DOES NATURE OR NURTURE CAUSE DISEASE?

© 2001 DNA Sciences, Inc. All rights reserved

Why do we get sick? An enduring question in medicine asks if diseases arise from nature or nurture. Do we get sick because of some built-in aspect of our bodies, or because some aspect of the environment affects us?

Introduction

In the last century, researchers have learned that many diseases arise from variations in the genes we inherit from our parents. And in the last three decades, an explosion of genetic information has implicated genes in nearly every disease, and even in behaviors.

Do scientists now think that all diseases are genetic in origin? No. Instead, medical researchers see diseases as arising from both genes and the environment. In some cases, genes predominate. In other cases, the environment does. But most diseases arise from a complex combination of genetic influences and environmental influences. You could line up all diseases on a scale from purely genetic to purely environmental. The result would be a curve, with most diseases in the middle, arising from both genetic and environmental causes.

Extremes of the spectrum -- purely environmental disease

Some diseases lie at the extreme ends of this spectrum. Imagine that an entirely random event causes you an injury -- say a meteorite crashes through your roof. Clearly, genetics has nothing to do with your injury. But that doesn't mean that genetics plays no role in accidents. Scientists suspect that the genes you inherit may influence how likely you are to take up risky activities, such as mountain climbing or scuba diving.

Alcohol is involved in many accidents, and alcoholism has a significant genetic component. What's more, how long it takes you to recover from that meteorite injury may well depend on your genes. But the point is clear: there are some medical problems that arise by chance.

Extremes of the spectrum -- purely genetic disease

At the other extreme, if you inherit a gene for sickle hemoglobin from each of your parents, you will have sickle cell anemia, a life-threatening illness. Here, the environment plays no part in your getting the disease -- if you get the genes, you get the disease. Your own behavior may affect when and how severely the disease strikes, however. Sickle cell attacks are more common when the body isn't getting enough oxygen, such as when exercising heavily, or living at high altitudes. Scientists believe that some 2,500 diseases are simply genetic in origin [2].

The middle of the spectrum -- genetic and environmental disease

Most diseases require contributions of genetics and environment. One example is a disease called PKU or phenylketonuria. A child cannot have PKU unless he or she inherits two copies of the defective gene, one from each parent. Before this genetic disease was well understood, children who inherited these gene variants developed severe mental retardation. Then, a few decades ago, scientists realized that the child will suffer no illness, unless he or she eats a chemical called phenylalanine.

So, the key to avoiding problems in this genetic disease is to carefully control the child's environment -- specifically, food. Phenylalanine is present in many, but not all, foods, and it takes knowledge and vigilance to avoid them all. (Look at a can of Diet Coke®™, for example. Notice it has a warning in bold letters that it contains phenylalanine.) Because the worst aspects of PKU can be avoided by avoiding foods with phenylalanine, most states require screening for PKU at birth.

The majority of diseases, however, result from a more complex interaction between genetics and environment. Several genes are often involved, and there are several environmental factors that contribute to these diseases. We showed asthma as an example in the figure above.

Cancer is a special case. It arises from a combination of many genetic defects, some caused by the environment and some potentially inherited. The number of inherited defects determines a person's susceptibility to cancer. We'll talk more about this later.

What do we mean by "environment"?

To a geneticist, the environment is everything that is not genetic! Some aspects of the environment that influence health and disease are listed below:

• Diet -- food, preservatives, coloring, method of preparation (smoked foods, for example), composition of diet (fats, carbohydrates, protein), and amount.
• Air -- clean air, smog, pollution, tobacco, chemical fumes in the workplace, dust (coal, cotton, etc.), humidity, temperature.
• Water -- everything we drink, cook, or bathe in. Also, fluoride, pesticides, minerals.
• Radiation -- sunlight, tanning lights, radiation (X rays, microwaves, radio waves).
• Infection -- bacteria, viruses, fungi, parasites. Also includes infection-related factors, such as sanitation and proximity to people, animals, or insects.

Genetic susceptibility

The genes you inherit can affect how likely you are to get a disease, and how that disease may affect you. If a person is genetically susceptible to a particular disease, that person's risk of getting the disease is higher.

Genetic susceptibility combines with environmental input to produce disease. But the combination need not be half and half. Genes can cause a slight susceptibility or a strong susceptibility. If the genetic contribution is weak, the environmental influence must be strong to produce disease, as we show in the diagram below.

Here are a few examples of diseases that have some genetic contribution and some environmental contribution. Genetic susceptibility is part of a spectrum of factors, including age and general health, that contribute to disease or protect against it.

Cancer

Cancer cells are very different from normal cells. It's not easy for a cell to become cancerous, because it must develop basic differences from normal cells:

• The ability to grow without constraints -- Most cells in our bodies live a certain length of time, then die. They divide into new cells for a limited part of their lifespan. By contrast, cancer cells seem to have no limit on their lifespan or their ability to divide into new cells.
• The ability to invade and spread -- Except for a few very specialized types, normal cells neither invade adjacent tissues nor travel in the body. Your kidney cells stay in your kidneys, and your liver cells stay in your liver. Cancer cells do not follow this rule. They grow into adjacent tissues and can spread anywhere in the body.

For a cancer cell to have these two properties, its basic genetic programming must be significantly different from a normal cell's. In other words, the genes of a cancer cell must be significantly different from genes of normal cells.

Does that mean that cancer is 100 percent genetic? In a sense, the answer is yes. For cancer to develop, scientists think that several genes (around two to ten) inside a cell must be damaged first.

Some genes may be damaged by factors in the environment -- radiation and toxic chemicals, for example. Damaged genes can also be inherited. Persons who inherit damaged genes are more susceptible to developing cancer, because less gene damage from the environment is required before the cancer threshold is crossed.

[Advanced: Repairing DNA] Damage to genes is a normal part of the life of all cells. So is the repair of such damage. But what happens if some or all of a cell's gene-repair mechanisms themselves are damaged? One example is the disease xeroderma pigmentosum (XP). In this genetic disease, a person lacks the ability to repair damaged DNA. This is a major problem, because the DNA in our skin cells is routinely damaged by sunlight. (The same ultraviolet rays that cause suntans also damage DNA.) In normal persons, this damage is quickly repaired. In people with XP, the damage is not repaired, and the effects become visible to the naked eye in a short time. Ultimately, the accumulated damage leads to cancer of the skin at a young age. XP illustrates how damage to DNA can accumulate and lead to cancer. It also illustrates that a person's genes can determine the degree of danger posed by the environment.

Fava-bean poisoning

Like PKU (see above), fava-bean poisoning arises from a combination of a genetic variant and poisons in the environment. Fava beans, also known as broad beans, contain two chemicals that are toxic to cells. Most people can safely break down these chemicals with an enzyme called G6PD. But some people do not make G6PD because of a genetic variant. In these people, the fava-bean toxins build up and damage red blood cells.

It would be wrong to say that fava-bean poisoning is the result of a genetic defect. It so happens that people who do not make G6PD are more resistant to malaria than those who do make it. Genetic variants in G6PD are most common among people living where malaria is common.

The case of the fava beans illustrates an important point: the impact of a gene variant depends on the environment. Where malaria is common, the inability to make G6PD is a good thing. Where malaria is uncommon, the inability to make G6PD can be a problem because it makes people susceptible to certain harmful side effects from a variety of medications. This is how evolution proceeds -- the environment determines which genes are useful and which are not.

[Advanced: More about fava] Actually, the situation with fava beans is a bit more complicated. The bean is most popular in precisely those parts of the world where it can make the most people sick (because they cannot make G6PD). Why is that? One theory is that people who lack G6PD, but eat the bean anyway, may get more protection against malaria than if they did not eat the bean. In people who lack G6PD, fava beans cause certain chemical changes in the blood. It turns out these chemical changes make life very difficult for the malaria parasite. When just the right amount of beans have been eaten -- enough to cause the chemical change, but not enough to make the person sick -- the resistance to malaria is highest. This seems to be a remarkable example in which the environment (cultural food habits) and genes evolved together, to form a natural anti-malaria prevention. It may be that, over thousands of years, people living on the Mediterranean shores of Europe and Africa have learned to walk the narrow road between malaria and fava-bean poisoning [1].

Medicines and genes

If genes affect your reaction to chemicals found in the environment, could they also affect your reaction to medicines? (Medicines are, after all, chemicals, too.) The answer is yes, and we discuss this at length in a separate article.

Other genetic susceptibilities

We discuss the genetics of many diseases and conditions on DNA.com™. We list a few of them below. You will find that each discussion returns to the same theme: genes and the environment interact to produce disease.

1. Diabetes
2. Asthma
3. Heart disease
4. Cancers of many kinds: breast, colon, prostate
5. Alzheimer's disease
6. Parkinson's disease

Conclusion

We are in the early stages of a genetic revolution in medicine. Many of the genetic diseases that we understand arise from large health effects of mutations in a single gene. But most diseases probably arise from the effects of variations in several genes, combined with a variety of environmental influences. As we learn more about genetics, we will begin to understand these complex interactions. We will no doubt learn that genetics plays a role in nearly all diseases. Also, we will learn that the genes influencing the development of a disease are often different from the genes influencing the progression of the disease. Each step along this path is likely to yield new approaches to treating or preventing disease.

References used in this article

[1] Desowitz RS. New Guinea Tapeworms and Jewish Grandmothers: Tales of Parasites and People. New York: Norton, 1987.

[2] Walter and Eliza Hall Institute (Australia): [full text].