Living Fossils Inspire Cures for Disease: How Some of the Oldest Organisms on Earth Might Serve as a Promising Source of Pharmaceutical Drugs

Long before humans, dinosaurs, or plants, some of the first creatures on Earth were primitive single-celled organisms that survived exclusively from the energy of light. These organisms are called cyanobacteria — but you may know them as blue-green algae. The first cyanobacteria lived about 3.5 billion years ago, and since then, they’ve played an integral role in shaping our planet. In fact, cyanobacteria were the first organism to introduce oxygen to the atmosphere, a process that instigated what scientists call the Great Oxygenation Event.

accumulation of blue-green algae
Cyanobacteria sitting on the surface of a lake

Cyanobacteria are photosynthetic, meaning they use energy from the sun to make food, and in the process, they release oxygen into the environment. Starting about 2.7 billion years ago, they released so much oxygen into the environment that they drastically changed the composition of the atmosphere. Many organisms did not survive this change, but others took advantage of this new world – including primitive fish, birds, and eventually, mammals. We are here today, thanks to ancient cyanobacteria.

Cyanobacteria have faced many challenges throughout history, including changes in the climate, extreme weather conditions, and the threat of predators. But despite these changes, these living fossils have continued to evolve since their first appearance, and they are still among us today.

What is the secret to their survival? Chemistry. Cyanobacteria use a variety of chemicals to protect themselves and to colonize new environments. Like little chemical factories, cyanobacteria possess the machinery they need to produce complex molecules that can protect them from viruses, bacteria, fungi, larvae, insects, and animals.

Recently, scientists have observed cyanobacteria’s resilience and have started to wonder: if they are so good at protecting them from the environment, can we borrow these molecules from them to protect us?

In the mid-1980s, scientists started to explore the medical use of cyanobacterial molecules. To begin their research, they took a trip into nature. Cyanobacteria can be found in any environment that has sunlight and moisture, including everywhere from the shallow seas in Hawaii, the rivers in Amazonia, the Great Lakes, and even your backyard! (How do you know if cyanobacteria have visited your neighborhood? After it rains, look for green slime on rocks and walls – this was probably formed by cyanobacteria.)

blue-green algae slime on a tree
Cyanobacteria on the bark of an oak tree.

Researchers look for this slime too. They scrape these cyanobacterial samples off of rocks and bring them to the laboratory to study them. In the lab, they use chemicals to extract the molecules to test their abilities to fight diseases such as cancer, bacterial and viral infections, and many others. If the extract shows activity against a disease (for example, if it kills cancer cells), the researchers try to determine the exact molecule within the extract that is responsible for the observed activity.

A New Cancer Drug

Cyanobacterial extracts may contain thousands of molecules, and detecting a useful one is like finding a needle in that haystack. Fortunately, scientists have developed several techniques that separate the many compounds in the extract. Using these approaches, research groups around the globe have discovered thousands of potentially useful cyanobacterial molecules since the 1980s. One successful example is a compound called dolastatin 10.

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A microscopic view of cyanobacteria

Dolastatin 10 was first reported in 1987 by Dr. George Pettit. Dr. Pettit found a mollusk (Dolabella auricularia) in the Indian Ocean, whose extract was effective in killing cancer cells. He purified the active substance and named it dolastatin 10. Later, in 2001, another research group discovered that dolastatin 10 was not produced by the mollusk itself, but by a cyanobacterium on which it feeds. In the 2005, dolastatin 10 was tested in human patients. The initial molecule didn’t do much, but later on, chemists developed a more potent version of the molecule and linked it to antibodies to improve its specificity to cancer cells. In 2011, this powerful combination became an anticancer drug called Brentuximab Vedotin.

Cyanobacteria are a promising source of new molecules, whose medicinal potential we have only recently started to explore. These ancient organisms’ chemical factories have undergone billions of years of evolution and refinement to produce metabolites that help them survive in all sorts of environments. It’s only a matter of time until we find out how these molecules can help us. The complexity of cyanobacterial molecules still amazes researchers and inspires them to develop new and better drugs. New strains and new molecules are out there waiting to be discovered. Who knows, the next great chemotherapy drug might be living in your backyard right now.

Camila M. Crnkovic is a Ph.D. Candidate in the Department of Medicinal Chemistry and Pharmacology at the University of Illinois at Chicago