The Death Of A Dogma: David Baltimore And Lessons For Modern Drug Discovery

By Ray Dogum, Chief Editor, Drug Discovery Online

As someone who is as curious as I am skeptical of strongly held beliefs, I’d like to honor a scientific contrarian who helped shape a new generation of discovery. David Baltimore passed away at 87 years old, on September 6, 2025. He was more than a Nobel laureate; he was widely regarded as a scientific visionary. At just 37, he co-discovered reverse transcriptase, an enzyme that flipped molecular biology on its head by showing that genetic information could flow from RNA back to DNA, not just the other way around. This discovery shattered the long-standing central dogma of biology, which had held sway since Francis Crick articulated it in 1958: DNA → RNA → Protein.

“Apparently the classical process of information transfer from DNA to RNA can be inverted.”
— David Baltimore, Nature, 1970

How Did the Central Dogma Survive So Long?

The central dogma of biology was elegant, intuitive, and deeply entrenched. It shaped textbooks, guided research funding, and influenced generations of scientists. But it was also incomplete. Baltimore’s discovery, alongside Renato Dulbecco’s and Howard Temin’s, was initially met with skepticism. Yet over time, their findings were replicated and accepted, earning them the 1975 Nobel Prize in Physiology or Medicine.

What’s wild is how long the dogma persisted despite cracks in its foundation. It took a young professor at MIT to challenge it and its dogmatic believers. Baltimore’s courage to question consensus is a lesson we should carry forward in drug discovery.

The Whitehead Institute: A Legacy of Disruption

In 1982, Baltimore helped found the Whitehead Institute for Biomedical Research, a self-governed powerhouse affiliated with MIT. Funded by philanthropist Jack Whitehead, the institute quickly became a global leader in molecular biology and genetics, contributing the largest single dataset to the Human Genome Project.

“The study of biology is partly an exercise in natural esthetics. We derive much of our pleasure as biologists from the continuing realization of how economical, elegant and intelligent are the accidents of evolution.”
— David Baltimore, Nobel Lecture

Dogma in Drug Discovery: A Double-Edged Sword

Drug discovery operates at the extreme bleeding edge of knowledge about our universe. It’s where biology meets chemistry, physics, computation, and human health. And yet, despite its complexity, the field is often guided by simplified models and assumptions—dogmas that can both accelerate and limit progress.

For decades, drug discovery has been dominated by the protein-centric paradigm: find a target protein, design a molecule to modulate it, and test it in disease models. This approach has yielded blockbuster drugs, but it’s also left many diseases untouched.

“As long as I have been in science... just about every five years there are major changes in technology that allow you to do things that you previously either said were just too hard or which you hadn’t imagined you could ever do.”
— David Baltimore, Interview with Vincent Racaniello

Today, new technologies like RNA therapeutics, gene editing, AI-driven modeling, and organoid platforms are challenging the old frameworks. But the real question is: Are we still clinging to outdated assumptions?

What Might Be the Next Dogma to Fall?

Here are a few contenders:

• The idea that aging is inevitable: Longevity science is pushing boundaries once thought immutable.
• The gene-centric view of disease: Research suggests that epigenetics, microbiomes, and environmental factors may play larger roles than previously thought in the manifestations of disease.
• The protein-first model of drug discovery: RNA-based therapies and non-coding RNAs are challenging this assumption.
• The reliance on animal models: Validated NAMs (New Approach Methodologies) are gaining traction, especially under initiatives like VQN.

Baltimore’s Real Legacy

David Baltimore didn’t just discover an enzyme; he dismantled a worldview. His life reminds us that science is not an effort toward absolute certainty, but a process of relentless questioning.

In drug discovery, where the stakes are high and the terrain is often uncharted, we must be vigilant. Dogma can guide, but it can also blind. Baltimore’s legacy urges us to ask: What are today’s dogmas? And who will be brave enough to challenge them?