A Century of Progress: 

Milestones in Sickle Cell Disease

Research and Care

Introduction

In 1910, Chicago physician James B. Herrick published a description of oddly shaped blood cells taken from dental student Walter 

Clement Noel, providing the first detail in Western medical literature of what has come to be known as sickle cell disease.

One hundred years later we know that the sickle-shaped cells are due to a defect in hemoglobin, the protein in red blood 

cells that carries oxygen throughout the body. A genetic alteration in the hemoglobin molecule causes the body to produce 

misshapen red blood cells, many of which take the characteristic “C”-shape that is the hallmark of sickle cell disease. 

What is Sickle Cell Disease?

Sickle cell disease, also known as sickle cell anemia, is inherited. 

People who have the disease inherit two copies of the sickle 

cell gene—one from each parent. The gene codes for production

of an abnormal hemoglobin. If a person inherits only one 

copy of the sickle cell gene, he or she will have sickle cell trait. 

People who have sickle cell trait do not have the disease, 

but they carry one of the genes that causes it. Similar to 

people who have sickle cell disease, people with sickle cell 

trait can pass the gene to their children. 

In the United States, sickle cell disease affects an estimated 

70,000 to 100,000 people, the majority of whom are African 

Americans. All states screen newborns for sickle cell disease. 

Sickle cell disease occurs in approximately one out of every 

500 African American births and one out of every 36,000 

Hispanic American births. In addition, about 2 million people 

in the United States have sickle cell trait.

The symptoms and complications of sickle cell disease vary 

widely. Some people have mild symptoms while others have 

very severe symptoms and are hospitalized frequently for 

treatment. Normal red cells pass smoothly through the blood 

vessels, but sickled cells are stiff and sticky. Sickled cells tend 

to form clumps that can block blood flow and lead to episodes 

of extreme pain, known as crises, as well as chronic damage 

to vital organs. Persons with sickle cell disease have life-long 

anemia because their red blood cells survive only about 

one-tenth as long as cells with normal hemoglobin.

Bone marrow transplants offer a cure to children and 

adolescents who have a matched bone marrow donor. 

Because of the limited availability of matched bone marrow 

donors, however, sickle cell disease has no widely available 

cure. Treatments are available to address symptoms 

and complications.

People who have sickle cell disease now lead longer, more 

productive lives. In the early 1970s, the average lifespan was 

only 14 years. Today, individuals with sickle cell disease are 

living into their forties or fifties, and beyond.

The National Heart, Lung, and Blood Institute

The National Heart, Lung, and Blood Institute (NHLBI), which 

is part of the National Institutes of Health, has funded sickle 

cell research since 1948, when the NHLBI was founded as the 

National Heart Institute. Since 1972, when the National Sickle 

Cell Disease Program began, the NHLBI has spent more than 

$1 billion on sickle cell research.

The NHLBI has played a crucial role in not only funding basic 

research but also devising and implementing large clinical 

trials, and conducting workshops and consensus meetings to 

guide the research agenda. Research on sickle cell disease 

and other diseases that affect hemoglobin has played a 

central role in the advancement of genetics and molecular 

biology and has sparked innovations in other areas of medicine.

More important, the contributions of clinical trial participants 

have been essential for the development of new treatments 

for sickle cell disease. Because of their contributions, we 

have gained an understanding of the molecular causes of the 

disease; developed effective approaches for preventing and 

treating its complications including infection, stroke, and lung 

disease; and even cured a small number of people using bone 

marrow transplantation.

Future

The past 100 years of sickle cell research have resulted in landmark discoveries that ushered in the era of molecular genetics.

The NHLBI continues to look ahead to find new and better treatments. Its revitalized research portfolio of basic, clinical, and 

translational research addresses the genetic factors affecting disease manifestations, regulation of hemoglobin synthesis, 

development of drugs to increase fetal hemoglobin production, and the development of animal models for preclinical studies. 

The Institute supports research on transplantation of blood-forming stem cells, gene therapy, a better understanding of and new 

treatments for pain, optimal uses of blood transfusion, and management of iron overload related to blood transfusions.

The Institute is also leading an effort to develop evidence-based clinical practice guidelines for the care of people who have 

sickle cell disease, which are expected to be released in 2011. The NHLBI is committed to working with other agencies within 

the Department of Health and Human Services to disseminate the clinical guidelines with an emphasis on use by primary care 

practitioners. To ensure that the new guidelines reach their intended audiences, the NHLBI will launch a public awareness and 

education campaign to focus nationwide attention on sickle cell disease as a serious public health issue.

The NHLBI recognizes that actively engaging patients, families, practitioners, and communities is essential to improving the 

lives of persons affected by sickle cell disease, and will continue to work with them, community-based groups and scientific 

organizations to do so.

Sickle Cell Disease and Clinical Trials

The NHLBI sponsors a number of important clinical trials designed to advance the search for better treatments of sickle cell 

disease. These studies would not be possible without the participation of volunteers who help researchers determine which 

treatments work. For information on current clinical trials, please visit: http://www.clinicaltrials.gov/.

More information on sickle cell disease is available at http://www.nhlbi.nih.gov/new/sicklecell.htm. 

NHLBI Health Information Center

P.O. Box 30105

Bethesda, MD 20824-0105

Phone: 301-592-8573

TTY: 240-629-3255

Fax: 301-592-8563

Discrimination Prohibited: Under provisions of applicable public laws enacted by Congress since 1964, no person in the United States shall, on the grounds 

of race, color, national origin, handicap, or age, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any 

program or activity (or, on the basis of sex, with respect to any education program or activity) receiving Federal financial assistance. In addition, Executive 

Order 11141 prohibits discrimination on the basis of age by contractors and subcontractors in the performance of Federal contracts, and Executive Order 

11246 states that no federally funded contractor may discriminate against any employee or applicant for employment because of race, color, religion, sex, 

or national origin. Therefore, the Heart, Lung, and Blood Institute must be operated in compliance with these laws and Executive Orders.

Photo credit for 1910 Herrick paper: Archives of Internal Medicine, 1910, VI(5):517-521, Copyright © 1910 American Medical Association. All right reserved.

Publication No: 10-7657

September 2010
1910

Chicago physician James B. Herrick 

first publishes a description of sickled 

cells in a blood sample from 20-year-old 

dental student Walter Clement Noel 

from Grenada. Term “sickle cell 

anemia” coined based on paper.

Sickled cells from 1910 Herrick paper

Dr. James Herrick

“ The shape of the reds was very 

irregular, but what especially 

attracted attention was the large 

number of thin, elongated, sickleshaped and crescent-shaped forms.” 

– Dr. James B. Herrick

1933

Scientists test 2,500 African Americans in 

Memphis; determine sickle cell trait and 

sickle cell disease are separate entities. 

1934

Painful sickle cell “crises” suggested 

to result from blockages of small 

blood vessels. 

1940

Researchers suggest exchange of 

oxygen for carbon dioxide occurring in 

small blood vessels may cause red blood 

cells to sickle and block blood vessels.

1945 

“ There are frequent abdominal 

crises which may mislead the best 

surgeon into operating for some 

acute surgical condition when 

the real diagnosis is sickle-cell 

anemia...” 

– Dr. John T. Givens, Journal of 

the National Medical Association

1948

The National Heart Institute established. 

First round of grants includes $8,640 

to Dr. James Neel to study inheritance 

of sickle cell disease. 

Dr. James Neel

Research suggests low concentration 

of sickled cells in blood from newborns 

with sickle cell disease due to high 

level of fetal hemoglobin in their red 

blood cells. 

“ There are many things yet to be 

learned about sickle cell anemia. 

Fame and distinction await the 

man who can solve the problems 

of this malady.” 

– Editorial, Journal of the 

National Medical Association

1949

Dr. Linus Pauling and others reveal 

that sickle cell disease due to abnormal 

hemoglobin protein molecule. Term 

“molecular disease” coined.

1949-1950

Inheritance of sickle cell disease 

independently described by two 

teams. Sickle cell genes needed from 

both parents to produce sickle cell 

disease. Receiving gene from one 

parent produces sickle cell trait. 

Public Awareness Poster

1951

Scientific American runs story on 

Pauling’s discovery of molecular 

nature of sickle cell disease, raising 

public awareness of the condition.

Dr. Linus Pauling

1953

Diagnostic tool developed to identify 

sickle cell disease and other conditions 

due to defective hemoglobin.

1954

Sickle cell trait found to protect 

against malaria. Finding explains why 

the prevalence of the sickle gene in 

Africa corresponds with regions where 

malaria is a major cause of death.

1955

Blood test developed to identify 

abnormal hemoglobin, a method 

still used today to confirm sickle cell 

disease diagnosis.

1957

Scientists show abnormality of 

sickle hemoglobin due to amino acid 

substitution in protein, making sickle 

cell disease the first genetic disorder 

whose molecular basis is known.

1959 

Marclan A. Walker, a 21-year-old West 

Virginia college student, describes 

life with sickle cell disease in the 

Ebony magazine story, “I’m living 

on borrowed time.” Story was later 

picked up by Time magazine.

1963

The three-dimensional structure of 

the hemoglobin protein deciphered 

using x-ray crystallography. 

Monumental accomplishment took 

over 20 years to complete. Dr. Max 

Perutz received the Nobel Prize for 

this work in 1967.

1968

Researchers describe red cells from 

individuals with sickle cell disease 

that remain sickled even when oxygen 

levels are restored. Cells termed 

“irreversibly sickled.” 

1969 

National Heart Institute becomes 

National Heart and Lung Institute.

1970

“ What has been little appreciated, 

despite all this study and interest, is 

the real importance of the disease 

as a community health problem.” 

– Dr. Robert B. Scott, 

Journal of the American 

Medical Association

1971 

The National Association for Sickle 

Cell Disease founded. It becomes 

the Sickle Cell Disease Association of 

America, Inc. in 1994. 

“ It is a sad and shameful fact 

that the causes of this disease 

have been largely neglected 

throughout our history. 

We cannot rewrite this record 

of neglect, but we can reverse it. 

To this end, this administration 

 is increasing its budget for 

research and treatment of 

sickle-cell anemia . . .” 

– President Richard Nixon, 

in his “Special Message to 

the Congress Proposing a 

National Health Strategy”

1972

National Sickle Cell Anemia Control 

Act provides for establishment 

of voluntary sickle cell disease 

screening; counseling; public and 

professional education; and research 

and training in diagnosing, treating, 

and controlling disease. Howard 

University’s Dr. Roland Scott played 

a leading role in advocating for the act.

Dr. Roland Scott

A milder variation of sickle cell 

disease found in Saudi Arabia 

associated with increased levels of 

fetal hemoglobin. Finding suggested 

increasing fetal hemoglobin levels 

could offer treatment target.

Bill Cosby stars in TV movie “To All 

My Friends On Shore,” which addresses 

sickle cell disease.

1972-1973

ational Sickle Cell Disease Program 

stablished. The National Heart 

nd Lung Institute begins funding 

omprehensive sickle cell centers and 

stablishes sickle cell branch at Institute. 

973

cientists develop neonatal screening 

ethods using blood spots on 

lter paper. 

idney Poitier directs and stars in 

ovie “A Warm December,” which 

as sickle cell disease as a central theme.

974

easibility of newborn screening for 

ickle cell disease demonstrated. 

ethod for prenatal diagnosis 

y sampling fetal blood from the 

mbilical vein developed.

975

ew York becomes first state to 

equire newborn screening for sickle 

ell disease.

976

ational Heart and Lung Institute 

ecomes the National Heart, Lung, 

nd Blood Institute (NHLBI).

N

e

a

c

e

1

S

m

fi

S

m

h

1

F

s

M

b

u

1

N

r

c

1

N

b

a

1978

Prenatal method to diagnose sickle cell 

disease using DNA samples reported.

The NHLBI launches multicenter study 

with 4,000-plus individuals from 

newborns to age 70. First study to 

document clinical course of disease 

from birth to adulthood.

1979

Red blood cells from patients with 

sickle cell disease shown to stick more 

readily to cells lining blood vessels 

than do normal red blood cells.

1980

Binding of sickled red blood cells to 

the inside of blood vessels shown to 

block blood flow. Extent of stickiness 

suggested as possible determinant of 

disease severity. 

1982

The NHLBI first publishes “The 

Management of Sickle Cell Disease.” 

The compound 5-azacytidine shown 

to elevate fetal hemoglobin levels.

1984

Several teams independently 

demonstrate that hydroxyurea 

increases fetal hemoglobin levels.

Bone marrow transplant performed 

to treat a child with leukemia. It also 

cures the child’s sickle cell disease.

1986

An NHLBI study shows penicillin as 

a preventive measure in children 

with sickle cell disease 3 months to 3 

years old can reduce the incidence of 

Streptococcus pneumonia infection, 

a major cause of childhood death, by 

84 percent. Practice later becomes 

widely adopted.

1987

IH Consensus Development Panel 

ecommends screening all U.S. 

ewborns for sickle cell disease 

nd giving penicillin to all affected 

nfants by 3 months of age. 

NIH Consensus Development 

Panel Report

ewborn screening for sickle cell 

isease required in 44 states, the 

istrict of Columbia, Puerto Rico, 

nd the U.S. Virgin Islands.

991

irst line of mice that have sickle 

ell disease developed to aid in 

nding treatments.

tudy shows even small increases in 

etal hemoglobin can result in fewer 

ain crises.

995

ajor NHLBI-sponsored study 

hows hydroxyurea reduces number 

f pain crises and related hospital 

isits by 50 percent. Treatment 

ncreases fetal hemoglobin levels 

nd is first effective therapy for 

everely affected adults with sickle 

ell disease. 

HLBI-sponsored study shows once 

 child with sickle cell disease is 5 

ears old, penicillin treatment can 

e stopped.

N

r

n

a

i

N

d

D

a

1

F

c

fi

S

f

p

1

M

s

o

v

i

a

s

c

N

a

y

b

1996

Method developed to use maternal 

blood sample for prenatal diagnosis 

of disease. 

Multicenter study of bone marrow 

transplantation in children with 

sickle cell disease finds the procedure 

can cure young sickle cell patients 

who have siblings that share a 

specific protein.

1997

Periodic blood transfusions in children 

with sickle cell disease who are at 

high risk for stroke shown to reduce 

risk of first stroke by 90 percent. 

“W ith the completion of [this 

study], we now know that we 

can effectively prevent the 

two leading causes of death in 

children with sickle cell disease: 

pneumococcal sepsis and stroke.” 

– “S ickle Cell Research for 

Treatment and Cure,” NHLBI

1998

The Food and Drug Administration 

approves hydroxyurea for sickle cell 

disease treatment in adults based on 

NHLBI-sponsored study.

2001

Program starts to collect 

umbilical cord blood from sibling 

donors in families with children 

who have sickle cell disease or 

thalassemias with the goal of future 

transplantation. 

Researchers use gene therapy to 

correct sickle cell disease in mice.

2002

The Health Resources and Services 

Administration Newborn Screening 

Program starts.

2003

Hydroxyurea therapy found to 

improve survival in adults most 

severely affected with disease.

2004

Study finds children with sickle 

cell disease at high risk for stroke 

who stop receiving periodic blood 

transfusions after 30-month 

minimum return to high risk 

of stroke. 

U.S. Postal Service issues Sickle Cell 

Disease Awareness postage stamp.

2006 

The NHLBI launches Sickle Cell 

Disease Clinical Research Network. 

NHLBI scientists find that a 

hormone, brain natriuretic peptide 

or BNP, detected in a simple blood 

test can identify people with sickle 

cell disease who have developed 

pulmonary hypertension, a lifethreatening complication.

2008

The Newborn Screening Saves 

Lives Act of 2007 establishes 

grants to provide for education and 

outreach on newborn screening and 

coordinated follow-up care. 

NIH Consensus Development Panel 

finds hydroxyurea treatment 

underused and recommends its 

increased use in adolescents 

and adults. 

 

NIH Consensus Development Panel Report

“ The compelling benefits of 

hydroxyurea warrant increased 

adoption of this drug as a 

frontline therapy in adults with 

sickle cell disease.” 

– Dr. Otis Brawley, 

conference panel chair

The NHLBI realigns Sickle Cell 

Disease Research Program by 

expanding support for basic 

research and developing a new 

Clinical Trials Research Network 

and evidence-based treatment. 

Also initiates development 

of evidence-based clinical 

practice guidelines.

2009

Study in NHLBI laboratory finds 

modified blood adult stem-cell 

transplant regimen reverses sickle 

cell disease in nine of 10 adults 

severely affected by disease. 

Clinical trial testing of drug 

treatment for pulmonary 

hypertension in adults with 

disease stopped early due to 

safety concerns. 

The NHLBI convenes workshop of 

researchers, health care providers, 

advocacy organizations, patients, 

and others to discuss key public 

outreach issues.

2010

“ I’m only a patient when I’m in 

the doctor’s office, I’m really a 

whole person living an active 

life; I just happen to live with 

sickle cell disease.” 

– Tiffany McCoy, a person who 

lives with sickle cell disease

Tiffany McCoy 

The NHLBI and the Centers for Disease 

Control and Prevention launch 

program to determine the number 

of people diagnosed with inherited 

blood disorders, including sickle 

cell disease. 

NHLBI-supported study shows 

adults with sickle cell disease may 

have changes in brain function. 

James B. Herrick Symposium 

— Sickle Cell Disease Care and 

Research: Past, Present and Future

commemorates 100th anniversary of 

Herrick’s paper that first identified 

sickle cell disease. Symposium 

brings together researchers, health 

care providers, advocacy groups, 

patients, and the public. 

For references on studies noted in 

the timeline, please visit 

http://www.nhlbi.nih.gov/new/

sicklecell.htm.