[Editor’s note: Gene editing could definitely prevent many single gene genetic disorders (e.g. Huntington’s disease, Marfan’s dyndrome, Cystic fibrosis et cetera). There are thousands of these genetic disorders known, and each one is individually rare. Most of these so-called Mendelian diseases can be prevented in offspring if gene editing were applied to zygotes or embryos (i.e. very early in development). A subset of these genetic disorders (those that do not affect development) could potentially be treated somatically later in life, in a way that doesn’t affect the germline. However the major causes of morbidity and death outside of infectious diseases are not genetic disorders, but are common late-onset diseases like cardiovascular disease, stroke, type-2 diabetes and many cancers. None of these common diseases are simple genetic disorders. They are all complex polygenic diseases that have a substantial non-genetic component. Nobody is free from risk of these common diseases. This article is about the diseases that will get most of us.]
The human body is a fantastically intricate system. Like any complex system that performs tasks, it can fail. The modes of failure in a system are those natural routes to failure that arise because of intrinsic properties of the system’s form and mechanisms of function. The human body relies on mitotic cellular division and DNA replication to grow from the single cell produced by fertilisation to an adult form consisting of trillions of individual cells working collectively to be a human.
Each of the trillions of mitotic cell divisions must copy ~6 billion base pairs, the fundamental informational units that make up DNA, the genetic material used by cells to perform their own tasks as members of the collective. Whereas this copying process is incredibly precise, representing one of the true wonders of the natural world, and not yet matched by any human nanoscale technology, it still is not error-free. So that as cells divide and the DNA in their genomes is copied, those copies accumulate errors and slowly but surely, as the number of cell divisions accumulates, cells become increasingly impaired in function. This is an intrinsic property of the form of the system, and leads to a natural mode of failure: cancer.
Cancer is a particular class of cellular impairment in which the cell fails to continue working for the collective purpose of functioning as a human, and instead embarks on a program of independent cellular proliferation, following a process with well-established hallmarks. The failure occurs because the DNA is not copied from one cell to another well enough in some part of the body. A specific set of changes randomly accumulate leading to a new cell that operates more independently. This cell then may produce, through further mitotic division, a growing population of cancer cells, that over time may form a tumour, metastasise and spread, disrupting the organisation of the system from which they have escaped genetic control.
Cancer is a natural mode of failure for all multicellular organisms, and the larger and more long-lived the organism the more common this type of failure will be, all else being equal (but see Peto’s paradox, and life-history strategies that explain it). So you see, a “cure for cancer” in a formal sense of eliminating its risk is not possible. Millions of years of evolution has resulted in a system which is already exquisitely well-prepared to identify and eliminate such rogue cells, long before they grow into tumours. A requirement of complex multicellularity is a system that can keep cells working collectively (long enough to raise offspring), and one part of that is policing cells that would otherwise go their own way. The human body’s immune system does not only fight extrinsic threats, but also intrinsic threats to the collective operation of the whole.
A human body is eliminating such pre-cancer cells through a system of immune surveillance on a continuous basis. But it doesn’t eliminate every single one, and by the time you die, if not by cancer, it is almost certain your body will contain a number of cell populations that are not following the collective program, and would have eventually caused failure if nothing else did. Cancer is a mode of failure in all multicellular organisms, shown to naturally occur even in basal metazoans. Yes, you can suppress its rate, and by various means reduce the risk of particular cancers, but you can not cure it in any fundamental sense, except by dying young of something else, or designing a single-celled human. Single-celled organisms, being radically different in form to complex multicellular organisms, obviously do not have this mode of failure at all.
During embryonic development a heart and circulatory system develops in the body and at some point the developing system becomes completely reliant on this circulatory system and its central chambered circulatory pump to continue functioning. This four-chambered pulsatile pump made out of striated muscle beats a couple of billion times in an average human life. Every beat is coordinated by a pacemaking signature of electrical signals causing a compression wave involving a few billion heart cells. If the electrical impulse does not develop through these cells properly the heart will stop beating.
The action of beating exacts physical wear and damage on its parts over time, and cells are repaired or replaced. When they are replaced mitotic division and DNA copying are involved. The heart circulates a population of tens of trillions of red blood cells around your body, and a far lesser number of nonetheless crucial white blood cells. New red blood cells are being produced at a rate of millions a second and after a lifetime of about four weeks are degraded into raw materials and waste at an equal rate. The whole body relies on the heart, in conjunction with the lungs and red blood cells to deliver oxygen to every tissue through a fine ramification of capillaries to individual cells, used in cellular respiration and the production of chemical energy by the mitochondria.
Because the heart is central to the functioning of the human body, it defines another natural mode of failure: heart failure. There are many ways for the heart to fail, and most fall under the general class of heart disease, or coronary artery disease. In fact diseases of the heart and cardiovascular system are among the most common causes of morbidity and death globally. The single largest risk factor for heart disease is age. As it is a mode of failure intrinsic to the form and function of the human body, heart disease can not be cured in a fundamental sense, besides by redesigning the system to not have a heart.
The mitochondria contains its own compact set of genetic instructions independent of the chromosomal DNA contained in the nucleus of each cell. During mitotic cell division, the mitochondria is responsible for its own division and replication, so that both daughter cells have mitochondria which each cell relies on for metabolism to produce chemical energy for all the cell’s functions. The mitochondria is a crucial sub-cellular actor in the body’s metabolic processes, without which, the body would fail.
This metabolic system encompasses sophisticated mechanisms for storing, retrieving and using chemical energy in different forms. Metabolic failure, either tissue-specific or systemically is a natural mode of failure for the human body and type-2 diabetes is an example of metabolic failure. Type-2 diabetes is a mode of failure for the human body that is intrinsic to the form and function of human metabolism and although the risk of this failure occurring at some particular age can be substantially reduced, it can not be eliminated, except by redesigning human metabolism.
We could make similar arguments for other complex late-onset diseases like stroke and Alzheimer’s. But in short, all the most common forms of morbidity and mortality in humans are complex late-onset diseases, and the risk of these diseases is not solely genetic, since there is no genotype that is absolutely protective for any of them. They should be correctly understood as natural modes of failure, whose probabilities may be reduced (or more likely delayed), but the risk of these maladies will never be eliminated, not even by gene editing.
Further reading about gene editing: