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I’ve got mild OCD, I have been analysing data exclusively for about 5 years now, and humans are naturally pattern-seeking creatures- plus I’ve moved to and worked in labs in three countries and talked with people from all over the world.

I won’t deny that I’m bipolar and prone to fits of paranoid delusion. However, looking back, I can’t help but wonder about whether or not my former, and possibly even some of my current, colleagues and labmates were given the impression (not by me) that I was a jerk, overly confident, a braggart, or worse.

When I say “not by me”, this is the part that sounds paranoid. I’ve speculated at length in my fiction blog about the existence of a stalker, and contemplation has led me to figure out who it actually could be- but because I have not a shred of evidence that I’ve ever met this person, let alone that she has been stalking me, I can’t make an accusation. So I write little fiction pieces when I get annoyed and call them my “Hamlet’s play” series, for obvious reasons.

One of the things I have consistently wondered is the hostile reception I’d get in many new workplaces, or how coworkers would be hostile for a time upon meeting me and only thaw after spending time interacting with me and, perhaps, learning what my actual email address is, or that I don’t actually believe awful things. It’s paranoid to think this, but what would happen if my introduction to a new lab was an email that made me look like an utter asshole, and then I’d have to spend a lot of time breaking down that assumption- or simply being shut out and unable to do so, as I suspect happened to me in Alaska. It would explain a lot.

I’m also wondering why people ignore my messages. Most of them are busy and I understand that, but in the case of one colleague in particular (Dr. S, the UCLA collaborator whose lab I did the preliminary experiments for this website’s science project in), his replies to me make no sense sometimes and he ignores me when I try to work with him to gain money to carry studies of the bacterium he has a patent on, studies which could form the basis of additional patents, or lucrative products his probiotic company could develop- it makes no sense. Plus some monosyllabic replies make me think that either this person is just ignoring me (always a possiblity), or, and this also sounds nuts, someone else is getting and replying to my messages. But why?

I can’t say for certain if I just need to interact more on the phone to be paid attention to, or if certain people are just not inclined to work with me because their initial impression of me was that I am a complete jerk, and they have not entirely overcome that, or if there is some other explanation I haven’t thought of. I can’t help sometimes but wonder, though, am I paranoid, or was there at least one person determined to destroy my working relationships with different people? I don’t know if I’ll ever know for certain, because how can I ask?

In other news, I had some productive conversations and some science ideas that I think are useful, and more on those later.

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.

Just had an unpleasant interaction with #Kolabtree science consulting site- canceled my account because they defended a clear scam artist as being a “distingushed scientist with a 25 year career”. If that is the case, why is this person claiming 5B in assets and having a commercial product that they want to test, also claiming to have fastq sequence files, BUT saying they don’t know enough about the human microbiome and they need an expert to give them input? The claim is that they want an “overseer” of a project involving these mystery fastq files, and need input into the design of the project, but they have a bioinformatician already, and they mentioned importing files like this is some difficult process? Why do they need a human microbiome expert if the study has already been conducted? Shouldn’t the designer of the study be able to explain the results? It’s clearly all bullshit, and I said so. Either they stole data from a competitor, and are trying to use it, or they plan on users clicking on links for the fastq downloads and phishing out banking information after that. What a garbage website.

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?

Hi, everyone! For the idea, you can skip to the fourth paragraph.

Being bipolar, I usually work in fits and starts- nothing for a while, then all of a sudden a ton of ideas and inspiration come to me and I will have the energy to sit and work on them, and I can actually manage to get quite a lot done. My coworkers and former employers can tell you that I will go through times where I send spates of emails with new ideas, and these sometimes get passed over because, well, a brand new idea is a lot to deal with.

For my environmental studies, I had a couple of ideas in this current spate of productivity: to take some reports I had written a year ago or so and use them (the ideas in them, which are mine) to write methods/review articles describing the analyses I did and using the data I analyzed as an example of how to do it. I personally think the data, which dealt primarily with a tillage experiment, is worth publishing on its own but it would be impossible to make solid claims (too few data points), so I think that I’ll wind up presenting it in the context of being an example data set in a methods paper (on ecological network analysis, and another paper would focus on some more abstract ideas I have for looking at things such as functional redundancy in ecosystems using network data, and probably public datasets).

So that’s good. But I’m most proud of the idea I had today, which evolved over the course of the day as I thought about how to use existing data on the probiotic I studied in 2014, Lactobacillus johnsonii 456. I don’t know what stage clinical trials are at with this probiotic, but as the day progressed, I realized: this idea can be used for ANY CLINICAL TRIAL that is sufficiently advanced to have a large number of patients.

Here is the idea:

1. Clinical trial with lots of people: treatment, no treatment.

2. Take samples or use archived samples to determine if patients were infected with the virus. 

3. You now have four groups: treatment, no treatment, both with and without viral exposure.

4. Statistical analysis to determine if the treatment can reduce the probability of infection and/or reduce the probability of experiencing severe effects of viral infection.

So instead of starting a trial now and hoping that the drugs studied will work, and waiting 12-18 months for a result, we can take a look at everything that’s being studied now which is close to ending. The wide spread of the COVID-19 virus means that a lot of people enrolled in most trials could have been exposed, and it’s not unreasonable to assume that there may be enough to make statistical tests valid, assuming that we can assay patients for exposure to the virus adequately. It may be possible to use epidemiological data and the residence of each patient to determine the probability of when patients were likely to be exposed, if this is required in determining effects. It should be possible to track symptoms, especially for patients requiring hospitalization. And if patients are monitored from now on with this analysis in mind, if they do become ill they can be watched to see what happens.

It’s not ideal, but it is a potentially effective way to leverage a large amount of existing work to rapidly find treatments which can help protect (or alternately, increase risks) from COVID-19. Current efforts to contain the virus are not sustainable- and in the case of the USA, there simply is not enough medical equipment to be able to treat cases adequately. While the government struggles to find a response and states also are doing their best, the research community can step up, and see if their clinical trials can be used to assist in the race to find treatments, or identify additional at-risk groups which may not yet be considered.

Update: I heard from Dr. Schiestl, my UCLA collaborator for the stuff I did in 2014, or someone at his address (I struggle a lot with wondering if these emails are actually from him- yay, bipolar) and he is supportive of me writing up a small paper describing my findings (recent ones, based on what is essentially sequence matching) with data I collected in 2014 from Lactobacillus johnsonii 456, and public database human proinflammatory cytokine genes (involved in the cytokine storms which cause lung damage and organ failure in severe cases of COVID-19). I figure this is important data, and it builds on my general hypotheses about how bacteria interact with eukaryotes, so I’m just going to submit that hypothesis paper (already written) and this new set of analyses involving proinflammatory cytokines. I’ll submit the hypothesis to biorxiv, and this followup relating to novel coronavirus in medrxiv. I’ll post when this is all ready to go. There will likely be problems with my analyses, because this is not really my area of expertise, but I’m very happy to inspire people to look at my data and their own data, and consider the novel ideas I’ve had about how bacteria interact with us, particularly in the context of fighting off this pandemic.

Update #2: papers submitted. It will take a little time for these papers to clear the review process (not peer review, which I intend to seek once I figure out who might want to publish really highly speculative papers, but just suitability for the archives). [Note: both papers rejected for not being full research articles, keep reading.]

I had a hard time figuring out what category to use for the submission to MedRxiv as “microbiome studies” is not a category on MedRxiv, and that’s basically it- plus, the clinical trial idea is possibly more important than the things I wrote about probiotics or dysbiosis, and that idea is really why I bothered to submit these papers now at all. I’m hoping all of both submissions will be useful, but I believe even if all my thoughts about bacteria are not, at least this one idea about trials should be worth mentioning and circulating. Once the papers are in the archives (fingers crossed), I’ll post links and start mentioning the clinical trial idea in letters to medical journals, since my attempts to reach clinical trial companies, health agencies, and newspapers have failed. It’s also possible that people have already thought of the clinical trial idea, but if they have, no one is talking about it.

Update #3: Well, this is a wrinkle. Submission to BioRxiv was rejected for being a hypothesis paper, not a full length research article. Too short. It’s so hard to publish a hypothesis with only preliminary data, and I haven’t been able to test the hypothesis myself. Every time I try to get a US lab to open a Grants.gov portal so I can write an NIH grant, for example, I get no assistance, and I can’t do work with UCLA mice and a UCLA bacterium and a UCLA collaborator unless it’s pretty much going to be at UCLA. This has gone on so long I’ve basically given up. It might not even matter, if the other submission is also rejected for being short.

Update #4: Well, as I half expected, my MedRxiv submission was also rejected for being a proposal, not a full research article. I think my next steps are, if my agitated reply to the staff at MedRxiv is ignored, to try to write letters to the editor about the trials idea in papers like Nature and Science and The Lancet, and hope there aren’t expensive page charges for that or a lengthy consideration process and messing with paper formatting. My hypothesis paper might go to mBio, and I’ll just fold the work I did relating to proinflammatory genes and so on into the supplementary information for that.

I’m more concerned about getting this idea about using clinical trial data out quickly, though. People are dying. The stuff I wrote about dysbiosis and COVID-19 symptoms, which draws upon both papers and is sketched out in the second, might be helpful longer term but I think the trial data idea is most important. The clinical trial idea I might be able to publish in The Conversation, and hope enough clinicians will see it.

I’m very tired today- I think that the stress of this pandemic plus staying up late for 3 nights in a row repeating analyses and revising and writing has caused a flare up in my bipolar disorder, and I’m just going to have to take it easy for a couple days while I try to think of what journals most clinicians read, and figure out how much submissions might cost. It’s also occurred to me to try to write letters to newspaper editors, but again, not right this second, I’m pretty tired and I don’t know if those would be published, either, or circulated to the right people. I wish I knew someone prominent who would help me with this, I honestly think I’ve come up with a very good idea but I’m not getting any help in circulating it to the people who need to see it.

Even Dr. S. isn’t saying “oh, hey, let me use this idea on my trials that are about to end” and that is pretty strange to me (and it makes me wonder, again, if it’s not actually him I am communicating with, hooray). All you need to do is swab all your patients for COVID-19 and then split them into infected vs non-infected for each treatment. It would be perhaps a bit expensive but any molecular biology lab can do the RT-PCR, provided that RNA is extracted safely first. The RNA alone isn’t dangerous. If you wanted to inactivate the virus to make it safer to handle, just soak it in proteases first to destroy the spike proteins, kill the proteases with heat treatment (which will not injure the RNA), and then you can just do the RT-PCR, provided the lipids and other sample contents don’t interfere with the reverse transcription or PCR and you work fast to prevent RNAses from destroying your samples. I wouldn’t be afraid to do this myself in a regular lab provided I got the sample after protease treatment, and provided I had evidence that such treatment destroyed the virus’s infectivity. And if you wanted to make this process safer, just have the technician swabbing people put protease in the sample tubes and start the incubation for the enzyme as soon as possible after. That way only one sample handler is exposed to intact viral particles.

It occurs to me that if you wanted to look at dysbiosis, it’s not perfect but you could assay the swab nucleic acids (archived, probably) for 16S and ITS sequences and determine the abundance (with qPCR) or composition (with barcoding) of bacterial and fungal communities as well. This is, again, more money but it is possible.

-Elizabeth Bent