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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