Introduction to the World of Mending Life

Dan Yarosh

MENDING LIFE:
WHY AND HOW CELLS PROTECT THEIR DNA
Essays on Genome Stability, Disease, Aging and Therapy

Introduction to the World of Mending Life

DNA repair has grown from a backwater curiosity of biochemistry to front and center of preventive medicine and cancer treatment. Discoveries have illuminated the influence of DNA damage and repair on immunology, stem cells, circadian rhythm, neurological disease and aging. Its tools allow precise genome editing.

Each week I will review an aspect of DNA repair and its relationship to the big questions and challenges of modern biology and medicine. I’ll summarize what we know and highlight what we don’t know (yet). I’ll be posting these weekly essays on Substack and on this website.

I first became interested in DNA/RNA in the early 1960s because of a widespread report that the tiny flatworm planaria would run a maze faster after they cannibalized other planaria who had been trained in the maze. The researcher James McConnell proposed that memories were stored in RNA and were transferred by consuming it. This was just at the time that the structure of DNA was unraveled, and the genetic code was unlocked. I was excited by the idea of a master molecule controlling cell function, heredity and now memory. The planaria discovery turned out to be a hoax, but I was hooked.

Then I learned that DNA could actually fix itself! This time it was no hoax. During high school I experimented with DNA damage and mutations in the laboratory of pioneer D. Peter Snustad at the University of Minnesota. After graduating from Macalester college in St. Paul, I went to study in the laboratory of DNA repair experts Carol and Harris Bernstein at the University of Arizona College of Medicine, where I graduated with a PhD in molecular biology. At the time (1978), there were very few schools offering this degree and almost no biotech companies in existence. DNA sequencing and restriction enzymes were in their infancy.

I won a National Science Foundation Postdoctoral Fellowship to study at Brookhaven National Laboratory with Richard Setlow, world renown leader in DNA repair. I then took my first job at the National Cancer Institute in Bethesda to study a newly discovered DNA repair pathway (essay 7).

After all that training I founded my own biotech company (Applied Genetics Inc.) to commercialize DNA repair. We made DNA repair enzymes and invented a method to deliver them into cells of the skin (essay 8). After 23 years of research and commercial success our company was acquired by Estee Lauder.

I have published 150 technical papers on DNA repair, and my inventions are covered by two dozen issued patents. In my career I have collaborated with brilliant scientists in laboratories all over the world. Sometimes the questions were technical molecular biology, and sometimes they were fundamental. The Bernstein’s asked the question “Why Are Babies Born Young?” The answer, of course, is DNA repair.

For much of the twentieth century, DNA repair was viewed as a focused bit of biochemistry — a molecular housekeeping function. We now understand that it is far more than that.

DNA repair governs:

Cancer risk and therapy response
Immune activation and suppression
Stem cell longevity
Aging and neurodegeneration
Circadian rhythm and metabolic health
The future of genome engineering

Repair pathways are not isolated molecular machines. They are embedded within immune signaling networks, metabolic circuits, developmental programs, and evolutionary pressures. They determine not only whether a cell survives damage — but how tissues age, how tumors evolve, and how we design therapies.

In this series over the next 13 weeks, I will highlight the breadth and depth of DNA repair’s role in so much of biology and medicine. Here are the topics I’ll be reviewing:

Weeks 1          Detection of Damage: How cells sense their DNA has been damaged, and what they do about it.
Weeks 2-4      Immunity and Inflammation: How DNA repair modulates the immune response.
Weeks 5-6      Genome Guardians: How DNA repair protects development and identity.
Weeks 7-9      Cancer Therapy: How DNA repair systems are targeted to improve patient treatment and prevent disease.

Weeks 10-12 Longevity Control: How mending DNA lengthens and improves the quality of life.
Week 13 Rewriting the Genome: How DNA repair systems are being used to edit the human genome.

DNA repair is not merely defensive. It shapes physiology. It influences disease. And increasingly, it enables us to rewrite the genome itself.

The story of DNA repair is the story of biological resilience against assault — and of scientific ingenuity.

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