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I’ve called this platform “the meaning of life and molecular biology”. Readers of a scientific persuasion might think, well, what does molecular biology have to do with “meaning”? The reason for this disconnect is that the contribution of molecular biology to our understanding of life has not been put into its proper societal, philosophical, and historical context. In this article, I aim to provide a clear definition of the molecular biology revolution. It has been alluded to on several occasions, but not formally outlined; we will discuss why that is the case towards the end of this article.
In short, what is the molecular revolution in biology?:
It is to peer into the molecular level of life for the first time. We didn’t have complete and direct access to it before the 1950s, and we gained access due to technological developments. These technologies helped us to unlock another level of reality, the molecular realm.
This irreversible change in perspective is why we should regard the molecular biology revolution alongside other scientific revolutions, such as the Darwinian and Copernican revolutions.
What were the key insights of the revolution?
The understanding that we, and all living things, are made up of the same atoms (matter) as the non-living Universe (stars, rocks, water).
That molecules (combinations of atoms) can encode information, most famously, in the form of DNA, which is universal to all of life on Earth.
That Information plays a profound role in the function and evolution of living beings, transforming our view of how life works.
That on a molecular level, the constant bombardment of molecules and atoms can be described as “the molecular storm” (2). The interior of cells, whether a bacterium or a human cell, is a crowded, chaotic place packed with molecules big and small (much like the image at the top of this article depicting a bacterial cell).
The Historical Context that gave rise to the Molecular Biology Revolution
Industrialisation and War
“The migration of many scientists to Great Britain and the United States before World War II, growing global communication needs, and a wartime focus on code-breaking, as well as the linked birth of computing, all helped give molecular biology its current form.” The words of science historian, Michel Morange, in the book The Black Box of Biology
By the first half of the 20th century, much of Europe and the Western world had been transformed by industrialisation. This set the stage for World War I and World War II, which introduced a new type of industrial warfare more deadly than ever. There was unprecedented destruction and loss of life, but also huge technological advancement as entire economies were repurposed to produce innovative weapons. Many of the new technologies developed were redirected into research and played a key role in the breakthroughs of 20th-century science (Figure 1).
The Birth of Modern Atomic Physics
Around 2,500 years ago, the philosophers of ancient Greece speculated that all matter, all the physical stuff we can see, is composed of atoms. They asserted that atoms are the fundamental and indivisible units of reality. Some 2,400 years later, in the early 20th century, physicists Niels Bohr and Ernest Rutherford had developed the first accurate atomic model.
Developments in the understanding of radioactivity, thanks to Marie Curie, Pierre Curie, and Henri Becquerel, had shown that atoms are not the indivisible unit of reality as the Greeks had suggested, as atoms themselves are composed of sub-atomic particles. The number of protons and neutrons in the centre of the atom (the nucleus) and the energy state of the electrons orbiting the nucleus determine the properties of the atom, and the different atoms can be organised into the periodic table of elements based on these properties. Atoms can join together to form molecules, which is mediated by the sharing of electrons between atoms. Many biological molecules, such as DNA or proteins, are long polymers composed of repeating units made up of hundreds, thousands, or even billions of atoms.
The next breakthrough was made possible by the discovery of X-rays by German scientist Wilhelm Conrad Röntgen in 1895. X-rays allow us to see in higher resolution than we can with regular light, and importantly for us, at the level of atoms. This is because X-rays have a shorter wavelength than visible light. The first experimentally determined structure, using a technique called X-ray crystallography, was that of the molecule sodium chloride (regular table salt) in 1914. In short, the method works by shining X-rays onto the sample, in this case, salt. The crystal diffracts the X-rays in a specific pattern, and this pattern can then be analyzed to determine the structure. Now, substances could be visualised in atomic detail for the first time: scientists had unlocked another zone of reality. In the following years, scientists used X-rays to examine increasingly complex molecules, as described in the next section.
It is important to note that other technologies were necessary for visualising life at the molecular level of reality. At around the same time as X-ray crystallography, electron microscopes and nuclear magnetic resonance techniques were also being developed. All of this work has shown that biological molecules are composed of the same atoms as the rest of the universe. That you and I are the universe, we are made up of the same atoms as non-living matter.
By the mid-1920s, atomic theory had undergone significant improvements thanks to developments in quantum mechanics. As a consequence, many physicists began to shift their focus to tackle the complex problem of life (3). Most notably, Erwin Schrodinger speculated on the nature of the inherited substance in his 1944 lecture series and book, What is Life?
Inception: The Molecular Revolution in Biology
The year 1953 was the birth of a new era. The landmark event was when Francis Crick and James Watson determined the double-helix structure of DNA (Figure 2). Crick had trained as a physicist and, inspired by Schrodinger’s work, was one of those individuals who jumped ship to biology. To determine the structure, Watson and Crick used the X-ray crystallography data of Maurice Wilkins, Rosalind Franklin, and Raymond Gosling. It was a spectacular achievement due in large part to Franklin’s expertise in crystallography. To give you an idea, even a short piece of DNA, say 10 letters long (and there is more on what we mean by letters in a moment), contains between 500 and 600 atoms!
Let’s give a special mention to the great X-ray crystallographer Dorothy Hodgkin. Hodgkin determined the structure (shape) of several biological molecules of profound scientific and medical benefit, including vitamin B12, insulin, and penicillin. The historic event that determined the structure of DNA has come to define the birth of molecular biology. Still, the truth is always more nuanced, as exemplified by Hodgkin’s work on smaller biological molecules. This is part of the difficulty in defining the revolution, as there were so many other monumental discoveries around this time, particularly in the 1940s.
By the late 1960s, scientists had discovered the exact mechanism by which DNA acts as a code. DNA information is written in the chemical language of bases, which we refer to as A, G, T, and C. This information is transcribed into a similar molecule, RNA, which carries the message (a process known as transcription). The message is taken to the ribosome, where it is translated into another chemical language —the language of amino acids. These processes are summarised in Figure 3. There are four different bases, or letters, in DNA, but there are 20 different amino acids. Regardless, the sequence of the DNA determines the sequence of the amino acids that are to be incorporated into the protein that is formed. The sequence of DNA that encodes a single protein is referred to as a gene (4). Importantly, amino acids are much more diverse and interesting than bases in terms of their chemistry. This is an essential point because proteins are the ones that do almost everything, from forming structures and harnessing energy to reading the DNA code and even making more DNA and RNA. We have become so enamoured with the historical narrative around DNA that it is sometimes overlooked that the first complete protein structure was determined (for the protein myoglobin) in 1959, to significantly less fanfare (but did still result in a Nobel prize).
How DNA is made (replicated), how it is read (transcribed), and how proteins are made based on the transcribed message (translated) were all determined in the 1950s and 1960s. By 1966, the exact sequence of DNA letters corresponding to each amino acid was known, and the code had been fully deciphered.
In 1961, André Michel Lwoff, Francois Jacob, and Jacques Monod gave the first description of how genes could be regulated, that is, switched ON or OFF (again, there is a crucial role for proteins in this process through transcription factors, which can either activate or repress the expression of a gene)
This really was the height of the revolution.
Furthermore, these fundamental processes are found in all living creatures, from bacterial cells to you and me. It is extraordinary to think that, as you sit to read or listen to this article, within you, there are all these tiny molecular processes occurring. DNA is being replicated, and proteins are being made, some of which then regulate the expression of genes.
This was a revolution on par with any other in the history of science.
The Structure of Scientific Revolutions
For philosopher of information Luciano Floridi, revolutions share common qualities in their capacity to transform our view of the external world and modify our conception of ourselves (internal). For example, in the 1500s, the Copernican revolution (named after astronomer Nicolas Copernicus) changed our understanding of the external Universe, placing the Sun at the centre of the solar system rather than the Earth, and internally this changed our perspective on ourselves as we were no longer at the centre or focal point of existence (Figure 1). Similarly, Charles Darwin (5) in 1859, with his theory of natural selection, explained how species evolve (Figure 1). Consequently, this displaced humanity from the centre of the natural world; it turns out we are just one of many branches on the tree of life. It's important to remember, though, that at this point, the nature of the inherited substance passed on to offspring from previous generations had not yet been identified.
Significantly, the effect of a revolution on society is to change our perspective irreversibly; this is what the philosopher of science Thomas Kuhn described as a paradigm shift (6).
I have spoken with Michel Morange, the author of the most recent and detailed history of the molecular biology revolution (7). With Michel's insight, I have gained a clearer understanding of why it is challenging to define the molecular revolution in concise terms. This is because of the classical model of scientific revolutions, as outlined by philosopher Thomas Kuhn in his 1962 book, The Structure of Scientific Revolutions. Kuhn overlooked the molecular revolution, although this may be due to its relative infancy at the time of his writing. However, the issue is that the structure for a scientific revolution proposed by Kuhn is narrowly focused on paradigm shifts, which overturn existing theories and replace them with new ones. He discusses how the new knowledge gained is “incommensurable” with the old model it replaces, which must be discarded. Instead, the molecular revolution in biology was about accessing a layer of reality that had until then been inaccessible or only glimpsed indirectly.
We now know that, from a distant vantage point, what may look like a sudden and explosive shift may in fact be the accumulation of gradual progress when the historical context is analyzed in detail (8). For example, the idea of evolution proposed by Darwin was more commensurable with the ideas of other scientists at that time, as well as those who preceded him, than the popular narrative portrays (9).
Molecular biology provided additional insights and detail into fields such as evolution, developmental biology, genetics, and medicine. However, it is essential that we do not stretch the criteria for a revolution too far, as this would render everything a revolution (e.g., the genetics revolution, the sequencing revolution). The molecular category is the fundamental and basic level of reality for understanding life. It is the foundation upon which the higher levels emerge, and in being broad, can include developments in genetics, biochemistry, metabolism, protein structure and function, gene regulation and expression, and avoids giving each of those sub-disciplines their own revolution (10).
The next phase of the revolution, following this explosive beginning, was tumultuous, with some scientists declaring in the 1970s that the biological meaning of life had been uncovered—a belief that remains to this day, at least for some. We will cover this more in an upcoming article, but in short, molecular biology suffered and continues to suffer from genetic reductionism, or a gene-centric bias. Unfortunately, this has had a limiting effect on our understanding of life. Furthermore, some aspects of the molecular realm have been repeatedly overlooked by the field of molecular biology, such as the role of “the molecular storm” and its relationship to thermodynamics and the utilization of energy by living organisms. We will discuss this in detail in a separate article.
This historical exploration has been a necessary and fascinating journey through the birth of molecular biology. But this is an ongoing revolution. And just as the inception of molecular biology was born out of the convergence of apparently disparate fields of physics, chemistry, and biology, there is a new era in this revolution, also a synthesis, and it is happening right now (11).
Superconvergence
The molecular revolution started with the determination of biological molecules using X-rays. This is a difficult, expensive, and time-consuming process, which is still carried out today alongside newer techniques, such as cryo-electron microscopy (don’t worry about that for now, though). However, there has been a shift towards a new technology for determining the structure of biological molecules.
In 2021, Google’s DeepMind team published AlphaFold. It utilizes artificial intelligence (AI) to predict protein structures, achieving an unprecedented level of accuracy. No physical experiments are carried out, it all happens in silico (by computation). When I studied molecular biology as an undergraduate, the lecturer discussed with the class whether it would ever be possible to predict a protein's structure (shape) directly from its amino acid sequence. Now it is.
“So far, AlphaFold has predicted over 200 million protein structures – nearly all catalogued proteins known to science. The AlphaFold Protein Structure Database makes this data freely available. So far, it has over two million users in 190 countries. That means it has already potentially saved millions of dollars and hundreds of millions of years in research time.” From the AlphaFold3 webpage.
Even in the short time since AlphaFold was initially released, it has been replaced with newer and better versions. Now, anyone armed with a DNA/RNA or protein sequence can predict the structures of all these molecules, and it is free of charge to use, and exceptionally quick compared to the computationally and time-intensive original methods. What is truly remarkable is AlphaFold's ability to now predict how these molecules may interact with each other, a feat that was previously very difficult to achieve. There are even versions of AlphaFold that help to design new drugs that interfere with protein activity to generate new disease treatments.
We have all been hearing about AI daily, not a day goes by without yet another news story. Usually these stories are negative. But there is a lot of good too, aside from the advances of AlphaFold, AI is helping doctors to interpret medical scans. Notably, AI in combination with a human doctor out performed either alone. This will help catch diseases such as cancer earlier and improve patient outcomes. It could also reduce the workload on over-worked healthcare professionals.
Jamie Metzl, in his 2024 book Superconvergence, describes the intersection of AI with science, medicine, synthetic biology, gene editing technologies (including gene therapy for disease treatment), and cutting-edge agricultural technologies.
“The superconvergence of intersecting technologies is unleashing the miracle of human innovation on a planetary level and giving us superpowers that will increasingly touch almost every aspect of the world inside and around us.” Jamie Metzl in Superconvergence 2024 (11).
An updated version of Superconvergence is scheduled for release this autumn. In the meantime, I spoke with Metzl as the pace of change is so dizzying that I wanted to get his most recent take on global events. In the original version, he explains how these God-like powers that humanity is developing must be governed in a coordinated and international manner. I wondered how he felt about recent events, for example, the planned U.S. exit from the W.H.O. He told me that he is “deeply concerned by America’s withdrawal from its global responsibilities and its commitment to global governance. However uneven this commitment has been over the past eight decades, it has always been the central foundation of the international order that has so massively benefitted most Americans and humans.”
The reality is that the molecular biology revolution, at least in this first phase from around 1950 to the present day, has brought about incalculable benefits to society. It has transformed every aspect of our modern lives, not least medicine, but also forensic science, agriculture, and biotechnology. But now we stand at the precipice of a new world, and I will conclude this article by leaving you with the cautionary words of Jamie Metzl.
“Our converging, God-like technologies do not come with their own built-in value systems. It’s up to us to infuse our best values into the development and application of those technologies. This requires coordinated societal governance, including governmental regulation. Without proper governance and guidelines, we have every reason to expect many things will go wrong. With appropriate governance, there is really no limit to the many things that can go right. Our future is never assured, which is why coming together to maximize benefits and minimize potential harms is so important.”
This article is written by Dr. Chris Earl, a writer and molecular biologist interested in the societal and philosophical ramifications of science.
References, notes, and further reading
(1) David S. Goodsell’s E. coli cell see Goodsell DS (2022) Integrative illustration of Escherichia coli. RCSB Protein Data Bank, doi: 10.2210/rcsb_pdb/goodsell-gallery-028.
(2) see- Graham, Liam. "The Molecular Storm." Molecular Storms: The Physics of Stars, Cells and the Origin of Life. Cham: Springer Nature Switzerland, 2023. 21-33.
(3) Some other notable physicists who re-focused their efforts on biological problems include: Linus Pauling, Max Delbrück, Leo Szilárd, Niels Bohr, and Francis Crick, who was himself trained as a physicist.
(4) The term gene is not as straightforward as this in reality. A gene often encodes a protein, but it can also encode a functional piece of RNA, where the RNA, rather than being a messenger for the code, actually does something in its own right. Important RNAs are involved in bringing amino acids to the ribosome (tRNA or transfer RNA), others are found in the ribosome (rRNA or ribosomal RNA), and others still can regulate the expression of other genes. There is even more to be said about what a gene is, and we will have to devote specific time to explore that question effectively in another article.
(5) Alfred Russel Wallace independently conceived the theory of evolution by natural selection alongside Charles Darwin.
(6) Kuhn, Thomas S. The structure of scientific revolutions. Vol. 962. Chicago: University of Chicago press, 1997.
(7) Morange, Michel. The black box of biology: A history of the molecular revolution. Harvard University Press, 2020.
(8) Morange, Michel. A history of biology. Princeton University Press, 2021.
(9) Kampourakis, Kostas, ed. Darwin Mythology: Debunking Myths, Correcting Falsehoods. Cambridge University Press, 2024.
(10) Another obstacle to clarity for the molecular biology revolution is due to the different meanings of molecular biology and historical infighting between biochemists and molecular biologists. Biochemists argued that molecular biology was a sub-discipline of biochemistry. In practical terms, molecular biology in the research and industrial settings is often used to mean working with DNA and manipulating DNA sequences narrowly. Biochemistry is often more closely associated with the properties (function and structure) of proteins. The molecular level of reality, as accessed through technological advancements in X-ray crystallography, electron microscopy, and other techniques, concerns the actions of DNA, RNA, proteins, energy (metabolism and catabolism), and structural components. I take the position of Doris Zallen, please take a look at the reference below.
You could argue that it started in the 1940s or even earlier, but for me, it was when we could visualise complex biological molecules for the first time. Finally, in contrast to my approach, Luciano Floridi places the role of information (in particular DNA) within the Turing (or information) revolution. However, I do not see DNA being part of a molecular biology revolution and an information revolution as mutually exclusive positions.
See the following references for even more discussion of the revolution:
Zallen, Doris T. "Redrawing the boundaries of molecular biology: The case of photosynthesis." Journal of the History of Biology 26.1 (1993): 65-87.
Cantor, Geoffrey N., et al. Companion to the history of modern science. Routledge, 2006. Chapter 32: The molecular revolution in biology.
Kay, Lily E. The molecular vision of life: Caltech, the Rockefeller Foundation, and the rise of the new biology. Oxford University Press, 1993.
Judson, Horace F., The eighth day of creation: Makers in the revolution in biology. Penguin, 1995.
(11) Metzl, Jamie. Superconvergence: How the Genetics, Biotech, and AI Revolutions Will Transform Our Lives, Work, and World. Timber Press, 2024.
