April 26, 2019 at 14:02Indigenous microbes at the height of fashion
Indibiome - is the new black (something very stylish) - this is the name of the article in English ( link to Habr ), here is a translation of my own text.
Indigenous microbes at the height of fashion, just like in the electronic and computer industries, microbe design bureaus will be able to satisfy the needs in healthcare, agriculture, food production, industry.
Indibiome is discussed in my previous article in Russian ( link ). indibiome is a root microbiome, originated from the term "indigenous peoples", the term is used below in the meaning of "inherent in a certain environment, localized and optimized for sustainable existence."
Microbes have always existed, however, technologies that allow efficient microbial manipulation, as well as accumulated genetic and experimental data on a variety of microbial communities, have reached the required level only in the last decade. Below is my concept of an interdisciplinary “indibiome development bureau”, and I will be glad to your feedback in the comments.
Computer and electronic applications are developed based on needs: the problem is first posed, and the solution is developed as a combination of the latest and most economical materials, elements, software libraries and existing devices. In the microbial world, everything still works basically differently: someone discovers outstanding microbial properties (an enzyme that can work at a higher temperature, the ability to drive away other harmful microbes, etc.), and then tries to create an application with this one property . From the point of view of cause and effect, we first observe the effect, and then try to manipulate the cause (microbe) in any possible application. This gives solutions in which microbes are the main part, and the sum of technologies is rare, it’s the same as producing microcircuits in new form factors,
A small idea of the difference between microbes and indibiome in the context of this article, indibiome is a set of different microbes in stable equilibrium, which is supported by microbial interactions. We studied individual microbes well enough, and many of these are embodied in billion-dollar technologies, while the understanding of the microbiome is far from complete because of the complexity that arises from many interactions. From the point of view of application, we usually use microbes for production: biodegradable substances, drugs (for example, insulin), fermentation of food and alcohol, etc. Sometimes, as a source of new molecules for medicine and biotechnology. Microbiomes (consortia of bacteria) are mainly considered along with the niche they occupy - intestinal microbiome and intestines, skin microbiome and skin, lake microbiome and lake. We focus on solutions that are useful for a niche when we try to influence the microbiome, in other words, the general approach is to solve the niche problem by adding, improving, manipulating the microbiome in it. A good clue when choosing a microbiome configuration may be the well-known niche microbiome - indibiom, for example, many brands in the field of vaginal care draw inspiration from recent studies of the vaginal microbiome (link to an article on Habré).
The first steps were taken in healthcare, since the intestinal microbiome and intestines are apparently one of the fundamental parts of human health, other areas are soil and skin, and then wherever the use of an open system can be beneficial. Moreover, you may be interested in the indibioms of buildings, cars, clothes, pets. Wherever this could solve problems, for example, ensuring the safety of food production using the indibiom of the factory building or protection against nosocomial infections in the hospital using the indibiom of the premises, or reducing the level of allergy to pets.
Understanding the complexity of the microbiome is only possible with multidisciplinary approaches. Once a niche-related problem has been selected: bioinformatics and literary search will narrow the field of research, molecular biology will be used for laboratory tests and manipulations, and finally engineering systems can be used to model the original niche (where, thanks to the ability of the sensors, the model can be digitized , see the project
SHIME and M-SHIME - ProDigest - a simulator of the intestine) and, finally, the microbiome must be delivered to the site using approaches from materials science. With this approach, even local de novo microbiomes can be formed.
All of the above facts lead us to the concept of microbiome design bureau. Industrial design and prototyping services are already working: a person comes up with stuffing and electronics projects, and the company develops a tablet, designs and 3D-prints the device’s shell, builds a prototype and produces internal operating software or connects it to the cloud. But it all started with a problem that needs to be solved, and some idea on how to do it. Microbial technologies at the end of 2020 are no longer rocket science, bacterial growth and cloning are available to everyone, as well as the purchase of microchips and data processing. Any solution can be tested within a few months.
At the moment, the technological drivers are academic institutions, mainly creating spin-offs as side projects with scientists from the main projects of the institution. This usually happens when a scientific team thinks about applying the discovered effect and actively moves forward. Spin offs are a commonplace in areas such as photonics (for example ), where research is for applications, and this practice is new to the world of microbes. Potentially, academic achievements in the field of microbiology contain various solutions to existing problems.
While the core of the solution will come from the microbiome area, “packaging of the solution” is even more exciting. Additional parts of the final decision can be obtained using the following breakthrough technologies:
Biodegradable materials - often serve as a means for continuous drug delivery, materials can be designed for selective degradation only by certain bacteria and, therefore, the entire solution acts as a therapeutic agent
Microfluidics - a laboratory on a chip, solutions that use bacteria as sensors or manufacturers in the
Data microformat science - such as digital maps of agriculture and soil microbiomes used for soil improvement strategies. We made a prototype antibiotic resistance map with infotanka , for example ( link )
Bioinformatics - could potentially create a new microbiome from bacteria with known genomes - so as to provide completely new metabolic chains
Fermentation technologies - fermentation processes can turn inedible food into nutritious and functional
The main expertise of the bureau is in microbiological applications, that is, in understanding technological pipelines for various industries in which microbial preparations are already used. This would allow the team to avoid an approach based on one area (that is, only in the field of medicine or oil production) and apply successful ideas in various directions.
The intersectoral team should be of an engineering level, and not Nobel Prize winners, this is important. The professionalism of the team should include: microbial cultivation, fermentation, organic chemistry, biodegradable materials, medical devices, soil microbiome, etc.
While the main center of expertise will look for initial solutions, a business developer should be able to evaluate costs and market value, iteratively increasing accuracy as the pilot project is completed.
Marketing and IP professionals should be used as consultants in the early stages of the product concept.
Any new solution in such a bureau will not be a blue ocean in terms of completely new markets, but it will enter the market of non-microbial solutions and demonstrate better efficiency. Moreover, the stability incorporated in the microbial composition should be used to conquer the market:
As a microbiome skin cream, it not only provides nutrition, but also creates a new type of self-sufficient skin microbiome, up to the point where the initial cream is not required. A new idea for the market is that you do not need to sell me many products all my life, you can create a sustainable system that you need to maintain from time to time. Microbial systems are recreated on your skin or in your garden and allow you to abandon the factories for the production of chemicals, warehouses, vehicles on gasoline engines.
Promising markets for finding solutions are: skin care, vaginal flora, room cleaning (home and industrial), fermented foods. In this area, the team should gain an understanding of the level of microbial and non-microbial solutions and unmet needs.
It would be wise at first to stay away from medical microbiomes, especially in the intestinal area, since this area is extremely competitive, very strictly regulated, includes expensive human trials and shows the longest time to market. The only exception here is the use of combinations of microbes already used in clinical practice, and already tested delivery forms, that is, a combination of approved technologies is close to the market. Markets on the periphery of medical supplies - sanitation, food and cosmetics - are very profitable, and there are already such trends as sustainability, environmental friendliness, lean manufacturing and consumption.
The products in this market can have interesting medical effects: a room cleaner can improve air quality, or a skin cream can help with skin diseases, these properties should be clinically tested as the product matures, naturally, we expect them to be based on creating a stable microbial environment.
After exploring the aforementioned markets with an analytical center, the first goal is to offer a microbial solution. Initially, the decision can be based on hypothetical microbial properties that can be found in nature or tested in the laboratory. Additional technologies that serve to deliver microbes, for example, at this stage can create properties that are absent from competitors. Interestingly, intellectual property can be the exact intersection of microbial and complementary technologies. Moreover, thanks to the experience of the Bureau, it will be able to implement similar solutions in different projects - this is the value of the Bureau - developing a framework for microbiological application.
The Scientific Advisory Council (SAB) and fellow scientists are the next train stop when discussing the solution. Using media materials on the development of technologies, data on bacterial genomes and networking, the solution to any new project should be discussed, criticized and adjusted. So there is a chance to get a specialist on a specific issue in the process of discussing a project - this gives incredible marketing value, a completely transparent approach to development is obvious.
The next step is laboratory testing. It’s best for the Bureau to have its own microbial laboratory, however the first steps can be fully completed by subcontracting or working in the co-working laboratories available in large cities. The result of the laboratory test phase is the confirmation of properties and preliminary checks, ideally confirming that the invented product works in laboratory conditions and should be transferred to the pilot phase of testing outside the laboratory.
What you need to start
Requires a team capable of preliminary work. The work will include a description of the technology and market analysis for different markets and solutions. 3-4 people who can analyze marketing, the FMCG market, medical devices, nutritional supplements, must decide how feasible projects in the proposed areas.
Techtransfer, customer focus and ongoing feedback
When creating a microbial product, the team should monitor potential corporate customers who can buy the technology, and at the same time be close to the end user of the product and monitor the focus group reaction. The next part is testing, for some products clinical trials are required (for example, for functional foods and cosmetics), but for simpler ones this can be done in the Bureau’s laboratory and the effectiveness can be compared with existing non-microbial approaches on the market.
Product prototype, design, production economics, marketing and sales plan, IP protection plan, test results - all this is the final stage of work at the Bureau. The product can be sent to the market. Ideally, sell a license, you can sell the whole technology or develop it together with a corporate partner or VC.
Vaginal well-being
Problem: Ineffective probiotic delivery
Solution: Biodegradable probiotic delivery system
Oral care
Problem: Printed mouthguards and gum health
Solution: A mouthguard tab with probiotics, (3D smile can be a great partner)
Skin care
Problem: Unstable effects of creams
Solution: cream with a new skin microbiome (SPLAT can be a great partner)
Power
problem: lack of fiber in the diet
solution: Bars for snacking especially for microbiome (BITE can be an excellent partner)
Cleaning space
problem: infection in hospitals
Solution: probiotic cleaning components for lasting protection (PIP already does this)
Solution 2: proprietary probiotic cleaning fluid reactor
Indigenous microbes at the height of fashion, just like in the electronic and computer industries, microbe design bureaus will be able to satisfy the needs in healthcare, agriculture, food production, industry.
Indibiome is discussed in my previous article in Russian ( link ). indibiome is a root microbiome, originated from the term "indigenous peoples", the term is used below in the meaning of "inherent in a certain environment, localized and optimized for sustainable existence."
Microbes have always existed, however, technologies that allow efficient microbial manipulation, as well as accumulated genetic and experimental data on a variety of microbial communities, have reached the required level only in the last decade. Below is my concept of an interdisciplinary “indibiome development bureau”, and I will be glad to your feedback in the comments.
Computer and electronic applications are developed based on needs: the problem is first posed, and the solution is developed as a combination of the latest and most economical materials, elements, software libraries and existing devices. In the microbial world, everything still works basically differently: someone discovers outstanding microbial properties (an enzyme that can work at a higher temperature, the ability to drive away other harmful microbes, etc.), and then tries to create an application with this one property . From the point of view of cause and effect, we first observe the effect, and then try to manipulate the cause (microbe) in any possible application. This gives solutions in which microbes are the main part, and the sum of technologies is rare, it’s the same as producing microcircuits in new form factors,
A small idea of the difference between microbes and indibiome in the context of this article, indibiome is a set of different microbes in stable equilibrium, which is supported by microbial interactions. We studied individual microbes well enough, and many of these are embodied in billion-dollar technologies, while the understanding of the microbiome is far from complete because of the complexity that arises from many interactions. From the point of view of application, we usually use microbes for production: biodegradable substances, drugs (for example, insulin), fermentation of food and alcohol, etc. Sometimes, as a source of new molecules for medicine and biotechnology. Microbiomes (consortia of bacteria) are mainly considered along with the niche they occupy - intestinal microbiome and intestines, skin microbiome and skin, lake microbiome and lake. We focus on solutions that are useful for a niche when we try to influence the microbiome, in other words, the general approach is to solve the niche problem by adding, improving, manipulating the microbiome in it. A good clue when choosing a microbiome configuration may be the well-known niche microbiome - indibiom, for example, many brands in the field of vaginal care draw inspiration from recent studies of the vaginal microbiome (link to an article on Habré).
The first steps were taken in healthcare, since the intestinal microbiome and intestines are apparently one of the fundamental parts of human health, other areas are soil and skin, and then wherever the use of an open system can be beneficial. Moreover, you may be interested in the indibioms of buildings, cars, clothes, pets. Wherever this could solve problems, for example, ensuring the safety of food production using the indibiom of the factory building or protection against nosocomial infections in the hospital using the indibiom of the premises, or reducing the level of allergy to pets.
Understanding the complexity of the microbiome is only possible with multidisciplinary approaches. Once a niche-related problem has been selected: bioinformatics and literary search will narrow the field of research, molecular biology will be used for laboratory tests and manipulations, and finally engineering systems can be used to model the original niche (where, thanks to the ability of the sensors, the model can be digitized , see the project
SHIME and M-SHIME - ProDigest - a simulator of the intestine) and, finally, the microbiome must be delivered to the site using approaches from materials science. With this approach, even local de novo microbiomes can be formed.
All of the above facts lead us to the concept of microbiome design bureau. Industrial design and prototyping services are already working: a person comes up with stuffing and electronics projects, and the company develops a tablet, designs and 3D-prints the device’s shell, builds a prototype and produces internal operating software or connects it to the cloud. But it all started with a problem that needs to be solved, and some idea on how to do it. Microbial technologies at the end of 2020 are no longer rocket science, bacterial growth and cloning are available to everyone, as well as the purchase of microchips and data processing. Any solution can be tested within a few months.
At the moment, the technological drivers are academic institutions, mainly creating spin-offs as side projects with scientists from the main projects of the institution. This usually happens when a scientific team thinks about applying the discovered effect and actively moves forward. Spin offs are a commonplace in areas such as photonics (for example ), where research is for applications, and this practice is new to the world of microbes. Potentially, academic achievements in the field of microbiology contain various solutions to existing problems.
While the core of the solution will come from the microbiome area, “packaging of the solution” is even more exciting. Additional parts of the final decision can be obtained using the following breakthrough technologies:
Biodegradable materials - often serve as a means for continuous drug delivery, materials can be designed for selective degradation only by certain bacteria and, therefore, the entire solution acts as a therapeutic agent
Microfluidics - a laboratory on a chip, solutions that use bacteria as sensors or manufacturers in the
Data microformat science - such as digital maps of agriculture and soil microbiomes used for soil improvement strategies. We made a prototype antibiotic resistance map with infotanka , for example ( link )
Bioinformatics - could potentially create a new microbiome from bacteria with known genomes - so as to provide completely new metabolic chains
Fermentation technologies - fermentation processes can turn inedible food into nutritious and functional
Core expertise
The main expertise of the bureau is in microbiological applications, that is, in understanding technological pipelines for various industries in which microbial preparations are already used. This would allow the team to avoid an approach based on one area (that is, only in the field of medicine or oil production) and apply successful ideas in various directions.
The intersectoral team should be of an engineering level, and not Nobel Prize winners, this is important. The professionalism of the team should include: microbial cultivation, fermentation, organic chemistry, biodegradable materials, medical devices, soil microbiome, etc.
While the main center of expertise will look for initial solutions, a business developer should be able to evaluate costs and market value, iteratively increasing accuracy as the pilot project is completed.
Marketing and IP professionals should be used as consultants in the early stages of the product concept.
Any new solution in such a bureau will not be a blue ocean in terms of completely new markets, but it will enter the market of non-microbial solutions and demonstrate better efficiency. Moreover, the stability incorporated in the microbial composition should be used to conquer the market:
As a microbiome skin cream, it not only provides nutrition, but also creates a new type of self-sufficient skin microbiome, up to the point where the initial cream is not required. A new idea for the market is that you do not need to sell me many products all my life, you can create a sustainable system that you need to maintain from time to time. Microbial systems are recreated on your skin or in your garden and allow you to abandon the factories for the production of chemicals, warehouses, vehicles on gasoline engines.
Promising markets for finding solutions are: skin care, vaginal flora, room cleaning (home and industrial), fermented foods. In this area, the team should gain an understanding of the level of microbial and non-microbial solutions and unmet needs.
It would be wise at first to stay away from medical microbiomes, especially in the intestinal area, since this area is extremely competitive, very strictly regulated, includes expensive human trials and shows the longest time to market. The only exception here is the use of combinations of microbes already used in clinical practice, and already tested delivery forms, that is, a combination of approved technologies is close to the market. Markets on the periphery of medical supplies - sanitation, food and cosmetics - are very profitable, and there are already such trends as sustainability, environmental friendliness, lean manufacturing and consumption.
The products in this market can have interesting medical effects: a room cleaner can improve air quality, or a skin cream can help with skin diseases, these properties should be clinically tested as the product matures, naturally, we expect them to be based on creating a stable microbial environment.
After exploring the aforementioned markets with an analytical center, the first goal is to offer a microbial solution. Initially, the decision can be based on hypothetical microbial properties that can be found in nature or tested in the laboratory. Additional technologies that serve to deliver microbes, for example, at this stage can create properties that are absent from competitors. Interestingly, intellectual property can be the exact intersection of microbial and complementary technologies. Moreover, thanks to the experience of the Bureau, it will be able to implement similar solutions in different projects - this is the value of the Bureau - developing a framework for microbiological application.
The Scientific Advisory Council (SAB) and fellow scientists are the next train stop when discussing the solution. Using media materials on the development of technologies, data on bacterial genomes and networking, the solution to any new project should be discussed, criticized and adjusted. So there is a chance to get a specialist on a specific issue in the process of discussing a project - this gives incredible marketing value, a completely transparent approach to development is obvious.
The next step is laboratory testing. It’s best for the Bureau to have its own microbial laboratory, however the first steps can be fully completed by subcontracting or working in the co-working laboratories available in large cities. The result of the laboratory test phase is the confirmation of properties and preliminary checks, ideally confirming that the invented product works in laboratory conditions and should be transferred to the pilot phase of testing outside the laboratory.
What you need to start
Requires a team capable of preliminary work. The work will include a description of the technology and market analysis for different markets and solutions. 3-4 people who can analyze marketing, the FMCG market, medical devices, nutritional supplements, must decide how feasible projects in the proposed areas.
Techtransfer, customer focus and ongoing feedback
When creating a microbial product, the team should monitor potential corporate customers who can buy the technology, and at the same time be close to the end user of the product and monitor the focus group reaction. The next part is testing, for some products clinical trials are required (for example, for functional foods and cosmetics), but for simpler ones this can be done in the Bureau’s laboratory and the effectiveness can be compared with existing non-microbial approaches on the market.
Product prototype, design, production economics, marketing and sales plan, IP protection plan, test results - all this is the final stage of work at the Bureau. The product can be sent to the market. Ideally, sell a license, you can sell the whole technology or develop it together with a corporate partner or VC.
Markets and Solutions
Vaginal well-being
Problem: Ineffective probiotic delivery
Solution: Biodegradable probiotic delivery system
Oral care
Problem: Printed mouthguards and gum health
Solution: A mouthguard tab with probiotics, (3D smile can be a great partner)
Skin care
Problem: Unstable effects of creams
Solution: cream with a new skin microbiome (SPLAT can be a great partner)
Power
problem: lack of fiber in the diet
solution: Bars for snacking especially for microbiome (BITE can be an excellent partner)
Cleaning space
problem: infection in hospitals
Solution: probiotic cleaning components for lasting protection (PIP already does this)
Solution 2: proprietary probiotic cleaning fluid reactor