Protein engineering, a Nobel celebration, and the resurgence of measles

This article is a preview from the Winter 2018 edition of New Humanist

Physics – Ceri Brenner

On Tuesday 2 October I jumped up from my desk and cheered. The Nobel Prize for Physics had just been announced for “ground-breaking inventions in the field of laser physics”. This year’s prize is a triple whammy of celebration for me, my colleagues at the Central Laser Facility and my research community.

First, half of the prize was awarded to Arthur Ashkin for developing the technique of optical tweezers, in recognition of the impact this has had on studies of biological systems. He discovered that at the focus of a laser beam, the light has delicate up and down pushing forces which can trap tiny objects like viruses, bacteria and even parts inside living cells, so that they can be held in place and studied up close. This technique is now widely used all around the world, including by my colleagues, and is a key technique for biology and biomedical science.

Second, the other half of the prize was awarded equally to Donna Strickland and Gerard Mourou for developing high intensity and very short pulses of laser light, in recognition of the impact this has had on medicine, industry and physics research. Intensity is a measure of how fast and over what area a given amount of energy is delivered. Since the invention of the laser in 1960, the intensity of lasers had steadily been increasing as improvements were made. However, by the early 1980s progress stalled because the laser light being generated was so intense that it was burning and fracturing the components of the laser system itself. Strickland and Mourou’s breakthrough was in developing a technique to overcome this issue to give ultrashort laser flashes and ever-increasing intensity. Their mechanism, called chirped pulse amplification, is what enabled lasers to be designed for eye surgery, for example, and is also why we have the super-intense lasers that I use in my research.

Third, this is the first time in 55 years that a woman has been recognised with a Nobel Physics Prize – ending a long period of women being wrongly overlooked for the important contributions they have made to Nobel-worthy physics breakthroughs. So three cheers for that.

Ceri Brenner is a physicist who works for the Science and Technology Facilities Council

Chemistry – Mark Lorch

Chemical engineering processes, used to manufacture everything from pharmaceuticals to plastics, generally require extreme conditions such as high temperatures, pressures and unpleasant chemical solvents. Meanwhile, natural protein molecules – enzymes – manage to control equally complicated chemical reactions within living things. They work under far more pleasant conditions. Protein engineers tinker with enzymes to make them catalyse different reactions. The obvious approach is via rational design, and is much like the way that a car mechanic might alter a piece here and there until the engine works more efficiently. Similarly, a protein engineer might tweak an atom here or there until the desired function is achieved. But rational design depends on detailed knowledge. What if you have no idea what the protein looks like or how it works?

Frances Arnold, one of the winners of this year’s Nobel Prize for Chemistry, solved that problem. She developed techniques that harness the power of evolution to engineer enzymes. Evolution occurs through three steps. First, there must be a series of variations (such as mutations). Second, the variations must cause differences in organism that lead to selection of the fittest. Last, the variations must be passed on to the next generation, when the cycle can be repeated. In nature, mutations may occur slowly and randomly and fitness is defined by how well an organism survives in the environment.

In direct evolution, a gene might be selected that produces a particular protein of interest. Maybe the enzyme speeds up a useful chemical reaction but it is unstable and only works for a few minutes. So a whole series of mutations are deliberately introduced. The genes producing a protein that works for longer than the natural enzyme get selected. These are then subjected to another round of mutations, and so on. Eventually, an enzyme emerges that fits the protein engineer’s criteria.
Due to Arnold’s work, we now have environmentally friendly processes that harness artificially evolved enzymes which can produce everything from pharmaceuticals to bio-fuels.

Mark Lorch is a chemist at the University of Hull

Biology – Lydia Leon

Measles is highly contagious. Before the first measles vaccine was introduced in 1963, and the subsequent Measles, Mumps and Rubella (MMR) vaccine in the early 1970s, epidemics caused around 2.6 million deaths a year, mostly children. In the decades since, global vaccination has been hugely effective: from 2000 to 2016 there was an 84 per cent drop in measles deaths globally – preventing 20 million deaths.

However, measles still kills many people each year – and 2018 has seen one of the worst outbreaks across Europe in recent history. Tens of thousands of new cases across the continent have resulted in dozens of deaths, many in countries that had previously eradicated or curbed the virus. The largest outbreak has been in Ukraine where over 30,000 cases had been reported by the start of October. In 2016 the World Health Organisation said that the UK had eradicated measles – but by early September this year, almost 900 cases were confirmed in the UK. According to Public Health England, inefction was most likely amongst unvaccinated teenagers and young people who missed out on MMR during a period of mistrust in the vaccine in the late 1990s.

This mistrust can largely be blamed on a debunked piece of research published in 1998 in the Lancet, purporting to link the MMR vaccine to autism and other disorders. The paper was later retracted and its primary author, Andrew Wakefield, struck off the medical register. Subsequent research has conclusively shown the vaccine to be safe and highly effective. But in the years following its publication, up to one million children in the UK may have missed out on MMR jabs, leaving them vulnerable to infection. Significant numbers of parents across the world still choose not to give their children the MMR vaccine. The WHO cites gaps in immunisation coverage as a key factor in the recent European outbreaks and setbacks to the ongoing global campaign to eliminate measles. The damage that Wakefield’s fraudulent paper has done to trust in the vaccine has reverberated across continents, and means that much remains to be done to eradicate measles.

Lydia Leon has a PhD in women’s health from University College London