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- Could a man cause fungi to destroy everything he touched?
- How could a man made entirely of cancer cells grow back his decapitated head?
- What sort of nutrition could be derived from a diet of human livers?
- Could a man burn up in the sun--simply because he believes he's a vampire?
- How could a salamander hand grow on a man's body?
- Could concentrated human pheromones really make Scully do "the wild thing" with a stranger?
Read an Excerpt
"Nature abhors normality. It can't go very long without creating a mutant."
Eugene Victor tooms stands outside a barred window at night. He's hungry for human liver. His prey is inside the house. The window is the only way in, but the bars area mere six inches apart. He raises his foot, fits it and his calf through the narrow opening. The night air caresses his nostrils with the scent of a particularly tasty liver. He presses his head against the cold metal bars, his body alive with hunger. His skull is wider than the opening. He twists his head, grimacing, pushing, pushing. And as he pushes, hidden muscles engage, stretching pliant bone, nerves, tendons, causing his skull and the brain within to deform, elongating and narrowing like the image in a fun-house mirror, until his head slips through the narrow opening. His chest follows, ribs and internal organs flattening, stretching, the pressure on his heart making each beat resound with the power of a seizure. His pelvis flattens, stretches, and then his thighs. Tooms steps through the window. Time for dinner.
The X-Files abounds with genetic mutants, "genetically different" human beings, as Mulder calls them. They have some incredible abilities. They can stretch, grow younger, regenerate body parts, even perform fission. Life as a mutant might not be all that bad, except for the funky diets. These mutants consume livers, tumors, pituitary hormones, and liquefied fat. Leonard Betts is made entire]y of cancer cells; John Barnett has the hand of a salamander; Flukeman is part fluke, part man. Some of these beings may have inherited their peculiarities from their parents, though most seem to be one of a kind. They raise a fascinating range of scientific questions, those "impertinent" questions Mulder believes form the essence of science. Could a man made totally of cancer survive and regenerate body parts? Could a salamander hand grow on a human? Could radiation spawn a mutant hybrid creature?
Mutants seem fairly commonplace in the world of The X-Files. How possible are such radical mutations? Could any one of us be a mutant? Before we can answer that last question, we need to take a whirlwind tour of the genome.
BIOLOGY 101 FOR FBI AGENTS PURSUING
A quick refresher course. Genes are made up of DNA, molecules whose double-helical structure looks rather like a spiral staircase or a ladder twisted around and around. Each rung of the ladder is made of a pair of nucleotides. Since there are only four different types of nucleotides in DNA, and each type can only bond with one other type, the number of possible rungs is only four. If we number the nucleotides one through four, then the possible rungs are 1-2, 2-1, 3-4, 4-3. Just as a computer breaks all information into sequences of zeros and ones, or your printer prints out a picture by simple dots of black or spaces of white, these four possible combinations, in different long sequences, can convey very complex information. Like a four-letter alphabet, this genetic code spells out the assembly and operating instructions for your body. Since the work of assembling and running your body is done by proteins, your DNA is basically a recipe book, carrying the recipes for many different proteins. Each of these protein recipes is called a gene. A gene may contain as few as one thousand nucleotide pairs or rungs, or as many as 2,300,000 pairs. An entire DNA strand, or ladder, carries thousands of genes. These DNA strands are called chromosomes, and since they are several inches long, the cells often keep them wound in tight bundles.
ARE YOUR PARENTS MUTANTS?
If you want to know whether you might be a mutant, a good place to start your investigation is with your parents, since you inherited your DNA from them. You inherited your traits, some good, some bad, from them. Did you also inherit mutations? Each person, over the course of his life, accumulates mutations. Your parents, between the time they were born and the time they conceived you, underwent genetic mutations that may have been passed on to you.
How would they have acquired mutations? Actually, mutation is a way of life. Out genes are constantly under attack. Environmental factors such as radiation, smoke, and chemicals can create in out bodies free radicals, dangerously reactive molecules that damage DNA.
Nutrition also plays a critical role. The lack of a simple nutrient, such as folic acid, can cause chromosomes to break. If a segment breaks off, it may be lost entirely, or it may become attached to a different chromosome, interfering with that chromosome's genetic material.
Our very own life processes also cause genetic damage. Out bodies create energy by oxidizing carbohydrates and fats, a process that also creates free radicals. Oxidation occurs with every breath we take.
Growth can also accidentally cause damage. When a cell divides, the DNA must duplicate itself to create one set for each daughter cell. The nucleotides split apart, each rung of the ladder breaking in half, unzipping. Each half then recreates its missing side, resulting in two identical sets of DNA. At least, they're usually identical. Sometimes errors can occur.
But while those mutations are unintentional, others exhibit a disturbing sense of purpose. Sometimes the genes shuffle and rearrange themselves intentionally. Mobile genes, also called "jumping genes" or transposons, don't sit quietly on their chromosome as they should. Instead, they multiply and insert themselves into multiple positions on their chromosome, as well as into different chromosomes, bullying their way around. These genes have been called selfish, working only for their survival rather than for yours. They simply want to make as many copies of themselves as they can. In some plants, these selfish genetic elements account for as much as 60 percent of DNA. Transposons can also carry neighboring genes with them in their exploits, rearranging DNA. They may insert themselves into the middle of an otherwise healthy gene, disrupting that gene's functioning. Some forms of cancer, hemophilia, and other diseases may develop as a result of these rearrangements.
Genetic invaders can also alter our DNA. Some viruses, including retroviruses like HIV, actually insert their DNA permanently into our chromosomes, much like transposons, and can cause similar disruptions. Genes have even been found that jump from one species to another, again damaging existing genes.
A single gene in out DNA may be damaged ten billion times in a lifetime. The resulting genetic mutation may be small--the substitution of one pair of nucleotides for another in a single gene; or it may be large--damage to a chromosome that affects hundreds of genes at once. So why doesn't all this rampant genetic tinkering kill us or make us into grotesque, zombified mutants?
Well, on the positive side, there is a chance that these mutations could be beneficial, actually aiding in out survival. Such positive mutations are the driving force behind evolution. The chances of a positive mutation in the genetic lottery, though, are pretty small. While most mutations have no effect, those that do are much more apt to have a negative rather than a positive one. The severity of this effect depends on where the damage occurs. Remember that each gene codes for, or carries the recipe for, a protein that helps out bodies to work. If genetic damage significantly changes that recipe (instead of 1 teaspoon of pepper, it now calls for 1 cup), then it can seriously impair body functions, or perhaps improve them. If it doesn't significantly change the recipe (the genetic equivalent of a typo), then the mutation won't do any harm. The reason most mutations have no effect at all is that at least 50 percent--and perhaps as much as 90 percent--of out DNA doesn't code for a protein and so doesn't seem to do much of anything (for example, all those multiple copies of transposons). Even if a dangerous mutation occurs, it usually is not spread because the damaged cell recognizes its flaw and either repairs itself or heroically self-destructs.
But with so much damage occurring, sometimes dangerous mutations happen--and sometimes they go undetected. More than five thousand human disorders, including many common ones such as cancer and aging (yes, aging is a disorder), are linked to genetic damage and defects.
So your parents, like their parents and their parents before them, built up genetic mutations in their bodies. These mutations couldn't have been too severe, or they wouldn't have survived long enough to reproduce. Since they did survive, they pass their DNA on to you. Their defects and mutations, however, only pass to you if they occurred in the germ cells (the egg and sperm) that form you. Otherwise, those mutations die with your parents. Mutations in the germ cells are rare because the body protects and repairs those cells more carefully than the cells in the rest of out bodies, ensuring the survival of the species. But germ cells face one mutagenic process that regular cells do not: meiosis.
Meiosis is the process by which germ cells are made. The precursors of the sperm and eggs, like all regular human cells, have forty-six chromosomes, two complete sets, one inherited from each parent. Your father, for example, will have one set that he inherited from your grandfather, and one that he inherited from your grandmother. These precursor cells must split so that each germ cell has only twenty-three chromosomes, one set. That way, when your parents' sperm and egg join, the fertilized egg--you--will have the correct total number of forty-six chromosomes. To split, the two sets of chromosomes line up using the buddy system, two by two, with comparable or homologous chromosomes pairing off. While they're waiting, these pairs overlap and exchange genetic material in a process called crossing over, allowing new combinations to be formed. This means that the chromosome you inherit from your father may not be identical to the one he inherited from his grandfather. It can have some of your grandmother's genes on it too. Crossing over is the major source of chromosomal mutations. Humans average two or three crossovers per chromosome! That's why no two germ cells are alike, and you can be so normal, while your sibling is a fat-sucking vampire.
While most crossing over simply creates different combinations of traits, more radical mutations may also occur. Segments of a chromosome can be lost, duplicated, or moved. In addition, if transposons have changed the order of genes ahead of time, this crossing over can create a jumbled mess.
After exchanging material, the homologous chromosomes are pulled away from each other, drawn to opposite ends of the dividing cell. Sometimes, though, the forty-six chromosomes are not split exactly in half, and a germ cell may get an extra copy of a chromosome, or lack a copy of a chromosome. This condition causes many birth defects and the majority of all miscarriages. It is almost always fatal.
So the egg and the sperm that will soon be you are formed. The older your mother is at your conception, the greater chance for mutations in her ova. Women are born with all their eggs, so these eggs age and are exposed to the same internal and external threats that the body is. Men produce fresh sperm throughout their lives, so your father's age at your conception is less important. Yet as all systems deteriorate with age, so the system for producing sperm is more prone to errors later in life. If a fertilized egg has too many damaging mutations, it will be immediately miscarried, without the mother aware that any fertilization has occurred. This happens in up to 25 percent of all pregnancies.
Your mother's egg and your father's sperm meet and join. You're a fertilized egg in the womb. You've got your genes, for better or worse, and they're not so horribly mutated that you'll immediately die. Can you at least develop in peace? Not exactly. You're actually most vulnerable right now, during your first three months of growth, when your organs are forming. Of the four million infants born annually in the U.S., 3-5 percent are born with birth defects. Many environmental factors can contribute to developmental abnormalities, including drugs, radiation, smoking, and nutrition. If your mother gets sick, drinks alcohol, or even uses certain acne medicine, she can negatively influence your development.
You survive these various hazards and are born, the doctor holding you up before your proud mother. Does she sigh in relief, or scream in horror?
WILL YOUR MOTHER SELL YOUR BABY PICTURE TO
THE NATIONAL INFORMER?
You surely area mutant. We are all mutants, in that some of our DNA has suffered damage somewhere along the way. That's pretty scary all by itself. But because mutations are so pervasive, the world is filled with examples of what mutations can do, and what they can't. Most of us mutants are considered "normal," and we are, since mutation is a normal part of life. Some aren't as lucky. Although I've treated the subject lightly so far, the consequences of serious genetic or developmental damage can be tragic: illness, deformity, disability, death. But even with all the mutations occurring in the world, we've never seen living mutants as radical as those shown on The X-Files. Genetic mutations that would give rise to a radically different--and still viable--human being from normal parents are extremely unlikely. Major chromosomal screw-ups certainly occur, but sperm with such defects are unlikely to be healthy enough to win the face to the egg, and eggs with those defects are unlikely to produce a viable fetus.
But we know these oddities are unlikely; that's part of what makes them so fascinating. They may be one in a billion, but that doesn't mean they're impossible. If they did arise, how might they survive? And how might they have developed their incredible abilities?
Of all the oddities Mulder and Scully have encountered, Leonard Betts would have to be one of the oddest. Leonard's body is made up entirely of cancer cells. He loses his head in a car accident, but that doesn't keep him from walking home and--after soaking a few hours in iodine--growing a new head! Leonard enjoys snacking on tumors, and has a talent for sniffing out tumors in others. He's even able to split in two, forming a duplicate of himself--a handy ability to have. But can someone live if his entire body is cancerous, if he is, in essence, one big tumor? To answer that, we need to look at what cancer is and how it works.
We have three hundred trillion cells in our bodies. Over the course of a human lifetime, ten thousand trillion cell divisions take place. On average, this means that every second, twenty-five million cells divide in our body. There. Did you feel it? Normally cells divide at the right time, in the right place, in the right way--a perfectly choreographed minuet. But sometimes they begin to divide much too rapidly, forgetting their proper place and duties, shoving other cells out of the way, pushing into places they don't belong, recruiting blood vessels to satisfy their needs, fooling the immune system into ignoring them. Dr. Dvorit Samid, associate professor of medicine at the University of Virginia and former section head of differentiation control at the National Cancer Institute, describes it like this: "A cancer cell has lost its respect for proper growth control commands. It has no respect for the social behavior one cell should show another. It grows as if the rest of the cells don't matter, causing anarchy." So instead of executing a minuet, a renegade group of cells is slam dancing. And we have cancer.
How does a cell change from good citizen to anarchist? The change seldom comes all at once. Several steps must be taken to produce a fully malignant cell. During the course of our lives, billions of cells may take the first step toward cancer. But the likelihood that all of the steps will occur in any single cell is very low. And if they do, the body has defense mechanisms that will kill a damaged cell or cause it to kill itself. But if those several steps do occur in a cell and it somehow isn't killed, it will produce more cancerous cells.
What are the steps a cell must go through in order to become cancerous? Several different key types of genes must be damaged or impaired. The first is called a proto-oncogene. Remember that a gene carries the recipe for a protein that helps do the work of the body. A gene is said to "express" itself in a cell if it is making its protein. At different times, under different conditions, different genes will be expressing themselves in different cells. But how do the genes know when to express themselves?
Let's take a step back for a minute. We all come from an initial cell that divides and divides, creating duplicates of itself. But gradually the cells differentiate, taking on various roles and characteristics. Although all daughter cells carry the same genes, they don't all express the same genes. Muscle cells express different genes than bone cells or liver cells. These differences allow these cells to take on distinct identities, properties, and duties. A genetic mutation can cause a gene to express itself--to make its protein--when it normally should not, or to not express itself when it should.
Why is damage to proto-oncogenes so dangerous? They carry the recipe for a protein that stimulates cell growth and division. When these proto-oncogenes are damaged, they lose all sense of control and express themselves when they should not, pouring out growth-stimulating proteins like psychotic gourmets. Damage turns mild-mannered proto-oncogenes into megalomaniacal oncogenes. And like a stuck accelerator pedal in a car, the oncogenes drive the engine of cell division faster and faster. Every cell in our bodies contains over one hundred proto-oncogenes.
For a cell to become cancerous, damage must also occur to a second type of gene, the tumor-suppressor genes. These suppressor genes act like the brakes on a car, expressing themselves with proteins that slow or stop cell division when appropriate. Damage to these genes causes them not to express themselves when they should, and so the genes don't put on the brakes. The cell continues to divide, the cancer to grow, with the tumor suppressor genes asleep on the job. Seventeen of these tumor-suppressor genes have been identified, and damage to one or more of them seems present in almost all forms of cancer. One key tumor-suppressor gene is p53, which when functioning properly prevents a damaged cell from reproducing and causes the cell to destroy itself if the damage cannot be repaired. The p53 gene exists in damaged form in about 50 percent of all cancers and has been found in fifty-two different types of cancer. Among those who inherit an abnormal p53 from parents, 90 percent get cancer by the age of fifty.
Damage to both proto-oncogenes and tumor-suppressor genes seems to contribute to the formation of every cancer. There are two different ways in which this damage can occur. The damage may be genetic, as in the mutations we discussed earlier, or it may be epigenetic. Instead of changing the DNA sequence as genetic damage does, epigenetic damage changes the expression of genes. The recipe may be intact, but if you spilled a pot of tomato sauce onto it, you can't read it anyway. Dr. Samid explains, "Particular molecules, methyl groups, can sit on the gene. If you have a lot of groups sitting there, the gene can become silent. It is not expressed." If this happens to a tumor-suppressor gene, again the brakes will go out on cell division.
The cause of this epigenetic damage is not yet understood, but it can lead to even more problems. Cells go through several stages in the transformation from healthy to malignant. The most interesting stage for our purposes is the first, in which the cell either fails to undergo differentiation or it dedifferentiates. This means that the cell does not display the specific characteristics it should; the correct genes are not expressing themselves. A muscle cell stops acting like a muscle cell, or a liver cell stops acting like a liver cell. The cells begin to act like more primitive embryonic cells, not aware that they have a specific role to play in the body but only knowing that they should divide as often as possible. Dr. Henry Brem, director of neurosurgical oncology and professor of neurosurgery and oncology at Johns Hopkins explains, "The more mature or differentiated a cell is, the more it will behave as it is supposed to behave. The less differentiated a cell is, the more it will act as an embryonic cell." So rather than maturing and taking on their appropriate duties, these slam dancers remain perpetually immature. Since they have no sense of their place or role in the body, they proliferate out of control, growing into areas they don't belong and serving no useful purpose. Dr. Samid believes the epigenetic damage is more often a contributor to cancer development than genetic damage.
Leonard Betts's cells, however, seem to behave in a differentiated way, despite their cancer. His body does not grow out of control, like one gigantic tumor; it has structure. He has eyes, a nose, a mouth. He breathes through lungs; in order for his body to work, he must have bones and muscles. Mulder theorizes that the cancer cells are somehow being guided into a constructive pattern. But the very fact that they are not growing out of control, that they are conforming to patterns and performing functions, seems to disqualify them as being cancerous. As Dr. Brem explains, "Cancer cells don't do what they're supposed to do. A glioblastoma [brain tumor] cell can't help you think; it can't help you initiate motor functions, even though it originated from a brain cell." That's why cancer is so bad. The cells take up valuable space, crowding out productive cells and doing nothing in return. Since Leonard Betts's cells are differentiated, we might wonder why they are even called cancerous.
Dr. Samid believes she knows why the pathologist in the episode makes this determination. "If a pathologist looks at the tissues and cells, he may call them cancer cells by appearance." Since cancer cells divide so rapidly, they are crowded together. Also, cancer cells have an abnormally small skirt of cytoplasm around their nucleus. Normally after a cell divides, the two daughter cells will rest for a while, making more cytoplasm to fill themselves out. But a cancer cell will not. Cancer also provides evidence of cell division where there shouldn't be any. For example, brain cells don't normally divide, so evidence of cell division in Leonard's brain would clearly indicate cancer.
But if Leonard's cells are cancerous and dividing out of control, how can they possibly remain differentiated and functional?
The answer may lie in Dr. Samid's research. Dr. Samid is working with a class of chemical compounds called aromatoids, which includes phenylacetate and phenylbutyrate. These compounds exist in both plants and animals in small quantities. They are also formed in our bodies as products of digestion. Dr. Samid and her colleagues have shown that these simple, small molecules can change which genes are expressed in a cell. "The cancer cell is expressing the wrong combination of genes. If you think of the cell as a piano, it's playing a defective tune. The aromatoids make the cell play a new tune, correcting the defective tune."
Remember the methyl groups, sitting on the genes and inhibiting their expression? The aromatoids clear them away, allowing the genes to once again express themselves. Returning to our cookbook analogy, the aromatoids clean away the tomato sauce stain, allowing the recipe to be read once again. The cancer cell doesn't die, but it begins to behave more maturely. Dr. Samid describes the transformation. "In skin cancer or melanoma, the cancer cell doesn't look like a skin cell. But when we treat it with aromatoids, the cancer cell begins to look like a skin cell, and it starts to make melanin, as a skin cell should." The cell is differentiating into its proper form.
While this helps with the epigenetic damage, genetic damage may still remain. But since the cancer cells are now behaving better, they are no longer such a threat to the body. Their rate of division slows, and they no longer shove their way into areas where they don't belong. They are contained. Some of the cells even regain their ability to sense their own damaged condition and kill themselves. Dr. Samid describes the effect of treatment with aromatoids. "The tumors grow slower at first, then stop growing, then start shrinking. They may not shrink away completely, but the patient feels better." With such treatment, a person may be able to coexist with cancer.
Cancer cells that have been treated with aromatoids, then, are somewhat differentiated but still cancerous, just like the cells of Leonard Betts. Dr. Samid agrees. "We can speculate that this person has a higher level of aromatoids or other differentiation-inducing molecules that will allow the cancer cells to function to some degree." So Leonard's cells might still be able to carry out their necessary functions, despite their cancerous mutations.
With aromatoid treatment, people may someday be able to live with their cancer. Leonard Betts has lust reached that goal first.
I'D LIKE A NEW HEAD, PLEASE, SIZE LARGE
What about Leonard Betts's ability to regenerate a head? Is there a connection between cancer and regeneration? Could cancer cells allow us to grow missing body parts?
A salamander can produce a new tail and new limbs. A newt can even regenerate its jaws, spinal cord, and ocular tissues. This has puzzled scientists because the cells involved in regeneration seem to abandon their established roles--to dedifferentiate, just as in cancer--and to take on new roles.
When a salamander loses an appendage, epidermal cells, from the outer layer of skin surrounding the wound, crawl over the wound and seal it. Then fibroblasts from the dermis, the under layer of skin, come out from the perimeter of the wound and migrate to the wound's center. A fibroblast is a cell that makes connective tissue in the body. The fibroblasts and epidermal cells form a protective layer over the wound. The cells beneath this protective layer--whether they are bone, blood, or skin cells--then dedifferentiate to an embryonic type of cell, similar to cancer cells. These accumulate and form a bump, the blastema, which then grows into a limb bud.
The pattern of the new limb develops slowly. The undifferentiated cells in the blastema begin, under the control of the fibroblasts, to differentiate into the various types of cells needed: cartilage, connective tissue, bone, nerve, and so on. Oddly, the regeneration begins with the distal or far end of the pattern first. So if an arm has been cut off, the blastema differentiates "finger" cells first, meaning that the specific combination of genes whose expression will cause the formation of a finger are activated. These finger cells notice that they are beside shoulder cells, and realize that in a healthy arm, this meeting should not be taking place. Dr. Susan Bryant, principal investigator at the Developmental Biology Center at the University of California, Irvine, stresses that this "confrontation and recognition" is critical. "If the cells recognize they have abnormal neighbors, then they will keep growing until they have normal neighbors." So the finger cells, realizing that they don't belong next to the shoulder, will stimulate the growth of cells to fill in the missing territory. In that way they will grow "hand" cells and "wrist" cells and "lower arm" cells and "upper arm" cells until at last all the neighbors are happy with each other.
According to Dr. Bryant, in order to regenerate a limb, "You have to have a group of cells that have information and can interact to make the appropriate shape, size, and pattern." The cells that hold the information are the dermal fibroblasts, which are different than fibroblasts found elsewhere in the body. These dermal fibroblasts have the ability to generate skin, bone, cartilage--everything but muscle, which must arise from broken-down muscle fibers and muscle satellite cells.
How do they do it? The initial migration of fibroblasts out from the dermis is critical to successful regeneration. If a flap of skin is grafted over the wound, the limb will not be regenerated, because the fibroblasts will see no need to migrate out over the wound. This migration, which leads fibroblasts from different spots around the circumference of the wound into confrontation, is essential. Like drug dealers from many different parts of the city running into each other at the same diner (as happens in "Kill Switch"), the meeting of these fibroblasts at the center of the wound tells them that something extraordinary is afoot. "It forces the cells to interact," Dr. Bryant explains.
In humans, the fibroblasts do not migrate from the dermis, which is one reason we are incapable of regenerating even a small hole in the skin. The human dermis does not regenerate itself; rather, cells from below come up to cause healing and scarring. Bryant states her belief that "out fibroblasts area little defective in some way that we have to figure out." One exception to this rule appears to be the human fingertip. If the fingertip is cut off and the skin is not sutured up, it will often regenerate, even recreating the fingerprint. Dr. Bryant theorizes this may be because the distal part of the pattern regenerates first, and at the fingertip we are at the distal part of the limb.
As for how humans might gain the power to regenerate more than a fingertip, there are several possibilities. The option used by Dr. Ridley in "Young at Heart" involves grafting a salamander blastema to a human. On the show, this method results in a squishy-looking four-fingered greenish yellow hybrid human/salamander hand on convict John Barnett's wrist.
Experiments have shown that salamander blastemas can be grafted to different parts of a salamander's body and result in a new limb. This occurs because regeneration is caused by local cell interactions (that confrontation and recognition again), not by a body-wide decision that a new arm is needed. Salamanders don't even need a previously formed blastema to grow a new arm. A ring or cuff of skin from around the wound grafted to the new site will provide the necessary epidermal cells and dermal fibroblasts. Grafting either skin or a blastema to a human, though, poses more problems. First, there's the danger of the immune system rejecting such foreign cells. Second, there's the risk of transmission of diseases between animal and human. Third, there are the differences in physiology. Scientists have tried grafting tissue from salamanders onto mice, but the grafts don't take. The cool body temperature at which salamander cells thrive has thus far proved too different from the warmer body temperature of mice. The same problem would arise in grafting salamander tissue onto humans. So Dr. Ridley's technique seems not the most likely candidate for success.
What techniques might be more likely to have us growing new limbs? First, we might take human embryonic cells, which have not yet differentiated, and apply them to a wound. After all, back when we were embryos, we had the ability to form a leg. Although no such known test has been attempted, a similar process has been tried with frogs. A limb bud from a larval frog was grafted onto a frog that had a leg amputated. The frog with the graft grew a new leg. In theory, Bryant admits, it could work with a human, "though it's unlikely to be acceptable."
Another possibility would be introducing the genes that seem to be associated with regeneration and seeing if they elicit any response. Dr. Bryant and her colleagues recently identified one gene, distalless, which seemed to "turn on" in a regenerating salamander limb. She is now trying to introduce this gene into chicks.
Yet another possibility would be to discover how to make our own cells dedifferentiate. Dr. Bryant and her colleagues have discovered a protein, FGF-2, which seems critical in the process.
Let's return now to Leonard Betts. Regeneration and cancer are clearly connected, since both involve cells dedifferentiating, though the nature of the connection is not yet understood. Tumors in salamanders and newts are extremely rare. In addition, salamander limbs injected with cancer cells do not grow tumors. Instead, they grow extra limbs. The cancer is somehow guided into a constructive pattern rather than a destructive one, the cancer cells differentiating into the various types of cells needed. It was this precise fact that inspired Dr. Samid to begin her study of cancer. Dr. Bryant attributes the formation of cancer cells into a limb to the local cell interactions exhibited by salamanders. A cancer cell's inappropriate behavior would "alert the neighbors," who would make sure that any growth is controlled and channeled into a useful pattern. Since human cells lack these local interactions, this "confrontation and recognition," they are effectively blind, letting those neighboring cancer cells get away with murder.
Leonard Betts's cells, though, do seem to undergo these local interactions. His cancer does not grow out of control, but rather is guided into a useful pattern. The new growth generated on his neck is not a tumor but a head. Since the exact process through which these local cell interactions take place is not yet understood, it's difficult to say why or how Leonard may have developed this characteristic. But since certain genes seem critical in controlling regeneration, and cancer is caused in part by genetic damage, perhaps the genetic mutations responsible for Leonard's cancer are also responsible for awakening in his cells the ability to interact with each other.
Dr. Samid approaches Leonard's ability to regenerate differently, considering the differentiation process in chemical terms. The salamander's cells may differentiate because a chemical, such as an aromatoid, may enter the dedifferentiated cells and tell them, "Grow up! Mature!" The differentiation process would be triggered just as it is in the cancer cells treated by Dr. Samid. In the case of Leonard, when he needs to grow a new head, the level of aromatoids in his body may decrease, allowing those vital cancer cells to dedifferentiate and proliferate once again, and when his tissue has expanded sufficiently, the aromatoids may increase, causing the cells to slow their growth and differentiate into their proper forms.
But why would Leonard soak his headless body in iodine? Dr. Bryant knows of no connection between iodine and regeneration. Another chemical, though, does affect regeneration. Retinoic acid changes the regional identity of cells. Dr. Bryant states, "If you take a frog going through metamorphosis from larva to adult, amputate his tail, and treat the wound with retinoic acid, instead of growing a new tail, it will grow a bunch of legs." Obviously something Leonard Betts should keep out of the medicine cabinet.
DO YOU WANT TO LIVE FOREVER?
While we discussed Dr. Ridley's experiments with regeneration in "Young at Heart," those are really just a hobby. His main goal in that episode is to learn how to reverse the aging process, which he has apparently done in John Barnett. Ridley claims he made his breakthrough by studying children with progeria.
Hutchinson-Gilford Progeria Syndrome was first discovered in 1886. Children with it appear normal at birth, but their growth slows dramatically by the end of their first year of life. They will never grow larger than a five-year-old. Some die as young as age seven, though others live up to their late twenties. This slow growth may sound like a prolonged youth, but those with progeria actually exhibit many of the symptoms of premature aging. They suffer from arthritis, respiratory problems, atherosclerosis (the fatty blockage of arteries), premature senility, and repeated nonhealing fractures. And although they remain small in size, their appearances become aged: Their faces look old and wizened with wrinkles, beaked noses, receding chins, and prominent scalp veins; their corneas become clouded; degeneration of the hair follicles leads to baldness and loss of eyebrows and eyelashes; and their skin becomes thin and parchmentlike.
This rare disease is inherited, though the exact gene that causes it has not yet been identified. Some scientists believe progeria is a dominant trait. This would mean that one of the parents would have to suffer from the disease (which would be unlikely, because of their short life span, and is not borne out in the research) or that one of the germ cells of the parents suffered a mutation (which researchers find plausible since babies with progeria tend to be born to older fathers, where mutations would be more likely). Others believe progeria is a recessive trait, meaning that the child must inherit the trait from both parents in order to suffer from the disease. They point to a number of cases in which parents of children with progeria are cousins or otherwise related, increasing the chance that they would both carry the gene. There is no known treatment.
In "Young at Heart," Dr. Ridley claims he has been able to reverse aging by using the genetic components of progeria. Yet most scientists feel that a study of progeria would be limited in what it could tell us about aging. Since progeria does not really resemble normal aging, different mechanisms are most likely involved; as we discussed above, a single-gene mutation is likely responsible for progeria, but not for aging. While the study of progeria would be unlikely to lead us to a method of stopping or reversing aging, it could, however, help us understand various processes associated with aging, such as atherosclerosis.
So what possibilities do exist for slowing or stopping the aging process? Before we can answer that, we need to understand why exactly we age. Scientists are still working on figuring this out. At least eight major theories exist, and it now seems that they are all at least partially true, making aging the most complex disease we know.
Scully cites one of these theories in "Home" when she explains that our bodies are merely vehicles for genes needing to replicate. This theory is called the "disposable soma" theory of aging, the soma being the body. The human body ages and wears out because its purpose is not to live forever. Its purpose is to reproduce. We are not nature's end, but its means, its means to continue the species. We are germ cell producers, storage banks, and maters. Once we mate, our job is done. Nature likes to create us so that we can mate as early as possible, to minimize the risk of death from outside forces before mating has occurred. This rapid maturation may work against a long life span, but that is not nature's concern. Scientists see nature as a careful investor searching for a balance between investments in maintenance of the body, or somatic maintenance, and investments in reproduction. It's sort of like deciding whether to spend money repairing and maintaining your current car or to put all your money toward buying a new car. If nature invested all her resources in maintenance of the body, the body could be maintained perfectly, and we would be theoretically immortal, with no reproduction required; if nature put all her energy into reproduction, we'd be popping out kids like there's no tomorrow, and there wouldn't be, for our bodies would quickly fall apart.
Nature has found that the most successful investment portfolio puts some of her resources into somatic maintenance (keeping us alive at least long enough to mate), but doesn't waste resources by keeping the soma around longer than it's needed (those repair bills get awfully high, after all).
Dr. Michael Rose at the University of California at Irvine demonstrated the connection between mating and life span using Drosophila, the fruit fly. He did not allow the flies to breed until they were old. In this case, a long life span then became a critical component to reproduction. In just fifteen generations the life span of the flies increased by a third.
Another theory looks at old age from an evolutionary perspective. Evolution explains how species develop through the survival of the fittest. Yet survival of the fittest has nothing to do with how well you age. Fitness is a state judged at the time of reproduction. If you are "the fittest" at the age of reproduction, then you will reproduce and your traits will be passed down. If you later become infirm and sickly, those traits have no effect on the survival and reproduction of your offspring. So evolution does not select us for longevity or health in old age, nor does it eliminate genes that cause harm late in life from the gene pool. This suggests that genetic traits that cause negative effects at old age have spread unchecked through our species.
Probably the most well-known theory relates aging to the presence of free radicals in the body. At the beginning of this chapter we briefly discussed free radicals, dangerously reactive molecules that damage DNA. Free radicals are caused by oxidation, the process by which our body creates energy. All cellular energy in all creatures is generated by means of electron-transfer reactions, in which electrons move from one molecule to another. In metabolic oxidation, electrons are pulled from carbohydrates and fats and shuffled through a series of reactions that extract energy from them. That energy is stored in a fuel called ATP (adenosine triphosphate), which is used to power out cells. At the end of the process, the electrons are picked up by oxygen molecules. Oxygen is naturally hungry for more electrons, and it does a good job of retrieving the electrons. If the oxygen picks up four electrons (along with four protons), it becomes two stable water molecules, and all is well. But if it picks up only one, two, or three electrons, an unstable, highly reactive free radical is created; a molecule desperate to bond with anything else in order to become stable. This is what makes oxidation a dangerous process, the same process that causes fires to burn, iron to rust, and rat to go rancid. As Dr. Bruce Ames, professor of biochemistry and molecular biology at the University of California at Berkeley points out, "We're all going rancid in some way." A free radical may bond to DNA, creating a big, unwieldy lesion. When the DNA attempts to replicate itself, this lesion can cause the wrong nucleotide to attach, thus creating a mutation. In similar ways, free radicals can damage proteins, deform the fatty membranes of our cells, and even cause DNA to break apart. Scientists have calculated that each cell in a rat's body gets hit by one hundred thousand of these toxic radicals each day. Since rats have a higher metabolic rate than humans, the rate in out bodies is somewhat lower, but it still amounts to a huge daily onslaught.
The free radical theory of aging stares that these radicals cause random damage to the body that accumulates over time and plays a fundamental role in the decline of physiological function. The majority of oxidative damage, it is believed, occurs in the mitochondria, the tiny power plants in the cytoplasm of our cells where oxidation takes place. The mitochondria have their own DNA, separate from the chromosomes in the cell nucleus. Due in part to oxidative damage, this DNA mutates at a much faster rate than DNA in the cell nucleus, and the mitochondria in general decay faster than the rest of the cell. Since the mitochondria power the cell, and thereby the body, damage to their DNA impairs the function of the entire body. And when mitochondria are damaged by free radicals, they produce even more radicals, accelerating the rate of damage. Repairing the mitochondrial DNA takes energy, and yet damage to the mitochondria reduces energy output. This lower energy output could contribute to signs of normal aging: loss of memory, hearing, vision, and stamina.
Outside factors can produce free radicals as well, such as cigarette smoke, pesticides, and even exercise. Flies confined to a small space, which limited their flying, lived twice as long as flies in a larger space. As you breathe faster, you generate more free radicals and hasten aging (aren't you glad you're sitting down reading a book?). To counter this attack, we can take antioxidants, such as vitamins C, E, selenium, and beta-carotene, which neutralize free radicals and slow oxidative damage. In studies, the life span of mice has been increased 30 percent by antioxidants.
The good news is that the body itself produces antioxidants. We have now begun identifying genes that regulate the production of these antioxidants. Dr. Thomas Johnson at the University of Colorado has discovered a gene in Caenorhabditis elegans, a microscopic worm, that regulates the production of two enzymes, catalase and superoxide dismutase (SOD), which serve as antioxidants. Disabling the gene increased the production of these enzymes and increased the life span of the worms by 70 percent. A similar technique might be used in the future to increase the human life span.
Now for the bad news. The rate of oxidation increases with age, and antioxidant defenses decrease with age, the natural antioxidants becoming less active. Nature keeps the repair mechanisms working only as long as she thinks necessary to ensure out survival as a species.
More bad news. Each cell is allowed only a certain number of divisions, called the Hayflick limit, until it is reduced to an inactive state, called cellular senescence. At the end of each chromosome is a safety cap, or telomere, which holds everything together and keeps the chromosome from fraying or being damaged. Each time a cell divides, each chromosome loses a bit off the end of its telomeres. In germ cells, these telomeres are repaired by an enzyme called telomerase (nature's investing in reproduction). But in the somatic cells--the rest of the cells in the body--no telomerase is produced, and the telomeres erode, eventually preventing the cell from dividing again. Now prevention of overdividing is good if you're young; it can help prevent cancer. Yet as you age, an increasing number of your cells become senescent. It hasn't yet been proven how these cells contribute to physiological decline, and many scientists think they don't, but the number of these senescent cells does increase with age. This erosion of telomeres is just one of many processes that can be positive early in life and cause deterioration later on. Recent research has shown that somatic cells extend their life span by twenty divisions when given the gene to produce telomerase.
You can see what a complex series of issues we face in the attempt to slow or reverse aging. The body fails for many different reasons and in many different ways. So the possibility that Dr. Ridley would have discovered a simple method of reversing the aging process seems unlikely. He could, however, have discovered how to influence one small part of it. In fact, we already know that much.
Antioxidants certainly slow the damage due to free radicals. Also, eating 40 percent fewer calories has reduced age-associated diseases in rats and extended their life spans by 30 percent. Eating less seems to result in the production of fewer free radicals, increased antioxidant activity, and less mitochondrial DNA damage. Dr. Ames admits that constant hunger has a drawback. "The rats get a little testy and will bite you."
Dr. Ames believes he has just taken a major step toward reversing the decay of mitochondria due to aging. One major source of mitochondrial impairment is damage to proteins that help the mitochondria do their job. Dr. Ames has found a way to help one of these damaged proteins keep functioning. The protein promotes a reaction in a material, or substrate, called carnetine. "Oxidation damage loosens up the proteins," Dr. Ames explains, "and they need more of a substrate to work on." Since the body is limited in how much carnetine it can produce, Dr. Ames provides more, thereby increasing the amount of substrate available to the proteins. He also provides more lipoic acid, a coenzyme that helps promote the carnetine reaction. Both of these substances, by the way, are available in health-food stores. Dr. Ames describes this process as "tuning up the mitochondria." The results are dramatic. "When we give these two to old rats, they get up and do the maccarena. These are the liveliest rats you ever saw." This technique does not repair or reverse the age-related damage, but it does eliminate the negative consequences of that damage. While we're developing many methods for slowing deterioration due to aging, actually reversing aging, as Dr. Ridley claims to have done in "Young at Heart," remains far beyond our reach.
One additional area that may be important in future aging research is nutrition. Dr. Ames believes nutritional supplements are key to extending life span. "Each human requires forty substances to make all his biochemistry go around." While we know what these substances are, we don't yet know the optimal quantities of each to maximize our life span. Future research may provide a nutritional formula for longer life. But this formula may already lie hidden within another X-file.
EAT YOUR LIVER!
Eugene Victor Tooms, a prototypical X-Files oddity from the episodes "Squeeze" and "Tooms," is over one hundred years old, yet he looks to be only in his twenties. He enjoys making nests out of bile and newspaper, collecting trophies from his victims, hibernating for thirty years at a stretch (no pun intended), and finding that perfect liver. In addition, he's able to squeeze through some incredibly tight spots. (Why do I feel as if I'm introducing him on Love Connection?) His social life aside, could Tooms's secret of flexibility, long life, and youthful appearance lie in his gourmet diet of five human livers every thirty years?
Many people--mothers especially--tout the nutritional value of liver. While nutritional information on the human liver is unfortunately scarce, beef liver contains huge quantities of iron, vitamin A, folic acid, vitamin [B.sub.12], vitamin K, and many other valuable vitamins, minerals, and amino acids. Dr. Judi Morrill at the Department of Nutrition and Food Sciences at San Jose State University says, "Liver is a really good source of iron, and for women who are anemic, it can be good. It's a high-cholesterol food, though, so people don't eat it much now. I don't particularly recommend people eat it at all."
Liver's nutritional fame arose in the 1920s, when scientists proved that patients with pernicious anemia, arising from an often fatal vitamin [B.sub.12] deficiency, could be cured by eating a special diet including a half pound of fresh liver per day. Dr. Michael Field, professor of medicine and physiology at Columbia College of Physicians and Surgeons and director of the Division of Gastroenterology at Columbia Presbyterian Medical Center, explains, "The liver stores vitamins, so it can provide many vitamins if you eat it. But vitamin pills are even better sources of vitamins." Perhaps Tooms has pernicious anemia due to a deficiency of [B.sub.12] and is treating himself with the high-liver diet he heard about back in the '20s. There is a genetic component to pernicious anemia, so we might theorize that this deficiency runs in Tooms's family and has led to the development of these quaint family traditions.
The problem with treating pernicious anemia with huge quantities of liver is that this diet may mask the deficiency rather than curing it. Those with pernicious anemia lack a certain substance called intrinsic Factor, which is excreted by stomach cells and allows us to absorb [B.sub.12]. Scientists believe pernicious anemia is an autoimmune disorder, in which the body's immune system attacks itself. In this case, the immune system attacks the specific stomach cells producing intrinsic factor, destroying them. Without this substance, the [B.sub.12] goes unabsorbed and a deficiency arises. While ingesting huge amounts of liver may allow some small amount of [B.sub.12] to penetrate the intestinal lining by itself--and other nutrients, such as folic acid, may cure the anemia -- the underlying [B.sub.12] deficiency may very well remain. Prolonged [B.sub.12] deficiency causes irreversible neurological damage that may result in unsteadiness, poor muscular coordination, mental slowness, confusion, delusion, and psychosis. The last four symptoms certainly seem present in Tooms. So Tooms may be trying unsuccessfully to eliminate his deficiency through diet and growing more and more delusional and psychotic. These days a [B.sub.12] deficiency is easily treated with vitamin [B.sub.12] injections that bypass absorption by the intestine.
Could this diet provide any explanation for Tooms's longevity? Within the human body, a person's liver releases enzymes that help to purify the blood. So, could eating a liver help to purify your system? Unfortunately, no. The digestive process breaks down enzymes into their building blocks, amino acids, so that any protective function they once had is lost.
A diet solely of livers would clearly involve serious nutritional deficits that would prove fatal to any normal person. We are forced to theorize either that Tooms's nutritional needs are different than a regular human's, or that he gets his calcium, fiber, and other nutrients from eating a variety of foods in addition to liver. Since the first theory prevents us from drawing any conclusions, let's explore the second. Even if he is eating supplemental foods, a diet so rich in liver would introduce a harmful excess of several elements. Too much iron causes intestinal bleeding and produces large quantities of free radicals in the body, which can cause extensive damage. Too much vitamin A, called hypervitaminosis A, causes toxic effects, including irritability, headaches, irresistible drowsiness, nausea, liver damage, bone and joint pain, loss of bone mass, bone fractures, and limitation of joint motion. Eating a lot of liver ironically damages one's own liver rather than enhancing its function. The drowsiness might in some small way be tied to his periods of hibernation, but how can Tooms possibly be as flexible as he is when this condition limits the mobility of his joints?
Now that I think about it, though, I don't believe I ever saw Tooms actually chowing down on a human liver. Yes, he did leave bite marks on a victim from gnawing one liver out with his teeth, but perhaps, after he got it out, he used it in some other way. Might he be able to create some sort of injection from the livers that would benefit his health and allow him to filter out excess vitamin A? Obviously nothing has been tried like this with the human liver. If he could isolate the [B.sub.12] from the livers, he could treat his pernicious anemia with injections as described earlier (though wouldn't a trip to the doctor's be easier?).
In addition to curing an illness, might the livers also somehow enhance his health? The liver of the dogfish shark contains a recently discovered steroid called squalamine that kills some bacteria and helps stop the spread of cancer. For a tumor to grow, it needs to cause nearby blood vessels to produce new offshoots to connect to it. The blood will nourish the cancer. Tumors send a message telling the endothelial cells lining the blood vessels to divide and form new vessels. Squalamine can inhibit this growth by making the endothelial cells too acidic to divide. Recent studies show squalamine slowing the growth of new blood vessels near tumors in rabbits' eyes by 43 percent. Squalamine is currently being tested for treatment of breast cancer.
Shark livers also provide Alkyglycerol (AKG), a family of compounds that help to produce and stimulate white blood cells, which fight infection and disease. AKG is also found in mother's milk, and serves as a natural booster to the immune system. Some scientists claim that AKG is an extraordinarily potent antioxidant that can slow aging.
Do human livers have these same beneficial compounds? Dr. Jay Moorin, chairman of Magainin Pharmaceuticals, believes that the reason we have receptors that allow us to benefit from squalamine is because we make similar substances in out own bodies. Molecular biologist Dr. Michael Zasloff, who discovered squalamine, believes that we may very well produce squalamine or a variation of it.
So if Tooms is processing these livers somehow to derive beneficial chemicals from them like vitamin [B.sub.2], squalamine, and AKG and then injecting himself with them, perhaps he would benefit. Whether that would slow the aging process to such a level that a man over one hundred years old would appear about twenty is doubtful, but it might help minimize those tiny lines around his eyes.
SHOULD YOU BE EXPECTING VISITORS THROUGH
Tooms's longevity and diet aren't even his most amazing characteristics. That honor goes to his extremely flexible body. He squeezes through a six-by-eighteen-inch air vent into a business office, slithers between bars on a window, shimmies down a six-by-twelve-inch chimney (are cookies and milk the wrong snack to leave for Santa?), and even seems to cram himself into a sewer pipe, nearly coming up through a toilet after a woman tries to Roto-rooter him (renewing a recurring fear I had as a child that a mummy would come up through the toilet while I was sitting there). So how small a space can a human being fit through?
Those most skilled in squeezing and stretching are, of course, the contortionists. Many contortionists are actually "genetically different" human beings. That's why, no matter how much we stretch, some of us still can't get our legs up behind out heads. The most important components in determining flexibility are out ligaments. Ligaments connect bones to other bones, and bones to tendons. They help to hold us together. The dominant element in ligaments is the protein collagen, which is made of three helices of protein twisted together into long fibers. When these fibers are relaxed, they are folded up like an accordion. When you pull on the fibers by bending your knee, they unfold and stretch. The collagen produced in different parts of out bodies differs somewhat, to make parts of us more elastic, and parts more firm. Some people, though, have the more elastic collagen throughout their bodies. Their hypermobility gives them the potential to become true contortionists.
For a few people, this flexibility can become a serious health problem, their collagen so elastic and loose that joints dislocate spontaneously. Dr. Gail Dolbear, assistant professor of obstetrics and gynecology for the State University of New York Health Science Center at Syracuse, says, "The bones can slide all over, being double-jointed so to speak." This condition, called Ehlers-Danlos Syndrome, arises from a dominant trait that can be inherited from just one parent. Ehlers-Danlos actually encompasses a group of disorders. In one, the joints exhibit severe hypermobility, but there are few other deformities. In other disorders within the group, the syndrome can also affect the skin, blood vessels, and intestines--which use collagen to maintain elasticity--and can make them dangerously pliable. Skin can be pulled inches away from the body. It tears, bruises, and scars easily, healing in thickened, wrinkled bunches. Gaping wounds are common and difficult to close. Arteries can spontaneously rupture. Bracing is sometimes necessary to stabilize joints.
Those for whom flexibility is not a health problem, though, are able to fit into some rather tight places. The Armenian Rubber Man, who has performed with the Jim Rose Circus Sideshow, can fit his entire body through the head of a 1970's tennis racket. As Jim Rose, who was featured in "Humbug," says, "If he gains a single pound or becomes constipated, his career is over!" Smaller than standard rackets used today, a typical 1970's racket is about eight inches wide and eleven inches long, with a face of about seventy square inches, making it comparable to many of the places Tooms squeezes through in his first episode. In the sequel episode, Tooms's powers seem to become more incredible. The barred window and the toilet are extreme examples of Tooms's ability that can't be explained by hypermobility. Those two openings are smaller than the adult human head, which tends to be rather inflexible, implying that Tooms's bones are actually able to deform and then reform. No fully formed animal with a skull has that kind of flexibility. That would defeat the whole protective purpose of the skull.
Children, though, have bones that are not fully formed. Some bones, in fact, are not completely formed until the late teens. Children's skulls are made up of several different sections that fit together like puzzle pieces, with small gaps, or sutures, in between. The soft spot on the back of a baby's skull is one of the larger gaps between these pieces. Dr. Dolbear explains how these pieces can allow deformation of the skull. "When babies squeeze through the pelvis at birth, these bone plates can come closer together, and even overlap. This is at some cost, because the brain underneath could literally be squeezed to death." More commonly, only slight brain damage occurs, and the brain compensates for the damage. As the child matures, these pieces of the skull fuse, increasing the protection to the brain and eliminating any possible compressibility. If Tooms's skull for some reason did not fuse, it would allow for some compression, though with associated brain damage (which may be why Tooms doesn't seem terribly brainy).
But could he get through a standard three-inch-diameter sewage pipe? Perhaps Tooms doesn't have a traditional skeleton. A shark's skeleton is made of cartilage, a tough, flexible tissue. Cartilage is actually the material that first forms our own skeletons when we are embryos, before it is replaced by bone. Cartilage is made of a network of collagen fibers embedded in a firm, gelatinous substance that has the consistency of plastic. Since we already theorized that Tooms has unusual collagen, theorizing that he might have a cartilage skeleton seems to carry a certain twisted logic. Humans do retain some cartilage beyond the embryonic stage, at the ends of growing bones, at the joints, in the nose, ears, and elsewhere. This cartilage varies in flexibility, just as collagen does. The cartilage in your ear, for example, is much more pliable than the cartilage in your nose. The cartilage skeleton allows the shark the flexibility to twist around and bite. A cartilage skeleton might allow Tooms to squeeze through the barred window.
A cartilage skeleton does present several drawbacks, though. The shark is more vulnerable, since it is less resistant to compression. A porpoise ramming a shark's underbelly can damage its internal organs, or ramming its head can actually break the skull apart. A cartilage skeleton would provide poor protection for Tooms's brain and internal organs. When Tooms, in his attempt to frame Mulder for assault, whacks his face with Mulder's shoe--hard enough to leave a tread mark--he probably would have cracked open a cartilage skull. Another weakness of a cartilage skeleton is that it can't support a lot of weight. Since a shark doesn't have to stand up and support its weight, that's not a problem. But for Tooms, it would be. To support our weight, we need the framework of a hard skeleton.
So while a cartilage skeleton might provide some hint of what is responsible for Tooms's distinct talent, his skeleton--and the rest of his body--must have a unique combination of properties, perhaps due to some unusual collagen his body produces. I still can't imagine how he could squeeze through a sewage pipe, but maybe he wasn't in there at all. That toilet may just have had a really wicked clog.
ARE MUTANTS BREEDING IN YOUR SEWAGE?
He's part fluke, part man--he's Flukeman! Our final, and most radical oddity, appears to be the result of environmental factors acting on genes. The beloved Flukeman in "The Host" arises out of the radioactive murk on a Russian freighter carrying waste from the Chernobyl Nuclear Power Station. Scully theorizes that the radiation caused radical mutations that allowed DNA in human sewage to combine with fluke DNA, creating one of the most delightfully disgusting oddities on the show: a hairless, vaguely man-shaped creature with pale wrinkly skin and a perpetually open mouth. Flukeman's main goal seems to be to reproduce. He injects his larvae into a human host through his bite. The larvae mature, are coughed up by the human host, and appear to live out their adult stage in water. Is Flukeman lust an oversized worm, or is he a true radioactive novelty? I can't wait to find out ...
A fluke, or trematode, is a type of flatworm. There are six thousand different species of fluke, and they range in size from a few tenths of an inch to four inches in length. Flukes are parasitic, usually feeding off two or three successive hosts--including humans. In each host they mature further, going through several immature or larval stages before reaching maturity or adulthood. Some attach themselves to the external surface of a host, though most attach themselves to internal organs. They use muscular suckers and hooks to form a firm attachment with the host. Most flukes are hermaphroditic, with both male and female sex organs.
Like the fluke found in the dead Russian sailor, the human liver fluke, Clonorchis sinensis, spends the adult stage of its life in the bile duct of a human or other fish-eating mammal. It feeds on the tissue and blood there, causes a tumorlike proliferation of the cells and may cause cirrhosis of the liver and eventually, death. To reproduce, the adult--between snacks on your liver--releases larvae in your bile duct. The larvae leave your body through your feces, and then wait to be eaten by a snail. Inside a snail, the larvae develop further through several immature forms, and finally leave the snail to burrow into the flesh of a fish, enclose themselves in protective cysts, and settle down for a nap. If you eat that fish raw, the cysts break down in your digestive tract and the immature flukes develop into adults in your small intestine within three to four days. Clonorchis is common in the Orient, where eating raw fish is popular. Over five million people are infected with flukes in China alone, with over forty million infected across the globe.
Flukeman's origination in sewage, then, makes some sense, since a contaminated sailor could have passed fluke larvae through his feces. In fact, flukes are highly prevalent in Russia, though their government kept this information secret until a few years ago. Those fluke larvae in the sewage, though, if acting normally, would need a snail or some other animal as intermediate host. As far as we can tell, Flukeman came into being without a host.
Since we don't really know the details of his origins, though, let's instead examine how he reproduces. His life cycle seems significantly simpler than that of a fluke. He attaches himself externally to a potential host for his larvae and injects them into a human host, where they mature. But hold on a minute. If Flukeman is having babies, should we really be calling him Flukeman? Flukewoman seems more likely. Likelier still would be that Flukie is hermaphroditic, as most flukes are, in which case the most appropriate name would be the politically correct Flukeperson. Scully says Flukie has no sex organs, but I think perhaps she just doesn't look in the right place, or doesn't recognize them when she sees them.
Back to Flukie's life cycle. Its active involvement in inserting the larvae into the host is very unusual for a fluke. The adult fluke actually does the opposite, living within a host and ejecting the larvae through the host's feces. Flukie's larvae appear to grow inside the host by feeding oft the liver, a common fluke activity. Then they're coughed up by the host. We see this with the sanitation worker, who hacks up a juicy worm while in the shower. Can we find any similar mechanism in flukes?
The lung fluke, Paragonimus westermani, has a similar life cycle to the human liver fluke, but it behaves differently inside its human host. To mature, this fluke migrates from your intestines to your lungs, where it grows to a half inch long and produces small cysts filled with eggs. The cysts rupture, and you unknowingly cough up the eggs and swallow them. The eggs travel through the digestive system, sheltered in a protective coat, and pass out through the feces.
This seems to partially mirror what happens with Flukie's babies. After feeding and growing in the liver, they migrate to the lungs where they are coughed up and out, hopefully escaping into water. If, instead, they were swallowed--like Paragonimus westermani--Flukie's babies would most likely die, since they are not sheltered within a cyst that would protect them from the stomach's digestive acids and enzymes.
Since the mammal or human host always functions as the terminal host for flukes (the place where the adults live), it's unlikely that Flukie's children would seek out another host after leaving their human home. This means the young Flukies use only one host, go through probably only one immature stage, and live their adult lives outside of any host. These are processes with no parallel among flukes.
So while Flukie has a number of characteristics in common with flukes, much of its life cycle is different. Could that be from the human influence in its genes? Scully calls him a "quasi-vertebrate," suggesting similarities with humans, who are vertebrates, but the extent of any skeletal similarities is uncertain. Humans do require only a single host to mature--our mothers. Flukie is able to survive out of water and to breathe air, suggesting additional similarities with humans. But attaching to a host to transfer children, and coughing up children, doesn't quite bring human beings to mind. Though either method seems easier than human childbirth.
IS IT JUST A FLUKE?
What about the underlying premise of "The Host"? Could radioactivity spawn a new mutant life-form? Radiation has been blamed for monstrous creatures from giant ants (Them!) to Godzilla. Are these flights of fantasy, or is the danger real?
The Russians provided us with out best recent test case when Chernobyl Nuclear Power Station blew up in 1986. Tons of radioactive debris were released over ten days and spread across the northern Ukraine and Europe, as far as Scandinavia, Italy, and the Atlantic Ocean. Seventeen million people were contaminated to some degree. Radioactive isotopes drifted through the air, infiltrated the food supply and seeped into the groundwater. In Byelorussia levels of radioactive strontium shot up to many times their normal quantities, increasing twenty-five times in white bread, ten in milk, and six in potatoes. Some entrepreneurs sold contaminated food in violation of the law until they were discovered, causing customers serious internal contamination. The total ionizing radiation released was ten times that of the atomic bombs dropped on Japan during World War II--with a far greater longevity.
Ionizing radiation is made up of high-speed particles and high-frequency electromagnetic energy. This radiation passes through matter and causes it to ionize, breaking apart molecules and atoms, forming positively and negatively charged particles. In the human body, such radiation hits molecules and breaks them up, creating free radicals, which we know damage DNA. Radiation can create so much genetic damage that the strands that make up DNA can actually be broken. Under normal circumstances, most of the damage caused by free radicals is repaired. But with radiation, the rate of damage accelerates so much that the repair mechanisms can't keep up with it. Damage to genes critical for a cell's survival goes unrepaired, chromosomes are damaged, and eventually cells die.
Cells that divide rapidly are the first to go. Since we have two copies of each gene, if a critical one is damaged, a backup still exists to keep the cell alive. But when the cell divides, only one cell will get the healthy gene, while the other with the damaged gene, may die. Broken chromosomes are not divided correctly between two daughter cells, causing further aberrations. Since blood, bone marrow, and spleen cells divide most rapidly, people exposed to radiation often suffer from leukemia. All this genetic damage can also cause cancer. The initial effects from Chernobyl included twenty-eight deaths due to huge doses of radioactivity, with skin lesions covering over 50 percent of the body; followed by hundreds of radiation-induced thyroid tumors, particularly in children; increased infant leukemia; and an increased level of birth defects. Over ten years later, thyroid cancer in children in parts of the Ukraine is now thirty times more prevalent than before.
Researchers anxious to measure the rate of mutation in the human population faced a difficult challenge. Since the normal, functional DNA in out bodies mutates extremely slowly, any increase in the mutation rate would be so small as to be unmeasurable. But as discussed earlier, we have other DNA in out bodies, "junk DNA," which does not code for any proteins and rarely has any effect on our bodies. Since junk DNA mutates at a much higher rate, changes are easier to detect.
Scientists studied blood samples of seventy-nine families living two hundred miles north of Chernobyl. Comparing the junk DNA of children born eight years after the explosion with their parents, they found that the mutation rate was twice as high as normal: The children had twice as many genetic differences from their parents as expected. Now these junk DNA mutations were not connected to any health problems in the children, and it's unlikely they would be, since they aren't changes to functional DNA. However, this acceleration may indicate that an equal acceleration in mutation is occurring in the functional DNA.
This finding surprised and shocked researchers, since studies of survivors of the atomic bombs dropped on Japan found only somatic mutations in survivors, with no evidence of mutations in the survivors' children. Mutations can only be passed on to children, remember, if they occur in the germ cells, and germ cell mutations are much more rare than somatic cell mutations. One important factor may be that the Japanese survivors received just one huge dose of radiation, while the Chernobyl survivors have been exposed to radioactive contamination for twelve years. Another factor may be additional pollution from other sources in the area. Whatever the reason, humans living near Chernobyl have suffered genetic damage to germ cells, which has now passed on to the next generation. The full consequences of these mutations remain unclear for now.
But some scientists believe that radiation and toxic chemicals are affecting the long-term evolution of species. The study of such multi-generational effects has formed a new field: evolutionary toxicology. Rather than studying the direct effects of radiation on the individual, the scientists of this new discipline study the indirect effects on a population. Evolution requires a variety of traits to exist within a species. This variety allows natural selection to occur, the organisms with the more favorable traits thriving, and those with less favorable traits dying off. If radiation and pollution trigger genetic mutations, then they are introducing more variety into populations and so putting the rate of evolution into overdrive.
But what are the effects of this increased variety? In most cases, the mutations caused by pollution or radiation are not helpful to the species, and so those mutated individuals are not "the fittest." They die oft, ultimately lessening the genetic diversity of the species. The few remaining animals, who have some quality favorable to survival, interbreed and repopulate the area, but now the population has a more narrow genetic base, which leaves them less able to adapt to new changes in the environment. Dr. John Bickham, professor of wildlife and fishery sciences at Texas A & M, explains, "You'll go to these places and you'll think, 'Great! The animals are still alive!' But what you see are the survivors, the ones that were genetically tested and were successful. The genetic constitution of those animals may be quite different than what was there before." You may think, "So what? Now they're better equipped to survive." The problem is that while these animals may be able to survive in radioactivity, their smaller genetic base makes them less able to adapt to future changes in the environment. Dr. Bickham says, "We're only beginning to understand what happens to populations exposed to environmental contaminations."
So how likely is Flukie to arise from "a primordial soup of radioactive sewage"? Dr. Bickham says that such dramatically different mutants are "not something we see in nature. Yes, radiation produces mutations, and yes, mutations can change organisms. The more different these organisms are from their progenitors, though, the less likely that they are going to be viable." The truth is that the results of radiation area lot less fun than Flukie, causing deterioration, illness, and death. As for whether such mutants could endanger other life, Dr. Bickham says, "It's more likely that such an organism will get eaten by something that hasn't changed rather than eating something that hasn't changed."
And that's really the case with all of out physical oddities. When our genes are horribly mutated, the tragic results die before birth or shortly after. Yet we are all mutants, and new mutations occur constantly all around us and within us, part of every life process, every breath, every birth. And with each bit of genetic chaos that infiltrates our systems, the infinitesimal chance persists that a radically different creature may one day be horn and survive.
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