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Science at the Boundaries

By David Vahey Science pushes the limits and boundaries of our knowledge, and in doing so improves our understanding of the universe we live in. Only time can tell whether this knowledge will be used to incrementally improve our own existence, or ultimately bring about our own annihilation.

Whether it be by conventional thermonuclear weapons, some bioengineered virus, or the rise of super AI -humanity's self-destructive element can never be overlooked. However, hidden amongst the gloomier headlines usually favoured by the press there have been some recent breakthroughs that humanity should be truly optimistic for! Despite a return to war in Europe and condemning climate predictions, it's vital that we should still celebrate these recent positive developments in science. Conquering the atom? Overreliance on fossil fuels, exposed financially by the war in Ukraine, obviously comes with huge costs to our planet as well as our wallets. In the short to medium term, our only hope comes from international co-operation to reduce CO2 amongst other pollutant levels, such that we do not irreversibly poison our planet and risk making our home planet inhabitable. However, recent scientific breakthroughs have yielded new technologies such as carbon capture, where we can take CO2 out from the atmosphere, as well as ever improving battery technology. Excitingly, the long-term utopian image of a 100% clean and renewable energy source took a major step forward this year with nuclear fusion. Unlike nuclear fission, which largely relies on the finite and dangerous Uranium-235, the fuel source can be renewably extracted from seawater in form of 'heavy' types, or isotopes, of hydrogen atoms. The basis of this enegy source is what powers the sun, and can be explained in simpler terms with the world's most famous equation: E = mc2. Where E = energy; m = mass, and c = speed of light. It seems Einstein's most famous - albeit simplified - equation could provide our long-term salvation by converting mass into colossal sums of energy via nuclear fusion. Incidentally, nuclear fusion is how the sun produces its energy: by converting hydrogen into helium. The two hydrogen nuclei collide and fuse together at phenomenal temperatures and pressures to produce a helium nucleus that has a lower mass (i.e. 'weighs' less) than the two individual hydrogen nuclei. Thus, as seen in Einstein's equation, this mass loss is converted into energy - as mass and energy cannot be created or destroyed, but can be converted into one another. As a result of this process, the sun loses 4.26 million metric tons per second in order to produce 3.8 x 1026 - or 384.6 septillion Watts per second of energy. To put that into perspective, the sun will, in four seconds, produce more energy than the sum total of every single person on Earth consuming annually as much energy as the entire human race consumes in a year. However, in order to tap this resource, scientists have to replicate the conditions within the Sun in a laboratory environment on Earth. If that was not difficult enough, for this to be beneficial, it has to produce more energy than is needed to maintain these harsh conditions - in excess of 100 million degrees Celsius. Because of this, while the first successful nuclear fusion experiment was in 1957, it wasn't until last year, in December 2022, that the US National Ignition Facility (NIF) achieved 'ignition', i.e triggering a nuclear reaction that generates more energy than it consumes. In this recent successful experiment, 192 lazers were used to deliver energy to a pea-sized gold cylinder containing a frozen pellet of two isotopes of a hydrogen atom - deuterium and tritium. The energy delivered by the lasers caused the capsule to collapse reaching conditions only previously observed in stars and thermonuclear weapons. This enabled the hydrogen isotopes to fuse into helium, and the resulting cascade of fusion reactions released around 54% more energy than was put into the reaction. This is a huge landmark in the future of nuclear fusion and the potential long-term future of powering the needs of humanity.

Unfortunately, there is still a way to go until we see traditional nuclear fission reactors and gas power stations decomissioned for fusion facilities.

Although the cascade reaction did realise more energy than the laser fired at the cylinder; the energy required to power the lasers themselves was around 10 times the amount of energy released into the fusion event. Also, there are challenges in how to extract this energy into useable power and electricity with the method used by NIF. This laser-based heating is unfortunately unlikely to be the method seen in commercial fusion since other methods are favoured by governments and industry. The laser method utilised by NIF involves the insertion of each pellet into the ignition chamber, the firing of lasers at the pellet to superheat it, and ultimately results in individual nuclear fusion events. Meanwhile, the more conventional (and less successful to date) 'tokamak' reactors are designed for continuous use, as they are self-heating and utilise the energy from the reaction to maintain the conditions necessary for fusion. These reactors would involve the superheating of plasma magnetically confined within a doughnut shaped vacuum chamber that could self-sustain the high temperatures. However, these reactors as of yet have not achieved 'ignition.' Evem with remaining challenges, this exciting breakthrough is an important step in our ability to exploit the power of the atom and nuclear energy in a clean and renewable way. Unlike uranium-based fission reactors, fusion reactors produce no long-lived radioactive nuclear waste. Perhaps it is Einstein's iconic equation, E=mc2, that will be humanity's salvation for our ever-growing hunger for energy with finite resources. Is biology the future of synthetic chemistry? Modern-day biology is perhaps the youngest of what we today regard as the three major sciences: Biology, Chemistry and Physics. Biology has grown from a study of natural history and physiology in the 19th century to a wide-ranging field, spanning cellular and molecular biology to biochemistry and genetics. Its young age is even reflected in the fact that there remains no Nobel Prize in Biology. It is probably fair to say that biology has faced an historical snobbishness from the two more physical sciences, since living things by their very nature are highly complicated. Therefore, as a result, efforts made to observe biological systems are far more imprecise and 'clumsy' compared to chemical or physical techniques. However, cutting edge science today is often at the fringes of these three sciences, and as modern analytical techniques have advanced, we can better understand and model these complicated biological systems. mRNA: RNA converts the genetic information contained within DNA to a format used to build proteins. CRISPR: Works like 'genetic scissors', this genetic engineering technique can cut out and insert genes using enzymes. Biosynthesis: The production of complex molecules within living organisms or cells. Recently biochemistry has offered cutting-edge solutions in the form of mRNA COVID vaccines and the development of CRISPR as a way of genetically modifying genetic material. These new approaches will enable us to better understand the role of genes and could potentially be applied in a form of targeted and personalised cancer treatment. For years, synthetic organic chemistry has largely had a monopoly on synthetic drug manufacture, and we owe the availability of a lot of modern medicines to organic chemists. However, can biology now provide answers that chemistry lacks, and become the future of drug synthesis in the 21st century? Biology and living organisms have evolved processes chemists could only dream of replicating int he lab. Enzymes within our own bodies are capable of making highly complex molecules at room temperature, room pressure, and biological pH without using any harmful solvents, toxic ragents, or expensive rare earth metals. Regrettably, it is usually highly specific to one reaction with highly tailored enzymes. Therefore, it would be hard to directly use these enzymes ex vivo in a reaction flask in the lab to create new molecules, as their shape and design is really only for one limited reaction under highly controlled conditions. A solution to this was found in 'directed evolution', which Arnold, Smith and Winter pioneered, and recently won the Nobel Prize in Chemistry 2018. Their idea was that we could tailor enzymes for a desired chemical reaction by "applying the principles of Darwin in the test tube." The process took the slow but effective process of natural selection from the natural world into the lab. Simply put, directed evolution starts with a target 'wild-type' natural enzyme, and mutants of this enzyme are generated and tested to see if the change to its genetics boosts its reactivity. Those that don't improve or get worse are discarded, however, those that do improve are removed, replicated and mutated again. The process is repeated iteratively until the target enzyme is highly specialised and effective in catalysing the desired process. This technique has been notably used last year by Merck in the development and synthesis of an exciting cancer drug candidate that has shown signs of tumour shrinkage in mice (MK-1454). In this trial, Merck optimised three enzymes using directed evolution in a one pot cascade reaction, synthesising MK-1454, with impressive yields. This discovery was describes in their 2022 publication in Nature. This notable finding would have previously been impossible without biological innovation to supplement conventional organic chemistry techniques. Curiously, one of these enzymes was developed from an enzyme found in bald eagles, although it would probably be best not mentioned to certain patriots from the USA. The future...

"Knowledge is power" - Sir Frances Bacon, 'Meditationes Sacrae' (1597)

This remains true today even in an era of fake news and 'alternative fact.' Science could offer a path to a post-carbon utopia with personalised gene-targeted medicine and even the ability to become an interplanetary species, all potentially within a few decades. However, science also reflects the worst of humanity offering incredibly dangerous, short-sighted and self-destruction paths - even global warming, as well-established as it is now, was predicted in secret by Exxon Mobil as early as the 1970s. Whilst a certain degree of scepticism is healthy, recent increasing levels of distrust in 'experts' is deeply concerning. All politicians, some more than others, as well as society as a whole, have been guilty of selecting scientific findings that justify their own world view, most notably recently with COVID. Instead, we should be shaping our view based on the sum of all evidence presented, and in lieu of a degree in biochemistry, molecular biology, or astrophysics, we need this evidence to be interpreted by relevant experts. That is not to say we should never question or probe their findings, but we need to restore trust in their expert fields such that we can make crucial decisions on the basis of evidence and objective truth, as opposed to emotion or rhetoric. Perhaps, ultimately the boundary we should be most concerned with is not a geographical or economic barrier, but at the frontier of politics and science. It's no exaggeration to say the future of our species will rise or fall at this divide.

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