The Contending Opinions on Three-Parent Embryo Safety, Part I
In our long stride toward the inevitable designer babies, the first manipulation has been the noble goal of creating babies free of the mitochondrial diseases carried by their mothers. This series will examine the issue rather thoroughly in four basic segments:
1. The basic cell biology involved.
2. The problem of defective mitochondria.
3. The technique involving three-parent embryo creation.
4. The current state of the ethics debate among governmental bodies here and in the United Kingdom.
Cell Biology
In order to understand the fullness of the debate, we need to understand some very basic facts about cells. Every human cell contains specialized compartments called Organelles (meaning, Little Organs). Just as the human body has organs for specialized function (heart, lungs, stomach, intestines, brain, liver, kidneys, etc.) so too every cell has little organs for specialized function:
Ribosomes make protein.
Nucleus houses the Chromosomal DNA.
Lysosomes do recycling of worn out parts.
Golgi Bodies modify and ship proteins to appropriate destinations
Endoplasmic Reticula make lipids and are sites of protein synthesis.
and then come the Mitochondria.
The mitochondria are frequently referred to as the powerhouse of the cell, because they take in by-products of glucose and extract large amounts of energy for use by the cell. It takes a great deal of energy for cells to function properly, and the mitochondrion is the place where that happens. That having been said, it is one of the gross oversimplifications in biological education to leave it at energy production and move on where the mitochondrion is concerned.
In fact, there are two scientific journals devoted entirely to mitochondrial research that immediately come to mind: Mitochondrion, and Mitochondrial Research. Suffice it to say that the scope of the mitochondrion and its effects on human physiology are broad and complicated.
For purposes of understanding three-parent embryo creation it helps to know the following. It is thought in evolutionary biology that at one time the mitochondrion was a free-standing, free-living cell that became incorporated into larger cells, with the result being a marriage that worked for both. It’s called the Endosymbiont Theory.
Mitochondria replicate themselves within cells, so when cells divide, each new cell gets an appropriate number of mitochondria. In this way, the mitochondria act somewhat as independent organisms would. Along the way, most of the mitochondrion’s 3,000 genes ended up being transferred to the cell nucleus. The following description comes from the United Mitochondrial Disease Foundation website. I have found them to be an excellent clearinghouse of information with writing that is very easy for the scientific layperson to follow:
The conventional teaching in biology and medicine is that mitochondria function only as “energy factories” for the cell. This over-simplification is a mistake which has slowed our progress toward understanding the biology underlying mitochondrial disease. It takes about 3000 genes to make a mitochondrion. Mitochondrial DNA encodes just 37 of these genes; the remaining genes are encoded in the cell nucleus and the resultant proteins are transported to the mitochondria. Only about 3% of the genes necessary to make a mitochondrion (100 of the 3000) are allocated for making ATP. More than 95% (2900 of 3000) are involved with other functions tied to the specialized duties of the differentiated cell in which it resides. These duties change as we develop from embryo to adult, and our tissues grow, mature, and adapt to the postnatal environment. These other, non-ATP-related functions are intimately involved with most of the major metabolic pathways used by a cell to build, break down, and recycle its molecular building blocks. Cells cannot even make the RNA and DNA they need to grow and function without mitochondria. The building blocks of RNA and DNA are purines and pyrimidines. Mitochondria contain the rate-limiting enzymes for pyrimidine biosynthesis (dihydroorotate dehydrogenase) and heme synthesis (d-amino levulinic acid synthetase) required to make hemoglobin [Note by G.N.: This is the molecule that binds oxygen in every red blood cell]. In the liver, mitochondria are specialized to detoxify ammonia in the urea cycle. Mitochondria are also required for cholesterol metabolism, for estrogen and testosterone synthesis, for neurotransmitter metabolism, and for free radical production and detoxification. They do all this in addition to breaking down (oxidizing) the fat, protein, and carbohydrates we eat and drink.
Do visit their website for specific information on the range of mitochondrial diseases.
Now, without frightening off the non-scientist or non-medical person, the above quote cracks the door ajar ever so slightly to allow a glimpse of the complexities involved at the biological level. Adding further, there needs to be coordination between the genes encoded on mitochondrial DNA (mtDNA) and the mitochondrial genes encoded on the DNA in the nucleus of the cell (nDNA).
To date, there are still too many unknowns in the cell biology and the pathophysiology at the cellular level. (That’s why the journals devoted to mitochondrial research are going strong, and will be for years to come.) We don’t know all of the coordinated function between mtDNA and nDNA within a given individual, and what other factors there may be (as yet unknown) that govern such function. In other words, are all mitochondrial defects solely attributable to mitochondrial genes (mt DNA and nDNA), or are there other genetic/biochemical defects in the individual at play here?
It matters when someone wishes to take the mitochondria from an egg cell, leaving the nDNA intact, and introducing mitochondria from another individual. It matters because the issues are not always so simple as mutations in genes.
Indeed there are other factors around the major genetic factors, and these are known as epigenetic factors. Epigenetics looks at factors involved in the regulation of genes, and when they get turned on and off. Adding still further to the complexity, there may be epigenetic factors in the nDNA that are unknown and alter the epigenetics of the mtDNA., and all of these factors in one kind of cell may well influence mitochondrial function in distant types of cells within the body.
Confused and bewildered yet?
That’s the point. We don’t know what we don’t know, and in mitochondrial disease there is quite a bit that we don’t know. It will be fertile ground for research for decades to come, and that points toward the abomination of three-parent embryo creation in human beings as a vast and unregulated medical experiment.
In the next article (Nov. 20, 2014), we’ll look at several mitochondrial diseases and consider what we do know of their etiology, and what we suspect we don’t yet know. Then in the third article we’ll consider the technique involving three-parent embryo creation and consider the ethical dimensions involved.
