by Michio Kaku
In hindsight, we can see what went wrong. Back in 1971, before the revolution in genetic engineering, the causes of cancer were a total mystery.
Now scientists realize that cancer is basically a disease of our genes. Whether caused by a virus, chemical exposure, radiation, or chance, cancer fundamentally involves mutations in four or more of our genes, in which a normal cell “forgets how to die.” The cell loses control over its reproduction and reproduces without limit, eventually killing the patient. The fact that it takes a sequence of four or more defective genes to cause cancer probably explains why it often kills decades after an original incident. For example, you might have a severe sunburn as a child. Many decades later, you might develop skin cancer at that same site. This means it probably took that long for the other mutations to occur and finally tip the cell into a cancerous mode.
There are at least two major types of these cancer genes, oncogenes and tumor suppressors, which function like the accelerator and brakes of a car. The oncogene acts like an accelerator stuck in the down position, so the car careens out of control, allowing the cell to reproduce without limit. The tumor suppressor normally acts like a brake, so when it is damaged, the cell is like a car that can’t stop.
The Cancer Genome Project plans to sequence the genes of most cancers. Since each cancer requires sequencing the human genome, the Cancer Genome Project is hundreds of times more ambitious than the original Human Genome Project.
Some of the first results of this long-awaited Cancer Genome Project were announced in 2009 concerning skin and lung cancer. The results were startling. Mike Stratton of the Wellcome Trust Sanger Institute said, “What we are seeing today is going to transform the way that we see cancer. We have never seen cancer revealed in this form before.”
Cells from a lung cancer cell had an astounding 23,000 individual mutations, while the melanoma cancer cell had 33,000 mutations. This means that a typical smoker develops one mutation for every fifteen cigarettes he or she smokes. (Lung cancer kills 1 million people every year around the world, mostly from smoking.)
The goal is to genetically analyze all types of cancers, of which there are more than 100. There are many tissues in the body, all of which can become cancerous; many types of cancers for each tissue; and tens of thousands of mutations within each type of cancer. Since each cancer involves tens of thousands of mutations, it will take many decades to isolate precisely which of these mutations causes the cell mechanism to go haywire. Scientists will develop cures for a wide variety of cancers but no one cure for all of them, since cancer itself is like a collection of diseases.
New treatments and therapies will also continually enter the market, all of them designed to hit cancer at its molecular and genetic roots. Some of the promising ones include:
• antiangiogenesis, or choking off the blood supply of a tumor so that it never grows
• nanoparticles, which are like “smart bombs” directed at cancer cells
• gene therapy, especially for gene p53
• new drugs that target just the cancer cells
• new vaccinations against viruses that can cause cancer, like the human papillomavirus (HPV), which can cause cervical cancer
Unfortunately, it is unlikely that we will find a magic bullet for cancer. Rather, we will cure cancer one step at a time. More than likely, the major reduction in death rates will come when we have DNA chips scattered throughout our environment, constantly monitoring us for cancer cells years before a tumor forms.
As Nobel laureate David Baltimore notes, “Cancer is an army of cells that fights our therapies in ways that I’m sure will keep us continually in the battle.”
GENE THERAPY
Despite the setbacks in gene therapy, researchers believe steady gains will be made into the coming decades. By midcentury, many think, gene therapy will be a standard method of treating a variety of genetic diseases. Much of the success that scientists have had in animal studies will eventually be translated into human studies.
So far, gene therapy has targeted diseases caused by mutations in a single gene. They will be the first to be cured. But many diseases are caused by mutations in multiple genes, along with triggers from the environment. These are much more difficult to treat, but they include such important diseases as diabetes, schizophrenia, Alzheimer’s, Parkinson’s, and heart disease. All of them show definite genetic patterns, but no single gene is responsible. For example, it is possible to have a schizophrenic whose identical twin is normal.
Over the years, there have been a number of announcements that scientists have been able to isolate some of the genes involved in schizophrenia by following the genetic history of certain families. However, it is embarrassing that these results are often not verifiable by other independent studies. So these results are flawed, or perhaps many genes are involved in schizophrenia. Plus, certain environmental factors seem to be involved.
By midcentury, gene therapy should become a well-established therapy, at least for diseases caused by single genes. But patients might not be content with just fixing genes. They may also want to improve them.
DESIGNER CHILDREN
By midcentury, scientists will go beyond just fixing broken genes to actually enhancing and improving them.
The desire to have superhuman ability is an ancient one, rooted deeply in Greek and Roman mythology and our dreams. The great hero Hercules, one of the most popular of all the Greek and Roman demigods, got his great powers not from exercise and diet but by an injection of divine genes. His mother was a beautiful mortal, Alcmene, who one day caught the attention of Zeus, who disguised himself as her husband to make love to her. When she became pregnant with his child, Zeus announced that the baby would one day become a great warrior. But Zeus’s wife, Hera, became jealous and secretly schemed to kill the baby by delaying his birth. Alcmene almost died in agony during a prolonged labor, but Hera’s plot was exposed at the last minute and Alcmene delivered an unusually large baby. Half man and half god, Hercules inherited the godlike strength of his father to accomplish heroic, legendary feats.
In the future, we might not be able to create divine genes, but we certainly will be able to create genes that will give us superhuman abilities. And like Hercules’ difficult delivery, there will be many difficulties bringing this technology to fruition.
By midcentury, “designer children” could become a reality. As Harvard biologist E. O. Wilson has said, “Homo sapiens, the first truly free species, is about to decommission natural selection, the force that made us …. Soon we must look deep within ourselves and decide what we wish to become.”
Already, scientists are teasing apart the genes that control basic functions. For example, the “smart mouse” gene, which increases the memory and performance of mice, was isolated in 1999. Mice that have the smart gene are better able to navigate mazes and remember things.
Scientists at Princeton University such as Joseph Tsien have created a strain of genetically altered mice with an extra gene called NR2B that helps to trigger the production of the neurotransmitter N-methyl-D-aspartate (NMDA) in the forebrain of mice. The creators of the smart mice have christened them Doogie mice (after the TV character Doogie Howser, MD).
These smart mice outperformed normal mice on a variety of tests. If a mouse is placed in a vat of milky water, it must find a platform hidden just beneath the surface where it can rest. Normal mice forget where this platform is and swim randomly around the vat, while smart mice make a beeline to it on the first try. If the mice are shown two objects, one an old one and one a new one, the normal mice do not pay attention to the new object. But the smart mice immediately recognize the presence of this new object.
What is most important is that scientists understand how these smart mice genes work: they regulate the synapses of the brain. If you think of the brain as a vast collection of freeways, then the synapse would be equivalent to a toll booth. If the toll is too high, then cars cannot pass through the gate: a message is stopp
ed within the brain. But if the toll is low, then cars can pass and the message is transmitted through the brain. Neurotransmitters like NMDA lower the toll at the synapse, making it possible for messages to pass freely. The smart mice have two copies of the NR2B gene, which in turn helps to produce the NMDA neurotransmitter.
These smart mice verify Hebb’s rule: learning takes place when certain neural pathways are reinforced. Specifically, these pathways could be reinforced by regulating the synapses that connect two nerve fibers, making it easier for signals to cross a synapse.
This result may help to explain certain peculiarities about learning. It’s been known that aging animals have a reduced ability to learn. Scientists see this throughout the animal kingdom. This might be explained because the NR2B gene becomes less active with age.
Also, as we saw earlier with Hebb’s rule, memories might be created when neurons form a strong connection. This might be true, since activating the NMDA receptor creates a strong connection.
MIGHTY MOUSE GENE
In addition, the “mighty mouse gene” has been isolated, which increases the muscle mass so that the mouse appears to be musclebound. It was first found in mice with unusually large muscles. Scientists now realize that the key lies in the myostatin gene, which helps to keep muscle growth in check. But in 1997, scientists found that when the myostatin gene is silenced in mice, muscle growth expands enormously.
Another breakthrough was made soon afterward in Germany, when scientists examined a newborn boy who had unusual muscles in his upper legs and arms. Ultrasound analysis showed that this boy’s muscles were twice as large as normal. By sequencing the genes of this baby and of his mother (who was a professional sprinter), they found a similar genetic pattern. In fact, an analysis of the boy’s blood showed no myostatin whatsoever.
Scientists at the Johns Hopkins Medical School were at first eager to make contact with patients suffering from degenerative muscle disorders who might benefit from this result, but they were disappointed to find that half the telephone calls to their office came from bodybuilders who wanted the gene to bulk themselves up, regardless of the consequences. Perhaps these bodybuilders were recalling the phenomenal success of Arnold Schwarzenegger, who has admitted to using steroids to jump-start his meteoric career. Because of the intense interest in the myostatin gene and ways to suppress it, even the Olympic Committee was forced to set up a special commission to look into it. Unlike steroids, which are relatively easy to detect via chemical tests, this new method, because it involves genes and the proteins they create, is much more difficult to detect.
Studies done on identical twins who have been separated at birth show that there is a wide variety of behavioral traits influenced by genetics. In fact, these studies show that roughly 50 percent of a twin’s behavior is influenced by genes, the other 50 percent by environment. These traits include memory, verbal reasoning, spatial reasoning, processing speed, extroversion, and thrill seeking.
Even behaviors once thought to be complex are now revealing their genetic roots. For example, prairie voles are monogamous. Laboratory mice are promiscuous. Larry Young at Emory University shocked the world of biotechnology by showing that the transfer of one gene from prairie voles could create mice that exhibited monogamous characteristics. Each animal has a different version of a certain receptor for a brain peptide associated with social behavior and mating. Young inserted the vole gene for this receptor into the mice and found that the mice then exhibited behaviors more like the monogamous voles.
Young said, “Although many genes are likely to be involved in the evolution of complex social behaviors such as monogamy … changes in the expression of a single gene can have an impact on the expression of components of these behaviors, such as affiliation.”
Depression and happiness may also have genetic roots. It has long been known that there are people who are happy even though they may have suffered tragic accidents. They always see the brighter side of things, even in the face of setbacks that may devastate another individual. These people also tend to be healthier than normal. Harvard psychologist Daniel Gilbert told me that there is a theory that might explain this. Perhaps we are born with a “happiness set point.” Day by day we may oscillate around this set point, but its level is fixed at birth. In the future, via drugs or gene therapy, one may be able to shift this set point, especially for those who are chronically depressed.
SIDE EFFECTS OF THE BIOTECH REVOLUTION
By midcentury, scientists will be able to isolate and alter many of the single genes that control a variety of human characteristics. But this does not mean humanity will immediately benefit from them. There is also the long, hard work of ironing out side effects and unwanted consequences, which will take decades.
For example, Achilles was invincible in combat, leading the victorious Greeks in their epic battle with the Trojans. However, his power had a fatal flaw. When he was a baby, his mother dipped him into the magic river Styx in order to make him invincible. Unfortunately, she had to hold him by the heel when she placed him into the river, leaving that one crucial point of vulnerability. Later, he would die during the Trojan War after being hit in the heel by an arrow.
Today, scientists are wondering if the new strains of creatures emerging from their laboratories also have a hidden Achilles’ heel. For example, today there are about thirty-three different “smart mouse” strains that have enhanced memory and performance. However, there is an unexpected side effect of having enhanced memory; smart mice are sometimes paralyzed by fear. If they are exposed to an extremely mild electric shock, for example, they will shiver in terror. “It’s as if they remember too much,” says Alcino Silva of UCLA, who developed his own strain of smart mice. Scientists now realize that forgetting may be as important as remembering in making sense of this world and organizing our knowledge. Perhaps we have to throw out a lot of files in order to organize our knowledge.
This is reminiscent of a case from the 1920s, documented by Russian neurologist A. R. Luria, of a man who had a photographic memory. After just a single reading of Dante’s Divine Comedy, he had memorized every word. This was helpful in his work as a newspaper reporter, but he was incapable of understanding figures of speech. Luria observed, “The obstacles to his understanding were overwhelming: each expression gave rise to an image; this, in turn, would conflict with another image that had been evoked.”
In fact, scientists believe that there has to be a balance between forgetting and remembering. If you forget too much, you may be able to forget the pain of previous mistakes, but you also forget key facts and skills. If you remember too much, you may be able to remember important details, but you might be paralyzed by the memory of every hurt and setback. Only a trade-off between these two may yield optimal understanding.
Bodybuilders are already flocking to different drugs and therapies that promise them fame and glory. The hormone erythropoietin (EPO) works by making more oxygen-containing red blood cells, which means increased endurance. Because EPO thickens the blood, it also has been linked to strokes and heart attacks. Insulin-like growth factors (IGF) are useful because they help proteins to bulk up muscles, but they have been linked to tumor growth.
Even if laws are passed banning genetic enhancements, they will be difficult to stop. For example, parents are genetically hardwired by evolution to want to give every advantage to their children. On the one hand, this might mean giving them violin, ballet, and sports lessons. But on the other hand, this might mean giving them genetic enhancements to improve their memory, attention span, athletic ability, and perhaps even their looks. If parents find out that their child is competing with a neighbor’s child who is rumored to have been genetically enhanced, there will be enormous pressure to give the same benefit to their child.
As Gregory Benford has said, “We all know that good-looking people do well. What parents could resist the argument that they were giving the child a powerful leg up (maybe literally) in a brave new competitive world?”
By midcentury, genetic enhancements may become commonplace. In fact, genetic enhancements may even be indispensable if we are to explore the solar system and live on inhospitable planets.
Some say that we should use designer genes to make us healthier and happier. Others say that we should allow for cosmetic enhancements. The big question will be how far this will go. In any event, it may become increasingly difficult to control the spread of “designer genes” that enhance looks and performance. We don’t want the human race to split into different genetic factions, the enhanced and the unenhanced, but society will have to democratically decide how far to push this technology.
Personally, I believe that laws will be passed to regulate this powerful technology, possibly to allow gene therapy when it cures disease and allows us to lead productive lives, but to restrict gene therapy for purely cosmetic reasons. This means that a black market might eventually develop to skirt these laws, so we might have to adjust to a society in which a small fraction of the population is genetically enhanced.
For the most part, this might not be a disaster. Already, one can use plastic surgery to improve appearance, so using genetic engineering to do this may be unnecessary. But the danger may arise when one tries to genetically change one’s personality. There are probably many genes that influence behavior, and they interact in complex ways, so tampering with behavioral genes may create unintended side effects. It may take decades to sort through all these side effects.