Genes / Diseases / Living Longer-Healthier Lives /
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Excerpts from "Visions : How Science Will
Revolutionize the 21st Century", by Michio Kaku

Hardcover (January 15, 1997)
http://www.amazon.com/exec/obidos/ASIN/0385484984

Paperback (September 15, 1998)
http://www.amazon.com/exec/obidos/ASIN/0385484992
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- - - begin excerpts - - -

... Part Three - The Biomolecular Revolution

... "We used to think the future was in the stars. Now
we know it's in our genes." -James Watson

... It may take many decades after 2020, but eventually
we will understand the intricate web of interactions
between genes.

... The "age genes", which some scientists believe might
control the aging process, may offer the key to increasing
our life span. Eventually doctors might treat aging as a
reversible phenomenon.

And beyond 2050, we may be able to manipulate life
itself.

... If we compare parents and children, or two siblings,
we find that, on average, they differ by about 1/20th of
one percent of their genetic code. ... And if we take two
humans purely at random, then we find that, on the aver-
age, their genetic code differs by about double that amount,
or 1/10th of one percent.

... By computing the "genetic distance" between any two
humans, we can also reconstruct the outline of the human
evolutionary family tree. ... We can now construct the
complete "family tree" of the human race, putting in all
the details that were lost thousands of years ago in pre-
history.

Analyzing just a few proteins and genes already has given
us startling insight into the origin of all the races and peo-
ples of the world. By 2020, when personalized DNA se-
quencing is possible, our ancestral family tree should be
nearly filled in, including all the branches which have been
forgotten for tens of thousands of years.

Not only does the map fill in gaps in the linguistic and
archaeological theories about the origin of humanity, it
even gives the dates at which missing branches in our
family tree diverged from other branches thousands of
years before the first written records.

... Hereditary Diseases: Ancient Scourge

By 2020, the biomolecular revolution may bring another
class of ancient diseases under control: hereditary dis-
eases.

... There are 5,000 human genetic diseases ... Genetic
diseases take a particularly heavy toll among the young,
resulting in one-fifth of all infant mortalities, half of all
miscarriages, and 80 percent of all cases of mental retar-
dation.

Genetic diseases ... if one considers diseases which are
polygenic [caused by more than 1 gene] or have a strong
genetic component (such as cancer, Alzheimer's disease,
diabetes, and cardiovascular disease), ... they account
for fully 75 percent of all deaths in the United States.

Although medicine was helpless for thousands of years
against these ancient diseases, molecular medicine prom-
ises us new therapies and strategies in the battle against
them, and possibly even cures.

However, it is a battle that must be waged indefinitely,
because there is a never-ending struggle between evolution
(which gradually eliminates these harmful genes by natural
selection) and mutations (which are constantly being re-
plenished by random errors, cosmic rays, toxins, environ-
mental contaminations, etc.).

In each generation, a few hundred mutations occur in the
DNA of each one of us. If we assume that a small percent-
age of these are harmful, then perhaps two or three harm-
ful genes creep into our bodies by mutation. Thus perhaps
10 billion new harmful genes enter the human gene pool
every generation. As a result, the battle against genetic
disease will never end.

... Historically, the most feared hereditary disease is Hunt-
ington's disease, which has long been associated with
witchcraft and devil worship ... Families of victims were
mercilessly harassed and exiled into camps as if they were
lepers.

Patients with Huntington's gradually lose control of their
muscles and their mind. The body often undergoes violent
convulsions and bizarre dancing movements until it is cov-
ered with black-and-blue spots.

Many die of respiratory problems or starvation, because
their violent flailing is so fierce they cannot be physically
fed. In the United States, it affects some 30,000 people and
150,000 more are at risk.

... Many genetic diseases affect specific races and ethnic
groups:

Cystic fibrosis. This is the most common genetic ailment
[non-polygenic] affecting Caucasians. CF is potentially
a widespread problem, because as many as one in every
25 Caucasians is a carrier. In the white population, it affects
one in 1,800 babies and strikes 35,000 young people in the
United States and Canada.

... CF is a parent's nightmare: the disease thickens the
mucus in children's lungs, which weakens the lungs and
clogs the pancreatic ducts, so the body cannot digest nu-
trients well.

... Tay-Sachs. Fortunately, screening for certain diseases
has brought some genetic defects under control, even
without gene therapy. Tay-Sachs is one example. It af-
fects one in 3,600 Jewish children of mainly Eastern Euro-
pean descent. With this population, as many as one in 30
is a carrier of this disease. Tay-Sachs attacks the nervous
system; children appear normal at birth, but then suffer
progressive mental retardation, blindness, loss of muscle
control, and usually death before age four.

Sickle-cell anemia. This disease strikes 4,000 children in
the United States, mainly African-Americans. Roughly
one in 500 African-Americans has this disease, but as
much as 10 percent of the entire African-American popu-
lation are carriers. It is a chronic disease in Africa, where
120,000 children are born with it each year.

... Here is a brief listing of some of the genetic errors that
have so far been isolated, which reveal how even the tini-
est of misspellings within the human genome can cause
unending suffering.

Huntington's disease. ... This gene is involved in produc-
ing two brain neurotransmitters, acetycholine and gamma
aminobutyric acid. In normal people, there is a repetition
of the triplet CAG, which may repeat 11 to 34 times. In
a diseased patient, the CAG repeats far more than that,
sometimes more than 80 times, and causes dramatically
reduced production of these two chemicals. The longer
the triplet repeats beyond a total of 40, the more severe
the disease.

Cystic fibrosis. ... the gene ... is 250,000 base pairs long.
CF can be caused by the omission of as few as three
base pairs, an infinitesimal fraction of the total. The muta-
tion is caused by the following deletion of nucleotides:

ATCTTT -> ATT

This, in turn, triggers cystic fibrosis by deleting just one
amino acid (phenylalanine) out of the 1,480 amino acids
for which the gene encodes.

Lesch-Nyhan syndrome. This disease is caused by a
single mutation which renders a key gene on the X chrom-
osome, which stretches for 50,000 base pairs, incapable
of producing the enzyme HGPRT.

... Duchenne's muscular dystrophy. In 1986, scientists
finally isolated the gene for Duchenne's, which produces
a protein called dystrophin. It's one of the longest genes
so far isolated, stretching across 2.5 million base pairs.
In fact, its extraordinary length explains its high rate of
mutation.

... Curing defective genes is no trivial task; the body con-
tains 100 trillion cells. However, millions of years of evolu-
tion have created perhaps the most efficient "vector" for
altering these cells: the virus. By first neutralizing a virus
(so it cannot make the patient sick), scientists can insert
the correct gene into the virus, and then insert the virus
into the patient.

... polygenic diseases, diseases caused by more than one
gene. ... One such disease is schizophrenia, which slowly
destroys the mind and spirit of a human being, leaving
him or her at the mercy of disembodied voices. Nature
[magazine] called it "arguably the worst disease affecting
mankind." This disease, which strikes 1 percent of the
human race, uses up 30 percent of all hospital beds in
the country, more than any other disease.

There is a definite genetic link to schizophrenia. However,
the link is weak: for twins, there is a 50 percent chance
that one twin will be schizophrenic if the other twin is,
which means that there is a definite genetic component
to the disease. But the fact that this is not a 100 percent
correlation indicates that many genes are involved, some
of which may be triggered by cues from the environment.

... Molecular Medicine ...

... bacteria and viruses are constantly mutating and evolv-
ing, sometimes millions of times faster than humans, to
evade and overcome our best defenses. Despite the efforts
by modern medicine, infectious diseases, which have been
on the earth for billions of years before humans, will proba-
bly be around for several billion more.

... The powerful convergence of the quantum, computer,
and DNA revolutions is giving birth to a new science,
"molecular medicine," which promises to offer new ways
of combating the challenges posed by these virulent in-
fectious diseases in the twenty-first century.

... One of the missions in the twenty-first century of the
Centers for Disease Control and Prevention ... is to control
the outbreak of viruses, "the greatest threat to the survival
of our species." The outbreak of a "Doomsday Virus,"
such as an airborne AIDS or Ebola virus, could threaten
the very existence of human life.

One of the greatest killers in human history has been the
virus for smallpox. This disease, which probably crossed
over from animals to humans about 10,000 years ago, has
been a deadly killer of humans ever since.

It laid waste to Alexander the Great's army in the fourth
century B.C. and killed Roman emperor Marcus Aurelius.
It has destroyed entire cultures and has torn apart great
empires. As late as the 1960s, it afflicted 10 million people
worldwide and killed more than 2 million people every
year.

[editorial aside - since the publication of this book, it has
become apparent that biotoxins, such as smallpox, remain
a potent threat being that most of the present-day human
population has not been vaccinated against the disease - as
such, current efforts are intense to build-up stockpiles of
vaccine in case they are needed when/if a smallpox attack
is initiated by individuals or entities determined to destroy
human life - end editorial aside]

... The Origins of Viruses

For most of human history, the origin of viral plagues was
a complete mystery, making them extremely difficult to pre-
vent.

... The influenza virus has been one of the great scourges
of humanity. The worldwide pandemic of 1918, for example,
killed over 20 million people, more than the number killed
during World War I.

Fully half the people on the entire planet were affected by
the disease. It killed half a million people in the United States
alone, making it the most deadly demographic catastrophe
in the century. It was so virulent that it actually depressed
the life expectancy in the United States from fifty-two to
thirty-nine years.

... the original 1918 flu virus disappeared without a trace,
leaving molecular biologists unable to determine precisely
why it killed so many millions of people. But in 1997 scien-
tists announced the major discovery that rare samples of
the 1918 flu virus were preserved in old tissue samples
left over from the pandemic ... this may one day save the
lives of millions if they can prevent a disastrous recurrence
of this deadly disease.

... By 2020, we should have an almost complete under-
standing of how viruses evolve and spread, which, in turn,
may help us to defeat one of the greatest challenges of the
twenty-first century: AIDS.

... the number of people in the world infected with AIDS:
21 million people, 42 percent of whom are women.

... Every day, 8,500 more people are infected with the HIV.
Of these, two-thirds are in sub-Saharan African countries.
This translates into a world tragedy for decades to come.

... By analyzing the HIV at the molecular level, scientists
are now explaining the mysteries surrounding AIDS, such
as why it takes ten years to kill its victims and why it is so
difficult to cure.

The HIV, far from being dormant for a decade, wages a
fierce, continuous battle with the body's immune system
from the moment of infection. The body's immune system
destroys the virus at the rate of about a billion particles per
day (about a third of the total).

The virus, in turn, destroys about a billion CD4 helper T
cells per day, which the body tries desperately to replenish.

This ferocious struggle, with literally billions of HIV parti-
cles and immune system helper cells dying each day, goes
on for several years, until the number of helper cells slowly
drops, from 1,000 cells per microliter of blood down to
200, at which point the symptoms for AIDS begin. Death
usually follows within two years.

... "A disease that's in a faraway place today may be in our
own backyard tomorrow. We are certainly not immune."

... The lesson here is that we are swimming in an ocean of
disease. Sitting in our chairs eating dinner, or idly walking
through a park, we are blissfully unaware that there are
millions of germs covering almost every square inch of
our surroundings. Inside our own body there are more
germs than the total number of humans who have ever
walked the earth.

We forget that for billions of years on this planet, our an-
cestors' immune systems waged a silent but relentless war
against disease, developing millions of different molecular
possibilities to destroy these unwelcome invaders.

As our DNA evolved to create new defenses against
these diseases, germs evolved ingenious mechanisms to
penetrate these defenses, in a never-ending dance of life
and death. As one author puts it: "Although man can build
a better mousetrap, nature always seems to build a better
mouse."

Unfortunately, bacteria have the upper hand, since they
can evolve as much in a day as we evolve in a thousand
years, which gives them a decided advantage in evolving
new mechanisms to evade our defenses.

... When doctors of 2020 look back at twentieth-century
science, they will be astonished at the shortsighted, foolish
policies of the past, marveling that doctors in the twentieth
century thought that winning a minor skirmish against bac-
teria was tantamount to winning the war.

The careless and rampant overuse of antibiotics today has
killed off all but the strongest and most resistant bacteria.
Our own bodies have become a Darwinian battleground
where only the nastiest mutant strains of bacteria survive
and thrive.

... Today, there are mutant strains of the pneumonia bac-
teria which are resistant to penicillin, cephalosporin, and
other antibiotics.

[editorial aside - my mother recently contracted a severe
case of pneumonia and died after a 3 week battle with the
disease, despite the intense use of antibiotics and all mea-
sures commensurate with modern medicine - end editorial
aside]

... perhaps the most interesting aspect of the future of
molecular medicine is that aging itself might prove to be
a treatable disease.

To Live Forever?

... "By design, the body should go on forever."
-Elliot Crooke, Stanford University

"I don't want to live forever through my works. I want to
live forever by not dying!" -Woody Allen

... Anyone who has ever stared in a mirror and watched
the inexorable spread of wrinkles, sagging features, and
graying hair has yearned for perpetual youth at some point.

Aging is no fun: it involves a profound loss in muscle
mass, increase in body fat (especially around the waist
in men and in the buttocks in women), weakening of our
bones, decline of our immune system, and loss of vigor.

No matter how rich, powerful, glamorous, or influential
you might be, to confront aging is to confront the reality
of your mortality.

... By rights, however, the body should live forever. Sur-
prisingly, certain organisms, in fact, live indefinitely. Cer-
tain cells, and even animals, routinely defy the laws of
aging and have no measurable life span. So if living for-
ever does not violate any known law of cell biology, then
why can't we stay eternally young?

A number of tantalizing and remarkable discoveries indi-
cate that the genetic and molecular origin of aging may
be within sight.

... From now to 2020, perhaps the best bet in terms of
delaying or maybe reversing some of the diseases and
symptoms of aging will be carefully monitored hormone
treatments.

... After 2020, however, when we have personalized DNA
sequencing, an entirely new avenue will open up-i.e., identi-
fying the fabled "age genes", if, in fact, they exist.

... From 2020 to 2050, yet another promising approach
will open up: growing new organs. ... Eventually, growing
new organs may become as common as heart and kidney
transplants today.

... Not only must science and medicine extend the human
life span; it must also reinvigorate and revitalize our bodies,
so we don't become a nation of nursing home patients.

Animals That Are "Immortal"

... All mammals eventually reach a fixed body size as they
age; however, certain animals which do not have a fixed
body size (such as some lobsters, flounders, sturgeons,
sharks, and alligators) simply increase in body size with
time but show no noticeable sign of aging.

These animals are "immortal" in the sense that their aging
process is so slow that it is either nonexistent or too slow
to be measured reliably in the laboratory.

Many textbooks incorrectly state that these animals have
a finite life span like other animals. These texts confuse
"life expectancy" with "life span." Life expectancy refers
to the average age an organism lives until it dies of disease,
predators, or starvation, whereas life span refers to the
maximum age an organism can live if these external causes
of death are removed.

This is the reason we do not see 500-year-old alligators
the size of houses prowling about - because they have
succumbed to the perils of living in the wild.

However, when these animals are kept in zoos, they are
largely removed from these external factors and simply
grow indefinitely, with almost no diminution of their
physical functions after reaching sexual maturity.

The classic example of this is the flounder. The male
flounder reaches a fixed size and ages normally. How-
ever, the female flounder grows indefinitely and shows
no signs of aging or loss of function with time.

The existence of animals with no fixed life span seems
to indicate that "age genes" do exist. Apparently, the
cells of these animals never lose their vigor or their
ability to reproduce.

... Generations of high school children gasp when they
read Shakespeare's Romeo and Juliet, for they are
amazed to discover that Juliet was only thirteen years
old.

We sometimes forget that, for most of human existence,
our lives were short, miserable, and brutish.

Sadly, for most of human history, we repeated the same
wretched cycle: as soon as we reached puberty, we were
expected to toil or hunt with our elders, find a mate and
produce children. We would then have a large number of
them, with most of them dying in childbirth.

... "It is astonishing to realize that the human species
survived hundreds of thousands of years, more than 99
percent of its time on this planet, with a life expectancy
of only eighteen years."

Since the industrial revolution, thanks to increased sanita-
tion, sewage systems, better food supplies, labor-saving
machines, the germ theory, and modern medicine, our
life expectancy in the United States has risen dramatically.

... "In the U.S., greater life expectancy . . . can be attri-
buted almost entirely to this mastery of infection, this
annihilation of the bugs."

... Perhaps the only theory with a proven track record of
extending the life span of animals is the caloric restriction
theory, which states that animals which consume calories
just above starvation levels live significantly longer than
the average.

... Across the animal kingdom, the life span of animals is
roughly inversely correlated to the metabolism rate. The
slower the metabolism rate, the longer the life span. When
the metabolism rate is artificially reduced by restricting
calories, the life span is also lengthened.

... Scientists despair of trying to make such a spartan diet
part of the American lifestyle. The faces of most Ameri-
cans, in fact, would turn pale green if they saw the 940-
calorie diet which might possibly increase their life span.

... mice on this calorie-deprived diet do not have offspring.
In fact, they do not mate at all! People on this kind of
restricted diet may become so sluggish that they eventually
lose interest in many of the things that make life worth
living.

... Perhaps once the mechanism behind caloric restriction
is understood, scientists may find a way to turn it on with-
out the caloric sacrifice.

... Beyond 2050, perhaps every organ in the body will be
replaceable, except the brain. Of course, extending our life
span is only one of many ancient dreams. Yet another
even more ambitious one is to control life itself, to make
new organisms that have never before walked the earth.
In this area, scientists are rapidly approaching the ability
to create new life forms.

Playing God

Designer Children and Clones

... "Are we going to control life? I think so. We all know
how imperfect we are. Why not make ourselves a little
better suited for survival? That's what we'll do. We'll make
ourselves a little better." -James Watson

... what are the scientific limits in creating new life forms?
Can science one day create new races of animals like chi-
meras, or even a new race of humans, "metahumans" or
"homo superior", with superhuman abilities?

... Manipulating the gene pool of plants and animals to
create new life forms is nothing new. Humans have been
playing with the genes of other species for over ten thou-
sand years, creating many of the familiar plants and ani-
mals that we see around us.

... Dogs, for example, were probably first domesticated
about 12,000 years ago from the grey wolf, Canis lupus,
eventually becoming the familiar Canis familiaris of today.
Intensive crossbreeding has produced a bewildering var-
iety of dogs bred for specific purposes.

... Cats, on the other hand, were domesticated relatively
recently, probably by the Egyptians about 5,000 years
ago from the wildcat, Felis silvestris.

... Although the genetic manipulation of plants and animals
has been going on for 10,000 years, only in the last twenty
years have scientists been able to crossbreed across differ-
ent species, putting genes taken from one species of plant
or animal into another. Since all life on earth probably
evolved from an original ancestral DNA or RNA molecule,
it is not surprising that DNA from one species can propa-
gate so easily with the genome of another.

Within a matter of minutes, it is now possible to short-cir-
cuit hundreds of millions of years of evolution and create
entirely new species of "transgenic" animals which have
never before walked the surface of the earth.

... Since 1978, insulin, once available only from the pan-
creas of pigs, has been produced by injecting the human
gene for insulin into E. coli bacteria. In a process some-
what like that of fermentation, which produces alcohol,
these modified E. coli can produce unlimited quantities
of human insulin.

... scores of other rare, valuable medicines have been
made by genetic engineering, including interleukin-2 (for
treatment of kidney cancer), factor VIII (for hemophilia),
hepatitis B vaccine, erythropoietin (for anemia), whooping
cough vaccine, and somatotropin (for pituitary dwarfism).

... Progress in developing transgenic animals will also
accelerate though 2020.

... While transgenic animals promise a bonanza of valuable
medicines, transgenic plants give the promise of increasing
our food crops. At present, human society is dangerously
vulnerable to even small disruptions in its food supply.
Approximately 250,000 species of flowering plants exist
on the earth, but only 150 plant species are cultivated for
agriculture. Of these, a mere nine (wheat, rice, corn, barley,
sorghum/millet, potato, sweet potato/yam, sugarcane, and
soybeans) constitute three-quarters of our food energy.

Thus a blight or infestation attacking certain key food crops
could cause widespread famine.

... From now to 2020, we should see progress in the follow-
ing areas: Pesticide-producing plants ... Disease-resistant
plants ... Herbicide-resistant plants ... Creating valuable
drug-producing plants.

... Clones

How far can we develop this technology?

... Even if human cloning is banned, it is possible that an
underground cloning industry may develop over time.

... the moral dilemmas raised by cloning pale in compari-
son to those raised by genetic engineering of humans.
Cloning only produces a carbon copy of an individual;
genetic engineering promises the ability to change the
human genome and hence the human race.

... Beyond 2050: Angels in America

... if one day we are able to manipulate the master genes
that control entire organs of the body, the question natur-
ally arises: will this knowledge give us the ability to create
"metahumans" or "homo superior" in the future?

... the overriding question this very discussion raises is:
is it ethical to manipulate the human genome? If so, under
what guidelines?

... Second Thoughts

The Genetics of a Brave New World

... "The very reductionism to the molecular level that is
fueling the medical revolution also poses the greatest
moral challenge we face. We need to decide to what
extent we want to design our descendants."
- Arthur Caplan, University of Pennsylvania Center
for Bioethics

The DNA Revolution gives us at least two startling diver-
gent visions of the future.

One vision, promoted by the biotech industry, is that
of health and prosperity: gene therapy will eliminate here-
ditary diseases and possibly cure cancer, bioengineering
will create new drugs to vanquish infectious diseases,
and gene splicing will create new animals and plants
which will feed the world's exploding population.

However, a much darker vision of the future was painted
by Aldous Huxley in his unsettling yet prophetic book
"Brave New World", written in 1932.

... In a democracy, only informed debate by an edu-
cated citizenry can make the mature decisions about a
technology so powerful that we can dream of controlling
life itself.

... biotechnology is impossible to contain. One cannot
restrict the flow of DNA; it's everywhere. Because the
technology can never be entirely banned, it is important
to discuss and decide which of the various technologies
should be allowed to flourish and which ones should be
restricted.

... There is no viable way to completely stop the pro-
gress of science - but we must find a way to carefully
control the excesses of technology. Certain aspects of
genetics research may need to be banned entirely. But
the best overall policy is to air the risks and potentials
of genetics research in public, and democratically pass
laws which will shape the direction of the technology
toward alleviating sickness and pain. ...

- - - end excerpts - - -