Exeter, Devon UK • Dec 5, 2023 • VOL XII

Exeter, Devon UK • [date-today] • VOL XII
Home Science Twinkle Winkle Little Star

Twinkle Winkle Little Star

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The C word. Painfully prevalent and responsible for over a quarter of all deaths in the UK during 2016, cancer is deadly. With over 200 different shades of the disease and one in two people born after 1960 in the UK being diagnosed with cancer in their lifetime, it’s not difficult to see why research into its treatment is taking precedence. But, might there be a shining star and burning beacon of hope in the pursuit of cancer treatment?

Plant Scientists at the John Innes Centre (JIC), in Norwich, have reason to believe so, after a sixty year- long forage for the secrets of the Madagascar Periwinkle plant. Fifteen years and thirty one chemical steps later, and the team of researchers at the Professor Sarah O’Connor laboratory, JIC, have made significant strides in Cancer research. They have successfully found the final missing genes of the Periwinkle plant genome needed to synthesise a crucial cancer- fighting drug: Vinblastine. The drug is one of a plethora of chemotherapy drugs named vinca alkaloids. Referred to as plant alkaloids, the first of these is derived from the vinca plant. Their job is to inhibit microtubule activity- a key cytoskeletal cellular component needed for the division of a cancer cell into 2 new cells. Hence, intravenous injection of Vinblastine into the bloodstream can block cancerous growth.

Madagascan perriwinkle. Source:pixabay

The precious Periwinkle is able to inhibit the rapid, uncontrolled cell division involved in Lyphomas, breast, lung, bladder and testicular cancers. From ornamental to monumental, this pink and white perennial plant seems to be something of a pharmacological phenomenon.

So, just how much should we be celebrating? Discovered in the 1950s by a group of Canadian researchers and approved by the US Food and Drug Administration for chemotherapeutic use, the anti-cancer capability of the Madagascar Periwinkle (Catharanthus roseus) isn’t exactly new. However, there has been a void in our understanding of the complex chemical pathways recruited by the plant; a hefty 500 kilograms of its dried leaves are required to produce just one gram of Vinblastine. Fortunately, a recent study – led by the author Dr Lorenzo Caputi – published in the peer-review journal, Science, harnesses current genome sequencing methods to isolate the last of the genes in the Vinblastine pathway.

It’s powerful enough to increase the survival rate from 10% to 95%

Identification of the Catharanthine and Tabersonine enzymes, crucial in the formation of Vinblastine precursor molecules, has allowed us to generate Vinblastine synthetically in a lab. Either by increasing the amount of Vinblastine produced by the plant or by inserting synthetic genes into hosts, such as other plants or yeast, this new knowledge unlocks important weapons to target the rapid multiplication of white blood cells observed in some Cancer types, such as Leukaemia. Indeed, with Vinblastine already in use for treatment of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphomas, it’s powerful enough to increase the survival rate from 10% to 95%.

Leukemia cells. Source: wiki commons

Importantly, the potential to increase Vinblastine’s yield via synthetic biology will see a domino effect: combatting the challenge of maintaining a steady reliable supply, likely to reduce the cost of drugs, and enabling more patients to access treatment. With considerable collaboration and competition within this field of research, Professor O’Connor forecasts that scientists will accomplish the production of ‘microgram quantities of Vinblastine or its precursors…in the next twelve to eighteen months.’

Far from an easy feat, it’s been a journey of perseverance, not without its pitfalls. In fact, along the trail of technicality, trial and error, Dr Caputi describes ‘one molecule…so volatile it’s known as angry-line”, in place of its convoluted title, Dihydroprecondylocarpine. Meanwhile, there are undeniably side effects of using the chemotherapy drug, Vinblastine (known as Velbe). One or more of the following side effects occurs in more than 10 in every 100 people: higher risk of infection (due to a reduction in the number of white blood cells in the immune system), breathlessness and pallor of the skin (resulting from a decrease in the number of red blood cells- anaemia- which causes a lack of oxygen reaching cells), tiredness during or after treatment and hair loss (on the scalp or body due to a reduction in hair follicle cell division). These may occur in addition to other common side effects of chemotherapy, including temporary amenorrhea (periods stopping), soreness of the mouth, and feeling or being sick.

scientists will be able to produce ‘microgram quantities of Vinblastine in the next 12- 18 months.

Do the risks outweigh the benefits, I hear you ask. Well, it’s truly a matter of choice. But, you can’t put a price on saving a person’s life. Risk taking brings revelation. We might not have been vin(blastin’)e our way to a direct cure for cancer, but we are closer than we’ve ever been before.


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