Biotechnology

Bioengineering Made Simple

Is Human Genetic Engineering Realistic?

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Few genetic researchers doubt that it will be possible someday to correct many of the thousands of inherited single-gene diseases that afflict our fellow human beings. However, many respected scientists believe that safe human genetic engineering may never be practical, since most human traits—both desirable and deleterious—are the result of the actions of multiple genes. This insight leads to the so-called combinatorial explosion.

A combinatorial explosion occurs when a huge number of possible combinations are created by increasing the number of entities that can be combined. For example, there are 86,493,225 ways to pull 12 rabbits out of a hat containing 30 rabbits, and more than 635 billion 13-card bridge hands that can be dealt from a 52-card deck. The combinatorial problem grows mind-bogglingly huge when one considers the various ways just 30,000 human genes and the 100,000 or so proteins they produce can be combined in human cells and tissues. So skeptics of genetic engineering argue that such a vast array of complicated interactions may well preclude safe and effective engineering in human beings for such multifactorial genetic illnesses as heart disease and cancer, and for beneficial traits like high intelligence. But perhaps this is too dismal a long-term view.

Other researchers are in the very early stages of attacking this problem. Now that the human genome—the complete genetic recipe for making a human being—is mapped, scientists are beginning to probe the complex ecology and interactions of genes to see how the recipe actually works to create a human.

One promising approach is to use biochips for testing tissues to see which genes are turned on or turned off during disease states. This kind of testing provides preliminary information about how genes interact to produce health or disease in various tissues. It also shows how old cells differ from young cells. By comparing gene states between diseased tissues and healthy tissues, researchers hope to identify gene and protein targets for pharmaceuticals that would restore diseased tissues to health.

Multiple gene testing also can identify the constellations of genes that make their bearers more susceptible to various diseases, such as heart disease or Alzheimer's. For example, a recent study tested for three genes that, when combined, improved by eightfold the ability to predict patients who are prone to dangerous blood clots, a condition known as venous thrombosis. In the future, one can imagine confronting this deleterious genetic condition through both pharmaceutical intervention, and the engineering of embryos with a different set of genes.

Such genetic engineering may not be as complicated as it sounds, since constellations of genes apparently sort themselves into specific sets, called haplotypes. Haplotypes are blocks of gene variants that travel together. In a sense, evolution, by testing various combinations of genes and devising haplotypes, has already cut through the combinatorial explosion for us. If individual genes are like the separate ingredients for a cake—flour, baking soda, sugar, salt, yeast and so forth—haplotypes are more like cake mixes in which all the ingredients are premixed in definite and predictable ways. So by using known haplotypes, genetic engineers will not be reinventing the wheel, they will simply be using already existing natural gene combinations, tested by evolution and time, to enhance a future child's health or mental agility.

The "virtual cell" is another project whose results will be invaluable to future genetic engineers. Researchers such as Stanford's Harley McAdams and Lucy Shapiro are trying to build computer models of human cells, tissues and organs to simulate complete genetic regulatory and metabolic pathways. Such models would be useful aids for testing pharmaceuticals "in silico." Virtual cell simulations could also help future genetic engineers to predict how prospective genetic changes would cascade through cells and tissues as well, thus enabling them to avoid bad unintended consequences.

Human genetic engineering is still a long way off, but as British chemist Michael Faraday once declared, "Nothing is too wonderful to be true, if it be consistent with the laws of nature."

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