Past Strive for Safety Innovations Paving the Way to Sustainable Health Future

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Elias Hakalehto, PhD, Adj. Prof.

Microbiologist, Biotechnologist

CEO, Finnoflag Oy

Vice President, International Society of Environmental Indicators

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First published on 18th of February, 2021

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On the glittering snowfields of Lapland or Klondike, we may feel the drying coldness on our faces as the Winter sun is shining uppermost. Its ultraviolet light is responsible for producing peroxides in the biological objects, thus eliminating potential pathogens by disrupting their vital molecules. This cleansing factor we feel on our chilled face as we happily speed up the dog sledges in the white vastness.

To discover novel openings or sources of health and wealth do not always preclude heavy investments in the beginning—just reasonable spending of assets whether they were the gold of the cold rivers or the healthcare funds. We need to get the right choice of the team of dogs in front of us, running and pulling fast and keeping the sledge in balance. The synchronized pace of development is a must even in our modern society. Ideas are like milk, which cannot be milked by enlarging the cowhouses' robot machines if the number of cows is not increased simultaneously. The inventiveness of the small and medium-size enterprises should be encouraged by the governments. Almost any improvement has started as a "small" idea. Its future scaling up will lead to common good and prosperity provided that the entrepreneurial sector's efforts are respected. We are vanishing opportunities if the creativity is put on the excise tax list.

Once again, we may find solutions for coping with the current unpleasant health situation using the past's wisdom and lessons. One of the most masculine writers, Jack London, published the book "The Scarlet Plague" in London Magazine in the year 1912, just before the World War 1 and the Spanish flu era, which both made a devastating toll amongst human populations. In Jack London's book, the catastrophic events were not considered immediate, but in 2013 they had led to an existential threat.

In fact, the original inhabitants of the new continent, where London wrote and situated most of his novels, were the victims of the old-world diseases. Their immune systems were not harnessed against the contagious viruses and bacteria, which were old ones on the other side of the Atlantic but brand-new ones for them. In many cases, just relatively small changes in a pathogen's constitution may lead to fatal consequences. - Correspondingly, it is not amazing how small molecular structures may make an antigen a vaccine. This explains the considerable challenges caused by the variant SARS-CoV-2 viruses today for the healthcare system. The modifications may play down the effectivity of vaccines in the worst case.

Moreover, as the outbreak of an epidemics or pandemics is a sign of broken balance in the communities on the ecosystem level. It is an outcry of the environment in every way. And that alarming bell should not be unheard. This kind of negligence could lead to:

a. the collapse of human defences under the external pressures and the strain caused by the infective agents (which every so often may be latent ones, or hiding or camouflaged pathogens, or so-called opportunistic pathogens, and

b. the moment when the host normal microflora or microbiome inevitably faces the altered situation and needs to reestablish and reformulate the balance (together with the multitude of host functions intended for tackling the illness).

As like the microbiological health of an individual is, to some extent, a reflection of the epidemics situation; also, the course of the pandemic is parallel to the healthy development of the individual members of the community. And this always is a net effect of many biological parameters, of several microbial strains' actions. - It is the a. (above) which tells us that the breakout of the hazardous agent(s) occurred, and the b. indicates the risk of novel aspects emerging, such as virus variants, new diseases, antibiotic-resistant bacterial strains popping up in the big picture. These could become new epidemic threats. Maybe we should get alarmed, or should we not?

One of the key answers to this question lies within the immune system. After the first response (caused by the immunogens) has ceased, the human system does not return to the pre-immunized state. Furthermore, as the phenomenon called "molecular mimicry" may then provoke cross-reactions between different pathogens. This, in turn, may initiate harsher infections in the aftermath of the pandemics. The population's danger could be a viral variant differing enough from the strains previously blocked by vaccinations, or an antibiotic-resistant bacterial epidemics which could put the healthcare system onto its knees.

Additionally, the ecological pressures on animals carrying zoonotic pathogens capable of shuttling between and causing disease in animals and men could onset novel epidemics. This was the situation with the Ebola virus in Africa whose variants were 20-90% fatal. This horrible case is well described in the book "Ebola - The Natural and Human History" by David Quammen (published by The Bodley Head in London in 2012). - Fortunately, the spread of the epidemics was this time confined by effective international action. But the amount of suffering, as well as the horror scenarios, were all too outrageous.

According to the scientific publication by Anthony S.Fauci in 2008 (in the Journal of Infectious Diseases), about 70% of the deaths caused by the "Spanish flu" about a century ago, were actually due to the pneumococcal infections following the influenza virus. In many cases, the pneumococcal lung disease was associated with various staphylococcal infections. My sophisticated guess is based on some unpublished research that many anaerobic pathogens were also "putting their spoon into the soup". In any case, the consequence of this catastrophically spread mixed infection was the death of tens of millions of humans in the countries weakened by war. Unfortunately, in this case, history could repeat itself. All the above-mentioned bacterial strains and such bacteria as tuberculosis-causing mycobacteria, Yersinia pestis, Vibrio cholerae, Salmonella typhi, to name a few, could become antibiotic-resistant.

In Autumn 1928, English physician Sir Alexander Fleming made his phenomenal discovery of mould antibiotic penicillin, preventing staphylococcal bacteria's growth on the Petri dish. He worked in his laboratory in the St. Mary´s Hospital in London. The industrialization of the product was accomplished about 15 years later in the USA. This was preceded by the Australian Howard Walter Florey investigating the antibiotic substance in the mould broth in Oxford starting in 1938. As a result of his studies and the work of several other scientists, including Dr Chain, a refugee from Berlin, Dr Florey and his associate Dr Heathley travelled to New York with a little bit of pulverized penicillin in one test tube and Fleming´s original mould strain Penicillium notatum in another test tube in their pocket. This crossing of the Atlantic Ocean took place during the darkest hours of the Second World War in Summer 1941. Although Florey and Heathley had no money in their pockets or their disposal, they supported the Rockefeller Foundation. Consequently, Dr Champs Lyons from Boston arrived in Bushnell hospital in Brighten City in Utah year 1943 with some penicillin for treating the soldiers wounded on the Pacific war front. Later on, it was told that the new miraculous antibiotic medicine saved two million human lives in World War 2.

In the current worrying global health situation, it would be most advisable to learn from history; to enhance the research for finding new antibiotics, antimicrobial substances, production of passive immunization means as suggested by Hakalehto and Kuronen some 25 years ago when proposing the use of chicken egg yolk antibodies against virus epidemics, finding of novel probiotics as the continuation of Lactobacillus rhamnosus GG strain which was studied and launched by Valio Corporation, Finland, laboratories in Helsinki. Then we hit a vein of "the gold of health", which could be further researched and extended by finding novel microbial strains and communities. By the way, it has been proven that microbiome balance could help to resist also SARS-CoV-2 viruses and many other harmful germs.  

This success story of the industrialization of one of the most significant inventions of Mankind, the antibiotics, precluded specific wartime conditions. Maybe during normal times the politicized scientific institutions or the administration, or the erroneous counter-productive "facts" or unfair competition in business-life, could have mitigated Fleming´s findings and the work of those who believed in the potential of the new medicine. The undeniable chain of inventions and research work of thousands of scientists and biochemical engineers has produced our clinical resilience against the diseases in recent decades to this very day. This chain can get broken if the hunger for money or power will overwhelm the progress by turning our minds and objectives to the times of the not-so-glorious past of Mankind when the rulers mitigated liberty.

Another encouraging example was the invention of biotechnological microbiology. During the years 1911-15, Sir Winston Churchill was the First Lord of Admiralty in Great Britain. He invited into his office a young scientist, Dr Chaim Weizmann, who later became the first president of Israel. Weizmann described in the autobiography his work which had produced the finding of "Weizmann´s bacterium or Clostridium acetobutylicum. "Facilities for this work lacked at the university, where biochemistry did not form part of the curriculum at that time, while the study of bacteriology was confined to medical school. I began to pay frequent visits to Pasteur Institute in Paris, where I worked in the bacteriological and microbiological departments" The anaerobic bacterial strains of several members of the genus Clostridium have been used in the recent biorefinery project of ours, in the European Union Baltic Sea biorefinery project ABOWE in 2012-14, which consisted of researchers from Poland, Germany, Sweden, Finland, Estonia and  Lithuania. The concept of non-aseptic cultures was introduced to produce valuable chemicals from the side streams. Later on, this concept has been piloted in several industrial settings including the "Zero Waste from Zero Waste" project in Tampere, Finland, where the lake bottom sediments of pulp and paper industries were exploited as raw materials for microbially produced biochemicals by the piloting studies conducted in 2018-19 by my company, Finnoflag Oy. The project consortium could turn all the side streams into products, the mentioned chemicals, energy gases, and organic fertilizers. These tests predicted the bright future when wastes will be valuable and wanted raw materials.

A century earlier, Sir Winston Churchill made a question to Chaim Weizmann: "Well, Dr Weizmann, we need thirty thousand tons of acetone. Can you make it?" Weizmann said himself having been "so terrified by this lordly request that I almost turned tail", but he answered: "So far I have succeeded in making a few hundred cubic meters of acetone at a time by the fermentation process. I do my work in the laboratory. I am not a technician; I am only a research chemist. But, if I were somehow able to produce a ton of acetone, I would multiply that by any factor you chose. Once the bacteriology of the process is established, it is only a question of brewing. I must get hold of a brewing engineer of one of the big distilleries, and we will set out the preliminary task. I shall naturally need my Government's support to obtain the people, the equipment, the emplacements and the rest of it. I myself can´t even determine what will be required." - This conversation yielded an entire field of industries which also helped in establishing the production of antibiotics when the time was right.

After WW2, valuable research work was carried on in many universities and research units to increase antibiotic production and extend their range and repertoire of antimicrobial substances. One of the leading institutes was the University College of London, where the undersigned had the opportunity to study in 1984-85 using the biochemical engineering unit's pilot plant. To listen to the lectures of professors Malcolm D. Lilly and Peter Dunnill and others telling about their pioneering work to increase the understanding of microscopic creatures' use for the production of chemical goods. Other departments participating in the Institute of Biotechnological Studies were the University of Kent at Canterbury with the memorable lectures of Prof. Alan T. Bull and others on microbial physiology as well as the Polytechnic of Central London (now the Westminster University), where the undersigned had the opportunity to work "on the bench" for constructing a plasmid vector for the first time in the world for the transfer of genes for antibiotics from filamentous streptomycetes bacteria into Escherichia coli. After we also succeeded in transferring the gene for clavulanic acid using this vector, it undoubtedly boosted the forthcoming antibiotic industries. The genus Streptomyces is the origins of 95% of today´s antibiotics. This work in London that I participated in was not published, but it undoubtedly constituted one relatively important step forward in antibiotics' industrial production.

Now, 36 years later, we should remember those days and the earlier days of struggles in the laboratories for investigating micro-organisms to achieve better living conditions for humans. This kind of success story cannot be anyone´s property but an option for joint planetary survival in the technological development which cannot be restricted by individual lust for profits or power, or any other obsolete obsessions. Could we turn the wheel? - When a sledge is sliding over the snowy fields, the aspirations could shine in the horizon as like the short Winter day.

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