Bio+Tech was started as a monthly gathering to bring together the best and the brightest entrepreneurial minds in biomedicine and combine them with leaders in the SF tech start-up world.  The idea was that we have an amazing collection of biomedical entrepreneurial minds in SF and with the advent of bio-incubators and tech breakthroughs, the barriers to starting a bio start-up continue to drop.  There’s also a curiosity about biomedicine in the tech realm.  Who better to infuse biomedical and informatics start-ups with entrepreneurial energy and push biomedicine start-ups over the entrepreneurial hump than folks from this bastion of entrepreneurial energy? Plus, the biomedical start-up world doesn’t network nearly to the same degree as does the tech start-up world – that’s critical to the tech start-up world’s success in the SF Bay Area.  Thus Bio [plus] Tech – not just the same old biotech complete with high barriers, lack of networking and support.  Six months in to the Bio+Tech experiment I’d say that so far it’s been a success.

As a note: When I talk about biomedical entrepreneurship I mean that broadly – whether informatics, biotech, pharma, bio-energy, etc – it’s all welcomed and encouraged at Bio+Tech. And, I can’t emphasize enough that not only are we looking to bring together biomedical folks, we’re also looking to bring tech folks – developers, co-founders, start-up managers, etc – in to the mix.  You absolutely do not need a PhD in biophysics to join the group.  Just a healthy interest in bio or medicine – trust me, you’ll blend right in to the group!

Bio+Tech has grown from a group of 10 in January to an average of about 30 people at each monthly gathering.  To boot, that growth has been achieved solely through word of mouth.  I’ve been to a lot of meet-ups and gatherings where there’s lots of noise and very little signal – Bio+Tech has been purposefully kept small to keep the quality of the level of interaction high.  This set up was inspired, in part, by the SF meet-up Founder Dating, which requires an actual application and recommendations from other start-up folks.  Jess Alter and her crew do an amazing job!  Go check it out if you’re looking for a tech start-up or a techie person to help you build your start-up.  I also want to give a shout out to Vinnie Lauria and his Silicon Valley NewTech Meetup as the founding source of inspiration behind Bio+Tech.

Bio+Tech isn’t quite as complicated as Founder Dating and not as large as the SV NewTech Meetup, but to join the invite list you do need to demonstrate a basic interest in biomedical, tech or bio-energy entrepreneurship.  All too often a lot of biotech meet-ups are crowded with sales people and other vendors who are more interested in selling than sharing ideas, tips, contacts or starting businesses.  That’s not to say that we don’t accept sales people in to the group – you just need a genuine interest in creating a company or joining a start-up.

Michael Shuster speaks on the changing IP landscape and how that affects biomedical entrepreneurship.

Want to join us? Each month, the time and date of Bio+Tech will be posted on its webpage, with the location in SF to be announced. If you’re not already on the invite list, feel free to contact me at windmiller@gmail[dot]com and let me know why you’d like to attend.  Just a little paragraph with your interests and what type of company you’re looking to start or join, and a link to your LinkedIn profile – nothing too complicated.  In return, I promise to do my best to connect like-minded people at the meet-up.

We’ve had a couple bio start-ups find co-founders or developers – heck, there’s even been cross-pollination of neuroscience-principles back in to a tech start-up’s social media algorithms!  Yes, it’s a bit nerdy, but I can honestly say that out of the 6 gatherings so far, everyone who has attended has been someone I’ve really enjoyed talking with and sharing ideas.

Each Bio+Tech starts with a good bit of mixing and conversation.  It’s kept that way to maximize interaction and to warm things up.  We then get together to introduce each other to the group – with 30 people I’m always amazed at how efficiently we get through the group.  This is an opportunity to introduce yourself to the group and also spot others with like minded interests.  And, of course, we welcome solicitations for co-founders or technical help or any other start-up needs to the group.  This is a chance to network and find those you’d be interested in working with.

Starting in August we’re going to try to have monthly speakers as well.  It’s a highly informal 10-20 minute talk from people in the biomedical start-up or in the tech start-up world designed to bring ideas and prime the conversation.  We’ve had Michael Shuster, partner at Fenwick & West, speak on the changing landscape of Intellectual Property (IP) and how that’s affecting start-up strategy and execution.  A lot of biomedical start-ups are realizing that execution is just as important as securing IP to start-up success.  This isn’t news to tech start-ups, but this shift in perspective is somewhat groundbreaking in biomedicine start-ups.  We’ve got John Wilbanks, VP of science at Science Commons speaking at our August gathering on the open sourcing of biomedical data sets and tools and how that is altering and encouraging opportunities in the biomedical start-up scene.

And, Bio+Tech is purposefully kept free.  Whether you’re an undergrad or grad student, or on your 5^th start-up, everyone is welcome and encouraged to come.  I believe firmly that cost should not be a barrier to attendance.  And, please pass this along to people you think would be interested in Bio+Tech – that’s how we keep new, fresh ideas coming in to the group!

Looking forward to seeing you on August 18^th.

I haven’t posted on genomics in a while, so it’s about time. Two weekends ago I attended the Sage Bionetworks and Science Commons 1^st annual Sage Congress here in San Francisco. The main aim of the conference was to begin to gather science folks from across the country and begin thinking about making scientific research and data sets more open. While that may seem like an easy task in the era of open source, it’s tricky from many perspectives and the effort still has a lot of skeptics. But, more on that soon – personally, I think Science Commons and Sage Bionetworks are brilliant ideas.

At the conference Anne Wojcicki, co-founder and president of 23andme gave the keynote on the last day of the conference (video at right). To be fair, in the past I’ve been skeptical of 23andme – particularly from a clinical perspective. And, the MD side of me remains skeptical of genetic testing in general – at this point we know too little to apply genomic information to clinical care. There are a few exceptions, like breast cancer and a few other diagnostics, but otherwise in my humble medical opinion tests like 23andme should be used with a skeptical eye from a clinical and medical perspective. Again, there are a few case examples of where genetic testing has helped, but those remain too few and far between.

All that said, something about Anne’s keynote struck a chord with me – the amount of phenotypic data that the company is gathering in conjunction with their tests holds tremendous promise. Consumers purchase the test, and once their results are delivered, 23andme asks the consumer to participate in a series of surveys about their health and physical traits. To date, as was mentioned time and time again at the Sage Congress, research efforts to link patient, clinical and genomic data have proven to be arduous, time consuming and expensive. But, 23andme is capturing it right out of the box.

It’s hard to really convey how valuable this data truly is. A lot of the genomic data and research the scientific community has done to date has been on a couple cells in a petri dish or in mice, etc. Less has been done in humans, but that’s changing. With the collection of millions of genetic data points per consumer plus their trait/phenotypic data via 23andme, that will all begin to change much more rapidly. Being able to directly correlate genes to their traits will be a powerful tool for researchers to help push our genetic understanding and medical knowledge forward.

How we think about DNA and our genetic information as consumers is changing. Here, a DNA gel is aligned as art.

What makes 23andme special is that they’re utilizing social media and other consumer internet approaches to engage consumers and get them to provide their data essentially for free. While this might sound intuitive to most internet junkies, it hasn’t been for much of the scientific community. Indeed, from my perspective at the Sage Congress, 23andme’s approach seemed to me met with a bit of skepticism from the community – and this was an even more open and broad thinking group of people. But, it’s working. Consumers are readily contributing information, but it’s because of 23andme’s social media and internet approach. Not only will it change consumer genetics, but I bet that 23andme’s approach will alter how we collect research data, which will in turn, accelerate breakthroughs.

This shift in thinking will be critical as genetic research and genetic testing moves forward. Genes are far from being directly causal – i.e. very rarely does one gene lead to one distinct feature. And to uncover the patterns of the chaotic interaction of genes and their environment, gathering the type of rich data that 23andme does with their surveys will be absolutely critical as we move forward. Part of the next movement in genetic testing and genetic discovery will also require new tools to deal with massive data sets and help us find those needle-in-the-haystack discoveries that shed new light on human health and disease.

Again, more DNA as art - we're beginning to re-think our relationship to our genetic information.

And, to boot, one large win for society with companies like 23andme is that they are making consumers more and more comfortable with the concept of genomic testing. That in and of itself is a tremendous value to the market and for research. In the future I predict that we’ll look back on efforts like 23andme as landmark and critical to helping us reach the next plateau of genetic discovery and understanding. And, because of that and 23andme’s awareness of that fact, I think they’ll be successful in the long run.

I’ve got a job for you!  How does this sound – spend your college days studying away (sorry, only minimal time for parties) worrying about standardized tests, spend 7-8 years after college training for your job, go in the financial hole on average $160,000 and for the first 4 years of your career earn $45,000.  Sound good?  There’s more.

Spend the rest of your career jamming in as many clients as possible a day – maybe upwards of 20 or so – worry about malpractice insurance, be squeezed by Medicare. And, while earning a respectable salary, there’s really no hope of raises outside of adjustments for inflation.  In fact, there’s a high probability outsiders will likely attack your salary and maybe even reduce it.  Did I mention about mountains of paperwork and clients wanting your professional opinion for free?

Sounds a bit dramatic, but that’s the negative side – aka the con side –  that a person faces when deciding whether or not to be a General Practitioner.  I was sparked to write this post when a friend of mine – Ab Brody, PhD, NP – tweeted about a new Journal of the American Medical Association (JAMA) article laying out some of the challenges in recruiting MDs to General Practice.  The current healthcare reform debate has renewed the debate over the types of MDs we need to train.

Indeed, there are lots of benefits to being a GP – not the least of which is the satisfaction of getting to know families, helping people overcome day-to-day medical issues, etc.  It’s truly rewarding.  But compared to other professions and medical specialties I have no idea of why, from a financial perspective or even a career fulfillment perspective why anyone would choose General Practice.

Dermatologists – same professional satisfaction.  Sure, you have to look at the occasional butt pimple, but you can make a dramatic difference in someone’s life.  Career satisfaction?  Check!  Good hours? Check!  Oh, and on average they make $351,000 annually.  Or, 2.5 times what a GP makes.

I’ve done the math – a GP, making the average salary and with the average student loan debt load will never be able to purchase a house in San Francisco without significant additional income.  If that same physician buys a modest house in Atlanta, by the time they’re 65 they’ll have almost $500k in the bank.  However, that’s much less than what other careers bring in. It’s more than a lot of people, but given the struggles they went through to become physicians, it’s not all that much.

To be sure, I’m writing this post to be incendiary and provocative.  I truly believe that GPs will be the heart of healthcare reform here in this country and I hope we start treating them like so.  Why?  Because we need them – they coordinate care, they’re the first line and if trained the right way they can be beacons of savings – to the tune of several billions of dollars of savings each year.  But, we need to fix the factors that I spend time lampooning above.

How do we get more smart, young physicians to become GPs?

So how can we rectify this issue? I think that the first step is to come clean and admit that it’s, at least a little bit, about the money.  There’s absolutely nothing wrong with wanting to earn a great living.  If someone offered you a better lifestyle, more pay, better hours, wouldn’t you take it?  We need to change how we reward our GPs – base their income on outcomes.  Patient outcomes, that is.  Promote tort reform to help avoid frivolous law suits.  Provide scholarship opportunities to help them with the financial hole they face out of school.  And, to boot, pay them commensurate with other areas of medicine.  We’ll all benefit from that!

The demands we place on GPs are too great – the malpractice threats, the paperwork, diminishing incomes/reimbursements, etc.  It’s a tremendous burden even outside the financial disparities.  Add both of those to the pot and it’s a surprise anyone becomes a GP.

It’s also a reputation issue, too. Or at least that’s the way I’d argue it.  My medical school, for one, highly praised those who went to specialty residencies.  Let me be clear – I’m exceptionally proud of all my classmates and their choices.  However, the school did a super lousy job pointing students to general med.  I’d even say that it was actively passively dismissed though the school’s emphasis on specialties and choosing a competitive specialty as the highest success.  In fact, we really didn’t have a fantastic role model to emulate in the GP space – compared to access to the best heart surgeons, cancer docs, orthopods, etc in the world.  IMHO.  I’d say a lot of med schools actively dissuade the pursuit of becoming a GP through how the schools grade, praise specialties, elevate their leaders, etc.  Becoming a GP was passively aggressively looked down upon.

Lots has to happen between now and then – I’m really curious to hear your thoughts.  Should GPs be paid better salaries? What role should they play in our healthcare system?

Been busy working on some consulting engagements recently.  That’s a good thing for me, but bad thing for Medicine Think.  I’m working on a new entry for later this week, but for now I’d like to share one of my favorite graphics from Bud Caddell over at What Consumes Me created this awhile ago and I’ve been meaning to share.

Sometimes, as a one-man consulting business you feel a pressure crunch that most big firms don’t face.  It almost feels like what an artist or graphic artist must feel.  Most folks want things for free, they have some sort of expectation and only few ever plan on compensation.  The trouble is that I find most of the consulting problems that come my way to be really, really interesting.  I’m happy to report that I’m bringing Square6 closer to the middle!

And, for those of you who love infographics – head over to What Consumes Me! Fantastic work!

The Tesla Roadster Sport - really, there's nothing like it

Here’s a non-traditional Medicine Think entry, but I wanted to share my first drive of an all-electric car – the Tesla Roadster Sport.

I feel like last night I had one of those rare experiences where you feel like you’ve seen the future.  It might sound like a hyperbole, but that’s what it felt like to test drive the Tesla Roadster Sport.  And, no, I’m not in the market for one, but after driving it, I really wish I had about $110,000 in disposable cash laying around.

So, what is it about the Tesla that makes it feel so futuristic?  It’s an all-electric car – there’s no hybrid or gas component – it’s a 100% electric motor.  That means that from the moment you put your foot on the “gas” (is it more appropriate to call it an accelerator pedal? The “electric?” The “juice?”) it’s a different driving experience than you’ve ever had.  The only similarity is that there are four tires, the car looks like a Lotus Elise, and there’s a steering wheel – most other experiences are different.

There’s no engine noise.  Honestly, you don’t miss it.  An electric motor, by nature, has 100% of torque at 0 RPM – that means the thing accelerates so rapidly that it’s hard to believe.  0-60 in 3.6 seconds – that’s Lamborghini fast.  Instead of having to “rev” the car up, all the power is there and ready to go when you push down on the pedal.  It’s unlike any car I’ve ever been in.

There are no gears – nothing to shift, no transmission beyond forward and reverse.  After the car bolts to speed, the engine itself has a tremendous amount of braking power.  The moment you let up from the accelerator, the car begins to drag to a stop.  You literally don’t need a brake other than to come to a full stop at stop lights.  Put another way, to maintain speed, you have to keep the pedal down – even on downward slopes where gas power cars would shift to neutral or have a very low factor of engine braking.

Apparently, a lot of Tesla’s patents and intellectual property in how the car electronically mimics the way we drive today in gas cars.   By that, I mean it’s not in the nature of an electric car to cruise forward when you let up on the brake.  But the Tesla does – that’s a purposeful design and apparently very hard to do in an electric car.  From my understanding, this technical achievement will be difficult for others to mimic.  Apparently this technology bleeds over in to how the car accelerates smoothly and the car reaches cruising speed.  Whatever they’re doing it’s definitely working.

With the electric engine comes the need to store the electricity to power the car.  The battery “pack” alone weighs just shy of 1000 pounds.  That’s a lot of weight.  It’s positioned mid-car just like in a gas powered sports car, which helps balance the handling overall.  Regardless, the 1000 pounds is a lot of weight, especially when the car weighs a mere 2,700 pounds overall.

Otherwise, the car is definitely a stiff little roadster and to be honest I had a hard time seeing through the windshield.  I’d love for the car to have a few more inches, and I hope that comes at a later date.  Maybe by the time I can afford one.

It was truly an exhilarating ride, and I don’t think it really hit me until I stood up and I felt like I had just stepped out of a rollercoaster – the same shakes and legs feeling almost like rubber.  I don’t know if that was because I’m a pretty novice sports car driver, or the all-electric roadster really is that cool.  My gut sense is that the car really is that cool.  I was on a high for the entire rest of the night – I’m not kidding.

And, this sense had nothing to do with the environmentally friendly nature of the car.  That said, I’d be really curious of the overall carbon footprint of a mile in a Tesla versus an efficient gas car.  How many carbon emissions are released during the production of the electricity to power the car?  Is it really less than driving a mile in a gas car?  Either way, the electric car really is that cool.

Heading back tomorrow to get a behind the scenes look at the dealership and shop in Seattle.  More to come!

UPDATE: Please RSVP to: windmiller [at] gmail

This Wednesday night – January 20^th at 7pm I’ll be hosting what I hope will be the first of many meet-ups for entrepreneurially minded biotech and bioinformatics people here in San Francisco.  It’ll be at Crossroads Café in SOMA. In February the meetup will most likely be moved to a more permanent location at i/o Ventures, a start-up incubator space in the city.  Information will be updated on the meet-up’s page on Medicine Think and on my @medicinethink Twitter account (follow me!).  Feel free to pass this info on to interested friends.

Genome Valance by Ben Fry. Ben's expertise is helping to graphically represent and interpret massive data sets and information. This piece represents genomic analysis using BLAST. I picked this piece specifically because it takes a new look at how to represent and understand genomics and informatics - something I hope this meetup will help to encourage more of. More about his work from Ben at http://benfry.com/genomevalence/ (click to enlarge)

So, why the meetup?  I’ve spent the past 4 years in San Francisco in both the tech and biotech realms.  Actually, I’ve been a passively active member of the tech community – out of interest I go to events and meetups with friends.  I meet people through my wife who’s in tech PR.  I’m actually pretty well immersed in the community without really trying that hard – it’s a pretty open and warm community.

But as I’ve actively tried to network and attend events in the biotech and genomics space, it’s been much more difficult.  While I’m just about one or two degrees from most of the tech crowd here in SF, I can’t say the same about the biotech space.  And, perhaps with some good reason – the biotech/life science/genomics space rely pretty heavily on intellectual property and trade secrets, so that stunts people’s ability to be social.  Despite that, I think there’s much more room for building a more solid general community outside of the big players and established start-ups.

One of the beautiful things about the tech community in SF is the intermingling of different specialties and cross-pollination of ideas.  This leads to start-ups, improved technologies and a more healthy and vibrant tech community.  Often, these ideas, through start-ups, are passed up to the larger players through acquisitions – so from early start-ups to big behemoths the entire community benefits from this networking and open community.

The biotech community here could use more of this attitude and community.  San Francisco and the University of California has made a substantial investment in the Mission Bay neighborhood – there are very, very few areas in the country that have the foundation for success as does this very special part of SF.  And with visionary institutes like QB3, which is based at UCSF and Berkeley, I see a whole new generation of PhD and other grad students with an entrepreneurial energy that hasn’t been created at other campuses.  Combine that with Stanford’s legacy of doing the same thing and you’ve got the seeds for an amazing industry and community.

Don’t get me wrong, the Bay Area is already a leader in biotech – clearly there’s a lot going on.  But to take it to the next level, the community also has to kick it up a notch.  I hope this meet-up can serve as a partial catalyst (of course, there will need to be many, many more events, etc) to tap in to both the tech and biotech communities here and bring together a diverse and energetic crowd.  Ideally, I’d like to promote an interdisciplinary meetup – between not only biotech and bioinformatics people, but to bring in members of the tech community.  I think tech could greatly inform how bioinformatics and biotech does business – from improving how data is handled, to user interface and analytics and beyond – there is much room for tech to impact the biotech community.  And, to a certain extent, tech would also benefit from some of the thinking from leaders in biotech.  From algorithm and natural language specialties, to managing massive data sets and making meaning, to scalable software, SF and Silicon Valley is well positioned to inform biotech and informatics and help solidify the Bay Area as a leader in biotech and informatics.

If you’re in SF or the surrounding areas, please come by Wednesday at 7 to the Crossroads Café. Even if you are a tech person with a curiosity about biotech, genomics, personal medicine and the like, without a super deep background or expertise, we’d love to have you.  I think these two groups have much to learn from each other and that this type of social interaction will lead to new ideas, energy and companies that will help take the Bay Area to the next level and retain a leadership in the life sciences.

What do you think?  What would you like to see at these types of meetups?

In the past I wrote about getting a start-up off the ground. More precisely, about how to take an idea and give it legs and maybe get it running – how to mold an idea and begin to improve it. I call this socializing the idea (with the next steps being socializing the company/concept). But, how do you take it to the next level? Making that transition between idea to fully operating start-up is tough, particularly if you’ve not done it in the past (read: if you haven’t been a successful entrepreneur in the past).

A good friend, who has successfully sold two pretty large start-ups, gave me the advice that angel (or seed) investors tend to only invest under three conditions: 1) you’ve been successful in the past, 2) they know you personally (worked with you, are a family member, want to get in good with your family, etc), or 3) are intimately tied and invested in the space you’re working in. While I took in his advice, I’m not sure we followed it well in my first start-up. None of us in the venture had successfully launched a start-up, we didn’t come from money and most investors didn’t like to invest in the healthcare space (at least at the time). Turns out my friend was more right than I could have guessed. This made it incredibly hard to pitch to angels, and ultimately we didn’t get funding (but that’s another story).

One other thing about starting that I’ve learned over the past 4 years is that often times it has taken companies a lot more effort than they showed or they had some sort of secret weapon to getting started. Almost no one company starts go smoothly or easily. One company in particular that comes to mind was lauded as having been an amazing story and elevated its founder to a great reputation. They raised a little under a million dollars and sold for $25M. That’s a great story. Then you peel back the layers back and realize that one of the co-founder’s father invested a majority of that initial $1M (they didn’t raise it from a typical angel investor) and that father was also an executive at the company that eventually acquired the start-up. Don’t get me wrong, this start up still took a tremendous amount of work to get the product to grow and to accumulate users. But, as a note to up and coming entrepreneurs, stories like this one, including the message that was told to the public and meetups regarding the ease they had fundraising are often misleading. It’s still a success story, but definitely not as shiny as it initially seemed.

But where does that leave first time entrepreneurs without a track record or the good fortune of befriending a Silicon Valley maven or a PhD in computer science? A couple new efforts have really filled that niche for talented, but new entrepreneurs. The most well known and a pioneer of these efforts is Y-Combinator – a Silicon Valley and Boston based effort that hold biannual “try-outs” for new start-ups. Essentially, you make an appointment for the try-out session, pitch to Y-Combinators’ board and if they like you they’ll give you some minimal seed funding ($10k) and help set you up with the resources you need. More importantly, being accepted as a Y-Combinator company pulls you in to their social circle which works wonders in being connected to partners, customers, getting advice or going for a larger funding round. Perhaps most important in this effort than having a great idea is who you know and who you have access to – funding from Y-Combinator can help you gain that toe-hold and help you jump in to the game. They also have great partners, including Paul Graham who has a widely read start-up blog. In other words, it’s less about the amount of funding and much much more about the connections being one of their companies brings you.

Now, utilizing efforts like Y-Combinator doesn’t come without a price – namely that it’s reported that they take 10% of equity in a company. That’s definitely very, very expensive. However, at the same time it’s indispensable if you are new to the start-up game, particularly in the Bay Area. Other, less well known efforts are also taking root, including Adeo Ressi’s The Founder Institute. Their model is a little different – they take a smaller chunk of the company if it gets funded and then splits the profits from this equity pool amongst other founders. It’s too much to really explain here, but suffice it to say that the Founder Institute is more about gaining connections than anything else.

A third option is a location in San Francisco named Dogpatch Labs. Run by Polaris Ventures, Dogpatch Labs gives entrepreneurs very inexpensive, shared workspace with other start-ups. It’s more about community and connecting with your fellow entrepreneurs, but it’s also a great networking tool. In this case, entrepreneurs and young companies need to pony up some cash for the space, but in a place like San Francisco, a resource like Dogpatch Labs is invaluable to the start-up community.

Last and certainly not least is i/o Ventures. Just announced today (January 6, 2010), i/o Ventures looks to be both a small seed round along with a new, open workspace in SF. It’s got an impressive list of advisors and other folks surrounding it, including the likes of Michael Arrington. Pretty amazing exposure and a mashup of some of the concepts from other incubators/labs. Sounds like they’ll be shelling out more money for a smaller percentage of the company as well (compared to Y-Combinator’s $10k and 10% take). Watch out for these guys in the future.

Overall, these efforts give an amazing amount of camaraderie, work space, inspiration and most importantly legitimacy in the eyes of potential users, customers, and funders. It’s a fantastic way to start if you’re new to the game. I’m sure there are other spaces like these, including Hacker Dojo in Mountain View, CA – more of a meeting of the minds and place for work inspiration and perspiration. Did I miss something? Who else should be included in this list? Leave a comment about them below!

In two previous posts I highlighted some of the coming changes in DNA sequencing and some of the up and coming companies that will help us with the onslaught of data. But I’ve neglected to begin to explain why these technologies will be so transformative and why that matters for biomedicine.  Back in 2003 both the National Institutes of Health and Celera made a big splash as they announced that the human genome had been decoded.  While true – we had the basic sequence of the human genome – the A-T-G-Cs of it all, we didn’t really know what we were looking at.  Just because we have all 3 billion letters of the human genome sequence, doesn’t mean we know what it actually does. (Image above of a DNA strand courtesy Richards Center, Yale University)

Well, that’s only partially true – we do have lots of scientific research and understanding of certain genetic mechanisms and functions of genes.  But as of yet that knowledge has been somewhat limited and pretty elementary with respect to actual impact on clinical medicine and human health.  Very few diseases, like sickle cell anemia, can be traced back to only one mutation – a relatively simple genetic explanation (Picture at right: regular red blood cells with sickled disease red blood cells, courtesy NIDDK).  We know that multiple genes are linked to heart disease or cancer or arthritis and we’re discovering new links every day.  However, most of the the connections are still pretty weak and don’t fully explain the true genetic nature of some diseases.

And, one more thing, I’d be pretty skeptical of the commercial genetic tests that are available from companies like 23&me and Navigenics (among others).  While they have strong people behind the company, the data they’re using is still pretty weak with respect to predicting disease.  Take those tests as a novelty, not as a sure thing diagnosis – please feel free to write me and I’d be happy to explain more.

For another example, let’s take a look at cancer and its genetic root.  Scientists used to search for a single “cancer gene” – when we found one, we realized it was only a small fraction of the story and there were many other genes that had related effects that contributed to cancer.  The same thing applies to heart disease and even seemingly simple traits like eye color.  In a way, the more we learn, the more we discover we didn’t know as much as we thought we did.  It got more complicated.

To complicate the public’s understanding, the genetic model we all learn in school is Mendel and his peas.  It’s a good educational example because one gene leads to either smooth or wrinkled peas; another gene confers either green or yellow color – making the peas a really simple and useful example to explain basic genetics.  However, very, very few genes and phenotypes work this way in human genetics.

One reason the human genome, as we know it today, is not as quite as useful as all the hype in the media is that what we call the human genome project is really the genome of just two people.  It’s a roadmap of sorts to help with genetic research – it, by itself, explains very little in the way of human variation and disease (I’d like to say though, that much like the moon landing, there was a certain gravitas to actually completing the genome – it has inspired scientists and has certainly aided with scientific progress).  The genome map doesn’t have all of the gene variants figured out – it’s a raw map and it’s up to us to figure out where those genetic variants are.  More over, diseases like cancer and heart disease have many, many genetic components, making it even harder to figure out which gene has which function.  In other words, biomedical genomics is very different than the genomics lay people learn and understand.

To understand where cancer related and heart disease related genes are and what roles they play in disease, we’re going to need breakthrough technologies to not only sequence DNA, but also handle all the information that comes out of that process.  Each human genome, depending on how it’s sequenced, is between 250 gigabytes and 2 terabytes of information and costs between $100K-$500K.  That’s a lot of data and moolah, especially considering the hard drive in your computer is probably 250 gigabytes or smaller!  Each cell in your body contains more information than the disk drive in your computer.  Not too shabby of a machine, eh?  I digress.  As we progress, new models of sequencing and data solutions will become much more economically feasible, making it possible to do the necessary research.

An example of how genomics will change medicine was published last year in a New England Journal of Medicine article.  In it researchers describe how they obtained two complete genetic sequences from a person – one of a leukemia cell and the other of a healthy skin cell.  Essentially the researchers compared the cancer genome with the healthy genome and analyzed the genetic differences. When they compared the cancer genome to the healthy genome they found 3 mutations that they expected to find based off of prior leukemia research.  However, they also found 7 genes that they had no idea were involved in leukemia – the researchers arguably tripled the genetic understanding of leukemia with just this one study.  Now, with these new gene targets, researchers and doctors will have a better understanding of leukemia as a disease, which will shed insight in to next generation therapies and maybe even a cure someday.

Now, that study cost approximately $500,000 for the genomes alone – $250,000 for each genome.  With new sequencing technologies we’ll be able to get that cost down to under $100 in a matter of a couple of years. The leukemia study mentioned above was just a proof of concept that illustrated our ability to better understand disease genetics and pathophysiology  by comparing only two different genomes. To get a full and accurate understanding, these same scientists will need thousands of genomes to compare – and that’s just for each, individual disease!

Over time this genomic research will become common place and will yield great advances in biomedicine.  At this point we need more cost effective technology that will make it affordable to perform the necessary research with enough genomes to really matter.  To close this post, though, I strongly caution that this work may not directly lead to a cure.  My bet is that the research will help us to better understand that which we don’t know we don’t know.  It is a leap in to the right direction and will prove incredibly helpful.  It’s an exciting time.  In future articles I’ll dive deeper in to the genetic mechanisms of cancer and then other, new breakthroughs in genomic technologies.

It’s been a little over a year since Sequoia’s infamous slide deck “leaked” to the internet proclaiming the end of the good times for start-ups.  The presentation contains tons of graphs detailing the oncoming downward spiral and suggested that start-ups tighten their belts in order to survive.  Clearly that was great advice, but my main issue with that message is that start-ups should be frugal to begin with and those who need a warning to cut back probably aren’t going to survive anyway.  Bill Gurley of Benchmark also issued a missive at the same time that listed about 10 do’s and don’ts for start-up survival.  Again, aren’t these things start-ups should do anyway to ensure survival?

I bring this up because at the time many commenters and columnists called out these warnings as disingenuous – the message conveyed by Sequoia and Benchmark was something VCs should tell their portfolio companies anyway, and by issuing such a warning (and highly publicizing it through an organized leak) they only served to create a panic.  A panic that tips the scale in their favor – the “harsher” the conditions, the more the risk, the lower the pre-money valuation for companies.  Sure, the economy was down, but VCs artificially raised the level of “economic harshness” through these missives, which actually benefitted them with lower pre-money valuations and thus larger chunks of companies. That or they’re madly brilliant – turning every day entrepreneur advice into a scare that benefits their portfolio.

That said, I think its good advice and good practice to remind companies to reevaluate their spending and burn rate – I object to the way it was done.  I think that Bijan Sabet, a partner at Spark said it nicely in a recent blog post: “we can all do better“.  What made me think of these notes from last year was Fred Wilson’s (of Union Square Ventures) post today that calls out VCs who say they need to command a specific percentage of a company.  He’s “calling bullshit” on VCs who make such comments.  And I believe him – it’s a disingenuous thing for a VC to do – to focus on a percentage rather than the true value they add to a company.  In a way, stating a desired percentage artificially deflates a company’s pre-money valuation, rather than focusing on what the company is really worth.  VCs, by only thinking in company percentages, are overreaching.  I applaud Fred for his message – as does Josh Kopelman of First Round Capital, who takes Fred’s VC greed point even further and says it’s a mistake for a VC’s required returns to drive company’s outcomes, rather than the other way around.  Again, I agree and am happy to see some VCs making this message.

But, on second thought, VCs are driven by returns – the largest return they can make to their LPs.  I think it’s a mistake to think this means “more altruistic” VCs will take a lower percentage of a company – afterall, they’re in it for the business, too. As an entrepreneur you have to take their points with a hint of caution. VCs are still out to get the most out of their companies, and part of that is taking as large of a percentage of a company as is possible.  A smart VC will balance the yin of the percent they take from the company with the yang of maintaining the founders incentive in making their company successful, but that often doesn’t happen.

It’s semi-noble Fred and Josh to express their vantage points, but it’s also smart business because they improve their image with founders.  I don’t have data, but it would be interesting to compare the average percentage of companies a VC takes versus the overall financial success of those companies.  Or, the macro performance of their funds.  Curious if some of my professor friends have insight on this?

Overall, I have to say thanks to Josh and Fred for making their posts, I think that the message is spot on, but I also feel that founders should take these statements with a gain of salt and always be aware of a VC’s true focus.

An amazing amount of books and sites and resources exist to help you start a business.  Whether you want to open a custom bakery shop or start the next big thing in life science, there’s someone out there willing to give you advice. Too many voices, with too many opinions, some trying to help, others not so much.  Knowing who and what to listen to is perhaps the toughest first decision you’ll have to make.  Most authors write books with hundreds of pages, telling you to write elaborate business plans, to create massive financial models in excel and so on.  My experience tells me this is wrong – at least for the most part.  Make no mistake – most of these authors and advisors are there to sell books or consulting service, so buyer beware.

My rule of thumb for just about everything in life is the K.I.S.S. principle – Keep It Simple, Stupid.  And I mean that the more complicated something becomes, the higher likelihood that it’s wrong.  Don’t get me wrong, I have made these mistakes – my co-founders and I became inundated by advice and books and speakers and lectures, etc.  For the most part, young companies need to validate their ideas and create a plan and messaging that will help them convey their idea, build a solid company and recruit quality help, including strong investors.

I’m a fan of finding multiple sources and integrating the different messages and figuring out the common themes and utilizing those common themes as my starting point.  I say this as opposed to following only one “guru” for advice.  In other words, I start by figuring out how to start.  As much as I think he’s a book salesman rather than a great help, Guy Kawasaki does have some excellent points when it comes to what topics to think about.  His first, incredibly important piece of advice is to make meaning with your company.  Think about what your idea accomplishes – does it matter to people?  Does it create value for them? How does it create that value and how will you sustain your advantage?  While I hope your business accomplishes some social good, more importantly it will create value for all of its clients and customers, which in turn is good for socioeconomics.  If it creates a social good, too, then mazel tov. Take this idea and force yourself to condense it to something you can explain in 20 seconds – it’s called an elevator pitch.  This will help you clarify your idea, force you to communicate concisely and effectively, and ensure you adhere to the KISS principle.

His second point comes buried in his 10/20/30 Rule.  Also available on YouTube.  After assessing the big picture of your idea and beginning to lay your thought foundation, Guy’s 10 slide outline can really help guide the way you think about your company.  It can help focus your thoughts and remind you of the important bases to cover.  It also serves to remind you to be succinct and to really know what you’re talking about.  Sequoia has a more robust example of these slides on their business ideas page.  Their outline is more in depth than you have to be at this point, but it serves again as a proper outline of things to think about.  By covering these topics you will begin to be prepared to test out your idea and will prepare you to handle many of the initial questions that will come your way.

Once you have some of this down, my next suggestion, before you put too much more thought in to the depth of the idea and company is to begin to socialize the idea with your friends and trusted colleagues.  Once you’ve gone through and understand the outline of your idea, running it past your friends will not only help you become more succinct and force you to really know your business idea, but it also helps to jump start the social component of starting a company.  Utilizing your network is a huge must at this point.  Use your contacts and their expertise to refine your idea.  Use their networks to begin to get in touch with other experts or investors.  Not so much to pitch, but to air out the idea and get feedback.  This exercise will yield an incredibly useful set of opinions and improvements – not only in your idea, but also in how you present it and skillfully get your points across to other people.  Finally, don’t be afraid to share your idea.  To be sure, don’t go blabbing all the proprietary technology or thoughts, but accurate highlights of your idea will be necessary for proper feedback.

I’d suggest starting this process 2-6 months before you really want to get going on actually building the business.  One of the lessons that I had to learn was that ideas really do need time to marinate.  Prior to my first start-up, I would have ignored this piece of advice, but these days, I think it’s critical.  Don’t sit on your idea too long, but do socialize it, improve it, and along the way begin to map out how you’d like to see it develop and turn it in to a business.

An additional resource to start with is by my friend David Weekly – he has a great presentation on lean start-ups – video here.  Also good is Aaron Patzer’s presentation on Minto.com and it’s beginnings. Video here.  While I heavily suggest not getting mired in the details at this stage, I would recommend familiarizing yourself with these topics and putting them in your consciousness somewhere for later use.  Learning these things also takes a good amount of time to really sink in.  Stanford has a great entrepreneurship video series and VentureBeat also has a phenomenal resource for entrepreneurs called Entrepreneur Corner. Again, don’t get bogged down, but do start watching.  Great lessons to learn.

Come up with the idea, flesh it out and then socialize it.  Thoroughly.  Next steps, well, those will be my next post.