GENETICS The Future of Medicine
DNA contains instructions for everything our cells do, from conception until death. Studying the human genome—all the DNA in our

cells—allows us to explore fundamental details about ourselves. The

Human Genome Project, the international quest to understand the

genomes of humans and other organisms, will shed light on a wide

range of basic questions, like how many genes we have, how cells

work, how living things evolved, how single cells develop into complex

creatures, and what exactly happens when we become ill. Besides

answering innumerable questions about our molecular selves, a deeper understanding of the fundamental mechanisms of life promises to

lead to an era of molecular medicine, with precise new ways to prevent, diagnose and treat disease.

The Human Genome Project (HGP) began in the United States in

1990, when the National Institutes of Health and the Department of

Energy joined forces with international partners to decipher the

massive amount of information contained in our genomes. The HGP

began with a set of ambitious goals but has exceeded nearly all of its

targets. Frequently ahead of schedule, HGP scientists have produced

an increasingly detailed series of maps that help geneticists navigate through human DNA. They have mapped and sequenced the

genomes of important experimental organisms. They completed a

working draft covering 90 percent of the genome in 2000, and by

2003, they will finish the sequence with an accuracy greater than

99.99 percent—fewer than one mistake every 10,000 letters. 

The HGP began transforming biology as soon as it started, because

the information it generates has been disseminated rapidly through

unrestricted, public databases. That information fuels today’s heady

pace of discoveries into the genetic basis of a wide range of disorders. These include diseases caused by changes in single genes to

more common diseases—like cancer, Alzheimer disease, diabetes, and

heart disease—where several genes in interaction with environmental

factors influence who develops a disease and when. 

The Human Genome

Project

Exploring Our 

Molecular Selves

The Future of Medicine
1

Map and sequence the human genome

• Build genetic and physical maps spanning the human 

genome.

• Determine the sequence of the estimated 3 billion letters 

of human DNA, to greater than 99.99 percent accuracy.

• Chart variations in DNA spelling among human beings.

• Map all the human genes.

• Begin to label the functions of genes and other parts 

of the genome.

Map and sequence the genomes of important model 

organisms 

(The approximate number of letters, or base pairs, in each

species’ genome is given in parentheses.)

• The bacterium Escherichia coli (4.6 million)

• The yeast Saccharomyces cerevisiae (12 million)

• The roundworm Caenorhabditis elegans (97 million)

• The fruit fly Drosophila melanogaster (165 million)

• The mouse Mus musculus (3 billion)

• Other organisms (rat, zebrafish, chimpanzee, dog) 

will follow

Collect and distribute data

• Distribute genomic information and the tools for using it 

to the research community.

• Release within 24 hours all sequence data that spans 

more than 2000 base pairs.

• Create and run databases.

• Develop software for large-scale DNA analysis.

• Develop tools for comparing and interpreting 

genomic information.

• Share information with the wider public.

Study the ethical, legal, and social implications of genetic

research

Train researchers

Develop technologies

• Make large-scale sequencing faster and cheaper.

• Develop technologies for finding sequence variations.

• Develop ways to study functions of genes on a 

genomic scale.

Transfer technologies to the private sector

Goals of the 

Human Genome 

Project 

Human Genome Project
Genes are made of DNA, a long, thread-like molecule. Almost all human

cells contain 23 pairs of chromosomes; each chromosome contains a

molecule of DNA with hundreds to thousands of genes arrayed along it.

Genes usually code for proteins, the diverse molecules that perform a

wide variety of specialized tasks. For example, proteins transmit messages between cells, fight infections, turn genes on or off, sense light

and scents and flavors, and form structures, such as tendons and hair. 

The instructions for making proteins are written with a four-letter 

alphabet—A, G, C, and T—where each letter represents one of the four

chemical units strung together in DNA. 

A single misspelling in the DNA sequence can make a protein 

malfunction, which, in turn, may cause disease.

Alterations in our genes are responsible for an estimated 5000 

clearly hereditary diseases, like Huntington disease, cystic fibrosis, and

sickle cell anemia. The spellings of many other genes influence the

development of common illnesses that arise through the interaction 

of genes with the environment.

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Unlocking the mysteries 
3

Connecting a gene with a disease was a slow, arduous, painstaking,

and frequently imprecise process before the advent of the HGP.

In 1989, geneticists had tracked down only four genes associated with

disease by sorting through heredity. By 1998, the same list included

more than 100 genes. Consider two gene hunts, eight years apart: in

1989, scientists found the gene for cystic fibrosis after a 9-year search;

eight years later, a gene for Parkinson disease was mapped in only 

9 days, and precisely described within 9 months. 

With more and more DNA sequence deposited in electronic databases,

researchers spend less time collecting data with their own experiments

and more time analyzing the wealth of data available to them. They can

electronically scan long stretches of DNA to find genes in the sequence

that may be responsible for a particular disease. Those are called candidate genes. If a candidate gene actually does play a role in a disease, it

should be spelled differently in people with the disease compared to

those without it; the alteration in spelling somehow disrupts the normal

function of the gene product. For example, rare cases of early-onset

Parkinson disease can result from a change in just one DNA letter, which

in turn, changes one of the 140 amino acids that make up a key protein. 

The gigabytes of DNA sequence data flowing from the HGP and the progressively more detailed catalog of human sequence variations are helping scientists study increasingly complex genetic questions. Instead of

restricting their studies to conditions caused by mutations in single

genes, scientists can now study the genetic basis for complex diseases,

like diabetes and Alzheimer disease, that involve several genes. 

Gene Discovery 

Gene Discovery

of health and disease
Basic Genetics 

Basic Genetics 

Human cell 

Almost all of the 100 trillion cells in

the human body contain a copy of

the entire human genome, the complete set of genetic instructions necessary to build a human being. 

4

Cell nucleus 

The nucleus is a separate compartment 

in the cell that contains 6 feet of DNA

packed into 23 pairs of chromosomes. 

We each inherit one set of 23 chromosomes from our mother, and another 

set from our father. Egg and sperm cells

carry single sets of 23 chromosomes.

Gene 

Each gene contains a segment of

DNA, typically several thousand base

pairs long, that is copied into a molecule of RNA. Usually, the information

in RNA is translated to make a protein. 

Chromosome 

Each of the human chromosomes contains hundreds to thousands of genes,

the major functional units of DNA. 

DNA

DNA, or deoxyribonucleic acid, is a

long molecule made of two twisting,

paired strands. Each strand is made of

four chemical units, called nucleotide

bases, strung together in a precise

order, just as letters string together to

make specific words. The bases are

adenine (A), guanine (G), cytosine (C),

and thymine (T). The bases on opposite

strands pair specifically; an A always

pairs with a T, and a C always with a G.

Each such pair is called a base pair of

DNA.

Basic G

• •

• •

•
RNA 

RNA, or ribonucleic

acid, is chemically

similar to DNA,

except it is singlestranded, not double-stranded; it 

contains the base

uracil (U) instead of

thymine (T); it can

migrate out of the

nucleus. The

sequences of most

RNA molecules are

translated to make

proteins.

Basic Genetics Glossary 5

Protein 

Proteins make up essential parts of 

tissues and guide chemical reactions 

in living things. They are made of 20 

different building blocks called amino

acids. The DNA sequence of a gene

determines the amino acid sequence of

the protein that gene encodes. The

amino acid sequence of the protein is, in

turn, responsible for the protein’s shape

and function. 

Normal CF sequence

Mutated CF sequence 

Person 1

Person 2

C G G TA C T T G A G G C T A 

CGGTACT C G A G G C T A 

ATT ATC ATC TTT GGT GTT TCC 

ATT ATC TTT GGT GTT TCC

enetics

Genome

A genome is all the DNA— the 

complete genetic inheritance—in an

organism. The human genome is

contained in 23 pairs of chromosomes housed in the nucleus and the

small circle of DNA present in 

mitochondria, the organelles that

process energy. The number of

genes in the approximately 3 billion

base pairs of human DNA is still not

known, but is probably between

35,000 and 100,000.

Mutation

Mutations are changes in DNA spelling

that can prevent proteins from functioning normally and cause health 

problems. 

Three DNA bases are 

deleted in the mutated 

sequence, resulting in 

the deletion of an amino 

acid (phenylalanine) 

from the CF protein. 

People with the 

abnormal protein 

develop cystic fibrosis. 

• •

•

•

•

▼ ■ ■ ▲ ◆ ● ★

▼ ■ ▲ ◆ ● ★

SNP

SNP

Pronounced “snip,” SNPs are singlenucleotide polymorphisms or one-letter

variations in the DNA sequence. SNPs

contribute to differences among individuals. The majority have no effect, others

cause subtle differences in countless

characteristics, like appearance, 

while some affect the risk for certain

diseases. 
Knowing the DNA sequence of a gene reveals the basic structure of

the protein that gene encodes. Scientists can sometimes deduce the 

3-dimensional shape and function of the protein as well. Often, they 

can classify the protein because of similarities to other proteins. For

instance, when scientists discovered the gene for cystic fibrosis, the

sequence immediately suggested that the CF protein is a gatekeeper

embedded in the membrane that surrounds a cell. The sequence also

implied that the protein specifically allows salt to pass through the 

membrane. This fit nicely with the idea that a problem with the 

transport of salt and water might cause CF and explain why mucus 

tends to dry up in the lungs of people with the disease.

Experimental animals play an important role in helping scientists understand the biological function of genes. Human genes have relatives in

the genomes of other animals. Even species as seemingly different from

us as yeast, roundworms, or fruit flies share many similar genes. In fact,

comparing DNA from different species and finding stretches where the

sequence is conserved can highlight particularly important features.

Often, insights about human diseases come when a newly discovered

human disease gene has a close relative in another species such as the

mouse or even the fruit fly—species where the role of that gene can be

studied and placed in context. For example, the role of some human 

genes in cancer is understood better than otherwise possible because 

scientists have studied related genes in flies, finding that many 

of them guide embryonic development. In both cases—preventing 

cancer and developing normally—cell communication 

is key.

Understanding 

Biological 

Function

Biological

even roundworms and fruit flies share

6
7

With the genome sequenced and a

complete catalog of genes in hand, 

scientists can begin to study gene

activity comprehensively. They can 

use microarrays like the one shown, for

example, to see how tens of thousands

of genes are turned on or off in different types of cells and in response to

different stimuli. They can begin to

study the complete array of genetic

interactions in cells. 

Function

many similiar genes with us

Gene Function
8

Genetic 
Examining how a particular gene is spelled in an individual can serve

quite a few uses:

Diagnosis Genetic analysis now can classify some conditions, like colon

cancer and skin cancer, into finer categories. This is important since classifying diseases more precisely can suggest more appropriate treatments. The same approach will soon be possible for heart disease, schizophrenia, and many other medical conditions, as the genetic underpinnings for these diseases become more completely understood. 

Pharmacogenomics is a new word that scientists and drug developers

use. It describes the idea of tailoring drugs for patients, whose individual

response can be predicted by genetic fingerprinting. For example, cancer

patients facing chemotherapy may experience fewer side effects and

improve their prognoses by first getting a genetic fingerprint of their

tumor. This fingerprint can reveal which chemotherapy choices are most

likely to be effective. Better understanding of genetics promises a future

of precise, customized medical treatments.

Prognosis Diagnosing ailments more precisely will lead to more reliable

predictions about the course of a disease. For example, a genetic workup can inform a patient with high cholesterol levels how damaging that

condition is likely to be. And doctors treating prostate cancer will be 

able to predict how aggressive a tumor will be. For many diseases, such

genetic information will help patients and doctors weigh the risks and

benefits of different treatments.

Prevention Once scientists figure out what DNA sequence changes in 

a gene can cause disease, healthy people can be tested to see whether

they risk developing conditions like heart disease, diabetes, or prostate

cancer later in life. In many cases, this advance warning can be a cue to

start a vigilant screening program, to take preventive medicines, or to

make diet or lifestyle changes that might prevent the disease altogether. 

For example, those at risk for colon cancer could undergo frequent

colonoscopies; those with hereditary hemochromatosis, a common 

disorder of iron metabolism, could donate blood periodically to remove

excess iron and prevent damage to the body. Some women at risk for

breast cancer could benefit from tamoxifen; a young person at risk for

developing lung cancer may become particularly motivated to quit

smoking; those with familial hypercholesterolemia could begin treatment

to lower their cholesterol levels and prevent heart attacks and strokes.

Unfortunately, our ability to predict a disease sometimes precedes our

ability to prevent or treat it. For example, a genetic test has been available for Huntington disease for years, but no treatment is available yet.

As a result, only a minority of people at risk have chosen to be tested. 

9

Genetic Testing and 

Gene-based Medicine

Testing

Genetic Medicine
10

Gene-base
11

d Therapy

Newborn screening A particular form of predictive testing, newborn

screening can sometimes help a great deal. For example, babies in the

United States and a few other countries are routinely screened for

phenylketonuria (PKU), a metabolic disorder that prevents the breakdown of phenylalanine, one of the building blocks of proteins and a component of the artificial sweetener Aspartame. Excess phenylalanine in

the body is toxic to the nervous system. In the past, children with the

condition became severely mentally retarded, but the screening program

identifies children with the enzyme deficiency, allowing them to grow

normally on a diet that strictly avoids phenylalanine. 

Carrier screening For some genetic conditions, people who will never

be ill themselves can pass a disease to their children. Some couples

choose to be tested for this risk before they marry, especially in communities where a feared childhood disease is particularly common. For

example, carrier testing for Tay-Sachs disease, which kills young children

and is particularly common in some Jewish and Canadian populations,

has been available and widely used for years. 

Gene therapy Replacing a misspelled gene with a functional gene has

long been an appealing idea. Small groups of patients have undergone

gene therapy in clinical trials for more than a decade, but this remains

an experimental treatment. Eventually, it likely will become a common

treatment for some conditions. 

Gene-based therapy Great medical benefit likely will derive from drug

design that’s guided by an understanding of how genes work and what

exactly happens at the molecular level to cause disease. For example,

the causes of adult-onset diabetes and the resulting complications

remain difficult to decipher and, so, to treat. But researchers are optimistic that a more precise understanding of the underlying causes will

lead to better therapies. In many cases, instead of trying to replace a

gene, it will be more effective and simpler to replace the protein the

gene would give rise to. Alternatively, it may be possible to administer 

a small molecule that interacts with the protein—as many drugs do—and

changes its behavior.

One of the first examples of such a rationally-designed drug targets 

the genetic flaw that causes chronic myelogenous leukemia, a form of

leukemia that mostly affects adults. An unusual joining of chromosomes

9 and 22 produces an abnormal protein that spurs the uncontrolled

growth of white blood cells. Scientists have designed a drug that 

specifically attaches to the abnormal protein and blocks its activity. 

In preliminary tests, blood counts returned to normal in all patients

treated with the drug. And, compared with other forms of cancer 

treatment, the patients experienced very mild side effects.

Instead of having to rely on chance and screening thousands of molecules to find an effective drug, which is how most drugs we use today

were found, scientists will begin the process of drug discovery with a

clearer notion of what they’re looking for. And because rationally

designed drugs are more likely to act very specifically, they will be less

likely to have damaging side effects.

Genetic Medicine
12
Molecular biology has long held out the promise of transforming medicine from a matter of serendipity to a rational

pursuit grounded in a fundamental understanding of the

mechanisms of life. Genomics will hasten the advance 

of molecular biology into the practice of medicine. 

As the molecular foundations of diseases become clearer, 

we may be able to prevent them in many cases and in

other cases, design accurate, individualized treatments 

for them. Genetic tests will routinely predict individual

susceptibility to disease. Diagnoses of many conditions 

will be much more thorough and specific than now. New

drugs, derived from a detailed molecular understanding 

of common illnesses like diabetes and high blood pressure,

will target molecules logically. Drugs like those for cancer

will routinely be matched to a patient's likely response.

Decades from now, many potential diseases may be 

cured at the molecular level before they arise. 

All these changes aren't likely to come quickly. It will take

a long time to understand the human genome. But access

to genome sequence will increasingly shape the practice 

of health care over the coming decades, as well as shed

light on many of the mysteries of biology. 

Disease with 

Genetic 

Component

Development of Genetic Medicine

Prevention 

Pharmacogenomics

T I M E

Gene Therapy

Drug Therapy

Map

Gene(s) Identify 

Gene(s)

Understand 

Underlying Biology

Written by Karin Jegalian

Diagnostics
Howard Hughes Medical Institute

www.hhmi.org

Nature

International Weekly Journal of Science

www.nature.com/genomics

Pharmaceutical Research and 

Manufacturers of America

hhtp://genomics.phrma.org/

Science

Global Weekly of Research

www.scienceonline.org

American Society of Human Genetics

www.faseb.org/genetics/ashg/ashgmenu.htm

NIH Publication No. 00–4873 

Produced by

National Human Genome Research Institute

National Institutes of Health

www.nhgri.nih.gov

With co-sponsorship by

Office of Biological and Environmental Research

U.S. Department of Energy

www.ornl.gov/hgmis