Life, Death, Everything in Between (and Before)

It was no doubt a tall task for the organizers of this year’s Lindau Nobel Laureate Meetings to curate programmes that would cover a theme as far-reaching and open-to-interpretation as “Life”. Looking back, it’s safe to say that they did a thorough job. Multiple Talks and Panel Discussions between chemists, physicists, biologists and economists addressed the topic of “Life” through a range of lenses from the scientific to the philosophical, from the ethical to the practical.

“We are complex matter,” declared Jean-Marie Lehn, at his session titled Age, Death, and the Rhythms of Life. In 1987, Lehn had shared a Nobel Prize in Chemistry for kickstarting the field of supramolecular chemistry, which helps us discern the passage from condensed matter to organized matter, a transition that was necessary for chemistry to give rise to biology billions of years ago. For long, he has been concerned by how a molecule is able to “know” who is who, a property he calls molecular recognition. Lehn believes that self-organisation of matter was not an accident, but “a necessity, a consequence, and a cosmic imperative.”

Chemists like Lehn have shed light on how chemistry must have become primed for life, but can we ever really know how the switch from complex molecules to living organisms actually happened? In no mood to wait until physicists invent time travel, Jack W. Szostak has a few tricks up his sleeve. “The origin of life is like a brick wall,” described the biologist and a winner of the 2009 Nobel Prize in Physiology or Medicine. Our best bet, he said, is to target the smaller pieces of the puzzle and focus on addressing those experimentally. There are at least two approaches towards this. Some scientists are starting bottom up, the way chemists Stanley Miller and Harold Urey did in 1953, where they attempt to recreate the chemical environments that existed at the time when Earth was yet to be inhabited by life. The other is the top-down approach, where scientists look at how biology works and then work backwards, discerning the most conserved elements of life along the way. Szostak employs this approach in his lab. One of their objects of study is the protocell, something Szostak has described as “a really, really simple primordial cell that could assemble from chemicals that were around early on, on the surface of Earth”. For over two decades now, Szostak’s lab has been trying to build a synthetic cellular system that undergoes Darwinian evolution.

“We want the bottom-up and top-down pictures to meet in the middle with a coherent set of chemical processes that will get us into self assembly,” he said, during a panel discussion titled Why We Are Here, Why We Live, and Why We Die. “The goal is to understand what realistic steps chemistry took to transform into biology. How were the right molecules generated and how did they self-assemble to protocells that could evolve and give us this diversity of life.”

The Extraterrestrial Perspective

Seated beside Szostak during the panel discussion was someone who is just as keen as him to answer the question of the origin of life. Didier Queloz is an astronomer who shared the 2019 Nobel Prize in Physics for co-discovering the first planet orbiting another star, thereby kickstarting the exoplanet revolution. He began his comments with the acknowledgement that the idea of life beyond Earth had been considered and deliberated on by humans since time immemorial, but it wasn’t until the launch of the Viking spacecrafts in 1975 that there were experimental efforts towards it.

After Queloz discovered 51 Pegasi b in 1995, astronomers have detected over 6,000 such exoplanets in the Milky Way. Today, astronomers are not only discovering exoplanets, but thanks to cutting edge space telescopes like the James Webb and the Nancy Grace Roman Telescopes they are able to characterize exoplanets and deduce the nature of their atmospheres. Yet, most exoplanets detected so far orbit too close to their stars. “The moment where life was made is obscure and strange,” he remarked.

To illustrate how little we still know, Queloz pointed to our ignorance of what lies beneath 20 centimeters of the surface of Mars, a planet we usually think of as a desert planet. To this, Szostak interjected with a half-serious comment that finding life on Mars wasn’t enough, as that life would most likely share an origin with life on Earth. “So what we need is for you astronomers to find life on an exoplanet,” he said, eliciting a chuckle from Queloz.

Making and Unmaking

For the time being, scientists are busy poking and prodding at the workings of life on Earth, in the process gathering clues about how it all came to be. One of them is Aaron Ciechanover, who shared the 2004 Nobel Prize in Chemistry “for the discovery of ubiquitin-mediated protein degradation”, and was part of the same session as Jean-Marie Lehn. Ciechanover emphasised the role of quality control in maintaining life. “Life is completely dependent on optimum temperature, temperature and oxygen level,” he remarked, offering the example of the 22,000 odd proteins in every cell in the human body. The cell relies on sophisticated quality control mechanisms to maintain these proteins, but also to destroy them when their time is up.

Biologists today are increasingly interested in what happens when our time is up – in other words, death. This shouldn’t be surprising considering our societies are getting older and fertility rates around the world are hitting all time lows. In his book Why We Die: The New Science of Ageing and the Quest for Immortality, Laureate Venki Ramakrishnan captivates readers with the history of our understanding of why we age and die.

“Just during the course of this talk, millions of our cells have been dying,” he informed the audience, while on the panel alongside Didier Queloz and Jack W. Szostak. Ramakrishnan believes that human beings have been aware of their mortality for a very long time, and this awareness – perpetuated by language, communication and pattern recognition – set apart humans as a species.  

In 2013, scientists came up with a list of nine (later revised to 13) molecular, cellular, and systemic processes underlying the complex phenomenon of aging. They called them the “hallmarks of aging”. “Now the question is: is it possible to interfere with these hallmarks to help us live longer,” said Ramakrishnan. Indeed, scientists have been successful in designing interventions that make mice look younger and live longer. He also credited techniques like cellular reprogramming, which seem to allow cells to go back in time.

Ramakrishnan chalks down science’s renewed interest in aging and death partially to the small group of people (including tech billionaires) who are interested in “defeating death and living forever”. However, he urged caution because while anti-aging research may indeed extend our lifespans, it need not ensure a healthier life. “Are we talking about healthy aging or just slower decline,” he asked. Moreover, he shared his own misgivings about the prospect of extending life: “In my opinion, it will create a stagnant society and intergenerational problems with the same people accumulating money, power, and influence.”

Over the course of the Meeting a number of other Laureates shared Ramakrishnan’s concerns. Ciechanover reminded the audience that aging was not a disease, and expressed concern about what new diseases may emerge if we do start living an extra 50 years. “Think about retirement,” he urged, “the funds, social security, and the burden on the economy…” He advocated for science to focus on healthy aging, rather than on extending lifespan.

Real Talk

The session titled Lessons from Life tackled the theme of life from a practical point of view. Avram Hershko, Tim Hunt, Louis J. Ignarro, Katalin Karikó, and Robert C. Merton shared personal reflections on their scientific lives, while 600+ Young Scientists in the audience craned their necks to catch gems of wisdom as they navigate the exciting but often tumultuous early stage of their careers. “Plan your career out carefully, create your own path, and leave a trail,” advised Ignarro, after describing how he overcame his struggles with English and a brief detour from academia.

Hershko challenged the idea of hypothesis-driven experiments: “In the real lab, this doesn’t always happen, so forget about it! It is more important to have a good question than to have a good theory.” He also revealed that “most experiments don’t work”, and urged young researchers to not get disheartened when they don’t. “It means you’re being original.” Hunt informed the audience not to believe everything they read but to find out for themselves. “It’s slow, but it puts your feet firmly on the ground,” he said.

Early education plays a significant role in nurturing scientific curiosity and ability, said Karikó, adding that this does not depend on an elite school education. The daughter of a butcher, she described how at age five, she and her sibling would collect pieces of fat and make soap. Later in university, she was amused that her classmates were unaware that soap was made from fat. “Each of us learns science differently, wherever we are,” she reminded us. And finally, Merton, the only economist at the meeting, shared his takeaways from a lifetime of modeling, and insights about making decisions in times of uncertainty.

After a forum like this one, it is unsurprising that Young Scientists leave fired up to do groundbreaking work like the Laureates they have been fortunate to be hanging out with for nearly a week. However, the Laureates brought them back to Earth by highlighting the futility of chasing scientific fame and glory. “Look for important questions,” said Ignarro, “but look at them globally, not only at a very specific level. You cannot do your research because you want a Nobel Prize!”