About: This is a wonderful story, from my perspective, on what happened this week, in our World. This week we take five heavy steps in 2020 and two light steps in 2021. A solid start, for sure.

Everywhere

The Software Of Life: The Hard Story of Katalin Kariko

Ever wondered how we got a Vaccine for Covid-19 so quickly? This is the incredible, fascinating story of how an indefatigable, never-say-give-up biochemist provided the foundation and the springboard for making this possible.

I quote this unforgettable, powerful – my all time favourite – speech by Howard Roark, in a court, in Ayn Rand’s classic, ‘The Fountainhead’, defending his unconventional method of approach to work.

“Throughout the centuries there were men (also meaning women) who took first steps down new roads armed with nothing but their own vision. Their goals differed, but they all had this in common: that the step was the first, the road new, the vision un-borrowed, and the response they received-hatred. The great creators-the thinkers, the artists, the scientists, the inventors-stood alone against the men of their time. Every great new thought was opposed. Every great new invention was denounced. The first motor was considered foolish. The airplane was considered impossible. The power loom was considered vicious. Anaesthesia was considered sinful. But the men of un-borrowed vision went ahead. They fought, they suffered, and they paid. But they won”. Let’s take the next step on this week’s road.

The announcement of the discovery of messenger ribonucleic acid (mRNA) – one of the fundamental building blocks of life – and cracking of the genetic code happened within weeks of each other in a climax of scientific excitement in the year 1961. We have all, by now, become awfully familiar with mRNA, haven’t we?

For more than a decade, researchers in the US and Europe had been attempting to unravel exactly how the deoxyribonucleic acid (DNA) is involved in the creation of proteins – the long strings of amino acids, and the carrier of genetic information, that are sine quo non to the growth and functioning of all life forms. It was discovered that mRNA is the answer. These molecules act like digital tape recorders, repeatedly copying instructions from DNA in the cell nucleus, and carrying them to protein-making and synthesizing structures called ribosomes. Without this key role, DNA would be nothing but a useless string of chemicals, and so some have dubbed mRNA the ‘software of life.’ Now, onto our biochemist, the mRNA Scientist.

Katalin Kariko was born in the year 1955, in a Christian family in Szolnok, Central Hungary. She grew up in Kisujzellas on the Great Hungarian Plain where her father worked as a butcher. Fascinated by science, Kariko began her career, at age 23, at the Biological Research Centre in the University of Szeged, Hungary, where she obtained her PhD. Kariko was first exposed to the functions of mRNA as an under-graduate student in 1976, during a lecture at the University and has been intrigued ever since. Her PhD was on studying how mRNA might be used to target viruses. While the concept of gene therapy was also beginning to take off at the same time, she felt mRNA had the potential to become a game-changer in kicking-up the body’s cells to fight infections.

Communist Hungary being always hungry for resources couldn’t feed Kariko’s hunger, leave alone her appetite, for research, and in 1985 the University sacked her.

With little opportunities elsewhere, Kariko got a job at the Temple University, Philadelphia, USA and decided to immigrate. Hungarians being forbidden to take money outside the country, she sold the family car in the black market, and hid the money by sewing it up inside her two-year old daughter’s stuffed toy teddy bear.

It did not take long for the American Dream to crash-land. And after four years, Kariko was forced to leave Temple University and join the neighbouring University of Pennsylvania (UPenn), following a dispute with her boss, who even attempted to have her deported.

By the early to mid 1990s, the initial excitement surrounding mRNA was beginning to thin-out and fade. While scientists had cracked the problem of how to create their own mRNA, a new hurdle had emerged: when injected into animals it induced such a severe inflammatory response from the immune system that the animal died. Any thoughts of human trials was impossible.

However, Kariko was determined to solve this problem. But many other scientists were turning away from the field, and her bosses at UPenn felt mRNA had shown itself to be impractical, and she was wasting her time. They issued an ultimatum, if she wanted to continue working with mRNA she would lose her prestigious faculty position, and face a substantial pay cut.

Meanwhile, Kariko was diagnosed with cancer and her husband who had gone back to Hungary, to complete unfinished business, got stranded over a Visa issue.

While undergoing surgery, Kariko thought it over: decided to stay in UPenn, accept the humiliation of being demoted, and continue to doggedly pursue the problem. This led to a chance meeting with Drew Weissman, a respected immunologist, who moved to UPenn in 1977, which would both change the course of her career, and that of science.

While Kariko’s academic status at UPenn remained lowly, Weissman had the necessary funding to finance her experiments, and the two began a partnership.

Kariko and Weissman realised that the key to creating a form of mRNA which could be administered safely, was to identify which of the underlying nucleosides – the letters of RNA’s genetic code – were provoking the immune system and replace them with something else ‘more friendly’. In the early 2000s, Kariko stumbled upon a study which showed that one of these letters, Uridine, could trigger certain immune receptors. It was the crucial piece of information she had been searching for.

Every strand of mRNA is made up of four molecular building blocks called nucleosides. But in its altered, synthetic form, one of those building blocks, like a misaligned wheel on a car, was throwing everything off by signalling the immune system. So Kariko and Weissman simply substituted it with a slightly tweaked version, creating a hybrid mRNA that could sneak its way into cells without overly alerting the body’s defences.

In 2005, Kariko and Weissman published their Study, announcing a specifically modified form of mRNA, which replaced Uridine with an analog – a molecule which looked the same, but did not induce an immune response. It was a clever biological trick, and one which worked. When mice were injected with this modified mRNA, they lived. Kariko and Weissman filed a patent, established a company, but then found there was no interest shown in their work. Nobody invited them anywhere to talk about it, nothing at all.

Unknown to them, some scientists were quietly paying attention and reading the fine print of their publication. And in 2010 a Biotech company called Moderna, was founded with a group of Harvard and MIT professors, with the specific aim of using modified mRNA to create vaccines and therapeutics. A decade on, Moderna is now one of the leaders in the Covid-19 vaccine research and production, as part of America’s ‘Operation Warp Speed’ which goal is to produce and deliver 300 million doses of safe and effective vaccines with the initial doses available by January 2021. Around the same time Moderna was founded, Kariko and Weissman finally managed to commercialise their finding, licensing their technology to a small German company called BioNTech, after five years of trying and failing.

Both Moderna and BioNTech, which was founded by a Turkish born entrepreneur, had their focus on the lucrative fields of cancer immunotherapy, cardiovascular and metabolic diseases. Now that Kariko and Weissman’s discovery made it possible to safely administer mRNA to patients, some of the original goals for mRNA back in the 1970s, suddenly become viable possibilities, again.

In 2013, Kariko accepted an offer to become Senior Vice President at BioNTech after UPenn refused to reinstate her to the faculty position she had been demoted from in 1995. She was told, UPenn concluded that she wasn’t ‘Faculty Quality’. When she said she was leaving they laughed at her and said, ‘BioNTech doesn’t even have a website.’ Kariko has been at the helm of BioNTech’s Covid-19 vaccine development ever since, and the Official Vaccine co-developed with Pfizer has now been approved for use.The rest, they say, is history.

With the Covid-19 pandemic requiring vaccine development on an unprecedented scale, mRNA vaccine approaches held a clear advantage over the more traditional but time consuming method of using a dead or inactivated form of the virus to create an immune response. Basically, the mRNA tells cells what proteins to make, essential to keeping our bodies alive and heathy. The mRNA degrades quickly and the instructions it gives the body aren’t permanent, making the technology and ideal platform for a variety of applications.

After so many years of adversity, and struggling to convince people that her research was worthwhile, she is still trying to comprehend the fact that her breakthrough in mRNA technology could now change the lives of billions around the world, and help end the pandemic. She has passed on the strong-willed message to her daughter, Susan Francia, who won the gold medal in the US Rowing Team, in the 2008 and 2012 Olympics.

Katalin Kariko deserves a Noble Prize. Medicine, or Chemistry – you decide!

The World of Abortions

This Wednesday, Argentina, South America’s third-most populous, catholic-majority country, legalised abortion in an historic vote to give millions of women access to legal terminations under a new law supported by its President, Alberto Fernández.

The law will legalize abortion in all cases up to 14 weeks of pregnancy. Abortion in Argentina, is currently only permitted when a pregnancy results from rape or endangers the life or health of the woman. In all other circumstances, abortion is illegal and is punishable by up to fifteen years in jail.

According to a study report nearly 40,000 women and children in Argentina were hospitalized in 2016 as a result of unsafe, clandestine abortions or miscarriages.

Let’s do a quick flashback, when India passed a similar, important legislation in January 2020, which went largely un-noticed and un-applauded. India amended its Medical Termination of Pregnancy (MTP) Act allowing women to seek abortions as part of reproductive rights and gender justice placing India in the top league of countries serving women who wish to make individual choices based on their own perspectives and situations. The new law leans forward a lot, is empathetic, and looks at a very sensitive issue with a human face.

India’s MTP Act raised the upper limit of MTP from 20 to 24 weeks for women, including rape survivors, victims of incest, differently-abled women and minors. Failure of contraception is also acknowledged, and MTP is now available to ‘any woman or her partner’ replacing the old provision for ‘only married woman or her husband.’ It proposes requirement of opinion of one Registered Medical Practitioner (RMP) for termination of pregnancy up to 20 weeks. It also provides for the requirement of opinion of two RMPs for termination of pregnancy of 20 to 24 weeks. It seeks to increase the upper limit from 20 to 24 weeks for survivors of rape, victims of incest and other vulnerable women. For unmarried women, the Bill seeks to relax the contraceptive-failure condition for ‘any woman or her partner’ from the present provision for ‘only married woman or her husband’, allowing them to medically terminate the pregnancy.

Whoa, unbelievable things happening inside us! I’ve always believed that a woman should have complete control over her body, and make informed choices depending on the predicament she is in.

The striking Indian farmers should have applauded this law, which is as path-breaking at the new Farm Laws. Sometimes, we simply do to know what is good for us until we plough, seed and watch the results swell – and occupy space!

Rajinican’t: In World Inthavaaram, 2020-49, I talked about 70 year old South-Indian Tamil superstar Rajinikanth’s decision to enter Indian Politics.

https://kumargovindan.wordpress.com/2020/12/05/world-inthavaaram-2020-49/

This time around, after many tireless flicks of the cigarette, it missed the lips. The Actor was hospitalised with irregular blood pressure during a shooting of his 168th film ‘Annaatthe’ (meaning, elder brother) and the movie crew got infected with Covid-19. This was weeks before he was to make an announcement of launch of a casteless, boundary less New Political Party on 31st December 2020 to take on the mighty parochial, chauvinist Dravidian Parties of Tamilnadu. The Doctors on discharging him from Hospital put the brakes on his ventures outside the bed and advised complete bed-rest for at least a week. In 2016 Rajini has undergone a kidney transplant and has been plagued with health issues over the years. Given the stranglehold of the pandemic, making it awfully difficult to meet people and convince them to vote for him, Rajini decided to quit politics even before he entered it, citing health issues. God sent him an email (probably a mRNA hit him in Hospital?), while lying on his Hospital Bed, and Rajini read it well.

Millions of his fans were disappointed. But, I think it’s a bold decision. Made me wonder why he was ‘still acting’ when he was planning to launch his political career in a couple of days? Appears that he wanted to finish the shooting, of the already started film, before plunging into full-time politics. It wasn’t to be. Wisdom is making intelligent choices on things you can and cannot do. Cigarette-flicking takes the pressure off the head, putting it in the hands…and it works!

The Ancient World

Every new year becomes seemingly brighter, once we unravel and learn more about new things of ancient life on Earth; the way our ancestors lived – well, actually the way they ate their food.

Archaeologists digging in the ancient Roman city of Pompeii have made the extraordinary find of a hot food and drinks snacks shop – known as a termopolium – that served up the ancient equivalent of street food to locals and passersby. The shop, with its bright frescoes and terracotta jars, was discovered in 2019 and unveiled last Saturday. It is expected to be opened to the public – for viewings only – this year. Once the travel restrictions are lifted, buy yourself a ticket to Pompeii for an ancient snack?

Pompeii, 23 km southeast of Naples, Italy, was home to about 13,000 people when it was buried in a volcanic eruption from ‘loudly thinking’ Mount Vesuvius, in 79 CE.

Traces of nearly 2,000-year-old food were found in some of the deep terra cotta jars containing hot food which the shop-keeper probably lowered into a counter with circular holes. The front of the counter was decorated with brightly coloured frescoes, some depicting animals that were part of the ingredients in the food sold, such as a colourful rooster and two ducks hanging upside down. Traces of pork, fish, snails and beef had been found in the containers, a discovery which is a ‘testimony to the great variety of animal products used to prepare dishes.’

For sure the Romans ate well!

The UN has declared 2021 as the International Year of Peace and Trust, while it’s also the International Year of Fruits and Vegetables.

Happy New Year 2021. The best is yet to come! And there’s lots to eat.