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Unbounding the Future:

the Nanotechnology Revolution


Chapter 10

Nanomedicine

Our bodies are filled with intricate, active molecular structures. When those structures are damaged, health suffers. Modern medicine can affect the workings of the body in many ways, but from a molecular viewpoint it remains crude indeed. Molecular manufacturing can construct a range of medical instruments and devices with far greater abilities. The body is an enormously complex world of molecules. With nanotechnology to help, we can learn to repair it.

The Molecular Body

To understand what nanotechnology can do for medicine, we need a picture of the body from a molecular perspective. The human body can be seen as a workyard, construction site, and battleground for molecular machines. It works remarkably well, using systems so complex that medical science still doesn't understand many of them. Failures, though, are all too common.

The Body As Workyard

Molecular machines do the daily work of the body. When we chew and swallow, muscles drive our motions. Muscle fibers contain bundles of molecular fibers that shorten by sliding past one another.

In the stomach and intestines, the molecular machines we call digestive enzymes break down the complex molecules in foods, forming smaller molecules for use as fuel or as building blocks. Molecular devices in the lining of the digestive tract carry useful molecules to the bloodstream.

Meanwhile, in the lungs, molecular storage devices called hemoglobin molecules pick up oxygen. Driven by molecular fibers, the heart pumps blood laden with fuel and oxygen to cells. In the muscles, fuel and oxygen drive contraction based on sliding molecular fibers. In the brain, they drive the molecular pumps that charge nerve cells for action. In the liver, they drive molecular machines that build and break down a whole host of molecules. And so the story continues through all the work of the body.

Yet each of these functions sometimes fails, whether through damage or inborn defect.

The Body As Construction Site

In growing, healing, and renewing tissue, the body is a construction site. Cells take building materials from the bloodstream. Molecular machinery programmed by the cell's genes uses these materials to build biological structures: to lay down bone and collagen, to build whole new cells, to renew skin, and to heal wounds.

With the exception of tooth fillings and other artificial implants, everything in the human body is constructed by molecular machines. These molecular machines build molecules, including more molecular machines. They clear away structures that are old or out of place, sometimes using machinery like digestive enzymes to take structures apart.

During tissue construction, whole cells move about, amoebalike: extending part of themselves forward, attaching, pulling their material along, and letting go of the former attachment site behind them. Individual cells contain a dynamic pattern of molecules made of components that can break down but can also be replaced. Some molecular machines in the cell specialize in digesting molecules that show signs of damage, allowing them to be replaced by fresh molecules made according to genetic instructions. Components inside cells form their complex patterns by self-assembly, that is, by sticking to the proper partners.

Failures in construction increase as we age. Teeth wear and crack and aren't replaced; hair follicles stop working; skin sags and wrinkles. The eye's shape becomes more rigid, ruining close vision. Younger bodies can knit together broken bones quickly, making them stronger than before, but osteoporosis can make older bones so fragile that they break under minor stress.

Sometimes construction is botched from the beginning due to a missing or defective genetic code. In hemophilia, bleeding fails to stop due to the lack of blood clotting factor. Construction of muscle tissue is disrupted in 1 in 3,300 male births by muscular dystrophy, in which muscles are gradually replaced by scar tissue and fat; the molecule "dystrophin" is missing. Sickle cell anemia results from abnormal hemoglobin molecules.

Paraplegics and quadriplegics know that some parts of the body don't heal well. The spinal cord is an extreme—and extremely serious—case, but scarring and improper regrowth of tissues result from many accidents. If tissues always regrew properly, injury would do no permanent physical damage.

The Body As Battlefield

Assaults from outside the body turn it into a battlefield where the aggressors sometimes get the upper hand. From parasitic worms to protozoa to fungi to bacteria to viruses, organisms of many kinds have learned to live by entering the body and using their molecular machinery to build more of themselves from the body's building blocks. To meet this onslaught, the body musters the defenses of the immune system—an armada of its own molecular machines. Your body's own amoebalike white blood cells patrol the bloodstream and move out into tissues, threading their way between other cells, searching for invaders.

How can the immune system distinguish the hundreds of kinds of cells that should be in the body from the invading cells and viruses that shouldn't? This has been the central question of the complex science of immunology. The answer, as yet only partially understood, involves a complex interplay of molecules that recognize other molecules by sticking to them in a selective fashion. These include free-floating antibodies—which are a bit like bumbling guided missiles—and similar molecules that are bound to the surface of white blood cells and other cells of the immune system, enabling them to recognize foreign surfaces on contact.

This system makes life possible, defending our bodies from the fate of meat left at room temperature. Still, it lets us down in two basic ways.

First, the immune system does not respond to all invaders, or responds inadequately. Malaria, tuberculosis, herpes, and AIDS all have their strategies for evading destruction. Cancer is a special case in which the invaders are altered cells of the body itself, sometimes successfully masquerading as healthy cells and escaping detection.

Second, the immune system sometimes overresponds, attacking cells that should be left alone. Certain kinds of arthritis, as well as lupus and rheumatic fever, are caused by this mistake. Between attacking when it shouldn't and not attacking when it should, the immune system often fails, causing suffering and death.

Medicine Today

When the body's working, building, and battling goes awry, we turn to medicine for diagnosis and treatment. Today's methods, though, have obvious shortcomings.

Crude Methods

Diagnostic procedures vary widely, from asking a patient questions, through looking at X-ray shadows, through exploratory surgery and the microscopic and chemical analysis of materials from the body. Doctors can diagnose many ills, but others remain mysteries. Even a diagnosis does not imply understanding: doctors could diagnose infections before they knew about germs, and today can diagnose many syndromes with unknown causes. After years of experimentation and untold loss of life, they can even treat what they don't understand—a drug may help, though no one knows why.

Leaving aside such therapies as heating, massaging, irradiating, and so forth, the two main forms of treatment are surgery and drugs. From a molecular perspective, neither is sophisticated.

Surgery is a direct, manual approach to fixing the body, now practiced by highly trained specialists. Surgeons sew together torn tissues and skin to enable healing, cut out cancer, clear out clogged arteries, and even install pacemakers and replacement organs. It's direct, but it can be dangerous: anesthetics, infections, organ rejection, and missed cancer cells can all cause failure. Surgeons lack fine-scale control. The body works by means of molecular machines, most working inside cells. Surgeons can see neither molecules nor cells, and can repair neither.

Drug therapies affect the body at the molecular level. Some therapies—like insulin for diabetics—provide materials the body lacks. Most—like antibiotics for infections—introduce materials no human body produces. A drug consists of small molecules; in our simulated molecular world, many would fit in the palm of your hand. These molecules are dumped into the body (sometimes directed to a particular region by a needle or the like), where they mix and wander through blood and tissue. They typically bump into other molecules of all sorts in all places, but only stick to and affect molecules of certain kinds.

Antibiotics like penicillin are selective poisons. They stick to molecular machines in bacteria and jam them, thus fighting infection. Viruses are a harder case because they are simpler and have fewer vulnerable molecular machines. Worms, fungi, and protozoa are also difficult, because their molecular machines are more like those found in the human body, and hence harder to jam selectively. Cancer is the most difficult of all. Cancerous growths consist of human cells, and attempts to poison the cancer cells typically poison the rest of the patient as well.

Other drug molecules bind to molecules in the human body and modify their behavior. Some decrease the secretion of stomach acid, others stimulate the kidneys, many affect the molecular dynamics of the brain. Designing drug molecules to bind to specific targets is a growth industry today, and provides one of the many short-term payoffs that is spurring developments in molecular engineering.

Limited Abilities

Current medicine is limited both by its understanding and by its tools. In many ways, it is still more an art than a science. Mark Pearson of Du Pont points out, "In some areas, medicine has become much more scientific, and in others not much at all. We're still short of what I would consider a reasonable scientific level. Many people don't realize that we just don't know fundamentally how things work. It's like having an automobile, and hoping that by taking things apart, we'll understand something of how they operate. We know there's an engine in the front and we know it's under the hood, we have an idea that it's big and heavy, but we don't really see the rings that allow pistons to slide in the block. We don't even understand that controlled explosions are responsible for providing the energy that drives the machine."

Better tools could provide both better knowledge and better ways to apply that knowledge for healing. Today's surgery can rearrange blood vessels, but is far too coarse to rearrange or repair cells. Today's drug therapies can target some specific molecules, but only some, and only on the basis of type. Doctors today can't affect molecules in one cell while leaving identical molecules in a neighboring cell untouched because medicine today cannot apply surgical control to the molecular level.

Nanotechnology in Medicine

Developments in nanotechnology will result in improved medical sensors. As protein chemist Bill DeGrado notes, "Probably the first use you may see would be in diagnostics: being able to take a tiny amount of blood from somebody, just a pinprick, and diagnose for a hundred different things. Biological systems are already able to do that, and I think we should be able to design molecules or assemblies of molecules that mimic the biological system."

In the longer term, though, the story of nanotechnology in medicine will be the story of extending surgical control to the molecular level. The easiest applications will be aids to the immune system, which selectively attack invaders outside tissues. More difficult applications will require that medical nanomachines mimic white blood cells by entering tissues to interact with their cells. Further applications will involve the complexities of molecular-level surgery on individual cells.

As we look at how to solve various problems, you'll notice that some that look difficult today will become easy, while others that might seem easier turn out to be more difficult. The seeming difficulty of treating disorders is always changing: Once polio was frequent and incurable, today it is easily prevented. Syphilis once caused steady physical decline leading to insanity and death; now it is cured with a shot.

Athlete's foot has never been seen as a great scourge, yet it remains hard to cure. Likewise with the common cold. This pattern will continue: Deadly diseases may be easily dealt with, while minor ills remain incurable, or vice versa. As we will see, a mature nanotechnology-based medicine will be able to deal with almost any physical problem, but the order of difficulty may be surprising. Nature cares nothing for our sense of appropriateness. Horribleness and difficulty just aren't the same thing.

Working Outside Tissues

One approach to nanomedicine would make use of microscopic mobile devices built using molecular-manufacturing equipment. These would resemble the ecosystem protectors and mobile cleanup machines discussed in the last chapter. Like them, they would either be biodegradable, self-collecting, or collected by something else once they were done working. Like them, they would be more difficult to develop than simple, fixed-location nanomachines, yet clearly feasible and useful. Development will start with the simpler applications, so let's begin by looking at what can be done without entering living tissues.

The skin is the body's largest organ, and its exposed position subjects it to a lot of abuse. This exposed position, though, also makes it easier to treat. Among the earlier applications of molecular manufacturing may be those popular, quasimedical products, cosmetics. A cream packed with nanomachines could do a better and more selective job of cleaning than any product can today. It could remove the right amount of dead skin, remove excess oils, add missing oils, apply the right amounts of natural moisturizing compounds, and even achieve the elusive goal of "deep pore cleaning" by actually reaching down into pores and cleaning them out. The cream could be a smart material with smooth-on, peel-off convenience.

The mouth, teeth, and gums are amazingly troublesome. Today, daily dental care is an endless cycle of brushing and flossing, of losing ground to tooth decay and gum disease as slowly as possible. A mouthwash full of smart nanomachines could do all that brushing and flossing do and more, and with far less effort—making it more likely to be used.

This mouthwash would identify and destroy pathogenic bacteria while allowing the harmless flora of the mouth to flourish in a healthy ecosystem. Further, the devices would identify particles of food, plaque, or tartar, and lift them from teeth to be rinsed away. Being suspended in liquid and able to swim about, devices would be able to reach surfaces beyond reach of toothbrush bristles or the fibers of floss. As short-lifetime medical nanodevices, they could be built to last only a few minutes in the body before falling apart into materials of the sort found in foods (such as fiber). With this sort of daily dental care from an early age, tooth decay and gum disease would likely never arise. If under way, they would be greatly lessened.

Going beyond this superficial treatment would involve moving among and modifying cells. Let's consider what can be done with this treatment inside the body, but outside the body's tissues. The bloodstream carries everything from nutrients to immune-system cells, with chemical signals and infectious organisms besides.

FIGURE 11: IMMUNE MACHINES

Medical nanodevices could augment the immune system by finding and disabling unwanted bacteria and viruses. The immune device in the foreground has found a virus; the other has touched a red blood cell. Adapted from Scientific American, January 1988.

Here, it is useful to think in terms of medical nanomachines that resemble small submarines, like the ones in Figure 11. Each of these is large enough to carry a nanocomputer as powerful as a mid-1980s mainframe, along with a huge database (a billion bytes), a complete set of instruments for identifying biological surfaces, and tools for clobbering viruses, bacteria, and other invaders. Immune cells, as we've seen, travel through the bloodstream checking surfaces for foreignness and—when working properly—attacking and eliminating what should not be there. These immune machines would do both more and less. With their onboard sensors and computers, they will be able to react to the same molecular signals that the immune system does, but with greater discrimination. Before being sent into the body on their search-and-destroy mission, they could be programmed with a set of characteristics that lets them clearly distinguish their targets from everything else. The body's immune system can respond only to invading organisms that had been encountered by that individual's body. Immune machines, however, could be programmed to respond to anything that had been encountered by world medicine.

Immune machines can be designed for use in the bloodstream or the digestive tract (the mouthwash described above used these abilities in hunting down harmful bacteria). They could float and circulate, as antibiotics do, while searching for intruders to neutralize. To escape being engulfed by white blood cells making their own patrols, immune machines could display standard molecules on their surface-molecules the body knows and trusts already—like a fellow police officer wearing a familiar uniform.

When an invader is identified, it can be punctured, letting its contents spill out and ending its effectiveness. If the contents were known to be hazardous by themselves, then the immune machine could hold on to it long enough to dismantle it more completely.

How will these devices know when it's time to depart? If the physician in charge is sure the task will be finished within, say, one day, the devices prescribed could be of a type designed to fall apart after twenty-four hours. If the treatment time needed is variable, the physician could monitor progress and stop action at the appropriate time by sending a specific molecule—aspirin perhaps, or something even safer—as a signal to stop work. The inactivated devices would then be cleared out along with other waste eliminated from the body.

Working Within Tissues

In most parts of the body, the finest blood vessels, capillaries, pass within a few cell diameters of every point. Certain white blood cells can leave these vessels to move among the neighboring cells. Immune machines and similar devices, being even smaller, could do likewise. In some tissues, this will be easy, in some harder, but with careful design and testing, essentially any point of the body should become accessible for healing repairs.

Merely fighting organisms in the bloodstream would be a major advance, cutting their numbers and inhibiting their spread. Roving medical nanomachines, though, will be able to hunt down invaders throughout the body and eliminate them entirely.

Eliminating Invaders

Cancers are a prime example. The immune system recognizes and eliminates most potential cancers, but some get by. Physicians can recognize cancer cells by their appearance and by molecular markers, but they cannot always remove them all through surgery, and often cannot find a selective poison. Immune machines, however, will have no difficulty identifying cancer cells, and will ultimately be able to track them down and destroy them wherever they may be growing. Destroying every cancer cell will cure the cancer.

Bacteria, protozoa, worms, and other parasites have even more obvious molecular markers. Once identified, they could be destroyed, ridding the body of the disease they cause. Immune machines thus could deal with tuberculosis, strep throat, leprosy, malaria, amoebic dysentery, sleeping sickness, river blindness, hookworm, flukes, candida, valley fever, antibiotic-resistant bacteria, and even athlete's foot. All are caused by invading cells or larger organisms (such as worms). Health officials estimate that parasitic diseases, common in the Third World, affect more than one billion people. For many of these diseases, no satisfactory drug treatment exists. All can eventually be eliminated as threats to human health by a sufficiently advanced form of nanomedicine.

Herding Cells

Destroying invaders will be helpful, but injuries and structural problems pose other problems. Truly advanced medicine will be able to build up and restructure tissues. Here, medical nanodevices can stimulate and guide the body's own construction and repair mechanisms to restore healthy tissue.

What is healthy tissue? It consists of normal cells in normal patterns in a normal matrix all organized in a normal relationship to the surrounding tissues. Surgeons today (with their huge, crude tools) can fix some problems at the tissue level. A wound disrupts the healthy relationship between two different pieces of tissue, and surgical glues and sutures can partly remedy this problem by holding the tissues in a position that promotes healing. Likewise, coronary artery bypass surgery brings about a more healthy overall configuration of tissues—one that provides working plumbing to supply blood to the heart muscle. Surgeons cut and stitch, but then they must rely on the tissue to heal its wounds as best it can.

Healing establishes healthy relationships on a finer scale. Cells must divide, grow, migrate, and fill gaps. They must reorganize to form properly connected networks of fine blood vessels. And cells must lay down materials to form the structural, intercellular matrix—collagen to provide the proper shape and toughness, or mineral grains to provide rigidity, as in bone. Often, they lay down unwanted scar tissue instead, blocking proper healing.

With enough knowledge of how these processes work (and nanoinstruments can help gather that knowledge) and with good enough software to guide the process—a more difficult challenge—medical nanomachines will be able to guide this healing process. The problem here is to guide the motion and behavior of a mob of active, living cells—a process that can be termed cell herding.

Cells respond to a host of signals from their environment: to chemicals in the surrounding fluids, to signal molecules on neighboring cells, and to mechanical forces applied to them. Cell-herding devices would use these signals to spur cell division where it is needed and to discourage it where it is not. They would nudge cells to encourage them to migrate in appropriate directions, or would simply pick them up, move them along, and deliver them where needed, encouraging them to nestle into a proper relationship with their neighbors. Finally, they would stimulate cells to surround themselves with the proper intercellular-matrix materials. Or—like the owner of a small dog who, on a cold day, wraps the beast in a wool jacket—they would directly build the proper surrounding structures for the cell in its new location.

In this way, cooperating teams of cell-herding devices could guide the healing or restructuring of tissues, ensuring that their cells form healthy patterns and a healthy matrix and that those tissues have a healthy relationship to their surroundings. Where necessary, cells could even be adjusted internally, as we will discuss later.

Rebuilding Tissues

Again, skin provides easy examples and may be a natural place to start in practice. People often want hair where they have bare skin, and bare skin where they have hair. Cell herding machines could move or destroy hair follicle cells to eliminate an unwanted hair, or grow more of the needed cells and arrange them into a working follicle where a hair is desired. By adjusting the size of the follicle and the properties of some of the cells, hairs could be made coarser, or finer, or straighter, or curlier. All these changes would involve no pain, toxic chemicals, or stench. Cell-herding devices could move down into the living layers of skin, removing unwanted cells, stimulating the growth of new cells, narrowing unnaturally prominent blood vessels, insuring good circulation by guiding the growth of any needed normal blood vessels, and moving cells and fibers around so as to eliminate even deep wrinkles.

At the opposite end of the spectrum, cell herding will revolutionize treatment of life-threatening conditions. For example, the most common cause of heart disease is reduced or interrupted supply of blood to the heart muscle. In pumping oxygenated blood to the rest of the body, the heart diverts a portion for its own use though the coronary arteries. When these blood vessels become constricted, we speak of coronary-artery disease. When they are blocked, causing heart muscle tissue to die, we speak of someone "having a coronary," another term for heart attack.

Devices working in the bloodstream could nibble away at atherosclerotic deposits, widening the affected blood vessels. Cell herding devices could restore artery walls and artery linings to health, by ensuring that the right cells and supporting structures are in the right places. This would prevent most heart attacks.

But what if a heart attack has already destroyed muscle tissue, leaving the patient with a scarred, damaged, and poorly functioning heart? Once again, cell-herding devices could accomplish repairs, working their way into the scar tissue and removing it bit by bit, replacing it with fresh muscle fiber. If need be, this new fiber can be grown by applying a series of internal molecular stimuli to selected heart muscle cells to "remind" them of the instructions for growth that they used decades earlier during embryonic development.

Cell-herding capabilities should also be able to deal with the various forms of arthritis. Where this is due to attacks from the body's own immune system, the cells producing the damaging antibodies can be identified and eliminated. Then a cell-herding system would work inside the joint where it would remove diseased tissues, calcified spurs, and so forth, then rework patterns of cells and intercellular material to form a healthy, smoothly working, and pain-free joint. Clearly, learning to repair hearts and learning to repair joints will have some basic technologies in common, but much of the research and development will have to be devoted to specific tissues and specific circumstances. A similar process—but again, specially adapted to the circumstances at hand—could be used to strengthen and reshape bone, correcting osteoporosis.

In dentistry, this sort of process could be used to fill cavities, not with amalgam, but with natural dentin and enamel. Reversing the ravages of periodontal disease will someday be straightforward, with nanomedical devices to clean pockets, join tissues, and guide regrowth. Even missing teeth could be regrown, with enough control over cell behavior.

Working on Cells

Moving through tissues without leaving a trail of disruption will require devices able to manipulate and direct the motions of cells, and to repair them. Much remains to be learned—and will be easy to learn with nanoscale tools—but today's knowledge of cells is enough for a start on the problem of how to do surgery on cells.

Cell biology is a booming field, even today. Cells can be made to live and grow in laboratory cultures if they are placed in a liquid with suitable nutrients, oxygen, and the rest. Even with today's crude techniques, much has been learned about how cells respond to different chemicals, to different neighbors, and even to being poked and cut with needles. Conducting a rough sort of surgery on individual cells has been routine for many years in scientific laboratories.

Today, researchers can inject new DNA into cells using a tiny needle; small punctures in a cell membrane automatically reseal. But both these techniques use tools that on a cellular scale are large and clumsy—like doing surgery with an ax or a wrecking ball, instead of a scalpel. Nano-scale tools will enable medical procedures involving delicate surgery on individual cells.

Eliminating Viruses by Cell Surgery

Some viral diseases will respond to treatments that destroy viruses in the nose and throat, or in the bloodstream. The flu and common cold are examples. Many others would be greatly improved by this, but not eliminated. All viruses work by injecting their genes into a cell and taking over its molecular machinery, using it to produce more viruses. This is part of what makes viral illnesses so hard to treat—most of the action is performed by the body's own molecular machines, which can't be interfered with on a wholesale basis. When the immune system deals with a viral illness, it both attacks free virus particles before they enter cells, and attacks infected cells before they can churn out too many more virus particles.

Some viruses, though, insert their genes among the genes of the cell, and lay low. The cell can seem entirely normal to the immune system, for months or years, until the viral genes are triggered into action and begin the infective process anew. This pattern is responsible for the persistence of herpes infections, and for the slow, deadly progress of AIDS.

These viruses can be eliminated by molecular-level cellular surgery. The required devices could be small enough to fit entirely within the cell, if need be. Greg Fahy, who heads the Organ Cryopreservation Project at the American Red Cross's Jerome Holland Transplantation Laboratory, writes, "Calculations imply that molecular sensors, molecular computers, and molecular effectors can be combined into a device small enough to fit easily inside a single cell and powerful enough to repair molecular and structural defects (or to degrade foreign structures such as viruses and bacteria) as rapidly as they accumulate. . . .There is no reason such systems cannot be built and function as designed."

Equally well, a cell surgery device located outside a cell could reach through the membrane with long probes. At the ends of the probes would be tools and sensors along with, perhaps, a small auxiliary computer. These would be able to reach through multiple membranes, unpackage and uncoil DNA, read it, repackage it, and recoil it, "proofreading" the DNA by comparing the sequences in one cell to the sequences of other cells.

On reading the genetic sequence spelling out the message of the AIDS virus, a molecular surgery machine could be programmed to respond like an immune machine, destroying the cell. But it would seem to make more sense simply to cut out the AIDS virus genes themselves, and reconnect the ends as they were before infection. By doing this, and killing any viruses found in the cell, the procedure would restore the cell to health.

Molecular Repairs

Cells are made of billions of molecules, each built by molecular machines. These molecules self-assemble to form larger structures, many in dynamic patterns, perpetually disintegrating and reforming. Cell-surgery devices will be able to make molecules of sorts that may be lacking, while destroying molecules that are damaged or present in excess. They will be able not only to remove viral genes, but to repair chemical and radiation-caused damage to the cell's own genes. Advanced cell surgery devices would be able to repair cells almost regardless of their initial state of damage.

By activating and inactivating a cell's genes, they will be able to stimulate cell division and guide what types of cells are formed. This will be a great aid to cell herding and to healing tissues.

As surgeons today rely on the spontaneous, self-organizing ability of cells and tissues to join and heal the parts they manipulate, so cell-surgery devices will rely on the spontaneous self-organizing capabilities of molecules to join and "heal" the parts they put together. Healing of a surgical wound involves sweeping up dead cells, growing new cells, and a slow and genuinely painful process of tissue reorganization. In contrast, the joining of molecules is almost instantaneous and occurs on a scale far below that of the most sensitive pain receptor. "Healing" will not begin after the repair devices have done their work, as it does in conventional surgery: rather, when they complete their work, the tissue will have been healed.

Healing Body and Limb

The ability to herd cells and to perform molecular repairs and cell surgery will open new vistas for medicine. These abilities apply on a small scale, but their effects can be large scale.

Correcting Chemistry

In many diseases, the body as a whole suffers from misregulation of the signaling molecules that travel through its fluids. Many are rare: Cushing's disease, Grave's disease, Paget's disease, Addison's disease, Conn's syndrome, Prader-Labhart-Willi syndrome. Others are common: millions of older women suffer from osteoporosis, the weakening of bones that can accompany lowered estrogen levels.

Diabetes kills frequently enough to rank in the top ten causes of death in the United States; the number of individuals known to have it doubles every fifteen years. It is the leading cause of blindness in the United States, with other complications including kidney damage, cataracts, and cardiovascular damage. Today's molecular medicine tries to solve these troubles by supplying missing molecules: diabetics inject additional insulin. While helpful, this doesn't cure the disease or eliminate all symptoms. In an era of molecular surgery, physicians could choose instead to repair the defective organ, so it can regulate its own chemicals again, and to readjust the metabolic properties of other cells in the body to match. This would be a true healing, far better than today's partial fix.

Only now are researchers making progress on another frequent problem of metabolic regulation: obesity. Once this was thought to have one simple cause (consuming excess calories) and one main result (greater roundness than favored by today's aesthetics), but both assumptions proved wrong. Obesity is a serious medical problem, increasing the risk of diabetes mellitus, osteoarthritis, degenerative diseases of the heart, arteries, and kidneys, and shortening life expectancy. And the supposed cause, simple overeating, has been shown to be incorrect—something dieters had always suspected, as they watched thinner colleagues gorge and yet gain no weight.

The ability to lay in stores of fat was a great benefit to people once upon a time, when food supplies were irregular, nomadism and marauding bands made food storage difficult and risky, and starvation was a common cause of death. Our bodies are still adapted to that world, and regulate fat reserves accordingly. This is why dieting often has perverse effects. The body, when starved, responds by attempting to build up greater reserves of fat at its next opportunity. The main effect of exercise in weight reduction isn't to burn up calories, but to signal the body to adapt itself for efficient mobility.

Obesity therefore seems to be a matter of chemical signals within the body, signals to store fat for famine or to become lean for motion. Nanomedicine will be able to regulate these signals in the bloodstream, and to adjust how individual cells respond to them in the body. The latter would even make possible the elusive "spot reduction program" to reshape the distribution of body fat.

Here, as with many potential applications of nanotechnology, the problem may be solved by other means first. Some problems, though, will almost surely require nanomedicine.

New Organs and Limbs

So far we've seen how medical nanotechnology would be used in the simpler applications outside tissues—such as in the blood—then inside tissues, and finally inside cells. Consider how these abilities will fit together for victims of automobile and motorcycle accidents.

Nanomanufactured medical devices will be of dramatic value to those who have suffered massive trauma. Take the case of a patient with a crushed or severed spinal cord high in the back or in the neck. The latest research gives hope that when such patients are treated promptly after the injury, paralysis may be at least partially avoidable, sometimes. But those whose injuries weren't treated—including virtually all of today's patients—remain paralyzed. While research continues on a variety of techniques for attempting to aid a spontaneous healing process, prospects for reversing this sort of damage using conventional medicine remain bleak.

With the techniques discussed above, it will become possible to remove scar tissue and to guide cell growth so as to produce healthy arrangements of the cells on a microscopic scale. With the right molecular-scale poking and prodding of the cell nucleus, even nerve cells of the sorts found in the brain and spinal cord can be induced to divide. Where nerve cells have been destroyed, there need be no shortage of replacements. These technologies will eventually enable medicine to heal damaged spinal cords, reversing paralysis.

The ability to guide cell growth and division and to direct the organization of tissues will be sufficient to regrow entire organs and limbs, not merely to repair what has been damaged. This will enable medicine to restore physical health despite the most grievous injuries.

If this seems hard to believe, recall that medical advances have shocked the world before now. To those in the past, the idea of cutting people open with knives painlessly would have seemed miraculous, but surgical anesthesia is now routine. Likewise with bacterial infections and antibiotics, with the eradication of smallpox, and the vaccine for polio: Each tamed a deadly terror, and each is now half-forgotten history. Our gut sense of what seems likely has little to do with what can and cannot be done by medical technology. It has more to do with our habitual fears, including the fear of vain hopes. Yet what amazes one generation seems obvious and even boring to the next. The first baby born after each breakthrough grows up wondering what all the excitement was about.

Besides, nano-scale medicine won't be a cure-all. Consider a fifty-year-old mentally retarded man, with a mind like a two-year-old's, or a woman with a brain tumor that has spread to the point that her personality has changed: How could they be "healed"? No healing of tissues could replace a missed lifetime of adult experience, nor can it replace lost information from a severely damaged brain. The best physicians could do would be to bring the patients to some physically healthy condition. One can wish for more, but sometimes it won't be possible.

First Aid

Throughout the centuries, medicine has been constrained to maintain functioning tissues, since once tissues stop functioning, they can't heal themselves. With molecular surgery to carry out the healing directly, medical priorities change drastically—function is no longer absolutely necessary. In fact, a physician able to use molecular surgery would prefer to operate on nonfunctioning, structurally stable tissue than on tissue that has been allowed to continue malfunctioning until its structure was lost.

Brain tumors are an example: They destroy the brain's structure, and with it the patient's skills, memories, and personality. Physicians in the future should be able to immediately interrupt this process, to stop the functioning of the brain to stabilize the patient for treatment.

Techniques available today can stop tissue function while preserving tissue structure. Greg Fahy, in his work on organ preservation at the American Red Cross, is developing a technique for vitrifying animal kidneys—making them into a low-temperature, crystal-free glass—with the goal of maintaining their structure such that, when brought back to room temperature, they can be transplanted. Some kidneys have been cooled to -30 C, warmed back up, and then functioned after transplantation.

A variety of other procedures can also stabilize tissues on a long-term basis. These procedures enable many cells—but not whole tissues—to survive and recover without help; advanced molecular repair and cell surgery will presumably tip the balance, enabling cells, tissues, and organs to recover and heal. When applied to stabilizing a whole patient, such a condition can be called biostasis. A patient in biostasis can be kept there indefinitely until the required medical help arrives. So in the future, the question "Can this patient be restored to health?" will be answered "Yes, if the patient's brain is intact, and with it the patient's mind."

Sandra Lee Adamson of the National Space Society has her eyes on distant goals. Some have proposed that travel to the stars would take generations, preventing anyone on Earth from ever making the trip. But she notes that biostasis will "give hope to some fearless adventurers who will risk suspension and subsequent reanimation so they can see the stars for themselves."

Plague Insurance

Medical nanotechnologies promise to extend healthy life, but if history is any guide, they may also avert sudden massive death. The word plague is rarely heard today, except in relation to AIDS; it calls up visions of the Black Death of the Middle Ages, when one third of Europe died in 1346-50. A virulent influenza struck in 1918, half lost in the news of the First World War: how many of us realize that it killed at least 20 million? People often act as though plagues were gone for good, as if sanitation and antibiotics had vanquished them. But as doctors are forever telling their patients, antibiotics kill bacteria, but are useless for viruses. The flu, the common cold, herpes, and AIDS—none has a really effective treatment, because all are caused by viruses. In some African countries, as much as 10 percent of the population is estimated to be infected with the AIDS-causing HIV virus. Without a cure soon, the steep rise in deaths from AIDS still lies in the future. AIDS stands as a grim reminder that the great plagues of history are not behind us.

The Threat

New diseases continue to appear today as they have throughout history. Today's population, far larger than that of any previous century, provides a huge, fertile territory for their spread.

Today's transportation systems can spread viruses from continent to continent in a single day. When ships sailed or churned their way across the seas, an infected passenger was likely to show full-blown disease before arrival, permitting quarantine. But few diseases can be guaranteed to show themselves in the hours of a single aircraft flight.

So far as is known, every species of organism, from bacterium to whale, is afflicted with viruses. Animal viruses sometimes "jump the species gap" to infect other animals, or people. Most scientists believe that the ancestors of the AIDS virus could, until recently, infect only certain African monkeys. Then these viruses made the interspecies jump. A similar jump occurred in the 1960s when scientists in West Germany, working with cells from monkeys in Uganda, suddenly fell ill. Dozens were infected, and several died of a disease that caused both blood clots and bleeding, caused by what is now named the Marburg virus. What if the Marburg virus had spread with a sneeze, like influenza or the common cold?

We think of human plagues as a health problem, but when they hit our fellow species, we tend to see them from an environmental perspective. In the late 1980s, over half the harbor-seal population in large parts of the North Sea suddenly died, leading many at first to blame pollution. The cause, though, appears to be a distemper virus that made the jump from dogs. Biologists worry that the virus could infect seal species around the world, since distemper virus can spread by aerosols—that is, by coughing—and seals live in close physical contact. So far its mortality rate has been 60 to 70 percent.

What of AIDS itself: Could it change and give rise to a form able to spread, say, as colds do? Nobel Laureate Howard M. Temin has said, "I think that we can very confidently say that this can't happen." Nobel Laureate Joshua Lederberg, president of Rockefeller University in New York City, replied, "I don't share your confidence about what can and cannot happen." He points out that "there is no reason a great plague could not happen again. . . .We live in evolutionary competition with microbes—bacteria and viruses. There is no guarantee that we will be the survivors."

Our Inadequate Abilities

Bacterial diseases are mostly controllable today. Sanitation limits the ways in which plague can spread. These measures are just good enough to lull us into imagining the problem is solved.

Viruses are common, viruses mutate; some spread through the air, and some are deadly. Plagues show that fast-spreading diseases can be deadly, and effective antiviral drugs are still rare.

The only really effective treatments for viral diseases are preventive, not curative. They work either by preventing exposure, or by exposing the body beforehand to dead or harmless or fragmentary forms of the virus, to prepare the immune system for future exposure. As the long struggle for an AIDS vaccine shows, one cannot count on modern medicine to identify a new virus and produce an effective vaccine within a single month or year or even a single decade. But influenza epidemics spread fast, and Marburg II or AIDS II or something entirely new and deadly may do the same.

Doing Better

The deaths from the next great plague could have begun in a village last week, or could begin next year, or a year before we learn to deal with new viral illnesses promptly and effectively. With luck, the plague will wait until a year after.

Immune machines could be set to kill a new virus as soon as it is identified. The instruments nanotechnology brings will make viral identification easy. Some day, the means will be in place to defend human life against viral catastrophe.

From eliminating viruses to repairing individual cells, improving our control of the molecular world will improve health care. Immune machines working in the bloodstream seem about as complex as some engineering projects human beings have already completed—projects like large satellites. Other medical nanotechnologies seem to be of a higher order of complexity.

On Solving Hard Problems

Somewhere in the progression from relatively simple immune devices to molecular surgery, we've crossed the fuzzy line between systems that teams of clever biomedical engineers could design in a reasonable length of time and ones that might take decades or prove impossibly complex. Designing a nanomachine capable of entering a cell, reading its DNA, finding and removing a deadly viral DNA sequence, and then restoring the cell to normal would be a monumental job. Such tasks are advanced applications of nanotechnology, far beyond mere computers, manufacturing equipment, and half-witted "smart materials."

To succeed within a reasonable number of years, we may need to automate much of the engineering process, including software engineering. Today's best expert systems are nowhere near sophisticated enough. The software must be able to apply physical principles, engineering rules, and fast computation to generate and test new designs. Call it automated engineering.

Automated engineering will prove useful in advanced nanomedicine because of the sheer number of small problems to be solved. The human body contains hundreds of kinds of cells forming a huge number of tissues and organs. Taken as a whole (and ignoring the immune system), the body contains hundreds of thousands of different kinds of molecules. Performing complex molecular repairs on a damaged cell might require solving millions of separate, repetitive problems. The molecular machinery in cell surgery devices will need to be controlled by complex software, and it would be best to be able to delegate the task of writing that software to an automated system. Until then, or until a lot of more conventional design work gets done, nanomedicine will have to focus on simpler problems.

Aging

Where does aging fit in the spectrum of difficulty? The deterioration that comes with aging is increasingly recognized as a form of disease, one that weakens the body and makes it susceptible to a host of other diseases. Aging, in this view, is as natural as smallpox and bubonic plague, and more surely fatal. Unlike bubonic plague, however, aging results from internal malfunctions in the molecular machinery of the body, and a medical condition with so many different symptoms could be complex.

Surprisingly, substantial progress is being made with present techniques, without even a rudimentary ability to perform cell surgery in a medical context. Some researchers believe that aging is primarily the result of a fairly small number of regulatory processes, and many of these have already been shown to be alterable. If so, aging may be tackled successfully before even simple cell repair is available. But the human aging process is not well enough understood to enable a confident projection of this; for example, the number of regulatory processes is not yet known. A thorough solution may well require advanced nanotechnology-based medicine, but a thorough solution seems possible. The result would not be immortality, just much longer, healthier lives for those who want them.

Restoring Species

A challenging problem related to medicine (and to biostasis) is that of species restoration. Today, researchers are carefully preserving samples from species now becoming extinct. In some cases, all they have are tissue samples. For other species, they've been able to save germ cells in the hope that they will be able to implant fertilized eggs into related species and thus bring the (nearly?) extinct species back.

Each cell typically contains the organism's complete genetic information, but what can be done with this? Many researchers today collect samples for preservation thinking only of the implantation scenario: one that they know has already been made to work. Other researchers are taking a broader view: the Center for Genetic Resources and Heritage at the University of Queensland is a leader in the effort. Daryl Edmondson, coordinator of the gene library, explains that the center is unique because it will "actively collect data. Most other libraries simply collate their own collections." Director John Mattick describes it as a "genetic Louvre" and points out that if genes from today's endangered species aren't preserved, "subsequent generations will see we had the technology to keep [DNA] software and will ask why we didn't do it." With this information and the sorts of molecular repair and cell-surgery capabilities we have discussed, lost species can someday be returned to active life again as habitats are restored.

One such center isn't enough: the Queensland center focuses on Australian species (naturally enough) and has limited funds. Besides, anything so precious as the genetic information of an endangered species should be stored in many separate locations for safety. We need to take out an insurance policy on Earth's genetic diversity with a broader network of genetic libraries, concentrating special attention on gathering biological samples from the fast-disappearing rain forests. Scientific study can wait: the urgency of the situation calls for a vacuum-cleaner approach. The Foresight Institute is promoting this effort through its BioArchive Project; interested readers can write to the address at the end of the Afterword.


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