Honeybees have always been “ahead of human time” in how they protect themselves. It’s not just how they sting but how they protect their colonies from invaders.
That protective strategy is the focus of international research, led by a Galway company, which is working on new antidotes to malaria and a number of respiratory illnesses, including Covid-19 and the cause of the next possible pandemic.
Enzymes produced by honeybees which have been combined with marine plasma are producing “very promising results”, says respiratory scientist Dr Daniel O’Toole of University of Galway’s school of medicine.
O’Toole is one member of the team extending from Galway to Ghana, Poland and Lebanon, which has been put together by cellNUA Teo to test a combination which they have labelled as “Beemar”.
Beemar — as in bee enzymes and marine plasma — relies on “adaptive and innate immunity to provide protection against a wide range of pathogens”, explains cellNUA’s managing director Declan Clarke, who holds an MSc in marine science.
It may also provide a platform to deal with “Pandemic X”, he says.
Clarke, formerly of the Marine Institute, teamed up with John Kelleher to form the company — originally named Cell Health Nutrition — to explore what was initially a hypothesis involving two natural ingredients.
Lysozyme, one of the honeybee enzymes, is found in different fluids such as chicken egg albumen and is equipped to fight against bacteria.
Marine plasma, as in concentrated seawater, has 78 trace elements and minerals and is produced by zooplankton after feeding on phytoplankton blooms. The combination “stimulates the nuclei in the body’s cells to produce some of the genetic material it is being protected against”, while the marine plasma protects the surrounding tissue from infection during the vaccination and treatment process, Clarke says.
He credits the company’s co-founder and head of science, Dr Rania el Helou, who is based in the Lebanese capital, Beirut, with making the initial breakthrough.
Kelleher had been travelling the world in search of a platform that drew on nature’s intelligence to disrupt the field of infectious disease therapies.
“By the time he hired myself and the team in Lebanon, five years ago, he was already working with a group of other scientists across the globe,” says el Helou. “It was a joint decision to do comparative genomics to sequence and isolate as many compatible molecules for exploitation, and not just lysozymes.”
The malaria parasite entering the bloodstream has two forms, asexual and sexual, and most anti-malarial drugs target the sexual form
— Prof Kwadwo Asamoah Kusi
The team opted for the honeybee, believing it could be exploited ethically for advances in human health. “Choose a ‘too similar’ species, and you fall into the trap of either failure of treatment or anaphylaxis,” she says.
“The honeybee shares more similarities with humans than with other insects and with ancient genes that were lost in the line of evolution,” she adds.
“Long before written language was invented, long before man discovered fire and centuries before the first villages were built, the inherent bee survived many apocalyptic pathogens,” notes el Helou.
Healthy colonies have developed an ability to formulate an immunity by applying the lysozymes to recognise “invaders” and “break down their cells”.
Alexander Fleming, the “father of sciences”, championed the properties of lysozymes, and had great hopes for its future applications. “Penicillin, his second discovery, was embraced as the ideal mass production antibiotic after the Pearl Harbour attack of 1941,” she says.
The lysozyme found through hens is a popular antimicrobial for beer and cheese manufacturing, but “comparing the honeybee lysozyme — plus its cluster — to the hen version is the equivalent of comparing a Swarovski crystal to a diamond”, explains el Helou.
“Chief among the many advantages of this particular enzyme is the fact that it is nano-therapeutical, as provided by nature — the smaller the peptide or the molecule, the greater its chance to instruct the cell,” she says.
“We have demonstrated its efficacy in diverse virus families, including polio, adenovirus, influenza, herpes, equine herpes and Sars-Covid 2. By the last quarter of this year, we aim to have robust data on the antibacterial branch of the platform.”
The extract has to come from healthy honeybee colonies. Under the patented process and platforms, harvesting four or five times a year is from the “zabrus” of the hive, as in the larval cap, where there is no impact on the colony.
“The European bee has been hybridised because beekeepers favoured a more docile bee that does not sting them,” el Helou says.
“Regrettably, in their pursuit of higher honey output, they ended up with bees with reduced immune systems that can hardly combat colony-specific diseases,” she says, acknowledging this “does not negate the other contributing factors of colony collapse, such as pesticide use or single crop agriculture. At cellNUA we have developed advanced protocols for our own hive maintenance, and we do prefer non-hybridised bees.”
It is fantastic for us to know as researchers that there are thousands of years of safety and security behind this
— Dr Daniel O’Toole
Their research teams have set up hives in Rechmaya in Lebanon; in Wroclaw, Poland, with plans to expand into Germany and Italy this year. They also have hives in Accra, Ghana, and have recently established a new apiary in Maryland, US, in collaboration with the University of Maryland.
In Ghana, the results are proving very promising in relation to malaria, says Prof Kwadwo Asamoah Kusi who is principal investigator at the Noguchi Memorial Institute for Medical Research, Ghana.
“The malaria parasite entering the bloodstream has two forms, asexual and sexual, and most anti-malarial drugs target the sexual form,” he adds.
“We are about to test the “Beemar” combination against the form of parasite that the mosquito picks up, and we are repeating tests both in-vitro and in live animals,” he says.
“So far, results are quite agreeable. The mice we used for animal trials were given a high dose of Beemar for seven days, and a lower dose for 30 days, and we didn’t see any pathologies,” he confirms.
“If we can prove its effectiveness with malaria, it will be an African solution to an African problem,” he believes. “We have established hives in the eastern part of Ghana using a different type of bee. We also plan to study the bee venom to see if it has properties, as stings are meant to build the immune system.”
Clarke explains that the Polish link in the chain is led by Dr Barbara Bażanów, adjunct professor at the Wroclaw University of Environmental and Life Sciences, where the first animal trials took place.
Back in Galway, Dr O’Toole says they have seen enough to know that Beemar works in a lot of contexts. “We know it is antiviral and we know it is antibacterial, and the research with our partners is determining which part does what.”
“The more composition that our partners can tell us — about what does what — the easier the regulatory pathway,” O’Toole explains.
His laboratory has been testing the beehive extracts and marine plasma in parallel, sometimes together and sometimes separately and has found marine plasma to be “absolutely fantastic for supporting cells during transport”.
“There are commercial products to protect cells which are being shipped for cell therapy, but the marine plasma was better than the commercial material in supporting the cells at four degrees or room temperature,” he says.
cellNua is ‘probably the first team to fully understand how the honeybee has evolved over millions of years by beating both known and unknown diseases caused by all types of pathogens’
— John Kelleher
As for the hive extracts, he says that “we can pour incredible amounts of stuff on any cells we have and it is not toxic”.
“It is fantastic for us to know as researchers that there are thousands of years of safety and security behind this. Coming from a beehive you know it is going to be plain sailing on the toxicology testing front,” O’Toole continues.
“It has passed all those tests with flying colours in the in-vitro work, and we have applied to the Health Products Regulatory Authority for licences to move it on to the animal work.”
Some Beemar products which don’t require clinical trials and which aim to be effective against respiratory illnesses will be going to market sooner rather than later, in the form of a nasal spray, available in the US from next year, Clarke says.
The company has been working with Gaeltacht State agency Údarás na Gaeltachta to establish a research and development and manufacturing hub to support product release in the US.
Kelleher says that cellNua is “probably the first team to fully understand how the honeybee has evolved over millions of years by beating both known and unknown diseases caused by all types of pathogens”.
“Much more importantly, we have been able to apply this science and knowledge to help humans to do the same,” he says.
He believes that, all going to plan, his team is “very well placed to tackle the unknowns ... such as pandemic X”.
