I remember when I first started doing protein engineering. I opened up a file of the 3-dimensional atomic level structure of a protein using VMD and started to move and manipulate the molecule. I couldn’t look away. I felt like I was staring into the soul of life. I was hooked. I wanted to understand how life worked on the molecular level and spent my PhD doing exactly that. I became passionate, spending my time commuting on memorizing the amino acid names, structures and functions. I would listen to lectures on Biochemistry, Cell Biology outside my normal coursework and regularly read textbooks on Physical Chemistry and Statistical Mechanics. But I'ma be honest, to be a groundbreaking gene designer requires dedication that dedication first. Doesn't matter how much book smarts you have. Find that spark and the rest is tears in the rain.
So you want to be a gene designer?
One of the things that always angered me about academic science was that there was no easy measure of a good scientist. There are no metrics like there are with sports or entertainment. No leading goal scorer or Billboard #1. I would work my ass off every day and was lucky if anyone ever showed me any kind of appreciation. That’s just the way it is. There really is no educational plan to help you perform at your best. Instead, knowledge is Leroy Jenkins-ed into your gourd as fast it can be without regard for its usefulness. While I don’t think I would be where I am today without going to grad school. I think there are better ways.
Honestly, it shouldn't take anyone 5 years to learn what you do during a PhD. If you focus and specialize, you can be doing your own experiments in months. But, you need a place to start. And I say, find something that gives you goosebumps. For me, it's that cyberpunk future. Blade Runner, Cyberpunk 2077, I can’t help but squeal a little. Don't think too hard about it. Go with what you feel and use that core idea for inspiration. Then get to making that world reality.
Obviously, I want to hock my wares. The ODIN’s Bioengineering 101 kit is an amazing place to start. If you actually dig into every paper and activity in the class, you will come out of it with a solid foundation. The videos are all available on our Youtube for free, but honestly you NEED hands-on experience to really be a scientist, Molecular Biology of the Cell Chapter 2, Verse 11. There I said it. Just like you're not a footballer if you no longer play football matches, you can't be a scientist if you don't do experiments. Sorry not sorry, to all the academics who just write grants and papers and no longer work at the bench. So, yeah, you need to buy stuff. I want people to get over this fact. It seems to plague every genetic biohacking choom. Is there a hobby in the world that you don’t need to buy stuff? A basic lab and supplies will cost a few hundred dollars. I mean, you can get a kit to start engineering human cells for the cost of a PS5.
I’m not going to lie. There is no short-cut to being a good scientist, the same as in every professional endeavor. You need to spend time and effort. Don’t get me wrong, you can be Jane gene moder who does this stuff part-time for fun but I’m talking more to the people who are actually trying to crack the code of life and build something truly original. For that, it’s gotta be your life’s work. I hate to break it to you but you aren’t gonna Sheck Wes the Mo Bamba of genetic engineering. Or maybe Kary Mullis did that with PCR? Anyways, I challenge anyone to make a more obscure sleeper hit comparison.
Take things one step at a time. Make it a goal to read one paper every day or do one experiment. That is usually a much more sustainable way to build up knowledge and experience. Read a few pages of Molecular Biology of the Cell. Start to focus in on your topic. Generally, it’s hard to be a Jill of all trades and focusing on plants or animals or fungi is the best path forward. Finding research papers that are related to your interests is more an exercise in being good at keyword searches than anything. It’s not rare that I have read 10 papers before I actually figure out how scientists in the field refer to a specific technique. Or worse, are willing to divulge in the methods section what they actually did.
Setup a business. Some scientific companies will make your life difficult when trying to order products and chemicals, no matter if they are hazardous or not. First, search eBay, it’s usually always easier and cheaper to get stuff from there. If not, you can register for an EIN from the federal government for free. Make a basic website and get a personalized email address all for like $30. This makes it so much easier for scientific companies to trust you. If they won’t ship to your personal address get a PO Box. You can just append your box number to the post office address and it looks like a business suite or something. It’s not against the law to lie and say you have a PhD and that can make your life much easier. Don’t underestimate the idiocy of scientific supply companies. I have many many stories of company not being willing to ship me plastic goods because it was to a residential address or was for personal use. Don’t let that happen to you.
Do experiments that you know you can replicate before trying something new. You’re going to fail alot. Especially when trying to translate research done by academics to your personal lab. Science publishing wasn’t designed with the end user in mind. So before going all HAM and trying to make a dragon on your first experiment, find an experiment that others have done that is well documented and replicate it. This lets you understand the experiment and where you can go wrong. When starting a new set of experiments I always use the first go as practice. It helps take the pressure off and gives you the opportunity to fail without much risk. It’s a really good strategy for me. You are going to fail but minimizing how much you fail is possible by setting yourself up for success.
You really don’t need much equipment. You don’t need a good microscope or autoclave (use your oven in a pinch). No sterile water or flow hood. I have even spent most of my non-traditional career with only a general food fridge and freezer. For incubators, chicken egg incubators work great. If you have money to spend get the growth media, chemicals, DNA, enzymes or reagents you will need.
Outsource work as much as possible. I’ve been in this situation myself. You think you are going to save money by trying to edit some plasmid DNA yourself. The truth is that the amount of time and reagents you put into it is usually much more expensive than if you would have just paid Genscript the $150 to do it for you. I know, $150 can be alot of money sometimes. Be stingy. Contrary to popular belief you probably don’t need a freezer full of restriction enzymes. You can wash a reuse most plastics or better yet, use glass, as it’s much more sustainable. Contact other gene moders and biohackers to exchange strains for the cost of shipping instead of paying a company a bunch of money. You don’t need to break the bank to do most genetic engineering so spend your money where it counts.
Embrace the lack of sterile environment. When I was in graduate school I was told everything needed a flow hood. The idea that you could purify RNA in your garage was insane. The lore goes that RNA melts faster than Nazi skulls being exposed to the ark of the covenant. And then I purified it in my garage and reverse transcribed it and did PCR. Then I did mammalian and human cell culture. I have never autoclaved agar media more than microwaving it enough to melt and mix. The list goes on. Lots of people in non-traditional environments try really hard to make things more sterile than even professional labs and to me that’s a big mistake. Learn to work within your boundaries. Understand that you, yes, you, yourself are the most likely cause of contamination. Wear gloves, spray yourself with isopropyl alcohol. Wear a mask if you need to.
The reason the experiment didn’t work is you. It’s pretty typical to see chooms complain about their reagents going bad. The truth is that in my long illustrious career I don’t think there has ever been a case where a reagent I purchased went bad or was bad. You’re the problem and the sooner you start blame yourself the quicker you are able to figure out why your experiment failed and fix it.
If you want good experimental ideas you need to consume information. Nowadays, I don't really read textbooks. That’s for when you are building your base of knowledge. After that, it should just be scientific papers. When I see a paper or topic that interests me, I download a bunch of papers on that topic using Sci-Hub. I try and understand the protocols and what the experiments would actually entail and I price out how much an experiment would cost. Then if everything seems reasonable I give it a shot. If costs are very high, I try and understand how I can cut costs or build up to the experiment by doing smaller experiments first.
To do groundbreaking experiments that others haven’t done you need to consume information others aren’t consuming. To me, I search for stories in which others have challenged the dogma of the field they work in. A sculptor, filmmaker or chef it doesn’t matter. The weirder the better. You’re not looking for specifics, you’re looking for inspiration in how to combine the knowledge you already have in new ways. Exciting your imagination is just as important as knowing things. Challenging the dogma is the easiest way to do something interesting.
Do stuff. This is the most important. Seriously, when I first started doing genetic biohacking I was baffled by how many people just talked about stuff and how few people actually did stuff. I started doing simple stuff and people started paying attention. This has kind of become my life motto now. If you put stuff out into the world you will get opportunities and jobs and connections. If you don’t do stuff and tell people about it how will anyone ever know?
Love it. This reminds me of or points to a manifesto in the making.
While I do agree that science demand actual work and not just reading and reciting information, there are a couple of things that I found alarming.
1. It's important to understand that the entire Cyberpunk genre is built upon a dystopian foundation. The movies you list are not something to aspire to or squeal over. While this genre includes interesting ideas, it's important to understand that these are written as cautionary tales. Quite frankly, no one should take your advice here, including yourself. To strive for "cyberpunk" is to strive for a future with unprecedented levels of inequality, abuse, and an environment where life is pretty low (hence why cyberpunk is considered a "lowlife" genre). It's like striving for world war 3 to wipe out most of us so we can live in the rubble because we like the apocalyptic v i b e s. It's fucking stupid. Biohacking, which has the science of life at its core, only makes sense if it revolves around protopia — not dystopia. To improve the human condition, not more pointless tech gadget bullshit.
2. Reading Molecular Biology of the Cell won't magically give you the ability to do anything. Even if you get through a couple of chapters, collecting information is not knowledge. First off, you come from a university background...Realistically, what do you know about amateur hacking? You're not self-made. From day one, and these are your words... "I remember when I first started doing protein engineering. I opened up a file of the 3-dimensional atomic level structure of a protein using VMD and started to move and manipulate the molecule. I couldn’t look away. I felt like I was staring into the soul of life. I was hooked." Dude...you came in as a PROTEIN ENGINEER! Like.... 🤦♂️ Your passion grew out of a university, not at home. I'm not trying to insult you here, but think about it. What made you even download and open up VMD in the first place? How did you even know about it? How to use it? Why you even need it? You don't understand what it means to enter this space as an amateur, where all you have are books, pirated software, and DIY equipment. You had all the necessary pre-requisites and resources to launch your new passion. It's important to understand this distinction because you try to make it sound easy, when the reality is that there are a million things that need to fall into their right place before one can even begin to know where to look or why.
The reality is that you need chemistry. You need to be really fucking good at chemistry and you need to have a solid philosophy of science that will guide your imagination as your foundation to amount to anything. With the direction things are going, you'll need computational chemistry, not just wet chem. Unless you're doing microchemistry, it's becoming infeasible to experiment in chem. Instead, we need to resort to simultion. This means serious mathematics, physics, quantum chemistry, programming, and so on. Just look at people like George Church, Tom Knight, Doudna, Zhang, and anyone else dealing in gene editing and is actually good at it....Look at anyone that does real science and you'll see what I mean. Chem chem chem chem chem....all in their history. Yet, you make it seem like we just need a few chapters of Bruce Alberts and a little bit of equipment.
Eric Drexler wrote on this dilemma a bit: https://web.archive.org/web/20120203080103/http://metamodern.com/2009/05/27/how-to-learn-about-everything/
This isn't a world for specialists. You need to study....a lot. Jack of all trades, master of all trades. One these trades is chemistry and you seem to think you can dance around it, when you yourself didn't. You studied chemistry. For those reading this worthless comment and don't know, Biophysics (which is what Zayner has a degree in) overlaps physical chemistry and biochemistry — both of which are considered advanced chemistry that you can't do without a solid background in mathematics and organic chemistry.
Instead of selling kits to make people believe they can do anything meaningful, you should maybe consider being truthful. You need serious chem. Perhaps make chemistry kits that compliment your gene editing kits.