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Biohacking


I have an opinion piece on Biohacking coming out in the upcoming print edition of Comstock’s Magazine. As a scientist, I like things to be referenced and annotated, so here is my effort to support the claims and information included in the piece.

  • Good intro to garage  biohacking with Josiah Zayner : Link
  • Article on Liz Parrish and her telomere self-experiment: Link
  • Article on Brian Hanley and his personal gene therapy work: Link
  • Article in Outside Magazine on Josiah Zayner with the FBI interview and comment: Link
  • Self-administration of a HIV therapy on a home couch, while live-streaming on Facebook: Link
  • Companies are offering RFID implant chips to their employees: Link
  • The Open Discovery Institute, aka The Odin, DIY Bacterial Gene Engineering CRISPR Kit: Link
  • Makerspaces that offer science classes and lab equipment for community based projects:
    Oakland, Counter Culture Labs
    Seattle, Sound Bio
    New York, Genspace
    Los Angeles, The Lab
    A more complete list can be found over at DIYbio.org
  • Article on the rising cost of prescription drugs: Link
  • An article on biohackers responding to the rising price of the EpiPen: Link
  • The Four Thieves Vinegar Collective that is behind the EpiPencil, Daraprim synthesis, and is currently working on an at-home mini chemical reactor. Link
  • A project to combat the high price of insulin: Link
  • The Sacramento startup and science scene:
    Hackerlab
    UC Davis Venture Catalyst
    HM Clause / UC Davis Life Science Innovation Center
    Inventopia

As for a biohacking scene in Sacramento, there are currently two good resources for fledgling biotechs to get shared lab space with the HM Clause Innovation center and Inventopia, both linked above. But for hacking together ideas, teaching classes, or playing with DNA, Eric Ullrich over at Hackerlab has expressed interest in facilitating biohacking classes and even setup of some wet lab space. There is definitely energy around the idea in Sacramento, but it has yet to reach critical mass. The opinion piece in Comstock’s was intended to share the topic of biohacking with the broader business community in our region, but also to send up a flare to any other scientists that are interested in getting something going.

So if you are interested in setting up local biohacking meetings or joining up for some projects, shoot me an email over at biohacksac.org. Let’s make something happen!

-BZ

Death Valley to White Mountain 2017

I like to surround myself with people who push me. I also like friends that make me want to be a better person. Recently I had the chance to join an adventure that would surely push me, and I would be surrounded by good friends. And if we pulled it off, it would be a memorable trip…

The idea: To ride a bike from the lowest point in California, to the highest peak that you could ride a bike. Starting from -285′ below sea level at Badwater Basin in Death Valley, and riding to 14,252′ at the top of White Mountain some 210 miles away. It would be a total elevation change of 14,537′ with a total ascent of over 22,000′. On top of that, the best window to make the summit called for doing the ride in under 24 hours, or we would be coming down the mountain in the dark. The plan was ambitious to say the least, but my friend Jeremy was up for the task. Having recently completed the Death Ride and a Double Century in 100+F heat, if anyone could do it then he could. At 190 pounds, I’m not a stellar climber on the bike. But I was excited to join the adventure to support him however possible.

Planning: September was the optimal month for the trip, as the high temperatures in Death Valley were bearable, but it is also before the snows begin on White Mountain. We picked a date that we were both available, and put it on the calendar. I rounded up an old buddy that was my wheelman during grad school,knowing that he is always up for a challenge. I also convinced my new colleague that it would be an epic weekend of bikes and the beautiful Eastern Sierras.

As the date approached we closely watched the weather. The high temperature in Death Valley was only 100F, which was pleasant compared to the 120F just a few weeks earlier. And despite a chance of some flurries on the mountain, the weather looked solid. We borrowed a Sprinter van / RV to act as the sag wagon for most of the trip, and I set up my Sportwagen with 4 bike racks to get us up the gravel road to the summit gate, and back again.

The date arrived, and we were off.

Our start in Badwater was uneventful, and the heat wasn’t as bad as we thought it would be. I rode with Jeremy for the first 17 miles, as we snapped a number of selfies and took in the beautiful landscape of Death Valley.

We started around 6:00PM, and what happened in the next 12 hours was somewhat of a blur. For the flat sections, Dave and I traded off accompanying Jeremy for mental and physical support. Tyrel hopped on his mountain bike and rode with Jeremy for a questionable descent in the middle of the night.

Lights, cameras, action! Descending the big hill in Death Valley in the middle of the night.

Otherwise we tried rotating through the riding, driving, and sleeping duties as best we could. I recall driving ahead of the riders into Independence, CA, where I found a place to park that they could see the van. Then I was sleeping in the front seat of the sprinter van, only to be woken up by the voices of Jeremy and Dave. In a total brain fog, I hurriedly gathered my cycling helmet and gear and got on my bike for the next leg. Riding through the night was brutal, but quite an experience.

At a casino truckstop just before sunrise. Somewhere between Keeler and Big Pine CA.

As we rode the 80 relatively flat miles from Keeler to Big Pine, a headwind seemed to keep our speedometers at 14mph. We kept thinking that “this was supposed to be the easy section!”, but we soldiered on. Once we hit Big Pine, we picked up the second car and headed into the hills. Jeremy rode solo up into the hills, and we leapfrogged with the cars to try and give him aid stations and support along the way.

The views from White Mountain were spectacular.

In seemingly no time at all, we made it to the Ancient Bristlecone Pine Forest, or the end of the pavement on our journey. Jeremy had rocketed up the hills, a sign that he was feeling good and pushing on. At this point there was 18 miles of a dirt/gravel road, and then the final 7 miles beyond the gate and up to the summit. Tyrel only has a mountain bike, so having only done the big mid-night descent, he had fresh legs and was ready to ride.

Dave doing his best photographer impersonation while we waited for Jeremy and Tyrel to climb the hills.

The 18 miles of dirt road was challenging, and the 20 hours of riding was taking a toll on Jeremy. We kept offering food and beverage options to him, but it was clear that he was struggling to eat enough. We pushed on, and eventually made it to the gate.

Link: An amazing view from one of the ridges leading up to the White Mountain summit.

Energized by being only 7 miles away from the summit, we had to give it a shot. For the final summit push, all four of us would ride our mountain bikes up the rough and rocky trail. Having to leave the car behind at the gate, we also had to be self-sufficient with our food, water, winter clothing, emergency supplies, and lights for possibly descending in the dark. I bundled up, threw on my backback of gear, and we headed up the mountain.

Jeremy and Tyrel were riding surprisingly well, and they were up around the corner from Dave and I. When we turned the corner, we saw Jeremy on the ground and just knew that something wasn’t right. He was falling apart, and to use the athlete’s term, he had “bonked.” I tried getting him some food, anything that sounded good to him. A fig bar and some gatorade. I was hoping that he just needed a pick-me-up and we could continue on. After a few minutes it seemed to be working, and we decided to walk our bikes up to the next level spot up the trail. We had come so far, and the summit was so close, but we all knew that it wasn’t worth risking our safety or our lives for the trip.

The question that decided our fate: “If you push to the top, are you going to be able to make it back down?”  Any answer other than yes was not acceptable. After a hesitation, we decided to turn back.  We took pictures, we shook hands, hugged, and cried. It had been such a long journey with very little sleep, we were looking forward to getting off the mountain in the daylight and getting a good meal.

Calling it with 1500′ to go. Taking pictures and saying goodbye to the summit.

Getting off the mountain ended up being a shenanigan with the Sportwagen, loaded up with four guys, bikes, gear, and a really terrible road. The poor clearance was one issue, but the road was so terrible that it was rocking the bikes on the top of the car so badly that we broke t-slot bolt and a couple of bikes came loose. This made the drive back to the Ancient Bristlecone Pine Forest parking lot quite sketchy and memorable…

We will go back. Maybe not for a solo attempt, but definitely for a team relay event where we all contribute to the early miles, and then all ride together to the summit. I started out not knowing anything about White Mountain, and now I have an intense desire to go back and finish what we started.

-BZ

You are what you read


A 45 minute commute in each direction can be a major time sink each day. I have gone through a number of phases, first using the time to listen to the news. That got repetitive in a hurry and was a huge downer. Then I tried using the time to make calls, for both work and personal items- but I ended up needing a little more time to decompress before reaching home. Over the last couple of years I have settled into a nice routine of listening to audio books on my commute, and I wish I had discovered them sooner.

I’m not sure if it counts as “reading” from the literal sense of the word, but “listening” doesn’t have the same ring to it. I subscribe to Audible, so I get one audio book per month. I tend to supplement with additional credits every now and then, so I’m averaging a book every few weeks. With two young kids, working at a startup and a 1.5 hour total commute, and also trying to fit in exercise, I’m happy to be reading anything at all!

I love the smell of old books. The plant is like a visitor to a mausoleum…

I keep track of what I have been reading over on My Bookshelf. I know there are apps/services like Good Reads, or other places to keep track and share books on social media. I think that is great for people that want to share with their friends and family, but I see my bookshelf as an extension of my education, so I proudly display my books as a mark of what I’m reading with the broader public. “You are what you read”, said Oscar Wilde (attributed).

I tend to gravitate towards business and science, but there are some clear deviations in my list. I am always looking for good books to liven my commute, so if you have a good recommendation, please share!

-BZ

Cannabis sativa

I work on cannabis.

As a PhD biochemist and former cancer researcher, it feels a little dirty to admit. But let me explain…

I love plants. My favorite plant is Sarcodes sanguinea, a native of the high Sierras that is a brilliant red hue because it lost it’s chlorophyll and parasitizes fungi for food:

A fabulous Sarcodes seen while riding my cyclocross bike on the East side of Lake Davis before the Lost and Found Gravel Grinder, June 2017.

I planted lemon, lime, fig, pomegranate, olive, pear, and apple trees in my back yard. I also have a rockin’ garden, and I love teaching my kids where their food comes from:

My main garden in full force, June 2017.

I also have a soft spot for interesting plant chemistries. While at U.C. Davis I worked with antioxidants produced from broccoli and other cruciferous vegetables. I have worked with the biochemical pathways producing the stevia sweetener, and contrast that with working on the genetics of noxious plants that are toxic to humans.

I am an  endurance athlete, and I like to cycle or trail run for hours. Mostly from the health benefits, but I do enjoy the endorphin rush from an epic workout. I’m generally risk-averse, and I’m an Eagle Scout in most senses of the stereotype.

But I work on cannabis. Or more specifically, cannabinoids that originate from the cannabis plant.

Cannabis sativa. Pot. Weed. Marijuana. Ganja. Reefer. (Insert your favorite slang here). Yeah, that cannabis.

It is weird to me how some people think that I am part of a counter-culture movement full of pot-smoking hippies (or whatever the equivalent is for the millenial generation – pot smoking, avocado-toast-eating, millenials?). In actuality, we are a bunch of over-educated, lab-coat clad nerds, drinking coffee and geeking out about the amazing chemistry of cannabinoids and the corresponding human cannabinoid receptor system.

Nerds!!!

As Alexander Shulgin wrote in PiHKAL, “Among the drugs that are currently illegal, I have chosen not to use marijuana, as I feel the light-headed intoxication, and benign alteration of consciousness does not adequately compensate for an uncomfortable feeling that I am wasting time.”

None of us partake in cannabis for recreational or medicinal uses, and whenever a question on human use comes up- we are forced to consult Google to learn about typical usage and exposures. I personally, and our startup are fully compliant with all state and federal regulations, and we have all necessary approvals to perform our research. When it comes down to it, we are just doing science. Some plant biochemistry, some mammalian receptor biology. But our work could have an impact on inflammatory bowel disorders, colon cancer, and some other potential applications that could be pretty damn cool.

A friend from grad school was concerned that by researching cannabis, I may be a marked scientist- unable to rejoin the ranks of the normal scientists hard at work on cancer, neurobiology, and other respectable areas of study. I completely disagree. What I have found is that the cannabinoid and cannabinoid-receptor research field has been stifled by undue regulatory pressure for so many years, so instead of being a dead-end for science, it is ripe for discovery.

Pharmacological uses of non-psychotropic cannabinoids

The cannabinoid receptor is the most abundant G-protein coupled receptor in the brain, hence, people get really high with THC exposure (an agonist). CBD on the other hand is an inverse-agonist, so it has somewhat of an opposite effect on our receptors and doesn’t get people “high”. It is on the fast-track to be approved for treatment of specific epilepsy subtypes, is in multiple clinical studies for schizophrenia, and has tremendous potential as an anti-inflammatory. So the pharmaceutical applications are real, and have even been vetted by the Food and Drug Administration.

Cannabinoid receptors are also found throughout the body, and to use the “lock and key” analogy for enzymes- we have discovered locked doors throughout the body- now we just need to figure out the keys, and what doors we can open with this new knowledge. The therapeutic  potential for cannabinoids is unmistakable. I look forward to seeing what doors we can open with our work.

-BZ

Paella!

I fell in love with paella on my honeymoon in Barcelona. Eating fresh seafood on the coast or eating a mixta style further inland, the versatility of the dish and ability to improvise with ingredients is fun and artful. And of course the beautiful presentation of the delicious shrimp, chorizo, chicken, calimari, mussels, clams, all placed neatly in a bed of golden saffron rice is both functionally and aesthetically beautiful! My wife gave me a paella pan a couple years ago, and we have been experimenting ever since. First paella was on the stove. Then multiple paellas on the charcoal BBQ. Some temperamental charcoal caused one paella to burn on the bottom and remain undercooked on top, so my wife got me a 2-ring propane burner that would accommodate our 40cm and our 55cm paella pans. Since receiving the burner, making paella has been far more predictable and enjoyable. I have been meaning to document one of my paella recipes, and finally I took the time to carefully measure and keep track of my steps. In addition with sharing my recipe, I now have a grocery list for future paellas!

20170121_190511

20170121 paella for 4 (with plenty of leftovers!):
Based on the mixta paella recipe in La Paella

In Stockpot:
1lb clams simmered 30′ in 5c h2o

In saute pan:
0.5lb mussels simmered 5′ in .33c h2o

In 55cm pan over medium burner:
Olive oil as needed
1lb boneless chicken thighs, fat trimmed, salt and peppered, par cooked and set aside.

1 onion diced
1 red pepper diced – cook down with onion
14.5oz can diced roasted tomatoes
11oz chorizo sliced
3c paella rice (Matiz black label)
0.5tsp sweet pimenton, 0.5t spicy pimenton
0.5t saffron
1.5c peas
5c stock from simmered clams
0.33c stock from mussels
3c chicken stock
20 ish shrimp, quick sear on one side, placed around edge in rice/broth
.4lb squid cut to rings, quick fry and placed across the top

Cook until rice is done, cover with foil and let rest 5 minutes. Serve and enjoy!

A few notes:
The 55cm pan can handle way more volume than this, but I would rather go low on the big pan than overload the smaller pan. Also I sparingly add mussels. I prefer the clams, shrimp, and the Spanish chorizo, but that’s just my taste. And don’t drink too many beers or rioja while making la paella- that can complicate things in a hurry!

-BZ

Best Biochemists in Movies

I don’t know of many movies that actually portray a biochemist, but there are a handful out there. In most of them, the biochemist is somewhat dorky, but either hardens up and uses a gun, or gets thrown in prison for embezzlement and lying to the FBI. These are my personal favorites:

1. Nicolas Cage as Stanley Goodspeed in The Rock.

Stanley Goodspeed

“Listen, I’m just a bio-chemist. Most of the time I work in a glass jar and lead a very uneventful life. I drive a Volvo. A beige one. But what I’m dealing with here, is one of the deadliest substances the earth has ever known so whaddaya say you cut me some friggin’ slack?”

My personal favorite, especially the quote about biochemists being boring and driving beige volvos.

2. Matt Damon as Marc Whitacre in The Informant.

Marc Whitacre

“Archer Daniels Midland. Most people have never head of us, but chances are, they’ve never had a meal we’re not a part of. Just read the side of the package. That’s us. Now ADM is taking dextrose from the corn and turning it into an amino acid called lysine. It’s all very scientific, but if you’re a stockholder, all that matters is corn goes in one end and profit comes out the other.”

A quirky movie about the real life Marc Whitacre (Nutritional Biochemistry PhD) who exposed price fixing at ADM, but also got caught embezzling from the company and thrown in prison. After serving 8 years, Whitacre is now out and serving as COO of a company in California.

I love his inner monologue. It reminds me of my own inner monologue…

3. Rachel Weisz as Marta Shearing in the Bourne Legacy.

Marta Shearing

“Well, if you’re going to reprogram human genetic material, you need a delivery system, and nothing works better than virus. It’s like a suitcase.”

Dr. Marta Shearing is a biochemist involved in hacking Jason Bourne’s metabolism, requiring him and the other covert operatives to take a special nutrient pill or their body will shut down.  A built in self-destruct of sorts. Thinking about this approach in real life- knock out a gene involved in a core metabolic pathway, and then supplement the final metabolite of that pathway. Feasible on the surface, and a virus would be the best way to do it. Hmm…

Startup Quotations

A fun image borrowed from yhponline.com on their UK Startups page

As I approach my fourth year of grinding it out in a startup biotech, I thought I would collect my favorite quotations of startups and productivity. As I read more about business and startups I keep finding new quotes that encapsulate the feeling of a startup, so I hope to add to this list as time goes on.

Move fast and break things. (attributed to Facebook, and humorously depicted on XKCD).

A ‘startup’ is a company confused about: 1. what its product is, 2. who its customers are, 3. how to make money.” – Dave McClure of 500 Startups.

The reality is, Silicon Valley capitalism is very simple:
Investors are people with more money than time.
Employees are people with more time than money.
Entrepreneurs are the seductive go-between.
Marketing is like sex: only losers pay for it.” – Antonio Garcia Martinez in Chaos Monkeys: Obscene Fortune and Random Failure in Silicon Valley.

Done is better than perfect. (described as a Facebook slogan in Chaos Monkeys).

A good idea on Monday is better than a great idea on Friday. (not sure where I heard this one).

Build. Measure. Learn. (repeat).  – Eric Ries, The Lean Startup

Startups are an odd creature that I am still working on taming (assuming you can tame it!). The energy and speed are addictive, and despite all of the struggles, I wouldn’t trade it for anything.

-BZ

Turkey Bowl

TB 2016 Logo
Every Thanksgiving our group of old high school buddies gets together and plays mud football. It started out as some good dirty fun playing tackle football on one of a handful of fields in Loomis. After the broken wrist incident of 2005, we switched to flag-football (as shown in the x-ray pictures in the 2006 invite). A few years older, we now live in the suburbs, but we continue our tradition and round up as many of the usual suspects for a game of Turkey Day football.

Here is a collection of the website and video invitations from 2002-2006. They started off as just basic image slideshows, then added in some music in 2004,  and a full blown video in 2005. The image quality started off pretty poor, because half of the pictures are crappy digital pictures of my 35mm prints, and the rest were probably my crappy digital camera in action! At some point we had enough significant others with cameras taking pictures, so the picture quality improved in the later years.

On that note- if you have any pictures from the old Turkey Bowl games, email me and I can share them with everyone.

2002: Turkey Bowl V

2003: Turkey Bowl VI

2004: Turkey Bowl VII (turn up your sound- and ignore the typo…)

2005: Turkey Bowl VIII

(if the video doesn’t embed, just watch it here)

2006: Turkey Bowl IX

This year marks the 19th consecutive year of playing mud football on Thanksgiving morning. It feels like we should definitely do something special for the 20th edition next year, but maybe we can organize something fun for Turkey Bowl XIX. Let me know if you have any thoughts and we can make something happen.

-BZ

The Budget Biotech

The bench beaver is always watching you

I have been toying with the idea of starting my own biotech startup in my garage, and want to determine the lowest amount of upfront investment it would take to set up a functional molecular biology lab.

OK, a little background to help the discussion. Straight out of grad school I took a job with a startup biotech developing strains for fermentation of high value small molecules. When I arrived the lab had a few tables and some basic equipment, but being that an electrical engineer did the initial purchasing it wasn’t quite ready for much biochemistry. So my first job was to outfit the lab with the necessary equipment and consumables to get things moving. I quickly realized how expensive laboratory equipment and research reagents were without the generous academic discounts I had grown accustomed to. We pieced together a mixture of new and used equipment, took advantage of lab startup promotional deals, and ultimately assembled a fully functional molecular biology lab on a pretty modest budget.

Taking what I learned from setting up my first biotech lab, I know I can do better. How much better? I think it should be possible to assemble a functional molecular biology lab for under $1,000. But wait you say- that is just enough to buy a decent set of pipetters- how could you set up an entire lab for that?

Precisely. That is the heart of the challenge. To create a budget-minded biotech that is functional, but doesn’t cost an arm and a leg. As I wrote up in a previous article, “biotech shouldn’t be so dang expensive!”

I think it all depends on how you define the core functionality. To me, the minimum functionality needed is to clone genes and express proteins. I am focusing on the steps from source DNA to expressed recombinant protein. So basically from PCR through cloning in E.coli, to expression of proteins.

Things I am not including in the $1,000: Analytical (in my case HPLC or LCMS), basic infrastructure like tables, stools, computer, etc., and little things like surge protectors or extension cords. And I may take the liberty of culturing my own competent cells to cut down on that cost. Vector backbone will be an open-source design to get around IP conflicts and keep things cheap. We’ll see how far we can stretch $1,000 and go from there.

I am looking mainly at functional but well-loved equipment on ebay and craigslist, and even some homemade or hacked projects capable of carrying out the job at hand. EBay has some amazing deals. So does Amazon (I usually avoid Thermo subsidiaries as much as I avoid Wally World!). And if you are willing to do some soldering, coding, and 3D printing, you can make just about anything in the lab. I acknowledge that reliability will undoubtedly be less than brand new equipment still on warranty, but of the three-legged stool of quality, cost, and time- this exercise is focused primarily on cost.

Here is my initial list of equipment, projected cost, and notes on procurement. Let me know what you think, where you think I can cut the cost down, or if there are any glaring errors in my choices or logic. I plan to revise and post updates to my budget biotech quest, so hopefully this is only the beginning!

-BZ

EQUIPMENT
Item Cost Notes
pcr – thermal cycler $200.00 used… Ebay. Or ghetto fab water bath and servo setup?
gel rig $53.00 kit from iorodeo.com
light box $80.00 mini kit from iorodeo.com or build myself
pipetters $100.00 2 pipettes at 50 each. P20 and P200 to start
water baths $12.99 crock pots with arduino thermostat (DS18B20 and SSR)
-20C freezer / fridge $50.00 total budget – cheap chest – or used on CL
incubator $50.00 Cooler/chest freezer with hairdryer/heatgun heater and extra fan? Or foam insulation box.
autoclave $83.99 pressure cooker- presto on amazon. Ikea?
centrifuge $80.00 used Brinkman on Ebay
flame for plate work $60.00 Ebay flame/regulator kit
Micro scale $25.00 amazon
microwave? $20.00 craigslist
gel power supply $15.00 homebuilt (budget molecular biology power supply)
rotary shaker $140.00 used old NewBrunswick on ebay
pH meter $20.00 Amazon or Ebay
TOTAL EQUIPMENT: $989.98
CONSUMABLES
Item Cost Notes
tips $10.00 Ebay- bulk tips – need upfront tip box
weigh boats $10.00 or papers
DNA stain $68.00 SYBR Safe – cheaper alternatives with blue LED illuminator?
gel buffer TAE homemade
DNA polymerase $39.00 mastermind from geneandcell.com
dNTPs included in mastermind mix
DNA buffer TAE homemade
gel extraction kit NA45 paper? Simple protocol? Kit…
1kb ladder $89.00 geneandcell.com
load dye bromophenol blue
comp cells homemade – but lack of -80 will affect competency
Total Consumables: $216.00
Total Combined: $1,205.98 over budget already! And chemicals not even included yet!

Why Zippypickle?

People have asked me, what’s behind the name Zippypickle? Well, my name is Brandon Zipp, and my friends just call me Zipp. During my freshman year in high school we were at track practice, and I still remember the interaction well. While standing in line waiting to do the long jump, a classmate that I didn’t know asked my name. I said Zipp, and he pondered for a second. He then responded, “I’m going to call you Zippypickle.” I’m not sure where he came up with it, but it was unique and fun. When it came time to register for my first hotmail email address, I tried a few combinations with Brandon and Zipp, but the basic configurations were already taken. So I tried Zippypickle, and poof- it has been my go-to nickname/username since then.

At one point I thought I would start a brewery or a business called Zippypickle, and even sketched out a logo for it. What could be more fitting than a cowboy riding a bucking pickle?

Zippypickle Cowboy

I recall someone saying that a cowboy riding a pickle would be too phallic. Hence the molecule as the logo for the Zippypickle blog…

-BZ

Zippypickle Mini Molecule