By Bill Caswell
Special to Ontario Construction News
By now you probably will have heard of CRISPR, as standing for a DNA manipulating tool. Where is this leading and how can your business life affect the outcome?
An arms race
Work with viruses that attack bacteria clearly showed that an arms race between these two single-celled creatures, bacteria and viruses, had been going on for several hundred million years, enough time for the bacteria to develop effective countermeasures against viruses.
Inside the bacteria
Francisco Mojica of Spain, like many scientists, studied bacteria, because being a single-celled creature, it was considered easy to work with. In 1977, he pioneered research illustrating that within the DNA of the bacteria’s single cell was a chain (now called CRISPR) that was an automatic defence against viruses. First, CRISPR would recognize the virus from the long list of enemies over the centuries. Then an adapted snake-like CRISPR chain would go toward the virus. One end of the CRISPR chain was equipped with a clamp that would seize the virus while the other end was like a cleaver and would chop up the virus into hundreds of pieces. Goodbye virus.
Well, it didn’t take long for scientists to realize that this was a very handy tool to have. Could humans make use of it?
The race begins
Not surprisingly, several laboratories around the world began investigating CRISPR to see if it could be put into action within human DNA. Lo and behold, answers were found. Not only might CRISPR deal with viruses in humans, CRISPR might deal with defective genes within human DNA. Perhaps It could be used to eliminate disease-causing mutations within human genes.
Whoops! DNA, genes, mutations, and other such terms need clarification. Let’s get to some of the more popular terms. (If you’re not into details, just skip the next lengthy section.)
DNA, bases, mutations, genes, chromosomes, RNA, and the whole gang
DNA is a very large molecule that exists in the same form in every one of the 30 trillion cells within our human body. It also exists in animals and plants. It is the musical score of the human or plant life, its symphony of action, so to speak. There is one musical score for a Beethoven symphony and a very different score for a Mozart symphony; and so, in many ways, your DNA is quite different from my DNA. DNA defines each of us uniquely. Other parts of the body read that score in order to play their instruments. So, some genes read the score to make me turn bald at age 26!
DNA has the ability to replicate itself, so that when the body creates new skin cells to replace the dying ones that we wash off every morning, the replacement cells carry exactly the same DNA message. The DNA molecule is humongous, made up of three billion base pairs (see base definition that follows) identified as AT-GC in DNA (and AU-GC in RNA, which we will come to shortly).
The order switches around, TA-CG, AT-GC, etc. While, on the surface, four identifiers might not seem like many choices to create three billion different combinations of DNA links, think of what we humans have been able to do with only two identifiers, 0 and 1 of the binary code: movies, streaming, Zoom, cellphone videos, etc. The actual structure of DNA is a pair of helixes (made of sugar and phosphate) that contain the base pairs of AT and of GC like ascending steps of a ladder within the helixes that shape the DNA molecule.
Acids and bases
All chemical bonds have a certain measure of acidity. It happens to be called pH and ranges from 1 to 7 for acids and 8 to 14 for bases, but that doesn’t matter to our story. Orange juice is acidic (actually vitamin C) whereas baking soda can form a base. As stated above, our DNA ladder is made up of a series of base pairs. The letters A, T, G, C identify bases named adenine, cytosine, guanine, and thymine. (As well, U identifies the base, uracil, within RNA – see below.)
Mutations are errors in the copying of cells (and the DNA within the cells simultaneously). Just as a photocopier might print an erroneous speck every 500 copies, cells create a reproduction error, rarely – say, every 100,000,000 copies. While that may not seem a very high probability for the occurrence of an error, our cell reproduction at 300 billion cells being replicated every day in a human leads to a significant number of errors (i.e., mutations).
Diseases such as Huntington’s Disease, sickle cell disorder, congenital blindness, and deafness are often caused by erroneous (mutant) genes that we pass on to, and become activated (expressed) in, our children.
Genes and chromosomes are divisions within the DNA. Groups or pieces of the DNA ladder collectively make up the chords and bars of the music. We know that our DNA has about 23,000 genes with specifically different characteristics. Those 23,000 genes are grouped (unequally) into 46 chromosomes, 23 having originally come from dad and 23 having come from mom when the first cell of you was created.
Dad’s 23 are different than mom’s 23, yet they are complementary so that you have a complete deck of 46 different cards (chromosomes). The variety of chromosome mixtures is such that your brother and you look and behave quite differently; you might have dad’s hair colour, while your brother might have mom’s hair colour. Also, that mix helps identify cells with different roles, such as heart cells differing from liver cells.
RNA (also a long molecule in every cell from which DNA has evolved) differs from DNA in that: (a) its four base components are AU-GC (not AT-GC – uracil being in place, rather than thymine); (b) it is structured around a single helix, rather than a double helix; and (c) it has one more oxygen atom in its sugar-phosphate backbone. The role of RNA (i) besides making replicates of itself, is (ii) to act as a messenger for DNA, and (iii) to make proteins (and enzymes – a type of protein that converts the format of other proteins, such as those we eat, into a usable form for human absorption).
The whole gang operates together as follows. DNA is the music score. RNA carries that music down to, and helps, fabricate the workers in the cells (musicians), namely proteins – yes, proteins do all the work – and enzymes (which are special protein molecules that adapt the action to the situation, i.e., catalysts). The music (DNA) says it’s time to move an eye muscle, so the RNA reads that message from the right chromosome and within that, from the right genes that get the proteins and enzymes to blow the horn on C flat…i.e., immediately make the muscle movement happen.
Progress with CRISPR
We recently learned how to apply CRISPR as a gene-manipulating tool (called gene editing), earning its scientific researchers Nobel prizes (Jennifer Doudna and Emmanuelle Charpentier). It is now clear that gene editing can serve the purpose of removing some of our most debilitating diseases.
It was put into action to fight COVID-19 with amazing success – an unheard of 95% vaccine effectiveness (when the goal was 50% effectiveness). It is clear now that our fight against viruses is nearly under control. It is also clear that with CRISPR we are on the path to eliminating our susceptibility to all harmful viruses, perhaps five or 10 years from now (just as bacteria have).
The next step
Scientists speculated that if we can manipulate genes with CRISPR tools, perhaps we can manipulate genes to make our embryos taller, or smarter, or more handsome. That is, we can create a super race. The movie GATTACA (using letters of the bases), starring Ethan Hawke and Uma Thurman, follows such a theme. Scientists and rule-making politicians agreed internationally that moving in such a direction was filled with too many unknowns to be pursued freely and a type of preventive moratorium was established.
Attempts to hold back science
I remember in the 1980s, in the early days of Internet, a common agreement that Internet would pursue the aim of increased communications and not be tainted with ads and commercialism. See where such a human agreement has taken us?
The atomic bomb, understood to be a danger in the wrong hands, was subsequently opposed by many of the scientists who helped build it. Although its development was limited by international agreement, rogue states (Iraq, Iran, North Korea, Russia, etc.) have followed their own path in efforts to develop their own version of this pending disaster.
So, too, with CRISPR; a rogue American-Chinese scientist, He Jiankui, who was part of the international scientific CRISPR society, secretly applied CRISPR to a human embryo, on a set of Chinese twins (for disease prevention). He proudly announced his success at an international CRISPR conference, much to the horror of many attendees.
Although America did not take action, the Chinese government acted swiftly, arresting He when he was in China. He was fined nearly $500,000, banned for life from working in reproductive science, and is now serving out a three-year jail sentence in China for his bravado. The twins, fortunately, are healthy three-year-olds today and free from a hereditary disease.
The question is: How long will CRISPR be held back? The answer probably is: Not forever. Legally or illegally, some effort to construct a super race is bound to occur.
What can you as a business leader do? The answer is: become informed. Don’t allow your ignorance to promote your silence. Learn about CRISPR. Follow its progress. No longer belong to the silent majority.
Where to start? Perhaps you might try looking over a best seller such as The Code Breaker.1
Here’s hoping for your social contribution.
1 Walter Isaacson, The Code Breaker (Toronto: Simon & Schuster Paperbacks, 2021).