Antibodies and Quantum Dots: The Evolution From Lab to Industry

Most researchers aren’t thinking of applications when they start out, but every so often, things head in that direction. If successful, the commercialization of their work could revolutionize aspects of life and lifestyle. Two of the most successful such scientists delivered back-to-back Lectures on the Monday of the 74^th Lindau Nobel Laureate Meeting: Moungi G. Bawendi who won a 2023 Chemistry prize for “for the discovery and synthesis of quantum dots”, and Gregory Winter who won a 2018 Chemistry prize “for the phage display of peptides and antibodies”.

Bawendi’s breakthroughs made it possible for quantum dot technology to be used by biologists to map cells and tissues and chemists to drive chemical reactions. But the “big application”, according to him, came later when electronics companies such as Sony and Samsung adopted the technology to develop QLED-based] computer and television screens.

Evolving Goals

Interestingly, Bawendi had no such ambitions when he joined Bell Labs as a postdoctoral researcher in 1988. By then, it was known that materials behaved very differently when reduced to nano-quantities. For example, while gold particles in bulk appear in their trademark shimmery colour, when converted to nanoparticles, they appear in various other colours depending on size. All Bawendi cared about then was the “pure physics” of how a material’s properties evolve as it progresses from a few atoms to bulk quantities. What happens in the middle of this progression? “My curiosity wasn’t motivated by anything visionary,” he said at his lecture, “we just really wanted to know!”

Evolution was a key aspect of Gregory Winter’s award-winning work as well. He developed a way to evolve antibodies, a technology that has been employed to create pharmaceuticals that treat diseases such as rheumatoid arthritis. In his Lecture, Winter mentioned that he wasn’t concerned with antibodies when he started out. “I was more interested in catalysis and the origin of life, and all the other things that seem to stimulate all biologists,” he said. Along the way, he stumbled into the realisation that it was possible to turn mouse antibodies into their human counterparts. “It was such an exciting revelation that I abandoned work on catalysis and set about creating a model humanised antibody.”

When it came time for Winter to file for a patent, he found himself embroiled in a battle. Initially, the United Kingdom’s Medical Research Council (MRC) and National Research and Development Corporation (NRDC) insisted that the patent be assigned exclusively to Celltech, a biotechnology company linked to the MRC. This led to a tumultuous period for Winter, who vehemently opposed the idea that his publicly funded work be used to profit a single company as opposed to the wider public. “I completely disagreed with this. I believed that this would strangle the rollout of humanised antibodies to other companies who could potentially use the technology to create a wave of new drugs,” he said.

Tumultuous Times

For Winter, the journey to compromise was lined with risks of losing his job, conflicts with influential leaders of science and bureaucrats. But he persisted, and in 2002, he succeeded in developing the first FDA-approved pharmaceutical entirely based on a human antibody: adalimumab. “Commercial and political factors interacted in the emergence of antibodies as a pharmaceutical,” he summarised in his Lecture.

It seems that even Nobel Laureates go through periods of hopelessness and frustration, and Bawendi had his own story to tell. Buoyed by partial successes in synthesizing quantum dots of one particular size at Bell Labs, he started his new lab in MIT, expecting to pick up where he left off. To his dismay, the method simply did not seem to work anymore. “I spent a lot of money on reagents, my first three students joined and we hit our heads against the wall, trying to repeat [what I did in Bell Labs], but it was going nowhere,” he recollected. Bawendi even wondered whether this would be the end of his career.

The team had to start from scratch and revisit everything Bawendi learned at his previous laboratory before things finally began to click. “We figured it out by finding the right precursors, the right conditions …intuition and trial-and-error,” he said, reminding the audience that it took him three years to write his first paper at MIT. This was the paper that changed the field dramatically. Until then, quantum dot technology was unable to take off because the nanoparticles produced were inconsistent in their size and quality. Bawendi’s 1993 paper described a process by which scientists could have ‘exquisite control’ of the size of the nanoparticles produced.

Importance of Industry

Very early on in his lecture, Bawendi made a statement: “Discoveries take time.” By the end of Winter’s Lecture, it was evident that so does commercialization. Notwithstanding his patenting troubles, there was one experience that confirmed to Winter that this was a fight worth fighting. He had been requested for a meeting by the first patient who received humanized antibodies to treat her terminal non-Hodgkin’s lymphoma. The patient asked him “Perhaps you will tell me how long I have got to live.” Winter had no idea, as they weren’t even sure if her body would reject the humanized antibodies. He told her that it could be “a few weeks, a few months, a year or more.” To his astonishment, the woman replied firmly: “Two months is enough.”

It turned out that the woman’s husband was on his deathbed and all she wanted was to be with him when he passed on. “I am not a hardened medic, I was not used to these kinds of personal interactions, so her comments shook me to my core,” Winter said. The conversation changed the focus of Winter’s research towards clinical applications. In the end, the antibodies did their job and the patient survived for another year. Winter believes that she may have lived longer if there were any antibodies left to treat her. “That highlighted to me the importance of working with industry to manufacture products. There is a limit to how much you can do in an academic setting.”