Introduction: The Evolution of

Scientific Medicine

In order to fully appreciate the changes that

nanomedicine and nanodrugs will inevitably bring,

it is useful first to review the history and development

of current medical practice.

A study of the history of "scientific" or Western

medical practice suggests a continuity in certain

aspects of the medical process even since ancient

times. For instance the basic precepts of observation

and diagnosis, followed by treatment can be

seen from ancient time through today. Another

important reason to study the history of medicine

is to gain a deeper appreciation of the long, hard

struggle to improve human health, a struggle that

is expected to advance dramatically in the 21st

century.

20th Century Medicine

The 20th century saw more discoveries and

advances in medical science than all previous centuries

combined. In this period, medicine became

more powerful than ever before as scientists

gained knowledge of matters and processes of illness

that, at the beginning of the century, were still

unknown or mysterious. Unlike earlier eras, 20th

century physicians could actually cure some diseases,

reverse some physical traumas, and save

many lives that could not be saved before.

In the first half of the 20th century, acceptance

of the germ theory of infection and the discovery

of leukocytes led to the rapid emergence of

immunology. This allowed medical scientists to

produce protective vaccines which largely eliminated

many diseases that were previously prevalent

and dangerous, including whooping cough,

measles, and diphtheria . Biochemists were also

able to synthesize vitamins which were recognized

as essential constituents of a healthy diet, thus

allowing the elimination of vitamin deficiency diseases

such as scurvy, rickets, osteomalacia,

beriberi, pellagra, xerophthalmia, nyctalopia, and

pernicious anemia, via dietary supplements. Many

metabolic diseases became treatable due to biochemical

investigations. For example, the discovery

of insulin in 1921 rapidly transformed diabetes

from an invariably and often rapidly fatal disease

into one that could be at least partially controlled,

allowing sufferers many years of good life.

Blood group specification made transfusions

convenient, facilitating dramatic advances in many

branches of medicine, especially surgery. At the

close of the 20th century, heart, lung, heart-lung,

and liver transplants were standard procedures.

Two pivotal events transformed scientific medicine

from a merely rational basis to a molecular

basis, thus laying the groundwork for 21st century

nanomedicine. The first pivotal event was the drug

revolution, among which the most useful and spectacular

were the antibiotics introduced between

1935-1945 and widely used ever since.

Antibiotics are significant because they actively

interfere with microbial metabolism and growth at

the molecular level. The first antibiotic drugs were

the sulphonamides, in 1935. Then penicillin

became available in the 1940s, initially in very

small quantities, then mass-produced by Pfizer during

and after World War II. For the first time, physicians

had true cures for many diseases, especially

the most common bacterial diseases. Antifungal,

anti-parasitic, and antiviral drugs of more limited

effectiveness soon followed.

The 20th century also produced drugs that

altered mood and levels of consciousness.

Barbiturates were first introduced in 1903 followed

by phenobarbitone in 1912 and Evipan, the barbiturate

anesthetic, in 1932. By mid-century these highly

addictive drugs began to be replaced by the

somewhat less-addictive benzodiazepines, including

Valium and Librium. Tranquilizers, largely the

phenothiazines such as chlorpromazine and antimanics

such as lithium carbonate, came to be

widely used in psychiatry as effective medications

for major mental illnesses including schizophrenia

and manic depression.

The second pivotal event was the genetics revolution,

starting with the discovery in 1953 of the

information-carrying double-helix structure of DNA

by Francis Crick and John B. Watson followed in

the 1980s by the ability to chemically read the

genetic code, isolate specific genes and clone them

for further study.

Thus the late 20th century is best regarded as

the molecular age of basic biological science.

DNA sequencing techniques permitted precise identification

of the exact structural alteration of the gene in

an increasing number of hereditary diseases. Gene

therapy — both pharmacologic modification of

specific gene action and physical replacement of

damaged genetic segments — became possible in

experimental systems.

However, the greatest medical revolution of all

awaits the ability to engineer and fabricate whole

devices and systems at the molecular scale. Along

this course lies nanotechnology and molecular

manufacturing from which nanodrugs and

nanomedicine will inevitably spring.

21st Century Medicine

It is always somewhat presumptuous to

attempt to predict the future, but in this case we

are on solid ground because of the groundwork

established in the last two decades of the 20th century.

First, antibiotics that interfered with

pathogens at the molecular level were introduced.

Next, the ongoing revolutions in genomics, proteomics

and bioinformatics provided detailed and

precise knowledge of the workings of the human

body at the molecular level. Our understanding of

life advanced from organs, to tissues, to cells, and

finally to molecules, in the 20th century. In the first

two years of the 21st century the entire human

genome was mapped. This map will inferentially

incorporate a complete catalog of all human proteins,

lipids, carbohydrates, nucleoproteins and

other molecules, including full sequence, structure,

and much functional information. Only some systemic

functional knowledge, particularly neurological,

is lacking.

In the coming century, the principal focus will

shift from medical science to medical engineering.

Nanodrugs and nanomedicine will involve designing

and building a vast proliferation of incredibly

efficacious molecular devices, and then deploying

these devices in patients to establish and maintain

a continuous state of human healthiness.

In brief, nanodrugs and nanmedicine will

employ molecular machine systems to address

medical problems, and will use molecular knowledge

to maintain human health at the molecular

scale.

In the 21st century, new tools for nanodrugs

and nanomedical testing and observation will

include clinical in vivo cytography; real-time wholebody

microbiotic surveys; immediate access to laboratory-

quality data on the patient (e.g. blood tests

such as blood counts, dissolved gases and solutes,

vitamin and ion assays); physiological function and

challenge tests; tissue composition including direct

organelle counts in specified tissue populations;

quantitative flowcharts of in cyto secondary messenger

molecules, extracellular hormones and neuropeptides;

per-compartment cytoglucose inventories;

and so forth. Before a proper diagnosis can be

made, the physician will also establish the patient's

personal functional and structural baseline against

which any deviations can be noted and corrected,

in keeping with the normative model of disease

Nanotechnology & NanoDrugs in Medicine

Developments in nanotechnology and nanodrugs

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

and nanodrugs 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 nanodrugs

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.

NanoDrugs & Cancer

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 nanodrugs, 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 nanodrugs

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 nanodrugs and nanomedicine .

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, nanodrugs will stimulate

and guide the body's own construction and

repair mechanisms to restore healthy tissue.

NanoDrugs & Heart Disease

At the opposite end of the spectrum, nanodrugs

and medicines 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.

Nano-drugs working in the bloodstream could

nibble away at atherosclerotic deposits, widening

the affected blood vessels. Nano-drugs and medicines

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, nanodrugs 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.

NanoDrugs & Arthritis

Nanodrugs 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 the nanodrug

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 nanodrugs to clean pockets, join tissues, and

guide regrowth. Even missing teeth could be

regrown, with enough control over cell behavior.

NanoDrugs In The Fight Against Obesity

Perhaps the great promise that nanodrugs and

nanomedicine have to offer is the treatment and

management of metabolic regulation including 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 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. Nanodrugs

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.

NanoDrugs & 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 nanodrugs and 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.

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About The Author

DR. FLOYD E. TAUB,

MD is among today’s most

acclaimed biomedical

researchers. His work in the

development of NanoDrugs™

caps a distinguished career on

the forefront of cutting-edge

medicine. Dr. Taub worked for

years in the Laboratory of Biochemistry at the

National Institutes of Health (NIH), where his

breakthroughs included the first array image processing

system to quantify DNA hybridization, and

plus other achievements in the field of autoimmune

diseases. He went on to found two highly successful

biotech firms.

Dr. Taub is a graduate of the Northwestern

University School of Medicine, and trained in

pathology at the University of Colorado. He is

Board Certified in Anatomic Pathology, and

licensed in Maryland and California.