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Social Benefits of a Successful Biomedical Retired Chairman and CEO, Merck and Company HE PHARMACEUTICAL INDUSTRY has as its objectivethe discovery of important new medicines and vaccines to pre- Tvent and alleviate diseases and to improve health and the qual- ity of life. Merck has been doing that successfully since 1933, whenGeorge W. Merck opened the first laboratory in Rahway, New Jersey.
Through the efforts of its research scientists, the company has contrib-uted drugs and vaccines in numerous therapeutic areas. In 1975, BillCampbell and his research team discovered a medicine for control ofanimal parasites (worms) that ultimately gave Merck an opportunityfew companies have ever had in history.
Campbell’s research group was searching for a medicine that would kill worms in domestic animals—horses, cattle, sheep, and pigs.
To discover such a medicine, they utilized a very simple system: theyput worms into the abdomen of a mouse, then fed the mouse culturesof soil microorganisms that had been collected around the world. Soilmicroorganisms make many interesting substances—including manyantibiotics. Bill believed he might find a microorganism that wouldmake a substance that would kill worms. The Campbell team screenedsoil samples sent from many parts of the world—a total of about fortythousand samples. Only one gave a very interesting response—it killedall the worms implanted in the mouse, and it did this even when theculture broth was enormously diluted, indicating that the active sub-stance in the broth was extremely potent. The substance was isolated,identified, slightly altered chemically to improve its safety, and thentested widely for its effect on many different parasites in the MerckResearch Laboratories. The unique soil microorganism came from thelaboratory of Dr. Satoshi Omura of the Kitasato Institute of Japan.
This exciting new drug, called Ivermectin, was tested against all the economically important parasites that plague the business of farmers PROCEEDINGS OF THE AMERICAN PHILOSOPHICAL SOCIETY
VOL. 145, NO. 4, DECEMBER 2001
who raise livestock. These worms cause billions of dollars of damageto livestock in the United States and other countries around the world.
The amazing thing about this drug was that it not only killed all theworms inside treated cattle, but also killed biting insects on the hides ofthe animals after a single oral or injected dose. Its amazing potency andeffectiveness against a broad array of animal parasites caused the com-pany to develop this drug for most domestic animals—including cattle,horses, sheep, pigs, and, ultimately, dogs (for heart worm). In variousformulations beginning in 1978, it would become the world’s leadingveterinarian product, the best-selling animal drug in history. But whenCampbell’s parasitologists tested Ivermectin for possible use in humans,they discovered that it was not effective against hookworms and tape-worms, some of the most important parasites in humans; thus it wouldnever become an important medicine for people. It was put aside forthat purpose.
In 1980, Dr. Mohammed Aziz, stimulated by an observation in Campbell’s laboratory that Ivermectin was able to kill a commerciallyunimportant horse parasite that existed as a microfilarium during itslife cycle, asked whether he could study a human microfilarial disease,river blindness. Dr. Aziz had worked earlier in his career in the WorldHealth Organization and had been stationed in sub-Saharan Africa,where he saw many patients suffering from river blindness. This dis-ease is caused by a parasite, Onchocerca volvulus, which infects abouteighteen million people. It is transmitted by the bite of a black fly thatbreeds in the fast-flowing rivers of Africa and Latin America—hencethe name river blindness. The disease cycle begins when a black flybites an infected person and picks up from the skin microscopic formsof the parasite, called microfilariae. The microfilariae undergo develop-ment inside the fly, so that when the fly bites another individual, itinjects into the skin a more highly developed form of the parasite. Inthe skin the developing parasites become mature males, about eightinches long, and females, about fifteen inches long. The males andfemales live together in lumps in the skin and produce millions ofmicrofilariae, tiny worms that crawl throughout the skin causing incred-ible itching wherever they reach. Infected people constantly scratchtheir infested skin. The microfilariae also enter the eyes, where theycause inflammation and scarring with ultimate blindness. In some WestAfrican villages most of the people are infected and 60 percent of thepeople more than fifty-five years of age are blind. The World HealthOrganization (WHO) estimates that ninety million are at risk for thisinfection.
Dr. Aziz went to Dakar, Senegal, where he carried out a very simple clinical study. He took tiny skin snips over the hips of infected persons and counted the number of worms (microfilariae) under a microscope.
He then gave them a single oral dose of the new drug, which werenamed Mectizan®, the human formulation of Ivermectin. Testing thesame way one month later, he was astonished to find the microfilariaewere all gone. When he repeated the skin snips after three months, theywere still completely gone—with a single dose. Dr. Aziz then under-took large-scale clinical studies with full Merck support to establish thesafety and effectiveness of Mectizan® in patients infected with this par-asite. These studies established that the drug could be given as a singledose once per year. The microfilariae began to reappear in the skin onlyat the end of a year because these people were constantly bitten by fliesand re-infected. Although the medicine did not kill the adult parasites,the adult females were not able to release new microfilariae after theyhad been treated with Mectizan®. It became clear that annual dosingcould control this disease.
As a result of the Aziz clinical studies, we knew that Mectizan® could potentially prevent river blindness. But we also recognized thatthis disease is prevalent among the poorest people of the world. Insome of these poverty-stricken countries, only $1 a year per person canbe budgeted for public health. It was clear that we would not be able tosell the medicine to these people, who would not be able to afford iteven at a price of pennies per year. We then requested governments inAfrica, Europe, and the United States to purchase Mectizan® fromMerck (at a low price) and to supply it free to those who were infectedor at risk of infection, but none agreed to do this.
In October of 1987, the French government informed Merck that it was about to approve the drug. We had gone to France for approvalrather than to the U.S. Food and Drug Administration because riverblindness does not exist in the United States. In France there werepeople who had lived in Africa; some were infected and participated inthe clinical trials. Since the tests were successful, the government waswilling to approve Mectizan® for human use.
Merck faced the fact that its researchers had discovered and devel- oped Mectizan®, a medicine that could prevent river blindness. We alsorecognized that, if Mectizan® were widely used throughout the areaswhere the disease is epidemic, the disease could be eradicated. Sinceonly humans are carriers of this parasite, if everyone in the disease areawere treated with Mectizan®, all the microfilariae would be killed, andthe flies would have no source for this parasite. The disease would dis-appear. Faced with the possibility that the medicine would not be avail-able to most people with this disease, Merck announced in October1987 that it would contribute the drug free to anyone in the worldwho needed it, for as long as it was required.
We then established an independent committee of experts to de- cide which distribution programs were qualified to receive supplies ofMectizan® (Mectizan® Expert Committee). We asked Dr. William H.
Foege, who had served as director of the U.S. Centers for Disease Con-trol and was then executive director of the Carter Center in Atlanta, tochair this committee. He has led that group since 1987. AlthoughMerck would supply the medicine free, we did not have the infrastruc-ture to distribute the drug in the remote places where the infectedpeople often lived. A number of large organizations, including theWorld Health Organization and the World Bank, as well as a numberof smaller foundations dedicated to diseases of the eye, undertook themajor challenge of distribution.
Ten years after the contribution program was started, Merck had treated about nineteen million people, and Merck has reaffirmed itscommitment to reach about fifty million people per year. If that isaccomplished and continued for ten to fifteen years, it is projected thatriver blindness, like smallpox, would be eradicated.
Merck became one of the largest and certainly most inventive phar- maceutical companies in the world based on the accomplishments ofits research scientists. Millions of people throughout the world bene-fited from Merck discoveries for treatment of diseases prevalent in thedeveloped world, such as glaucoma, high blood pressure, heart failure,coronary heart disease, benign prostate enlargement, bacterial andviral infections, and arthritis. People around the world share the bene-fits of these discoveries. It is entirely appropriate that a medicine devel-oped by this innovative company for a disease such as river blindness,which occurs almost exclusively in the developing world, be madeavailable to these impoverished people. The ultimate pay-back toMerck is that the company is able to continue recruiting some of thebest scientists in the world. They join Merck knowing that importantdiscoveries of the Merck laboratories will reach the patients who mightbe helped, no matter what their economic status.

Source: http://www.amphilsoc.org/sites/default/files/proceedings/415.pdf