Piecing the Puzzle

Larry Krotz

• Publisher: University of Manitoba Press
• Year: 2012
• ISBN:
  9780887554223
• Topic: Medicine
• Subtopic: Diseases & Allergies

In 1979, Dr. Allan Ronald, a specialist in infectious diseases from Canada, and Dr. Herbert Nsanze, head of medical microbiology at University of Nairobi, met through the World Health Organization. Ronald had just completed a successful project that cured a chancroid (genital ulcer) epidemic in Winnipeg and Nsanze asked him to come to Kenya to help with Kenya's "sexual diseases problem." That initial invitation led to a groundbreaking international scientific collaboration that would uncover critical pieces in the complex puzzle that became today's HIV/AIDS pandemic. In Piecing the Puzzle, journalist and documentary filmmaker Larry Krotz chronicles the fascinating history of the pioneering Kenyan, Canadian, Belgian, and American research team that uncovered HIV/AIDS in Kenya, their scientific breakthroughs and setbacks, and their exceptional thirty-year relationship that began a new era of global health collaboration.

CHAPTER ONE

Waging War With Infectious Diseases

January at the Equator is the height of summer. In Nairobi, the capital of Kenya, the sun shines fiercely, though the days, if you find shade, are extraordinarily pleasant and the nights exquisite. Rains in December have greened everything up and now this city of 3 million, with its mix of old British style colonial buildings, middle-class estates, and crammed, tin-roofed shantytowns with open sewers only short distances from bucolic avenues lined with diplomats’ estates, is busy and thriving. A striking presence is that of the Chinese. Throughout Africa, the world’s newest superpower is busy extracting resources and donating physical projects. Here in Nairobi, through completely gutted sections of downtown, the Chinese government is building an eight-lane highway heading north. Near the airport you pass beneath an arch of friendship erected between the peoples of China and Kenya, a symbol of things present and enticingly—or ominously—to come. Otherwise the great mill of life goes on much as always, labourers lugging heavily loaded handcarts struggle through intersections next to smoke-belching lorries and shiny air-conditioned Land Rovers. At a nicely appointed hotel on the edge of downtown, another reality of Kenyan life is about to unfold: a scientific meeting on HIV/AIDS.

On Monday morning participants start to gather. Four hundred are expected over the course of five days. Today nurses and doctors who last week toiled inside the smudged walls of shantytown clinics with patients queued down the dark hallways, line up themselves—for tea and coffee by the swimming pool bar of the Mayfair Court. John Mungai, whom I last saw crammed sideways into his cubbyhole office at the Baba Dogo clinic on the far side of town where he counsels men about to get HIV tests, is hardly recognizable, smiling broadly in his spiffy suit. Laboratory technicians have disembarked from buses boarded long hours ago at the far ends of the country, from Kisumu, west on the shores of Lake Victoria, and Mombasa, by the Indian Ocean. Professors in the medical school at the University of Nairobi have told their students they’ll be away for a couple of days.

Foreign visitors are here as well and will make up about a third of the assembly. It used to be almost all foreigners, and the fact that there are now so many (mostly young) Kenyan faces among the participants is a true testament to some of the event’s signature achievements—inclusiveness and mentoring. But the foreigners come too—escaping winter in the northern hemisphere—guaranteeing the uniqueness and strength of the event, that it is most definitively a two-way enterprise. Researchers have arrived from Canada—Winnipeg, Vancouver, Ottawa, and Toronto; from the U.S.—Seattle, Chicago, San Francisco. And from Europe—the U.K., Belgium, and Sweden. Old hands who have been coming here every January since the late 1980s mingle with young scientists who were mere infants in those early days of the meeting. The Annual Review Meeting 2010 of the University of Nairobi STD/AIDS Collaborative Group will listen to 118 presentations, almost all of which will describe work in progress. Some, indeed, is research that will never see publication, but what is important is the opportunity to share the work, to get feedback from colleagues and senior scientists, some of them giants in the field. This is not properly a conference, but a meeting, though the old-timers still call it a “retreat,” which is how it began twenty years ago when there weren’t 400 participants but only a couple of dozen. “We insisted the big shots come together all at the same time so we could present our work to them and to each other,” recalls Marleen Temmerman, who has come from Belgium. In the 1980s Temmerman—whose down-to-earth demeanour belies her lofty credentials as a top-tier researcher—was a youthful obstetrician newly arrived for a stint in Kenya that would stretch into eight years. Now her resume is gilded: head of the department of obstetrics at Ghent University Hospital, a nominee for the lifetime achievement award granted by the British Medical Journal, and, to boot, a senator in the Belgian Parliament. She maintains her hand in Kenya through her position as director of the International Centre for Reproductive Health (ICHR). Temmerman travels with two journalists from Brussels who are preparing a newspaper feature about her.

As things get underway, it becomes readily apparent that presenters are approaching the vast subject of HIV/AIDS from all sides. The research papers, each of which will be given a fifteen-minute treatment, are as diverse as “Risk factors and potential intervention targets in HIV-1 discordant couples,” which struggles with the problem of limiting HIV spread when one partner is infected and the other is not, and “Male circumcision for HIV prevention in Nyanza,” which marshals research to assess the success of the prevention strategy of circumcising young men. Doctors from Winnipeg who have spent more than a decade poring over the genetic profile of HIV-resistant sex workers in attempts to learn more about the mysteries of the immune system will deliver their thoughts: “Setting up multiple barricades along the HIV infection pathway.” A contingent of anthropologists from the universities of Illinois and Nairobi who have been trying to figure out how to intervene around cultural practices that are risky for HIV spread will present: “Widow inheritance and sexual networks in Siaya District.” Anthropology and sociology mix with biology and microbiology. A group of Kenyans and Canadians will describe their efforts to get people to use cell phones (ubiquitous here now, even among the poor) to stay in touch with clinics and manage their health, in particular, keeping them regular with regard to the daily ingestion of their antiretroviral therapies. The audiences are earnest and attentive, and empty chairs are hard to find in the darkened conference room during the long mornings and afternoons. Outside, on the patios of the hotel complex, the work goes on non-stop. Whatever the first meeting might have looked like two decades ago, it would not have been governed, as this one is, by the laptop. One of the most dramatic changes is technology; it is now somehow the most satisfying of all possible worlds to be in your room, in a coffee shop, or seated at a table by the pool, thousands of kilometres—in some cases ten time zones—away from home with your entire office available from inside the little machine in front of you. BlackBerrys are everywhere, with nary a pencil or sheet of paper to be seen. Projected on screens in every meeting room, charts, pie graphs, and numbers are the uniform currency of science, used at one end to prove a point and, at the other, to raise grant money.

The meeting itself is about one main thing, making progress in the war on a disease that has traumatized Kenya, as it has all of southern Africa. This January meeting is a tradition, a meeting among researchers who, no matter how wide or diverse their membership becomes, devoutly think of one another as colleagues. Initially the Kenyans, Canadians, Americans, and Europeans came together around a single, small, overcrowded clinic in the middle of the city even before the onslaught of HIV/AIDS, and then discovered themselves uniquely positioned to take on a major role both in research around the new virus as well as in the enormous task of marshalling care for the thousands and ultimately millions in this region who would become infected by it. The collaboration, grown now to the more than 400 people who have signed up here, is described by seventy-two-year-old King Holmes as “generous and ecumenical.” Holmes has come from Seattle, where he is director, since 1989, of the Center for AIDS and STDs at the University of Washington and founding chair of that university’s department of global health. This collaboration “is something I could contrast, without naming names,” he opines, “to other places where the groups are continually jealously fighting with each other rather than collaborating.”

The context is public health: preventative health, epidemiology, control of this epidemic now into its second generation. The recently coined term “global health” recognizes at long last that the health of populations, especially with regard to infectious diseases, is no longer (if it ever was) a local question. The principle is that the health of every nation depends on the health of all others and this, as an esteemed Lancet journal panel noted more than a decade ago, “is not an empty piety, but an epidemiological fact.”¹ The field of global health is also the landing place for people who spend their waking hours thinking about what are commonly called IDs, infectious diseases.

As we settle into the twenty-first century, it can be said that the real war of the worlds is a battle engaged not between organized societies and human or political terrorists, dramatic and tension-filled as those conflicts may be, but between human beings and microbes, the bacteria and viruses that occupy the vast unseen spaces both around us and within us. Microbes are by far the most abundant forms of life on earth, constituting some twenty-five times the total biomass of all animal life.² They are everywhere—in the air, the water, the soil, inside our bodies. The vast majority of the more than a million known types are harmless, in fact beneficial and essential to processes like digestion of food or decomposition of waste matter. But on the more sobering side, 1,415 are identified as capable of causing our death. This is the group that takes the attention of the infectious disease specialists.

Bacteria are free-living organisms containing a single chromosome and the ability to reproduce themselves. Viruses are something else, defined colourfully by the biologist awarded the Nobel Prize for medicine in 1960, Peter Medawar, as “a piece of nucleic acid surrounded by bad news.”³ Truly parasites, microbes, in order to survive, need hosts, something or somebody to live off. They are promiscuous and voracious in their appetite for ever-new hosts. To fulfill this need, they have developed a variety of means of getting around, as well as means to latch onto ever new and fertile hosts. Some viruses, like SARS, can be transmitted through the air, pushed by the force of a sneeze or a cough, or by simple breathing. Others, like the bubonic plague, which travelled on fleas, or malaria, which needs to pass through a mosquito, hitchhike from one subject to the next on the backs of “vectors.” Some, like cholera and other gastroenteritis-causing microbes, are carried by fecal contamination in food and drinking water. Another group (syphilis, gonorrhea, HIV, and over thirty others) jump from one human to the next when people engage in sexual contact. Microbes vary in their virulence. In the case of poliomyelitis, the dreadful infection that persisted in the West right up to the middle of the last century, less than one in a hundred of those infected by the polio virus came down with the paralytic disease. Smallpox, by contrast, has regularly killed a third of those infected and scarred, blinded, or maimed the rest. With HIV, infection rates as a function of exposure have proven incredibly variable. Scientists such as Michael Oldstone gauge the risk overall as fairly low; approximately 5 percent of those exposed get infected.⁴ The hazard per sex act is undoubtedly even lower, and the risks of infection as a function of exposure swing wildly under the sway of a myriad of influences.

For all of history, with the exception of the last 150 years, we humans and our ancestors have survived (sometimes barely) the onslaught of infectious diseases without the least understanding of their cause, and with virtually no effective treatments. Superstition, for most of our history, was as likely as not to rule the day. Occasionally, something resembling “science” was applied; Hippocrates, the Greek “father of modern medicine,” importantly distinguished between those diseases that are endemic, that is, confined to doing their damage within a specific locale or neighbourhood, and those that are epidemic, that threaten to spread beyond that locale and into the wider world. But two thousand years would pass before his successors, physicians like Louis Pasteur and Robert Koch,⁵ would develop and, more importantly, popularize the germ theory of infectious disease. It wasn’t magic or God that brought plagues, but unclean water or sick people mingling with the rest of the population and sharing those invisible microbes. Meanwhile epidemics, the rapid spread of virulent diseases, plagued the world on a regular basis with kill numbers that put competing catastrophes such as wars, earthquakes, and tsunamis to shame. Extraordinary numbers died: 30 to 70 percent of Europe in the Black Death in the fourteenth century; 300 million in the twentieth century alone from smallpox; infinitely more killed by the influenza that followed the First World War in 1918–19 than died on the battlefields; 30 million dead and counting in our own time from HIV/AIDS.

Briefly, during the period of the discovery and perfection of the first vaccines and then the first antibiotics, all of which happened in little more than a century between the 1840s and the 1960s, or between the Crimean and Vietnam wars, what happened was a growing belief that the diseases that had ravaged the world could be—indeed, had been—tamed. Extraordinary accomplishments had certainly been registered. The mighty weapons of vaccines and antibiotics—antibiotics such as penicillin and sulpha drugs to kill bacterial infections, and vaccines to protect against viral ones—were unleashed. And these, combined with public sanitation, the concerted attack against perinatal mortality, the saving of greater numbers of both infants and birthing mothers at the time of childbirth, and greater protection of children in their first years of life literally changed the world, or certainly great parts of it. Epidemics were hit with increasingly standard strategies: vaccines to augment natural immunity, clean-up of stagnant water and open sewage to get rid of vectors, quarantines to isolate the infected. In 1967, nearing the end of that heady period, United States surgeon general William Stewart famously told the world that the book on infectious diseases could be closed.

Then, in the 1970s, something happened. New and sometimes lethal microbes began to emerge, surprising everybody, as they have done ever since, hitting us at the rate of around one a year with the frequency now apparently increasing.⁶ What, everybody had to wonder, had happened, or, is happening? One explanatory factor is resistance to drugs on the part of exceedingly clever and ever-shifting microbes. Their mutated forms have now found ways to fight off the antibiotic drugs that had briefly threatened to obliterate them. A second factor is the arrival of new zoonotic viruses (H1N1, SARS, and HIV), that is, diseases that have jumped from animals to humans. This transition is not new, but has always happened; smallpox, for example, was probably originally a monkey pox. But each time it occurs it creates a new equilibrium. HIV, we now know, has been transferred to humans several times since the 1930s, likely from chimpanzee “bush meat,” though it did not spread significantly until the 1970s.⁷ A third factor is more rapid, more extensive, and more popular global travel along with changes in human behaviour. Global travel has always been a factor in the spread of diseases, transporting new infections to locations where the citizenry has no immunity. In the thirteenth century, diseases travelled with the crusaders and with traders to and from the Orient. In the fifteenth century, they accompanied the Spanish to the New World (the Spanish famously carried smallpox to devastate the Aboriginal inhabitants of the Americas while succumbing themselves to yellow fever, which they had not seen before). Now when great numbers of us travel both for business and pleasure at extraordinary rates, as well emigrate permanently, diseases—SARS, HIV, West Nile, drug-resistant tuberculosis, to name but a few—all too often travel with us.

What all this meant was that if you were a medical graduate in the late 1970s or 1980s you would find infectious diseases suddenly back on the menu as a challenging and honourable, not to mention potentially profitable, calling. After a hiatus of less than a generation, the world of the ID specialist has returned as a field with a growing cadre of experts and postings and an increasing cachet. “In the 1970s people were saying infectious diseases is a go-nowhere career—we’re about to have it all under control,” a young physician on the cusp of her career told me. “Well, we know that didn’t happen.” This young woman with a bright future is part of the next generation, which can once again get excited about infectious diseases and see it as a field of mission in bringing about a newly minted project of global health.

In 1968, at about the same time the U.S. surgeon general was declaring the battle against infectious diseases won, a young Canadian physician was returning home from graduate studies at the Universities of Maryland and Washington in that very field. The University of Washington was a world leader in infectious diseases research, and Allan Ronald, who had been there from 1965 to 1968 as a trainee, was excited by his experiences. Ronald was born on a farm near Portage la Prairie, Manitoba, into a deeply religious family out of which he was the first to head off to pursue higher education. When he came back to Winnipeg, he did not feel in sync with voices like Stewart’s, but believed infectious diseases would continue to need strong academic leadership. His life’s work, he thought, ought to be to try to replicate what he had encountered in Seattle. He decided he wanted to make his home province of Manitoba and the University of Manitoba a leader in the field. “Not that we would be Harvard or Johns Hopkins,” he says referring to the large American universities with their vast endowments and iconic imprints, but there was, he believed, a place for smaller, regional players. The territory would benefit rather than suffer from decentralization. What was necessary was to understand how important the field was and to commit to it. While in Maryland, he had observed the Americans at the National Communicable Disease Center in Atlanta (which in 1970 would be renamed Centers for Disease Control, the CDC) and its epidemiology branch under the leadership of Dr Alexander Langmuir. He had been deeply impressed; Langmuir had an unobstructed sense of mission, dec...

Table of contents

• Cover
• Title
• Copyright
• Contents
• Acknowledgements
• Note on Sources
• Introduction
• Chapter 1: Waging War with Infectious Diseases
• Chapter 2: The African Epidemic
• Chapter 3: Educating Around AIDS
• Chapter 4: Research Strategies
• Chapter 5: Secrets of the Sex Workers
• Chapter 6: The Vaccine Quest; and More Lessons From the Immune System
• Chapter 7: The Kenyan Side: Squaring the Collaboration
• Chapter 8: An Experiment in Kisumu
• Chapter 9: Legitimizing Circumcision
• Chapter 10: Unfinished Business
• Conclusion: AIDS World
• Afterword: By King Holmes, Herbert Nsanze, Peter Piot, and Allan Ronald
• Selected Bibliography
• Notes
• Index