A recent chemists’ roundtable in Dublin, overseen by the Royal Irish Academy, showcased fascinating insights from two esteemed Nobel laureates within the chemistry sector. These were Prof David MacMillan, the 2021 laureate, and Prof Frances Arnold, who secured her award back in 2018. Both actively concurred that having adequate knowledge rather than extensive is vastly crucial in pioneering research to provoke inquiries that are challenging to the current orthodox views.
This assembly was part of the EuChemS congress, which had Prof Pat Guiry, president of the Institute of Chemistry of Ireland, conferring the dialogue. Arnold offered the unique idea that an absence of learning in some cases might induce the creation of novel concepts. MacMillan supported her stance, describing it as an unusual concoction of wanting to comprehend enough but also refraining from knowing excessively. Accordance to him, ample knowledge could hinder the attempts to venture into unknown fields, as that could lead to over-confidence or an illusion of superiority in knowledge.
Arnold humorously admitted to getting blamed daily for her inadequate knowledge. Yet, it was clear she had pioneered a new chemistry branch when her radical research came to light. Her and MacMillan’s innovations have had significant implications across numerous disciplines and opened up the fundamental concept of catalysis to infinite new opportunities. Increasing the speed of chemical reactions is the main function of Catalysts.
MacMillan, who is affiliated with the US’s Princeton University, received the Nobel Prize for his work on asymmetric organocatalysis—an accurate technique for molecule formation. He won the award jointly with Ben List from the Max Planck Institute in Germany. Both scientists have introduced groundbreaking methods for constructing and manoeuvring small organic molecules to promote chemical reactions. MacMillan is also a pioneer in the field of photoredox catalysis, encapsulating the power of conventional visible light to break and remake atomic bonds, one electron at a time.
Constructed from organic, carbon-based compounds, organocatalysts offer a green alternative to their traditional metal counterparts, which are often costly, scarce, and harmful. These non-toxic, biodegradable molecules are employed to build new drugs and materials in labs without the need for protective gear. The impact of this discovery is vast, touching industries, pharmaceuticals, and everyday items like clothes, shampoos, and renewable fuels.
MacMillan, an enthusiastic football follower and undergraduate, was once given a dressing-down by his Glasgow University professor whilst engrossed in a World Cup qualifier game between Scotland and Cyprus for disregarding the importance of “enantiomers”. He later came to understand their significance more profoundly when he won the Nobel Prize for his ingenious method of creating these mirror-image molecules.
Two decades ago, metals or enzymes, large proteins inclusive of enantiomers, were often used as catalysts to speed up chemical reactions in the production of drugs or chemical substances. However, metals were polluting agents and enzymes were incredibly intricate.
As biological catalysts, enzymes help construct some substances in the human body and breakdown others. Their methodologies only require a small portion of proteins and have made the field of chemistry less hazardous and more sustainable.
As MacMillan puts it, their innovation was something simple that no one else had considered. It represented the classic case of science overlooking simpler routes while persisting in one direction.
Arnold, who works at Caltech in the US, was recognised for her work on “the directed evolution of enzymes”, a bioengineering method that uses random genetic mutations to engineer improved lab-synthesised enzymes adhering to evolutionary principles.
This directed evolution technique is pivotal in producing everything from biofuels to medications. The process of creating enzymes using this method has replaced harmful chemicals in many commercial procedures.
Despite their establishments in prestigious institutions like Princeton and Caltech, Arnold and MacMillan’s backgrounds were unconventional. Arnold did everything possible to avoid chemistry, having worked in a pizza shop, as a cocktail waitress, and as a taxi driver, before studying aerospace engineering and solar energy. It was later that she switched her focus to chemistry.
With an assured self-belief inherited at birth, MacMillan has mastered the art of separating constructive criticism from noise, using it as a tool for growth. Despite his childhood eccentricities, or as his father would light-heartedly term it – curiosity, he always stood out. His elder brother was his inspiration, breaking barriers as the first in their school to pursue university education. His initial job earned more than their father, a long-serving steelworker of three decades. Prompted by this, their parents urged MacMillan to follow suit.
Although he initially found physics challenging, MacMillan was captivated by the logic and practicality presented by organic chemistry during his second year at university. Eventually, he shifted focus to chemistry, fuelled partly by a fascination for the American lifestyle characterized by sports and television.
During his initial years in research, he often found himself conducting detailed investigations while ensconced in a glove box for long periods. He found the approach counterintuitive, spurring him to explore the potential of small organics in catalysis.
His thinking resonated with Arnold’s perspective of enzymes’ future dominance. They both saw the inexorable rise of this technology, placing them in the outliers of scientific thought. Arnold’s realization of unexplainable genetic mutations through directing evolution led her to pioneer an entirely new field. She was certain of its ability to resolve impossible problems, giving her the confidence to boast of potentially leading the new discipline globally.
The journey led them to the prestigious Nobel Prize, a milestone that transformed their lives significantly. It was almost like adopting a new profession, where constant attention and solicited opinions became the norm. A philanthropic spirit emerged in MacMillan, launching a successful initiative in Scotland that supported financially challenged students to continue their university education.
Arnold serves as the co-chair for the Council of Advisors on Science and Technology for the American president. Having contributed to the council for over three and a half years, Arnold expresses a feeling of fatigue yet finds the correlation between science and policy making intriguing, despite the overwhelming complexity. Arnold asserts that the impacts of science permeate various aspects including climate shifts, extreme weather patterns, preservation of public health and patient safety among others, all of which are issues taken into account by the council.
Conversations around artificial intelligence (AI) come up naturally. However, their perspectives deviate from the conventional apprehension that perceives AI as an unmanageable beast. For MacMillan’s part, he posits that though AI might not provide the best solutions within the field of chemistry, it has remarkable potential for posing valuable questions. Specifically, questions on the possibility of novel molecular combinations that could yield significant advantage and guide chemists on areas to focus their research.
Arnold echoes these sentiments, advocating for the powerful capability of evolution as a design process that can be applied to a broad array of problems. He further argues that AI and machine learning could well compliment this as evolution is ideally suited for such.