Jan. 8, 2017, 7:58 p.m.

Eligo Bioscience: Guardian of Your Secret World, the Microbiome

If you ask the average person what they know about the human microbiome, they probably won’t have much to tell you. You can’t blame them though, as can be seen from the figure below, the number of scientific papers on the microbiome has surged only recently.

So what exactly is the human microbiome? The human microbiome is a collection of microorganisms - bacteria, viruses, fungi and archaea throughout the human body. They’re on your skin, in your lungs, and in your gut. The bacteria, which have been the main focus so far of human microbiome research, can be further subdivided into three categories: commensal, symbiotic and pathogenic. Commensal bacteria are bacteria that benefit from the human body but offer no benefit to us. Symbiotic bacteria benefit from living inside of us and are good for our health. Pathogenic bacteria are those that are capable of causing disease. With these three types taken together, a crude estimate is that there are 10 trillions of these microorganisms in your body, meaning there are 10x more of these microorganisms than there are human cells. The bacteria living in the microbiome protect us from harm by boosting our immune system, while also being the cause of inflammation, tuberculosis and pneumonia.

One of the main things that held microbiome research back several years ago was the high cost of DNA sequencing. As the cost of sequencing decreased, there was an increase of data mining activity to better understand the genomic composition of the microbiome. The end result was larger datasets that researchers could use to extrapolate results from and publish papers with. Unfortunately since this is still a nascent field, there is a lot of room for improvement. Primarily the lack of reproducible papers and discrepancies from diagnostics companies means standards must be set in place for research to be more impactful.

I had a chance to talk with Xavier Duportet, the CEO of Eligo Bioscience a company on the frontier of helping protect our microbiome from pathogenic bacteria. Duportet, who earned his PhD in Synthetic Biology while at INRIA and MIT has raised $3 million so far to help treat and sculpt the microbiome. His company’s thesis is that our current approach with antibiotics is a crude method that can cause unintended, dangerous consequences and that a more elegant solution is needed.

The response from the company is to use a synthetic biology platform that combines a nuclease (i.e. CRISPR/Cas system) with protein-based nano-delivery vectors (engineered phage capsids) to develop what they’ve dubbed “eligobiotics”, a new generation of highly precise anti microbials. As opposed to antibiotics which destroy bacteria regardless of whether they are symbiotic or pathogenic, eligobiotics can be programmed to eliminate bacteria based on their genetic sequence. This precision is similar to having a poison that only wipes out a small part of the bacterial population, as opposed to antibiotics, which not only wipe out pathogenic bacteria but also harms symbiotic bacteria essential for your health.

If Eligo prove themselves in clinical trials, it’ll be as important as the discovery of Penicillin - Christian Brechot, President of Pasteur Institute
Duportet shared his enthusiasm for the new technology being developed at Eligo Bioscience, which has been published in major peer-reviewed journals (Nature Biotechnology) and which has already been shown to efficiently and precisely eradicate highly pathogenic and antibiotic-resistant Staphylococcus aureus and Escherichia coli bacteria. Early research has shown that eligobiotics work in petri dishes and also in more complex animal models, which gives serious hopes for future development.

Duportet explained to me that his company, like many biotech companies, started with a research paper and the support of professors. In fact when Duportet brought the results of the Rockefeller team with whom he was working with to a close professor at MIT working next door to his lab, they realized that they happened to both be working on similar technologies, and as a result decided to join forces. The Paris-based company, which has attracted other scientists from MIT, Stanford, Inserm and Institut Pasteur, as well as former executives from large big pharma, is now about to raise their Series A round. Their goal is to push the technology to the clinic and test it in humans in the next two years. Duportet hopes to first create efficient and targeted therapies to treat highly deadly bacterial diseases in children and elderly people, and then later on focus on targeting more complex diseases that are beginning to be associated with the microbiome.

For a long time, the scientific community has for a long time been warning the world of “superbugs”, bacteria that have developed a resistance to our antibiotics. The rise of “superbugs” is indeed becoming one of the most worrying threats for the population globally, with worrisome predictions from the World Health Organization that infections caused by antibiotic resistant bacteria will be the main cause of deaths in 2050, with more than 10 million people dying from antibiotic resistant infections per year.

While the path to regulatory approval for drugs is a long one, Duportet is confident that the company’s highly precise antimicrobials will be pivotal not only in battling “superbugs”, but also by helping keep our microbiome healthy.

This post originally appeared in: https://www.huffingtonpost.com/entry/eligo-guardian-of-your-secret-world-the-microbiome_us_586d6cbbe4b021b75256f047

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Nov. 26, 2016, 7:53 p.m.

Exploring The Tactics of Scientific Peak Performer Patrick David Hsu

Patrick David Hsu isn’t your regular 24 year old. While completing his graduate studies at Harvard, he contributed to the revolutionary CRISPR technology, improving the efficiency and accuracy of gene editing technologies significantly. This feat earned him a PhD and a spot on the Forbes 30 Under 30 list at the ripe age of 22. He holds multiple patents, with patents pending related to CRISPR and was awarded $1M for his research through the prestigious National Institute of Health Director’s Early Independence Award. He now runs his own lab as a principal investigator in the Molecular and Cellular Biology Laboratory at the Salk Institute for Biological Studies where his lab focuses on finding treatments for neurodegenerative diseases and complex genetic disorders.

So how exactly was Patrick able to accomplish so much at an age when most people are still struggling to pay off their student debt? I had a chance to sit down with him at the Hello Tomorrow Summit in Paris to uncover actionable insights that others can emulate.

Develop Superior Pattern Matching Capabilities

As Isaac Newton famously once said “If I have seen further than others, it is by standing upon the shoulders of giants.” To be able to achieve any significant breakthroughs one must first learn the fundamentals from the giants of that field. In Patrick’s case, this meant diligently learning and pursuing his undergraduate studies at UC Berkeley and then his graduate work at Harvard. Here he was exposed to a variety of prolific thinkers within the field of biology ranging from the researchers who discovered the double helix in DNA (Watson & Crick) to the man who shocked the world by proposing the once radical Theory of Evolution (Charles Darwin). Even when he contemplated leaving his PhD program to become a software engineer, he relented when he realized just how much more he still needed to learn.

“Biology is essentially a huge exercise in pattern matching” - Patrick David Hsu
The whole idea behind building superior pattern matching capabilities relies on two things: rapidly synthesizing information and finding patterns from the set of your current knowledge. Through his early career as a researcher, Patrick was able to develop the skill of sifting through vast amounts of information and identifying the key points necessary for a research paper for publication. The actual ability to recognize patterns comes down to sheer perseverance and force of will. Very rarely was Patrick able to find the right pattern on the first try. It was more important to be able to learn from his failures and adjust the patterns he was looking for up until that pivotal breakthrough.

While not everyone is working on breakthrough biological concepts, the idea of pattern matching applies to just about every field. Want to turn that lead into a sale? Better learn how to emulate the pattern that increases your closing rate. Want to finish writing that book? Why not start by synthesizing information from other great authors, and then use those tried and true patterns to fuel your own artistic breakthrough.

Learn Through Osmosis

The hollywood myth of the lone scientist working on their projects in the secrecy of their garage is just that - a hollywood myth. In Patrick’s case, a huge catalyst for his current level of success was being in an intellectual environment that brought the best out of him. For example his PhD advisor, Feng, was able to impart the importance of an elegant idea that could then be demonstrated in the laboratory. It wasn’t something that was taught in a lecture, instead it was something Patrick was able to observe through continuous exposure to a brilliant mind.

“Sharing is something that people don’t talk about enough, it dramatically sped up CRISPR adoption.” - Patrick David Hsu speaking to MIT Technology Review.

By surrounding yourself with others who are smarter than you, you open yourself up to gather additional data points that you otherwise would have ignored or missed. A casual water cooler conversation or joke may turn into a profound insight in the right context. Implicit in this advice is that if you’re the dumbest person in the room, as Patrick tries to be, then you must be able to pause and listen. Staying humble and realizing that you know very little, is yet another way to increase your rate of knowledge acquisition as you expose yourself to those smarter than yourself.

Drain the Shallows

In an era of always being connected, perhaps the best strategy to take is one where you aren’t connected at all. Patrick, along with Cal Newport, the author of Deep Work and professor of distributed algorithms at Georgetown university, both espouse the importance of being unplugged and free from distractions. In our conversation Patrick reminisced of the days when we all had flip phones, and didn’t have the allure of a Facebook or Snapchat notification to tug at our attention.

Research by Foroughi et al backs up Patrick’s assertion that letting distractions dominate our lives will ultimately lead to work that’s lower quality. Patrick himself tries to avoid the mentally dead state of scrolling through a Facebook or Instagram feed as a result of checking notifications as much as possible - comparing it to mindlessly watching cartoons as a kid. Instead he prefers to focus on intent, engaging in a variety of activities, whether it’s learning a new dance move, contemplating Hegel or building tools to combat Alzheimer’s.

Anders Ericson in his bestselling book, Peak Performance, makes the argument that the path to becoming a peak performer comes down to deliberate practice for extended periods of time. As much as we’d like to believe the idea of a genetically gifted individual being able to achieve everything effortlessly, it ultimately comes down to hard work and sacrifices. To be able to implement the three pieces of advice Patrick offers us, it will take a degree of discipline and commitment that not many of us are willing to take on. We say we want to become a published author, a successful business owner, or late night comedian, but how many of us are actually willing to put in the grueling hours it takes to become an expert at our craft?

Without a doubt, Patrick’s performance thus far is remarkable and yet at the end of the day it all came down to his determination and perseverance to conquer topics that frustrated and dissuaded others his age. In an age where few can focus on one task for more than 30 minutes without the hit of dopamine that comes from looking at their notifications, Patrick serves as a shining example of what can be possible if you dedicate yourself to the pursuit of excellence in a field of your choosing.

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March 29, 2016, 7:50 p.m.

How To Avoid Hiring The Wrong Person

Co-authored with Cooper Harris

Hiring your first few employees can often be as hard as choosing your co-founders. Especially in the early days of your startup, when you’re often only months from running out of money, hiring the wrong person can be disastrous.

Yet it’s hard to accurately vet potential candidates. Cold job interviews can be an unreliable litmus test for hiring. Even the traditional green-light for someone who’s graduated from an Ivy league school has been proven more noise than signal. And if, like us, you spend the first six months of your startup under a rock, your social capital may begin to dry up.

So with no real barometer for reliable talent, and a fast-evaporating social network, where should early founders snag that elusive star talent?

Below we’ll outline how to squeeze those last drops of talent out of your own social circles, how to incentivize current employees to lure in potential candidates in their networks, and how to entice “super-connectors” to recruit through their own far-reaching nets. Together, these methods can be an incredibly effective hiring practice -- a comprehensive employee-referral-engine as good as any high-level recruiter.

To do this, you’ll want to tap into your own network, your employees’ network, and a super connectors’ network.

Tap Into Your Network

Your friends are often the best source of early hires. Pitching one or two of your smartest friends and getting them to join your startup (or at least champion it) is crucial in those early days when nobody talented wants to join a no-name fledgling company with little to no funding. But how do you go about pitching your friends?

First, figure out what motivates them. Would they buy into your vision for the company or are they interested in progressing their career? Customize your pitch for them.

Next , figure out a venue for the pitch. Do you bring it up at a bar you often frequent, a nice restaurant, or at a shooting range? Find the one that suits your friend the best.

Finally, when pitching, be sure to communicate the excitement and vision you have for the company while also giving the person an easy out if they need it. It may be the case that the engineer friend of yours at SpaceX won’t be able to join simply because she’s supporting her parents back home. Too much pressure may put pressure on your friendship.

Tap Into Your Employees’ Networks

Companies such as Microsoft, Facebook and Google have all established employee referral programs that give employees monetary rewards for referring friends who get hired. Why?

Smart people know other smart people. If you hired an outstanding front-end software engineer, chances are they are friends with other outstanding software developers. If you ask most startups whom they hired for their first employees, it's almost never a stranger. Most often, it's their college roommate, next door neighbor or best friend’s boyfriend from high school. In order to capitalize on this potential talent pool, it's important for a company to establish a culture of friend referrals.

First, communicate with the team the type of candidate you're hiring, the skills you're looking for, and the bonus you'll give if a referral is hired. Then make sure your employees have the information they need to talk about your company's impact and answer any friends' questions. Finally, providing the employee with a flex budget of even $500 a month will allow them to wine and dine potential candidates without worrying about paying for meals themselves.

Tap Into Superconnectors’ Networks

So what exactly is a superconnector, and why are they so important? A superconnector is someone who has an abundant network comprised of many weak ties. These people might be reporters, authors, VCs, philanthropists or board members of Fortune 500 companies.

But oftentimes, due to their large network, superconnectors are overwhelmed with opportunities. That’s why it's important to figure out how you can align both your objectives so they get value from helping you. Perhaps they’re incentivized by profit, and offering advisory shares or consultant fees would entice them to help your startup. More likely, the company is building something the superconnector is passionate about and involving them as a mentor would excite them.

The question remains: where do you find these superconnectors if you have none in your network? We reached out to our friend, No. 1 superconnector guru Keith Ferrazzi. Keith, best-selling author of "Never Eat Alone" and "Who’s Got Your Back," offered this advice:

“Conferences are always a great place to start, if you do your research. Know who's attending and how you can be of service to them, then create your own event [during the conference]. I like to schedule my own dinner and invite people I'd like to bring into my network to get to know them on a personal basis. Invite good friends and a few weak ties and encourage them to bring a guest. But keep it relatively small – whatever size you can manage so everyone can interact but not feel overwhelmed.”

The early hires you make at your company will set its cultural DNA for years to come and set you on a quick path to success or failure. By hiring people who’ve been vetted by you or people in your network, you’re able to ensure you’re hiring the best. So what are you waiting for? Call up that Facebook engineer you went to middle school with and see if she wants a job.

Andrei Lyskov, a business development associate at Soylent, also contributed to this article.

Originally appeared in https://www.forbes.com/sites/theyec/2016/03/29/how-to-avoid-hiring-the-wrong-person/3/#575b865c379a

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Nov. 5, 2015, 7:55 p.m.

Don't Sell Your Soul: "Valuation Has No Effect on Your Company," insists Jason Fried of Basecamp

“I’ve seen peoples ego’s destroy lives," said Jason Fried of Basecamp, "this desire to be something they can’t be or someone they’re not, or acquire something they don’t have," in a conversation with Derek Andersen at the Startup Grind Conference, and in a follow-up interview.

In an environment where startups are being assessed not on the soundness of their business but on the amounts they've raised in venture capital or how quickly they liquidate their assets through an acquisition or IPO, Silicon Valley founders have grown equally egos proportionate to their inflated valuations, suggests Freid. “Very few companies actually need to raise venture funding," he insisted, especially when “a valuation has no effect on you or your company."

The co-founder and president of Basecamp, Freid's company boasts over 15 million users - all without accepting venture money - except for a "contribution" made by Amazon's Jeff Bezos, that is. Basecamp's pride and claim to fame is its culture: employees have created a work-life balance with perks like monthlong sabbaticals, four day work weeks and vacations that are completely paid for by the company.

Fried used his time on the Startup Grind stage to inject some reality into the Silicon Valley bubble, urging founders to let go of the ego-driven fundraising culture, and to build sustainable, profitable businesses instead. Fried believes that by not accepting any money from venture capitalists, he’s been able to preserve his companies culture and build a personal life worth living. It's that what it's all about?

How Basecamp Grew to a $100 Billion Valuation
Fried made headlines a few months ago when his company was valued at $100B, all shared through a tongue-in-cheek Silicon Valley style press release, with a twist: Basecamp had sold 0.000000001% of the company in exchange for $1. The Signal v Noise piece is full of too-true jabs at Silicon Valley's funding models, including our favorite:

In order to increase the value of the company, 37signals has decided to stop generating revenues. “When it comes to valuation, making money is a real obstacle. Our profitability has been a real drag on our valuation,” said Mr. Fried. “Once you have profits, it’s impossible to just make stuff up. That’s why we’re switching to a ‘freeconomics’ model. We’ll give away everything for free and let the market speculate about how much money we could make if we wanted to make money. That way, the sky’s the limit!”

It was yet another attempt by Fried to paint the ludicrous nature of the valuations entrepreneurs are chasing after. Instead of focusing on the media hype about companies with high valuations, Fried instead tells entrepreneurs to focus on customers and getting revenue through the door.

Advice for Founders Dealing with Ego
Founder's Ego is a condition affecting a majority of entrepreneurs, especially first-timers - including, at one point, Freid himself. Freid went on to talk about the importance of founders to check their ego at the door, which includes not raising an absurd amount of money simply because everyone else is raising that much.

“The most important thing for me to get over my ego was to ask myself the question of why?”

Why do I feel that I need to raise money?

Why do I want to have to report to a board of directors?

Fried believes these are questions that many founders are simply glazing over, which he believes is the reason for so many overblown valuations. He strongly urges founders to consider the implications of taking venture money, and to disassociate their ego with the decision.

With investors watering at the mouth to get a piece of Basecamp, Freid has always been able to say no - because he knew taking venture money would dilute his vision for the company, and get in the way of his life outside of Basecamp - most notably, that of raising a family.

So next time you’re deciding on whether to raise money or not, ask yourself why? If its out of ego and status seeking, you may want to reconsider your decision.

Originally appeared in: https://www.startupgrind.com/blog/dont-sell-your-soul-valuation-has-no-effect-on-your-company-insists-jason-fried-of-basecamp/?lipi=urn%3Ali%3Apage%3Ad_flagship3_profile_view_base%3BFqf95fF0Ttmk2EcFSsCXfQ%3D%3D

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