Notes on Engineering Health, February 2022

Some Random Thoughts

“Two men send their servants to bring water at the same time and cause them to meet. Unaware of the plan, the servants view the meeting as random.” With this story dating to 400 B.C., Democritus explained his vision of a deterministic world. In his telling, randomness could not exist and was simply a lack of knowledge rather than an actual phenomenon. If one had a “vast intelligence” like the one of Laplace’s demon, a thought experiment published in 1814, one could determine every action taken or to be taken.

The idea of a fully deterministic world held sway in the West until very recently. While tools to describe the unknown were developed in the 16th century when Italian mathematicians began to formalize the odds associated with various games of chance, it was not until the early part of the 20th century that the formal analysis of randomness and the mathematical foundations for probability were introduced, leading to their axiomatization in 1933. This work combined with the development of quantum mechanics in the mid-1920’s finally put to bed the fully deterministic worldview. Reality at its most basic layer turns out to be entirely probabilistic in nature.

Combining the understanding that reality is probabilistic at the sub-atomic scale with the Newtonian mechanics we experience at the macro-scale remains a challenging area of thought. Two interesting examples of areas where ideas about randomness are being applied together are in biology and computer science:

1. A recent discovery, published in Nature, showed that mutations, a key element in the evolution of species and the development of diseases, previously thought to occur randomly as DNA replicates, may not happen so haphazardly after all. By looking to see whether mutations happened evenly between gene and non-gene regions of a genome, scientists discovered that Arabidopsis thaliana, a common roadside weed and major model organism of plant biology, can shield the most “essential” genes in its DNA from changes while leaving other sections of its genome to accumulate mutations. This unexpected finding thus described both random and non-random events influencing the development of the genome, and open a new way to think about mechanisms of tumorigenesis as well as ways to engineer improved processes for directed evolution.

2. Randomness is vital for computer security. The ability to generate random strings of numbers and letters makes possible secure encryption that allows people to store data or communicate secretly even if an adversary sees all coded messages. In these instances, the more random the string, the more secure the data. However, short of having the encryption key hidden in your subconscious, creating truly random numbers is surprisingly hard. Especially if all you have available to do it is digital hardware and deterministic software. Both are designed to behave predictably. Therefore, hardware and software designers, trying to find unpredictability, have to look outside of their normal operating environment to find it. Software typically seeks to use external events (user’s mouse clicks, Ethernet packet arrival intervals, or atmospheric noise) to create randomness. There are challenges in finding enough of these seemingly random events, however, to satisfy what is needed for all encrypted operations. Various groups are working at creating high-quality randomness from low-quality (but abundant) sources. And quantum computing looms as a potential solution, though when it will be ready for broad-based commercial use remains very unclear.

It is hard to think or write about anything else this week other than the terrible ongoing events in Ukraine. Russia’s unprovoked attack is a stark reminder that seemingly stable liberal democracies are not impervious to the frightening descent into war and all its attendant randomness. We stand with the people of Ukraine and hope that the world will act together to reject Putin’s deterministic attempt to violently and illegally impose on their sovereignty and freedom.

Jonathan Friedlander, PhD & Geoffrey W. Smith

First Five

First Five is our list of essential media for the month which spans a range of content including scientific papers, books, podcasts, and videos. For our full list of interesting media in health, science, and technology, updated regularly, follow us on Twitter or Instagram.

1/ Under Pressure
Being stressed about doing well on a test might not be limited to humans. According to a new study, monkeys, like people, can “choke” under pressure.

2/ An Apple a Day…
A young adult in the U.S. could add more than a decade to their life expectancy by changing their diet from a typical Western diet to an optimized diet that includes more legumes, whole grains, and nuts, and less red and processed meat, according to a new study. For older people, the anticipated gains to life expectancy from such dietary changes would be smaller but still substantial.

3/ More Health, Less Healthcare
A new report, from the American College of Lifestyle Medicine, and published in the Journal of Family Practice, argues that 90% of U.S. health care dollars are spent on preventable disease and that the practice of medicine needs to be upended, focusing less on pharmaceutical treatments and instead more on lifestyle medicine that is rooted in six behaviors: better eating, physical activity, restorative sleep, social connection, avoidance of risky substances, and stress management. Read more here and h/t to our friends at Building H for pushing this theme.

4/ Triggered
A new study provides compelling evidence of a causal relationship between Epstein-Barr virus (EBV) and multiple sclerosis (MS). It suggests that most MS cases could be prevented by stopping EBV infection and that targeting EBV could lead to the discovery of a cure for MS. This discovery may have repercussions for the understanding of other auto-immune disorders and their links to viral infections.

5/ Small Wolves, Small Dogs
Popular belief has been that small dogs, such as Pomeranians and Chihuahuas, exist because once dogs were domesticated, humans wanted small, cute companions. But researchers now identify a genetic mutation in a growth hormone-regulating gene that corresponds to small body size in dogs that was present in wolves over 50,000 years ago, long before domestication.

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Terray Therapeutics
Participated in Series A funding led by Madrona Venture Group with additional participation from a broad syndicate of new and existing investors including Two Sigma Ventures, KdT Ventures, Goldcrest Capital, XTX Ventures, Sahsen Ventures, Greentrail Capital and Alexandria Venture Investments. This financing follows a previously unannounced $20 million seed round that Digitalis Ventures co-led with Two Sigma Ventures.
Endpoints News > C&EN > Biospace > MedCityNews >

PORTFOLIO NEWS

BioMilq
Hacking Mother’s Milk
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20 Women Trailblazing the Future of Food Science
Vegan Women Summit >

Brella Insurance
Startup supplemental insurer Brella banks $15M series A funding round
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Cayaba Care
Top 58 Women’s health startups
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Elemental Machines
Elemental Machines ships sensor-enabled smart lab system
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What will digital transformation in research labs look like?
The Science Advisory Board >

Sridhar Iyengar on Figuring Out the Key Element to Success
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Faeth Therapeutics
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Findhelp
Findhelp Ranked #1 2022 “Best in KLAS” Social Determinants of Health Network
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Findhelp Emerges as Leading Service to Help Providers Address the SDoH
RAC monitor >

Findhelp Provides Native Social Care Closed-Loop Referrals with Epic’s Community Referral Network (CRN)
Yahoo! >

Centurion Health launches nationwide reentry initiative with Findhelp partnership
PRNewswire >

Good Therapeutics
Good Therapeutics lands $8M to develop protein drugs that work only where needed in the body
GeekWire >

Targeted Molecule Therapeutics and the Role of Cytokines in Oncological Treatment with John Mulligan
Finding Genius Podcast >

Kingdom Supercultures
Meet the New Generation of Microbial Farmers
Modern Farmer >

Dairy Dialog Podcast 170: Kingdom Supercultures
Dairy Reporter >

Second Genome
Second Genome Presents New Preclinical Data for SG-5–00455, Potential First-in-Class Development Candidate Targeting PAI-1/2 for the Treatment of Inflammatory Bowel Disease (IBD)
Yahoo! >

Second Genome Nominates Development Candidate Targeting PAI-1/2 for the Treatment of Inflammatory Bowel Disease (IBD)
PRNewswire >

Somatix
Top 41 Remote Patient Monitoring startups
Medical Startups >

LG announces the first 50 participants in its LG Nova program
TechCrunch >

Portfolio Job Opportunities
Digitalis portfolio companies are hiring
See Open Positions >

Digitalis Commons

Public-Interest Technologies for Better Health

Digitalis Commons is a non-profit that partners with groups and individuals striving to address complex health problems by building public-interest technology solutions that are frontier-advancing, open-access, and scalable.

Digitalis Commons is proud to continue to support Columbia’s Program for Diversity and Inclusion in Commercialization and Entrepreneurship (DICE). DICE aims to support early-career individuals who identify as being from traditionally underrepresented groups in science entrepreneurship and commercialization as defined by the NIH. Building on the success of the first DICE cycle in 2021, this year’s cycle will be expanded to include both life science and physical science DICE Fellows. DICE will provide eligible Columbia graduate students and postdocs with educational programming, mentorship, networking, and funding opportunities to prepare participants for careers in bringing life science and physical science innovation to market. For more information, check out the program page and contact techventures@columbia.edu with questions.

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