A KILLER CURE

TAK­ING THE ST­ING OUT OF HIV

Guru Magazine - - Contents - JANSKE NEL

If a swarm of killer bees de­cides to at­tack you, run. Keep run­ning and don’t stop. Th­ese nasty blighters can st­ing a man to death. Iron­i­cally, their venom could also help save mil­lions by help­ing to rid the world of HIV. Guest writer Janske Nel ex­plains how on page 19.

It is a blaz­ingly sunny De­cem­ber af­ter­noon in a small town at the south­ern tip of Africa. The air is hot and heavy. No wind or breeze stirs the tree tops. Sara, a mother of two, is work­ing in the gar­den, metic­u­lously up­root­ing weeds, prun­ing hedges, and trim­ming the trees cov­er­ing her per­fectly pink hy­drangeas. Sud­denly, the air around her is filled with a dron­ing, an­gry sound as a black cloud rises up from the tree fo­liage. In­stinct takes over, and Sara cov­ers her face and runs. Adren­a­line and panic tem­po­rar­ily keep the pain at bay, but the mul­ti­ple stings she re­ceives from a swarm of African honey bees – or killer bees as they are known in most parts of the world – de­mand to be felt even­tu­ally. The in­tense pain seizes her; she col­lapses, and dark­ness de­scends. Lit­tle does she know that what’s cours­ing through her veins, and could be killing her, could hold a cure for a disease that is dec­i­mat­ing her beloved coun­try.

The mur­der­ous helper

In South Africa, the le­gends and myths sur­round­ing the beau­ti­fully coloured gold­enyel­low and black striped stingers are passed down through the gen­er­a­tions: a horde of thou­sands of bees will re­lent­lessly chase you for al­most half a kilo­me­tre once the nest is dis­turbed, and the venom from be­tween 500–1100 stings can kill an adult hu­man. Ven­oms like those of the African honey bee, are cock­tails of sub­stances that can have a harm­ful ef­fect on the hu­man body, the in­gre­di­ents of each cock­tail be­ing unique to each species of ven­omous crea­ture. For many ven­oms there are no anti-ven­oms (more cor­rectly called ‘an­tivenins’) avail­able. How­ever, an on­go­ing rev­o­lu­tion in med­i­cal re­search is look­ing past the need to de­velop an­tivenins to fo­cus in­stead on the ther­a­peu­tic prop­er­ties of the ven­oms them­selves: what if venom-tox­ins could be used to cure in­stead of kill? This is not a new idea. The great 15th cen­tury philoso­pher Paracel­sus once said; “In all things there is poi­son; there is noth­ing with­out poi­son. It only de­pends upon the doses, whether a poi­son is a poi­son or not”. So, over the years, hun­dreds of ven­oms have been stud­ied for their po­ten­tial ther­a­peu­tic ef­fects, with some of the most deadly ven­oms pro­vid­ing the most po­tent treat­ments. Since 1974, re­searchers have been ex­plor­ing the an­ti­cancer po­ten­tial of ven­oms from snake species such as the Elap­i­dae fam­ily (which in­clude Cape and Egyp­tian co­bras), Viperi­dae fam­ily (rat­tlesnakes), and Cro­tal­i­dae fam­ily (pit vipers). Toxin from Agk­istrodon con­tor­trix (the cop­per­head snake) has been shown to re­duce the spread of tu­mours, while the pu­ri­fied venom from the Tas­ma­nian tiger snake has been found to slow the growth of neu­rob­las­toma cells (tu­mours of the head and brain). Cur­rently, pu­ri­fied venom-tox­ins from snakes are used in drugs for high blood pres­sure, strokes, kid­ney dis­eases, di­a­betes, heart fail­ure, and even deaf­ness – as well as be­ing used as anaes­thet­ics. Am­phib­ian skin also car­ries fas­ci­nat­ing ven­oms that can be used to heal wounds, kill can­cer cells, and de­stroy mi­crobes – with the lat­ter be­ing the sub­ject of par­tic­u­larly fer­vent re­search given the rise of mi­crobes that are im­mune to most cur­rently-avail­able an­tibi­otics. Bee, wasp, cen­tipede and scor­pion ven­oms have also been tested for their abil­ity to ef­fec­tively treat leukaemia, liver can­cer and mul­ti­ple scle­ro­sis; and as treat­ments to de­stroy the bac­te­ria as­so­ci­ated with sex­u­ally trans­mit­ted dis­eases such as chlamy­dia, and can­dida in­fec­tions.

Zoom­ing in on a cure for HIV

But the use of ven­oms as the ba­sis of po­ten­tial medicines isn’t with­out ma­jor chal­lenges. Af­ter all, ven­oms – by their very na­ture – are meant to kill. To un­lock the heal­ing power of ven­oms a way must be found to cross the line from toxin to ther­apy. And this is where the fields of nanomedicine and nan­otech­nol­ogy are step­ping up to the chal­lenge.

Nan­otech­nol­ogy is a field of re­search that works with par­ti­cles at the nanoscale – ob­jects sized be­tween 1 and 100 nanome­tres (1 nm = one bil­lionth of a me­tre). To put this into per­spec­tive, an atom is 0.1 nm wide, viruses are be­tween 10–100 nm in size, and the di­am­e­ter of a hu­man hair is a bulky 100 000 nm. Nanomedicine, the field of re­search that de­vel­ops nanopar­ti­cles for use in medicine, has as one goal: the de­sign of drug de­liv­ery sys­tems that are safer, eas­ier to con­trol, and more ef­fec­tive than tra­di­tional medicines. It is here that venom and nan­otech­nol­ogy are com­ing to­gether in a har­mo­nious re­la­tion­ship that could dras­ti­cally im­prove hu­man lives, es­pe­cially in South Africa. South Africa is a coun­try amongst those with the high­est rates of HIV/Aids in the world. It is es­ti­mated that over five mil­lion South Africans have so far con­tracted the virus – a stag­ger­ing 10% of the coun­try’s over­all pop­u­la­tion. Thou­sands of kilo­me­tres away, at the Wash­ing­ton Univer­sity School of Medicine in the US, re­searchers have turned to bee venom to try and find a so­lu­tion to the rapid spread of HIV. Their weapon of choice: nanopar­ti­cles coated with a highly po­tent toxin from bee venom called melit­tin. Melit­tin isn’t a com­plete new­comer to the world of medicine: it is al­ready known to be an anti-can­cer agent, ca­pa­ble of at­tack­ing re­nal, lung, liver, ovar­ian, prostate, blad­der, and breast can­cer. Its ef­fect comes from its abil­ity to de­stroy cell mem­branes, caus­ing cells to rip apart. (This also ex­plains why a bee st­ing is so un­pleas­ant!) It may come as lit­tle relief to Sara and the thou­sands of other peo­ple who are in­jured and killed by bees ev­ery year, but the mar­riage of venom – feared by mankind for mil­len­nia – and nan­otech­nol­ogy, a small but ever-grow­ing field, could have a rev­o­lu­tion­ary ef­fect on our abil­ity to fight dis­eases that kill mil­lions. Per­haps coun­tries like South Africa, which are home to the most ven­omous crea­tures, should re-eval­u­ate how they look at their buzzing, slith­er­ing, scut­tling and scary neigh - bours – not as mor­tal en­e­mies, crea­tures that bring and power to heal.

but as the po­ten­tial

Ref­er­ences:

Spatial for­ag­ing pat­terns and colony en­ergy sta­tus in the African bee A lytic pep­tide with an­ti­cancer prop­er­ties Cy­tolytic pep­tide nanopar­ti­cles (‘NanoBees’) for can­cer ther­apy. Cy­tolytic nanopar­ti­cles at­ten­u­ate HIV-1 in­fec­tiv­ity Anti-can­cer ef­fect of bee venom toxin and melit­tin in ovar­ian can­cer cells through in­duc­tion of death re­cep­tors and in­hi­bi­tion of JAK2/STAT3 path­way Bee venom in can­cer ther­apy Nanopar­ti­cle-con­ju­gated an­i­mal venom-tox­ins and their pos­si­ble ther­a­peu­tic po­ten­tial

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