to a process that we call transformation, where a normal cell can change into a cancer cell. That is something that happens, as we will see with the book after next. Cancer has many defining characteristics and features but, for me, an essential component of it is genetic defects. Then what we observe about it is its uncontrolled cell division, coupled with invasion of other tissue. It goes beyond the boundaries, where normal cells are supposed to remain. The combination of the two, uncontrolled cell division plus invasion, for me, defines cancer. Yes, because the cells will be very disorganised. Their nuclei will be large. You will see the invasion of the basement membrane, which is the membrane in which the cells are supposed to be organised. This is for epithelial cancers. So yes, by examining a tissue section, you can tell whether or not it’s cancer. You take sections, you paraffin-embed them and you look at them under the microscope."