Survival of the Sickest: A Medical Maverick Discovers Why We Need Disease

[WEB EXCLUSIVE]

By Mike Perry

Review of Survival of the Sickest: A Medical Maverick Discovers Why We Need Disease by Dr. Sharon Moalem, with Jonathan Prince (William Morrow & Company, 2007)

Normally we have a clear distinction in our minds between states of “health” and “disease” – or think we do. Survival of the Sickest challenges this thinking in numerous ways. Overall our bodies play host to around three pounds of microbes that comprise about 1,000 different types and many trillions of individual organisms. These are mostly found in the digestive system and play useful roles ranging from helping to break down food products to protecting us against harmful organisms. Certain bacteria, for instance, help protect us from harmful bacteria, and when people have digestive problems from taking antibiotics it is sometimes ironically because the protective bacteria have been compromised. In effect we harbor a vast multitude of “diseases” that are necessary to keep us healthy!

In addition to microbes there are inherited disorders that actually appear to have benefited our ancestors and/or may in mild forms be beneficial today. A case of possible past benefit is hemochromatosis, in which iron is retained in the system and builds up to harmful levels over a period of decades. (Too much iron has complications such as liver failure, heart failure, diabetes, arthritis, and eventually, death.) On the other hand, the body’s locking down the iron supply has the effect of withholding it from macrophages – white blood cells that fight infection. These then become more effective against a microbe such as the (presumed) bubonic plague bacillus, Yersinia pestis, which in turn is adept at stealing iron when available and thereby furthering its own cause. Another ailment, Type 1 or juvenile diabetes (not a consequence of hemochromatosis), may have protected against a severe, sudden ice age that occurred about 13,000 years ago. Why? Because, in effect, the elevated blood sugar levels were at least marginally effective as a cryoprotectant! The discussion of this issue turns briefly to cryonics, with emphasis on how difficult it is to cryoprotect tissues and how much damage is caused by current cryonics procedures; some consideration of developments such as vitrification that minimizes this damage would have provided a fairer treatment. Another disorder, sickle cell anemia, in a milder, genetically recessive form protects today against malaria. The list goes on.

Another interesting area covered in the book is epigenetics. The genome, it turns out, is not all that counts in specifying how the organism develops from a fertilized egg cell or zygote. Two mice with essentially the same genome will have a very different appearance, one being fat and yellow-furred, the other lean and brown. The difference is not in the genes but the epigenes, which are molecular groups that attach to the genome and affect whether a given gene will be “expressed” or active in the developing organism. Epigenes in this case are acquired during fetal development, by feeding certain nutritional supplements to the mothers. (Human versions of the same sort of supplements, including vitamin B₁₂, folic acid, betaine, and choline, are given to expectant mothers today.) Epigenes in certain circumstances lead to behavioral changes. If, for example, the (human) mother eats a lot of junk food, high in calories but low in nutrients, the baby could acquire an epigenetically-induced disposition to overeat, its system having been put on notice that “food is scarce.” In fact it was not the food but the nutrients in it that were scarce. But the overeating could lead to obesity, and offspring with the same disposition. In this way, then, epigenes provide a way for acquired characteristics to be inherited, a limited vindication of Charles Darwin’s oft-maligned precursor J. B. Lamarck.

One other important feature of human life is what we call aging, a process that eventually kills us if something else doesn’t do it first. Theories of why we age are varied but one property of aging tissues stands out: the shortening of telomeres. Telomeres are caps on the ends of chromosomes in the cell nuclei that provide necessary protection so the main part of the chromosome stays intact as the cell divides. Each time a cell divides the telomeres (usually) get shorter. When the telomeres are too short the protection of chromosomes is compromised; one consequence is that the cells lose their ability to divide so that dying cells are not replaced. When tumor cells reach this “Hayflick Limit” (named after biologist Leonard Hayflick who discovered this effect in the 1960s) the tumor stops growing and after a time dies. The shortening of telomeres, then, is a built-in defense against cancer, but it has the downside that eventually, healthy dividing cells reach the Hayflick limit (after fifty or sixty divisions) so the tissue cannot replenish itself and the organism dies. In the rare genetic disorder known as Hutchinson-Gilford progeria syndrome or HGPS the rate of aging is greatly accelerated so that victims normally die in their teens or earlier and suffer complications such as hair loss, wrinkles, arthritis, and hardening of the arteries while still children. HGPS is usually caused by a single, spontaneous mutation. If such a great acceleration in aging is possible in so simple a manner, the author speculates, then maybe aging itself has been “programmed” by natural selection, a form of “biological planned obsolescence” to help gene survival, albeit at the expense of individuals. Finding and understanding such a “program” could put us on a faster track to treating and curing aging, though it remains to be seen whether nature has really arranged things this way (opinions vary).

In all the book explores many fascinating findings and lines of research, suggesting our biology is complicated indeed but that answers to basic questions are gradually being found. On the other hand, I would have preferred more focus on matters of greatest interest, mainly, how we can overcome all sorts of things that make us sick, not excepting aging itself. As one case in point, though much was said about HGPS and how it is a rapid form of aging that we’d certainly like to treat, it was not mentioned that HGPS sufferers have shortened telomeres [1], at least roughly approximating the condition of elderly, normal humans. I got the feeling that there was more interest in relating a series of interesting anecdotes than in addressing how to better the human condition in fundamental ways (among them curing aging and radically extending the human lifespan), even though some of the research clearly has that potential.

Notes

[1] See, for example, Michelle L. Decker et al., “Telomere length in Hutchinson-Gilford Progeria Syndrome,” Mechanisms of Ageing and Development 130(6), 377-83 (Jun. 2009).