This year marks the 100th birthday of the widely used medical reference book "The Merck Manual," published by the pharmaceutical giant Merck & Co.

The manual's pocket-size first edition, printed in 1899, listed cod liver oil as a treatment for nervousness and cocaine as a remedy for hysteria. The new centennial edition runs 2,833 pages; its index alone is 177 pages long.

Medicine has come a long way in 100 years.

The editors of The Merck Manual's centennial edition have compiled a list of the 20th century's most significant advances in medicine. Here is their Top 10.

1. Infectious Disease Control.

A century ago, infectious disease was the most common cause of death in the United States. Better control of infectious disease is the biggest reason for the added life expectancy of an American baby born today. Many scourges of the early 20th century, such as tuberculosis, polio, gangrene and influenza, have been held at least partly in check. The main factors include development of antibiotics, which fight bacterial infections; improved sanitation; and a better understanding of the human immune system.

Not that infectious disease is no longer a threat. AIDS remains a rampant epidemic. Tuberculosis, including types resistant to bacteria, is experiencing a resurgence. And new threats such as Ebola virus keep showing up.

2. Immunization.

Mass vaccination campaigns during this century have helped control and even wipe out common killer diseases. The smallpox virus was eradicated during the 1980s. Polio has nearly been eliminated from the United States, and incidence has fallen by 90 percent worldwide in the past decade.

Childhood immunization in the United States has dramatically reduced the incidence of such diseases as diphtheria, whooping cough, tetanus, mumps and measles. Currently recommended childhood vaccines include those against hepatitis B; diphtheria, tetanus and pertussis; childhood meningitis; polio; measles, mumps and rubella; and chickenpox.

3. Vitamins.

Early this century, scientists began to identify substances in food that contain ingredients essential to life and critical to preventing diseases such as scurvy, beriberi, fatal pernicious anemia and rickets. The list of essential vitamins gradually grew to 13, plus vital minerals such as iron and potassium. The 1934 edition of The Merck Manual was the first to include a table of vitamins.

Scientists continue to discover new benefits for "old" vitamins.

For example, folic acid (or folate, a B vitamin) is now known to help prevent neural tube defects such as spina bifida in infants when it is taken by women early in pregnancy.

4. The Framingham Heart Study.

Since 1948, more than 5,000 adults living in or near Framingham, Mass., have participated in one of the most important epidemiological studies in medicine--the Framingham Heart Study. Information obtained over the years from several generations of Framingham residents has led to a greater understanding of cardiovascular disease and its risk factors--such as cigarette smoking and high blood pressure.

While heart disease remains the leading killer of Americans, death rates from cardiovascular illness have fallen steadily during the past 50 years.

The section on cardiovascular disease in the centennial Merck Manual includes nearly 300 pages, more than than entire first edition of the manual.

5. Drugs By Design

Until this century, medical drugs were discovered largely through serendipity. Many well-known early drugs--such as aspirin, digitalis and morphine--were made from flowers, herbs, seeds or tree bark.

With better knowledge of chemistry and the human body, pharmaceutical research became less random. By the 1970s, scientists began to design medicines by deliberately manipulating molecules to act upon a specific part of the body's cells to elicit a specific response. The first drugs designed in this manner were propranolol, a beta blocker for the treatment of chest pain and high blood pressure, and cimetidine, an anti-ulcer medicine.

6. Molecular Genetics.

No field of scientific research has more potential for improving human health than molecular genetics. The first test for genetic defects in fetuses was developed in 1966. Genetic engineering arose in the 1970s as a new way to develop and produce insulin for diabetics, along with a widening variety of other drugs. A technique known as polymerase chain reaction, invented in the 1980s, made it possible to create millions of copies of specific genes. That helped improve detection of viruses and cancers and the matching of donors and recipients of organ transplants. It also led to the Human Genome Project, the ongoing effort to identify and map every one of the estimated 80,000 genes that provide chemical instructions for building and maintaining a human body.

Molecular genetics forms the basis for the still-unrealized promise of gene therapy: the treatment of diseases by manipulating or replacing genes.

7. Health Care Consumerism.

The doctor-patient relationship used to be mainly a one-way street, where doctors dispensed medical information and patients followed those directions without question.

Today, by gathering information from libraries, the news media, patient advocacy and support groups and the Internet, patients have become increasingly knowledgeable about their own health and the treatments available to them. They are more likely than ever to involve themselves directly in medical decisions.

8. Cancer Diagnosis and Treatment.

Even a generation ago, doctors could offer few treatments and little hope for a patient with cancer. Since then, an explosion of knowledge has improved medicine's ability to understand, detect, diagnose and treat cancers.

While cancer remains the nation's second-leading cause of death (after heart disease), the death rate from all cancers has edged down in the past decade, reversing a longtime trend. The probability that a person with cancer will be alive at least five years after diagnosis has also increased markedly.

"Most cancers are potentially curable if detected at an early stage," according to the latest Merck Manual.

9. Organ Transplantation.

The first successful kidney transplant was done more than 40 years ago, between identical twins. Advances in surgery, medication and tissue typing have reduced the risk of organ rejection and opened up the possibilities of transplantation to a growing number of patients. By 1995, one-year survival rates in kidney transplant patients reached 98 percent.

The first successful heart and liver transplants were performed in 1967, and surgeons have also learned how to transplant lungs, pancreases and corneas, among other organs. Only the shortage of donor organs has held in check the growth of transplantation in recent years.

10. Diagnostic Technology.

At the beginning of this century, a physical exam involved taking a medical history and a pulse, but not much else. Today's physical involves a variety of diagnostic tools--including blood tests, the blood pressure cuff and electrocardiograms to record the pace and rhythm of the heartbeat. Other diagnostic tools include Pap smears to detect cervical cancer and an array of techniques by which doctors peer inside the body without surgery: ultrasound, CT scans, MRI scans and mammography. These tests not only help diagnose disease but also help identify risk factors for conditions that have not developed yet.

CAPTION: Children attending a school in Los Angeles in 1955 were among the first to be inoculated with the Salk vaccine for polio.

CAPTION: South Africa's Christiaan Barnard, left, studies a model of the heart with surgeons Michael DeBakey and Adrian Kantrowitz shortly after Barnard completed the first successful heart transplant in 1967.