THE FORTNIGHTLY CLUB
Founded 24 January 1895
Meeting Number 1801
December 2, 2010
“Why We Are The Way We Are”
Boyd A. Nies, M. D.
Assembly Room, A. K. Smiley Public Library
Evolutionary or Darwinian Medicine only recently has been recognized as a
distinct area for research. Using evolutionary principles, this discipline has
already generated a number of possible causes of human disease. Many of
these hypotheses have strong supporting evidence, while others require
further study. Insights into the etiology of other diseases will likely
emerge in the future. Although clinical applications of these evolutionary
hypotheses so far have been few, it is hoped that as more information
becomes available, new areas of treatment and prevention of human disease
Key Words: Evolutionary Medicine; Darwinian Medicine
Background of the Author
Boyd A. Nies was born and raised in Orange, California. He graduated from Stanford University in 1956 and from the Stanford University School of Medicine in 1959. An internship and residency in internal medicine at the UCLA Medical Center and the Wadsworth Veterans Administration Hospital was followed by sub-specialty training in medical oncology at the National Cancer Institute in Bethesda, Maryland and hematology at the Stanford University Medical Center. From 1965 to 1995, he practiced hematology and medical oncology in Redlands and San Bernardino. He subsequently was the Medical Director of the St. Bernardine Hospice for 2 years. During retirement he has been a board member of the Watchorn Lincoln Memorial Association, the Friends of A. K. Smiley Public Library, and Lifestream (formerly the Blood Bank of San Bernardino and Riverside Counties), as well as serving on many committees and boards of the First United Methodist Church. He has been married to the former Helen Salter for 53 years. They have 3 children and 6 grandchildren.
WHY WE ARE THE WAY WE ARE
My purpose in presenting this paper is to introduce you to evolutionary or Darwinian medicine. This relatively new discipline introduces new ways of looking at possible causes of human diseases.
Before going further, let us first consider Charles Darwin and his ideas of evolution. Darwin was born on February 12, 1809, remarkably the same birth date as Abraham Lincoln. (In this community, we have heard much about Lincoln during the celebration of the 200th anniversary of his birth, but relatively little about Darwin.) As a boy Charles was interested in nature, spending much of his time in the countryside. He was a poor student and his father, Robert Darwin, who was a physician, worried about Charles’ loss of focus, fearing that he might become a disgrace to himself and his family. His father first sent him to the University of Edinburgh Medical School to study medicine, but Charles found the lectures dull and could not stand the gore associated with surgery of that day. Charles was then sent to Christ College, Cambridge, with the idea that he would become an Anglican clergyman. Instead, he became interested in beetle collecting, natural history, and geology. Shortly after graduation in 1831 he had an opportunity to serve as a naturalist aboard the HMS Beagle on a planned 2 year trip to chart the coastline of South America. Pictures of the Beagle show it to be a small and probably fragile ship. Ships of a similar design were known to sailors of the day as “floating coffins”. Robert Darwin initially opposed his son’s journey, but eventually agreed not only to pay for Charles’ expenses, but also for those of an assistant.
On that trip which ended up lasting five years, Darwin studied geology and natural history. While the crew of the ship was involved in surveying, he was able to spend much of that time on land, providing relief from the severe sea sickness which he suffered from while on ship. Darwin collected fossils including those of an extinct giant sloth and of an extinct giant armadillo. He was also able to spend some time as a cowboy with the Argentine gauchos. But it was his stop in the Galapagos Islands in September and October 1835 that amazed him and subsequently influenced him the most. He noted peculiar animals there including a marine iguana which ate seaweed. He also observed that each island had its own plant and animal life including individual species of tortoises and finches.
After his return in 1836, he married his cousin, Emma Wedgwood. Together they had 10 children, eight of whom survived infancy. He began organizing his thinking to explain the findings noted on his Beagle voyage. Evolution was not a new concept at that time; in fact, Charles Darwin’s grandfather, Erasmus Darwin, a free thinker, had been a leading advocate of evolution. However, the way that evolutionary changes took place was not clear. The French natural philosopher, Jean-Baptise Lamarck proposed that characteristics acquired during life could be passed on to the next generation. For example, Lamarck believed that giraffes’ long necks were developed due to stretching in an attempt to reach food and then that characteristic was passed on to the next generation. Darwin found that explanation unconvincing as the primary mechanism for the process of evolution. He was impressed by the changes in dogs and pigeons which could be produced by selective breeding, a process which he termed “artificial selection”. However, it was not until 1844 that his famous theory of “natural selection” was thoroughly developed. Darwin’s idea was that those organisms best adapted to their environment would have a better chance of surviving and reproducing. Over time those characteristics would increase in frequency in the population. Over long periods of time this process could lead to new species. His closest colleagues urged him to publish his theory, but he was hesitant to do so. He had difficulty in explaining how advantageous traits could persist without being “swamped” by the much more numerous less advantageous traits in the population. (The concept of dominant and recessive genes was not widely accepted until the early 20th century.) Geologists and physicists of that time had different estimates of the age of the earth and thus Darwin was concerned that there might not be enough time for the slow process of natural selection to work. However, when Darwin received an essay from Alfred Russel Wallace proposing a similar idea, he decided that he would have to present his theory in writing or that Wallace would receive the primary credit. It was arranged that both Wallace’s essay along with excerpts from a previously private essay by Darwin would be presented at a scientific meeting in 1858. In the following year, 1859, Darwin published his famous book: “On the Origin of the Species”. Recent genetic studies have provided powerful evidence in support of natural selection as the primary explanation as to how evolution occurs.
In some instances relatively rapid evolution can be observed. In the early 1800’s in England, pepper moths were white with black speckles. They tended to congregate on the trees which were of a similar color, so that they were camouflaged from the birds which wished to eat them. With the onset of the Industrial Revolution, there was production of a lot of soot in the industrial areas. So the tree bark often became black. Whereas previously the pepper moths were as described with only about one in 200 being black, by the late 1800’s most of the moths became black. When the pollution from the factories became less, the pepper moths again became white with speckles.
A more recent example is that of bacteria becoming resistant to antibiotics. As soon as an antibiotic is introduced, it gradually becomes less effective, since those forms of the bacteria resistant to the antibiotic have a reproductive advantage. The methicillin resistant Staphylococcus aureus (the so-called MRSA) is perhaps the best known example of this phenomenon. Infections with MRSA have become such a serious problem that deaths attributed to MRSA now exceed deaths from AIDS in the U.S.
With that as an introduction, let us now go on to consider how modern diseases may have had their roots of our evolutionary past.
Scientists now believe that humans (homo sapiens) appeared about 200,000 – 250,000 years ago in Africa. They were predominantly what we now call hunter-gatherers. Our Paleolithic ancestors continued with that mode of existence until about 10,000 years ago when agriculture began to be practiced. Thus for most of our existence we have been hunter-gatherers and much of our physiology is still accustomed to that way of life.
Adaptations mismatched to modern life
Adaptations which may have been appropriate in the past, now are mismatched to modern life.
Obesity: Why are many of us fat? The proximate causes are that we eat too much, we eat the wrong things, and we don’t exercise enough. The ultimate cause, however, may be different. One can imagine a hunter- gatherer ancestor generally having a marginal diet but then gorging himself when a large killed animal is available. Very likely, then, our ancestors developed an efficiency in using the energy from the food that they ate. The storage of fat was useful under those circumstances, but today, with abundant food available at all times, it is not. Low birth weight in babies, presumably due to less than optimum nutrition from the mother, seems to turn on a switch which makes those children more efficient in conserving energy. Particularly if those individuals are then exposed to abundant food during childhood, they become overweight and thus later have a higher rate of diabetes, heart disease, and stroke. It may be that this “switch” (epigenetic mark) may actually be passed on to future generations.
Allergies: The incidence of asthma and other allergies has markedly increased in modern times. In most of human history, chronic infections, particularly with parasitic worms, were common. Exposure to those infections “down loaded” (in a sense toned down) the immune system so that it was relatively unaffected by other allergens. Another way of thinking about this is that humans and their associated microorganisms (microbiomes) have evolved together and in many instances a symbiotic equilibrium developed. In the relatively clean environments of modern developed countries, the immune systems of many individuals have become overly reactive to allergens such as peanuts, dust mites, and pet dander, causing asthma and other allergic phenomena. In some instances, theoretically, so many antibodies may be produced that they may leak through our surveillance systems, causing autoimmune diseases such as lupus, ulcerative colitis, Crohn’s disease, type I diabetes, and others. Trials using a species of pig whipworm, thought to be innocuous to humans, to treat peanut allergy, ulcerative colitis, Crohn’s disease, and multiple sclerosis, are underway in the U. S. and Europe. Preliminary results, particularly in Crohn’s disease are promising.
Breast cancer: The incidence of breast cancer has markedly increased in modern times. Women in prior times typically had their first birth at a young age and spent most of their reproductive years either pregnant or lactating. Thus, they had fewer menstrual cycles than modern women. Ovulation is associated with a burst of hormones which increase the risk of breast cancer. It is estimated that modern women have up to 400 menstrual cycles during their lives, whereas in prior times 100 menses per lifetime was the norm. Even in the 1990s, breast cancer rates in Colombia, Coast Rica, and Ecuador were 20-30 per 100,000 versus 100-150 per 100,000 females in the U.S. and Western Europe. The “pill” inhibits the ovulation, but in that case, of course, exogenous hormones are given. There is a fine line in getting just the right amount of estrogen to prevent osteoporosis but not enough to increase breast cancer risk.
Morning sickness: How could there possibly be a benefit for morning sickness? The time that this occurs is usually early in pregnancy about the time that fetal vulnerability is at its maximum. It may be that morning sickness evolved in order to protect the developing fetus from toxic foods which the mother might eat during that time. Very likely the foods that were eaten in the Paleolithic era were more toxic than those produced today. Supporting evidence for this theory is the fact that women who have no nausea during pregnancy are more likely to miscarry or have children with birth defects. In the same vein, the dislike of strongly flavored vegetables such as onions and broccoli by many children may be explained by the fact that children are more susceptible to toxic materials than adults. Further research on these subjects needs to be done of, course. One criticism of the “embryo protection hypothesis” is that it makes sense only in women who were well nourished prior to pregnancy. Severe consequences to the fetus would likely occur if the mother were already poorly nourished and then developed morning sickness.
“Mental Disorders”: Attention-Deficit Hyperactive Disorder (ADHD) may well have been a beneficial adaptation during much of human history. During the Paleolithic era the possibility of being eaten by a wild animal was a constant threat, giving hyperactive children an advantage over those children with a quiet focus. Likewise a certain degree of anxiety and obsessive-compulsiveness would have also been desirable then.
Lactase deficiency: Children are born with the enzyme, lactase, so that they are able to digest milk for the first few years of life. Later the enzyme often disappears. Prior to the domestication of milk giving animals such as cows and goats about 8,000 years ago, lactase was not needed except in infants. When milk became available to adults, the lack of that enzyme caused gastrointestinal symptoms such as intestinal cramps, diarrhea, excessive gas, nausea and vomiting which could be a serious problem if milk were a primary source of nutrition. A single dominant gene controls the production of lactase, so that it should spread relatively rapidly if the ability to digest milk was important. Today lactase persistence has a high frequency in northern Europe and in certain African tribes, where milk drinking has been going on for a long time. Even today, an estimated 325 generations after milk became available to adults, many people are still deficient in that enzyme. Other more complex mismatched adaptations very likely take even longer for major genetic changes to occur.
Diseases in which adaptations are beneficial only in carriers
Sickle Cell Anemia: Sickle cell anemia is a terrible disease. The red blood cells in this condition when exposed to lower concentrations of oxygen become crescent or sickle shaped. These cells do not carry oxygen as well as the normal deformable disk shaped red blood cells and are more likely to block small vessels. Patients with this disease frequently have painful episodes (“crises”) due to obstruction of blood vessels, which may affect many different areas of the body. If untreated, many patients with this disease die before their reproductive years and most patients do not live beyond the age of 40. Why then does this disease persist? The answer is that carriers of the disease, who are essentially healthy under most circumstances, are less susceptible to malaria. Those areas where the prevalence of malaria is the highest are also the areas where the prevalence of the sickle cell gene is the highest. This resistance to malaria may explain other inherited red cell defects such as thalassemia (Mediterranean or Cooley’s anemia) and glucose 6 phosphate deficiency.
Other Diseases: There is some evidence that carriers of cystic fibrosis may be more resistant to cholera. The Tay-Sachs gene, which when inherited from both parents causes a fatal neurologic disease, may confer resistance to tuberculosis and be associated with superior intelligence. More recently, a gene which increases the frequency of kidney failure has been found to protect against sleeping sickness.
Limitations of the evolutionary process
Slowness of natural selection vs. rapid environmental change: The pace of natural selection remains relatively slow as compared to the increasingly rapid changes in the environment. As we have seen, this phenomenon has produced mismatches between previously beneficial adaptations and modern life.
Natural selection is limited to acting on an existing platform: The adaptation produced by natural selection may be beneficial, but its design often is less than it could be if it were planned from scratch. In a sense, we are more cobbled together than designed. For example, the human spine evolved from the spine of animals that walked on all 4 limbs. Due to humans’ upright posture, their spines became weight bearing and thus more stressed. Hence, the problem of frequent back pain in humans. Also to conform with the upright posture, the pelvis had to be rotated and narrowed. The birth process in humans thus became more difficult compared to lower mammals. Another example is the eye in humans and other vertebrates, which has blood vessels and nerves in front of the light sensitive cells. A better design, to prevent obscuring the photosensitive cells, would have been for the nerves and blood vessels to come in from behind.
Natural selection cannot go backward: The appendix apparently no longer serves a useful purpose. Evolution can do away with the appendix only by slowly making it smaller over time. As the appendix becomes smaller, its cavity shrinks, increasing the chance of blockage and subsequent infection.
Compromises: No trait is optimum for all possibilities. For example, if our bones were larger and more dense, there would be fewer fractures, but we would be less flexible. If the brain of the fetus was larger, the period of post partum development would be shorter, but childbirth would be even more difficult. Factors that limit cell growth may protect us from cancer and birth defects, but increase the chance of cell aging.
Evolutionary defense mechanisms may not always be helpful: We have already discussed the adverse effects of an exuberant immune system causing disturbing allergies and possibly autoimmune diseases. Responses to infection such as fever, vomiting and diarrhea may be beneficial in helping to rid the body of infectious agents, but if excessive can cause their own problems.
In the pre-historic era, a leading cause of death would have been an attack by a large animal. The response to trauma: vasoconstriction, increased blood clotting, and an increased inflammatory response would have been entirely appropriate at that time. The same type of response now produced by anxiety or smoking may over time cause atherosclerosis, thus shortening life.
Evolution is concerned with reproductive potential, not specifically with long-term survival: Natural selection does not operate efficiently later in life. Mutations which are neutral for reproductive potential but are potentially harmful may later accumulate hastening the process of aging. In addition, some genes that promote reproductive success may be inherently less effective in maintenance and repair.
Conclusion: Evolutionary or Darwinian Medicine only recently has been recognized as a distinct area for research. Using evolutionary principles, this discipline has already generated a number of possible causes of human disease. Many of these hypotheses have strong supporting evidence, while others require further study. Insights into the etiology of other diseases will likely surface in the future. Although clinical applications of these findings so far have been few, it is hoped that as more information becomes available, new areas of treatment and prevention of human disease will emerge.
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