Features
PCR and eccentric genius who invented it
By Prof Kirthi Tennakone
(Email: ktenna@yahoo.co.uk )
Hardly a day passes without the letters, PCR, – the acronym for polymerase chain reaction — being mentioned. To most of us PCR sounds just a test for knowing whether someone has contracted COVID-19 or not.
The polymerase chain reaction is a game changing technique offering diverse and far reaching applications beyond a gold standard for COVID-19 detection.
It is fascinating and entertaining to learn about polymerase chain reaction and its discoverer Kary Mullis, nicknamed untamed genius.
The invention of PCR is intimately connected to our understanding of the cause of biological inheritance. The reason why we have features resembling our parents. A mystery that lead to the discovery of DNA and development of the science of life thereafter. Brief digression into this subject helps to fathom what PCR really means.
Understanding the cause of biological
inheritance and discovery of DNA
Humans have wondered why progeny resemble parents and have some physical and mental traits of the latter. A sprout from a minuscule banyan seed always grows into a gigantus of the same kind but never a tender mustard plant. The ancient Greeks believed that a creature to be born or a plant to germinate subsisted inside the sperm and the seed respectively in their miniature forms. A different idea gained ground later and lasted for more than 2,000 years that physical traits acquired by parents indirectly pass to the offspring. A proponent of this hypothesis in recent times was the French naturalist Lamarck. If Lamarckism were true, amputation of the tails of successive offspring of mice would eventually lead to a generation of tailless rodents. All such experiments failed.
Lamarckism did not confront creationism and intelligent design to the hurt religious establishment. It attracted communists as a way of improving the society to meet ideological aspirations and enhance crop production. The infamous agronomist Lysenko mistrusting proven science attempted to reform Soviet agriculture believing Lamarckian ideals. He probably faked experimental results to justify his thesis and advised famers to abandon use of fertilizers and grow of each crop intensely segregated in order to increase the yield. The result was a famine that starved millions – a good lesson for those who advocate pseudoscience promoting quackeries as remedies for COVID-19 or recommend withdrawal of fertilizer on basis of unreliable claims.
When the world was deluded by Lamarckism, definitive clues as to what really causes inheritance followed from the seminal works two revolutionaries, Charles Darwin and Gregor Mendel.
Darwin in his presentation of the theory of evolution noted that the decedents of a given species, sometimes include one’s with distinct variations in their characteristics, referred to as mutants. If the new qualities acquired by the mutants fits the environment, they survived and continuation of evolution via natural selection led to the emergence of new species.
Another question crucial to understand the cause of inheritance has been how the traits of male and female sexual partners were represented in the offspring? Without resorting to experiment and careful analysis, the conservative stream of biologists continued to believe it should be a blend of the maternal and paternal traits. In late 1890s, the work of the Austrian monk Gregor Mendel, a mathematician and a botanist as well, provided a conflicting answer. In an experiment lasting for eight years Mendel planted different strains peas, cross-pollinated them and germinated the seeds brought forth to see features of the of linage such as the height to which they grew and the colour of flowers. His results did not indicate blending of traits, instead the original attributes appeared in each generation with different probabilities. Crossing tall and dwarf varieties never procreated medium size plants; instead, they were either tall or dwarf. Mendel concluded that traits were passed to the progeny as distinct qualities – what we refer to as genes today.
The work of Darwin and Mendel compounded by subsequent findings, pinpointed the inescapable conclusion that a chemical substance transmitted inheritance. Many believed it should be a protein. In 1942, the prescient Austrian physicist Erwin Schrodinger, famous for the quantum theory, expressed an alternative opinion. He hypothesized that the heredity determining entity, needed to be a molecule capable of encoding information and replication. Aroused by Schrodinger’s proposition, chemists all over the world competitively researched to identify the causative agent. In early 1950s, American biologist Watson and British physicist Crick, showed that the genetic material found in cells of animals and plants was deoxyribonucleic acid DNA – a lengthy molecule constituted basically of two strands of four different repeated subunits. Molecules of DNA encode information using these units as a four letter alphabet.
Cells of every organism contain DNA characteristic to the species and unique to each individual. The order in which millions of these units sequentially are arranged in a helical chain, is analogous to an instruction manual detailing the development of the organism. Short sequences of the four units in the chain represent genes, dictating special instructions, just like a sentence or a paragraph in the manual.
Polymerase chain reaction (PCR) and its uses
PCR is a technique of amplifying million-fold a tiny quantity of DNA representing a sequence of interest in minutes so that it could be detected even in minutest quantities – justifying the use of the term chain reaction with polymerase as the catalyst ensuing the reaction. In the analogy of DNA to an instruction manual, PCR would be like inserting a book mark to fix a certain page and copying that page many times.
In finest detail DNA is unique to each individual, whether it is a human or a bacterium. The difference between DNAs of individuals in a given species is minuscule. Yet, the identity of a person can be established from DNA in the smear of saliva over a stamp by PCR. Again just like finding a needle in a hay stack, minute quantities of a specific type of DNA in a sample containing excessive quantities of DNAs from background sources, can be selectively ascertained by running a PCR. The technique finds wide range of applications in medical diagnostics, forensics and criminology, archaeology and paleontology, phylogenetics, cloning, gene editing etc.
How is PCR detecting corona virus?
The genetic material of the corona virus is RNA – a single strand of DNA. The test first converts RNA into DNA making it double stranded and then selectively amplify a fragment of DNA covering a specific sequence using special reagents. The amplification enables detection by a screening system. Test is extremely sensitive; in fact, too sensitive, responding to even the dead fragments of the virus.
The impact of PCR on forensics and criminology is unprecedented. The technique has enabled not only identification of criminals but also the exoneration of innocent. A man on death row for eight years has been released and compensated as PCR became available.
Kary Mullis: The man who discovered PCR
Kary Mullis born in Southern United States 1944 was exceptional and radical. As a high schooler he meddled with chemicals at home and created an ingenious technique for making rocket fuels. His homemade rockets propelled miles into the sky frightening pilots maneuvering airplanes to land. Having earned a bachelor’s degree in chemistry from Georgia Institute of Technology he moved to University of California, Berkeley to pursue studies towards a doctoral degree in chemistry. A fashionable field of study at that time was chemistry of DNA or molecular biology. Instead of following courses in biochemistry needed for the thesis, he opted for astrophysics, saying he could learn the former discipline talking to colleagues. He wrote an article on a fundamental problem in astrophysics and succeeded getting it printed in the prestigious journal Nature. He was a surfing enthusiast and guitarist.
At the oral examination for qualifying to register as a doctoral candidate, Mullis was found to be unprepared and weak in conventional biochemistry. However, his paper on an astrophysical subject rather than biochemistry saved him from disqualification. The committee decided despite odd behaviour and unpreparedness, the man was talented and granted him approval for registration. Mullis earned a Ph.D. in 1973 and decided to give up research to become a writer and worked in a restaurant. Later, one of his friends persuaded him to a job in a biochemical company, at least to earn a living. There, he worked in a laboratory devoted to DNA chemistry, often quarrelling with coworkers. In early 1980s, he came up with the idea of PCR, but no one took him seriously. The paper he wrote was rejected twice and finally published in a less acclaimed journal. Soon the world acknowledged the utmost significance of his work and Mullis shared 1993 chemistry Nobel Prize. He resorted to eccentric behaviour criticizing the establishment and mainstream thinking, earning reputation as the untamed genius. When he was invited to a high-standing conference on molecular biology, he projected three slides of female nudes, lambasted the way of funding research and vanished! In an interview, Mullis has said Nobel Prize serves as a licence to do things unacceptable.
Kary Mullis, who passed away in 2019, will be remembered as a demarcater of biology into two epochs – before PCR and after PCR. Fortunately, the pandemic is post – PCR. Otherwise the situation would have taken a more deadly and devastating turn.
The invention of PCR stands as a prime example to highlight how fundamental studies motivating creativity, foresight and hard work can pay off unexpectedly. A constant reminder to research and academic institutions to retain this spirit of accommodating the most talented and not the mediocre who entertain trivialities for the shake of survival. The latter even amend (adulterate) the established mandates for fostering advanced studies to suit them. And deceiving the policymaker and general public, stating the amendments (adulterations) were affected to meet national interest (self-interest).
Would a man of the calibre of Kary Mullis be considered for employment or allowed to continue in our institutions? Will a committee here act with the same altruism and consideration as the one that endorsed the candidature of Kary Mullis?
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There’s an ill more dangerous and pervasive than the Coronavirus that’s currently sweeping Sri Lanka. That is the fear to express one’s convictions. Across the public sector of the country in particular many persons holding high office are stringently regulating and controlling the voices of their consciences and this bodes ill for all and the country.
The corrupting impact of fear was discussed in this column a couple of weeks ago when dealing with the military coup in Myanmar. It stands to the enduring credit of ousted Myanmarese Head of Government Aung San Suu Kyi that she, perhaps for the first time in the history of modern political thought, singled out fear, and not power, as the principal cause of corruption within the individual; powerful or otherwise.
To be sure, power corrupts but the corrupting impact of fear is graver and more devastating. For instance, the fear in a person holding ministerial office or in a senior public sector official, that he would lose position and power as a result of speaking out his convictions and sincere beliefs on matters of the first importance, would lead to a country’s ills going unaddressed and uncorrected.
Besides, the individual concerned would be devaluing himself in the eyes of all irrevocably and revealing himself to be a person who would be willing to compromise his moral integrity for petty worldly gain or a ‘mess of pottage’. This happens all the while in Lankan public life. Some of those who have wielded and are wielding immense power in Sri Lanka leave very much to be desired from these standards.
It could be said that fear has prevented Sri Lanka from growing in every vital respect over the decades and has earned for itself the notoriety of being a directionless country.
All these ills and more are contained in the current controversy in Sri Lanka over the disposal of the bodies of Covid victims, for example. The Sri Lankan polity has no choice but to abide by scientific advice on this question. Since authorities of the standing of even the WHO have declared that the burial of the bodies of those dying of Covid could not prove to be injurious to the wider public, the Sri Lankan health authorities could go ahead and sanction the burying of the bodies concerned. What’s preventing the local authorities from taking this course since they claim to be on the side of science? Who or what are they fearing? This is the issue that’s crying out to be probed and answered.
Considering the need for absolute truthfulness and honesty on the part of all relevant persons and quarters in matters such as these, the latter have no choice but to resign from their positions if they are prevented from following the dictates of their consciences. If they are firmly convinced that burials could bring no harm, they are obliged to take up the position that burials should be allowed.
If any ‘higher authority’ is preventing them from allowing burials, our ministers and officials are conscience-bound to renounce their positions in protest, rather than behave compromisingly and engage in ‘double think’ and ‘double talk’. By adopting the latter course they are helping none but keeping the country in a state of chronic uncertainty, which is a handy recipe for social instabiliy and division.
In the Sri Lankan context, the failure on the part of the quarters that matter to follow scientific advice on the burials question could result in the aggravation of Islamophobia, or hatred of the practitioners of Islam, in the country. Sri Lanka could do without this latter phobia and hatred on account of its implications for national stability and development. The 30 year war against separatist forces was all about the prevention by military means of ‘nation-breaking’. The disastrous results for Sri Lanka from this war are continuing to weigh it down and are part of the international offensive against Sri Lanka in the UNHCR.
However, Islamophobia is an almost world wide phenomenon. It was greatly strengthened during Donald Trump’s presidential tenure in the US. While in office Trump resorted to the divisive ruling strategy of quite a few populist authoritarian rulers of the South. Essentially, the manoeuvre is to divide and rule by pandering to the racial prejudices of majority communities.
It has happened continually in Sri Lanka. In the initial post-independence years and for several decades after, it was a case of some populist politicians of the South whipping-up anti-Tamil sentiments. Some Tamil politicians did likewise in respect of the majority community. No doubt, both such quarters have done Sri Lanka immeasurable harm. By failing to follow scientific advice on the burial question and by not doing what is right, Sri Lanka’s current authorities are opening themselves to the charge that they are pandering to religious extremists among the majority community.
The murderous, destructive course of action adopted by some extremist sections among Muslim communities world wide, including of course Sri Lanka, has not earned the condemnation it deserves from moderate Muslims who make-up the preponderant majority in the Muslim community. It is up to moderate opinion in the latter collectivity to come out more strongly and persuasively against religious extremists in their midst. It will prove to have a cementing and unifying impact among communities.
It is not sufficiently appreciated by governments in the global South in particular that by voicing for religious and racial unity and by working consistently towards it, they would be strengthening democratic development, which is an essential condition for a country’s growth in all senses.
A ‘divided house’ is doomed to fall; this is the lesson of history. ‘National security’ cannot be had without human security and peaceful living among communities is central to the latter. There cannot be any ‘double talk’ or ‘politically correct’ opinions on this question. Truth and falsehood are the only valid categories of thought and speech.
Those in authority everywhere claiming to be democratic need to adopt a scientific outlook on this issue as well. Studies conducted on plural societies in South Asia, for example, reveal that the promotion of friendly, cordial ties among communities invariably brings about healing among estranged groups and produces social peace. This is the truth that is waiting to be acted upon.
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By Sanjeewa Jayaweera
It was on 3rd January 1972 that our family arrived in Karachi from Moscow. Our departure from Moscow had been delayed for a few weeks due to the military confrontation between Pakistan and India. It ended on 16th December 1971. After that, international flights were not permitted for some time.
The contrast between Moscow and Karachi was unbelievable. First and foremost, Moscow’s temperature was near minus 40 degrees centigrade, while in Karachi, it was sunny and a warm 28 degrees centigrade. However, what struck us most was the extreme warmth with which the airport authorities greeted our family. As my father was a diplomat, we were quickly ushered to the airport’s VIP Lounge. We were in transit on our way to Rawalpindi, the airport serving the capital of Islamabad.
We quickly realized that the word “we are from Sri Lanka” opened all doors just as saying “open sesame” gained entry to Aladdin’s cave! The broad smile, extreme courtesy, and genuine warmth we received from the Pakistani people were unbelievable.
This was all to do with Mrs Sirima Bandaranaike’s decision to allow Pakistani aircraft to land in Colombo to refuel on the way to Dhaka in East Pakistan during the military confrontation between Pakistan and India. It was a brave decision by Mrs Bandaranaike (Mrs B), and the successive governments and Sri Lanka people are still enjoying the fruits of it. Pakistan has been a steadfast and loyal supporter of our country. They have come to our assistance time and again in times of great need when many have turned their back on us. They have indeed been an “all-weather” friend of our country.
Getting back to 1972, I was an early beneficiary of Pakistani people’s love for Sri Lankans. I failed the entrance exam to gain entry to the only English medium school in Islamabad! However, when I met the Principal, along with my father, he said, “Sanjeewa, although you failed the entrance exam, I will this time make an exception as Sri Lankans are our dear friends.” After that, the joke around the family dinner table was that I owed my education in Pakistan to Mrs B!
At school, my brother and I were extended a warm welcome and always greeted “our good friends from Sri Lanka.” I felt when playing cricket for our college; our runs were cheered more loudly than of others.
One particular incident that I remember well was when the Embassy received a telex from the Foreign inistry. It requested that our High Commissioner seek an immediate meeting with the Prime Minister of Pakistan, Mr Zulifikar Ali Bhutto (ZB), and convey a message from Mrs B. The message requested that an urgent shipment of rice be dispatched to Sri Lanka as there would be an imminent rice shortage. As the Ambassador was not in the station, the responsibility devolved on my father.
It usually takes about a week or more to get an audience with the Prime Minister (PM) of a foreign country due to their busy schedule. However, given the urgency, my father spoke to the Foreign Ministry’s Permanent Sectary, who fortunately was our neighbour and sought an urgent appointment. My father received a call from the PM’s secretary around 10 P.M asking him to come over to the PM’s residence. My father met ZB around midnight. ZB was about to retire to bed and, as such, was in his pyjamas and gown enjoying a cigar! He had greeted my father and had asked, “Mr Jayaweera, what can we do for great friend Madam Bandaranaike?. My father conveyed the message from Colombo and quietly mentioned that there would be riots in the country if there is no rice!
ZB had immediately got the Food Commissioner of Pakistan on the line and said, “I want a shipload of rice to be in Colombo within the next 72 hours!” The Food Commissioner reverted within a few minutes, saying that nothing was available and the last export shipment had left the port only a few hours ago to another country. ZB had instructed to turn the ship around and send it to Colombo. This despite protests from the Food Commissioner about terms and conditions of the Letter of Credit prohibiting non-delivery. Sri Lanka got its delivery of rice!
The next was the visit of Mrs B to Pakistan. On arrival in Rawalpindi airport, she was given a hero’s welcome, which Pakistan had previously only offered to President Gaddafi of Libya, who financially backed Pakistan with his oil money. That day, I missed school and accompanied my parents to the airport. On our way, we witnessed thousands of people had gathered by the roadside to welcome Mrs B.
When we walked to the airport’s tarmac, thousands of people were standing in temporary stands waving Sri Lanka and Pakistan flags and chanting “Sri Lanka Pakistan Zindabad.” The noise emanating from the crowd was as loud and passionate as the cheering that the Pakistani cricket team received during a test match. It was electric!
I believe she was only the second head of state given the privilege of addressing both assemblies of Parliament. The other being Gaddafi. There was genuine affection from Mrs B amongst the people of Pakistan.
I always remember the indefatigable efforts of Mr Abdul Haffez Kardar, a cabinet minister and the President of the Pakistan Cricket Board. From around 1973 onwards, he passionately championed Sri Lanka’s cause to be admitted as a full member of the International Cricket Council (ICC) and granted test status. Every year, he would propose at the ICC’s annual meeting, but England and Australia’s veto kept us out until 1981.
I always felt that our Cricket Board made a mistake by not inviting Pakistan to play our inaugural test match. We should have appreciated Mr Kardar and Pakistan’s efforts. In 1974 the Pakistan board invited our team for a tour involving three test matches and a few first-class games. Most of those who played in our first test match was part of that tour, and no doubt gained significant exposure playing against a highly talented Pakistani team.
Several Pakistani greats were part of the Pakistan and India team that played a match soon after the Central Bank bomb in Colombo to prove that it was safe to play cricket in Colombo. It was a magnificent gesture by both Pakistan and India. Our greatest cricket triumph was in Pakistan when we won the World Cup in 1996. I am sure the players and those who watched the match on TV will remember the passionate support our team received that night from the Pakistani crowd. It was like playing at home!
I also recall reading about how the Pakistani government air freighted several Multi Barrell artillery guns and ammunition to Sri Lanka when the A rmy camp in Jaffna was under severe threat from the LTTE. This was even more important than the shipload of rice that ZB sent. This was crucial as most other countries refused to sell arms to our country during the war.
Time and again, Pakistan has steadfastly supported our country’s cause at the UNHCR. No doubt this year, too, their diplomats will work tirelessly to assist our country.
We extend a warm welcome to Mr Imran Khan, the Prime Minister of Pakistan. He is a truly inspirational individual who was undoubtedly an excellent cricketer. Since retirement from cricket, he has decided to get involved in politics, and after several years of patiently building up his support base, he won the last parliamentary elections. I hope that just as much as he galvanized Sri Lankan cricketers, his political journey would act as a catalyst for people like Kumar Sangakkara and Mahela Jayawardene to get involved in politics. Cricket has been called a “gentleman’s game.” Whilst politics is far from it!.
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Believe me, seeing certain videos, on social media, depicting action, on the dance floor, at some of these entertainment venues, got me wondering whether this Coronavirus pandemic is REAL!
To those having a good time, at these particular venues, and, I guess, the management, as well, what the world is experiencing now doesn’t seem to be their concerned.
Obviously, such irresponsible behaviour could create more problems for those who are battling to halt the spread of Covid-19, and the new viriant of Covid, in our part of the world.
The videos, on display, on social media, show certain venues, packed to capacity – with hardly anyone wearing a mask, and social distancing…only a dream..
How can one think of social distancing while gyrating, on a dance floor, that is over crowded!
If this trend continues, it wouldn’t be a surprise if Coronavirus makes its presence felt…at such venues.
And, then, what happens to the entertainment scene, and those involved in this field, especially the musicians? No work, whatsoever!
Lots of countries have closed nightclubs, and venues, where people gather, in order to curtail the spread of this deadly virus that has already claimed the lives of thousands.
Thailand did it and the country is still having lots of restrictions, where entertainment is concerned, and that is probably the reason why Thailand has been able to control the spread of the Coronavirus.
With a population of over 69 million, they have had (so far), a little over 25,000 cases, and 83 deaths, while we, with a population of around 21 million, have over 80,000 cases, and more than 450 deaths.
I’m not saying we should do away with entertainment – totally – but we need to follow a format, connected with the ‘new normal,’ where masks and social distancing are mandatory requirements at these venues. And, dancing, I believe, should be banned, at least temporarily, as one can’t maintain the required social distance, while on the dance floor, especially after drinks.
Police spokesman DIG Ajith Rohana keeps emphasising, on TV, radio, and in the newspapers, the need to adhere to the health regulations, now in force, and that those who fail to do so would be penalised.
He has also stated that plainclothes officers would move around to apprehend such offenders.
Perhaps, he should instruct his officers to pay surprise visits to some of these entertainment venues.
He would certainly have more than a bus load of offenders to be whisked off for PCR/Rapid Antigen tests!
I need to quote what Dr. H.T. Wickremasinghe said in his article, published in The Island of Tuesday, February 16th, 2021:
“…let me conclude, while emphasising the need to continue our general public health measures, such as wearing masks, social distancing, and avoiding crowded gatherings, to reduce the risk of contact with an infected person.
“There is no science to beat common sense.”
But…do some of our folks have this thing called COMMON SENSE!
