Category Archives: Uncategorized

biochemistry, cannabinoid, Startup, Uncategorized

Crohn’s and Colitis

I recently went to an event hosted by the Crohn’s and Colitis Foundation (CCF)’s Northern California chapter. The event was an educational symposium for patients and families with IBD, and I was impressed with the CCF organization as well as the amazing community of patients and caregivers. I want to thank Kayla Kraich for all of her hard work organizing such a nice and welcoming event.

I went to the CCF event to learn more about IBD, and specifically biologic treatments for IBD, their benefits, as well as their limitations. Our startup is developing a new small-molecule treatment of IBD, so I would like to stay on top of the standard of care and see what else is going on in the field.

I grabbed a cup of coffee, sat down, and waited for the talks to start. The people sitting around me all looked like happy and healthy adults leading vibrant lives. The guy in front of me looked about my age, well dressed, clean-cut, and maybe a touch sciencey. I thought, hey, maybe he is another researcher? The first talk focused on biologics for IBD, when they are indicated, pros and cons, etc. At the end of the talk the MD invited up a panel of patients to talk about their experience with biologics. The man in front of me stood up and joined the patient panel. When he shared his story of battling IBD since he was 15, it was eye-opening. I have heard that IBD is one of the most disruptive diseases that can be largely hidden from the outside world.

At the first break, the woman sitting next to me introduced herself. Right after her name, she launched into her history with ulcerative colitis, her multiple surgeries, and how she ultimately tamed her disease with a balance of diet and medications. At the end of her quick life story, she then said, “what about you Brandon?”

I have to admit that I felt like a poser. I don’t have IBD. I haven’t had multiple surgeries. I haven’t seen numerous doctors, received infusions of antibodies, worried about infections from a suppressed immune system. I haven’t struggled to knock down GI flares with steroids, and then dealing with their crazy side effects. Nor have I endured the never-ending visits to the bathroom (a metric for ulcerative colitis activity is the number of daily bowel movements, with the highest tier being anything over 10 times a day).

I told her that I’m just a researcher, but we are working on IBD and have a new drug that we are rapidly advancing to the clinic. She put me at ease with her genuine appreciation for my research, and although I felt insignificant and like I didn’t belong, she welcomed me to the event and wished me the best of luck in our work.

At this point, I may have drank a couple cups of coffee trying to remain alert and sharp during the morning talks, so I made my first trip to the men’s room.

What I encountered in the men’s room was subtle at first, but after recounting the experience and putting it into context with the diseases of the colon, it started to make sense. On my first trip to the men’s room I noticed a number of people coming and going, but the notable interaction was with someone who introduced himself while walking from the urinal to the sinks. The man was very extroverted, and the tone and content of the conversation could have taken place in any setting. Only this time, it was in the men’s room. And that level of forward communication in the men’s room seemed a little odd to me.

Back to the talks, the next speaker gave a nice overview of IBD (the MD and I overlapped as undergrads at UC Davis- go Ags!). After this second talk, my bladder was losing the battle to the coffee and water I was drinking, so I made my second trip to the men’s room. This trip, there was another very genuine introduction and discussion that started in the bathroom. I chatted, and eventually made my way back to the conference room, and didn’t think much of it.

After the talks I headed home, and during the drive I reflected on the great talks and on my interactions with the amazing members of the CCF community. And of course those very genuine interactions that I had in the men’s room…

And then it hit me.

For a patient population that uses the restroom so much, the CCF community is very, very comfortable in the bathroom. Especially at an event filled with fellow patients, doctors, and caregivers, and when it is hard to tell who has what disease, everyone wearing a CCF nametag must seem like an ally. I laughed out loud when I put it together. And then the realization actually felt heavy on my face and my chest. There was a lifelong struggle that was underneath the interactions with the people in the bathroom. I have now attended two CCF events, at which the first item of business was telling everyone the location of the bathrooms. My gastrointestinal health is something I have always taken for granted, but I am now looking at it with a new perspective.

The more that I learn about Crohn’s and Colitis, it just kills me to think of what IBD sufferers are going through. As we are so preoccupied with the pharmacology and interactions of our drug compounds in lab, we don’t often think about of these complications that IBD patients suffer daily. I am extremely grateful for how welcoming and open the CCF community has been with me. It leaves me feeling hungry for our upcoming clinical trials, and it reaffirms that IBD is a worthy cause that I am grateful to be working on.

-BZ

Uncategorized

The Grind

It’s a grind. Grinding it out. The startup grind.

Why does it have to be such a grind?

I’m currently reading Creativity Inc. by Ed Catmull, and it is a great storytelling about the early days and business foundation at Pixar animation studios. I was disturbed by Ed’s recounting of the overlap between their second and third movies, A Bug’s Life and Toy Story 2. It seems that story and production issues required the team to grind out long hours, 7 days a week, for a period of over 6 months. The climax of the story is that Pixar employees were working so hard and so focused on the project, that one morning an employee was supposed to drop his child off at daycare, only to forget and leave the kid in the back seat of the car. The wife also worked at Pixar, so she dropped by her husband’s desk a few hours later and asked “How was dropoff?”, only for the two of them to rush furiously out to the hot car to revive their unconscious child. Fortunately the child survived.

The story resonated with me, as I’m in another period of long days and working on weekends.

Why do we do this to ourselves and to our employees?  Is it the manic personalities of artists, scientists, and creative types?  Is it the culture of startups? Is it the notion of grinding it out in the short term for long term gains? Pay now, play later?

This topic has come up multiple times in the past week on my Twitter and LinkedIn feeds. It also reminds me of an article Dan Lyons wrote for the New York Times about “hustle” in Silicon Valley.

It is clear there is a problem. But what are possible solutions?

If there is a tremendous amount of work volume and a hard deadline, why overburden employees rather than bring on additional help? In a startup, and definitely in science, there are squishy deadlines and moving targets. It can be hard to justify staffing up if the finish line is constantly in question. But for Pixar it seemed like there was a hard deadline, and they had just experience tremendous success with Toy Story 1. What gives Ed?

Another way to confront the grind is reigning in over-workers. I have seen multiple articles about strictly adhering to a 9 to 5, or maintaining reasonable hours and prioritizing balance. The common theme is that employees are better rested and more “balanced” and thus will be better workers for the time they are at work. It sounds so simple in theory, but in practice when it is 5:15pm and there is still a mountain of work to do (and you have a crazy work ethic), it is hard to leave things unfinished. It is also hard to leave when your team is still there and working. This is not borne out of one-upsmanship, but more because of team/staff solidarity and wanting to support the team and the bigger mission.

Another option is to leave the startup world entirely, and retreat to a big established incumbent. But that would mean giving up the richness and breadth of experience that comes with a role at a startup.

If Ed Catmull at a fledgling Pixar couldn’t figure out how to prevent the grind, then I can’t feel too bad for struggling with it myself.

Grind on.

biochemistry, Biohacking, GarageBio, Hacking, Proteins, Uncategorized

Biohacking


I have an opinion piece on Biohacking in the Innovation 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

Uncategorized

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

biochemistry, cannabinoid, Proteins, Startup, Uncategorized

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

Uncategorized

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

Arduino, Fermentation, GarageBio, Hacking, Startup, Uncategorized

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!
Uncategorized

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

Arduino, Fermentation, Hacking, Proteins, Uncategorized

Builds I’ll get to eventually

So I’m swamped with work right now, but I have a number of projects that I want to write up and share. For now I’ll just show some of my old pictures and give a quick overview, and hopefully it motivates me to finish everything. Hopefully…

Mini bioreactor controller
Arduino controlled peristaltic pumps via relays with 20x4 LCD
I tried making a mini bioreactor unit to support smaller spinflasks with feeding and to operate the mini flowcell spectrophotometer, and got it to work decently well. There were two peristaltic pumps from Adafruit, a 20×4 LCD to show the time and culture status info, and some buttons for manual advance of the pumps.

Temp display and datalogger
High temperature display and SD datalogger
To monitor vessel temperature while running processes, I used a DS18B20 digital temp sensor with my perma/proto Uno. I now use Arduino pro mini’s for my embedded projects, but back then I didn’t know what was up.

Millisecond light timer switch
arduino, ds1307 RTC module, and relays to switch things quickly
I did a project that required turning a light on for one second every 24 hours. Conventional analog light timers give you half hour resolution, and some digital light timers can get down to the minute. We needed seconds, so I turned to an arduino with a DS1307 real time clock module to keep time, and relays to handle the heavy lifting.

Light sensor and datalogger
photoresistors via arduino to micro sd datalog
To make sure I was switching the lights at the correct time and duration, I used a different arduino to measure the light levels and datalog them to a micro SD card on an ethernet shield. Photoresistors, arduino, sd card. Boom.

Bioreactor datalogging and sending to the cloud
BioFlo 3000 arduino connection
Old bioreactors are cheap and capable, but they’re not very digitally advanced. But the old data access ports can be tapped into for datalogging and triggering alarms through an arduino. This is a custom cable with Cat5 cable soldered to a 9 pin din connector to a New Brunswick BioFlo 3000 bioreactor. Different iterations had different capabilities, but pulling the data off the machine and either datalogging, or uploading the data to an M2X server, or email alerts were used for different experiments.

3D printed protein crystal structure models
3D protein model crystal structure
I know it has been done before, but I had to include a picture of my 3D printed protein model. They are just too cool!

I’ll try to sit down one of these days and start to write things up, but if there is something you want more information about, email me or leave a message in the comments section!

-BZ