For example, autistic savants can perform miraculous feats of memorization and calculation. But they have difficulty tying their shoelaces, getting a job, or functioning in society. The late Kim Peek, who was so remarkable that the movie Rain Man Rain Man was based on his extraordinary life, memorized every word in 12,000 books and could perform calculations that only a computer could check. Yet he had an IQ of 73, had difficulty holding a conversation, and needed constant help to survive. Without his father"s a.s.sistance, he was largely helpless. In other words, the superfast computers of the future will be like autistic savants, able to memorize vast amounts of information, but not much more, unable to survive in the real world on their own. was based on his extraordinary life, memorized every word in 12,000 books and could perform calculations that only a computer could check. Yet he had an IQ of 73, had difficulty holding a conversation, and needed constant help to survive. Without his father"s a.s.sistance, he was largely helpless. In other words, the superfast computers of the future will be like autistic savants, able to memorize vast amounts of information, but not much more, unable to survive in the real world on their own.
Even if computers begin to match the computing speed of the brain, they will still lack the necessary software and programming to make everything work. Matching the computing speed of the brain is just the humble beginning.
Third, even if intelligent robots are possible, it is not clear if a robot can make a copy of itself that is smarter than the original. The mathematics behind self-replicating robots was first developed by the mathematician John von Neumann, who invented game theory and helped to develop the electronic computer. He pioneered the question of determining the minimum number of a.s.sumptions before a machine could create a copy of itself. However, he never addressed the question of whether a robot can make a copy of itself that is smarter than it. In fact, the very definition of "smart" is problematic, since there is no universally accepted definition of "smart."
Certainly, a robot might be able to create a copy of itself with more memory and processing ability by simply upgrading and adding more chips. But does this mean the copy is smarter, or just faster? For example, an adding machine is millions of times faster than a human, with much more memory and processing speed, but it is certainly not smarter. So intelligence is more than just memory and speed.
Fourth, although hardware may progress exponentially, software may not. While hardware has grown by the ability to etch smaller and smaller transistors onto a wafer, software is totally different; it requires a human to sit down with a pencil and paper and write code. That is the bottleneck: the human.
Software, like all human creative activity, progresses in fits and starts, with brilliant insights and long stretches of drudgery and stagnation. Unlike simply etching more transistors onto silicon, which has grown like clockwork, software depends on the unpredictable nature of human creativity and whim. Therefore all predictions of a steady, exponential growth in computer power have to be qualified. A chain is no stronger than its weakest link, and the weakest link is software and programming done by humans.
Engineering progress often grows exponentially, especially when it is a simple matter of achieving greater efficiency, such as etching more and more transistors onto a silicon wafer. But when it comes to basic research, which requires luck, skill, and unexpected strokes of genius, progress is more like "punctuated equilibrium," with long stretches of time when not much happens, with sudden breakthroughs that change the entire terrain. If we look at the history of basic research, from Newton to Einstein to the present day, we see that punctuated equilibrium more accurately describes the way in which progress is made.
Fifth, as we have seen in the research for reverse engineering the brain, the staggering cost and sheer size of the project will probably delay it into the middle of this century. And then making sense of all this data may take many more decades, pushing the final reverse engineering of the brain to late in this century.
Sixth, there probably won"t be a "big bang," when machines suddenly become conscious. As before, if we define consciousness as including the ability to make plans for the future by running simulations of the future, then there is a spectrum of consciousness. Machines will slowly climb up this scale, giving us plenty of time to prepare. This will happen toward the end of this century, I believe, so there is ample time to discuss various options available to us. Also, consciousness in machines will probably have its own peculiarities. So a form of "silicon consciousness" rather than pure human consciousness will develop first.
But this raises another question. Although there are mechanical ways to enhance our bodies, there are also biological ways. In fact, the whole thrust of evolution is the selection of better genes, so why not shortcut millions of years of evolution and take control of our genetic destiny?
No one really has the guts to say it, but if we could make better human beings by knowing how to add genes, why shouldn"t we?
-JAMES WATSON, n.o.bEL LAUREATE I don"t really think our bodies are going to have any secrets left within this century. And so, anything that we can manage to think about will probably have a reality.
-DAVID BALTIMORE, n.o.bEL LAUREATE I don"t think the time is quite right, but it"s close. I"m afraid, unfortunately, that I"m in the last generation to die.
-GERALD SUSSMAN
The G.o.ds of mythology possessed the ultimate power: the power over life and death, the ability to heal the sick and prolong life. Foremost in our prayers to the G.o.ds was deliverance from disease and illness.
In Greek and Roman mythology, there is the tale of Eos, the beautiful G.o.ddess of the dawn. One day, she fell deeply in love with a handsome mortal, t.i.thonus. She had a perfect body and was immortal, but t.i.thonus would eventually age, wither away, and perish. Determined to save her lover from this dismal fate, she beseeched Zeus, the father of the G.o.ds, to grant t.i.thonus the gift of immortality so that they could spend eternity together. Taking pity on these lovers, he granted Eos her wish.
But Eos, in her haste, forgot to ask for eternal youth for him. So t.i.thonus became immortal, but his body aged. Unable to die, he became more and more decrepit and decayed, living an eternity with pain and suffering.
So that is the challenge facing the science of the twenty-first century. Scientists are now reading the book of life, which includes the complete human genome, and which promises us miraculous advances in understanding aging. But life extension without health and vigor can be an eternal punishment, as t.i.thonus tragically found out.
By the end of this century, we too shall have much of this mythical power over life and death. And this power won"t be limited to healing the sick but will be used to enhance the human body and even create new life-forms. It won"t be through prayers and incantations, however, but through the miracle of biotechnology.
One of the scientists who is unlocking the secrets of life is Robert Lanza, a man in a hurry. He is a new breed of biologist, young, energetic, and full of fresh ideas-so many breakthroughs to be made and so little time. Lanza is riding the crest of the biotech revolution. Like a kid in a candy store, he delights in delving into uncharted territory, making breakthroughs in a wide range of hot-b.u.t.ton topics.
A generation or two ago, the pace was much different. You might find biologists leisurely examining obscure worms and bugs, patiently studying their detailed anatomy and agonizing over what Latin names to give them.
Not Lanza.
I met him one day at a radio studio for an interview and was immediately impressed by his youth and boundless creativity. He was, as usual, rushing between experiments. He told me he got his start in this fast-moving field in the most unusual way. He came from a modest working-cla.s.s family south of Boston, where few went to college. But while in high school, he heard the astonishing news about the unraveling of DNA. He was hooked. He decided on a science project: cloning a chicken in his room. His bewildered parents did not know what he was doing, but they gave him their blessing.
Determined to get his project off the ground, he went to Harvard to get advice. Not knowing anyone, he asked a man he thought was a janitor for some directions. Intrigued, the janitor took him to his office. Lanza found out later that the janitor was actually one of the senior researchers at the lab. Impressed by the sheer audacity of this brash young high school student, he introduced Lanza to other scientists there, including many n.o.bel-caliber researchers, who would change his life. Lanza compares himself to Matt Damon"s character in the movie Good Will Hunting, Good Will Hunting, where a scruffy, street-smart working-cla.s.s kid astonishes the professors at MIT, dazzling them with his mathematical genius. where a scruffy, street-smart working-cla.s.s kid astonishes the professors at MIT, dazzling them with his mathematical genius.
Today, Lanza is chief scientific officer of Advanced Cell Technology, with hundreds of papers and inventions to his credit. In 2003, he made headlines when the San Diego Zoo asked him to clone a banteng, an endangered species of wild ox, from the body of one that had died twenty-five years before. Lanza successfully extracted usable cells from the carca.s.s, processed them, and sent them to a farm in Utah. There, the fertilized cell was implanted into a female cow. Ten months later he got news that his latest creation had just been born. On another day, he might be working on "tissue engineering," which may eventually create a human body shop from which we can order new organs, grown from our own cells, to replace organs that are diseased or have worn out. Another day, he could be working on cloning human embryo cells. He was part of the historic team that cloned the world"s first human embryo for the purpose of generating embryonic stem cells.
THREE STAGES OF MEDICINE.
Lanza is riding a tidal wave of discovery, created by unleashing the knowledge hidden within our DNA. Historically, medicine has gone through at least three major stages. In the first, which lasted for tens of thousands of years, medicine was dominated by superst.i.tion, witchcraft, and hearsay. With most babies dying at birth, the average life expectancy hovered around eighteen to twenty years. Some useful medicinal herbs and chemicals were discovered during this period, like aspirin, but for the most part there was no systematic way of finding new therapies. Unfortunately, any remedies that actually worked were closely guarded secrets. The "doctor" earned his income by pleasing wealthy patients and had a vested interest in keeping his potions and chants secret.
During this period, one of the founders of the Mayo Clinic kept a private diary when he made the rounds of his patients. He candidly wrote in his diary that there were only two active ingredients in his black bag that actually worked: a hacksaw and morphine. The hacksaw was used to cut off diseased limbs, and the morphine was used to deaden the pain of the amputation. They worked every time. Everything else in his black bag was snake oil and a fake, he lamented sadly.
The second stage of medicine began in the nineteenth century, with the coming of the germ theory and better sanitation. Life expectancy in the United States in 1900 rose to forty-nine years. When tens of thousands of soldiers were dying on the European battlefields of World War I, there was an urgent need for doctors to conduct real experiments, with reproducible results, which were then published in medical journals. The kings of Europe, horrified that their best and brightest were being slaughtered, demanded real results, not hocus-pocus. Doctors, instead of trying to please wealthy patrons, now fought for legitimacy and fame by publishing papers in peer-reviewed journals. This set the stage for advances in antibiotics and vaccines that increased life expectancy to seventy years and beyond.
The third stage of medicine is molecular medicine. We are seeing the merger of physics and medicine, reducing medicine to atoms, molecules, and genes. This historic transformation began in the 1940s, when Austrian physicist Erwin Schrodinger, one of the founders of the quantum theory, wrote an influential book called What Is Life? What Is Life? He rejected the notion that there was some mysterious spirit, or life force, that animated living things. Instead, he speculated that all life was based on a code of some sort, and that this was encoded on a molecule. By finding that molecule, he conjectured, one could unravel the secret of life. Physicist Francis Crick, inspired by Schrodinger"s book, teamed up with geneticist James Watson to prove that DNA was this fabled molecule. In 1953, in one of the most important discoveries of all time, Watson and Crick unlocked the structure of DNA, a double helix. When unraveled, a single strand of DNA stretches about six feet long. On it is contained a sequence of 3 billion nucleic acids, called A,T,C,G (adenine, thymine, cytosine, and guanine), that carry the code. By reading the precise sequence of these nucleic acids placed along the DNA molecule, one could read the book of life. He rejected the notion that there was some mysterious spirit, or life force, that animated living things. Instead, he speculated that all life was based on a code of some sort, and that this was encoded on a molecule. By finding that molecule, he conjectured, one could unravel the secret of life. Physicist Francis Crick, inspired by Schrodinger"s book, teamed up with geneticist James Watson to prove that DNA was this fabled molecule. In 1953, in one of the most important discoveries of all time, Watson and Crick unlocked the structure of DNA, a double helix. When unraveled, a single strand of DNA stretches about six feet long. On it is contained a sequence of 3 billion nucleic acids, called A,T,C,G (adenine, thymine, cytosine, and guanine), that carry the code. By reading the precise sequence of these nucleic acids placed along the DNA molecule, one could read the book of life.
The rapid advances in molecular genetics finally led to the creation of the Human Genome Project, truly a milestone in the history of medicine. A ma.s.sive, crash program to sequence all the genes of the human body, it cost about $3 billion and involved the work of hundreds of scientists collaborating around the world. When it was finally completed in 2003, it heralded a new era in science. Eventually, everyone will have his or her personalized genome available on a CD-ROM. It will list all your approximately 25,000 genes; it will be your "owner"s manual."
n.o.bel laureate David Baltimore summed it up when he said, "Biology is today an information science."
GENOMIC MEDICINE.
What is driving this remarkable explosion in medicine is, in part, the quantum theory and the computer revolution. The quantum theory has given us amazingly detailed models of how the atoms are arranged in each protein and DNA molecule. Atom for atom, we know how to build the molecules of life from scratch. And gene sequencing-which used to be a long, tedious, and expensive process-is all automated with robots now. Originally, it cost several million dollars to sequence all the genes in a single human body. It is so expensive and time-consuming that only a handful of people (including the scientists who perfected this technology) have had their genomes read. But within a few more years, this exotic technology may come to the average person.
(I vividly recall keynoting a conference in the late 1990s in Frankfurt, Germany, about the future of medicine. I predicted that by 2020, personal genomes would be a real possibility, and that everyone might have a CD or chip with his or her genes described on it. But one partic.i.p.ant became quite indignant. He rose and said that this dream was impossible. There were simply too many genes, and it would cost too much to offer personal genomes to the average person. The Human Genome Project had cost $3 billion; the cost to sequence one person"s genes could not possibly drop that much. Discussing the issue with him later, it gradually became clear what the problem was. He was thinking linearly. But Moore"s law was driving down the costs, making it possible to sequence DNA using robots, computers, and automatic machines. He failed to understand the profound impact of Moore"s law on biology. Looking back at that incident, I now realize that if there was a mistake in that prediction, it was in overestimating the time it would take to offer personal genomics.) For example, Stanford engineer Stephen R. Quake has perfected the latest development in gene sequencing. He has now driven down the cost to $50,000 and foresees the price plunging to $1,000 in the next few years. Scientists have long speculated that when the price of human gene sequencing drops to $1,000, this could open the floodgates to ma.s.s gene sequencing, so a large proportion of the human race may benefit from this technology. Within a few decades, the price of sequencing all your genes may cost less than $100, no more expensive than a standard blood test.
(The key to this latest breakthrough is to take a shortcut. Quake compares a person"s DNA to DNA sequences that have already been done of others. He breaks up the human genome into units of DNA containing 32 bits of information. Then he has a computer program that compares these 32-bit fragments to the completed genomes of other people. Since any two humans are almost identical in their DNA, differing on average by less than .1 percent, this means that a computer can rapidly get a match among these 32-bit fragments.) Quake became the eighth person in the world to have his genome fully sequenced. He had a personal interest in this project as well, since he scanned his personal genome for evidence of heart disease. Unfortunately, his genome indicated that he inherited one version of a gene a.s.sociated with heart disease. "You have to have a strong stomach when you look at your own genome," he lamented.
I know that eerie feeling. I had my own genome partially scanned and placed on a CD-ROM for a BBC-TV/Discovery special that I hosted. A doctor extracted some blood from my arm; sent it to the laboratory at Vanderbilt University; and then, two weeks later, a CD-ROM came back in the mail, listing thousands of my genes. Holding this disk in my hands gave me a funny feeling, knowing that it contained a partial blueprint for my body. In principle, this disk could be used to create a reasonable copy of myself.
But it also piqued my curiosity, since the secrets of my body were contained on that CD-ROM. For example, I could see if I had a particular gene that increased my chances of getting Alzheimer"s disease. I was concerned, since my mother died of Alzheimer"s. (Fortunately, I do not have the gene.) Also, four of my genes were matched with the genome of thousands of people around the world, who had also had their genes a.n.a.lyzed. Then, the locations of the individuals who had a perfect match with my four genes were placed on a map of the earth. By a.n.a.lyzing the dots on the map of the earth, I could see a long trail of dots, originating near Tibet and then stretching through China and to j.a.pan. It was amazing that this trail of dots traced the ancient migration patterns of my mother"s ancestors, going back thousands of years. My ancestors left no written records of their ancient migration, but the telltale map of their travels was etched into my blood and DNA. (You can also trace the ancestry of your father. The mitochondrial genes are pa.s.sed down unchanged from mother to daughter, while the Y chromosome is pa.s.sed down from father to son. Hence, by a.n.a.lyzing these genes, one can trace the ancestry of your mother or your father"s line.) I imagine in the near future, many people will have the same strange feeling I did, holding the blueprint of their bodies in their hands and reading the intimate secrets, including dangerous diseases, lurking in the genome and the ancient migration patterns of their ancestors.
But for scientists, this is opening an entirely new branch of science, called bioinformatics, or using computers to rapidly scan and a.n.a.lyze the genome of thousands of organisms. For example, by inserting the genomes of several hundred individuals suffering from a certain disease into a computer, one might be able to calculate the precise location of the damaged DNA. In fact, some of the world"s most powerful computers are involved in bioinformatics, a.n.a.lyzing millions of genes found in plants and animals for certain key genes.
This could even revolutionize TV detective shows like CSI. CSI. Given tiny sc.r.a.ps of DNA (found in hair follicles, saliva, or bloodstains), one might be able to determine not just the person"s hair color, eye color, ethnicity, height, and medical history, but perhaps also his face. Today, police artists can mold an approximate sculpture of a victim"s face using only the skull. In the future, a computer might be able to reconstruct a person"s facial features given just some dandruff or blood from that person. (The fact that identical twins have remarkably similar faces means that genetics alone, even in the presence of environmental factors, can determine much of a person"s face.) Given tiny sc.r.a.ps of DNA (found in hair follicles, saliva, or bloodstains), one might be able to determine not just the person"s hair color, eye color, ethnicity, height, and medical history, but perhaps also his face. Today, police artists can mold an approximate sculpture of a victim"s face using only the skull. In the future, a computer might be able to reconstruct a person"s facial features given just some dandruff or blood from that person. (The fact that identical twins have remarkably similar faces means that genetics alone, even in the presence of environmental factors, can determine much of a person"s face.) VISIT TO THE DOCTOR.
As we mentioned in the previous chapters, your visit to the doctor"s office will be radically changed. When you talk to the doctor in your wall screen, you will probably be talking to a software program. Your bathroom will have more sensors than a modern hospital, silently detecting cancer cells years before a tumor forms. For example, about 50 percent of all common cancers involve a mutation in the gene p53 that can be easily detected using these sensors.
If there is evidence of cancer, then nanoparticles will be injected directly into your bloodstream, which will, like smart bombs, deliver cancer-fighting drugs directly to the cancer cells. We will view chemotherapy today like we view leeches of the past century. (We will discuss the details of nanotechnology, DNA chips, nanoparticles, and nan.o.bots in more detail in the next chapter.) And if the "doctor" in your wall screen cannot cure a disease or injury to an organ, you will simply grow another. In the United States alone, there are 91,000 people awaiting an organ transplant. Eighteen die every day, waiting for an organ that never comes.
In the future, we will have tricorders-like these in Star Trek Star Trek-that can diagnose almost any disease; portable MRI detectors and DNA chips will make this possible. (photo credit 3.1)
If your virtual doctor finds something wrong, such as a diseased organ, then he might order a new one to be grown directly from your own cells. "Tissue engineering" is one of the hottest fields in medicine, making possible a "human body shop." So far, scientists can grow skin, blood, blood vessels, heart valves, cartilage, bone, noses, and ears in the lab from your own cells. The first major organ, the bladder, was grown in 2007, the first windpipe in 2009. So far, the only organs that have been grown are relatively simple, involving only a few types of tissues and few structures. Within five years, the first liver and pancreas might be grown, with enormous implications for public health. n.o.bel laureate Walter Gilbert told me that he foresees a time, just a few decades into the future, when practically every organ of the body will be grown from your own cells.
Tissue engineering grows new organs by first extracting a few cells from your body. These cells are then injected into a plastic mold that looks like a sponge shaped in the form of the organ in question. The plastic mold is made of biodegradable polyglycolic acid. The cells are treated with certain growth factors to stimulate cell growth, causing them to grow into the mold. Eventually, the mold disintegrates, leaving behind a perfect organ.
I had the opportunity to visit Anthony Atala"s laboratory at Wake Forest University in North Carolina and witness this miraculous technology firsthand. As I walked through his laboratory, I saw bottles that contained living human organs. I could see blood vessels and bladders; I saw heart valves that were constantly opening and closing because liquids were being pumped through them. Seeing all these living human organs in bottles, I almost felt as if I were walking through Dr. Frankenstein"s laboratory, but there were several crucial differences. Back in the nineteenth century, doctors were ignorant of the body"s rejection mechanism, which makes it impossible to graft new organs. Plus, doctors did not know how to stop the infections that would inevitably contaminate any organ after surgery. So Atala, instead of creating a monster, is opening an entirely new lifesaving medical technology that may one day change the face of medicine.
One future target for his laboratory is to grow a human liver, perhaps within five years. The liver is not that complicated and consists of only a few types of tissue. Lab-grown livers could save thousands of lives, especially those in desperate need of liver transplants. It could also save the lives of alcoholics suffering from cirrhosis. (Unfortunately, it could also encourage people to keep bad habits, knowing that they can get replacement organs for their damaged ones.) If organs of the body, like the windpipe and the bladder, can be grown now, what is to prevent scientists from growing every organ of the body? One basic problem is how to grow the tiny capillaries that provide blood for the cells. Every cell in the body has to be in contact with a blood supply. In addition, there is the problem of growing complex structures. The kidney, which purifies the blood of toxins, is composed of millions of tiny filters, so a mold for these filters is quite difficult to create.
But the most difficult organ to grow is the human brain. Although re-creating 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 Inst.i.tute 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, 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.) 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 Inst.i.tute 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 this 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 pa.s.sed 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 pa.s.sed 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 Inst.i.tutes 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 n.o.bility. 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 n.o.bility, 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 s.e.x cells, so that the repaired gene can be pa.s.sed 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 a.n.a.lyzing 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 a.n.a.lyses 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.