On Morphogenesis

1/ Morphogenesis is the process by which organisms develop their specific dimensions and forms. It's nature's own sculpting technique, where cells organize themselves into tissues, organs, and entire bodies. This process begins from the earliest stages of embryonic development and continues throughout an organism's life involving a variety of mechanisms, including cell growth, cell movement, and programmed cell death, all orchestrated by an intricate network of genes and signaling molecules.

2/ Three themes that have been prominent in morphogenesis research include:
• Mechanical forces: how do physical forces, such as tension and compression, influence cell behavior and tissue formation?
• Gene regulatory networks: how do genes and gene networks control physical shape and structure?
• Environmental influences: how do environmental factors, including climate change, affect morphogenesis in various species?

3/ Morphogenesis has long attracted mathematical types to biology. One of the most famous is D’Arcy Thompson, a prolific Scottish mathematician and biologist who published On Growth and Form in 1917. This lengthy tome (793 pages in the original edition, 1,116 pages in the second edition of 1942) sought to bring together physics and biology through an analysis of the physical limitations to the growth and structure of organisms. Thompson’s aim was to generalize the underlying mathematical and physical characteristics of form across all of biology. His argument was that growth and form are inextricably intertwined; one aspect cannot be appropriately explained without referring to the other. Remarkably, this door stopper remains in print today.

4/ Alan Turing is a seminal figure in the creation of modern computing. Less well known is that his sole paper on biology proposed a theory of morphogenesis inspired at least in part by D’Arcy Thompson. The paper entitled, The Chemical Basis of Morphogenesis, was published in 1952 and sought to explain how patterns in nature such as stripes and spirals (which came to be referred to as Turing patterns) could arise from a homogenous, uniform state. Turing proposed (correctly) that “identical biological cells differentiate and change shape through a process called intercellular reaction-diffusion. In this model, a system of chemicals react with each other and diffuse across a space—say between cells in an embryo. These chemical reactions need an inhibitory agent, to suppress the reaction, and an excitatory agent, to activate the reaction. This chemical reaction, diffused across an embryo, will create patterns of chemically different cells.” This reaction-diffusion model for morphogenesis has been an important one in theoretical biology, and perhaps in law enforcement, as Turing patterns have been proposed as responsible for the formation of human fingerprints. The abstract for the paper noted (helpfully?), “The full understanding of the paper requires a good knowledge of mathematics, some biology, and some elementary chemistry. Since readers cannot be expected to be experts in all of these subjects, a number of elementary facts are explained, which can be found in text-books, but whose omission would make the paper difficult reading.”

5/ Morphogenesis is essential for the evolution of new forms and helps to explain how diverse life forms arose from common ancestors. As a result, it is a crucial component of the field of evolutionary developmental biology. This field was helped into existence by Stephen Jay Gould who is well known for his popular science writing and for his theory of punctuated equilibrium. In his first technical book, Ontogeny and Phylogeny, published in 1977, Gould detailed the relationship between embryonic development (ontogeny) and biological evolution (phylogeny). In a review of the book published in the journal Paleobiology the reviewer noted that “[s]ome problems in evolutionary biology are at once so obviously important and so intrinsically difficult that few tackle them,” continuing the challenging theme noted in Turing’s abstract.

6/ Recent work led by Princeton scientist Shane Campbell-Staton has described the almost real-time evolution of physical (morphologic) characteristics in elephants in response to pressures from human behavior such as poaching, war, and climate change.

7/ We have noted before in this newsletter the work of Tufts University scientist Michael Levin whose research on morphogenesis has particularly focused on bioelectric mechanisms that guide the development and regeneration of complex anatomical structures. His work is particularly notable for its interdisciplinary nature, combining biology, physics, computer science, and mathematics to tackle fundamental questions about how living systems develop and maintain their form.

8/ While clearly not for the faint of heart, a deeper understanding of morphogenesis could point the way to deeply impactful interventions such as the regeneration of organs, treatment of birth defects, and the amelioration of degenerative diseases.

– Geoffrey W. Smith



First Five
First Five is our curated list of articles, studies, and publications for the month.

‍1/ Socio-genomics
Socio-genomics—the influence of one person's genotype on the observable traits of another—is an emerging field of genomics. Recent research suggests that "Peers' genetic predispositions for psychiatric and substance use disorders are associated with an individual's own risk of developing the same disorders in young adulthood. What our data exemplifies is the long reach of social genetic effects.” Read more here >

2/ Gobbledygook
“Legal documents are notoriously difficult to understand, even for lawyers. This raises the question: Why are these documents written in a style that makes them so impenetrable? [Recent research suggests that] just as ‘magic spells’ use special rhymes and archaic terms to signal their power, the convoluted language of legalese acts to convey a sense of authority. … [T]he researchers found that even non-lawyers use this type of language when asked to write laws.” Read more here >

3/ Promised cures, tainted cells
“Families pay thousands of dollars to store their children’s stem cells with the hope of a healthier future. But the cells are rarely useful, and sometimes contaminated.” Read more here >

4/ Professor’s privilege
“Prior to the 2000s, many European countries practiced something called ‘the professor’s privilege’ wherein university professors retained patent rights to inventions they made while employed at the university. This was a ‘privilege’ because the norm is for patent ownership to be assigned to the organization that employs an inventor; professors were an exception to this norm. American universities, in contrast, had long followed a different approach, where patent rights were typically assigned to the university, who managed commercialization efforts. Professors then split the proceeds of commercializing their inventions with the university. There had long been a sense that commercialization of university research worked better in America, and in the 2000s a number of European countries reformed their laws to move them closer in spirit to the American system. Professors lost their privilege and universities got more into the commercialization game. If the goal of this reform was to encourage more professors to invent things that could be commercialized, several papers indicate this policy was a mistake.” Read more here >

5/ Academic freedom = more innovation
“The innovative strength of a society depends on the level of academic freedom. An international team has now demonstrated this relationship. The researchers analyzed patent applications and patent citations in a sample from around 160 countries over the 1900–2015 period in relation to indicators used in the Academic Freedom Index. In view of the global decline in academic freedom over the past 10 years, the researchers predict a loss in innovative output.” Read more here >



Did you Know?
In this section of our newsletter, we hope to demystify common terms and notions in our work as investors.

Equity financing vs. debt financing
Equity financing is a method of raising capital in which a company sells ownership shares or equity to investors. When a company chooses equity financing, it doesn't have to repay the funds raised like it would with a loan. Instead, investors become partial owners of the company, holding shares that represent a portion of its ownership. This approach is especially attractive to startups and early-stage companies, as it allows them to secure capital without the immediate financial burden of repaying debt. Furthermore, investors who opt for equity financing typically share in the risks and rewards of the business's performance.

Debt financing, on the other hand, involves borrowing money from various sources, such as banks, financial institutions, or even private lenders. In this case, the company agrees to repay the borrowed funds, typically with interest, over a specified period. This repayment obligation can come with a fixed schedule, including regular interest payments. The advantage of debt financing is that it allows companies to access capital without diluting ownership, but it comes with the burden of repayment and interest expenses, which can impact cash flow.

– Haiming Chen & Dylan Henderson

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