Covid-19 has shown what modern biomedicine can do

covid-19 has had social, economic and political impacts beyond those of any other health crisis in modern history….a range of safe and effective vaccines based on various novel approaches was available within a year. One of the technologies used—directly injected mrna—opens up all sorts of further possibilities.

Testing and tracing could have worked better against covid-19

The first outbreak of a novel disease is the opening scene of a whodunnit. ...For covid-19, the mystery was solved almost as soon as it had begun….On January 12th 2020 the world knew its enemy—soon thereafter named sars-cov-2—down to the last letter of its genome….

They required suitably equipped laboratories. ...Dr Gabriel learned two lessons in the process. The first is that uniformity matters a lot. ...The second is that you need software to track the whole process. ...By March 2021 it could handle 200,000 tests a day and was serving customers as far afield as New York.

where did that person—the index case, in public-health speak—pick up the virus? To whom might they have given it?...Some, such as Singapore and Taiwan, benefited in this from their experience with sars in the mid-2000s....In South Korea, for instance, contact tracers were able to download a list of all financial transactions made by those who tested positive….Western governments acted in a slower, less thoroughgoing way.

A much discussed alternative to such programmes was to use the world’s most ubiquitous tracking devices: smartphones. ...But everything is peer-to-peer; neither the big tech companies nor the public-health authorities get a list of contacts….None of the successful contact-tracing systems in East Asia relies on such things to any significant extent….

Even without good tracing, self isolation of those who tested positive helped slow the spread of the disease. But despite its familiarity, reliability and sensitivity, it has real disadvantages….One is that it needs labs, and is carried out most efficiently in big ones….Another problem is that though the presence of viral RNA clearly shows that a person has been infected, it says very little about where they stand in the course of the disease….

In public-health terms what is needed is a test that spots people who are actually infectious….And one of the basic rules of modern biotechnology is that when you want to find a protein, use an antibody….A combination of local, automated pcr and lateral-flow tests could be the basis of an ideal testing system.

Well conceived drug trials have saved hundreds of thousands of lives

In february 2020 doctors from the World Health Organisation (who), visiting China to see the ward- and morgue-filling reality of covid-19, found more than 200 clinical trials under way….But the trials were all too small to see if those hopes were being borne out.

In March 2020 the who set up Solidarity, a trial which eventually enrolled 12,000 patients in 30 countries….Six months on, none of the treatments was found to reduce mortality or the need for mechanical ventilation; nor did they shorten hospital stays.

Antivirals, by contrast, must either tweak the inner workings of cells to make them inimical to viruses or target one of the handful of viral proteins required for infection or replication….Fifty countries, including America, have approved it (Remdesivir) for use, but the who remains unconvinced of its merits.

If antivirals have underwhelmed, a cheap anti-inflammatory drug has been a life saver….Dexamethasone, the benefits of which recovery had demonstrated by June 2020, is a corticosteroid which acts as an anti-inflammatory….RECOVERY showed that the best time to start dexamethasone is when patients first needed to be given oxygen.

This February the recovery trial showed that tocilizumab, another drug which dampens down immune responses, also reduces the risk of death from covid-19, confirming results from an earlier European trial….The pharmaceutical industry tends to use the antibodies it makes in cell cultures to different ends...And in the most impressive of all medicine’s responses to the covid-19 pandemic, new vaccine technology is now putting those production lines to use in millions of people every day.

Novel vaccines have performed remarkably quickly and well

On november 30th 1803 the María Pita, a 160-tonne corvette, set sail from Spain for the New World. ...The initial challenge faced by the man in charge of this expedition, Francisco Balmis, was how to get viable cowpox across the ocean. ...Creating vaccines is a job for biology, and doing biology requires living systems.

When the first, spectacularly positive results from phase 3 trials of the Pfizer/BioNTech mrna vaccine were released on November 9th they did not just offer a pandemic exit strategy….medicine has begun to look like programming.

For a long time vaccine production was an often messy and sometimes disgusting business. ...In the 1968 flu pandemic Maurice Hilleman, and American virologist, got through chicken eggs by the tonne as he grew 9m vaccine doses in their yolks in just four months….But the manufacturing systems that are being used to make the vaccines against covid-19 currently being administered at a rate of millions per day are something else again….Instead they just send a message: the genetic sequence which describes the sars-cov-2 spike protein.

The new vaccines deliver their message in two different ways. In the Oxford/AstraZeneca, Johnson&Johnson and Sputnik V vaccines it is contained in a protein shell derived from an adenovirus….An important part of this is that the message in the DNA is independent of the particles into which it is packed and of the cultured cells that do the packing....The second of the new technologies, mRNA, works on similarly modular lines, but is yet more radical….The mRNA thus produced is then packaged into tiny particles of lipid—the inert material from which the membranes around cells are made.

Easily made, precisely programmed mRNA vaccines are being looked at for a number of infectious diseases—including malaria—as well as in cancer immunotherapy….GreenLight intends to use production processes similar to those used by the vaccine-makers to produce a different sort of rna molecule which can be used as a pesticide targeted against the Colorado Beetle.

At the moment it is the adenovirus vaccines, not those based on mRNA, that are being produced at the greatest scale and lower cost, handily outcompeting the older techniques using inactivated sars-cov-2 which have been tried in China. ...Whether this will make mRNA vaccines the dominant ones within the next few years remains an open question. But whether it does or not, efforts towards that end will give the world an entirely new bioindustrial infrastructure, one capable of putting ideas into cells, both human and otherwise, more easily than ever before.

Watching SARS-CoV-2 evolve is fascinating and frightening

Genome sequencing, crucial to the original identification of SARS-CoV-2 and to providing the templates for the vaccines against it, also offered a new way to watch the pandemic unfold. Viruses often make mistakes when they copy their genomes, a crucial step in reproduction, and that means they accumulate mutations pretty quickly….

Its rapid spread made B.1.1.7 a “variant of concern” even before evidence began to demonstrate that it is more likely to cause disease than the original strain. ...In all three cases mutations are concentrated in the gene which describes the spike protein: one mutation in that gene, N501Y, is common to all three. ... it suggests this mutation helps the virus….If evolution were to have goals for it, they would be that it should bind to the target better and that the bits that do that binding should be harder for antibodies to neutralise. The mutations that have accumulated in the variants of concern seem to do just that.

These variants are a problem for Eli Lilly and Regeneron, the companies offering antibodies as drugs against the virus. ...More worrying is what the new variants mean for vaccination. ...The mRNA and adenovirus companies are making sure they can load the gene sequence for a new version of the spike protein into their production systems if need be. Novavax would need to re-engineer the cells used to produce its version of spike.

Spotting variants wherever they turn up, and assessing quickly what added risk they pose, must now be a central part of fighting the virus….And it may also end up being a way to monitor the transition, if it happens, of SARS-CoV-2 to endemicity. ...The idea that SARS-CoV-2 might go the same way and evolve, eventually, into something no more threatening than a cold might sound like wishful thinking. But it is possible.

Putting the viruses of the world into a panopticon is no longer impossible

To keep an eye on how a single pathogen navigates, mutation by mutation, through a worldwide landscape of adaptation would have been unthinkable more than ten years ago. In the face of a pandemic, it has proved possible….As to outlandishness: rna vaccination seemed like a wild idea less than a decade ago, and impractical to implement much more recently. Now it has shifted the boundaries of the possible. It cannot be the only elegant biotechnological notion lurking in relative obscurity that has the potential to be realised.

The Global Immunological Observatory (gio), an idea conceived by Jessica Metcalf, a disease ecologist at Princeton University, and Michael Mina, an epidemiologist at Harvard University, aim to use modern lab techniques to spot incipient health crises before they take off by providing near-real-time insight into what infections are where….The GIO would ideally test every tiny sample of blood for hundreds of thousands of distinct antibodies. ...there are tools that might be up to the job. ...“[It] allows us to get a readout simultaneously of hundreds of thousands of different antibodies that somebody might have,” says Dr Mina….A system to provide hundreds of thousands of blood samples, even tiny ones, would require a lot of planning and broad goodwill. But Dr Mina thinks blood already taken for other reasons could provide a worthwhile starting point for the project….If GIO had been operating in late 2019 and early 2020, it would have seen antibodies to a range of coronaviruses starting to turn up in various places, a molecular shadow alerting it to a new pathogen it could not yet see directly, but which, after a little sequencing, it would understand intimately.

For extreme events, though, other sorts of data may be needed, from across the animal kingdom….Jonna Mazet, an epidemiologist at the University of California, Davis, and Dennis Carroll, an infectious-disease expert formerly with America’s international development agency, estimate that up to 827,000 of them could cross over into humans. Dr Mazet and Dr Carroll arrived at that daunting number when analysing what it would take to make all those unknowns known….In 2018 Dr Mazet and Dr Carroll sketched out a Global Virome Project (gvp) which would build on the procedures and protocols used in predict:...With the right information infrastructure, the next pandemic could be spotted almost before it has begun.

Safe harbours

the idea of forecasting disease by accumulating and mapping data would have resonated with him. FitzRoy took a very similar approach when, in 1860, he invented what he called the “weather forecast”....FitzRoy was convinced that with atmospheric pressure for ports around Britain plotted on a map, and with a general understanding of northern-hemisphere storms, such tragedies could be averted….FitzRoy had a good idea; but he lacked the data and tools to make it work.

Today’s biology utterly outclasses FitzRoy’s meteorology. ...This does not mean it can easily be fashioned into a prediction system;...But as The Economist wrote in 1866, receiving unreliable storm warnings still has benefits….

People may never glance at their phones to see the viral forecast for their children’s school, as some boosters might imagine, or get this winter’s must-have antibodies delivered by Amazon. But unless the lessons of covid-19 are ignored, and the technological advances it has pulled out of the lab allowed to gather dust, the world can expect better testing, better drugs, better vaccines and better foresight in crises to come—and between them, too.

Chemical Reaction Engineering...of My Brain

Mar 27 2021 Tech Quarterly - Summary