December 28, 1998

The Long View from the Watonwan River
Main Street Genius
Roots Along a Canoe Route
From a Millenarian's Quest to Beowulf Genomics

The Human Genome: What it means for science, medicine and society    The Wellcome Trust

The Long View from the Watonwan River

It's a long way from the rhythmic strokes of a canoe paddle on the Minnesota frontier to the pinnacle of 21st century biomedical science. But the journey is worthwhile if you believe that the loftiest endeavors can have simple origins.

Early this month I gave a talk to an editorial group of the Health Information Division of Mayo Medical Ventures. Mayo is a recognized leader in using the Internet to provide health information for consumers and organizations.

I was invited to demonstrate MBBNet and explain how it serves Minnesota's entrepreneurial community, people like the "Physician Entrepreneurs" shown in a portrait hanging on the wall of the meeting room, William and Charles Mayo.

Mayo Medical Ventures is located in an office building just east of the Clinic in downtown Rochester. From the vantage point of a 9th-floor window, my host directed my attention to a two-story building on the block to the southeast.

It was the famous pharmacy where William Worrall Mayo and his sons began their journey into medical history last century.

It was also where Dr. Mayo, once an assistant to the great English chemist John Dalton, taught physical chemistry to the nephew of a surgeon friend who practiced in Garden City, just south of Mankato.

The surgeon, Jacob Wellcome, had come to know Dr. Mayo during the Civil War and the Dakota conflict of 1862. His nephew was learning to compound medicine in his father's drug store on Main Street, S.C. Wellcome & Company. That is, when he wasn't out canoeing on Watonwan River.

The boy was Henry Solomon Wellcome, the inventor of the modern pharmaceutical industry, the quintessential entrepreneur.

Wellcome's name was plenty big in its time--he was courted by royalty, presidents, prime ministers, celebrities, and tribal chieftains--but through compounding interests it has become cosmic since his death in 1936.

Today no name is associated with medicine, its past, present, and certainly its future, in quite the same way. Indeed, guided by his famous will, "rulings in biotechnology and genetics are being handed down that will help shape the future of the human race itself," in the words of London's Sunday Times.

For example:

• England's Wellcome Trust is the world's largest biomedical research charity, twice as big as the Howard Hughes Medical Institute in the U.S., with investments of $17 billion. And like its namesake, one of the most traveled men of his time, its reach is truly global, with outposts in Thailand, Vietnam, Malawi, and Kenya.

• Glaxo Wellcome PLC, at $13 billion in annual revenues, is one of the world's largest pharmaceutical companies. It has a growing arsenal of antiviral drugs. Ziagen is the latest, a drug for treating HIV/AIDS that had its roots in the laboratory of University medicinal chemist Robert Vince.

• "Wellcome" is inextricably intertwined with archives, collections, exhibits and scholarship on the history of medicine. Roy Porter, author of the recent book The Greatest Benefit to Mankind: A Medical History of Humanity  is a resident professor at the Wellcome Institute for the History of Medicine

And the Wellcome name is front and center in the Human Genome Project, the massive effort to decipher all the genes in the human genetic endowment. The Wellcome Trust has proposed an international agreement whereby up to half of the genome could be sequenced in the UK.

A couple weeks ago the Sanger Centre at the Wellcome Trust Genome Campus in Cambridgeshire, England announced that the first genetic "blueprint" of an animal, that of the nematode worm Caenorhabditis elegans, has been completed.

A terrific scientific achievement, in the view of many, and a collaborative one involving British and American scientists. "Not only is it an example of international partnership and cooperation with strong British involvement, but a world scientific first--the first multi-cellular animal to be completely sequenced," said Lord Sainsbury, Britain's Minister of Science.

"This research will ultimately contribute towards interpretation of other genomes, including the human, and help to ensure that we revolutionise healthcare," Sainsbury said.

Main Street Genius

It was as if Wellcome himself had written Lord Sainsbury's script. Though adopted and knighted by the United Kingdom, he was an American at the core and a tireless advocate of British-American collaboration after his departure for London in 1880.

That was the year, after consulting with the Mayo brothers, that he joined with his fellow graduate of the Philadelphia School of Pharmacy, Silas Burroughs, to form Burroughs, Wellcome & Co. What Wellcome brought to the firm over the next two decades revolutionized the pharmaceutical industry.

• Wellcome saw the value of advertising and marketing as no one else. The American experience with patent medicines and elixirs and traveling medicine shows, which he had witnessed first hand on Main Street, proved to him beyond a doubt that investment in advertising would reap rewards.

• Wellcome had the knack of his Yankee kin for making the sale. As one of the first traveling drug salesmen, for McKesson & Robbins during the 1870s, he was perfectly positioned to ride the British Lion in its imperial globe-trotting.

• The inventor of "Wellcome's Invisible Ink" in Garden City saw the value of innovation in packaging. His compressed pills, or "Tabloids," were much more convenient that the standard liquids and powders.

• Wellcome established the research base of the industry with the creation of his Physiological Research Laboratory in 1894, just in time to exploit the scientific advances of Louis Pasteur in Paris and Robert Koch in Berlin and others pursuing the "germ theory of disease."

The first I ever heard of Wellcome's Minnesota roots was during a talk given by Nobel laureate George Hitchings of Burroughs Wellcome in the fall of 1990. Speaking to a modest gathering at Coffman Union on the University's Minneapolis campus, Hitchings related that during his previous visit to the Twin Cities he and others had taken a drive down to Garden City, where they picnicked in honor of the cofounder of Burroughs Wellcome.

In turn, medical leaders from the Midwest have witnessed the magnificence of Henry Wellcome's legacy in London. The father of a friend of mine, a former chief of pathology at the Mayo Clinic and longtime dean of the University of Wisconsin Medical School, told me he visited the Wellcome Institute for the History of Medicine while he was serving in the Navy.

A novel connection was made when Tilli Tansey, historian of modern medical science at the Wellcome Institute, brought my online essay on Henry Wellcome to the attention of her colleagues in 1996.

Roots Along a Canoe Route

The British critic J. B. Priestly saw the river as the central metaphor, the arterial pulse of the American literary experience, with Mark Twain its chief exponent.

Twain's description of the river in Life on the Mississippi  came to mind when I began to look into the early life of Henry Wellcome. Indeed, I was not terribly surprised to learn that they became friends during the years Twain lived in London.

Wellcome's boyhood canoe outings on Watonwan River easily transcended their place, a modest stream in the Minnesota River Basin. The water he creased took him to six continents, the atmospherics of London's high-society, and earthbound ruins of ancient civilizations which he helped to uncover through his archeological excavations in the Sudan.

The skills he developed navigating the river's currents came into play during daytrips on the Thames River near the headquarters of his pharmaceutical empire on London's Snow Hill.

His frontier skills were put to the test on expeditions into the South American rain forests to find medicinal alkaloids and into the heart of Africa in country explored by his friend Henry Morton Stanley where he set up hospitals. And they served him in the Panama Canal Zone. There, at the request of the Taft Administration, he toured the "reeking Panama swamps" to examine the effort to rid the region of mosquitoes.

Later, the Penobscot River and the surrounding Maine woods became his sanitorium when his business put him on the brink of a breakdown and he was ordered by his doctor to go on a retreat.

But what would give someone raised on the Midwestern frontier in the middle of the last century the vision and drive to succeed the way he did?

And how do you reconcile such modest beginnings with a megabillion dollar industry and now a scientific enterprise about to sort us out precisely in a code consisting of the letters A, T, G, and C?

From a Millenarian's Quest to Beowulf Genomics

Henry Wellcome was raised in the fertile soil of evangelical reform. The temperance crusades of his boyhood community had their origin in Maine in the 1840s, where the temperance movement coincided with the "Advent Awakening."

William Miller, a farmer from New York, began preaching in the 1830s that the second coming of Christ was imminent. Soon much of New York and New England was in a fever pitch. But when the end failed to come on Miller's predicted date, October 22, 1844, the "Great Disappointment" that followed precipitated a migration westward to the Great Lakes.

Henry Wellcome's extended family was deeply involved in early Adventism. His father and two of his uncles were ordained ministers. One of his uncles was Adventism's first historian. When the family moved from Maine to the Midwest, it brought with it the same millenarianism found in Mormonism and other religious movements of the American frontier.

The thousand year "earthly kingdom" predicted by early Adventism never came to pass, but the "soft-spined preacher-style bible" on display at a shrine at the Wellcome Trust's marble-clad headquarters in London symbolizes a deep vein in the American psyche: The comfortable mingling of business acumen and religious belief, manifested both in sales and management.

Books like Og Mandino's The Greatest Salesman in the World and Laurie Beth Jones's Jesus CEO  carry the inspirational messages today that Henry Wellcome found in his bible.

Yet in addition to making the sale and managing the firm, Wellcome's underlying evangelism also harbored a drive to discover the unknown and put it to work for the benefit of human and veterinary medicine.

His last will and testament combined these uncomfortable bedfellows--profits and philanthropy--and they coexisted until 1986. That year the governors of the Trust floated the pharmaceutical company, then called the Wellcome Foundation and subsequently renamed Wellcome PLC, on the stock market. The Trust's wealth ballooned.

Wellcome PLC merged with Glaxo in 1995 to become Glaxo Wellcome. Today the Trust has less than a five percent financial interest in Glaxo Wellcome and is completely independent of the company. It can use its money as it wishes in accordance with the founder's wishes to "support scientific research which may conduce to the improvement of the physical conditions of mankind."

Wellcome's laboratories pioneered research on infectious and tropical diseases a century ago. Today, Beowulf Genomics, an initiative of the Wellcome Trust, aims "to assist in accelerating the pace of research into microbial pathogens" by providing funding to sequence their genomes.

Work is well underway on deciphering Campylobacter, Streptomyces, Salmonella, Mycobacterium tuberculosis, Bordetalla pertussis, Candida albicans, Trypanosoma  and many other bacteria, fungi, and parasites that have plagued humans and animals through the ages.

As public health officials around the world warn us of a global resurgence of infectious disease, Henry Wellcome's mounting legacy is quick to the task, as though the founder himself were right there in the laboratories among the scientists urging them on. Recently, the Wellcome Trust and the Burroughs Wellcome Fund of Durham, North Carolina announced a joint venture to provide grant support for collaborative research in infectious diseases of the developing world.

The Trust's growing influence on British science policy prompted Britain's New Scientist  magazine to ask: "If the young Henry Wellcome had invested in light bulbs rather than pills would Britain now be pursuing electronics research?

"Perhaps it doesn't matter because the course of history is full of chaotic influences, even one as strange as the birth of a boy in Wisconsin in 1853 influencing British science policy in 1998."

Far-flung influences like those of the rhythmic strokes of a canoe paddle on the effort to decode the human genome.

    --William Hoffman    hoffm003@tc.umn.edu