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

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 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.

Why I Don’t Necessarily Hate Shkreli

Screen Shot 2016-02-14 at 15.06.02
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.