After 15 years in tech and a life-changing psychedelic trip, I decided to self-learn genetic engineering and share it with the world[1][2] while I look for a meaningful biotech venture to found.
What you can do today from your kitchen or home lab is remarkable. For instance, I taught myself PCR (polymerase chain reaction) and recently published my first genetic sequence at GenBank from fungi that I cultured, extracted, sequenced and aligned. I'm planning to have developed my first GMO yeast in the next 90 days.
If you're interested, I also host the EverymanBio Podcast (YouTube & iTunes) where I talk to folks doing incredible work in the biotech / startup / diybio community.
I love biology yet I could not have described more opposite interests. I have zero interests in producing gmo in my kitchen, but I am definitely hooked on plants interaction and selection in open fields.
Biology is pretty broad a field. Science of the living.
When it comes to biology applied to agriculture, I prefer eco systemic research to genetics, as a personal taste but I don’t even think those are mutually exclusive.
Maybe an example is appropriate.
Monocrop cultures are efficient short term, easy to control ... but also simplistic and brutal. In this system, gmo can help reduce the nefarious intrants (fertilizers, pesticides ...). This sounds like optimization.
Alternative cultural models, multicrops for instance, are saner but implies many technical and economical issues that still have to be dealt with. This is more like an architectural change.
One occurs naturally and thus happens all around us without human interaction. So there's value in understanding how things work without any input from humans.
One is more like studying a natural process while the other is the mechanics of that process.
Yes exactly. The fruit might be the same at the end of the day; red, round, juicy. But there is more that goes into growing fruit than just reaping the end product. There is fertilizers which run off into lakes [1], pesticides and herbicides that get into the soil increasingly making soil less fertile [2], market cornering tactics like seed patenting [3]. I think it is more important to study how to make nature do the work of growing food abundantly with as little side-effects as possible, instead of engineering it to with no caution for side-effects.
GMOs are the somewhat intentional introduction of genes from another organism while breeding approaches often involve radiation to expedite random mutations which may have less obvious changes that are not safe.
Nearly everybody in the first world is eating food which has been modified by radiation to expedite mutations for many decades (since the Green Revolution) and I don't think anybody has shown any convincing evidence that the products have been systemically unsafe.
To be fair, GMOs can just as easily be unsafe; the difference in that regard is that with GMOs there are fewer ways things might go wrong, and they're much more easily enumerated and examined.
The best example of an "unsafe GMO" would be this: https://pubmed.ncbi.nlm.nih.gov/8594427/ (brazil nut proteins were transferred to soybeans; the proteins happened to be ones that cause brazil nut allergy. If this had been rolled out in large scale, probably some fraction of consumers would die).
I'd say that one is studying a plant and its interaction with the environment/other organisms whether the other is more interested in the inner works of a fungi. It is a matter os perspective, one is doing ecology and the other one is more weighted to genetics.
In high school, biology class meant memorizing modules of the human heart and pricking my finger to find out what my blood type was (I stayed home sick that day). "Loving biology" meant carrying around AP Bio books thicker than an unabridged Webster dictionary. No thanks.
Then later in college, my friend said it would be fun if we both took the genetics class he needed to take for his pre-med reqs. I agreed, and then bombed the class exam after exam.
One day right before Thanksgiving, when all the students are checked out, the profs got up and demoed their research.
They got up and showed us BLAST, the 3 GB human genome, and software tools to search the genome. Most importantly, these 2 professors, masters of the genetics universe as they were, made lots of mistakes while demoing the software. They "oops"ed their way through this and that and said it was ok because the human genome had just recently been sequenced and it was all still new.
"It's a UNIX system! I know this" popped into my head, and I promptly declared myself a biotech entrepreneur. After class I went up to the teachers and told them I would build them better software tools for genetics. Then I wrote every department in school I could find who used digital genomes to build them better tools. Tools for understanding the most important language the universe had ever written.
14 years later, in the wake of that realization is the first hackerspace for biotech BioCurious [1], an open source DNA copy machine OpenPCR [2], and lots of great work with the iGEM [3] and DIYbio [4] communities.
These days the fun continues as I'm engineering the biggest living system out there [5], planet Earth.
This is a really inspiring comment. I'm an engineering student who's kind of mentally stuck between the worlds of computing and bio. I want to do research in biotech, but I'm having trouble finding the will to do it for some reason.
In a different vein, I've recently started designing a really cheap atomic force microscope, which I plan to open-source, so I think that may be a valuable addition to the bio and nanotech diy community.
Planning on using off-the-shelf probes in your AFM? How cheap can you get those nowadays? I remember being worried about crashing them too often with our modest lab budget.
No, I'll be manufacturing them. There are alternative ways of making cantilevers with atomically-sharp tips. Tungsten wire, for instance, can be etched down to less than a few nanometers. And the quartz clocks in almost all electronic devices can be decapped and used as an oscillator.
> I've recently started designing a really cheap atomic force microscope, which I plan to open-source, so I think that may be a valuable addition to the bio and nanotech diy community.
Yeah lots of single molecule studies (strength of an actin filament, how much force needed to 'unfold' various proteins, etc). And this was 20 years ago when I was in grad school. Haven't kept up with the state of the art today.
interesting. all the people doing that in my day (also 20 years ago) used fluorescent microscopes (Ron Vale) with labelled protein. I can't see how you could unfold a protein using AFM, since it's in vacuum state, although I totally understand how optical tweezers would be fine to do this in solution.
i asked this elsehwere in the thread, and if you scroll lower you'll see why i want to learn but this is going to sound like a bit of a ramble as im tired and feeling passionate and emotional right now but bear with me...
..if i want to learn more bio not bc i want to hack or edit genes or whatever but because of reasons such as:
understanding autoimmune diseases,
the treatments for them,
relationship to other issues,
medication and their mechanism of actions,
and just a whole host of other stuff
basically i want to learn how to help people i know who suffer from multiple autoimmune diseases and the mental health/daily life and fertility struggles associated with them,
Go to scholar.google.com, search "autoimmune disease treatment", filter by last five years, use sci-hub to read the paper. Repeat until you learn enough to find your next step forward.
Absolutely not. You probably won't understand 10% of what you read. Better: go to your local university library, check out a good medicine/biology textbooks, and read that. Then go read the papers.
> But the real issue still stands: Bio is hyper complex and it takes a long time to get used to the nomenclature and ideas.
That is exactly the point, which I believe the article author either glossed over or didn't fully appreciate.
I have a B.Sc. in general biology and am about to get my M.Sc. in ecology. I do scientific work at a university and read (ecological) research papers every day. Out of curiosity, I just followed joshuamcginnis' advice and did the Google Scholar search.
I failed to understand the first three items that came up.
The basic principles of biology are usually not actually that complicated, at least when you compare them to particle physics or compiler design or stuff like that. But biology is still hugely, hugely complex, because you simply have so many interacting parts - and yes, you only really understand it when you know about an appreciable fraction of those parts.
That is why they spent the first 1.5 years of our degree simply drilling knowledge into us as fast as we could absorb it. Because it's only once you have a broad overview of how everything works, that you can start to grasp (and reason about) how anything works in detail.
Biology is fascinating. There are millions of cool things to learn and yes, most teachers could probably do a much better job of teaching it. But if you really want to understand it, you just have to put in the effort.
i mean i want to learn about everything before that too, like history, links, diagnoses - to be sure, as well as testing/tracking metrics and the likes,
also reading is the easy part, but what about understanding? when im running into medical terms/and other things im not familiar with or equipped to understand, where do you go? bc i find myself ending down different rabbit holes and my productivty diminishes and my thinking gets scattered
Biologist here. I would start with a textbook called Janeways Immunobiology. It is the textbook that all of us have used to learn immunology and should be accessible for anyone with a high-school understanding of biology.
The book already has many explanations of autoimmune diseases, so it should be everything you need.
Seconding this. I would also add that Biochemistry was really the class that first gave me the "I should have loved biology" feeling, so whatever the equivalent Biochem textbook is might be interesting as well.
University textbooks. They are written with the goal of building that foundational knowledge.
Scientific papers are great, but they assume a lot of pre-existing knowledge, whereas a textbook is designed to expose you to the concepts without any prior assumptions.
It can take me weeks if not months to fully comprehend a new paper. One paper will require that I look up a lot of new terms, watch a lot of videos explaining the terms and repeating the process for the cited references. It sounds like you need more structure so I would suggest you take notes, set goals, organize your materials and schedule time for focusing on particular topics, tasks or techniques.
It’s hard to do that when I’m entirely new. Idk where to start or what raw knowledge I possess that combined with biology would achieve the results I want.
I know the end goal though, I want there to be an option, a fix or a painless way to manage autoimmune diseases, things like hormone and metabolic response imbalances -thyroid, androgen, progesterone, insulin - etc they all share a link to deadly lifelong debilitating diseases That make living hell for so many people and I want to take that away for them or at least generations down the line.
I know I’m a rambling scattered mess right now I thank you for being patient
Be aware that on the scale of complexity, the immune system is at the deep end of the pool. Your motives may be admirable, but the chances of you jumping straight in and emerging with the Olympic gold medal are good as zero.
If you want to get into the science of it then I’d suggest you start with general courses in biochem and physiology at the undergrad level and build your way up from there†. Expect to invest a good hard 10-20 years of your life getting up to speed, with no hard guarantees of success at the end of it.
Or, if you just want to help people right now, go get yourself involved in charitable fundraising for an organization that’s already working the problem. Still no guarantees, but at least they’ve got a big head start. Just don’t end up on a list like this, ’kay:
† Courses I flunked myself, BTW, but at least I learned just how much I don’t know—an insight I’ve subsequently found both invaluable and frighteningly scarce in tech.
I'm an electronics/embedded programming guy and I "accidentally" learned biology by listening to a great bunch of podcasts while going to sleep and commuting.
At first you won't get all the terminology, but if you keep listening you'll eventually get it (that's how it worked for me).
The cool thing is that you'll dive right into the state of the art of academic research by the very people who do the research and write the papers. It's geared towards people like you and me: the curious general public.
Since you mentioned autoimmune diseases and medication, I recommend starting with: https://www.microbe.tv/immune/
If you have any particular disease you're interested in I would just do a search on that page and dive right in.
They also have weekly (almost daily now) updates on SARS-CoV2 where they seem to be ahead of the MSM by weeks to months: https://www.microbe.tv/twiv/twiv-683/
They talk with not just virologists and immunologists, but also people in industry who develop vaccines/meds, people who organize clinical trials and PEOPLE LIVE FROM SPACE: https://www.microbe.tv/twiv/twiv-682/
> At first you won't get all the terminology, but if you keep listening you'll eventually get it (that's how it worked for me).
It's kinda like a cooking show. At first, you have no idea what they are doing, but after season three you just know that they don't have enough time to do a proper raspberry vinaigrette before the gong strike.
A good place to start would be to see if there's anything on NCBI Bookshelf, and then search pubmed for recent review articles. And then you can drill down further using their citations.
I recommend this as an entry level course series, I actually attended Dr. Peffer's lectures on campus (as a non student) after nearly 10 years after completing my BSc in Cellular and Molecular biology. She holds a post Doc and research position on Campus and really likes Ed-tech and the 'gamification' of Education as a whole; she is what I wished I had when I was doing my undergrad.
When you want to get really into, head over to Josiah Zayner's, The Odin [0], where he takes Bio-hacker methods to Gene Editing and synthetic Biology. He sells kits and has weekly podcasts [1] of his experiments and observations for people to follow along. They did a COVID vaccine trial on themselves, and then moved on to making lab-grown meat, which was actually very cool way to get into the space and the community.
I just want to point out that there is no such thing as genetic engineering. This isn't a nitpick, but an important point that investors and laymen alike can benefit from understanding, particularly in regard to avoid being deceived by exuberant claims of progress by so-called "genetic engineering" startups. The top comment [1] from another HN thread sums it up pretty well. Here's an important excerpt:
...engineering is a tradition built on minimizing variation, while biology is a science founded on understanding a built-in mechanism for generating variation. "Life finds a way"....evolution is always driving against the engineered design
An engineer can design a system that creates 1000 screws with minimal variation. He understands all the effects of the different steel chemical makeups, he understands how to change the pitch and length to his specifications; he understands how to achieve each and every property of that screw, and once created, the screw will not act against its makeup.
A "genetic engineer" is presented with a million million variables. In altering a variable, he may observe some change – maybe some bioluminescence in fungus, some hairlessness in a mouse. But how much also changed that he cannot possibly observe? What other variables were dependent on the altered variable? As it is life, ever in flux, how much more will it change, itself, and its environment?
"Genetic engineering" should rather be called "unprecedented biological experimentation". This is important because "engineering" implies certainty, replicability. Altering some gene isn't engineering. It isn't minimizing variation in a system – it is introducing even more variation into that system. "Genetic engineering" certainly sounds cool and promising. But before you buy into a startup that employs "genetic engineering", don't be so certain; biology is much harder, much more complex, than screws.
Your comment makes interesting points but I don't think I agree with the main point.
If engineering is "the application of scientific and mathematical principles to practical ends", the search for practical uses of genetics, could be called, fairly, genetic engineering.
Genetic engineers sound a lot like machine learning engineers— tweaking huge complicated models which can only be understood through observation/experimentation. Often times the training is stochastic and not directly repeatable too.
It is awesome that you're getting started in this community! Here are just a few very biased recommendations of interesting folks for your podcast:
There are a bunch of different cliches (community bio vs biohacking vs citizen bio vs grinders vs transhumanists are all VERY different), but I'd recommend checking out a few of the conferences. iGEM is going on right now which is super cool, and BioHTP and Biosummit are 2 I always recommend. Since you're into fungi, there are a few cool folks in the DIYbio community you might want to talk to - Rolando Cruz Perez (in Endy Lab right now, off to do amazing fungi things soon! PhD on standardizing fungi growth conditions for distribution of strains) and Phil Ross (Mycoworks CTO, extremely eccentric, very artist, supremely interesting)
If you haven't followed them, David Ishee on Facebook+Twitter and Sebastian Cocioba on Facebook are also real good to follow. I love David's spirit+integrity of hacking and science, and Sebastian radiates an aurora of childlike wonder (specifically in plants) that is inspiring but calming. Might want to also give Josiah Zayner a follow, he is an interesting case of definitely knows-what-he-is-doing but still extremely controversial. He's a generous and kind guy though, and it is extremely respectable what he does.
Gabriel Licinia is another interesting individual in the DIYbio community you might want to reach out to - him and Justin Atkin (the thought emporium on youtube) are some of the few folks who actually do things in the community. Real science and real cool. Gabe is the local angry man who'll always tell ya if something is BS on the DIYbio facebook groups. Those 2 also work with Andreas Stuermer, who is a fantastic DNA designer. Those 3 are quite a superpower.
On the startup side, I'd recommend checking out Ryan Bethencourt's stuff. He is a great guy, transitioned from diy->startup stuff, and often helps others do too. I personally like Elliot Roth's company Spira and what they are doing with cyanobacteria and photosynthetic organisms. The future is cyanobacteria!
On the non-profit side, I really like what the BioBricks Foundation is doing and what the Open Bioeconomy Lab is doing.
Hope some of those things help! Glad your P.olymerase C.rap R.eaction worked - GMO yeast is easier IMO, just follow the culture timings and you'll be fine. Also Sanger is terrible, and Nanopore is awesome. I'd be happy to talk with you too if you'd like - I've been around for a bit, and I love helping other people get started in these communities!
PS: on your website you say you want to "Learn to navigate GenBank". Please be prepared to be disappointed.
Hi there - thanks for the thoughtful response and great list of contacts! I'm actually in talks with a few of them already. Rolando Cruz Perez, I didn't know about and will reach out to chat soon. Appreciate your support!
if i want to learn more bio not bc i want to hack or edit genes or whatever but because of reasons such as:
understanding autoimmune diseases,
the treatments for them,
relationship to other issues,
medication and their mechanism of actions,
and just a whole host of other stuff
basically i want to learn how to help people i know who suffer from multiple autoimmune diseases and the mental health/daily life and fertility struggles associated with them,
Thanks for the link. Interesting comment there, which somewhat reminds me of the current COVID-19 situation:
"The way the different countries failed to come together in the face of a world-wide catastrophe was plausible. The turn against science... while only briefly touched on, the way the angry masses turned on scientists was believable." by Clackamas in 2008.
I suffer from pretty bad depression and have been battling with it for a while using all available treatments. Someone recommended I try psilocybin mushrooms. I learned how to grow them, grew them and then had my wife help facilitate a safe well-intentioned trip using 7g of dried mushrooms. Happy to answer any questions about it. It was a profound experience. It isn't a cure but it's certainly a tool in my toolbox that has helped reshaped my life in a real and lasting way.
I was depressed, yes. But 7g wasn't my first experience with psilocybin. I was just saying that generally, I would not recommend 7g for newcomers. As for being irresponsible, I don't know man. I grew a Schedule 1 drug and then consumed it on my own terms in a way that affected no one but myself in a positive manner. There were risks involved, but when weighed against how I felt at the time, I took the chance.
It’s hard to quantify how strong based purely on dose size, but yeah 7g is double what I would consider a strong dose. I did that amount once in high school and I didn’t touch them again for several years haha.
People have wildly different reactions, some of my friends can take 14g+ and be fine, others are barely able to talk after 2g. Plus potency varies wildly between crops and strains.
Also, there are different types of shrooms, saw at least 7 types last in Amsterdam, potency varied significantly. Also, how empty your stomach is makes world of difference. Also, method of consumption - dried vs fresh, raw/cooked, or like me mixing it with raw lemon juice (makes trip shorter but way more intense - 3g trips were full beyond reality with good setting).
Plus individual variation in digestion/enzymes/receptors/god knows what else is most probably also important.
In my personal opinion there is a threeshold you have to hit with psylocipin before you can fully let go. 2g would feel emotional worse to me than 7. I take up to 1g semi regularly against my migraines which is just a little below turning super emotional.
Edit:// for reference i am talking about dried golden teachers. There are stronger variants out there.
By serendipity, I discovered a few YouTubers around that time who were showing how to do synthetic biology and biotech step-by-step on the cheap. After the trip, it dawned on me that perhaps I should put my intellectual abilities to work in this new field as it might bring the connection to life and meaning that I've struggled to find in tech.
What you can do today from your kitchen or home lab is remarkable. For instance, I taught myself PCR (polymerase chain reaction) and recently published my first genetic sequence at GenBank from fungi that I cultured, extracted, sequenced and aligned. I'm planning to have developed my first GMO yeast in the next 90 days.
If you're interested, I also host the EverymanBio Podcast (YouTube & iTunes) where I talk to folks doing incredible work in the biotech / startup / diybio community.
[1] http://everymanbio.com/
[2] https://www.instagram.com/everymanbio/
[3] https://www.linkedin.com/in/joshuamcginnis/