Gene Logic

December 22, 1995 at 12:00 AM EDT


PAUL HOFFMAN: Few things in life are harder to accept than genetic disease. How cruel it seems for nature to sentence a person before he or she is even born to the fate of premature death. These people harbor microscopic defects in their genes. They’re walking time bombs. Sometimes their fuse is long, and they reach adulthood before the disease explodes, such as the case with Lou Gehrig’s or Huntington’s Disease. Other times, like the “bubble boy syndrome,” they have a short fuse, and the disease flares up in early childhood.

From a scientific point of view, the endurance of genetic disease is a profound mystery. There are some 100,000 different genes in our body, and evolution apparently works to eliminate any genes that are not beneficial to the survival of the species. How then can genes persist that pre- program people to die before their time?

The mystery is even greater in the case of genetic diseases that kill children. A gene that causes disease too soon would seem to contribute to its own demise by killing off its victims before they were old enough to pass on the gene to children of their own.

So is there any logic at all to genetic disease? Scientists are discovering in nature a kind of cold-hearted logic, a calculus of life and death. UCLA Medical School Professor Jared Diamond says genetic diseases may persist, because while they condemn some people to death, they confer life on others. Take the gene for sickle cell anemia.

The gene tends to be confined to specific racial and ethnic groups, namely blacks from equatorial Africa and their descendants, certain Mediterranean and Arabic populations, and people in India. What these diverse groups have in common, besides a propensity for sickle cell anemia, is that they or their ancestors inhabited tropical parts of the old world. The sickle cell gene turns out to afford protection against the tropical disease, malaria.

Like most other genes, you inherit two copies, one from your father, and one from your mother. It takes two bad copies of the sickle cell gene for you to come down with sickle cell anemia. Two bad copies will change the shape of your red blood cells from circles to sickles. But one bad copy will not sufficiently alter your blood cells to cause disease. Instead, it will actually increase your chances in life by making your blood cells resistant to malaria, the deadliest infectious scourge in the world which kills more than 3 million people each year.

Evolution, says Professor Diamond, has struck a grim bargain, letting a few of its children to succumb to anemia so that the rest of its children will evade malaria. Another gene that was recently found to be double-edged is the gene for cystic fibrosis, the most common fatal genetic disorder among Caucasians.

This aberrant gene slows the flow of water out of cells in our body. If we inherit two bad copies of the gene, the flow is virtually shut off. Thick, sticky mucous builds up in the lungs and the gut because there’s no water to wash it away. The mucous obstructs breathing and digestion and serves as a fertile breeding ground for all sorts of nasty infections. But the presence of only one bad copy of the cystic fibrosis gene appears to be a godsend. Apparently, our cells then retain more water than normal but not to the extent that deadly mucous can accumulate.

The water-retaining cells offer protection against diarrhea-inducing bacteria such as cholera, E-coli, and salmonella, which despite modern medicine, still kill an astonishing number of people by dehydrating them. E-coli alone is responsible for the deaths of 1.5 million children.

Again, nature seems to be playing a grizzly numbers game, sacrificing some of its children to cystic fibrosis so that a far larger number can escape the scourge of deadly diarrhea. Nature may be cruel and calculating, but it is not illogical.

I’m Paul Hoffman.