2015 Nobel Prize highlights importance of botanical chemistry

1600 years ago, a Chinese physician wrote in a book called "Emergency Prescriptions Kept Up One's Sleeve", that soaking a plant now known as Artemisia annua  in water, and then drinking the juice, can reduce fever. This text was rediscovered in the second half of the 20th century by a then obscure Chinese pharmacologist, Tu Youyou. Ms Tu was working on a secret project to find a novel cure for malaria. She found that artemisia extract was highly efficient in combating the malaria parasite. Her work led to the development of the drug artemisinin, which is now widely used in malaria treatment in Africa.  Ms. Tu's role in the discovery of artemisinin remained hidden from the West for most of her life. But now at the age of 85, she has been recognized with the 2015 Nobel Prize in Medicine for her work

An illustration describing Ms Tu's work displayed during the press conference announcing the winners of the Nobel Medicine Prize. Linked from and The Telegraph: Nobel Prize for Chinese traditional medicine expert who developed malaria cure. Photo: AFP

This reminds us that many of our medicines have their roots in botany. The ancient Greek physician Hippocrates described a bitter substance, now known to be salicylic acid, from willow bark that could ease aches and reduce fevers. Other cultures in the ancient Middle East also used willow bark as a medicine, as did Native Americans. Centuries later, we know salicylic acid as the chemical precursor for aspirin (which is acetylsalicylic acid), and salicylic acid itself is a key ingredient in many modern anti-acne face washes.

The Pacific Yew is a conifer found primarily in the Pacific Northwest. Its thin scaly back would probably go unnoticed if not for the fact that it contains a chemical called paclitaxel, or more commonly known as the chemotherapy drug Taxol. Taxol was discovered in the mid 1960s as part of a large-scale program to identify natural products which might be used against cancer. In 1992 Taxol was approved by the FDA for use in fighting breast, ovarian and lung (and a few other) cancers.

And what would life be like without the opium poppy, the source of morphine or codeine. The medicinal (and likely recreational) uses of opium poppy have been known for thousands of years. And the increasingly legal uses of cannabinoids in western medical protocols cannot be ignored.

These are prime examples of how a deep knowledge of botanical diversity and chemistry can lead to incredibly important applications.

Unfortunately, education towards and development of expertise in these fields over the past decades were not a priority for many universities, where plant biology outside of the study of model organisms was looked down upon. At Tel Aviv University we've recognized the importance of botanical pharmacology. As Dean of the Faculty of Life Sciences, together with the Dean of the Faculty of Medicine, we have initiated a search for a botanical pharmacologist whose position will be divided between our two Faculties, between plant biology and pharmacology. Such interdisciplinary research is critical for exploiting the medicinal potential hidden in plants.

The chemistry of pot

We all know that THC (Δ⁹-Tetrahydrocannabinol) is the main active ingredient of marijuana. However, you may not be aware of the high-tech research going into figuring out how pot plants make THC.

A recent paper published in the Proceedings of the National Academy of Sciences of the United States of America (affectionately known as PNAS) illustrates how some of this research is carried out.

To produce THC, cannabis employs a number of differenet enymes which work in a linear series simplified below:

hexanoyl-CoA + malonylCoA --> OA --> CBGA --> THCA --> THC

Each of the arrows is a different enzyme. A big challenge in understanding how cannabis makes THC (and maybe to be able to make it artificially) is identifying each of the enzymes. As the biochemistry behind this pathway is very complex, this has not been a simple matter.

trichomes on a Cannabis sativa leaf

The lab of Jonathan Page in Saskatchewan figures that the genes encoding these enzymes should be specifically enriched in the THC-rich trichomes, the sticky, furry things on cannabis leaves. They first identified all the genes that are expressed in these trichomes, and then, using their knowledge of enzymology, sought out particular genes that looked like a particular class of enzymes that could potentially take part in the chemistry of the first arrow. They found three candidate genes, and then put each into E.coli to make the proteins. When they added these proteins to hexanoyl-CoA and malonylCoA, the precuursors of OA, they found OA is the mixture. In other words, they identified gene encoding the enzyme for the first arrow. 


When they put this gene in yeast, the yeast started making OA. Just think of the possibilities for beer if they wold add the genes for the arrows...

Guest Blog Linda Leaming: Meeting Himalayan Medicinal Plants

Linda Leaming lives in paradise. Her book MARRIED TO BHUTAN is the story of her life in one of the most magical and beautiful places on earth, the Himalayan Kingdom of Bhutan.

The caretaker's garden

I never feel more happy or alive than when I'm walking in the mountains of Bhutan. One of my favorite walks is to WangdueTse (Wang-d-SAY), a famous, old temple on the outskirts of Thimphu with giant iron statues and an ancient mud floor. It takes half a day from my house in the hills above the city, and it's a marvelous escape into another world. The hike takes me down the big hill where we live, around the bend and then up the switchback road to Sangaygang (San-GAY-gang). At Sangaygang, high above the city, I walk past the caretaker's cottage and note his nice garden, and then it's over a big mound and I'm in the woods headed to the temple.

Khempa (Tibetan Sage)

Surrounded by the forest, there's that insular, rich aroma of nature and life. Rotting plants, pine sap, urine, fresh air, flowers, and wood smoke, all blend together, and it's the smell I love most. One plant, called khempa by the Bhutanese, is gloriously making itself known on the edge of the trail this spring morning. It has a sort of pungent, musky, eucalyptus smell and is used liberally here as a medicinal plant. A spoonful of the juice helps with sinusitis, and a hot bath with an armful of its leaves will cure back pain. Bhutan in the Himalayas is the land of medicinal plants. There are over of them 500 cataloged, and many as yet unrecorded. In Thimphu we live near the Traditional Hospital, which uses many traditional herbs and plants for healing. Here's a blog post I wrote about going to the traditional hospital.

    

Poppies

Papaver someniferum (Opium poppy)

What would life be like without the opium poppy? No poppy seed bagels. No beautiful poppy flowers. No Dorothy falling asleep in the poppy fields in the Wizard of Oz. No morphine or codeine. The use of poppy as a pain killer is probably it's claim to fame and, when misused as in heroin, to infamy. The medicinal uses of opium poppy have been known for thousands of years. Turkey, India and surprisingly Australia, provide most of the worlds legal opium poppy. I once saw some opium poppy growing in a road divider on the way to Hadassah Hospital. Obviously it was planted for convenient use in the hospital, and not for any illicit uses.

The Indian Date

Tamarindus indica (Tamarind)

The Tamarind tree is little known in the west, but common in Africa and Asia. It name comes from the Arabic and Hebrew words tamar , which means "date", and hind, which means "India". Its fruit can be eaten, turned into a drink, or used to flavor ice cream. Both its fruit and bark are used in traditional medicines and modern studies have shown that they contain chemicals that can work as anitibiotics. In Asian temples, the fruit pulp is used to polish brass Buddhas.

Yew and cancer

Taxus brevifolia (Pacific Yew)

The Pacific Yew is a conifer found primarily in the Pacific Northwest. Its thin scaly back would probably go unnoticed if not for the fact that it contains a chemical called paclitaxel, or more commonly known as the chemotherapy drug Taxol. Taxol was discovered in the mid 1960s as part of a large-scale program to identify natural products which might be used against cancer. In 1992 Taxol was approved by the FDA for use in fighting breast, ovarian and lung (and a few other) cancers. This is a prime example of how a deep knowledge of biodiversity can lead to incredibly important applications.

With Parsely and Sage and Thyme

Rosemarinus officinalis (rosemary)

The rosemary shrub get its name due to its hardy nature. Rosemarinus means "dew of the sea" and rosemary plants can often grow with no water other than the humidity in the sea breeze. In addition to its culinary uses, rosemary may have pharmaceutical potential. A recent study showed that rosemary can influence both mood and cognition in people!

No yams, no Pill

Dioscorea mexicana (Mexican yam).
photo by Nhu Nguyen

Mexican yams were the original source of the chemicals that were used in the first oral contraceptives (affectionately known as The Pill) in the mid-20th century. These inedible wild yams (not to be confused with sweet potatoes, which belong to a different family of plants, but are are sometimes mistakenly referred to as "yams")  contain a chemical called diosgenin, a type of phytoestrogen. Scientists at the Mexican pharmaceutical company Syntex extracted Diosgenin from these yams and used it to make progesterone which in turn was used in the early versions of The Pill. In nature, Mexican yams are found in the rain forests of southern Mexico and Central American and are cultivated today primarily for the interesting "turtle shell" look of the tuber root.