Book Notes: Microbes, Gene Editing and a Terrible Disease

It is something I don’t talk about very often but I love science, biology , biotech and in I try to stay up to date on these topics so from time to time I try to read scientific divulgation books.

I had some pending books on my “to-read list” so in November I bought three of those books (birthday present to myself) and spent the Christmas holidays reading them. I’ll share some notes in this post.

1. The emperor of all Maladies: This has become a classic book on the subject of cancer and has received extensive media coverage (it even became a PBS documentary). The books tells the story of cancer, how the first treatments were developed and why it is so complex and hard to cure. Some Insights and facts that caught my attention reading this book:

  • Until “very recently” , we were in the dark ages of medicine: From the perspective of scientific and technological progress, the 1800’s don’t feel so far away. I don’t know why but in my head I had imagined these period somehow as being part of our “modernity”, yet it was only in 1846 that we started using anesthesia to do surgeries, and in 1867 we started using carbolic acid to perform surgeries. No doubt surgeries were perceived as a last resource remedy. Imagine the agony and the risk involved in a simple surgery.
  • As a disease Cancer has been documented since very ancient times. In 1862 Edwin Smith an American Egyptologist, purchased a Papyrus in Luxor, Egypt from an Egyptian dealer. It happened to be an ancient medical text, describing 48 cases of injuries, fractures, wounds, dislocations and yes, a case (number 45) that seems to describe a breast tumor.
  • How aggressive , disruptive and experimental the evolution of treatments have been. In our attempt to eradicate malignant cancer cells the treatment itself almost kills us.
  • A lot of progress has been made both in treating and preventing cancer and there are genetic treatment that have demonstrated excellent results but the book explains that part of the complexity in our fight to defeat cancer is that it exploits the fundamental logic of evolution unlike any other illness. Even though we are closer than ever to target very specific mutations (as described in the other books covered in this article) we are not even close to understand the million ways that the approximately 20,000 proteins in our cell interact with dozens if not hundreds of other proteins so that altering one specific mutation to prevent cancer does not lead to an unexpected additional mutation worst that the original.

2 . I Contain Multitudes: We have always perceived microbes and parasites as something to avoid at all costs, they are to blame for terrible diseases. Ed Yong’s book take us on a tour to the latest research about microbes and gives a more nuanced and balanced view about these very special creatures that live inside and among us.

With the use of Metagenomics we are now able to detect at a very precise degree, what combination of microbes exist in a biological sample. The latests research shows that microbes are very relevant to our general well-being, so we shouldn’t try to avoid them,and instead we should strive to get a balanced mix of microbes. They not only influence how we digest food. They play a major role in our complete immune system, our mental well being and are related to diseases as Autism, IBD, Depression and Obesity to name a few. The immune system isn’t just a means of controlling microbes. It is at least partly controlled by microbes.

It has been shown that the use of Probiotics doesn’t really make a big difference in our gut microbiome balance, but when we eat certain foods, we feed our microbes and indirectly promote the growth of some microbes over the other, this is called Prebiotics.

Just as genetic sequencing gave birth to companies like 23andMe offering sequencing as a commercial product to end users. There are a few companies now that can give you personalized health recommendations based on your gut biome and also early success stories in therapeutic use.

It is worth noting that, as a Science Journalist, Ed Yong made a terrific job covering Covid-19 during 2020 in the Atlantic. I also recommend taking a look at his TED talk.


3. Editing Humanity: This is the most recent of the three books. It covers the story of how the new CRISPR gene editing techniques developed. The scientists and labs behind them (also the patent disputes). The breakthroughs and innovation in disease treatment currently being developed and the inevitable arrival of the possibility of human genomic editing and the implications to us as a society.

CRISPR is part of the bacteria inmune system, it is a mechanism that allow bacteria to defend against viruses by cutting their DNA ( viruses are some of the bacterias fiercest enemies).

This book, tells the story of how the mechanism was first discovered by a Spanish scientist and confirmed by some researchers from a Danish dairy company, then it describes how this mechanism was engineered (taking advantage of the latest mRNA research) , so that we could tell the enzymes the exact piece of DNA to cut and replace it with a new sequence.

The book also explains how error prone the first experiments where with the basic CRISPR Cas9 mechanism and how the technology is evolving to become a precise “molecular editor” capable of replacing single bases without cutting DNA.

One major difference in the approach to gene editing is whether it used to edit someone cell to repair an unwanted mutation that causes a disease (somatic gene editing) versus editing a single reproductive cell or gamete, just before the fertilization takes places.

The first approach involves fixing DNA in millions of cells and is error prone, the second approach involves just editing one single cell but it makes the change heritable, so it basically implies the potential ability to alter human evolution. This has triggered a lot of debate in the scientific community, specially because most of the tools and supplies to perform have a very low barrier to entry.


Final Thoughts

Since I read Ray Kurzweil’s book The Singularity Is Near: When Humans Transcend Biology (back in 2005) I have tried to follow up on the promise of Genetics, Nanotechnology and Robotics. Of the three , I guess Nanotechnology really has not delivered on Kurzweil expectations (who by the way , works at Google since 2012), but Robotics has continued to evolve to a very impressive degree, you can check the Boston Dynamics Christmas christmas robot dance.
But of the three, I think nothing has evolved as fast, as genetics and biotech in general.

We have been hearing that software is eating the world, but now we also now that bio is eating the world. Advances in Biotechnology are evolving at neck breaking speed. Just a few years ago this all sounded like science fiction but just as I was finished reading these books DeepMind announced the Protein Folding problem has practically been solved.

Like the Silicon Valley Startup ecosystem, there is a whole ecosystem of biotech startups. This is also leading to a whole new wave of investment opportunities.

Having the ability to edit genes in a precise way while also solving the folding problem are two major achievements, I wonder why they receive so little attention.

I am sure in the following years (months?) we will be hearing a lot of new discoveries and breakthroughs.

February 6 Readings

Mexico’s President Is Spoiling for a Fight With Washington.

Managing Your Investments Late in the Cycle: Nobody knows for sure whether equities will keep rising or for how long, but knowing a little market history can help ease the anxiety.

The Rise and Fall of Bitcoin Billionaire Arthur Hayes.

This Is Where Empathy Lives in the Brain, and How It Works.

February 2 Readings

On Attitudes to Risk: GameStop, Covid and how we perceive Risk.

Worrisome New Coronavirus Strains Are Emerging. Why Now? (Wired)

The problem with prediction: Cognitive scientists and corporations alike see human minds as predictive machines. Right or wrong, they will change how we think

What to Know About Music’s Copyright Gold Rush.

Virgin Hyperloop Releases Concept Video of Future We Want to Become Reality (Gizmondo):

February 1 Readings

Currencies, Commodities, Collectibles and Cryptos (from NYU’s Prof. Aswath Damodaran)
The Bit Short: Inside Crypto’s Doomsday Machine

Both Michael Lewis (The Big Short” , “Moneyball”) and Malcolm Gladwell (“Outliers”, “The Tipping Point”) have new books.

Superforecasting: The Art & Science of Prediction (Book Summary from Richard Hughes Jones)

The Unauthorized Story of Andreessen Horowitz


January 30 Readings

Ten computer codes that transformed science: From Fortran to arXiv.org, these advances in programming and platforms sent biology, climate science and physics into warp speed.

Two interesting profiles on the Reddit Gamestop craze in NYT and WSJ ( via Matt Levine’s Money Stuff).

So You Turned $300k Into $3 Million. Now What?

The 2020 Jazz Critics Poll: It’s After The End Of The World

Book Notes: The Psychology of Money


In 2018 Morgan Housel (ex-WSJ columnist and Collaborative Fund partner) wrote a report outlining the most important flaws, biases, and causes of “Bad Behaviour” affecting people’s dealing with their money, the report became very popular, so he decided to write a book and deep dive into those topics. These are some notes from the book:

  1. No one is crazy: Money decisions are hard and some biases are “hardwired” into our own perceptions and experiences, but “no one is crazy”.
  2. Luck and Risk: We should avoid confusing luck with good judgment and bad outcomes with bad judgment. This topic is what Annie Duke calls “resulting” in her book Thinking in Bets.
  3. Never Enough: When setting financial goals, know when enough is enough. Know when to stop the goal post from moving.
  4. Confounding Compounding: Basic finance but highly underrated point, just slightly above average but constant and consistent returns are very powerful.
  5. Getting Wealthy vs Staying Wealthy:Never risk the option to be around long enough for compounding biggest benefits to take effect.
  6. Tails you Win: You have to get used to the fact that big returns come from tail events. You can be wrong half the time and still make a fortune (Avoid Loss Aversion , take risks)
  7. Freedom: Time is the highest dividend money pays
  8. Man in the Car Paradox: Money rarely gains the admiration we imagine.Being nice does.
  9. Wealth is what you don’t see: The world is filled with people who look modest but are actually wealthy and people who look rich who live at the razors edge of insolvency.
  10. Save: That’s it. Just Save. It will give you flexibility and the chance to wait for good opportunities in your career and in your investments.
  11. Reasonable vs Rational: Do not aim to be coldly rational when making financial decisions. Aim to be just pretty reasonable. Reasonable is more realistic, and you have a better chance of sticking with it for the long run.
  12. Surprise: Few things stay the same for very long, wich means we can’t treat historians as prophets. That doesn’t mean we should avoid history when when thinking about money. But there’s an important nuance: The further back in history you look, the more general your takeaways should be. General things like people’s relationship to greed and fear, how they behave under stress, and how they respond to incentives tend to be stable in time. The history of money is useful for that kind of stuff.
  13. Room for Error: The wisdom in having room for error is acknowledging that uncertainty, randomness, and chance are an ever present part of life. Margin of Safety is the only effective way to safely navigate a world that is governed by odds, not certainties. You have to take risks to get ahead, but no risk that can wipe you out is ever worth taking: You can be risk loving and yet completely averse to ruin.
  14. You’ll change: Avoid Sunk Costs fallacy and adjust your strategy or financial decisions as necessary.
  15. Nothing is Free: Returns require to accept volatility as the price you have to pay. Market returns are never free and never will be. They demand you pay a price, like any other product.
  16. You and Me: Identify what is your personal investment strategy i.e. what “game” are you playing and avoid taking advice from people playing a different game that yours.
  17. Seduction of Pessimism: Optimism is the best bet for most people because the world tends to get better for most people most of the time. But pessimism holds a special place in our hearts. The short sting of pessimism prevails while the powerful pull of optimism goes unnoticed. Once again , we should be care of loss aversion.
  18. When you’ll believe anything: The more you want something to be true, the more likely you are to believe a story that overestimates the odds of it being true. As has been studied extensively we frequently fall prey to Confirmation Bias and Hindsight Bias

The book ends with two additional chapters , chapter 19 summarizes the previous points. And chapter 20 gives an account of how the author manages his finances when it comes to savings and investing.

At the end of the book there is one additional Chapter that gives an account of why the average us consumer think the way they do (from an Historical Perspective).

I enjoyed the book, it does a good work summarizing some of the most common cognitive bias applied to finance and money.

Book Notes: Capitalism Without Capital




Why market valuations for some companies are so high when the traditional way of analyzing those companies through their fundamentals don’t support those valuations?

Why it seems that Investment indicators are in low levels when interest rates are so low? Is there an additional element hidden in plain sight that could constitute what could be call there is a “Dark Matter of Investments” ?

What is the relevance of Organizational Design, Process Engineering, Training, Innovation management for companies?

The answer to these and other relevant questions is the growth in relevance of intangible assets.

The book resumes decades of research in intangible investments: How to measure them, what are their characteristics and how they event might explain some atypical behaviors of the stock market

In this post I will write some of the notes I took while reading the book

Basic Concepts

Investment: What happens when a producer either acquires a fixed asset or spend resources to improve it.

Asset: An economic resource that is expected to provide a benefit over a period of time.

Intangible Assets: Complex pricing systems, ambitious branding, marketing campaigns, detailed process, new product designs, new business models, training.

Over time , intangible investments (investing in intangible assets) have steadily increased . Data suggest intangible investment overtook tangible investment around the time of the global financial crisis.

Is it possible that the rise of intangible investment is nothing more than a consequence of improvements in IT? Is the intangible economy a sort of corollary of Moore’s Law or an epiphenomenon of what Erik Brynjolfsson and Andrew McAffe call the Second Machine Age? Or is it that IT and the research that lead to it was shaped by and economy hungry for intangible investments rather than intangible investment happening as a response to the serendipitous invention of various forms of IT

How to measure Intangible Investments

Measuring investments is a very relevant component of GDP , but the “investment” concept was strictly limited to physical stuff . It did not take long for economists to start questioning this.

In 1962 Fritz Machlup (one of the first economists to examine knowledge as an economic resource) wrote a book entitled “The Production and Distribution of Knowledge in the United States” in which he asked whether different types of knowledge were valuable things that could be produced and started to measure spending on everything from research and development to advertising and branding to training.

Recognizing that Research and Development and Knowledge Production was a vital force in raising GDP a working group of the OECD ment in Frascati, Italy in 1963, to agree on a common framework for measuring R&D, codifying the approach in what became known as the “Frascati Manual” , revised in several subsequent editions, the latest being in 2015.

The thing that reignited economists interest in the measurement of intangible investments where computers and software development. In 1999 the US BEA introduced software as an investment tinto the calculation of IS GDP.

The idea of a new economy also prompted economist to examine the role of knowledge investment more generally. Theorist worked out economic models where knowledge played a key role in promoting growth, either via spillovers of knowledge from one producer to another, or via the competitive process of investment in continuous product improvement.

Then began a painstaking process of defining and measuring the different types of investment. In 2005 Corrado, Hulten and Sichel produced the first set of estimates for the United States.

Types of Intangibles

Computerized Information: Software and Databases
Innovative Property: R&D, Patents, Copyrights.
Economic Competencies: Training, Market Research, Creating Distinctive Business Models.

How to measure Intangible Investments

Measuring intangible investment is a not as straightforward as measuring tangible investments. First we need to find out how much firms are spending, but not all of that spending will be dedicated specifically to the creation of a long-lived asset. The process has a lot of subtleties .

For example when software development is done in-house, staticians imagine there is a software “factory” inside the firm and try to measure how much spending it takes to run the factory, but how much time is dedicated to the creation of a long-lived asset. For programmers might spend 90 percent of their time but how much time should be assigned to managers ?
How about Marketing, Organizational Capital and Training? Should those be treated as an Investment?

Not all of this questions have been settled yet , but it is a fact that they are very relevant , an example of this is that the intangibles agenda is central to the OECD Innovation Strategy.


Characteristics and Implications of Intangible Investments

The Four ‘S’ of Intangible Investments:

Scalability: Intangible assets can usually be used over and over in multiple places at the same time. The idea that knowledge is scalable is not new and it has been studied extensively , it sits at the heart of Endogenous Growth Theory. In an economy where investments are highly scalable:

1. There will be some Intangible-Intensive companies that have grown very large.
2. A relative small numbers of dominant large companies
3. Business looking to compete with the owners of scalable assets are in a tough position. Winner-takes-all scenarios are likely the norm


SunkenNess: If a business makes an intangible investment and later on decides it wants to back out, it’s often hard to reverse the decision and try to get back the investment’s cost by selling the created asset, it is usually a Sunken Cost.

If intangibles are generally sunken costs, then why invest? Because some of the returns might be very high. But also, an investment in knowledge , even if it fails to create a marketable asset directly, might still be valuable if it creates information that resolves uncertainty form the firm. What is called “Option Value”and the Options approach to Capital Investment.

SpillOvers: It is relatively easy for other businesses to take advantage of intangible investments they don’t make themselves.

As a civilization we have been making rules about the ownership of tangible investments since at least 4,000 years ( there is evidence in ancient clay tablets from Mesopotamia).

With intangible investments is more recent with the development of industrial patents, countries started to tweak their patent and copyright systems to encourage more invention.

There is a premium on the ability to manage spillovers: companies that can make the most of their own intangibles, or that are especially good at exploiting spillovers from others investments will do particularly well.

A significant part of the strategy of intangible-rich companies is combining and managing their intangibles in such a way as to minimize the spillovers and maximize the benefits they get from them

Being well networked, knowing about important developments in ones field, and having the standing to bring together collaborations, ask for favors, and coordinate partnerships become more important in a business where investments have greater spillovers

All this means that in an “intangible-intensive” economy, the ability to make good the problem of spillovers becomes very important. This calls for a particular range of skills:
-Technical Skills or Engineering Knowledge
-In some cases, legal expertise or a talent for deal-making
-Softer Skills like leadership and networking.

Synergies: Ideas and other ideas go well together: This is especially true in the field of technology.

Brian Arthur in his 2009 book “The nature of technology” states that technological Innovations are “combinatorial”. Any given technology depends on the bringing together of already-existing ideas. “Every novel technology is created from existing ones, and therefore….every technology stands upon a pyramid of others that made it possible in a succession that goes back to the earliest phenomena that humans captured”.

Intangible investments also show synergies with tangible assets, in particular information technologies. The relationship between investment in computers (tangible) and investment in processes, supply chain development, and organizational change (all intangibles), has been documented in detail by Erik Brynjolfsson. In his 2002 paper “Intangible Assets: Computers and Organizational Capital” he concludes that the business that got the most out of their software were the ones that invested in organizational change too and that the organizational complements to firms’ installed computer capital are treated by investors as intangible assets.


The intangible investments explanation to Secular Stagnation

Secular Stagnation is a condition when there is negligible or no economic growth in a market-based economy, when growth is measured based on the level of investments, it is a puzzle for some economists when there is a low level of investment even when there are Low Interest Rates.

However it is somehow strange that:
-corporate profits are higher than ever.
-profits are not evenly distributed
-Decrease in Productivity

An intangible explanation:
1. Mismeasurement: Intangible investment is not included in national accounts.
2. Leaders are better are appropiating spillovers and Laggards have low incentives to invest.


Financing the intangible economy: How all these affects banks?

Intangible investments also will have an impact in the financial services industry. If one of the main criterias to lend to businesses is to analyze if there is tangible investments that can be used as collateral to minimize risk. We should expect the following tendencies:

-Shift away from bank lending as a means for financing business or new debt products secured against intellectual property

-Shift toward the use of equity

-Changes in financial accounting standards to include intangible investments in balance sheets.

-Increase in private companies, to avoid disclosure because of spillover-rich intangibles.

-Or block investing in an ecosistem even if there is spillovers, it wouldn matter (Aqui poner una referencia al the problem of twelve https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3247337)

Competing, Maging and Investing in the Intangible Economy

What will succesful companies look like in an intangible-rich economy, and how can managers an investors create and invest in them?


Competing
How can firms improve performance that is sustainable? By Doing something distinctive or having a distinctive asset. It’s more likely that intangible assets can be distinctive, things as Reputation, Product Design and Trained employees providing customer service.

Even more valuable, weaving all these assets together make the organization itself an intangible asset.

Managing
1. In “Synergistic” firms, maybe only the managers know whats going on, since only the managers can see the big picture and realize how the synergies might link up.
2. In intangible-intensive firms there will be a premium on managers who can share information both up and down the organization and keep loyal workers sticking to the firm.
A well managed organization:
-Continuously monitoring & improving processes.
-Setting Comprehensive and stretching targets
-Promoting high performing employees or fixing underperforming ones
How can managers build a good organization in an intangible intensive firm?
Choosing the right organizational design, depending on whether your organizational predominantly uses or produces intangible assets.

Producer: Allows information to flow, promotes serendipitous interactions, keep key talent, promote skills to manage the innovation process.

User: More hierarchies, shor-term targets.

The intangible economy will place a premium on good organization and management. With more sunk costs, spillovers, and the opportunity for scale and synergies, the need for additional coordination rises, and so good organization and management will be in higher demand.

Are you creating intangible assets (writing software, doing design, producing research)?. If so, you probably want a flat organization with more autonomy, fewer targets, and more access to the boss. This allows information to flow, helps serendipitous interactions, and keeps the key talent.


Investing:
How can an outside investor detect if a firm is building its intangible assets?
Can investors get information about intangibles from accounting data? Baruch Lev answers this question ins his 2016 book The End of Accounting (excerpt from the book in the WSJ can be found here). According to Lev, much of companies intangible investments are hidden from view, because by current accounting standards, intangible investments are expended (charge the entire cost of the asset in one year to costs) when they should be capitalized (recognizing that the spending created and asset) . In consequence financial accounts have become much less informative of company earnings.

So what should investors do? One option is to avoid the problem of finding out the information altogether and buy shares in every company. i.e. Diversify.

But also an alternative strategy arises for investors who can identify good intangible investments and back companies that make them. Asset Managers can serve investors by being much more canny about a firm, going beyond the information in the accounts. Understanding the deep innards of the company and the way that external conditions will allow it to use it’s intangible assets will be a highly valued skill.

Conclusions

Intangible investments theory has been studied by more than two decades, I guess the interest in intangible investments has gained relevance because we have more evidence that the hypothesis proposed in the original research seems to be correct.

Recently , Michael J. Mauboussin from Morgan Stanley published an excellent paper where he analyzes the implications for the investment management profession. The key insight: Understanding the magnitude and return on investment provides an investor with a better understanding of a company’s future earnings. The challenge is that the mix of investment has shifted over time and is today more intangible than tangible. That means the recording of investments has largely migrated from the balance sheet to the income statement. An investor’s job has not changed but the analytical approach has.

Sarah Ponczek from Bloomberg also published an article where she writes about the influence on intangible investments in the recent market rally, a remarkable example: “The value of Moderna Inc.’s intangible assets heavily rely on the biotech firm’s ability to develop and distribute a coronavirus vaccine. Consider the math: Moderna’s market-cap amounts to about $28 billion, yet the company’s tangible book value (what can be found on its balance sheet) is less than $1.2 billion. That means $26.9 billion — or 96% — of Moderna’s market value is derived from intangibles.”

Besides the valuation and economic implications I found the book very useful for professionals whose jobs revolves around, Digital Transformation , Strategy/Business Development or Portafolio/Program Management , since it gives a robust explanation of the relevance of Business Process Engineering , Managing correctly the intangible investment process in Software Projects, Managing correctly the innovation process through Open Innovation Programs, and how companies should treat Employee Training Spending as an Investment