Genetics Said to Make Us Vulnerable to Diseases

There’s a long list of diseases people keep dying from. Sickle cell anemia. Malaria. Cystic fibrosis. Cholera.

Why?

Most people live normal lives, but suffer from dozens of pesky ailments.

Some become near-sighted.

Some eyes have blind spots.

Some people choke because of bad body design.

Some become anguished with fevers and pain and cough.

Are these faults in the genes? Can people blame their ancestors who walked the African savanna millions of years ago foraging for simple foods, stalked by wild animals and starvation?

The trouble, to some experts, seems to stem from the long, complicated process, called natural selection, in which the fittest survived, but at a price.

They say we are trying to meet modern stress with bodies designed for simpler times. They imply we are out-of-date in reverse.

It is the basis of a new idea of medicine that pits Charles Darwin and natural selection against today’s pragmatic realities.

The archivists say our bodies are imperfect because of an incredible amalgam of natural compromises. We are a mosaic of chance.

“A lot of things we think of as disease are really defenses,” said Dr. Randolph Nesse of the University of Michigan, co-author of a new book, “Why People Get Sick.”

Is fever a disease? Nah. Fever is good for us. Natural selection has shaped fever as a defense against infection. How about nausea and vomiting?

Well, imagine if you couldn’t vomit. That toxin would be sitting down there and it would kill you.

Cough? Every doctor knows and most patients know that after surgery you’d better have a person cough, otherwise they’re going to get pneumonia and die.

Pain? What happens to people who are born without pain? Most of them are dead by the time they are 30 or 35.

“So all of these things that seem like diseases are not diseases. They’re defenses against diseases.”

Nesse (pronounced Nessie) asks why we still have wisdom teeth and the appendix if they are reservoirs for infection.

Why are they where they are and why hasn’t natural selection eliminated them over the millennia?

His guess is the appendix was once important when our ancestors ate more plant food and it acted as a bacterial reservoir to digest it.

Now, it is vestigial but in people with small appendixes infection can set in, cause pain and eventually burst, flooding the abdomen with poisons.

“Up until now, no one has tried to ask for serious evolutionary explanations for disease,” Nesse said.

“I think there are good reasons for that. . . . There are no evolutionary explanations for disease; there are only evolutionary explanations for vulnerability to diseases.”

He and others in Darwinian medicine think those explanations are essential to the better treatment of disease. They’d like to add a paragraph for every disease listed in medical texts.

Darwinian thought can answer the “arms race” that is waged between the body and microorganisms. Viruses and bacteria are certain to win. “They just outrun us,” Nesse said. And their strategies outwit the body’s defenses as they mutate to avoid them.

For example, the E. Coli bacterium reproduces three or four times in the human body in a single day.

The cold viruses mimic certain receptors to get into the human cell.

The streptococcal organism can hide in the cells themselves.

The rabies virus travels up human nerve pathways and goes straight to the amygdala of the brain which controls aggression.

It also goes to the salivary glands where it produces so much virus-laden saliva that the infected person can’t swallow.

“Literally the rabies virus takes over the behavioral control of the body in order to spread itself,” Nesse said.

Of course, today the AIDS virus is the most notorious.

And one of Nesse’s cohorts, Dr. David Mindell, is searching for evolutionary clues to the origin of the HIV viruses in an evolutionary sense.

He is constructing evolutionary trees for the various human and simian viruses and one cat virus that stymie immunological processes.

“The conventional view is that the virus has been in humans for only about 40 years,” Mindell said. “But based on the evidence, the support for that isn’t particularly strong.”

In fact, he said, the alternative explanation--that the virus has been around for hundreds, perhaps thousands of years--is equally strong.

“It could be an old virus that is newly causing disease,” Mindell said. “At one point we were living with it. It may have caused some local epidemics, but it was milder, less conspicuous. It’s quite possible that a change in human behavior (for instance, prostitution in socially disrupted countries or drug injection in developed countries) changed the selection pressure on this virus, this parasite we carry, and that led to a change in virulence.”

The virus has two stages, one in which it goes right into the human DNA and sits there for a decade or two.

The second when it comes out of the cytoplasm and, using its own enzyme, replicates rapidly and mutates at a high rate.

But even the defective mutants can be valuable to the virus, since some will be able to elude various drug or immune responses that fight them.

“We tend to think that there are a lot of defective genes that cause disease as they arise by mutation,” Nesse said.

But this is not so.

Most genetic disease is caused by genes that have some other beneficial purpose.

One example is the gene that causes cystic fibrosis, a disease that causes great suffering and premature death.

It exists in one out of 25 Caucasians and one out of 2,500 is born with the disease when both parents carry the gene.

The gene is so common, Nesse said, “that it has to have some advantage, otherwise it wouldn’t be there. So we speculated that maybe, conceivably, it is because it has to do with transport in the body of chlorine. Maybe it makes it less likely you’re going to die of diarrhea. Indeed, a wonderful story came out a few months ago showing if you inject the cholera toxin into a mouse that has one cystic fibrosis gene, you get half as much diarrhea.

“Do you say the sickle-cell gene is abnormal? It evolved because it saves lives from malaria. Even though when you get two doses of it [one from each parent], it causes sickle-cell disease.”

Sickle-cell anemia is characterized by severe pain and abnormal red blood cells that are not carrying oxygen sufficiently to the various organs.

Through natural selection the gene gained in the population because people who had the gene did not succumb to malaria.

Where malaria is rare, sickle-cell frequency is less. African-Americans who have lived in malaria-free areas do indeed have less sickle-cell disease than Africans who still have to endure the tropical climate that encourages mosquitoes and malaria.

Nesse thinks the same line of questioning may serve to unravel some of the yet unknown secrets of Tay-Sachs disease, which appears to be genetic among Ashkenazi or Eastern European Jews.

Up to 10% carry the gene. Many die young.

“Everything’s a compromise,” Nesse said. “We walk upright and save a lot of calories and get backache. We have an immune system that protects us against infection and yet that immune system damages our tissues. We have a capacity to repair damage by having cells that divide. . . . The same mechanism leads to cancer.”

Nesse sees all manner of design flaws that natural selection has encouraged.

Some people suffer from retinal detachment which laser surgery now welds back in place. There’s nothing, he said, to hold the retina in.

“The nerves and blood vessels in the eye have to go through the back of the retina, through the blind spot, and spread over the retina which makes a whole bunch of shadows. What a stupid design. Instead of one whole image there are all these lines. . . . So not only do we have the blind spot, we have the shadows and the eye has to wiggle all the time and the brain has to have a lot of processing power to make the image stand still.”

The eye of the squid is more appropriately designed, delivering an image all in one piece.

Natural selection is also responsible for people choking, by letting the windpipe and the esophagus cross at uncomfortably close quarters, allowing food to go down the wrong way.

Why? Because at some point in prehistory amphibians needed nostrils on top to get air while swimming. Which made the windpipe cross the esophagus.

Nearsightedness, myopia, is controlled to a considerable degree by genes.

So why haven’t those genes been eliminated by natural selection?

If we had remained gatherers of food, we probably would not be afflicted.

If both parents are myopic, something over 12% of youngsters will be wearing glasses by late childhood.

But it is not genes alone that cause the trouble.

“Nearsightedness was rare in Eskimos prior to this century, as it is in most hunter-gatherer populations today,” Nesse wrote in “Technology Review” of the Massachusetts Institute of Technology.

“But in the decades after Eskimo children began attending school, the rate of myopia quickly increases to the same 25% prevalence found in most modern societies.”

A rather remarkable experiment with young chicks and monkeys corroborated the mechanics. Researchers put cloudy lenses over the eyes and the eyeballs kept growing until they were profoundly nearsighted. And the effect is irreversible.

Why do women get morning sickness?

An independent biologist in Seattle, Margie Profet, established a hypothesis that it, too, is a product of natural selection, a mechanism for protecting the fetus at its most vulnerable phase.

She asked why didn’t natural selection eliminate this form of nausea.

“You don’t want to be vomiting during pregnancy and losing precious calories at the same time you’re trying to develop the fetus,” Nesse said. “There must be some benefit.”

Profet observed that morning sickness starts two weeks into pregnancy and ends quite suddenly right after the first trimester. Women tend to be quite picky about what they eat during that time.

“She put all that together and she came up with an idea. Maybe the nausea makes them avoid foods that are going to be toxic to their fetus,” Nesse said.

“And this fit very nicely. In the first place, tissue starts to differentiate in about two weeks and is complete by the end of the first trimester.”

Profet looked at the statistics to see if women who do not have morning sickness are more likely to have abnormal babies, and found that to be the case.

Other researchers are looking at the relationship between birth weight and high blood pressure. The conclusion is that bigger is not better.

The bigger one is, the more difficulty the kidneys have accommodating the body, and blood pressure may be a damaging accommodation the evolving human body makes for size.

All in all, Charles Darwin might have been both pleased and displeased by the efforts of Darwinian doctors whom he might have seen as trying to find truth in a fuzzy old photograph as he did, or as trying to find truth in a current snapshot.

But Nesse sees the new line of questioning as both useful and potentially elucidating.

“Bad things happen to all people,” he said, “because their bodies are not objects of perfection; they are objects of compromise. They were not designed to maximize our welfare; they were designed to maximize the transmission of our genes.”