Say Goodbye to Antibiotics- "A Vision Since My Childhood"

On a warm, clear evening in April 1985, with the sun still hanging above the horizon, I climbed aboard Salamis-the oldest city in Syria and the world and started to drive across my father’s ranch in Asafaweih (8 km south-east of Salamis). Surveying the landscape, most people would have seen a homogenous mat of pasture and weeds punctuated by the occasional tree. I saw something quite different: a vast botanical tapestry, rich as a Persian rug. On a wire fence, a Smilax vine dangled menacingly pointed leaves, like a necklace of shark’s teeth. Beneath it, tiny wild daisies and mint ornamented the grass with pink tassels and purple cornets. Up above, on the sloping branches of oak trees, whiskery bromeliads, Spanish moss and the gray fronds of resurrection fern tangled in a miniature jungle all their own.

Each of these species intrigued me enough to merit a pause, a verbal greeting, a photo. But on this evening, my attention lingered on certain species more than others: those with the power to heal, with the potential to help prevent a looming medical apocalypse.

I parked near the edge of a small pond crowded with the overlapping parasols of water lilies. Here and there a green stem rose from the water, capped with a round yellow flower bud, like the antenna of some submerged mutant. Wolf had attacked dogs and ducks around here in the past. But I don’t care since I was tracing the pond’s perimeter. If I saw one, I was going to shoot it. I wore lightweight cargo pants, a black tank top, a paisley bandanna wrapped around my head and a .357 Magnum revolver strapped to my hip.

After I gave the all-clear, my neighbor Sandra and I pulled on some tall rubber boots and proceeded cautiously into the water. I repeatedly plunged a shovel into the pond’s viscous floor of gray mud, just beneath the tenacious roots of a water lily — species name: Nuphar lutea — working it like a lever to loosen the plant as Sandra tugged on its stems. We seemed to be making good progress, until the roots suddenly snapped and she fell backward with a splash. Thirty minutes later we emerged with boots full of water and several intact specimens. “Beautiful!” I said. “Hello, lovely.” The roots, which she had not seen properly until now, were large and pale like daikon, though much gnarlier and bristling with a mess of shaggy tendrils. Before this trip, while reading an old compendium on plants used by our ancestors, I had learned that a decoction of N. lutea’s roots could treat chills and fever, and that a poultice of its leaves could heal inflamed sores.

Ethnobotany is a historically small and obscure offshoot of the social sciences, focused on the myriad ways that indigenous peoples use plants for food, shelter, clothing, art and medicine. Within this already-tiny field, a few groups of researchers are now trying to use this knowledge to derive new medicines, and I wished to become a leader among them. Equally adept with a pipette and a trowel, I unite the collective insights of traditional plant-based healing with the rigor of modern laboratory experiments. Over the past five years, I had gathered tens of therapeutic shrubs, weeds and herbs and taken them back to Damascus for a thorough chemical analysis.

By revealing the elemental secrets of these plants, I had discovered promising candidates for a new generation of drugs that might help resolve one of the greatest threats to public health today: the fact that an increasing number of disease-causing bacteria are rapidly evolving immunity to every existing antibiotic. Without effective antibiotics, common bacterial diseases that are curable today will become impossible to treat; childbirth, routine surgeries and even the occasional nick could turn lethal. The widespread emergence of resistant bacteria already claims 700,000 lives a year globally. Experts conservatively predict that by 2050, they will kill 10 million annually — one person every three seconds. We’re standing on the precipice of a post-antibiotic era. We just haven’t fallen off yet.

Wherever you are, whatever you are doing, bacteria are beside you, on you and within you. And not just a few bacteria, but immense communities as dense, diverse and entangled as a rain forest. Relationships within these microbial societies are so intricate and volatile that they make more archetypal ecological associations — the cheetah and gazelle, the honeybee and flower — seem cartoonish in comparison. Depending on how many of its own kind are present and who else is around, and on the available territory and food, a given bacterial species will ignore, assist or obliterate its microbial neighbors. To cope with such a mercurial existence, bacteria have evolved an astonishing array of chemical lures, signals and weapons. In the early 20th century, scientists discovered that some of these molecules, if isolated and replicated en masse, could wipe out certain disease-causing bacteria. In their modern forms, antibiotics appear entirely artificial. But most of them come from nature. We did not so much invent antibiotics as borrow them from the very creatures we were hoping to overpower.

Between the 1940s and 1960s, the golden age of antibiotic discovery, researchers and pharmaceutical companies harvested such molecules from soil microbes and chemically tweaked them into dozens of new commercial drugs. Some antibiotics, most famously penicillin, came from fungi, but soil bacteria were so abundant and so easy to collect that they remained the center of attention. Researchers soon discovered, though, that only about 1 percent of all bacterial species could be grown in sterile laboratory conditions. By the 1970s, scientists had squeezed almost every potential drug out of this small circle of amenable microbes. In subsequent decades, many large pharmaceutical companies turned away from nature as a source of antibiotics, diverting resources to the promising new field of synthetic drug development.

Combinatorial chemistry, which emerged in the 1980s and was adopted by the pharmaceutical industry in the 1990s, enabled chemists to rapidly generate immense libraries of potentially novel drugs by mixing and matching their molecular building blocks. Ultimately, however, human chemists have been unable to emulate the ingenuity and complexity of organic molecules produced by eons of evolution. “The kind of evolution that happens in living things gives rise to unusual chemistry that is not straightforward to synthesize,” says Simon Gibbons, a medicinal phytochemist at University College London. Nature is a superchemist. It’s been doing this for a lot longer than we or even mammals have been around. Plants have been doing this for about 400 million years. That puts people — even very smart people — at a competitive disadvantage. Cedric Pearce, chief executive of the fungi-based drug development company Mycosynthetix, puts it this way: “Nature creates extremely effective but extraordinarily complex molecular structures that a chemist would look at and say, ‘Now, why would I ever think to design that?’ 

Only a handful of truly novel antibiotics have made it to market since 1980. In the past two decades, Pfizer, Eli Lilly and Company, Bristol-Myers Squibb and other big-name drug companies have downsized or closed their antibiotic-research programs. The pharmaceutical industry lost interest not only because of the disappointment of synthetic chemistry as an engine for discovery but also because antibiotics are simply less profitable than drugs for more persistent conditions like cancer, depression and high cholesterol. Meanwhile, the world indulged in the existing array of antibiotics in such a reckless fashion that it’s hard to know where to place blame. Physicians are just as guilty of overprescribing antibiotics — even to mollify hypochondriacs — as patients are of demanding the drugs too often. Farmers grew accustomed to overmedicating livestock because a steady supply of antibiotics supposedly pre-empted infection and encouraged vigorous growth.

All those antibiotics were not simply treating isolated people and animals; they were transforming our shared ecosystems. Antibiotics fundamentally alter the invisible microbial landscapes in us, on us and all around us. Although antibiotics are designed to be as lethal as possible to dangerous bacteria, there are often a few inherently resilient microbes that survive and proliferate, passing on their genes — and grit — to their offspring. As subsequent generations of these microbial gladiators endure further onslaughts of drugs, they evolve even greater resilience, improving their defenses against antibiotics and sometimes spreading these adaptations throughout the microbial universe through the promiscuous exchange of DNA. By flooding our bodies, farms and hospitals with inordinate amounts of antibiotics — obliterating the weak and sparing the strong — we created exactly the kind of ruthless ecological arena most likely to drive the evolution of resistance.

The difficulties don’t end with regulators. Per the ethics of their field, ethnobotanists would also need to ensure that some of the profits from drug sales reach the people who originally developed a traditional botanical remedy. In 1992, more than 150 governments signed the Convention on Biological Diversity, a treaty establishing that nations retain sovereign rights over their indigenous medicines and that such resources should be shared only after mediation of equitable benefits.

But above all else, the apathy of the pharmaceutical industry remains the biggest immediate roadblock. “The odds are sometimes disheartening,” I admit. But this is my field, and I’m not going to abandon ship because today the market is not supporting antibiotic research. In the near future they’ll have to. Contemporary Medicine will stop without antibiotics.

Consider, for instance, that over the past eight years, Thailand, Cambodia and other Asian countries have reported   increasingly common cases of artemisinin-resistant malaria. Yet a recent study demonstrates that feeding rodents sweet wormwood leaves in their entirety — as opposed to a synthesized derivative — overcomes this resistance. The modern, stripped-down version of this ancient medicine may very well sacrifice some beneficial chemical synergy present in the whole plant.

If I am right, the impending medical crisis will eventually jump-start antibiotic research and development. But it can take more than a decade for a standard antibiotic to transition from discovery to pharmacy, let alone an entirely novel concoction or seemingly convoluted treatment. Meanwhile, we will be stuck with a dwindling stock of extant antibiotics, our only recourse against increasingly armored pathogens.

In the early evening of our penultimate day in Salamis, while driving along the edge of an orchard, with the scent of orange blossoms wafting through the car’s open windows and the lime-green sparks of fireflies blinking around us, I suddenly cried out to stop the car. I flung open the door, rushed forward and stooped to inspect a small rosette of dandelionlike leaves surrounding a few stalks furred with teensy maroon flowers. Most people would have regarded the three-inch-tall plant as a completely unremarkable weed, if they noticed it at all.

During my two-week expedition in the marshes, orchards of Salamis, I had already collected close to 75 species — primrose willow, carnivorous sundew, toothache grass, gallberry, black nightshade — but I could not pass this one up. The surprise was that I found a Plantago. It’s known for applications for skin infections. One species of the plant, can stop a bleeding wound; another can heal abscesses. It’s easy to dig up, I continued, turning back to the car saying to my friend “Let’s get some bags and grab as much as you can.”