Nature’s Medicine Cabinet

More than 70 percent of new drugs approved within the past 30 years originated from trees, sea creatures and other organisms that produce substances they need to survive. Since ancient times, people have been searching the Earth for natural products to use—from poison dart frog venom for hunting to herbs for healing wounds. Today, scientists are modifying them in the laboratory for our medicinal use. Here’s a peek at some of the products in nature’s medicine cabinet.

Vampire bat

A protein called draculin found in the saliva of vampire bats is in the last phases of clinical testing as a clot-buster for stroke patients. Vampire bats are able to drink blood from their victims because draculin keeps blood from clotting. The first phases of clinical trials have shown that the protein’s anti-coagulative properties could give doctors more time to treat stroke patients and lower the risk of bleeding in the brain.

Sea squirts

Sea squirts in the crystal waters of West Indies coral reefs and mangrove swamps are the source of an experimental cancer drug called Yondelis. The drug binds to DNA and damages specific genes, which slows cancer cell division, growth and spread. The first set of clinical studies has shown that the drug is safe for use in humans. Additional phases of clinical testing are underway to evaluate whether Yondelis effectively treats tumors of the muscles, tendons, supportive tissues and other types of cancer.

Gila monster

A hormone found in the saliva of the gila monster, a venomous lizard from the woodlands and deserts of the American Southwest, was modified to help people with type 2 diabetes maintain healthy blood sugar levels. Since gila monsters only eat about twice a year, their sugar storage hormone is active for much longer than insulin is in humans. The hormone-derived drug, Byetta, also slows the movement of food from the stomach into the small intestine, which often results in weight loss in diabetics.

Guggul tree

The guggul tree is native to India and has been used in Ayurvedic medicine since at least 600 B.C. to treat obesity and lipid disorders. Scientists are conducting preliminary studies to explore the cholesterol-lowering properties of guggulsterone, a compound in the sap of the guggul tree. Researchers think guggulsterone blocks receptors in liver cells and alters cholesterol break down. Studies have also suggested that guggulsterone has anti-inflammatory properties and can lower triglyceride levels.

Cinchona tree

The bark of the cinchona tree, found in the Amazon rainforest, is the source of the antimalarial drug quinine. Isolated by French chemists in the early 19th century, quinine treats malaria by altering the life cycle of the malaria parasite. Since then, scientists have designed other antimalarial drugs including chloroquine, mefloquine and other derivatives that are chemically similar to quinine. Another natural product, sweet wormwood plant, is the basis of the malarial treatment artemisinin.

Yew tree

A chemical produced by the Pacific yew tree is now the cancer-treating drug paclitaxel (Taxol). The plant-derived drug works by inhibiting the function of microtubules, structural elements that are needed for cell division. By preventing cancer cells from dividing, Taxol stops the cancer from growing. Taxol is used to treat a variety of cancers including breast, lung, prostate and ovarian cancer.

Cone snail

Cone snails in the waters near Australia, Indonesia and the Philippines have toxin-packed venom that’s being studied as a treatment for chronic pain. Prialt, a synthetic compound modeled after a toxin in the venom, is 1,000 times more powerful than morphine in treating certain kinds of chronic pain. The snail-derived drug jams nerve transmission in the spinal cord and blocks certain pain signals from reaching the brain. It’s prescribed to help manage the pain of people suffering from multiple sclerosis, AIDS and cancer.

Bishop’s weed

Psoralen, derived from a Nile-dwelling plant called Bishop’s weed, is a key component of photodynamic therapy, which is used to treat several cancers. Once activated by light, psoralen attaches tenaciously to the DNA of rapidly dividing cancer cells and kills them. Psoralen is also prescribed to increase the ultraviolet absorptivity of skin so UV light can then be used to treat severe skin conditions like psoriasis and eczema.

Snowdrops

Galantamine, a compound extracted from the bulbs and flowers of daffodils, spider lilies and snowdrops, is prescribed to stabilize and improve cognitive function in Alzheimer’s patients. It works by preventing the breakdown of acetylcholine, a chemical that sends messages between certain nerve cells and is important for learning and memory.

The vampire bat, gila monster, bishop’s weed and snowdrop images courtesy of iStock; Sea squirt image courtesy of Pharmamar; Commiphora wightii (guggul tree) Exit icon image courtesy of Vinayaraj V R under CC BY SA 3.0; Cone snail image courtesy of Kerry Matz, University of Utah; Cinchona tree Exit icon image courtesy of U.S. Geological Survey; Pacific yew tree image courtesy of Virginia Tech, Department of Forest Resources and Environmental Conservation.

Elements That Keep Us Alive Also Give Color to Fireworks

Looking up at the night sky this Fourth of July, you might wonder what gives fireworks their vivid colors. The bright hues result from chemical elements that are also essential for life. Chemists and other researchers have been uncovering their roles in a range of important biological processes.

By mass, about 96 percent of our bodies are made of four key elements: oxygen (65 percent), carbon (18.5 percent), hydrogen (9.5 percent) and nitrogen (3.3 percent). These elements do not give color to fireworks, but they are found in our body’s most abundant and important molecules, including water, proteins and DNA.

A dozen or so other elements—mostly metals—make up the remaining 4 percent. Present in minuscule amounts, these elements are involved in everything from transporting oxygen and releasing hormones to regulating blood pressure and maintaining bone strength. They also add a burst of color when put in to a fireworks recipe. Here are several examples. Continue reading

Designing Drugs That Kill Invasive Fungi Without Harming Humans

Top to bottom: Cryptococcus, Candida, Aspergillus, Pneumocystis
Invasive fungal infections kill more than 1 million people worldwide every year. Almost all of these deaths are due to fungi in one of these four groups. Credit: Centers for Disease Control and Prevention.

Invasive fungal infections—the kind that infect the bloodstream, lung and brain—are inordinately deadly. A big part of the problem is the lack of drugs that are both effective against the fungi and nontoxic to humans.

The situation might change in the future though, thanks to the work of a multidisciplinary research team led by chemist Martin Burke at the University of Illinois. For years, the team has focused on an antifungal agent called amphotericin B (AmB for short). Although impressively lethal to fungi, AmB is also notoriously toxic to human cells.

Most recently, the research team chemically modified the drug to create compounds that kill fungi, but don’t disrupt human cells. The scientists explain it all in the latest issue of Nature Chemical Biology.

Invasive fungal infections are so intractable because most antifungal drugs aren’t completely effective. Plus, fungi have a tendency to develop resistance to them. AmB is a notable exception. Isolated 50 years ago from Venezuelan dirt, AmB has evaded resistance and remains highly effective. Unfortunately, it causes side effects so debilitating that some doctors call it “ampho-terrible.” At high doses, it is fatal.

For decades, scientists believed that AmB molecules kill fungal cells by forming membrane-piercing pores, or ion channels, through which the cells’ innards leak out. Last year, Burke’s group overturned this well-established concept using evidence from nuclear magnetic resonance, chemistry and cell-based experiments. The researchers showed that AmB molecules assemble outside cells into lattice-like structures. These structures act as powerful sponges, sucking vital lipid molecules, called ergosterol, right out of the fungal cell membrane, destroying the cell. Continue reading

Unusual DNA Form May Help Virus Withstand Extreme Conditions

A, B and Z DNA.
DNA comes in three forms: A, B and Z. Credit: A-DNA, B-DNA and Z-DNA by Zephyris (Richard Wheeler) under CC BY-SA 3.0.

DNA researcher Rosalind Franklin Exit icon first described an unusual form of DNA called the A-form in the early 1950s (Franklin, who died in 1958, would have turned 95 next month). New research on a heat- and acid-loving virus has revealed surprising information about this DNA form, which is one of three known forms of DNA: A, B and Z.

“Many people have felt that this A-form of DNA is only found in the laboratory under very non-biological conditions, when DNA is dehydrated or dry,” says Edward Egelman Exit icon in a University of Virginia news release Exit icon about the recent study. But considered with earlier studies on bacteria by other researchers, the new findings suggest that the A-form “appears to be a general mechanism in biology for protecting DNA.” Continue reading

Mapping Our Skin’s Microbes and Molecules

Last month, we shared some facts about the microbes that inhabit us. Here’s another: From head to toe, our skin bacteria coexist with chemicals in hygiene products, fibers from clothes and proteins shed by dead or dying skin cells.

These images highlight the complex composition of our body’s largest organ. They show the association between microbial diversity (top images) and skin chemistry (middle images). The different colors note the abundance of a certain bacterium or molecule—red is high, and blue is low. The skin maps remind NIH Director Francis Collins of a 60’s rock album cover. Continue reading

Field Focus: Making Chemistry Greener

Bob Lees
NIGMS’ Bob Lees answers questions about green chemistry. Credit: National Institute of General Medical Sciences.

Chemists funded by NIGMS are working to develop “greener” processes for discovering, developing and manufacturing medicines and other molecules with therapeutic potential, as well as compounds used in biomedical research. One of our scientific experts, organic chemist Bob Lees, recently spoke to me about some of these efforts.

What is green chemistry?

Green chemistry is the design of chemical processes and products that are more environmentally friendly. Among the 12 guiding principles of green chemistry Exit icon are producing less waste, including fewer toxic byproducts; using more sustainable (renewable) or biodegradable materials; and saving energy. Continue reading

Zinc’s Role in Healthy Fertilization

Screen shot of the video
Fluorescent sensors at the cell surface show zinc-rich packages being released from the egg during fertilization. Credit: Northwestern Visualization. View video Exit icon

Whether aiding in early growth and development, ensuring a healthy nervous system or guarding the body from illness, zinc plays an important role in the human body.

Husband-and-wife team, Thomas O’Halloran Exit icon and Teresa Woodruff Exit icon, plus other researchers at Northwestern University, evaluated the role that zinc plays in healthy fertilization Exit icon. The study revealed how mouse eggs gather and release billions of zinc atoms at once in events called zinc sparks. These fluxes in zinc concentration are essential in regulating the biochemical processes that facilitate the egg-to-embryo transition.

The scientists developed a series of techniques to determine the amount and location of zinc atoms during an egg cell’s maturation and fertilization as well as in the following two hours. Special imaging methods allowed the researchers to also visualize the movement of zinc sparks in three dimensions. Continue reading

Remotely and Noninvasively Controlling Genes and Cells in Living Animals

Remote control car key.
Researchers are developing a system to remotely control genes or cells in living animals with radio wave technology similar to that used to operate remote control car keys. Credit: Stock image.

One of the items on biomedical researchers’ “to-do” list is devising noninvasive ways to control the activity of specific genes or cells in order to study what those genes or cells do and, ultimately, to treat a range of human diseases and disorders.

A team of scientists recently reported progress on a new, noninvasive system that could remotely and rapidly control biological targets in living animals Exit icon. The system can be activated remotely using either low-frequency radio waves or a magnetic field. Similar radio wave technology operates automatic garage-door openers and remote control car keys and is used in medicine to control electronic pacemakers noninvasively. Magnetic fields are used to activate sensors in burglar alarm systems and to turn your laptop to hibernate mode when the cover is closed. Continue reading

A Bright New Method for Rapidly Screening Cancer Drugs

Illustration of red, green and blue fluorescent proteins.
Chemists have devised a new approach to screening cancer drugs that uses gold nanoparticles with red, green and blue outputs provided by fluorescent proteins. Credit: University of Massachusetts Amherst.

Scientists may screen billions of chemical compounds before uncovering the few that effectively treat a disease. But identifying compounds that work is just the first step toward developing a new therapy. Scientists then have to determine exactly how those compounds function.

Different cancer therapies attack cancer cells in distinct ways. For example, some drugs kill cancer cells by causing their outer membranes to rapidly rupture in a process known as necrosis. Others cause more subtle changes to cell membranes, which result in a type of programmed cell death known as apoptosis.

If researchers could distinguish the membrane alterations of chemically treated cancer cells, they could quickly determine how that chemical compound brings about the cells’ death. A new sensor developed by a research team led by Vincent Rotello Exit icon of the University of Massachusetts Amherst can make these distinctions in minutes. Continue reading

New Streamlined Technique for Processing Biological Samples

Illustration of Slug flow microextraction.
Researchers have discovered a faster, easier and more affordable technique for processing biological samples. Credit: Weldon School of Biomedical Engineering, Purdue University.

It’s not unusual for the standard dose of a drug to work well for one person but be less effective for another. One reason for such differences is that individuals can break down drugs at different rates, leading to different concentrations of drugs and of their breakdown products (metabolites) in the bloodstream. A promising new process Exit icon called slug-flow microextraction could make it faster, easier and more affordable to regularly monitor drug metabolites so that medication dosages could be tailored to each patient’s needs, an approach known as personalized medicine. This technique could also allow researchers to better monitor people’s responses to new drug treatments during clinical trials. Continue reading