The Genome Editing Revolution — Humans using tech to repair themselves.
The mechanism for life on earth is so simple and so spontaneous that it is both hard to believe that it could have happened (how could it be that simple?) and at the same time, hard to believe that it could not have happened many times before in the universe. Yet that code that controls the expression of life can sometimes go wrong. It then drives the expression of disease. This article begins a series that explores recent discoveries in genomic science that now have the potential to cure patients of disease with a single injection.
Shortly after the day on earth when life first arose, a need emerged for that life to copy itself. Life that cannot repeat cannot exist. Those very first life forms on earth were microbes. Today, some 3.5 billion years after they first formed and designed a way to replicate, there exist an unknown number of different species on Earth. Every one has evolved from that first microbe.
But how could this happen with just a mix of chemicals? It seems that with some kind of spontaneous atomic force, or perhaps universal wisdom, a code was generated that allowed life to form and replicate. It was a simple code made up of four chemical bases or keys. With those four keys, now written into millions of lines of DNA code, all life is created. It has been that way forever.
But it seems far too simple. A chemical code, held in DNA, generates proteins from combinations of amino acids. Those proteins both send signals to other cells and also provide the structural components for the building of cells. But could all life really exist from a code of just four chemicals that signal the arrangement of proteins? In fact, when ‘genetic material’ was first separated in cells in the early 1940’s, the scientists that discovered it thought it far too simple to be a code responsible for life.
Yet ever since humans began living in tribal groups, they have understood that individuals inherit traits from their parents. It happens in plants and in animals. Offspring are like their parents. They pass on their physical build, eye colour, hair type and sometimes disease, to the next generation. Gregor Mendel had shown, in the 1850’s, that peas could pass on specific (single gene) traits from one generation to the next. But no one knew how until very recently.
In 1953 James Watson, Francis Crick, New Zealand scientist Maurice Wilkins and Rosalind Franklin, working at Cambridge University in England discovered the long repeated, twisted strand structure of DNA that exists in every single cell of any animal. This was the beginning of a true revolution in science. Here finally was the evidence that a molecular code existed for any plant or creature to copy itself, both in its own lifetime and into future generations. And a full copy of the whole organism’s genetic code was to be found in each and every cell in its body, along with a way to selectively turn on or off the genes required for that particular cell. This made retinal cells function for vision, neuronal cells function as nerves and muscle fibres form as muscles. Now, only six decades later we are at the beginning of a new epoch in biology that will allow us to repair disease within the very cells where that disease originates.
Humans have used genetic engineering in different ways since crops have been grown. A thousand years ago humans were selectively breeding plants and animals. Then in 1796 William Jenner, from St Georges Hospital in London, induced artificial immunisation in humans with similar but weaker viruses to build resistance to Smallpox. And in the 1970’s by ‘recombining’ the DNA of bacterial cells with DNA of human cells synthetic Insulin and Human Growth Hormone was created. These are all ways to manipulate the expression of genes to get an effect. But we have never been able to successfully target specific abnormalities in single nucleotide bases within a gene to reverse disease or even aging.
Last year, in 2019, the first two humans were cured of previously intractable genetic disease, using a new gene editing technology. Incredibly this treatment has the potential to cure disease with a single treatment; ‘once and done’ style. One patient had Sickle Cell Anaemia and the other, Beta Thalassemia. These are debilitating blood disorders that limit and shorten the life of the sufferer. They require ongoing, often painful medical treatment and they get progressively worse. Yet nearly a year after this new treatment, neither patient is symptomatic and neither have required further intervention.
These two blood disorders were good candidates for the first human clinical trials of CRISPR. They are known as Mendelian disorders, a description of any disease that is caused by DNA located in a single gene on a specific chromosome. However many other disorders are complex and multi-gene dependent which make them more difficult to edit. The expression and location of the DNA responsible in complex disorders may vary between individuals, across a number of genes. These are still potential candidates for gene editing but require much more accurate mapping.
When this amazing technology with hope to cure patients of disease was first discovered, researchers failed to grasp its full implications. Soon however, the possibility was seen to send in the enzyme and cut out bad or damaged segments in animal or plant cell code. The enzyme technology, called CRISPR, acts like molecular scissors, able to cut out a single, disease causing base pair within the DNA code. It offers a highly targeted way to edit our cellular programming. Without too much imagination it can be seen that we now have the potential to engineer our very own DNA to perhaps create super humans, or at least create humans that can both resist and be cured of any disease controlled by our genes.
What does this mean for medicine and treatment of disease?
Most disease is genetic in origin. At some level the DNA is affected, either being inherited badly, replicated incorrectly or damaged. DNA is held in the nucleus of every cell in the body and controls both cellular energy and cell division. When those processes go wrong it is often at the code level, in the DNA. That means that cancers, kidney disease, heart attacks or even infectious disease are influenced, by errors or damage in the instructions to the cells as the cell is created or when it divides. Sometimes that results from a bad copy of a parent’s genetic code from birth, sometimes it is an exact copy of a parents diseased gene that was previously unnoticed or unexpressed in the parent, sometimes an error occurs spontaneously and sometimes it results from environmental stress. UV light, psychological stress, exogenous chemicals, bad food and lack of exercise all damage our genes.
If a copying error occurs, we end up with increased cellular aging, senescence or even tumours. Thankfully our bodies have evolved ways to fix those coding blips. Cells and their DNA have built-in repair mechanisms that continuously scan and fix mismatch errors as they occur. But it’s not perfect. As we get older or as we suffer environmental stress the body becomes less able to repair itself and disease can manifest.
What does this mean for society?
There is currently a flurry of activity in research labs across the world trying to harness this enzymatic scissor technology. Patents are flying out of leading-edge research universities. Nobel Prizes are postulated and Venture Capitalists are starting to propose a new wave of investment opportunities to hedge against peaked-out traditional markets. And there is, at last hope for patients with debilitating genetic disease.
Perhaps slower to grasp the change in front of us are health systems and clinicians. The current talk of clinical medicine is dominated by promising immunotherapy and also by Artificial Intelligence. Immunotherapy is indeed showing good results in practice, in certain areas and has potential for cure in specific disease. Certainly, AI also could improve efficiencies in health systems both clinically and administratively. We are seeing that already in radiology, where machines can read some limited scans more accurately than radiologists. Big Data and AI are no doubt important. So too is Blockchain technology, to guard the ownership, integrity and security of our genomic and other data. But a future that removes lifelong disease burden from both individuals and society with single ‘once and done’ injections seems like Sci-Fi.
That Sci-Fi future is nearer than we think.
Kris Vette is an Emerging Technology Strategist. He runs Chain Ecosystems, a consultancy that enables organisations and people to posture themselves for success in a rapidly evolving world.
