Howard Schachman: The Centrifuge Pioneer Who Revolutionized Biochemistry
The 97-Year Legacy of a Scientific Giant
The 97-Year Legacy of a Scientific Giant
When Howard Kapnek Schachman died in 2016 at the remarkable age of 97, the scientific world lost one of its most passionate advocates for rigorous research and ethical science policy1 . Born in Philadelphia in 1918, Schachman began his scientific journey with a single-author paper in 1942 and continued shaping the field of biochemistry for nearly seven decades1 2 . His story is not just one of scientific discovery, but of a deep commitment to ensuring that science remained a force for good in society—a legacy that continues through the many scientists he mentored and the policies he helped shape.
Schachman's career began at a time when biochemistry was still in its relative infancy, and his work would help revolutionize how we study proteins and enzymes. But perhaps even more impressive than his scientific output was his unwavering dedication to scientific integrity and public service, values he held until his final days. Even at 97, with declining eyesight and manual dexterity, he continued teaching research ethics and creating his own PowerPoint slides—a testament to his lifelong passion for education2 .
Biochemistry Pioneer
Revolutionized protein study methods
Ethics Advocate
Championed scientific integrity
Dedicated Educator
Mentored generations of scientists
The Scientist and His Legacy: More Than Just Research
From Chemical Engineering to Biochemistry
Schachman's scientific journey nearly took a very different path. As a high school student, he was more interested in social and political issues than science and initially planned to become a rabbi3 . He began his college education in liberal arts before a family friend urged him to consider employment prospects, leading him to switch to chemical engineering3 .
Scientific Contributions and Technical Innovations
Schachman's most significant scientific contributions revolved around his expertise with the analytical ultracentrifuge, an instrument that uses high-speed rotation to separate and characterize macromolecules based on their size, shape, and density2 .
Key Technical Developments
"He made the cross-country road trip from Berkeley to a New Hampshire Gordon Conference with his family in his Model E centrifuge" - Jeremy Knowles2
The ATCase Breakthrough: Understanding Enzyme Regulation
The Allosteric Revolution
While Schachman's methodological work alone would have secured his scientific reputation, his most famous contribution to biochemistry came from his work on aspartate transcarbamoylase (ATCase), the enzyme that catalyzes the first committed step in pyrimidine biosynthesis1 .
In 1964, Schachman initiated a collaboration with junior colleague John Gerhart that would propel them to the forefront of the then-burgeoning field of allosteric regulation2 .
Schachman and Gerhart made the crucial discovery that ATCase could be separated into two different types of subunits: one responsible for the catalytic activity and the other associated with regulatory factors2 . Specifically, they found that ATP acted as an activator of the enzyme, while CTP functioned as an inhibitor1 .
This discovery placed Schachman and Gerhart at the center of a spirited scientific debate between two camps of thought regarding how allosteric regulation worked at the molecular level.
Methodology and Experimental Design
The experimental approach to understanding ATCase regulation required sophisticated protein characterization techniques, many of which Schachman had helped develop through his work with ultracentrifugation:
Subunit Separation
Carefully separating catalytic and regulatory subunits while maintaining functional integrity
Sedimentation Analysis
Ultracentrifugation techniques for molecular weight and shape characterization
Binding Studies
Studying how substrates and effectors interacted with different enzyme forms
Kinetic Assays
Measuring enzymatic activity under different conditions
This work was so fundamental that two of Schachman's ATCase papers were later designated as JBC Classics1 .
Research Reagent Solutions: The Biochemist's Toolkit
| Tool/Reagent | Function in Research | Significance |
|---|---|---|
| Analytical Ultracentrifuge | Separated macromolecules by size and density | Enabled precise characterization of proteins and their subunits |
| Synthetic Boundary Cell | Layered solutions during centrifugation | Created sharp boundaries for measuring hydrodynamic volumes |
| Aspartate Transcarbamoylase (ATCase) | Model enzyme for studying allosteric regulation | Provided insights into metabolic control mechanisms |
| Catalytic Subunits | Carried out enzymatic conversion of substrates | Helped demonstrate functional specialization in complex enzymes |
| Regulatory Subunits | Bound effector molecules (ATP/CTP) | Revealed how enzymes are controlled by cellular metabolites |
| Tobacco Mosaic Virus | Model system for studying subunit structure | Advanced understanding of viral assembly and protein interactions |
Analytical Ultracentrifuge
Schachman's primary research tool for macromolecule separation
Research Methodology
Innovative approaches to studying enzyme structure and function
Scientific Publications
Schachman's work resulted in numerous influential papers
Scientific Legacy and Public Policy: A Dual Commitment
Leadership in Scientific Societies
While maintaining his passion for research, Schachman also brought his considerable energy and deeply held beliefs to bear on science policy1 .
Leadership Roles
Throughout his career, Schachman remained a vocal critic of what he saw as threats to scientific integrity. He was particularly concerned about politically targeted research funding, excessive indirect costs charged by universities, and overzealous regulation of science2 .
Standing Up for Principles
Schachman's commitment to principle wasn't limited to the laboratory or scientific societies. Early in his career at UC Berkeley, he joined 200 faculty members who opposed the required signing of a loyalty oath mandated by the UC Regents2 .
"There are more good causes than you will have the time or stamina to pursue" - Howard Schachman2
During the Free Speech Movement that erupted at Berkeley in 1964, Schachman became one of the leaders of a self-constituted committee of 800 faculty who worked to find a sensible resolution to the conflict2 .
Dedication to Education and Ethics
Perhaps one of Schachman's most enduring legacies was his commitment to educating the next generation of scientists about research ethics. Each spring, he taught a course on the Ethical Conduct of Research required for NIH-funded students3 .
Afternoon Coffee Sessions
Schachman would hold sessions where he shared stories that challenged students and broadened their perspective5
University Values
He taught that "universities cannot separate themselves from the realities of the world"5
Lifelong Education
Continued teaching research ethics well into his 90s, updating material with current examples2
Conclusion: An Enduring Legacy
Howard Schachman's remarkable 97-year life represents the best of what science can offer—not just groundbreaking discoveries, but a commitment to integrity, education, and public service. From his early technical innovations with the ultracentrifuge to his seminal work on allosteric regulation with ATCase, and from his leadership in scientific societies to his steadfast defense of scientific integrity, Schachman left an indelible mark on biochemistry and molecular biology.
His legacy continues through the Howard K. Schachman Public Service Award, established by ASBMB in 2001 to recognize individuals who demonstrate dedication to public service in support of biomedical science2 . This award ensures that new generations of scientists will be recognized for embodying the same values that Schachman championed throughout his career.
"Big moments—of tension, of challenge, of change—are learning moments for us all" - Susan Wente, former student5
Perhaps most importantly, Schachman serves as a powerful example of how scientists can successfully bridge the worlds of specialized research and broader societal concerns. He demonstrated that one could be both a rigorous researcher and a committed public intellectual, both a dedicated teacher and a principled advocate.
An Enduring Scientific Legacy
Though the analytical ultracentrifuge that Schachman mastered has largely been supplanted by newer technologies, his commitment to methodological rigor, his passion for understanding fundamental biological processes, and his unwavering ethical compass remain as relevant as ever.