Focus May Be Your Worst Enemy in Biotech R&D Investing

My Fascination With Mega Research Initiatives
I like reading biotech research and how the industry brings products to market. I discovered something unusual about the mega-initiatives that try to tackle some of humanity’s biggest diseases.

Some Recent Mega Initiatives by Powerful Billionaires

I was thinking about this a lot lately as the news has seen rise of Mega Research initiatives. I’m referring to the new Chan Zuckerberg initiative, Microsoft’s claims about curing Cancer with AI, and Bill Gates’s initiatives in neurogenerative disease areas.

Gates says a lot in his blog post.

“Because we are at a pivotal moment when the conditions are ripe for transformative innovations, there are many important things this new group of national leaders—including whoever is elected in the U.S. in November—can accomplish over the next decade. There are four objectives I think we should prioritize:

  1. Provide everyone on earth with affordable energy without contributing to climate change.

  2. Develop a vaccine for HIV and a cure for neurodegenerative diseases.

  3. Protect the world from future health epidemics, which might be more infectious than Ebola and more deadly than Zika.

  4. Give every student and teacher new tools so all students get a world-class education.”

The Counterintuitive Solution to Finding Neurodegenerative Drug Targets

I think finding a cure for neurodegenerative diseases is a hunt for the Black Swan.

A lot of what I’ve found suggests that humanity’s best bet against Alzheimers, Parkinson’s, and other neurological diseases might even consist of not focusing research dollars on these areas.

Meta-research suggests that pseudorandom basic science research has had mega yields on biotech, far greater reaching than top-down initiatives.

If you look at the meta research closely, you will easily come to the conclusion that basic science funding is mission critical to the advancement of humanity.

Focus is a Scientist’s Best Friend
The evidence suggests we should get out of the way of scientists and pump them full of cash and reduce their context switching costs. (Paperwork can be exhausting – grant applications are no joke).

The Groundbreaking Innovations Come Without Warning and Without Attention, Unexpectedly. 

CRISPR-9 was discovered by accident while trying to understand how bacteria fight the flu. (CRISPR-9 is the acronym for gene editing brouhaha).

Penicillin was discovered via Alexander Fleming’s random mold observation.

Roentgen discovered X-ray tech by accident when he shot electric current through a special gass in a glass tube. Roentgen found out that he’d made a ray that passed through light elements, but interacted with heavy ones; the X-ray.

Vaccines were accidental too. (Edward Jenner – cowpox)

In reference to Nixon’s war on cancer:

“Despite the Herculean effort and enormous expense, only a few drugs for the treatment of cancer were found through NCI’s centrally directed, targeted program. Over a twenty-year period of screening more than 144,000 plant extracts, representing about 15,000 species, not a single plant-based anticancer drug reached approved status. This failure stands in stark contrast to the discovery in the late 1950s of a major group of plant-derived cancer drugs, the Vinca Alcaloids -a discovery that came about by chance, not through directed research.” – Happy Accidents: Serendipity in Modern Medical Breakthroughs.

Every Few Years, Someone is Peddling an Initiative. They rarely work out. 

Edit: -10-26-2016 –
The exception case here is the Human Genome Project as so prodigiously/graciously pointed out to me by Keith Robison of the OmicsOmics blog, which anyone who is trying to learn more about life sciences and drug discovery SHOULD read.


Keith even wrote a response blog post a few days later. I think the main point I was trying to make here is not that genome sequencing wasn’t useful, but that high expectations on it are probably not warranted. I feel honored to be covered by Keith. 🙂

Vaccines Need Constant Supervision, But For Everything Else, Let’s Back the Scientists on Basic Science

I still think Vaccine research is absolutely mission critical, anytime a politician says they want to attack a disease, we should probably rethink the efficacy of statements like these.

A Worthy Books On The Topic of Accidental Scientific Discovery:

Happy Accidents: Serendipity in Modern Medical Breakthroughs

Why is India so Behind? – The Question I Get From Westerners

I get asked a lot about why India is so behind from white westerners who just visited and want to help the country. This type of question comes up often and it’s worth answering.
I’m more well informed as to the nuances of why/how a country with an overeducated technical class is so far behind than most people.
My formal training sits at the intersection of large scale systems, policy, material feedstocks, and my father has essentially been an agronomist for 50 years— so the problem at large shines brightly in front of me. I also traveled 6000 Km through India on motorcycles, trains, planes, etc…. from North to South and visited many pieces of the country’s infrastructure.
If anyone tells you that India is behind because of its people or culture, you can simply point to the ridiculously successful diasporas of Indians all over the planet. This is a dumb ethnocentric view that lacks context.
The technocrat class of Indians is savage and if you removed Indians from US academic teams, you’d see a decline in winning.
So why? Why are Indians so behind? With so many smart people? Why do brains drain? Why is the country in relative shambles?
India and other developing countries are largely behind not because of their culture but because of their ability to generate energy sovereignty and independence.
We have not been allowed to develop quick and speedy solutions because of the way western countries block us from acquiring nuclear hardware and uranium.
India has 4x the population of the USA and generates 1/3rd the energy with constant blackouts.
We have 100M+ people working in agriculture. This is the efficiency price we pay for a non-refrigerated supply chain and being short on fertilizer — the primary efficiency driver in farming. You need electricity to power both of those things.
India is outside the Nuclear Non-Proliferation Treaty due to its weapons programme, and for ~35 years it was excluded from trading Nuclear technologies and materials(uranium). This basically held us back til 2009.
“Since 2010, a fundamental incompatibility between India’s civil liability law and international conventions limits foreign technology provision.” – essentially, westerners don’t want us to have Nuclear capabilities.
Because of this myriad of complex laws, India’s substitute came in the form of unwieldy Fast Breeder Reactor(FBR) Thorium plants.
FBRs work by utilizing unmoderated neutrons to ‘breed’ fissile plutonium and possibly transuranics —- usually Uranium 238…..but I’ve heard its flexible enough to make fissile Uranium 233 too directly from Thorium.
Basically, India has had to over-invest in futuristic technologies to use Thorium b/c the west blocks us from using the current vaccine/solution to our problems that we know will work — Uranium.

Tech is Characterized by Power – Law. Lots of Output, Very Few Winners

There’s 200,000 new apps that come out each month, but very few will be successful.

There’s 8-10 genetic marker tests that come out each day, very few if any are decipherable/can be tied to as an indicator of disease. There’s ~60k genetic tests on the market.

3000 types of steel exist, and 80% of them were invented in the last 20 years. A small minority of them make up the majority of usage.

Proteins, Sugars, and Fats: A Quick Rule of Thumb

My friend Alexander Girau at advanotech gave me a quick primer on Proteins, Sugars, and Fats. I found this relevant as I began exploring ketosis and veganism last year out of curiosity.

Figured I’d share it here:

Proteins (amimo acids):

8/9 (one is isomeric) essential (for humans) amino acids associated with making proteins.

20/21 common amino acids associated with making proteins.

250 general amino acids that compose other biomolecules.


Can be separated in several ways but mainly by chain length (monomer, dimer and poly)and structure (linear, cyclic).…/Resources/cfb/carbohydrates.htm

Fats (Lipids):

Dietary fats are triglycerides separated based on hydrogen content (saturation) and isomeric stricture (cis-trans). However, they are generally known as a lipid.

Other lipid-like molecules include: steroids, phospholipids, waxes, fatty alcohols, fatty acids.

About A Year Ago, I Met Someone Who Saved Millions of Lives

About a year ago, I met someone pretty interesting. I think his story is one worth sharing.
He spent the last 8 years figuring out how to save Indians from roadside disasters after his nephew died in a roadside accident where good Samaritans didn’t step in.
At that time, India did not have forward thinking Good Samaritan laws.
This man spent 8 years…think about that… nearly a decade fighting to issue a hard-reset in one of the world’s most difficult bureaucracies. His name is Piyush Thewari. He’s the founder of SaveLife. 

One of the World’s Addressable Problems: Indian Roadside Death Stats
  • 1M+ people in India have lost their lives to road accidents in the last 10 years.
  • 10% of total global road deaths occur here making India the leader in roadside deaths.
  • In 2013 alone, almost 140,000 people were killed and close to 500,000 were seriously injured or permanently disabled
  • 50%: Number of road crash victims who die of treatable injuries
  • 74% of Bystanders are unlikely to assist a victim of serious injury
  • 88% of Bystanders who are unlikely to assist a victim of serious injury, stated that they were reluctant to help for fear of legal hassles, including repeated police questioning and court appearances.
  • 77% of Bystanders who are unlikely to assist injured victims also stated that hospitals unnecessarily detain Good Samaritans and refuse treatment if money is not paid for treatment.
If you want to read more about him, here it is:

The Germans, Their Renewables, and Much Ado About Nothing

There’s been some recent news with positive sentiment toward Solar Power in Germany creating super positive outcomes, but I believe it’s worth pointing out that this is much ado about nothing.

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Germans produce power semi randomly.
They then put strain on the power-grid and pretend it’s renewable.

Customers didn’t and won’t get any money from the power companies, instead they paid the same rate they always do.
The negative price happened a level higher up, at the electricity exhange Epex Spot. ( it’s in Liepzig.

This is where power companies buy and sell electric energy and here, they could actually get paid if they were able to accept and use electric power.

It’s the wholesale price (you get delivery in mega-watts hours) not the retail price who indeed pay the same rate all year round…

The market speculators are the ones who really made the money.

I know this because I used to communicate with utilities about electricity consumption a lot. I used to electricity options when I designed manufacturing plants.

There’s a marketplace of electricity where they sell it like bananas and stuff.

I think it’s great that Germany is pushing R&D on renewables, but I haven’t seen any evidence to date that suggests if everyone goes solar that it will make any sort of double digit percentage impact on humanity’s CO2 emissions.

If anything it’s a distraction from carbon capture requirements on coal plants, something we must push the government into doing.

I’m just hopeful that humanity starts getting rid of coal and taxes carbon credits. The solar and wind hype won’t have an impact on the carbon emitted by dirty sources.

My point here is not knocking solar but simply pointing out that it’s the wrong battle to think solar vs. coal/oil. This sort of rhetoric, passion, and lobbying should be spent on regulating carbon capture requirements to make extreme impacts on CO2 emissions.

The Lack of Substance in Liz Parrish’s Bio-Viva Claims

I’ve gotten about 60 messages about Liz Parrish’s outfit and the test on herself to lengthen her telomeres.

I don’t think there’s any substance to any of her claims and life extension.
(Her article:…/first-gene-therapy-successful…/)

A few very critical questions:

  1. What if anything does telomere lengthening have to do with life extension? (It’s multi-factorial) Correlation is not causation.. See:
  2. Why did she use a lab that’s on quackwatch to do the tests? (…/…/nonstandard.html)
  3. Haven’t we already proven telomere lengthening and muscle hacks in animal models?
  4. What type of AAV is she using to transfect her cells with telomerase? (Take a look at the animal studies:,…/10.1186/1743-422X-10-74)
  5. How many cells had their telomeres lengthened? (I bet you it was a petty amount…..100 to 1 says they’re not all that good at actually delivering genes)

There’s actual chemists/biologists busting their ass at places like genentech and top research universities to solve missing mendelian inheritance the long difficult way.

They’re true pioneers staring down the barrel of a gun loaded with the world’s most difficult NP-Hard problems. This Parrish outfit steals their thunder.

Aging isn’t something you can simply disrupt with a silicon valley mindset.

I’ve met organic chemists who have spent upwards of 30 years developing drugs and haven’t put a single drug on the market. Their work was still super valuable.

Initial Thoughts on Software Eating Biology

I read Vijay Pande’s piece on the A16Z blog from start to finish multiple times. It’s worth checking out if you haven’t seen it already.

I have zero biochemistry background, so take most of my commentary with a reasonable grain of salt. I run a site that helps chronically ill patients aggregate their medical records and find relevant clinical trials. We also make a product that helps patients and their families translate difficult to read research papers into understandable content.

My Initial Thoughts.

I perceive that the speed of the tools matters less than we think it does. This is purely speculative and an opinion.

A pharma expert recently pushed the question to me:

How is it possible that the technologies that most people think are important for drug discovery have become hundreds, thousands, or billions of times cheaper, while the cost of R&D, per drug discovered, increased roughly 100 fold between 1950 and 2010?

Meta-research suggests we need more predictive validity/predictive modeling than we do faster tools. In simple words, “we need more maths.” —-

One of the parts of the interview that struck me was this question about software connecting the dots.

a16z: How can you make the claim that software connects the dots? Because when I think of bio, I think of tissue and flesh; I don’t think of computation and algorithms. How do those two actually come together?

Vijay: Let’s take machine learning. You can now do so much with image recognition there. And a big part of medicine involves images. Sure, when you go to your doctor, a bit of listening happens, but most of it is really about analyzing your x-rays (radiology), examining your skin (dermatology), or looking at your eyes (ophthalmology).Of course, these doctors aren’t just using their eyes; they’re applying and honing decades of medical training to do the pattern recognition, which in many cases is very subtle and requires significant expertise. There’s going to be many examples like this where computation can do something beyond what a human being can. It’s not limited to just vision. Think of all the inputs that humans take in with their senses; each of those are amenable to machine learning and deep learning: Listening with a stethoscope. Smelling something. And so on.In many cases, algorithms can do better than humans. Just as computer vision has had a huge impact in non-medical areas, it’s now getting to the point where it can set a new gold standard. If the gold standard in radiology is to predict what radiologists would do, computers can go beyond that. In radiation oncology for example the gold standard would be to predict the biopsy results … without having to actually put the patient through one.

I think Pande’s comments are very in line with reality and we’re already starting to see such technology in place, at companies like

Given that cost of MRIs in the USA is aberrationally high, will we still need predictive algorithms of biopsies then?

The efficacy of biopsies as a precaution still seems to be up in the air for colorectal cancer/UC….

Curious to see more maths done in this entire arena. In any case, Pande is worth following on twitter.

Thoughts on CDixon’s What’s Next in Computing Piece

I follow Cdixon on Twitter. He’s an investor at A16Z. I wanted to

I’ve been reading his post What’s Next in Computing. and figured it was worth adding something about the nature of EDA’s open source progress. The piece is worth a sit down and read.

He makes a good key point that I wanted to expand upon.

Moore’s Law and SOCs.

“We are now entering an era in which processors and sensors are getting so small and cheap that there will be many more computers than there are people.

There are two reasons for this. One is the steady progress of the semiconductor industry over the past 50 years (Moore’s law). The second is what Chris Anderson calls “the peace dividend of the smartphone war”: the runaway success of smartphones led to massive investments in processors and sensors. If you disassemble a modern drone, VR headset, or IoT devices, you’ll find mostly smartphone components.

In the modern semiconductor era, the focus has shifted from standalone CPUs to bundles of specialized chips known as systems-on-a-chip.”

The Next Generation of EDA

What I think is worthy of mention is the growth of Fabs, Foundries, open source software(SPICE etc..) and the ability of a small group of chip designers to produce mixed-signal chip fully functional prototypes in a package without spending $100K+ on EDA Software, of which there’s only 3 players: Cadence, Synopsys, and Mentor Graphics. I’ve met people on the r/chip_design subreddit who have created chips for actual products for basement prices. <$10K

I was part of company working in this space to change the way chips are designed. There’s one such company in the bay area producing 180nm Mixed Signal analog chips for less than $5K to get to silicon.

I believe EDA software is the blocking element. It lives in the stone age.

Version control, forking, etc.. and a lot of the paradigms of software design have not been given to the world of chip designers. They live as if in an anachronism and our chip design education is in the stone ages.

On a side note, Moore’s law is arguably a self-fulfilling prophecy.

It’s also worth adding that exponential growth doesn’t happen in the physical world, it happens on S-curves, like every other technology.

Why I Don’t Necessarily Hate Shkreli

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The skinny on Martin Shkreli, the acquirer of Turing Pharmaceuticals.

Raise a couple of hundred million.
Buy orphan drug. (Drugs with less than 3000 patients)
Insurance companies +FDA won’t pay for or certify the viability of cheaper foreign generics/biosimilars.
Make Insurance companies foot the bill.
If the patient doesn’t have insurance, give it away for free or mostly nothing.

By law, the federal government cannot negotiate prices with drug companies. I think, this is something that has to be modified to some extent. This is the elephant in the room.

At the time of Shkreli’s major announcement and well prior to it, it seems that patients could buy Daraprim online from Canada at $2.50/pill.