Abstract
This abstract describes the scientific basis of the origin of life on Earth. Life has never been on Earth like as it is today. It has evolved over millions of years from a single cell microbe to a trillion-cell human being. The history of the evolution of life on Earth is trapped as fossils in the geological formation of rocks trapped in the Earth. The lowest level of the three and a half billion-year-old rocks contains the fossil of the simplest life forms. As we moved up to study geological formation of the younger and younger layers of rocks, we observe accumulation of mutations over millions of years, resulting in the increase complexity of fossil records. We have recently learned a technique to extract DNA from the fossils. Using modern technique developed during genome sequencing, our analysis of the DNA from the fossil revealed the structures of ancient life forms. The sequencing of human genome has provided us with a genetic toolkit which contains molecular scissors (enzymes such as restriction enzyme, like EcoR1, DNA polymerase, DNA ligase etc.), to cut, paste, copy, and sequence a gene. This abstract also describes how we can move a gene from one species to another to benefit the bourgeoning population of the world by providing new food, new fuel, and new medicine to treat every disease known to mankind.
Keywords: Nucleotide Synthesis; Evolution of Genes; RNA World; Human Genome; Genomic Medicine; AZQ
Historical Background
Has all life always been on planet Earth as it is today? Why
don’t we see in our Zoo animals like Dinosaurs, Woolly Mammoths,
Mastodons or Saber Tooth Tigers? The answer is that life has not
always been on planet Earth as it is today. All ancient animals
are dead and gone and become extinct. The nucleus of all living
creatures carries DNA (Deoxy Ribonucleic Acid) which holds the
information not only to store the information but also to pass it
on to the next generation. DNA is made of four chemicals called
nucleotides bases and they are Adenine (A), Thiamine (T), Guanine
(G) and Cytosine (C). They come in pairs. The pairing of A/T bases
and G/C bases imply a double helical structure. The one chain of
A/T bases running opposite of the other chain of G/C bases. The
double helical structure of the nucleotide base pairs solves the
mystery of life. It shows how the information to create life is stored,
copied and passed on to the future generations.
The essence of life is information and the information to
convert non-living chemicals to living creatures is written on the
double helical structure DNA. The living cell has no Soul, no Holy
Spirit, no Vital Force and no Devine Intervention. Now, we know
that Life is a series of coordinated chemical reactions of nucleotide
bases. Different life forms are the result of the slow process of
Natural Selection. Once we discovered that the secret of life resides
on DNA, we could manipulate life that is we could cut paste and
copy the DNA to create a new life form in the test-tube that never
existed before. This new life form will carry instructions not only
to clean up our environmental pollution, but also to provide the
most nutritious food for the burgeoning population of the world,
to provide new fuel to run the engine of modern society, and to
provide new medicine to treat every disease known to mankind.
If you are a religious person and believe that creation of life is a
miracle. You understand the origin of life from a different point of view that is from the point of view of religious faith based on belief
system that says that there is a Creator who created life on Earth.
What it tells me is that to know the way to Creator is to study
Creation of life? Most religions believe that Heaven declared the
Glory of God, it shows his handy work, there is a Creator who has
done it. If that is true than I must study creation trying to read the
mind of God. There is a tremendous creation of drive build into the
Cosmos. I respect your belief. For scientists, evolution of life is the
result of four and a half billion years of biological evolution. We see
life evolves everywhere on Earth. For example, during springtime,
you see the plants grow and flowers bloom; we see children are
born and grow up. Life begins with a single cell and grows up to
become a full human being. It is not a violation of natural laws. It is a
fact of the fundamental Natural Law. I don’t see the conflict between
Science and Religions. I respect people of Faith. Some people have
deep faith, that is their spiritual way of knowing the Origin and the
Creation of life on Earth.
I am a scientist. I look at the origin of life from a different point of
view, the rational and scientific way. The Objective truth is verified
by the experimental evidence. For example, Water boils at one
hundred degrees Centigrade and freeze at Zero degree Centigrade.
You could conduct this experiment either in New York or New Delhi,
the result should be reproducible, and verifiable. This is how I see
the world. Your way of looking at life is different from mine. Your
point of view is different, but it is not wrong. It is different. It was
Charles Darwin who provided the most rational answer. Charles
Darwin was one of the greatest biologists ever lived. In 1859, in his
book, the Origin of Species, he stated that Life evolves, and Nature
selects. What he meant was that the designs and complexity of living
creatures on Earth was due to slow evolutionary processes from
the simplest to the most complex species is not by the act of any
Divine Intervention, but by the slow process of Natural Selection
responding to the surrounding environment.
Species which evolve traits over billions of years to respond to
the changing environment survive and the rest of the species that
resist evolution die. Their fossils remained trapped in the layers of
rocks as the proof of their existence. Soon after the formation of
our Solar System about four and a half billion years ago, the hot
surface of our Earth cooled. The ancient fossil records show that
within a half a billion years, the first life form appeared called
the Pre-Cambrian era. During the Pre-Cambrian era which lasted
for about 25 million years, there were hundreds of new species
evolved from Pre-Cambrian era to the Cambrian Explosion. Most of
the pre-Cambrian life forms were unicellular soft tissues creatures
which decomposed over the years and their fossils impressions on
the rock could be preserved. Only creatures evolved hard shells
near the beginning of the Cambrian Explosion were fossilized in
the earliest sedimentary rocks. From the pre-Cambrian era, the
only creatures that left their fossils behind are the Trilobites, the
multicellular crab like creatures which crawled at the bottom of the
ancients’ riverbeds.
Darwin critiques argue that the earliest life should be
unicellular creatures not multicellular Trilobites. They forgot that
unicellular soft tissue creatures don’t fossilized and there were
millions of soft tissue creatures during the Pre-Cambrian Era. As
we approach near the Cambrian Explosion during the 25 million
years, the multicellular hard-shell creatures appeared. The only
hard-shell creatures from the Pre-Cambrian era like Trilobites left
their fossils behind. Darwin’s critiques will be proved wrong. We
have recently learned a technique to extract DNA from the fossils.
Using the new technique, a group of German scientists extracted
DNA from our ancient ancestors Neanderthal and completely
sequenced (decoded) their Genome. Neanderthal died over 30,000
years ago. We could use the same technique to extract the DNA of
creature of Pre-Cambrian Era. Any fossil or their impression left on
the pre-Cebrian rocks could be extracted and sequence to prove the
evolution of life from the simplest to the complex forms.
The toolkit developed during the sequencing of human
genome helped us sequence the fossils of all ancient creatures
for comparison. Now, we can sequence the simplest genome of
a microbes, from mouse to monkey to men and compare to see
how the simplest to complex organism evolved. How the four
nucleotides, the building blocks of life, originated on Earth by the
interaction of Carbon, Nitrogen, Oxygen to form nucleotide and
how they organized themselves to become alive. Life is a series of
coordinated chemical reactions of basic building blocks called the
nucleotide bases. If you sequence the genome from the simplest to
the most complex life form and compare their genomes, you see
how the same four nucleotide aggregate differently over ions in
response to the surrounding environment (Figure 1).
Figure 1: Dr. Khan is the Discoverer of AZQ (US Patent 4,146,622 & 4,233,215), a Novel Experimental Drug Specifically Designed to shut off a Gene that causes Brain Cancer for which he receives a 17-year Royalty for his invention (License Number L-0I9- 0I/0). To this date, more than 300 research papers have been published on AZQ. The award ceremony was broadcast live worldwide by the Voice of America (VOA). Dr. Khan is the first Indian to receive one of America’s highest awards in Medicine.
Cambrian Explosion
Darwin had the greatest foresight. By comparing the fossils,
he brought from Galapagos, he saw the evidence of evolution.
Planetology is the study of layers of rocks to trace the evidence
and ecology of plants and animals from the distant past to the
present day. Most fossils are found in the sedimentary rocks and
clay deposited on the layers of rocks. One layer deposited on the top
of other. Trapped in these layers are millions of years old fossil at
various stages of evolution. As the rivers dried up, the sedimentary
rocks become hard. The sedimentary rocks unfold like pages of a
gigantic book. The earliest fossil of simple structures is found in the
lowest or the oldest layers. As he examined younger and younger
rocks, he found complexity of structures. No human bones were
ever found in any of these ancient rocks. During the pre-Cambrian
era, about 450 million years ago when the climate changed, the
Cambrian explosions occurred when the frozen Earth began to
warm.
The single cell living creature instead of growing by asexual
reproduction began to grow by sexual reproduction. The interaction
of two separate chromosomes resulted in variations in gene pool
which led to divergence of life forms and evolution from the simplest
to the more complex life forms called the Cambrian Explosion of life.
The progeny of the recombinant genes produced complexity. Only
those recombinant daughter cells which carry genes that produced
functional proteins survived and the rest died. The proof of the
Cambrian Explosion is trapped in the fossil record which lasted
for about 25 million years. Extracting fossils from the ancient,
eroded rocks is a real challenge. The erosion of sedimentary rocks
over the years is due to rain falls, windstorms, running waters, and
transportations of the rocks. Once DNA extraction is purified from
the fossils, its genome could be sequenced, and its date could be
estimated by Radioactive Dating method (Figure 2).
Radioactive Dating
Radioactive dating provides accurate measurements of the age of the ancient rocks and the fossils trapped inside those rocks. Heavy elements with large nucleus are unstable. Over a long period of time, their nucleus falls apart to more stable elements. By becoming stable, they release radiations such as alpha, beta and gamma radiations and they are called radioactive elements such as Radium, Thorium, Rubidium, Uranium etc. All radioactive elements release radiations at a steady measurable rate over millions of years. By measuring the ratio of the radioactive elements and its unstable end-product, it is possible to measure the age of the rock and the fossils trapped inside that rock. For example, radioactive element Uranium (Atomic weight = 238) over millions of years break down slowly through various isotopes to a more stable element Lead (Atomic Weight = 206). Uranium first breaks down to element Radium (Atomic Weight = 226) which is further broken down to Polonium (Atomic Weight = 218) which is further broken down to its another isotope Polonium (Atomic Weight = 210) and to its most stable element Lead (Atomic Wight = 206). Radioactive decay is a slow process. Over a million-year, one Gram of Uranium break down to 1/7000 Gram of element Lead. By measuring the ratio of the amount of Uranium to the amount of Lead in a rock, we can calculate the age of the Uranium rock and its fossils trapped inside it (Figure 3).
Figure 3: Discoverer of anti-cancer AZQ, after receiving 2004, Vaidya Ratna, The Gold Medal, One of India’s Highest Awards in Medicine, At The Rashtrapathi Bhavan (Presidential Palace), in Delhi, India, During a Reception held on April 2, 2004.
The Geologic Clock
Let me scan the origin of life on planet Earth from the very
beginning to the present day. The slow evolutionary changes can
be explained from three and a half billion years to the present day.
If we were to examine the fossil record based on the Geologic Time
Scale, we can divide this time period into three great eras. First,
The Paleozoic Era which starts from the very beginning of the
Pre-Cambrian Era from the 100 million to 400 million years ago.
Second, The Mesozoic Era beginning from 230 million years ago to
70 million years ago. Third, The Cenozoic Era beginning from the 63
million years ago to the present day. During the Pre-Cambrian Era,
primitive life forms appeared. No fossil was found of the soft body
creatures except some the impression of their fossils are found on
the ancient rocks. During the end of the Pre-Cambrian era, some
hard-shell fossils, made of Calcium Carbonate, like Trilobites are
found. During Cambrian Era, about 100 million years ago, primitive
animals appeared such as Algae, Orthopods; much later sponges,
worms and mollusks appeared.
A treasure of fossils was discovered in British Columbia,
Canada, called the Burgess Shale, found in the Canadian Rockies of
Canada. These are the fossils left behind by the Middle Cambrian
Era. Part of this treasure is on display at the Smithsonian Museum
in Washington, D.C., Among those fossils were sea cucumber,
worms and Trilobites. During the Ordovician Period, from 425
to 500 million years ago, bony life forms appeared which include
Tetracorals, echinoids, asteroids appeared for the first time on
the primitive Earth. During the Silurian Period, (from 425 to 405
million years ago), brought the most dramatic changes in the
Earth’s atmosphere. Plants appeared for the first time. Up to this
time period, Earth’s atmosphere was full of Nitrogen gas released
by the cooling the hot Nitrate Rocks. Earth’s atmosphere also
contained the Carbon dioxide contributed by the Volcanic eruption.
Plants carry Chloroplast Genome a procryptic life forms captured in
an early evolutionary process.
Genes in the Chloroplasts genome have the ability to capture
Carbon dioxide from the atmosphere and in the presence of sunlight
and convert to its food the Carbohydrate and release Oxygen as the
by-product. For the following 60 million years, at the beginning
of the Devonian period, the cooled part of the planet Earth, was
carpeted by the early plant life called the Blue Green Algae. Its main
function was to absorb Carbon dioxide from the atmosphere and
convert it to the Carbohydrate its food and release Oxygen as a part
of photosynthesis. Over millions of years, enormous amount of
Oxygen was released in the atmosphere. By the end of the Silurian
Period, the composition of the Earth’s atmosphere was changed
from pure Nitrogen gas to 80% Nitrogen and 20% Oxygen gas. The
gas Oxygen is extremely reactive, it reacted with the Oceans Iron
forming the Iron oxide. Billions of tons of Iron Oxide deposited on
the Ocean floor.
Oxygen is toxic to the Anerobic life forms. Creatures survive
in the presence of Oxygen thrived while Anerobic life forms died.
Complex life forms appeared. In the Oxygen atmosphere, fossils of
Fish and Amphibians were found along with the fossils of spiders,
millipedes, insects, and corals were discovered. The time, period
from 345 to 310 million years is designated as the Mississippian
period, during which the fossils of more complex life forms appeared which included Corals, Branchipodids, and Foraminifers.
From 210 to 280 million years ago appeared the Great Coal bearing
layers of rocks known as the Pennsylvania Period. It saw the low
land of great swamp forming the Coal forest. This period saw the
appearance of Clams, shell-fish, reptiles, and amphibians. From 280
to 230 million years ago, called the Permian Period which observed
the swampy part of the surface developing Coal-forest plants such
as Conifers, Tongue-fern, Oak, insects, beetles and dragon flies.
Because of the Climatic changes, the plants and animals of the
Permian Period become extinct.
This marked the end of the Paleozoic Era. The Mesozoic Era
began about 165 million years ago. It brought the Age of Reptilian.
With this Era came the Birds, Mammals, Insects and Flowering
Plants including Elm, Oak, Maples became common. New mountains
range slowly appeared. From 230 to 180 million years ago which
is called The Triassic Period saw the appearance of Dinosaurs that
mighty beast that ruled Planet Earth for about 150 million years.
They all died when a meteorite structs Planet Earth about 65
million years ago. They left behind their foot prints as their fossil
around the world. During the Jurassic Period, rain-forest spread
everywhere the Dinosaurs dominated the land, but the Ocean was
dominated by the Plesiosaur, the monstrous carnivorous of the
Seas. The Creataceous Period which begins about 135 to 70 million
years ago, marked the development of sedimentary rock made of
Chalk. The moment of the Tectonic Plates formed the mountain
range from Andes to Rockies, from Antarctica Northwestern Asia.
Plants thrived during the Creataceous Period. The fossil record
showed the appearance of Trees, shrubs, including Magnolia, Oak,
Maples, Birch, Holly, and Ivy which provided food for mammals,
birds, reptiles, and insects. Dinosaurs spread on all seven continents.
Their fossils are found all over the planet. As I said above, they
all disappeared around 65 million years ago, when a meteorite
structed at the Northern Mexico. The Cenozoic Era, called The Age
of Mammals, began about 70 million years ago to the present day.
The climatic changes resulted in the cooling of the polar regions and
warming climatic temperature everywhere. This climate change
stayed on to the present day. The Cenozoic Era, is dominated by
the Flowering Plants, and reptiles are replaced by Mammals. Birds
continue to expand everywhere. Finally, the Quaternary Period in
which we now live began with the melting of the 10,000 feet thick
ice sheet over much of the Northern hemisphere in which four
glaciers advanced which lasted about 11,000 years.
As the ice sheet melted away, it created suitable atmosphere
for the emergence of human being. Humans appearance on Earth
is a matter of only a few million years. Have we found human
fossil during any of the Geologic periods from the Pre-Cambrian
to Cenozoic Era? The answer is no. In 1974, the first human
fossil, Lucy, Australopithecus afarensis skeleton was discovered,
in a 3.2-million-year-old rock found by anthropologist Donald
Johansson in Hader, valley in Ethiopia. Chimps were living in the
Great Rift Valley for the past 25 million years. A more advanced
form of the Chimp called Austral opthecus appeared in East Africa.
He was an advanced forest man called Homo habilis. He was a
hunter gatherer of food who built tools. He was a direct ancestor
of Man and who lived about 20 million years ago. Next was the apeman,
Pithecanthropus, who lived about 500,000 years ago in Java
and China. Neanderthal man lived in Europe. He was also a hunter
gatherer and lived about 100,000 years ago.
They all died about 30,000 years ago. Cro-Magnon finally evolved
modern brain. Cro-Magnons, a term derived from the Cro-Magnon
rock shelter found in southwestern France, where the first human
fossils were found in 1868. Darwin’s extraordinary prediction was
confirmed by sequencing genomes or reading the book of lives of
over a thousand species on Earth. Of all the experiments in Biology,
the Sequencing of Human Genome was the greatest accomplishment
of all times. On April 3, 2003, Dr. Francis Collins, the Director of my
Institutes, The National Institutes of Health (NIH) announced that
we read the book in which God created life. We completely read
the book of life of a human being letter by letter, word by word,
sentence by sentence and chapter by chapter all 46 volumes called
the Chromosomes carrying the 24,000 chapters called the genes
and its text written in four nucleotides containing six billion four
hundred million letters. In a few sentences, he described the
completion of the Human Genome Project.
The greatest biological experiment ever conceived by human
mind. It will answer the most fundamental questions we have
asked ourselves since the dawn of human civilization. What does
it mean to be human? What is the nature of our memory and our
consciousness and our development from a single cell to a complete
human being; the biochemical nature of our senses; the processes of
our Aging. The scientific basis of our similarities and dissimilarities.
Similarities that all living creatures from a tiny blade of grass to
mighty Elephant, including man, mouse, monkey, mosquitoes,
and microbes all are made of the same chemical building blocks
and yet they are so diverse that no two individuals are alike, even
identical twins are not identical they grow up to become two
separate individuals. Essential components of life are RNA, DNA,
Proteins, Carbohydrates, Lipids, and Hormones. We always wonder
how these non-living chemicals could get together to create living
creatures. When did life evolve? Where was it evolved? And how life
evolved? Evolution of Life on Earth is not a miracle.
Life could have been evolved on Earth’s surface such as on the
oldest rocks found in Australia or it could have been evolved at the
bottom of the Ocean floor where Black Smokers are formed with
Lava emerging from under sea volcanoes reacted with surrounding
Hydrogen Sulfide gas which provides energy for life forms such as tubeworms and crabs who thrive on the Ocean floor. Life also could
have been evolved underground. Soil sample brought by miners
from the gold mines in South Africa two miles deep underground
contained micro worms. Such life form could be cultivated on a
Petri dish containing Agar mixed with nutrients. Early life could
have been unicellular life forms. When harvested within 24 hours,
the Petri dish could be filled with microbial life. Could life have been
brought on Earth by meteorites. Early Earth has no Water. Billions
of Comets brought Water on Earth. Would it be possible that some
of those Icy mountains contained life giving essential components?
Life could also be evolved on the surface of Earth. A million-lightning
strike Earth each day.
Could it be possible that at some remote corner of the Earth,
Lightning struck at cloud of gases such as Ammonia, Methane
and Sulfur on a Phosphate containing rocks making the essential
components of life like nucleotides which combined to form RNA
Which not only carry information like DNA and perform function
like amino acids. The polymerization of Formaldehyde in the
atmosphere could produce Carbohydrates another essential
component of life. The presence of Acetonitrile, Carbon dioxide,
Water in the presence of Ultraviolet light could produce the
nucleotides such as Adenine (A), Thiamine (T), Guanine (G) and
Cytosine (C) forming a binary code leading to RNA which start
replicating itself creating the first living anaerobic creature. RNA
molecule can catalyze reaction like enzyme such as protein, but also
it could store information like DNA. Were there creature in the RNA
world which thrived in the absence of Oxygen. Since no human was
present to witness the formation and evolution of first life on Earth,
we rely on its presence from the early fossils found in the layers of
ancient rocks.
Once a single replicating living cell appears on Earth,
complexity develops. In other words, all complex life forms are
evolved from simple life forms. Since no humans were present
to observe the beginning of life on Earth, we deduce their
evolutionary developments from their fossil records. Fossils are
the remains of the pre-historic life forms. To become fossilized,
the species must have developed hard parts such as bone or shell
and must be trapped in mud which slowly become hard rock. Soft
tissue creatures do not fossilize; their tissues decomposed. As I said
above, the Earth was formed about four and a half billion years ago.
The hot Earth cooled by the bombardment of the icy comets. Every
drop of Water on Earth was brought by the icy comets. The first life
form appeared on Earth about a billion year after the Earth was
formed about four and a half billion years ago. Over billions of years
of evolutionary process, chemicals reacted together to create Life.
One of the most essential components of Life that is Amino Acid
was created in the Lab.
In 1953 Stanley Miller, the student of the Nobel Laureate,
Harold Urey, at the Chicago University conducted an experiment
in the Lab to create life’s essential components the amino acids.
He created primitive Earth like conditions in the Lab. He took
two flasks connected with a condenser. One flask contained water
vapors and the other filled with gases found on the primitive Earth
such as Methane, Carbon dioxide and Ammonia. To mimic thunder
and lightning, a source of energy, on Earth, he sparked electric
current in the flask. The high energy electric spark, split the stable
molecules of Nitrogen, Oxygen, and Carbon, producing extremely
reactive ions which reacted with one another recombing to produce
a more stable new molecule. Within a week, the clear solution in the
flask became pink and dark. The analysis of the colored material
showed the formation of Amino Acids, the essential building blocks
of life which perform all body functions. In similar experiments,
Francis Crick and Lesli Orgel, attempted to synthesize Nucleotides
the replicating molecules which carry information to make life.
Using Formaldehyde, the other essential components of life such as
sugars and hormones were synthesized.
Chromosomes are thread-like structures located inside the
nucleus of animal and plant cells. Each chromosome is made of
double strand of a long chain of four nucleotides wrapped around
with protein called the deoxyribonucleic acid (DNA). As I stated
above, this is the information molecule which is passed on from
parents to offspring, DNA contains specific instructions that make
each type of living creature unique. As the living creatures evolve,
the complexity increases as the number of chromosomes increases.
The evolution of life on planet Earth is extremely slow process.
About a billion years after the formation of Earth that is about four
and a half billion years ago, life appeared. Bacteria Phage Phi-X
174 is perhaps the smallest organism, and it is made of over 5,000
nucleotide bases. It carries a single Chromosomes so has most
bacteria. As evolution proceeded, chromosome number increases,
and complexity appeared in both plants and animals to survive in
the changed environment. For example, while bacteria have a single
chromosome, Jack Jumper Ant has two Chromosomes.
Yellow fever mosquito has six chromosome; Fruit fly has 8
chromosomes; Swamp wallaby has 10 chromosomes; Nematode
has 12 chromosomes; the Australian daisy has 12 chromosomes;
the spider mice, Aloe Vera and cucumber has 14 chromosomes;
Garlic has 16 chromosomes; Itch Mite has 17 chromosomes; Radish,
Carrot, Cabbage and passion fruit have 18 chromosomes; Maize
and Cannabis have 20 chromosomes; Bean and Virginia Opossum
have 22 chromosomes; Snail, Melon, Rice, Sweet Chestnut have 24
chromosomes; Edible frog has 26 chromosomes; Axolotl has 28
chromosomes; Beg Bug has 29 chromosomes; Giraffe, American
mink and Pistachio have 30 chromosomes; Yeast, European honey
bee, American badger and Alfalfa have 32 chromosomes; Red fox, Sunflower and Porcupine have 34 Chromosomes; Yellow mongoose,
Tibetan sand fox, Starfish, Red panda, Meerkat and Earthworm
have 36 chromosomes; Tiger, Sea otter, Sable, Raccoon, Pig, Lion
and European mink have 38 chromosomes; Mouse, Mango, Hyena,
Ferret, Beaver and Peanut have 40 Chromosomes; Wolverine, Wheat,
Rat and Oats have 42 Chromosomes; Dolphin, Sable antelope, and
Human have 46 chromosomes; Water buffalo, Tobacco, Potato,
Orangutan, hare, Gorilla, Deer mouse, and Chimpanzee have 48
chromosomes; Zebrafish, Water Buffalo, Striped skunk, Pineapple
have 50 chromosomes; Spectacled Bear, Platypus, and Cotton have
52 chromosomes; Sheep, Hyrax, Racoon dog and Capuchin monkey
have 54 Chromosomes; Strawberry, Gaur, and Elephant have 56
chromosomes; Woolly mammoth has 58 chromosomes; Yak, Goat,
cow/Bull, American Bison, Bengal fox, have 60 chromosomes; Gypsy
moth, Donkey, and Scarlet Macaw have 62 chromosomes; Mule has
63 chromosomes; Guinea pig, Spotted skunk, Horse and Fennec fox
have 64 chromosomes; Gray fox, Red deer, Elk and Roadside hawk
have 68 chromosomes; White-tailed deer have 70 chromosomes;
Black nightshade and Bat-eared fox have 72 chromosomes; Asiatic
black bear, and American black bear have 74 chromosomes;
maned wolf, have 76 chromosomes; Grey wolf, Golden Jackal
Dog, Dingo have 78 Chromones; Turkey, Sugarcane, and Pigeon
have 80 chromosomes; Great white shark have 82 chromosomes;
Hedgehog genus have 88 chromosomes; Moon Worts, hedgehog
Genus and Grape fern have 90 chromosomes; Pitter’s crab-eating
rat. Prawn and Aquatic rat have 92 chromosomes; Kamaraj (fern)
have 94 chromosomes; Carp has 100 chromosomes; Red vizcacha
rat have 102 chromosomes; Walking catfish has 104 chromosomes;
American paddlefish have 120 chromosomes; Northern lamprey
has 174 chromosomes; Rattlesnake fern has 184 chromosomes;
Red king crab has 208 chromosomes; Field horsetail has 216
chromosomes; A. butterfly has 268 chromosomes; black mulberry
has 308 chromosomes; Atlas blue has 448 chromosomes; adderstongue
has 1260 chromosomes’ here is a Fern called Ophioglossum,
which has the highest number of chromosome count of any known
living organism, with 1,260 chromosomes.
This fern has roughly 630 pairs of chromosomes or 1,260
chromosomes per cell. The next generation of scientists will have
the opportunity to sequence the genomes of all above species
and their genes could be added to our GenBank to be used to
develop new food, new fuel and new medicine for the burgeoning
population of the world. From the above observations, it became
clear that humans are not the panicle of achievement of evolution.
Other creatures have more chromosomes than us. Our superiority
is in achieving consciousness, our language, and our ability to
communicate orally and in writing leaving our knowledge for the
future generations (Figure 4).
The Impact of Sequencing Human Genome on the understanding of the Origin of Life
As I said above, our entire book of life is written in four genetic
letters called nucleotides in a three-letter code called codon, and
they are A (adenine), T (thymine), G (guanine) and C (cytosine).
These four chemicals are called nucleotide. The essence of life is
information which is carried on these four nucleotides. These
nucleotides are found in the nucleus of all living cells including humans, plants, and animals. Instruction in a single gene is written
in thousands of AT/GC base pairs that are linked together in a
straight line and we call them DNA (Deoxyribose Nucleic Acid) -
Nobel prize was awarded to Crick, Watson & Morris Wilkins [1] for
discovering the double helical nature of the DNA structure which
is transcribed into a single stranded of RNA (in mRNA the less
water soluble methyl group in Thiamine, T, is converted to more
water soluble Uracil, U, by replacing Methyl group with a Hydroxyl
group) which leaves the nucleus and moves into Cytoplasm
where it is translated in Ribosomes into Amino Acids leading
to proteins). When thousands to millions of AT/GC base pairs
contain information to make a single protein, we call that portion
of AT/GC base pairs a gene (Nobel Prize was awarded to Khorana &
Nauenberg for making a functional gene).
A gene is a string of DNA. The starting Codon for a gene is AUG
which codes for the amino acid Methionine after several hundred
Codons for different amino acids, comes the stop codon. There
are three stop Codons, and they are UGG, UGA, UAG. After the
stop Codon, no more amino acids are added to the chain, and DNA
synthesis stops. If we count all the AT/GC base pairs in a single cell
of our body, we will find that there are 3.2 billion pairs of bases
present in the nucleus of every cell. The entire AT/GC sequence of
3.2 billion base-pair is called the Human Genome or the book of our
life which carries total genetic information to make us. The reading
of the total genetic information that make us human is called the
Human Genome. In 1990, US Congress authorized three billion
dollars to NIH to decipher the entire Human Genome under the title,
“The Human Genome Project.” We found that our genome contains
six billion four hundred million nucleotides bases half comes from
our father and another half comes from our mother.
Less than two percent of our Genome contains genes which code
for proteins. The other 98 percent of our genome contains switches,
promoters, terminators etc. The 46 Chromosomes present in each
cell of our body are the greatest library of the Human Book of Life
on planet Earth. The Chromosomes carry genes which are written
in nucleotides. Before sequencing (determining the number and
the order of the four nucleotides arranged on a Chromosomes),
it is essential to know how many genes are present on each
Chromosome in our Genome. The Human Genome Project has
identified not only the number of nucleotides on each Chromosome,
but also the number of genes on each chromosome. A single cell
is so small that we cannot even see with our naked eyes. We must
use a powerful microscope to enlarge its internal structure. Under
an electron microscope, we can enlarge that one cell up to nearly a
million times of its original size. Under the electron microscope, a
single cell looks as big as our house.
There is a good metaphor with our house. For example, our
house has a kitchen, the cell has a nucleus. Imagine for a moment,
that our kitchen has 23 volumes of cookbooks which contain 24,000
recipes to make different dishes for our breakfast, lunch and dinner.
The nucleus has 23 pairs of chromosomes which contain 24,000
genes which carry instructions to make proteins. Proteins interact
to make cells; cells interact to make tissues; tissues interact to
make an organ and several organs interact to make a man, a mouse
or a monkey. In every cell of our body, we carry sixteen thousand
good genes, six thousand mutated (bad) genes responsible for six
thousand diseases and two thousand Pseudo-genes that have lost
their functions, during evolutionary time. Our genome contains
six billion four hundred million nucleotides bases half comes from
our father and another half comes from our mother. Less than two
percent of our Genome contains genes which code for proteins.
The other 98 percent of our genome contains switches, promoters,
terminators etc.
The 46 chromosomes present in each cell of our body are the
greatest library of the Human Book of Life on planet Earth. The
Chromosomes carry genes which are written in nucleotides. Before
sequencing (determining the number and the order of the four
nucleotides on a chromosomes), it is essential to know how many
genes are present on each chromosome in our Genome (Figure 5).
The Human Genome: The greatest Catalog of Human Genes on planet Earth
Human Genome contains a catalog of traits written on genes
in nucleotide sequence. Our Genome also provides a catalog of all
24,000 genes; it also provides the number and location of each
gene on the chromosome. The catalog provides 16,000 good genes,
6,000 bad genes and 2,000 pseudogenes (they lost their function).
The Human Genome Project has identified the following genes on
each chromosome: We found that the chromosome-1 is the largest
chromosome carrying 263 million A, T, G and C nucleotide bases and
it has only 2,610 genes. The chromosome-2 contains 255 million
nucleotides bases and has only 1,748 genes. The chromosome-3
contains 214 million nucleotide bases and carries 1,381 genes.
The chromosome-4 contains 203 million nucleotide bases and
carries 1,024 genes. The chromosome-5 contains 194 million
nucleotide bases and carries 1,190 genes. The chromosome-6
contains 183 million nucleotide bases and carries 1,394 genes. The
chromosome-7 contains 171 million nucleotide bases and carries
1,378 genes. The chromosome-8 contains 155 million nucleotide
bases and carries 927 genes.
The chromosome-9 contains 145 million nucleotide bases and
carries 1,076 genes. The chromosome-10 contains 144 million
nucleotide bases and carries 983 genes. The chromosome-11
contains 144 million nucleotide bases and carries 1,692 genes.
The chromosome-12 contains 143 million nucleotide bases and
carries 1,268 genes. The chromosome-13 contains 114 million
nucleotide bases and carries 496 genes. The chromosome-14
contains 109 million nucleotide bases and carries 1,173 genes.
The chromosome-15 contains 106 million nucleotide bases and
carries 906 genes. The chromosome- 16 contains 98 million
nucleotide bases and carries 1,032 genes. The chromosome-17
contains 92 million nucleotide bases and carries 1,394 genes. The
chromosome-18 contains 85 million nucleotide bases and carries
400 genes. The chromosome-19 contains 67 million nucleotide
bases and carries 1,592 genes. The chromosome-20 contains 72
million nucleotide bases and carries 710 genes.
The chromosome-21 contains 50 million nucleotide bases
and carries 337 genes. The chromosome-22 contains 56 million
nucleotide bases and carries 701 genes. Finally, the sex chromosome
of all females called the chromosome-X contains 164 million
nucleotide bases and carries 1,141 genes. The male sperm called
chromosome-Y contains 59 million nucleotide bases and carries
255 genes. If you add up all genes in the 23 pairs of chromosomes,
they come up to 26,808 genes and yet we keep on mentioning
24,000 genes needed to keep us function normally. A gene codes for
a protein, not all 24,000 genes code for proteins. It is estimated that
less than 19,000 genes code for protein. Because of the alternative
splicing, each gene codes for more than one protein. All the genes in
our body make less than 50,000 protein which interact in millions
of different ways to give a single cell. Millions of cells interact to
give a tissue and hundreds of tissues interact to give an organ and
several organs interact to make a human [1-6].
Not all genes act simultaneously to make us function normally.
Current studies show that a minimum of 2,000 genes are enough
to keep human function normally; the remaining genes are backup
support system, and they are used when needed. The remaining
genes are called the pseudo genes. For example, millions of years
ago, humans and dogs shared some of the same ancestral genes;
we both carry the same olfactory genes needed to search for food
in dogs. Since humans don’t use these genes to smell for searching
food, these genes are broken and lost their functions in humans,
but we still carry them. We call them Pseudo genes. Recently, some
Japanese scientists have activated the pseudo genes, this work may
create ethical problem in future as more and more pseudo genes are
activated. Nature has good reasons to shut off those pseudogenes.
Our Genome provides the genetic road map of all our genes, past,
present and future.
For example, it can tell us how many good or bad genes we
inherit from our parents and how many of those gene we are going
to pass on to our children. If a family has too many bad genes,
and have a family history serious illnesses, they can break off the
information flow and stop having children or stop donating mutated
eggs and sperms. On April 3, 2003, several groups simultaneously
sequenced the entire Human Genome and confirmed that less than
two percent of the Genome codes for proteins the rest is the noncoding
regions which contains switches to turn the genes on or off,
pieces of DNA which act as promoters and enhancers of the genes.
Using restriction enzymes (which act as molecular scissors), we can
cut, paste, and copy genetic letters in the non-coding region which
could serve as markers and which has no effect, but a slight change
called mutations in the coding region makes a normal cell abnormal
or cancerous (Figure 6).
Figure 6: Dr. A. Hameed Khan, a Scientist at the National Institutes of Health (NIH) USA, an American Scientist of Indian Origin was awarded on April 2, 2004. Vaidya Ratna; The gold Medal, one of India’s Highest Awards in Medicine for his Discovery of AZQ (US Patent 4,146,622) which is now undergoing Clinical Trials for Treating Bran Cancer.
Our Search for Unknown Diseases Has Come to A Closure
There are two most powerful implications of the human Genome Sequencing. One of them is that we have come to closure. What it means is that we have the catalog of all genes in the Human Genome, we can search the entire genome and locate the desired gene. we will not wonder in the wilderness anymore. Everything there is to know about human health and traits are written on these genes in nucleotide sequences. Our Genomes provides the catalog of all genes.
Reference Sequence
We can scan the whole genome (Reference Sequence) for its
response to a given situation. When we look at a normal cell and
compare with an abnormal cell, we see the differences. Or when
we compare their gene expression looking for a specific proteins,
from a specific genes and for a specific nucleotide sequence, we
can identify a specific mutation responsible for the disease. In the
olden days, before sequencing human genome, when a patient
visits a physician for some unknown ailment, the Physician would
order several tests and would say to his patient, I don’t know what
is wrong with you, I will see if any of these tests show if my guess
is right and if he is wrong, he will recommend few more tests to
see if he could identify the illness. The guesswork and the trial-anderror
days are over. Now, after sequencing the human genome, the
physician would say to his patient, I don’t know what is wrong with
you, but I know where to find it. It is written in your Genome. It
would be easy for a Physician to scan the patient entire genome and
compare against the Reference Sequence to identify the mutations
responsible for causing the disease.
He will refer the patient to a biotechnology Lab. The Lab
Technician will take a small blood sample from the patient, separate
his WBC, extract DNA, sequence his Genome and compare with the
Reference Sequence letter by letter, word by word by word and
sentence by sentence and send the result to the Physician who can
easily identify the mutations responsible for causing the disease.
The result will provide the best diagnostic method to identify a
disease. Our Genome is not just a diagnostic road map of our genes,
it tells us to clone the good genes and shut off the bad genes. Using
the good genes, it also tells us to make its large-scale protein for
worldwide use such as Insulin and Human growth hormone. On the
other hand, identifying the bad genes and tell us to design novel
drugs to shut off bad genes responsible for causing serious diseases.
We have already demonstrated that using the genetic
engineering techniques, we can cut, paste, copy, and sequence a
good gene for industrial scale preparation as I said above such as
Insulin to treat 300 million of diabetic around the world. Genome
sequencing of bad genes start a new era of Genomic Medicine
which is based on the development of new drugs for treating a disease based on the genetic make-up of the individuals. The
next step would be to design drugs to shut off the mutated genes.
Gene Therapy will work if the disease is caused by a single gene
mutation. Drug Therapy will work if multiple genes are responsible
for causing diseases such as Cancers, Cardiovascular diseases, and
Alzheimer.
Genomic Medicine
The first step is to cut the human genome with specific enzyme
(prepare a Restriction Site Map) at the specific sites using restriction
enzymes (molecular scissors such as EcoR1) first accomplished by
El Salvador Luria, Max Delbruck, and Hamilton Smith. The fragment
of human DNA (a single gene) if not protected will be destroyed by
antibody. A naked gene is a piece of DNA (which has a start codon
AUG and after a few thousand nucleotide (codons) end at one of the
three stop codons UAG, UGA or UGG if not protected by recombinant
technology (making a hybrid) that is by recombining with the DNA
of Virus, or Plasmids, or Chloroplasts (for plants) which serves as
Vectors, will be destroyed by enzymes. One can store the fragments
or genes in the Vectors once the human DNA fragment is stabilized
in Vectors by recombinant technology; we can not only purify this
fragment (genes), but also, we can make millions of copies (clone)
of this fragment of DNA by transferring into the host cells such
as Bacteria, mammalian cells or Yeast cell which autonomously
replicates to produce library of genes.
Each Library contains millions of copies of identical genes
that produce same protein. Before the genetic revolution, Insulin
is extracted from pancreas of the slaughtered animals which
is used to treat old diseases such as diabetes; a tiny fragment of
impurity could set anaphylactic shock and kill the patients. Now,
highly pure human Insulin produced by Genetic Engineering is
used to treat 300 million diabetic patients worldwide without the
loss of a single life using the same recombinant technology. Other
products of Genomic Medicine such as Growth hormones and
hormone proteins to treat Hemophilia by factor VIII protein are
being developed as genomic medicines by recombinant technology.
The essence of life is information, and the information is located on
the four nucleotide bases A-T and G-C. According to Central Dogma
of Crick and Watson, the information on DNA is transcribed on RNA
which is translated in Ribosome to protein. Attempts are being
made to design drugs to attack cancer cells on all three levels that is
DNA, RNA and Protein.
Herceptin, a novel class of drug, has been successful in attacking
protein. Craig Milo has designed double stranded RNA to shut off
gene and prevents its translation into protein. Attack on DNA to
shut off a gene was carried out by Ross using highly toxic Nitrogen
Mustard. Gene Therapy cannot be applied to multiple genetic
defects such as cancers or heart diseases. Drug Therapy could be
used to develop novel treatments. Professor WCJ Ross of London
University was the first person who designed drugs to attack DNA
for Cancer Treatment. He designed drugs to cross-link both strands
of DNA that we inherit one strand from each parent. Cross-linking
agents such as Nitrogen mustard. The analogs of Nitrogen mustard
are extremely toxic and were used as chemical weapon during
the First World War. Hundreds of more toxic analogs of Nitrogen
Mustard were developed during the Second World War. Solders
exposed to Nitrogen Mustard showed a sharp decline of White
Blood Cells (WBC) from 5000 cell/CC to 500/CC [7,8].
Children suffering from Childhood Leukemia have a very WBC
count over 90,000/CC. Most of the WBCs are premature, defected,
and unable to defend the body from microbial infections. Ross
rationale was that cancer cells divide faster than the normal cell,
by using Nitrogen Mustard he could cross linking DNA and prevent
cell division. Once he demonstrated that he could shut off a gene by
cross-linking DNA; he could shut off any mutated gene of all 220
tissues present in a human by finding a dye that could specifically
color that tissue. He could attach the Nitrogen Mustard group to the
dye and attack the cancer genes in any one those tissues. Ross was
the first person to use war chemicals successfully to treat cancer.
Although such drugs are highly toxic more cancer cell will be
destroyed than the normal cells. Over decades, Ross made several
hundred derivatives of Nitrogen Mustard as cross-linking agents.
Some of the Nitrogen Mustards are useful for treating cancers such
as Chlorambucil for treating childhood leukemia (which brought
down the WBC level down to 5,000/CC) and Melphalan and
Myrophine for treating Pharyngeal Carcinomas.
[9-15]. Because of the high toxicity of Nitrogen Mustard, new
drugs could not be developed to treat other types of Oral or Lung
Cancers. As I showed above, we sequenced our entire genome, our
book of life, letter by letter word by word, sentence by sentence,
chapter by chapter all forty-six volumes written in six billion
four hundred million genetic letters (nucleotide) of a healthy
human being under the Human Genome Project. We can use our
healthy Genome as a Reference Sequence for comparison. Using
nano capillary method, it took us 13 years to sequence the entire
human genome at a cost of $3 billion. Now, we have developed
next generation sequencers like Nanopore technology which will
sequence the entire genome cheaper and faster. Using biopsy
sample, we can take a single cell from the Lung or Oral tumor of
smoker, sequence its genome, and compare with the Reference
sequence to identify the number and location of all mutations or
damage genes caused by smoking. Recently, we also completed the
1000-genome project which will provide thousand copies of the
same gene for comparison.
We also learned to convert Analog language of Biology into the
Digital language of computer. Now, we can write a program and design a computer to read and compare at the speed of light to
some other country. When comparing with the Reference Sequence
with the smoker’s gene sequence, it will identify all the mutations
with precision and accuracy. Once the mutations responsible for
causing Lung or Oral Carcinoma are identified, we can design drugs
to shut off those genes. At the London University, I was a graduate
student of Professor Ross then his Post-doctoral Fellow and then
his Special Assistant. For almost ten years, I worked with Professor
Ross making derivatives of Nitrogen Mustard as anticancer agents.
While Professor Ross was designing drugs to attack both strands of
DNA which are extremely toxic, as a part of my doctoral thesis, I was
assigned to design drugs to attack a single strand of DNA.
I was successful in designing a novel class of drugs which attack
only one strand of DNA. This class of drugs is called Aziridines
[16-18]. I made over 100 Aziridine dinitro-benzamide (CB1954)
analogs which attack the DNA of Walker Carcinoma 256 in Rat,
a solid aggressive tumor. Using the same rationale, it has taken
me about ten years to make (CB1954), a novel drug to shut off a
mutated gene responsible for causing Walker Carcinoma 256, a
solid aggressive tumor in Rat and about a quarter of a century to
make AZQ to shut off Glioblastoma gene in human responsible for
causing brain tumor. The following example explains how easy it is
to get Lung or Oral cancer by simply smoking a dozen of genetically
enhance high Nicotine content Cigarette and how expensive, timeconsuming,
and exhaustive it is to find a possible cure. The Drug
must be safe and effective. After a year use, if the FDA receives an
Adverse Effect Report, the Drug is withdrawn.
All the effort is wasted. Toxicity is measured as the ratio
between toxicity of normal cell compared to the abnormal cell. The
ratio is called the Therapeutic Index (TI). The TI of most Crosslinking
Nitrogen Mustard are ten, the Therapeutic Index of one of
the Aziridine (Aziridine dinitro benzamide) CB1954 is (T/I = 70)
which showed that CB1954 is seventy time more toxic to cancer
cells compared to normal cells. The Walker Tumor not only stopped
growing but also it shrank to normal size. I used a simple rationale,
the Aziridine attacks a single strand of DNA in acidic medium,
particularly the N-7 Guanine. The dye Dinitro-benzamide has
great affinity for Walker Tumor. The Aziridine dinitro benzamide
(CB1954) stain the tumor. CB1954 acts as a Prodrug that is it
remains inactive at neutral or basic pH but activated in acidic
solution. As the tumor grows, it uses Glucose as a source of energy.
Glucose is broken down to Lactic acid. It is the acid which attacks
the Aziridine ring. The ring opens to generate a Carbonium ion
which attacks the single strand of most negatively charged N-7
Guanine shutting off the Walker Carcinoma gene.
To continue my work, I was honored with the Institute of
Cancer Research post-doctoral fellowship award of the Royal
Cancer Hospital of London University. To increase the toxicity of
CB1954 to Walker Carcinoma, I made additional 20 analogs. When I
attached one more Carbonium generating moiety, Carbamate to the
Aziridine Dinitrobenzene, the compound Aziridine Dinitrobenzene
Carbamate was so toxic that its Therapeutic Index could not be
measured. Because of the safety reason, further work at the London
University was stopped. I used the same rationale to continue my
work in America when I was offered the Fogarty International
Postdoctoral Fellowship Award to continue my work at the National
Cancer Institute (NCI) of the National Institutes of Health (NIH) in
Bethesda, Maryland, USA. I brought the idea from London University
of attacking one strand of DNA using Aziridine, but I do not want to
use the same dye Dinitro benzamide.
One day, I heard a lecture at NIH in which the speaker stated
that methylated radio labeled Quinone crosses the Blood Brain
Barrier. When radiolabeled Quinone is injected intravenously in
mice, the entire radioactivity was concentrated in the Brain within
24 hours. I knew that Glioblastoma multiforme, the brain tumor in
humans, is a solid aggressive tumor like Walker Carcinoma in Rats.
I decided to use Quinone moiety as a carrier for Aziridine rings to
attack Glioblastoma. I remember by introducing just one Aziridine
and one Carbamate moiety to Dinitro Benzine ring, at the London
University I produced such a toxic compound against tumors whose
toxicity could not be measured. With the Quinone ring, I could
introduce two Aziridine rings and two Carbamate moieties and
could create havoc for Glioblastoma. Within three years, I made 45
analogs of Quinone. One of the Quinone carries two aziridines and
two carbamate moieties which was so toxic to Glioblastoma.
The tumor stop growing and started shrinking. I named the Diaziridine
Dicarbamate Quinone, AZQ. My major concern was how
toxic this compound would be to the normal brain cells. Fortunately,
brain cells do not divide, only cancer cells divide. AZQ acts as a
Prodrug. A Prodrug is compound carrying a chemical by masking
group that renders it inactive and nontoxic. Once the prodrug
reaches a treatment site in the body, removing the mask frees the
active drug to go only where it is needed, which helps avoid systemic
side effects. To grow rapidly, cancer cells use Glucose as a source of
energy. Glucose is broken down to produce Lactic acid. It is the acid
which activates the aziridine and carbamate moieties generating
Carbonium ions attacking Glioblastoma which stop growing and
start shrinking. My drug AZQ is successful in treating experimental
brain tumor because I rationally designed to attacks dividing DNA.
Radio labeled studies showed that AZQ bind to the cancer cells DNA
and destroy brain tumor and normal brain cells are not affected at
all. AZQ is a new generation of drugs.
Not so long ago, these cancers mean death. Now, we have changed
it from certain death to certain survival. The immunologists in our
laboratories are developing new treatment technique by making
radio labeled antigens to attack remaining cancer cells without harming normal cells. We have cured many forms of cancer. We
have eliminated childhood leukemia, Hodgkin disease, testicular
cancer and now AZQ type compounds which are being developed
rationally. While most anti-cancer drugs such as Adriamycin,
Mitomycin C, Bleomycin etc., in the market are selected after a
random trial of thousands of chemicals by NCI, AZQ is rationally
designed for attacking the DNA of cancer cells in the brain without
harming the normal cells. We are testing combinations of these
drugs to treat a variety of experimental cancers in animals [19-21].
In developing drugs for treatments, we poison bad DNA selectively.
All poisons are a class of chemicals that attacks all DNA good and
bad alike. Chemicals that cause cancer, at a safe level, can also cure
cancer. Science teaches us to selectively attack bad sets of DNAs
without harming the good sets of DNAs.
Poisons are injurious to living creatures. There is a small class
of chemical, when exposed to humans, disrupt the function of DNAs,
and make normal cells abnormal and they are called cancer causing
chemicals or carcinogens. I must confess, we still use surgery to cut
off a cancerous breast; we still burn cancer cells by radiations; and
we still poison cancer cells by chemicals. The largest killer of women
is breast cancer. After all the treatment, the remaining cancer cells
return as metastatic cells and kill breast cancer patients in three
years. A decade from now, these methods could be considered as
brutal and savage, but today that is all we have. We hope to develop
new treatment for Breast Cancer. Hopes means never ever to give
up. As I said above, I rationally design drugs to treat Brain cancer. I
am the discoverer of AZQ (US Patent No. 4,146,622 & 4,233,215). I
shared a 17-year royalty with two of my colleagues. The discovery
of AZQ has been a quarter century long effort starting from the
Royal Cancer Hospital, University of London, England and ending in
the National Cancer Institute, Washington, America.
Some may think that we are very lucky. The fact is that luck
has nothing to do with it. It is a shear hard work. I had already
made over one hundred derivatives of Aziridine drugs which
tested against experimental animal’s tumors and published with
Professor Ross before I came to America and joined NCI (National
Cancer Institute). Let me share with you how we sweated for
making AZQ. To introduce one successful drug for treating one
kind of cancer, over the last 25-year period, I conducted over 500
experiments, out of which 200 drugs were tested in thousands of
animals and only 45 drugs were considered valuable enough to be
patented by US government and only one drug, AZQ, has recently
undergoing extensive several Phase-III clinical trials which showed
that patients receiving AZQ live 20 to 24 months longer than the
untreated patients. This period gives physicians enough time to
develop alternative treatment to eliminate the remaining resistant
cancer cells by Immunotherapy. For the discovery of AZQ, I was
honored with the “2004 NIH Scientific Achievement Award”, one of
America’s highest awards in medicine (Figures 1-6).
Conclusion
The Impact of sequencing human genome on the origin of life is
considered. Has all life always been on planet Earth as it is today?
The answer is no. The sequencing of hundreds of living species
showed that the complexity of life begins with simpler life form
over millions of years. We have a common ancestor who came out
of a Darwin’s warm little pond over four billion years ago, the proof
of our common ancestor came from the sequencing the book of life
of many species and comparing their genomes. We discovered that
the book of life of all living creature from the tiny blade of grass to
the mighty Elephant including Man, Mouse and Monkey is written
using the same four genetic letters, that is the nucleotides, Adenine
(A) Thiamine (T), Guanine (G) and Cytosine (C) and it is written in
double helix. Life is simply a series of coordinated complex chemical
reactions inscribed on the strings of the above four nucleotides
called the DNA.
The proof of our evolution from the simpler to the more complex
forms of life came from the sequencing of their DNA extracted from
their fossils trapped in the ancient rocks. If you were to examine,
geologic formation of the layers of rocks from Pre-Cambrian era
to the present era, you will find no human fossils was discovered
until you come to the three million old rocks. Johnson and his team
found the first fossil of a bipedal chimp-human in a three and a half
million old rocks found near the Haggar Valley in Ethiopia. These
were the bones of an 18-year-old woman called Lucy. We have all
descended from her. She was the mother of us all. The faster we
learn this truth that you and I are brothers and sisters’ children
of the same mother, a black woman who was born in Africa three
and a half million years ago, the better it is for all of us then and
only then men and women of different races, different religions and
different nations will respect each other and treat each other like
brothers and sisters and time begins now.
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