Kary Mullis: The Nobel Prize Winner Who Invented PCR

Every day, countless molecular reactions occur in laboratories worldwide, with PCR playing a vital role. This technique, crucial for diagnosing diseases like Covid-19, amplifies specific genes, aiding in confirming cases and slowing infection spread. PCR’s transformation from a technical term to common knowledge is largely due to the Covid-19 pandemic, yet the story of its inventor, Kary Mullis, remains less known.

Kary Mullis, PhD, can be compared to James Watson, Francis Crick, and Rosalind Franklin; while they uncovered DNA, Mullis decoded it with PCR. He conceived the idea in 1983 and received the Nobel Prize a decade later for his groundbreaking work. PCR’s impact is undeniable; without it, numerous scientific advancements, including Covid-19 testing and the Human Genome Project, would not have been possible. According to Richard Doyle, PhD, PCR is synonymous with biotechnology itself. However, Mullis’ legacy extends beyond his scientific achievements, encompassing eccentric behaviors and controversial views.

Described as “eccentric” and “quirky” for his psychedelic use and unconventional beliefs, Mullis also faced criticism for disputing the link between HIV and AIDS and questioning climate change. His personal life was marked by problematic behavior, including alleged sexual harassment. This article delves into the life of Kary Mullis, exploring his scientific genius and his controversial persona, prompting us to consider how we should remember such a complex figure.

Early Life and Education of Kary Mullis

Born in 1944 in Lenoir, North Carolina, Kary Mullis displayed a keen curiosity from a young age. His interest in chemistry was sparked by a Gilbert Chemistry Set he received at age seven, igniting a desire to create explosions. This early fascination led him to pursue chemistry, obtaining a job at Columbia Organic, a supplier of research chemicals. By the time he enrolled at the Georgia Institute of Technology in Atlanta, he was deeply immersed in the world of chemistry.

At Georgia Tech, Mullis balanced his academic pursuits with family life, marrying Richards Haley and having a daughter. Despite these responsibilities, he excelled in his studies, graduating with a degree in chemistry. Mullis then faced a pivotal decision: biochemistry or astrophysics. He chose biochemistry, reasoning it would be more relatable than astrophysics, especially in social contexts. As he wrote in his memoir, discussing biochemistry, particularly its effects, would be more engaging than discussing neutral kaon decay rates.

Mullis then pursued his PhD at Berkeley during the 1960s counterculture revolution. He befriended a classmate with LSD, leading to his exploration of psychedelic chemicals, sometimes with negative outcomes. At Berkeley, after his PhD, Mullis bought a cabin in Mendocino County, frequently returning to plant trees, forage mushrooms, and, according to his account, encounter a glowing extraterrestrial raccoon. These formative experiences shaped Mullis into the unconventional scientist the world would come to know.

Career Beginnings and the Path to PCR

Following his PhD, Mullis briefly pursued writing before returning to research science. He moved back to Berkeley and took a job at the University of California at San Francisco (UCSF), studying rat brains. His inspiration to explore DNA synthesis was sparked by a talk on cloning the gene for somatostatin. In 1979, he joined Cetus Corporation, a biotechnology company, to synthesize oligonucleotides—short DNA or RNA strands. This role set the stage for his revolutionary idea.

In 1983, while driving with his then-girlfriend Jennifer to his cabin, Mullis conceived the idea for PCR. He described the moment as psychedelic, with electric molecules appearing between the road and his eyes. Mullis later questioned whether his LSD use contributed to his creativity, suggesting it may have played a role in his invention. He drew upon his understanding of computer programming, reasoning that to find a specific DNA segment, he needed to design DNA fragments to bookend gene sequences.

Mullis realized that under the right conditions, the isolated segment could replicate iteratively, leading to his “Holy shit!” moment. He envisioned the impact of his idea: widespread use in biology labs globally, fame, and the Nobel Prize. This roadside revelation marked the birth of PCR, a technique that would transform the world of molecular biology. Back at Cetus, Mullis and his colleagues faced challenges in making his vision a reality, setting the stage for a complex journey of refinement and recognition.

The Development and Challenges of PCR

At Cetus, Mullis and his colleagues, including Henry Erlich, Randall K. Saiki, Steven Scharf, Norman Arnheim, and Fred Faloona, aimed to develop an assay for diagnosing sickle cell anemia. While Erlich, Saiki, and Arnheim focused on human cells, Mullis and Faloona used a simpler system. Despite their efforts, Mullis struggled to get a signal; his method amplified all DNA segments instead of the specific fragment he sought. Erlich, Arnheim, Saiki, and Scharf successfully detected the beta-globin gene, but Mullis struggled.

When Erlich offered guidance, Mullis sometimes resisted these ideas. In 1985, Cetus researchers published the first paper on PCR in Science, with Mullis not as the primary author. Mullis sought to publish independently on the technique itself, but Nature and Science rejected his manuscript. Science suggested he publish in a secondary journal. Undeterred, Mullis’ paper was published two years later in Methods of Enzymology, and Science later recognized PCR as the “invention of the year.”

Mullis’ behavior at work further complicated matters. He stored beer in the radioisotope fridge and clashed with the safety officer. His tumultuous relationship with Jennifer extended into the workplace, with Mullis threatening to bring a gun to work. Despite these challenges, Erlich acknowledged Mullis’ brilliant idea and its enormous consequences. In 1986, Mullis left Cetus, receiving $10,000 for his idea, while Cetus retained the rights to PCR, later selling them for $300 million to Hoffmann-La Roche. This marked a turning point, highlighting the complex journey of PCR’s development and the challenges faced by its inventor.

Recognition, Controversies, and Personal Life

In 1991, DuPont tried to dispute Mullis’ patent for PCR, claiming it had been described in the early 1970s. Mullis’ former colleagues, including Erlich, supported his case as the sole inventor of PCR, highlighting the scientific community’s recognition of his contribution. In 1992, Mullis received the Japan Prize and, in 1993, the Nobel Prize in Chemistry. Mullis exclaimed, “I’ll take it!” celebrating with his friend Steve Judd by going surfing.

Emily Yoffe, a freelance writer, interviewed Mullis for Esquire. During the interview, Mullis sexually harassed her, underscoring his problematic behavior. Mullis’ controversies extended to his public views on AIDS, as he disputed the idea that HIV caused AIDS, leading to criticism from scientists like Angela Rasmussen. Some organizations rescinded invitations to Mullis, and GlaxoSmithKline paid him not to speak at their conference.

In 1997, Mullis began dating Nancy Cosgrove, who became his fourth wife and significantly influenced his life. Nancy helped him leave behind his eccentric behaviors, managing his public relations and travel. Mullis stopped speaking about AIDS, and Nancy supported his scientific endeavors, including Altermune Technologies, which explored new ideas for the immune system. Mullis’ story is one of both groundbreaking scientific achievement and personal controversy, raising questions about how we should remember him.

Mullis’ Legacy and the Broader Impact of PCR

Kary Mullis’ invention of PCR revolutionized science, yet his story is complex. Like James Watson and Richard Feynman, Mullis’ problematic behavior raises questions about the relationship between scientific genius and personal conduct. Richard Doyle notes that we don’t choose where good ideas come from, and Mullis’ story is one of change, reflecting the recursive nature of consciousness.

Some argue that Mullis shouldn’t receive sole credit for PCR, as other researchers contributed key ideas. David Gelfand’s work on Taq polymerase and Russell Higuchi’s development of quantitative PCR were crucial advancements. These contributions highlight the collaborative nature of scientific progress. In his memoir, Mullis described the Nobel as a “free pass,” but Angela Rasmussen argues that his problematic behavior, including espousing false scientific ideas and sexual harassment, should not be diminished.

Rasmussen argues that Mullis had an obligation to be publicly accountable, and his brilliant idea should be viewed in the context of his actions. Mullis’ legacy is a reminder that scientific contributions and personal conduct are intertwined, and we must consider both when evaluating the impact of individuals on society. While PCR has transformed the world, Mullis’ story prompts us to reflect on the complexities of scientific innovation and the responsibilities of public figures.

Conclusion: Remembering Kary Mullis

Kary Mullis’ invention of PCR has indelibly shaped modern science, offering a testing method for Covid-19 and facilitating advancements in genetics and biotechnology. His Nobel Prize recognizes his pivotal role in decoding the secrets of DNA. However, Mullis’ story is not without controversy. His eccentric behaviors, controversial views on HIV/AIDS, and allegations of sexual harassment present a complex picture of the scientist.

Mullis’ legacy challenges us to reconcile his scientific genius with his problematic personal conduct. While his invention has saved countless lives and propelled scientific discovery, his actions raise ethical questions about the responsibilities of public figures. As Angela Rasmussen argues, Mullis’ contributions should be viewed in the context of his actions, urging us to hold him accountable for his harmful behavior. The transformation he underwent later in life, guided by his wife Nancy, suggests the possibility of change and growth, even for complex individuals.

Ultimately, remembering Kary Mullis requires acknowledging both his extraordinary contributions to science and his significant flaws. His story underscores the importance of recognizing the multifaceted nature of human beings and the need to critically examine the legacies of even the most influential figures. Mullis’ life serves as a reminder that progress often comes from unexpected sources, and that we must grapple with the complexities of those who shape our world, embracing the good while confronting the problematic.

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