2016 Lasker~Koshland Special Achievement Award in Medical Science

Discoveries in DNA replication, and leadership in science and education

For fundamental discoveries in DNA replication and protein biochemistry; for visionary leadership in directing national and international scientific organizations to better people’s lives; and for passionate dedication to improving education in science and mathematics.

The 2016 Lasker~Koshland Award for Special Achievement in Medical Science honors a talented biochemist and visionary leader who has crusaded to enhance scientific education and bolster its influence on societies across the globe. In his research, Bruce M. Alberts (University of California, San Francisco) devised powerful experimental tools that helped him understand the mechanism by which cells copy DNA, thereby establishing a new paradigm of molecular machines that perform crucial physiological functions. Aiming to share not only what he knew about biochemistry, but to teach students how to think like scientists, he teamed up with a small group of colleagues to write an innovative cell biology textbook, now in its 6th edition, that has inspired countless individuals worldwide to find joy in experimentation, discovery, and logical reasoning. As president of the US National Academy of Sciences and in other roles, Alberts has advocated tirelessly to improve science education in the classroom and among the populace. He has championed the notion that science and the institutions that support it provide a crucial foundation for any successful nation, arguing that evidence-based knowledge and value systems are vital for sound decisions that enhance citizens’ welfare. Through his unassuming, honest, and effective approach, Alberts has earned universal respect and trust from scientists and policy-makers in every corner of the planet. 

Alberts’s first dramatic scientific insight grew from failure. In 1965, after five years of graduate school, he met with a group of distinguished Harvard professors for what he thought was a mere formality. Surely, these senior scientists would approve his degree, as they had for every student he knew of. Instead, he flunked.

As Alberts recovered from the shock and dejection (and conducted the additional experiments required to earn his PhD), he scrutinized his approach to research. For much of graduate school, he had been testing a pet theory. Confirmation would have been exciting, but negative results pointed only toward the conclusion that his idea was wrong.

This self-examination spurred a key decision. In the future, he would strive to design experiments that would yield useful information even if they did not turn out as predicted.

That vow prompted him to invent a technique that proved extremely fruitful. It allowed him to capture and analyze any proteins that adhere specifically to DNA. In 1970, he reported that one of the DNA-binding proteins he identified attaches to individual strands of the double helix and straightens them, thus enabling the enzyme that adds letters to a growing DNA chain to do its job easily. The existence of this so-called single-strand DNA-binding protein was a surprise, but research has since established that similar proteins play central roles in all cells.

Wanting to pin down how DNA is synthesized, he devised a strategy for purifying the proteins that are required to replicate a simple bacterial virus’s DNA. In 1975, he demonstrated that six proteins, together, can synthesize DNA in a manner that closely mimics the way this process occurs inside cells. According to conventional wisdom, each protein would act sequentially, after randomly colliding with the DNA template. In contrast, Alberts found that they come together to form a compact molecular machine whose parts move relative to one another. The constituents perform their distinct biochemical tasks in an ordered fashion, as the power stored in ATP’s renowned high-energy bonds provokes shape changes in the proteins that drive the DNA-copying reaction forward.

Alberts correctly recognized that this type of cellular apparatus would serve as an archetype for many other physiological processes. Today’s students can barely fathom an era when this view was not woven into the thread of molecular biology.

Educating students, preparing citizens

In the late 1970s, Alberts embarked on an ambitious endeavor to unite the historically descriptive field of cell biology with the emerging field of molecular biology in a new textbook. In 1983, he and his co-authors published the first edition of Molecular Biology of the Cell.

In crafting the book, Alberts and the team bridged not only novel subject matter, but also hatched a fresh approach to textbook writing. They wanted their descriptions to enlighten rather than merely summarize. Toward that end, they drafted chapters about their specialties and then swapped with their colleagues who did not know those topics. This unconventional strategy embedded neophytes in the process of shaping explanations, and it produced unprecedented clarity.

Prioritizing conceptual learning, the authors avoided vocabulary lists that tend to overwhelm, distract, and confuse students who don’t yet have a framework for the detailed terminology. Clear, informative images, designed to communicate the relevant message in a few seconds, complement the text.

Alberts’s passion for transforming how students learn science extends well beyond cell biology. In numerous roles, he has campaigned for science education that teaches problem solving rather than memorization of facts. Success in this realm, he argues, would equip people to participate in discussions about many issues that affect society and to think critically as they grapple with life’s daily challenges.

In 1993, Alberts took the helm of the National Academy of Sciences (NAS) and led a charge to transform science education in the US. As president of the organization for 12 years, he fueled the completion of robust national science education standards. In addition to establishing goals, these guidelines explain what active science-based learning is, why it works, and how to make it happen. Under Alberts’s leadership, the National Academies also published many strong reports about how to teach science at all levels.

Promoting science to better the world

For Alberts, the importance of science education reaches far beyond American classrooms. As NAS President, he dedicated himself to helping scientists in developing countries, especially those in Africa, gain influence on their governments, with the goal of encouraging evidence-based evaluation in areas such as health, agriculture, the environment, education, and energy. A firm believer that every nation needs its own scientists, who grasp local culture and needs, Alberts has pushed the idea that scientists and strong scientific institutions are essential even in the poorest and smallest countries. Only with avenues for collecting neutral, unbiased scientific advice can citizens and policymakers make logical and appropriate decisions that lead to robust and lasting economic productivity.

Alberts conducted much of this work through the InterAcademy Panel on International Issues (IAP),  a global association that launched in 1993. He contributed significantly to founding and running the organization, which now includes more than 100 science academies. Among other activities, members learn how to create rigorous in-country reports that governments can use to inform policy.

In 2000, the group spun off the InterAcademy Council to provide science-based advice to global organizations such as the United Nations on issues of common concern to all the world’s inhabitants. From its inception until 2009, Alberts co-chaired the body.

After his two terms at the National Academy of Sciences, Alberts continued his international pursuits, in part as one of President Barack Obama’s first science envoys. These individuals were appointed in 2011 to work with Muslim-majority countries on science and technology issues. Alberts has focused his efforts on Indonesia, the world's fourth most populous nation.

He quickly discovered that Indonesia did not have a competitive grant program to support research. Consequently, talented young scientists had no way to obtain funds to test their ideas or potential as investigators. Alberts worked with the World Bank and the Indonesian Academy of Sciences to help Indonesia develop a merit-based funding system, the Indonesian Science Fund, which launched this year.  

He also spearheaded a program that aims to forge trust between scientists in Indonesia and the United States. This venture, Frontiers of Science, assembles about 80 young Indonesian and American scientists to discuss topics of shared interest in Indonesia each year. It operates under the overarching hope that a sense of collaboration will reverberate beyond the scientific arena.

Alberts has lent his talents to many other enterprises and received numerous accolades and honorary degrees. He served as Editor-in-Chief at Science from 2008-2013 and is active on advisory boards of more than a dozen non-profit organizations. In 2012, President Obama awarded him the National Medal of Science.

Whether Alberts is untangling how cells copy DNA or rousing international bodies to mobilize science for society’s benefit, he approaches his passions with humility and openness. With deep, natural curiosity and an unwavering belief that science possesses monumental potential to aid humanity, he represents and advances the highest hopes and ambitions of every scientist. Alberts holds a steady beacon that draws us all toward a better world, shaped by a value system that stands on reason and defies prejudice.

by Evelyn Strauss

Key Publications of Bruce M. Alberts

Morris, C.F., Sinha, N.K., and Alberts, B.M.  (1975). Reconstruction of bacteriophage T4 DNA replication apparatus from purified components: rolling circle replication following de novo chain initiation on a single-stranded circular DNA template. Proc. Natl. Acad. Sci. USA. 72, 4800-4804.

Liu, L.F., Liu, C.-C., and Alberts, B.M. (1980). Type II DNA topoisomerases: enzymes that can unknot a topologically knotted DNA molecule via a reversible double-strand break.  Cell. 19, 697-707.

Alberts, B.M. (1984). The DNA enzymology of protein machines. Cold Spring Harb. Symp. Quant. Biol. 49, 1-12.

Alberts, B.M. (1985). Limits to growth: in biology, small science is good science. Cell. 41, 337-338.

Alberts, B.M. (1991). Viewpoint: elementary science education in the United States: how scientists can help. Curr. Biol. 1, 339-341.

Alberts, B. and Miake-Lye, R. (1992). Unscrambling the puzzle of biological machines: the importance of the details. Cell. 68, 415-420.

Commentary by Peter Walter and Keith Yamamoto in Cell


 

Award presentation by Joseph Goldstein

Our Special Achievement Awardee—Bruce Alberts—is a rare bird. But what type of rare bird?  He is clearly not a Bald Eagle or a Cackling Goose. But he may be a hybrid of a Pacific Loon and a Wild Turkey. Speaking of turkeys, I think the best way to describe Bruce is to invoke a culinary comparison: Bruce Alberts is the Julia Child of Science.  Let me explain.

Julia Child was a master chef, best-selling author, skillful teacher, and a passionate educator who touched the lives of millions by helping them discover that cooking can be exciting and fun.  “Ditto” for Bruce Alberts—master biochemist, best-selling author, skillful teacher, and a passionate educator who has touched the lives of millions by helping them discover that science can be exciting and fun.

The careers of Julia and Bruce began in much the same way. Both experienced a sudden awakening that changed their lives. Julia fell in love with French food and Bruce with science. Julia’s epicurean epiphany came at age 35 at a restaurant in Rouen during her first trip to France in 1948.  Her first French meal was simple: oysters on the half-shell, solemeuniere, a green salad, and a chocolate soufflé.  Until that moment, Julia knew nothing about French cuisine and didn’t know the difference between Cream of Wheat and Crème Brulée. Her idea of a good meal was a shrimp cocktail, meat and potatoes, and Jell-O for dessert. 

In a miraculous transformation over the next 12 years, Julia became an authority on French cuisine.  In 1961, she published her first book “Mastering the Art of French Cooking,” which remains in print to this day in its 18th edition. This book is a classic because it demystified French cooking.  French Baked Beans sounded less mysterious to Americans than “cassoulet.” In 1962 Julia was invited to appear on Boston public television to discuss her new book. She arrived at the TV studio with a dozen eggs, a whisk, and a hot plate, and during the interview she whipped up an on-air omelet. The audience went wild, and the rest is history.

And now to Bruce Alberts, our Julia Child of Science. Bruce’s true calling, like Julia’s, came in a flash—while standing in front of a classroom in Glencoe, Illinois. When Bruce was 12, his seventh grade science teacher asked him to explain how a television set works. That was back in 1950 when television was new, and Bruce had no idea how it worked. His scientific epiphany came when he realized that in order to teach how something works, you first have to understand it.

Bruce’s fascination with science led him to Harvard where he did graduate work in Paul Doty’s laboratory on the physical chemistry of nucleic acids. In 1960, he embarked on a series of ambitious experiments to figure out how a cell replicates its DNA when it divides into two daughter cells. The results were equivocal, and to Bruce’s consternation, a group of distinguished Harvard Professors—at the last moment—did not approve his degree. Julia Child suffered a similar fate at the Cordon Bleu Cooking School in Paris. In her final exam, one instructor failed her because she didn’t know that an oeuf mollet was a soft-boiled egg. Undaunted, Julia spent the next several months perfecting her French, retook the exam, and got her diploma. Like Julia, Bruce persevered, did 6 more months of experiments, and got his degree.

The traumatic wake-up call on a Crimson carpet propelled Bruce to become a great biochemist. In the 1960’s, DNA was thought to be replicated by a single enzyme, DNA polymerase. No one guessed that this enzyme would be only one component of an elaborate machine formed from multiple interacting proteins, each with a different function. Bruce developed new affinity chromatography methods for DNA and protein that allowed him to identify and purify the multiprotein machine that governs DNA replication. This work became the prototype for other protein machines in the cell, such as those that splice RNA and secrete hormones.

In the 12 years after his Harvard wake-up and shake-up, Bruce underwent a miraculous transformation. He had now become one of the leading biochemists in the world, and in 1976 he took over the Chair of Biochemistry at the University of California in San Francisco.  Here, he perfected his skills as a teacher, mentored young faculty members, and began to dream up innovative ways to connect working scientists with public school teachers. But probably most important of all, Bruce teamed up with 5 other scientists to write the most influential textbook of its kind, “Molecular Biology of the Cell.” The first edition was published 32 years ago in 1984 when Bruce was 47 years old, the same age as Julia Child when her first book appeared. 

Like “Mastering the Art of French Cooking,” “Molecular Biology of the Cell” has been a dazzling success.  It is now in its 6th edition, has been translated into 11 languages, and has been devoured by tens of millions of students as well as established researchers, all of whom praise it for its clarity, logic of its explanations, and splendid illustrations. Even though the current 6th edition has 7 authors, the material is integrated in such a way that it reads like the work of a single hand—the deft hand of its master chef, Bruce Alberts.

From 1993 to 2005, Bruce served as President of the US National Academy of Sciences. Like Julia who used public television as a bully pulpit to raise the food consciousness of the American public and enhance sophistication of their appetites, Bruce used the presidency of the NAS to inform the nation on the importance of science education and to champion the role of scientists in society. Under his 12-year leadership, the NAS and its two sister organizations published an unprecedented 200 reports on all aspects of education, from kindergarten to graduate school.

In his crusade for implementing national standards for education, Bruce urged that schools quit teaching dry and deadening facts that students memorize just to pass tests. According to the Gospel of Bruce, students should be taught how to think critically, solve problems rationally, and acquire the good taste needed for a successful career in science. Recall that the Albert’s philosophy actually began 66 years ago when a classroom of 12-year olds in Glencoe, Illinois were first exposed to the anatomical workings of a television set.

Speaking of television, Julia Child literally made public television. She was the first public TV star to become an internationally known figure. Her phenomenal success was the result of four things: missionary spirit, boundless curiosity, endearing klutziness, and a deep desire to teach and to teach well. This sounds like the perfect description of this year’s Special Achievement awardee—Bruce Alberts.

Bruce M. Alberts

Cell Essay


Acceptance Remarks, 2016 Lasker Awards Ceremony

I am honored to receive this recognition, especially as it carries Dan Koshland's name. I followed Dan’s work closely, and I had the privilege of co-designing a major DNA exhibit with him for the opening of the new Marion Koshland Science Museum, which Dan had funded in his wife's memory at the National Academy of Sciences. Dan and I went back and forth on every detail, and it is because of his wonderful sense of humor that the exhibit ended up featuring the shocking claim that “44 percent of a fruit fly's genes match yours.”

In my very limited time today, I want to focus on a major passion of mine, children's science education, in the hope of recruiting many more scientists to help with this endeavor. This science education should focus on practice: that is, learning to think and solve problems like a scientist. Our primary aim should not be to produce adults who know a lot of science facts; instead, we want everyone to insist that claims be evaluated using evidence and logic, as scientists do.

This type of science education is much more important for societies than even most scientists think.  Early in my 12-year presidency of the US National Academy of Sciences, it became strikingly obvious to me that the entire world badly needs much more of the creativity, rationality, openness, and tolerance that are inherent to science—what India's first Prime Minister, Jawaharlal Nehru had called a “scientific temper.” As our world becomes more crowded and contentious, with increasingly sophisticated and powerful weapons of war, the task of imparting a scientific temper to our fellow humans becomes ever-more urgent.  

As Nehru wrote in 1946: "the adventurous and yet critical temper of science, the search for truth and new knowledge, the refusal to accept anything without testing and trial, the capacity to change previous conclusions in the face of new evidence, the reliance on observed fact and not on pre-conceived theory…all this is necessary, not merely for the application of science, but for life itself and the solution of its many problems."  Can we ever hope to create a world that can endure—one in which most of its peoples have, through their education, acquired the tolerance and rationality that is associated with scientific habits of mind?

Between 1993 and 1995, the National Academies produced the first-ever National Science Education Standards for the United States.  From that massive effort, I became convinced that introducing high-quality, inquiry based science education at all levels, from age 5 through college, provides a great opportunity for developing the scientific temper that is critical for every nation. All parents should want this type of education for their children, because it also generates the types of problem-solving skills that adults need today to be successful in the workforce.

I am convinced that this can never happen without the deep, strong, and continuous involvement of the scientific community in each nation, and I welcome this award as an acknowledgement of this fact.

Key Publications of Bruce M. Alberts

Morris, C.F., Sinha, N.K., and Alberts, B.M.  (1975). Reconstruction of bacteriophage T4 DNA replication apparatus from purified components: rolling circle replication following de novo chain initiation on a single-stranded circular DNA template. Proc. Natl. Acad. Sci. USA. 72, 4800-4804.

Liu, L.F., Liu, C.-C., and Alberts, B.M. (1980). Type II DNA topoisomerases: enzymes that can unknot a topologically knotted DNA molecule via a reversible double-strand break.  Cell. 19, 697-707.

Alberts, B.M. (1984). The DNA enzymology of protein machines. Cold Spring Harb. Symp. Quant. Biol. 49, 1-12.

Alberts, B.M. (1985). Limits to growth: in biology, small science is good science. Cell. 41, 337-338.

Alberts, B.M. (1991). Viewpoint: elementary science education in the United States: how scientists can help. Curr. Biol. 1, 339-341.

Alberts, B. and Miake-Lye, R. (1992). Unscrambling the puzzle of biological machines: the importance of the details. Cell. 68, 415-420.