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josh_m josh_m
wrote...
4 years ago
I'm an amateur mushroom grower with quite a bit of experience in performing strain isolation techniques using agar in a sterile environment.

Lately, I've been thinking about the overlap in skills necessary to experiment in discovering new molecules with antibiotic properties. There are several YouTube videos with basic tutorials on how to culture a non-pathogenic microbe on agar, prepare the experimental compound and evaluate the cone of inhibition to determine its antibiotic properties.

According to the CDC Antibiotic Resistant Threats Report, 35K people die each of resistant infection and the number is only rising. I've also read that private investment from drug companies into the discovery of new antibiotics is also on the decline.

It seems to me that there is a real need for more experimentation and discovery of novel antibiotics and I'm seriously interested in dedicating a lot of my time and resources towards this goal.

Building on my mycological experience, I'd like to create a process wherein I've got an assembly line of documented and repeatable experiments running in my home lab. I figure if I can get process 2 new antibiotic experiments per week, I could do about 50 in a year and with a little luck, perhaps I could uncover something that might help save lives.

I have many questions that I'm hoping someone in academia, who is supportive of the many amateur auto didactic learners out there, can help answer for me.

Absolute answers aren't necessary - please feel free to simply point me to another resource where I can find the answer if it makes sense.

Questions:
* Firstly, I'm trying to determine what would be the most effective use of my resources that best optimizes my chances for making a valuable discovery in pursuit of discovering a novel antibiotic.

Related questions:
* How would I determine which compounds have already been tested and is there a central database of existing antibiotic compounds and their origins? Basically, how do I avoid running an experiment with a substance whose outcome is already known?
* Is it possible for me to get my hands on a larger assortment of safe microbes for testing?
* Which microbes would the highest value in experimental learning?
* Is there value in publishing my experiments and observations, regardless if I get a positive test?
* What is the best way to connect with the professional and academic community to share my data and possible discoveries?
* If I find a substance that appears to have antibiotic properties, what's next? Where do I take this learning to further explore it's efficacy and value?

I extend my sincere gratitude to those of you who read this and offer up your kind words of wisdom.


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wrote...
Educator
4 years ago
Discovering new antibiotics is easy, many chemicals can easily kill bacteria cells. The problem, however, if finding one that'll not harmful to the host organism as well. Unfortunately, very few chemicals can do both. I don't recommend doing this at home for several fundamental reasons. 1st, I'm assuming you don't have the proper equipment – working in a lab, they have thousands of dollars worth of equipment, from pipettes, to centrifuges, coolers, etc. All of these have been developed to reduce the chance of contamination or any factors that could manipulate the results. And, when working with microorganisms, simply breathing on the petri dish could affect your results. 2nd, once you've discovered a chemical that does what you're looking for, you'd need to send this chemical over to a lab that'd put it through a gas-liquid interface (chromatography) to give its analytical chemical properties. This can be an expensive process because once you've found what the chemical is made of, you then need to match why its specific chemical structure allows it to work within a cell. You'd also need to study how it enters the cell, what biochemical process it halts, and what enzymes it interacts with inside the pathogen -- all of these require years of research. 3rd, what antibiotics are you using, are they organic or inorganic? Organic are those that are extracted or produced from living things, while inorganic are usually metallic compounds. Both of these can have devastating effects on the human host, some might be toxic, others just plain deadly.

I'd suggest you first enrol in a microbiology course offered online to learn about the basic biology of microbes, and then an immunology course to see how pathogens evade the defense shields we've born with. From there you'll be able to piece together how it all works, and why big pharma companies have "stopped" researching for the next ampicillin.

Good Luck
wrote...
Donated
4 years ago
Not allowed to make links on our first post so here is the first post. Will follow-up with my original reply shortly.
wrote...
Donated
4 years ago Edited: 4 years ago, germinate_love
@bio_man, your thoughts and feedback are much appreciated. You bring up some great points and the information you've provided has already sent me down a path of better understanding the challenges involved in both finding novel antibiotics and also the competing incentive structures which are preventing new antibiotics from entering the market.

With that in mind, I do want to address a few of your objections. I should also make it clear that what I'm looking to do isn't to discover a new antibiotic and bring it to market A-Z as that is completely unfeasible for any one person to do. But it does bring me back to my original question which is where can an amateur make the most useful contribution towards the overall goal?

What I am proposing is that there is value in an amassing an army of clever amateurs, not unlike the amateur astronomer community, who can pick off some component(s) of the antibiotic problem and contribute in a way that accelerates or adds value to the well-funded startups and drug companies already dedicated to this purpose.

Quote
I'm assuming you don't have the proper equipment – working in a lab, they have thousands of dollars worth of equipment, from pipettes, to centrifuges, coolers, etc. All of these have been developed to reduce the chance of contamination or any factors that could manipulate the results. And, when working with microorganisms, simply breathing on the petri dish could affect your results.

Many of the hobbyist in the mycology community are quite well-equipped with the necessary equipment to mix our own agar, sterilize it, pour agar plates and perform cultures using proper sterile technique. This idea that breathing on a culture can impact the results rings true in mycology. Eliminating contamination through the use of sterile strain isolation techniques is one of the primary impetuses for amateur mycologists to do agar work in the first place.

Agar mixtures, sterile plates, pipettes, etc are all quite affordable (< $100) and readily available. A centrifuge is not necessary to perform a Kirby-Bauer assay, for example, a common method for testing antibiotic effectiveness in labs. There is nothing in this technique that cannot be replicated at home.

In short, it does not require expensive or technical equipment to create and test cultures n a home lab in such a manner that can be replicated and peer-reviewed by the scientific community.

Furthermore, many amateurs on YouTube have already demonstrated techniques for testing new antibiotics at home.  For example:

3-part Series on Instructable DYI antibiotics.

One criticism I have of these videos; however, is that they never address what happens if one discovers a compound with antibiotic properties. Should that information be shared back with the community? How? Or are the videos just an oversimplified lab to demonstrate a few fundamentals but with no real intention for anyone to actually use in discovering new antibiotics.

Quote
once you've discovered a chemical that does what you're looking for, you'd need to send this chemical over to a lab that'd put it through a gas-liquid interface (chromatography) to give its analytical chemical properties. ... You'd also need to study how it enters the cell, what biochemical process it halts, and what enzymes it interacts with inside the pathogen -- all of these require years of research.

This is a great point and I would agree it's not something that most amateurs should even attempt. However, given the sheer volume of research required once a molecule with antibiotic properties is found, I would argue that there are many approaches to doing the follow-up research. Part of solving the time/complexity issues is to break up the process into its components and find ways to innovate on the process itself. There is another place where I think the amateur community could be of real service given a clear mission from the scientific community.

One such company that is approaching the problem by utilizing new discovery methodologies is Tetraphase. Tackling the antibiotics problem from a multi-dimensional approach is also represented in the $500M investment portfolio of the non-profit Carb-X .

More exciting are open source projects like Mykrobe where anyone can upload a DNA sequence and it will look for antibiotic properties quickly, easily and for free.

Full DNA sequencers are now the size of USB drives and cost less than a $1000!

I am skeptical that there is no value to be had in the amateur community amassing a wealth of data in testing, sequencing and sharing the results of random antimicrobial molecules from the limitless number of micro-environments across the Earth.

MIT has already shown that machine learning can be used to discover novel antibiotics by comparing the chemical properties of known antibiotics and their method of action against molecules not formally seen or considered. This approach is great, but it requires a continuous flow of new data and that's another avenue where I believe the amateur community may be able to help.

Quote
what antibiotics are you using, are they organic or inorganic? Organic are those that are extracted or produced from living things, while inorganic are usually metallic compounds. Both of these can have devastating effects on the human host, some might be toxic, others just plain deadly.

Yes, toxicity is important. I don't think anyone is suggesting human trials begin at home. By the way, this again mirrors the amateur mycology community. New fungal species and mushrooms are discovered and encountered upon all the time and toxicity is an important component to the process, yet the community still encourages amateurs to explore, research and share.

Quote
I'd suggest you first enroll in a microbiology course offered online to learn about the basic biology of microbes, and then an immunology course to see how pathogens evade the defense shields we've born with. From there you'll be able to piece together how it all works, and why big pharma companies have "stopped" researching for the next ampicillin.

As an educator, I'm not surprised that you would recommend more education, especially in the manner in which you are accustomed. I don't disagree with the sentiment; we should all be learning and if one is to venture into an endeavor such as antibiotics research, it would behoove the researcher to acquire as much relevant and scientifically accurate knowledge as possible.

With that in mind, I must advocate for all of the autodidacts out there, such as myself, who have managed to self-learn through non-traditional means and still managed to, at the least, create quite a successful career for themselves, and at the most, make a real and impacting contribution to society.
 
The value of a college degree, unless it is in Computer Science or related engineering focused field, has plummeted while the amount of freely available, high quality online educational information has exploded.

Many self-learners use a project, lab, or hobby as the catalyst for learning. We have a problem, we research it until we know it backwards and forwards until we learn how to solve the problem. In my own personal experience, this has yielded far more long-lasting and useful education than a classroom setting where I'm learning copious information without putting it to practical use or having any connection to its relevancy at all.

By the way, if you were to survey software engineers across the USA, the vast majority (> 80%) would claim they are either fully or in-part self-taught in their craft.

I don't want to side bar the conversation too much, but there are multiple indicators and factors that suggest a big shift in how people educate themselves, not the least of which is the general failure of our academic institutions, the specialization / automation of the economy, the ease of access to high-quality online educational content, increase in remote employment, ease in prototyping a new business, rise in independent contractors, etc.

I'm not saying there aren't trade-offs to this movement and that there aren't real and tangible benefits to a traditional degree in a classroom settings - not at all. But I also think there is room for amateurs to tinker and bring forth great benefit to society. Look no further than to history to see the list of contributions made by my fellow autodidacts.

--
I once again extend my gratitude for your thoughts and input.
wrote...
Educator
4 years ago Edited: 4 years ago, bio_man
Quote
What I am proposing is that there is value in an amassing an army of clever amateurs, not unlike the amateur astronomer community, who can pick off some component(s) of the antibiotic problem and contribute in a way that accelerates or adds value to the well-funded startups and drug companies already dedicated to this purpose.

The science community is akin to an open source project you'd find online. Scientists have to be fully transparent about their methods and results, and those can be obtained by emailing the lead researcher through email whenever you want to replicate their exact protocol. Rarely, however, will you encounter an article that shows the discovery of a completely new antibiotic discovered from A-Z, because it's difficult to do, is costly, and takes a long time. Also, the way researchers are funded doesn't help the matter. If a major pharmaceutical company wanted to discover something new, countless experiments would need to take place, each building on the next.

A community of wannabe scientists online are no different than scientists working inside a lab, except that those working at home don't have the academic credentials that would otherwise be aquired from going to school. You're right, how you acquire your education isn't important - whether it be at a library or at school - but when you're enrolled in a four year program, you dedicate more of your energy to learn because you're paying to be there. You have assignments and tests that continually solidify your understanding of the topic, this is why I advocate learning this at an institutation. Usually people with your desires and perseverence choose to go to school and become accredited so that their knowledge and intelligence can be trusted by others. Face it, we live in a society where medical doctors are favored over naturopathic healers even though they both have one goal in common.

On that same note, one of the hardest courses I took in university was called organic chemistry. What made it hard were all the chemical reactions you needed to know by heart to produce a chemical of certain properties. This course is important for you as well because by knowing how chemicals can be manipulated, new drugs (antibiotics too) with different properties can be made by flipping a functional group or moving a set of molecules from one position to another. Ampicillin, penicillin, and amoxicillin are all chemically related; after penicillin was discovered, scientists tried manipulating it chemical to produce other variants, which lead to more available antibiotics. That being said, you'd definitely benefit from taking an organic chemistry course to learn about that can be done, but if you were to take it without having taken an introductory chemistry class, you'd be lost! This is why I advocate going to school, because you're not only paying to learn from the experts (the professors), you're paying for the program that were setup by educators like myself that help the student learn the topic correctly. It's long and painstaking, but it's a effective way to learn. Anyway, I don't want to steer this conversation away from the main topic.

Quote
By the way, if you were to survey software engineers across the USA, the vast majority (> 80%) would claim they are either fully or in-part self-taught in their craft.

The idea of having a dedicated community of scientist working alone at home isn't the same as having individual coders remotely building a piece of software. Most science experiments are timed, variables need to be controlled, and a team is required. Most coders learn how to code well before enrolling into university; I learned it when I was in grade 5. However, coding is subjective, while science is objective. Computer science is theoretical, it takes a scientific and mathematical approach to information and it's computation. Science is more practical, it is the process of designing, writing, testing, technique, etc. They share more differences than similarities, so it's not a fair, pound-for-pound comparison.

Apologies for any grammatical errors!
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