What I thought was a novel and useful set of ideas relating to small bacterial RNAs and human gene expression has, if I read it right, been published somewhere else- in fact, several places, including reviews.

Here is one example: Bacterial RNA as a signal to eukaryotic cells as part of the infection process. This is by a New Zealand group that published back in 2016, so around when I was ready to publish and trying to find grant money to actually test the hypothesis.

That being said, there is one aspect of my hypothesis paper that is still a testable hypothesis that no one else has thought of yet, which may have a significant impact on the treatment of many diseases impacted by gut microbiota-immune system interactions (this is quite a lot of them, possibly also including COVID-19). This has more to do with how to actually use bacterial vesicles or artificial variants containing sRNA assortments to actually treat disease, and I really cannot test this alone. I will determine how it meshes with the hypotheses I came up with more recently on how to determine ecosystem health based on microbial signatures (this was invented for soils analysis but may be applicable to any environment, including the human gut), and on my musings as to what parameters to measure to accurately assess the effects of medical treatments on humans (I’ve taken down that post, the contents of which I’ve shared only so far with a few people, and plan to re-post it with some citations added).

As for my treatment ideas, I’d really need a time machine to be able to protect them as patents or research papers, since other groups with similar lines of thinking, I would surmise, have had six years plus time to invent and establish primacy on them, so I guess I can console myself with the idea that, this time, I am actually right yet again, and have accurately predicted a real phenomenon based on intuition, reading, and what analysis I am able to do alone.

I have sadly neglected my attempt at a podcast, and today I’ll be doing a little research into current clinical trials of general interest, like the ones closest to ending, and discuss how clinical trials work. I planned to do this in May but bipolar symptoms and an assortment of other tasks got in my way. I console myself with the fact that now the trials are closer to ending and there is more information on their structure.

I typed out a new hypothesis that came to me today (really a series of them) and felt this was worth sharing, so I did. Then I realized that I really need to both explain the terminology and concepts better for this blog as well as add in URLs for cited information, and so I decided to unpublish it. I did advertise it on Twitter but I know I get very few hits so I figure it’s safe enough to take it down for now.

I’m also compiling ideas for how to talk about the Moderna vaccine and possibly the probiotic bacterium that Dr. S has been testing (the first hypothesis I had is based on work with this bacterium, which has effects against lymphoma development), in a podcast episode about how clinical trials work.

I have to reiterate that while I have been in communication with someone at the UCLA email address for Dr. S., the responses I’m getting are frankly a little uncharacteristic for a scientist, and I have questions about why this is. So while I complain a LOT about how I am not getting support, information, feedback, or help writing grants (such as setting up a grants.gov portal, which I literally cannot do myself), I don’t want anyone to assume that the actual person Dr. S is a terrible communicator and colleague, since (and I admit this sounds paranoid) it’s possible he’s not actually seeing or replying to the messages I’ve been sending. Why I think someone might have gone to the trouble of hacking someone’s official university email is a very long story and I would prefer to leave that out of this blog. Just don’t bother Dr. S. unless it’s to find out if he’s really been talking to me since I met him in 2014.

I’ve had to develop all my hypotheses by myself, in isolation, with little to no feedback from anyone else and none involved in the actual formation of the ideas. This is not typically how science is done and I really wish that I had had more help and support, because my thinking may be improved or my background knowledge more extensive if so, but I think that the actual hypothesis I wrote out today (which has been emailed to people with connections to Cedars-Siani and the Broad Institute, just in case someone finds these ideas useful, and they are timely, since they relate to COVID-19 treatments) is still thought-provoking.

When the work is ready I’ll repost it.

Thanks, Liz

I wrote this as part of an unrelated series of musings on how to best characterize mixtures of microorganisms from complex samples. Those musings remain so, but I thought the below was worth sharing. Dysbiosis is defined as a dysregulation of the gut microbiome such that its composition is altered, and this has negative impacts on the host organism.

Might also be useful for the study of bacteria that form biofilms which may keep out viruses in mucosal surfaces like lung, nasal, throat, or intestinal tissues: which bacteria are consistently positively or negatively associated with viral presence or infection and which form capsular material that might affect the ability of viral particles (like a coronavirus particle in the lungs) to infect? Does the gut-lung axis affect the composition or thickness of lung mucus, so making it more difficult to traverse in some patients but not others, and since gut microbiome composition is associated with so many pathologies (diabetes, heart disease, lung disease, obesity, psychological conditions, cancers, inflammatory diseases) might this by why there is a relationship between these pathologies (which may come with dysbiosis) and susceptibility to novel coronavirus as well as severe cytokine storms?

Your gut microbiome composition is affected by a lot of factors: sleep cycles, stress, diet, age, general health, exercise, and probably also your genetic makeup. This is still an emerging field of study and the complexity is appreciated but has not yet been untangled, so people marketing products claiming “this product boosts the immune system” are basically only doing that- marketing products. Beware of hype (and in the case of your immune system, making it more active might result in autoimmune disorders, so you really want to talk to an immunologist if you are concerned about your immune function- not some quack selling pills).

That being said, if it is possible for you to take healthy measures, like increasing exercise if you get too little, eating more colorful fruits and vegetables, getting consistent and adequate sleep, and managing stress in a healthy way, this would be expected to alter the composition of your gut microbiome if consistently applied, and it is known that these measures will help your general health (just ask your doctor). It’s never too late to take up healthy habits.

[Update: I finally have some feedback on my hypothesis paper. mBio does not accept with revisions, so it was rejected, but essentially I was informed that I should resubmit with the requested revisions. They are reasonable and the suggestions were helpful- this was the kind of feedback I have been trying to get from someone all along. It will take me some time because I’ve been quite ill lately, and some of the requested changes are substantial.]

In late March, early April, of 2020 I updated my hypothesis paper (the one dedicated to describing the ideas coming out of my 2014 preliminary research for Project: Cancer-Fighting Gut Bacteria, the crowdfunded project this site is dedicated to) and last month I submitted it to the journal mBio. I also wrote a short proposal on how to leverage existing clinical trials to assist in finding cures or risk factors for COVID-19 symptoms (that I put into a podcast, which is referenced here), and in the written proposal I included some new, very small analyses which described potential interactions of products from my cancer-fighting gut bacterium, a strain of Lactobacillus johnsonii, and pathways involved in inflammation and cytokine storms, which are the reason why people get very ill with COVID-19. This gut bacterium has been characterized by people with more medical and immunology expertise than I have as anti-inflammatory, and the products I found it produces could provide at least a partial explanation as to why that is, and how we can use this mechanism to make new forms of medicines.

I submitted this to bioRxiv, and of course, because the second paper was a proposal, it was rejected. I also had submitted my original hypothesis paper which describes the experiments I did to find and characterize the products I looked at, and speculates on where the bacterial products come from, how they can be used, and how communities of bacteria in the gut or elsewhere can be affected by their environment to change the spectrum of such products provided. That was rejected as being too short. So not a real paper, I suppose. I am optimistic that the paper I submitted to mBio (exactly the same one as to the archive) will eventually be reviewed and I’ll get some kind of verdict, although this process is not occurring quickly at the moment. The other piece I may publish once the mBio submission, if it is accepted, gets published, in blog form. It may inspire someone, although I realize that the majority of scientists in the world will never see this blog.

It occurs to me that some of the ideas I’ve had regarding how to look at interactions over time between soil and plants and their microbiomes (and finding drivers, and indicators of ecosystem health, for these systems) might be applicable to the gut ecosystem. For example, I had used network analyses of soil bacterial and fungal communities characterized by next-generation sequencing of barcodes to come up with a means by which “healthy” soils and systems can be identified, on a relative scale where you rank networks from different sites or treatments that are comparable. It occurs to me that this could be applicable to groups of mice or patients who can be sorted into categories based on symptoms, and provide gut microbiome samples. I also note that if you took samples over a period of time, and monitored symptoms or other indicators of health or disease, it may be possible to look at relationships across time points (so link a phenotypic host trait at time 1 with a microbiome state at time 2, or the opposite temporal direction) and find whether the state of the host of the microbiome drives the gut microbiome composition, or whether the microbiome drives the state of the host (ie. which changes first). I suspect you’d need many time points, and that this interaction goes both ways; the strength of the interactions (which drives which, host or gut microbes) will probably vary with environmental factors that we already know affect microbiomes, such as exercise levels, sleep, stress, diet, in addition to factors including host genotype. I would find an experiment or project designed to test this fascinating.

I am too tired most days to jump onto public database sites or petition PIs for data so I can test these ideas myself, and I realize that I may not have the statistical “chops” to see these ideas tested thoroughly enough alone. The obvious solution is to get a laboratory of my own and I really wish I could say I could, but I’ve tried for 25 years or so and I’ve never been offered this opportunity, so the only way I can do real science is to interest someone else with more resources in what I have to say, write a grant, and do the work. I really wish I could find someone who took me seriously enough to listen to my soil health and productivity ideas, let alone seeing how the analytical concepts may apply to medicine and veterinary sciences. I will be happy if a single researcher finds this post and is interested enough in the concepts to contact me (ebent@uoguelph.ca, although I have limited my forwarding from this address so it is not a fast way) and ask me to elaborate, or send the preliminary thoughts I already have had.

It doesn’t help that I’m bipolar and struggle often with depression that makes me fatigued and interferes with my ability to get things done quickly, and it also does not help that when I come up with truly out-of-the box thinking or ideas, people that know I am bipolar tend to want to see those ideas put forward by someone else first so they know they are not “crazy”.

I’m heartened that someone at Cornell was kind enough to write to me to describe some work going on that might be publicly available in about a year or two, so I can test my soil health indicator ideas then, I would assume. I might ask who the PIs are that he references in this large multi-lab study so that I can ask them individually if they would be interested in either providing me with data, or taking the analysis I’ve thought of seriously enough to test it with me before the data goes public. That will have to wait for another day.

I hope you have a productive day and apologize if you came here looking for information you did not yet find. I plan on discussing both how clinical trials work and how gut bacteria might affect inflammatory pathways (which affects a surprising number of different disease states, including cytokine storms that are present in the more serious cases of COVID-19) in future episodes of my poor, neglected podcast- I keep putting it aside for more pressing things and it never seems to be continued. I will try to make more time for it in the near future.

After 6 years of trying and much effort on my part, I decided to simply call it quits with investigating my hypothesis and see if I can’t just publish the hypothesis alone.

It was submitted to mBio and is under review. Things are going really slowly these days, so I am not expecting a speedy turnaround with a review, but at least it was not summarily rejected.

In other news, I am mostly now fully recovered from a bout of strange paranoid thoughts; there is not a lot of soil microbial ecology work on my plate at the moment (though I have an idea I want to continue to test), and so I’ll be getting to that just as soon as I finish my long-neglected second podcast episode, describing how clinical trials work. I want to focus on Moderna’s RNA vaccine. I am hoping to write the episode tomorrow if all goes well, and record it on Monday.

If you are wondering about my competence as a scientist because I suffer occasionally from symptoms of mental illness, I probably should remind you that the entire time I’m suffering from paranoid thoughts or worries about conspiracies, I am aware that I have this problem and I watch out for it. I use logic and reason to defuse the thoughts I have and tend not to buy fully into them, and let the actual delusions fade over time (as they do). I can’t say what other bipolar people experience or if they act irrationally (I tend not to, though I admit it takes me a lot of thinking to figure out if my fears are valid or not), and I would argue that the majority of mentally ill people are more at risk from society than the other way around. I am not ashamed of my diagnosis and I would argue that it’s a side effect of heightened intelligence and creativity, both things you want in a scientist.

Have a great day.

Update

Hello, readers!

My hypothesis paper is actually finished in a format that mBio would accept for a preliminary review, it’s just that I don’t want to try to publish it without testing the hypothesis and turning it into a real paper. I have not been able to contact Dr. S yet (and this reticence on a subject that should be dear to his heart, studies of the bacterium he patented, makes me wonder whom I am talking to at all, honestly- he’s been supportive but not offering scientific advice of any use, which makes me think I’m actually talking to someone else). The importance of Zoom at a time like this can’t be understated.

So while I finish things for my soil ecology lab job, I am keeping, in the back of my mind, a list of things to do to dust off the proposals I have written already and see if they can be funded by a non-NIH program, or if I can find someone else to help. It honestly would be so much easier if I had a laboratory of my own since the work really is not that difficult- the hardest part is finding a person with expertise in preclinical studies and lymphoma diagnostics, and a few pieces of equipment. The right collaborator would be fine. All the molecular work I’ve envisioned is not particularly hard- I’ve done the basic stuff already in a borrowed lab at UCLA in a few days in 2014, using bits and pieces of used kits and reagents. I work on a campus with a veterinary college, it is not impossible to find a cancer specialist. Just that I need to be able to interest someone in the work AND find a colleague that won’t leave me hanging. Money in hand helps a lot.

I know it’s likely they mock me for this blog, and at the same time avidly try to read between the lines to figure out what I’m really thinking or what the details of my work really are- this was my experience for 11 months and it was awful. They even had a “What Are You Thinking About” segment in “lab meetings” and I’d lie about what I was thinking about. Those segments stopped when I confided in several people that I had no intention of ever telling anyone what I was thinking of.

I’m glad I worked in a healthier environment after that, and while I continue to wonder about some of my colleagues (like Dr. S- he really has been underinvolved), I am so much more productive when I’m not paranoid all the time.

[Update: I still am struggling with paranoid symptoms but I am on the mend. In the meantime, I’ve made some good progress with soil ecology projects, and as for Project: Cancer-Fighting Gut Bacteria, I know it’s a tough sell just as a theory with no supporting evidence. I’ve had a colleague read the paper and he says it is “wild”, and not entirely convincing because of this. When I am feeling better I will see what I can do to write a grant with someone supportive with the right background, to finally nail this down.]

Hello, readers. I have contacted Dr. S. and am awaiting a reply on whether he would like to actually work with me on testing the hypothesis I had (which forms the basis for the project this website is devoted to, Project Cancer-Fighting Gut Bacteria), instead of simply publishing a hypothesis. In the meantime, I’ve been in touch with a few people who are interested in sharing my podcast episode one, which is devoted to an idea I have had which might be very useful, about leveraging existing clinical trial data.

While I work on podcast episode two, I have exhumed some soil microbial ecology ideas from a while ago (as much as a year or two ago!) and I’m seeing if I can get traction on those with my current research group. Much of what I want to do I can do alone, with sufficient data. So far things are promising.

I am reminded, each time I write to a new person or contact someone I already know, that whether I am listened to depends on whether people think I have anything of value to contribute. I am not a visible minority, but I feel for visible minority scientists- it’s hard enough to be taken seriously as an older woman on the fringes of the profession, without a “real job” to prove I have merit. I can’t imagine what it’s like to have to navigate that plus racial bias.

If I ever do get a “real job”, I wonder if the people who dismiss me now (or have consistently ignored me) will change their minds about me, and if they will even realize the unspoken, possibly unrealized reasons why? When I was young I thought scientific communities were merit-based, but as I grow older and see mediocre people with connections get fancy job titles and more respect than the people who actually understand more and think better, I have my doubts. There are some serious injustices in how science is conducted everywhere in the world, and the silencing of “insignificant” voices like mine, is, frankly, one of them.

How many brilliant minds are overlooked in every walk of life because people assume they can’t have anything valuable to contribute?

Hi! If you’ve been following this blog, you will realize that I’m both trying to promote an important idea about clinical trials with a podcast (other forms of communication will follow), and at the same time, either share or test an idea I had in 2013 which has developed a bit over time. I’ve written up this 2013 hypothesis in a paper I had planned to simply submit to the journal mBio, and if they took it, I planned on just leaving it at that, and hoping someone would eventually find it useful. However. I’m going to try one more time to talk to Dr. S. at UCLA and see if he wants to genuinely try for funds to test this hypothesis ourselves.

I’ve been getting very uninformative and non-scientific feedback from the emails I’m getting, which, combined with my bipolar disorder and natural tendency from that to become paranoid, is making me wonder- am I talking to who I think I am when I send and get replies via email, at all? I wrote about this in my fiction blog a little, but intercepting the emails between myself and Dr. S. would be a fairly elaborate scheme, merely to defraud me of the ability to talk to another scientist- and why would anyone do that? Since this is so highly improbable, I am inclined to think I’m just being paranoid. Which makes me think I need to take a step back and monitor my thought patterns, to see if I’m recovered from my symptoms or getting worse. A lot of people are under stress right now and it makes sense that I would be one of them.

In any case, I’m hanging on to my ideas for now, except the most important one about clinical trials, and I’ve actually gotten some useful advice on how to package that (by itself). That alone is heartening.

Please stay safe, and at home when you can.

I started a podcast which covers information I hope will give people something to look forward to, namely ways in which treatments or vaccines can be found to end the pandemic and our social isolation. In the first episode I focus on the idea I’ve had for leveraging clinical trials that are currently underway to fight the pandemic. I really do think this is an important idea. I mention this a lot, but I think it bears repeating.

Future episodes will focus on how clinical trials work, and existing research done by others into promising treatments or vaccines for COVID-19 infection.

The podcast link is here:

I am also planning on putting these episodes on YouTube, under the channel SolvingThePandemic. These videos to follow. [EDIT: The first episode video is here.]

Thanks for any support or sharing. -Liz

More later

Hey everyone- I’m suffering a LOT from bipolar delusions, and so I’m going to have to take it easy for a few days or so. My earlier post that is most interesting, about how to leverage existing clinical trials to fight the pandemic, is here. The papers I reference in it which I wrote or rewrote I’m just posting to this website. Links to come. [EDIT: I decided against this- I’ll publish them formally in time once I find an appropriate outlet.]

It’s occurred to me that the functional redundancy stuff I mentioned earlier for soil data might be applicable to studies of gut dysbiosis and there should be a lot of useful data in databases to work with, provided I can get adequate metadata, but I just need to rest a bit before I try to do this or anything else.

I’m thinking of submitting the hypothesis to mBio but the other stuff about COVID-19 and dysbiosis and inflammation, and the more important clinical trial idea, I don’t know how to package that; it was rejected from MedRxiv for “just being a proposal” so- a second hypothesis paper? Based on the first? Would anyone publish that?