by Michio Kaku
But the most difficult organ to grow is the human brain. Although recreating or growing a human brain seems unlikely for decades to come, it may instead be possible to inject young cells directly into the brain, which will incorporate them into the brain’s neural network. This injection of new brain cells, however, is random, so the patient will have to relearn many basic functions. But because the brain is “plastic”—that is, it constantly rewires itself after it learns a new task—it might be able to integrate these new neurons so that they fire correctly.
STEM CELLS
One step beyond this is to apply stem cell technology. So far, the human organs were grown using cells that were not stem cells but were cells specially treated to proliferate inside molds. In the near future, it should be possible to use stem cells directly.
Stem cells are the “mother of all cells,” and have the ability to change into any type of cell of the body. Each cell in our body has the complete genetic code necessary to create our entire body. But as our cells mature, they specialize, so many of the genes are inactivated. For example, although a skin cell may have the genes to turn into blood, these genes are turned off when an embryonic cell becomes an adult skin cell.
But embryonic stem cells retain this ability to regrow any type of cell throughout their life. Although embryonic stem cells are more highly prized by scientists, they are also more controversial, since an embryo has to be sacrificed in order to extract these cells, raising ethical issues. (However, Lanza and his colleagues have spearheaded ways in which to take adult stem cells, which have already turned into one type of cell, and then turn them into embryonic stem cells.)
Stem cells have the potential to cure a host of diseases, such as diabetes, heart disease, Alzheimer’s, Parkinson’s, even cancer. In fact, it is difficult to think of a disease in which stem cells will not have a major impact. One particular area of research is spinal cord injury, once thought to be totally incurable. In 1995, when the handsome actor Christopher Reeve suffered a severe spinal cord injury that left him totally paralyzed, there was no cure. However, in animal studies, great strides have been made in repairing the spinal cord with stem cells.
For example, Stephen Davies of the University of Colorado has had impressive success in treating spinal cord injuries in rats. He says, “I conducted some experiments where we transplanted adult neurons directly into adult central nervous systems. Real Frankenstein experiments. To our great surprise, adult neurons were able to send new nerve fibers from one side of the brain to the other in just one week.” In treating spinal cord injury, it was widely thought that any attempt to repair the nerves would create great pain and distress as well. Davies found that a key type of nerve cell, called an astrocyte, occurs in two varieties, with different outcomes.
Davies says, “By using the right astrocytes to repair spinal cord injuries, we have all the gains without the pain, while these other types of appear to provide the opposite—pain but no gain.” Moreover, the same techniques he is pioneering with stem cells will also work on victims of strokes and Alzheimer’s and Parkinson’s diseases, he believes.
Since virtually every cell of the body can be created by altering embryonic stem cells, the possibilities are endless. However, Doris Taylor, director of the Center for Cardiovascular Repair at the University of Minnesota, cautions that much work has yet to be done. “Embryonic stem cells represent the good, the bad, and the ugly. When they are good, they can be grown to large numbers in the lab and used to give rise to tissues, organs, or body parts. When they are bad, they don’t know when to stop growing and give rise to tumors. The ugly—well, we don’t understand all the cues, so we can’t control the outcome, and we aren’t ready to use them without more research in the lab,” she notes.
This is one of the main problems facing stem cell research: the fact that these stem cells, without chemical cues from the environment, might continue to proliferate wildly until they become cancerous. Scientists now realize that the subtle chemical messages that travel between cells, telling them when and where to grow and stop growing, are just as important as the cell itself.
Nonetheless, slow but real progress is being made, especially in animal studies. Taylor made headlines in 2008 when her team, for the first time in history, grew a beating mouse heart almost from scratch. Her team started with a mouse heart and dissolved the cells within that heart, leaving only the scaffolding, a heart-shaped matrix of proteins. Then they planted a mixture of heart stem cells into that matrix, and watched as the stem cells began to proliferate inside the scaffolding. Previously, scientists were able to grow individual heart cells in a petri dish. But this was the first time that an actual beating heart was grown in the laboratory.
Growing the heart was also an exciting personal event for her. She said, “It’s gorgeous. You can see the whole vascular tree, from arteries to the tiny veins that supply blood to every single heart cell.”
There is also one part of the U.S. government that is keenly interested in making breakthroughs in the area of tissue engineering: the U.S. Army. In past wars, the death rate on the battlefield was appalling, with entire regiments and battalions decimated and many dying of wounds. Now rapid-response medical evacuation teams fly the wounded from Iraq and Afghanistan to Europe or the United States, where they receive top-notch medical care. The survival rate for GIs has skyrocketed. And so has the number of soldiers who have lost arms and limbs. As a consequence, the U.S. Army has made it a priority to find a way to grow back limbs.
One breakthrough made by the Armed Forces Institute of Regenerative Medicine has been to use a radically new method of growing organs. Scientists have long known that salamanders have remarkable powers of regeneration, regrowing entire limbs after they are lost. These limbs grow back because salamander stem cells are stimulated to make new limbs. One theory that has borne fruit is being explored by Stephen Badylak of the University of Pittsburgh, who has successfully regrown fingertips. His team has created a “pixie dust” with the miraculous power of regrowing tissue. This dust is created not from cells but from the extracellular matrix that exists between cells. This matrix is important because it contains the signals that tell the stem cells to grow in a particular fashion. When this pixie dust is applied to a fingertip that has been cut off, it will stimulate not just the fingertip but also the nail, leaving an almost perfect copy of the original finger. Up to one-third of an inch of tissue and nail has been grown in this fashion. The next goal is to extend this process to see if an entire human limb can be regrown, just like the salamanders’.
CLONING
If we can grow various organs of the human body, then can we regrow an entire human being, creating an exact genetic copy, a clone? The answer is yes, in principle, but it has not been done, despite numerous reports to the contrary.
Clones are a favorite theme in Hollywood movies, but they usually get the science backward. In the movie The 6th Day, Arnold Schwarzenegger’s character battles the bad guys who have mastered the art of cloning human beings. More important, they have mastered the art of copying a person’s entire memory and then inserting it into the clone. When Schwarzenegger manages to eliminate one bad guy, a new one rises up with the same personality and memory. Things get messy when he finds out that a clone was made of him without his knowledge. (In reality, when an animal is cloned, the memories are not.)
The concept of cloning hit the world headlines in 1997, when Ian Wilmut of the Roslin Institute of the University of Edinburgh was able to clone Dolly the sheep. By taking a cell from an adult sheep, extracting the DNA within its nucleus, and then inserting this nucleus into an egg cell, Wilmut was able to accomplish the feat of bringing back a genetic copy of the original. I once asked him if he’d had any idea of the media firestorm that would be ignited by his historic discovery. He said no. He clearly understood the medical importance of his work but underestimated the public’s fascination with his discovery.
Soon, groups around the world began to duplicate thi
s feat, cloning a wide variety of animals, including mice, goats, cats, pigs, dogs, horses, and cattle. I once went with a BBC camera crew and visited Ron Marquess just outside Dallas, Texas, who has one of the largest cloned-cattle farms in the country. At the ranch, I was amazed to see first-, second-, and even third-generation cloned cattle—clones of clones of clones. Marquess told me that they would have to invent a new vocabulary to keep track of the various generations of cloned cattle.
One group of cattle caught my eye. There were about eight identical twins, all lined up. They walked, ran, ate, and slept precisely in a row. Although the calves had no conception they were clones of one another, they instinctively banded together and mimicked one another’s motions.
Marquess told me that cloning cattle was potentially a lucrative business. If you have a bull with superior physical characteristics, then it could fetch a handsome price if it was used for breeding. But if the bull died, then its genetic line would be lost with it unless its sperm had been collected and refrigerated. With cloning, one could keep the genetic line of prized bulls alive forever.
Although cloning has commercial applications for animals and animal husbandry, the implications for humans are less clear. Although there have been a number of sensational claims that human cloning has been achieved, all of them are probably bogus. So far, no one has successfully cloned a primate, let alone a human. Even cloning animals has proven to be difficult, given that hundreds of defective embryos are created for every one that reaches full term.
And even if human cloning becomes possible, there are social obstacles. First of all, many religions will oppose human cloning, similar to the way the Catholic Church opposed test tube babies back in 1978, when Louise Brown became the first baby in history to be conceived in a test tube. This means that laws will probably be passed banning the technology, or at least tightly regulating it. Second, the commercial demand for human cloning will be small. At most, probably only a fraction of the human race will be clones, even if it is legal. After all, we already have clones, in the form of identical twins (and triplets), so the novelty of human cloning will gradually wear off.
Originally, the demand for test tube babies was enormous, given the legions of infertile couples. But who will clone a human? Perhaps parents mourning the death of a child. Or, more likely, a wealthy, elderly man on his deathbed who has no heirs—or no heirs he particularly cares for—and wants to will all his money to himself as a child, in order to start all over again.
So in the future, although there might be laws passed preventing it, human clones will probably exist. However, they will represent only a tiny fraction of the human race and the social consequences will be quite small.
GENE THERAPY
Francis Collins, the current director of the National Institutes of Health and the man who led the government’s historic Human Genome Project, told me that “all of us have about a half-dozen genes which are pretty screwed up.” In the ancient past, we simply had to suffer from these often lethal genetic defects. In the future, he told me, we will cure many of them via gene therapy.
Genetic diseases have haunted humanity since the dawn of history, and at key moments may actually have influenced the course of history. For example, because of inbreeding among the royal families of Europe, genetic diseases have plagued generations of nobility. George III of England, for example, most likely suffered from acute intermittent porphyria, which causes temporary bouts of insanity. Some historians have speculated that this aggravated his relationship with the colonies, prompting them to declare their independence from England in 1776.
Queen Victoria was a carrier of the hemophilia gene, which causes uncontrolled bleeding. Because she had nine children, many of whom married into other royal houses of Europe, this spread the “royal disease” across the Continent. In Russia, Queen Victoria’s great-grandson Alexis, the son of Nicholas II, suffered from hemophilia, which could seemingly be temporarily controlled by the mystic Rasputin. This “mad monk” gained enough power to paralyze the Russian nobility, delay badly needed reforms, and, as some historians have speculated, help bring about the Bolshevik Revolution of 1917.
But in the future, gene therapy may be able to cure many of the 5,000 known genetic diseases, such as cystic fibrosis (which afflicts northern Europeans), Tay-Sachs disease (which affects Eastern European Jews), and sickle cell anemia (which afflicts African Americans). In the near future, it should be possible to cure many genetic diseases that are caused by the mutation of a single gene.
Gene therapy comes in two types: somatic and germ line.
Somatic gene therapy involves fixing the broken genes of a single individual. The therapeutic value disappears when the individual dies. More controversial is germ-line gene therapy, in which one fixes the genes of the sex cells, so that the repaired gene can be passed on to the next generation, almost forever.
Curing genetic disease follows a long but well-established route. First, one must find victims of a certain genetic disease and then painstakingly trace their family trees, going back many generations. By analyzing the genes of these individuals, one then tries to determine the precise location of the gene that may be damaged.
Then one takes a healthy version of that gene, inserts it into a “vector” (usually a harmless virus), and then injects it into the patient. The virus quickly inserts the “good gene” into the cells of the patient, potentially curing the patient of this disease. By 2001, there were more than 500 gene therapy trials under way or under review throughout the world.
However, progress has been slow and the results mixed. One problem is that the body often confuses this harmless virus, containing the “good gene,” with a dangerous virus and begins to attack it. This causes side effects that can negate the effect of the good gene. Another problem is that not enough of the virus inserts the good gene into its target cells correctly, so that the body cannot produce enough of the proper protein.
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.
COEXISTING WITH 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.