The Coming Plague (39 page)

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Authors: Laurie Garrett

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Three of the man's family members who cared for him fell ill. So did a man who lay in the bed alongside him in N'zara Hospital. A woman who frequented the hospital ward, tending to her ailing husband a few beds down from the first man, got Ebola. And the two nurses on the ward got the virus.
Every additional illness involved members of the families of those first five cases or close friends who tended to their illnesses or burial preparations. All infections could be tied to some direct blood or fluid contact between an ailing Ebola victim and another individual. The best nurses—those who provided the closest care for the patients—were five times more likely to be infected than their more aloof colleagues.
The team was able to find fifty-six Ebola cases, many hidden in the tall grasses. Sixty-five percent of those who got infected died.
Though it seemed obvious to McCormick that some Ebola-carrying animal or insect lurked inside the cotton factory, none of the fauna samples he sent to the CDC were Ebola-positive. Their inability to pinpoint the reservoir for Ebola would bother McCormick for years, nagging constantly at the back of his mind whenever he had reason to recall the events in N'zara. He would always tell anyone who asked, “It's probably the bats. We just have to get in there and capture a few more of them and we'll find the virus.”
Barring identifying the reservoir for Ebola and eliminating the culprits from the human ecology of the N'zara area, McCormick suspected isolated cases of the disease would always crop up.
“Because the cultural and social structure in Sudan tends to limit contact with severely ill persons to a few adults in a relatively secluded compound, sporadic cases of Ebola virus disease may have little impact on the community at large,” the team wrote, summarizing their findings.
47
“In this outbreak, however, the hospital appeared to be the focal point for dissemination of infection to several family units after the admission of the index patient.”
As was the case with Lassa, poorly run hospitals operating under conditions of extreme deprivation were the amplifiers of microbial invasions. What might have otherwise been individual illness, limited to one or two cases of Ebola, was magnified in a hospital setting in which unsterile equipment and needles were used repeatedly on numerous patients. N'zara Hospital couldn't afford mattresses for its steel bedframes or penicillin—it could hardly be expected to throw away every single plastic syringe simply because it had previously been used.
McCormick was at a loss for a solution. Once again, elimination of a disease threat seemed inextricably bound to economics and development. The poverty of southern Sudan exceeded anything he had seen before, and McCormick had little reason to hope that some government or agency with
the wherewithal to do so would deem it politically expedient to assist such godforsaken parts of the planet.
48
Yet McCormick felt certain that Ebola and other dangerous diseases would continue to haunt the most impoverished communities on earth, constantly threatening to explode into epidemics, some of which might one day lap at the shores of the planet's richest nations.
Out of such poverty, from the African Serengeti to the burned-out tenements of the Bronx, would soon come microbial invasions that would bear out McCormick's prophesy.
Revolution
GENETIC ENGINEERING AND THE DISCOVERY OF ONCOGENES
 
Man is embedded in nature. The biologic science of recent years has been making this a more urgent fact of life. The new, hard problem will be to cope with the dawning, intensifying realization of just how interlocked we are. The old, clung-to notions most of us have held about our special lordship are being deeply undermined.
—Lewis Thomas, 1975
 
Scientists at the Massachusetts Institute of Technology have completed the synthesis of the first man-made gene that is fully functional in a living cell.
—Massachusetts Institute of Technology press release, August 30, 1976
 
 
The revolution happened with such astonishing speed that few participants fully appreciated what had transpired. The collective consciousness of science and medicine changed in the blink of a historic eye, rendering those who failed to adapt obsolete overnight. In less than five years every aspect of biology and medicine was so thoroughly shaken to its core that science students trained afterward thought it had always been so. The excitement could be felt from the floors of the world's stock exchanges to the halls of parliaments worldwide.
Just as the hopeful spirits of the post-World War II scientific conquest of the microbes seemed to be flagging, humanity discovered genetic engineering.
When science learned how to manipulate the genetic material of plants, animals, and microbes—the DNA and RNA—an entirely new world revealed itself. Suddenly it seemed possible to understand the secrets of the microbes, appreciate at the molecular level how the human immune system destroyed (or failed to destroy) its microscopic challengers, and invent radically new weapons to use in waging war on disease.
Once again, optimism pervaded biological research. Once again, scientists predicted bold victories over everything from cancer to malaria. The speed of discovery from the early 1970s into the 1980s was dizzying, even for those who started it.
“I wasn't surprised about much of anything until 1966,” declared Sir Francis Crick in a 1983 interview. “But after that, well, the last ten years have surprised us enormously. We had no idea. No idea.”
The English scientist turned and nodded to his American colleague, James Watson, who readily agreed with Crick's assessment. Together in 1953 at Oxford University, with the unwitting “assistance” of X-ray crystallographer Rosalind Franklin, they discovered the relationship between an enormous and strange molecule, deoxyribonucleic acid, and human genetics. They proved that DNA contained the genetic code of life, a discovery for which the men shared the Nobel Prize in Medicine.
1
Reflecting thirty years later on the revolution that had transpired since, Watson said, “None of this could have been predicted. Now it's hard to imagine things going any faster. But it will be faster. Mysteries will tumble. All is now open to experimental attack, and problems we can't even foresee today will be identified and solved within less than a decade.”
His prophesy would prove remarkably accurate, as massive global computer interconnections and fax machines would become the preferred method of sharing the excitement of biological discovery, the pace becoming so furious that by the mid-1980s most researchers would consider journal publication of their findings a matter of historic obligation, rather than a primary method for informing their colleagues. By the time results were published, most molecular biologists would already be two or three experiments further along in their laboratories.
 
Since the early 1970s, biologists had been working on ways to chop up DNA and RNA in order to figure out what various pieces of the genetic code actually controlled. It had been determined that nearly all living systems had repair mechanisms to fix damaged DNA. In addition, they knew that something in the DNA regulated when the genes for, say, growing fingers were turned on and when they were switched off. There was also a sense that the malfunctioning of such genetic signals lay at the core of the causation of cancer, because tumor cells seemed to behave as if all their internal policing mechanisms were out of control.
Scientists soon realized that the world of DNA was replete with specialized proteins that busily moved up and down the vital molecule's lengthy sequence performing a myriad of tasks, ranging from snipping out a single defective nucleotide to making a copy of an entire DNA molecule, or chromosome. These proteins, which were themselves made according to instructions inside the DNA, were the key to regulation of the massive genetic code. Like switching signals in a vast computer data base that ensured desired bits of information were displayed on the VDT screen when—and only when—the human user wanted to see them, these proteins, particularly a group known as restriction enzymes, made sure that genes were expressed only when necessary, cut out if troublesome, inserted if
needed, and remained silent information stored in the DNA data banks at all other times.
The world's top molecular biologists concluded that the best way to decipher DNA was to manipulate these regulatory proteins and see what effect removal of this or that piece of DNA might have on the virus, bacteria, or cell it controlled. Scientists like Stanley Cohen and Paul Berg at Stanford University made batches of these proteins, mixed them with DNA, and watched the results. Berg and Cohen soon figured out how to excise minute, discrete pieces of DNA with the precision of molecular surgeons. They also learned how to insert genes into DNA sequences by opening up the DNA, attaching the desired segments, and then allowing the DNA to recombine, the new gene now having been incorporated.
2
In late 1973, Berg hit on an idea: put genes into harmless viruses, let the viruses infect cells, thereby carrying the genes inside. The genes might then be recombined into the cellular DNA. This was especially easy to achieve by using bacteriophages—viruses that infect bacteria—to carry experimental genes into well-understood, simple organisms, such as the
Escherichia coli
bacterium. Berg envisioned treating genetic deficiency diseases one day through just such a mechanism.
Berg's idea not only worked but caused an international upheaval in biology. Within a year every molecular biologist who could get her or his hands on the proper chemicals and viruses was using the genetic engineering technique to study life in a test tube. But Berg worried that his own experiments, using monkey virus SV40 to carry genes inside
E. coli
bacteria, could be dangerous, and in 1974 convened a meeting of the world's preeminent biologists to establish safety rules for their enterprise.
While some critics would attack genetic engineering research as ungodly or risky, the field was as unstoppable as a speeding locomotive. What was considered experimental in 1976 was routine by 1979. The SV40 experiments Berg and Cohen fretted over in 1974 were graduate student training exercises by 1980. And the term “genetic engineering” was transformed from an almost whimsical description of a handful of experiments performed in a few select laboratories during the mid-1970s to a label applied to a global multibillion-dollar industry in the 1980s.
For the disease detectives the revolution was a mixed blessing: on one hand it offered new tools for solving microbial mysteries, but it was also immediately obvious that funding—never generously available to parasitologists or infectious disease researchers—was becoming even scarcer as resources shifted toward molecular pursuits.
Bright, young scientists followed the excitement—and the money. And why not? Clearly, in 1976 the opportunity to work, for example, as one of twenty-four postdoctoral fellows in the MIT laboratory of Nobel laureate Har Gobind Khorana manufacturing the first fully functional man-made gene was a great deal more seductive pursuit than joining a team that used
old-fashioned light microscopes to count the number of malarial sporozoites in a mosquito.
Yet what the microbe hunters learned when they applied their newly honed genetic manipulation skills to the task only heightened their sense of concern. They soon discovered that microbes could share genes with one another that made them more formidable human enemies; many viruses not previously thought to do so could cause cancer; some microbes possessed the ability to chemically manipulate the human immune system to their advantage; and there were viruses that could hide for years on end inside human DNA.
It was Barbara McClintock who first suggested that genetic signals could move about, be mobile, producing changes in the fated appearance of an organism. During the 1940s and 1950s, well before Watson and Crick discovered the link between genes and the structure of DNA, McClintock studied maize plants at the Cold Spring Harbor Laboratory on Long Island, New York. She showed that genes could move from one position to another on maize chromosomes, causing radical changes in the appearance of corn kernels. The cause of these differences would not be inherited genes per se, but the movement or transpositioning of those genes. The movable genes were dubbed transposons.
3
Only years later would the full impact of her pioneering efforts finally be evident, and McClintock would be awarded the 1990 Nobel Prize in Medicine.
A decade after McClintock discovered transposons in maize, Joshua Lederberg showed that bacteria had movable bits of DNA that conferred the ability to resist antibiotics. And by the 1970s, when Berg and Cohen invented the techniques of genetic manipulation, scientists all over the world realized that certain bacterial genetic traits commonly jumped about from place to place within a cell's chromosome, or between bacteria. These were not rare events. In fact, it seemed that at the bacterial level, genetics, far from being the rigid blueprint envisioned less than a decade earlier, was more akin to a game of Scrabble in which each organism came into existence with a finite set of letter tiles, or genes, but jumbled those tiles around according to a set of rules creating a vast variety of different words.
4
These Scrabble tiles of movable genes could be in the form of discrete packages of DNA that moved about along the bacterial genome—Mc-Clintock's transposons. They could be singular genes that appeared to leap about almost at random, designated “jumping genes.” Or they could be highly stable rings of DNA, called plasmids, that sat silently in the bacterial cytoplasm waiting to be stimulated into biochemical action.
It became alarmingly obvious that microbes used this constant game of genetic Scrabble to their advantage in a variety of ways. Bacteria could occasionally undergo a process called sexual conjugation, stretching out portions of their membranes to meet one another and passing plasmids,
transposons, or jumping genes—including genes that conferred resistance to antibiotics.
Naturally, if humans could manipulate the Scrabble game to their advantage in the laboratory, so could the microbes in the real world. It wasn't a long intellectual leap from jumping bacterial genes, for example, to viewing viruses as well-packaged transposons capable of corralling the genetic resources of the bacterial, or even human, cells they invaded.
The quintessential example of Lederberg's notion of genetic entanglement was discovered by Howard Temin at the University of Wisconsin in Madison and David Baltimore at Massachusetts Institute of Technology: retroviruses. These tiny RNA viruses were unique in that they gained entry into cells and made reverse mirror-image copies of their RNA (running backward compared with the normal course of events) to produce a DNA version of their genes. And then they exploited vulnerable locations along the host's DNA to insert themselves, like a transposon, into the cell's genetic material. The retroviruses accomplished this feat through the use of a unique enzyme called reverse transcriptase, which performed the mirror-image flip of viral RNA genes into DNA.
Shortly after the discovery of retroviruses, National Cancer Institute scientists Robert Huebner and George Todaro proposed a theory to explain the ability of these viruses to cause cancer. They suggested that there were places along animal chromosomes where transposons rarely went, and into which a viral insertion could spell cellular disaster. According to their hypothesis, if a retrovirus inserted itself near certain host genes, those cellular segments of DNA would be switched on, and they, in turn, would cause wild cell growth and misbehavior—the hallmarks of cancer. Driving their theoretical point home, Huebner and Todaro named these cellular DNA sites of special viral vulnerability “oncogenes.”

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