by E. Paul Zehr
You may have noticed that I haven’t yet mentioned where the letters come from. That is, how do you get the amino acids in the first place? This is where we return to DNA to answer the question of how protein is made. Sometimes protein synthesis is likened to printing a document from a computer. In this analogy, the hard drive is the DNA, the “copy” of the document displayed on the screen is the messenger RNA, the printout is the polypeptide, the printer itself is the protein-manufacturing ribosomal complex, and the paper is the protein. Recall that we have four bases (A, T, C, and G) and two base pairs (A-T and C-G). Putting three base pairs together gives us a codon, which is the signal for starting and stopping the making of a protein.
Making proteins this way requires a cousin of DNA called RNA (for ribonucleic acid). RNA is set up similarly to DNA in that it also has four bases. However, in RNA the thymine (T) is replaced by uracil (U). There are several kinds of RNA, but creating proteins involves three main types: transfer RNA, which selects the “letters” (amino acids); messenger RNA, which determines the order in which they will be sequenced; and ribosomal RNA, which manufactures the proteins.
RNA acts to create proteins through a series of steps. The first step is to transcribe the DNA coding. During this transcription, the DNA helix is unwound to reveal the gene segments. The transcriptional RNA then forms the proper base pairs that match those found on the gene segment. After a few more steps, messenger RNA binds to the protein-building ribosomes and with the aid of translational RNA (yet another kind of RNA), the new protein is created. This process occurs in the cells of all living organisms. Although fantastically simple in principle, the process leads to the immensely diverse and complex life that we see, hear, and feel all around us.
This brings us to the issue of genetic coding for an entire animal and the concept of the genome. Perhaps you have heard of the Human Genome Project, which mapped most of the genes of the human body. As a result, we now have a great deal of information about the role of specific genes in athletic and exercise performance. We will look at the Human Genome Project in more detail later.
Introducing . . . Bob Wayne
To help us figure out what Bruce really achieved en route to bathood, let me introduce you to Robert “Blocco” Wayne—Bruce’s identical twin brother. Bob is an idler who does all the real partying that Bruce pretends to do, but he doesn’t bother with any of Bruce’s physical training. Throughout his life he didn’t do much . . . at all. When you look at Bob and Bruce side by side, there really is a difference, particularly in how much sun they block out. Let’s back up a few steps, though, and see Bruce and Bob together as kids. What could we learn about the potential each of them had for physical adaptation and skill development?
DC Comics once showed Batman with someone who could be considered a twin. In this case, it was an evil twin called “The Wrath,” who appeared in the story “The Player on the Other Side” (Batman Special #1, 1984). However, unlike the idea we are exploring in this chapter about real twins and real genetics—and real-imaginary Wayne twins—The Wrath was the evil mirror image of Batman in an alternate universe. The same events that shaped Bruce Wayne’s decision to be a crimefighter, the killing of his parents, motivated The Wrath to devote himself to a life of crime. As you probably anticipated, at the end of the story, the real Batman prevails and goodness is restored—in both universes, of course!
Let’s make a brief stop to consider the whole area of “twin studies” mentioned in the last chapter. Twin studies represent the best scientific way to do an experiment that can tell about the inherent genetic predisposition for certain things. For example, how likely it is that someone will develop a disease or a disorder. Or, of more relevance to our discussions here, how likely it is that a person would be good at something. The ideal experiment to look into this would be to separate the twins from birth so that both can develop independently of one another. The way I’ve introduced Bruce’s “lost” twin Bob here deliberately gets at this issue.
Above, I made reference to Bob becoming kind of a chubby, lazy, party boy in contrast to Bruce (as Batman) who became the most all-around fit human being to ever live! But is that realistic? If Bruce became something like “the Batman,” why didn’t Bob pursue something similar? Maybe even become another Batman, perhaps living on the West Coast?
We are beginning to move on to the effects of genetics or heredity as compared with that of our environmental conditions. How much of what is in our DNA defines our behavior and how much of our behavior is because of what we experience in our lives? This is often described as the “nature versus nurture” debate, and it doesn’t have a clean resolution. A key thing to remember about Batman is that, as a young Bruce Wayne, he had the unimaginably horrific experience of having both his parents murdered right in front of him. As depicted in both the 1989 Batman and the 2005 Batman Begins feature films and as originally described, briefly, in “The Batman and How He Came to Be” (Detective Comics #33, 1939), this event was the defining “environmental” (it’s a bit of a stretch to think of this as a “nurturing” event) moment of Bruce’s life. So, we can suggest that, since Bob did not have this same experience (despite still losing his imaginary parents), he wouldn’t have a “natural” inclination or desire to parallel Bruce’s development.
Studies looking at families suggested that the likelihood of participating in exercise does have a component of heritability. However, environmental factors (like nutrition) play a huge role as well. The complex interaction among environment (what happens to you and what you choose to do), heredity (what your genes predispose you to), and how you perform athletically is shown in a simple way in Figure 2.5. The biggest issue contradicting the complete dominance of either nature or nurture is that genetics, environment, and exercise all affect one another. This is immensely useful but makes it difficult when trying to define relative contributions. A key thing to consider is that genetic influences are often quite specific and may be revealed or maximized only in certain specific situations. For example, if someone has an inherent capacity to respond to strength-training exercise, it may be only for a specific type of exercise.
We can get an interesting view of what Bob could have achieved by considering real-life athletes who are identical twins. As of 2006, 10 sets of twins were active in the National Football League. The most well known are probably Tiki and Ronde Barber. The most recent were Daniel Bullocks (drafted by the Detroit Lions) and Josh Bullocks (drafted by the New Orleans Saints). Josh is 6′ (1.8 meters tall) and weighs 207 pounds (93 kilograms), and Daniel is 6′½″ (1.8 meters tall) and weighs 212 pounds (95 kilograms). These two really are similar in size and appearance. Because they followed the same physical activity choices and patterns, both maximized their potential to play in the NFL. Nancy Segal has documented an odd example of twins and skilled physical performance. In 2006, twin 62-year-olds were playing golf. On a 115-meter (128-yard), par 3 hole, each of them hit a hole in one. These examples demonstrate that genetic makeup is important. Also, important is that all these twins had lots of training—that is, similar environmental influences. The key thing about Bob is that he had the same genetic potential as did Bruce. However, since we are assuming that he never applied himself to the same dedicated training program as did his twin brother, he would never have achieved that potential or promise to become the West Coast Batman. Too bad. I think the “Dark Angel of Los Angeles” has a nice ring to it!
Figure 2.5. The interaction between genetic predisposition (genome), nutrition (environment), and exercise performance.
OK. So Bob and your newly found understanding of genetics and the nature/nurture debate gives you a pretty good idea about what might have happened if Bruce had lived his life differently. But a larger and very relevant question is: Would both Bob and Bruce respond to training the same way? Would you or I respond to exercise in the same way? Is adaptation to exercise stress one-size-fits-all? Scientists know quite a bit about how people respond and adapt to exercise, an
d much of the foundational concepts and information comes from lots of other critters . . . including rats!
Just how much can you learn about bats by studying rats? A whole lot, actually. It turns out that no matter what you do, you won’t suddenly become Lance Armstrong or Hulk Hogan.
Before we look more closely at this issue, let’s address a basic and relevant question: Why does something we learn from one animal species inform us about another animal species? When we are thinking about “nature,” we are really wondering about how much of a genetic link there is between different animals, including that intelligent being known as Homo sapiens (that’s you and me!). It is because of this tendency to share basic operational principles, such as how proteins are formed and how DNA is replicated, that fruit flies and mice can provide useful information for people. Therefore, studies of other species can have important implications for the development and function of humans.
Another reasonable question to ask is how much genetic material is shared across species? How much do we have in common with other animals? Answering this question has been made somewhat easier in recent years because of the tremendous work done to map the genetic coding for several different species. In living beings, from the humble bacteria to the human, genetic coding containing all heredity information is stored in the nucleus of the cell; this information is called the genome. For humans, our knowledge of the genome was greatly increased in recent years with the Human Genome Project, which mapped 92% of the human genetic code. This effort was achieved by both the public and private sectors operating separately. It may surprise you to know that this was accomplished by using genetic samples taken from less than a dozen people. In fact, the public portion of the project obtained data from only one individual (codename RP11, from Buffalo, New York).
What is of particular relevance for our discussion about Bob and Bruce Wayne, though, would be to know more about variation within the genome. In that arena, much work remains to be done. There are ongoing research projects entitled the International Hap-Mat Project and the Human Variome Project. The goal of these projects is to identify the extent of genetic variation across the human gene pool. This will have implications for human response to drug treatments, environmental conditions, and so on. It would also be quite useful for our own discussion about nature versus nurture.
Of importance for Batman and the issue of extreme physical performance is the extent of genetic contribution to exercise training response and physical fitness. In the 2004 update on the human gene map for performance and fitness phenotypes, almost 150 genes were identified that showed a relationship to variables around exercise performance and health. So, it seems that some important traits are inherited from our parents. Exactly how much of what your parents (and their parents, and their parents, going back into history) could do affects what you do? Many factors that are key to physical performance have about a 20 to 30% genetic contribution. Some factors may actually be closer to 50%. For example, as shown in Table 2.1, muscle strength and aerobic fitness both may have approximately 30% genetic contribution. What are the genes that are responsible for these differences? It has to do with mutations in one of the pairs of genes for a given trait. Remembering the alleles we discussed earlier, that means that changes in one allele may lead to the expression or enhancement of a certain phenotype. It is important to realize that this may happen, but it’s not inevitable!
TABLE 2.1. genetic contributions to physical fitness
A key area of research that suggested genetic influences could strongly affect physical performance came from studies looking at twins and other closely related family members and contrasting those observations with unrelated people. The main focus was to examine the heritability of performance-related traits like endurance or muscle strength.
Some key factors that affect muscle growth and performance are linked to human genetic mutations. As is typical in molecular biology, they have some pretty fantastic names. We will briefly discuss one that goes by the name of myostatin (a.k.a. growth differentiation factor 8).
Myostatin has a history grounded in animal husbandry and selective breeding. Although it didn’t go by the name myostatin back then, the effect of this growth factor was first described in cattle as “bovine muscular hypertrophy” by the British farmer H. Culley in 1807. A photograph of a thickly muscled bull is shown at the top of Figure 2.6. This is clearly an unusually muscular bovine, and its appearance led to the term “double muscled” as a descriptor. A cow that is double muscled has less bone, less fat, and much more muscle than does a typical cow. It should be mentioned that these animals don’t really have twice the number of muscles, but rather more and larger muscle fibers than normal animals. It turns out that “double muscling” arises because of a deletion in a gene regulating the activity of myostatin, which normally inhibits the growth of skeletal muscle. The deletion of the gene allows relatively unchecked growth to occur and results in the extreme double muscling.
After first being detected in cattle, this mutation has been shown also in the mouse and most recently in the whippet, a racing dog breed (see bottom of Figure 2.6). In the case of the whippet, the increase in musculature allowed dogs with this mutation to run much faster than their normally muscled friends.
There has also been one reported case of myostatin gene mutation in humans, which is shown in Figure 2.7. In the figure you can see obvious increases in muscle tissue at the hip and calf compared with a typical infant. The figure also shows ultrasound images contrasting areas and sizes of the muscles for the child with the mutation (left) and a child of the same age without the mutation. This boy continues to develop normally but with greatly enhanced strength. At the age of four and a half years, this child was able to hold two 6-pound (3-kg) dumbbells with his arms held straight out to the sides!
Figure 2.6. Double muscling in cattle and dogs. Courtesy Bellinge et al. (2005) (bull) and Elaine Ostrander (dogs).
Figure 2.7. Double muscling with myostatin gene deletion in a human child six days old (left) and seven months old (right). The black and white arrows point to increases in muscle tissue at the hip and calf. The ultrasound images below show the areas and sizes of the muscles for the child with the mutation (left) and a child of the same age without the mutation (right). Courtesy M. Schuelke et al. (2004).
The example of genetic differences of myostatin seems pretty extreme, and it is. What about the normal variation of genetic contributions? Given that you and Batman are both human beings, you share 99% of your genetic coding. So, how come you aren’t Batman? I hope I haven’t created too much emphasis on the nature part—that is, the genetic contribution. Even at the largest end of the spectrum we have discussed percentage contributions of 25–50%. That leaves 50–75% to be accounted for by other factors . . . like training! This book is after all entitled Becoming Batman, not Born as Batman! A very important role is played by the environment—the nurture part—in which someone grows up and develops as well as the kind of experiences one has.
Tom Brutsaert and Esteban Parra put it well when they said “elite athletes are those who respond in extraordinary ways to training in order to unlock an already present potential.” So, an elite athlete like Bruce Wayne may have possessed a well-endowed genetic potential at birth, but to realize that potential required years and years of training to become Batman. Bruce Wayne made a choice to train to become Batman. In so doing, he made maximum use of his genetic potential while immersing himself in various environments that would support that potential.
Most traits are a complex mixture of many different genes and interactions with the environment. Height is a good example, as there is no single gene coding for it. Instead diet and genetics play strong roles together. The best way to consider genetics and environmental factors was captured in the Batman graphic novel Child of Dreams (2003). In this story an evil mastermind is taking DNA and creating clones to fight Batman. His ultimate objective is to create another Batman. But, as Batman says clearly, “A
man isn’t just his DNA . . . he’s his intellect, his experiences . . . You’re not Batman . . . You’re not the things that I experienced, the events that shaped me.”
Now that we’ve met Bruce’s twin and seen the role of genetics, let’s look at the role of another type of chemical found throughout our bodies: the hormone.
CHAPTER 3
The Stress of Life
HOLY HORMONES, BATMAN!
Few fictional characters of any kind, let alone comic book characters, have enjoyed the kind of hold over their readers that Batman has exerted . . . More people have thrilled to the exploits of Batman than have ever heard of Hamlet or seen a play by Shakespeare.
—The Original Encyclopedia of Comic Book Heroes, Volume 1: Featuring Batman by Michael L. Fleisher
Although we mostly think of puberty as the time when young adolescent bodies are awash in a sea of hormones, our bloodstreams are actually teeming with hormones at every age. This is not a bad thing! Slow- and fast-acting chemical signals are quite effective at communicating across distances within the body to affect multiple organs and organ systems.
Getting Stressed Out?
As a result of the genetic similarity among species, many basic physiological processes operate in common ways in different species. One such process is that of stress and stress response. The word “stress” has roots in the Latin verb stringere, which means to draw tight, strain, exert, or tax. The concept of stress seems to be everywhere in our society. As I write this in 2007, just typing “stress” in an Internet search engine yields over 197 million hits! In the field of science alone there is a staggering amount of research being conducted concerning stress. Basic filtering of the search results by including “physiology” brings this number down to a more manageable 10 million hits. A search of the U.S. National Library of Medicine and National Institutes of Health’s PubMed search engine provides over 300,000 results. I hope you are getting the point that stress is a well-researched topic.