Physics of the Future: How Science Will Shape Human Destiny and Our Daily Lives by the Year 2100 (25 page)

Despite these complications, scientists in France announced in 2000 that they were able to cure children with severe combined immunodeficiency (SCID), who were born without a functioning immune system. Some SCID patients, like “David the bubble boy,” must live inside sterile plastic bubbles for the rest of their lives. Without an immune system, any illness could prove fatal. Genetic analyses of these patients show that their immune cells did indeed incorporate the new gene, as planned, hence activating their immune systems.

But there have been setbacks. In 1999, at the University of Pennsylvania, one patient died in a gene therapy trial, causing soul-searching within the medical community. It was the first death among the 1,100 patients undergoing this type of gene therapy. And by 2007, four of the ten patients who had been cured of one particular form of SCID developed a severe side effect, leukemia. Research in gene therapy for SCID is now focused on curing the disease without accidentally triggering a gene that can cause cancer. To date, seventeen patients who suffered from a different variety of SCID are free of both SCID and cancer, making it one of the few successes in this field.

One target for gene therapy is actually cancer. Almost 50 percent of all common cancers are linked to a damaged gene, p53. The p53 gene is long and complex; this makes it more probable that it will be damaged by environmental and chemical factors. So many gene therapy experiments are being conducted to insert a healthy p53 gene into patients. For example, cigarette smoke often causes characteristic mutations in three well-known sites within the p53 gene. Thus gene therapy, by replacing the damaged p53 gene, may one day be able to cure certain forms of lung cancer.

Progress has been slow but steady. In 2006, scientists at the National Institutes of Health in Maryland were able to successfully treat metastatic melanoma, a form of skin cancer, by altering killer T cells so that they specifically targeted cancer cells. This is the first study to show that gene therapy can be successfully used against some form of cancer. And in 2007, doctors at the University College and Moorfields Eye Hospital in London were able to use gene therapy to treat a certain form of inherited retinal disease (caused by mutations in the RPE65 gene).

Meanwhile, some couples are not waiting for gene therapy but are taking their genetic heritage into their own hands. A couple can create several fertilized embryos using in vitro fertilization. Each embryo can be tested for a specific genetic disease, and the couple can select the embryo free of the genetic disease to implant in the mother. In this way, genetic diseases can gradually be eliminated without using expensive gene therapy techniques. This process is currently being done with some Orthodox Jews in Brooklyn who have a high risk of Tay-Sachs disease.

One disease, however, will probably remain deadly throughout this century—cancer.

Back in 1971, President Richard Nixon, amid great fanfare and publicity, solemnly announced a war on cancer. By throwing money at cancer, he believed a cure would soon be at hand. But forty years (and $200 billion) later, cancer is the second-leading cause of death in the United States, responsible for 25 percent of all deaths. The death rate from cancer has dropped only 5 percent from 1950 to 2005 (adjusting for age and other factors). It is estimated that cancer will claim the lives of 562,000 Americans this year alone, or more than 1,000 people per day. Cancer rates have fallen for a few types of the disease but have remained stubbornly flat in others. And the treatment for cancer, involving poisoning, slicing, and zapping human tissue, leaves a trail of tears for the patients, who often wonder which is worse, the disease or the treatment.

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.”

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.

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 stopped 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.