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?
by Dr Gotabhya Ranasinghe
Senior Consultant Cardiologist
National Hospital Sri Lanka
When we sought a meeting with Hon Dr. Ramesh Pathirana, Minister of Health, he graciously cleared his busy schedule to accommodate us. Renowned for his attentive listening and deep understanding, Minister Pathirana is dedicated to advancing the health sector. His openness and transparency exemplify the qualities of an exemplary politician and minister.
Dr. Palitha Mahipala, the current Health Secretary, demonstrates both commendable enthusiasm and unwavering support. This combination of attributes makes him a highly compatible colleague for the esteemed Minister of Health.
Our discussion centered on a project that has been in the works for the past 30 years, one that no other minister had managed to advance.
Minister Pathirana, however, recognized the project’s significance and its potential to revolutionize care for heart patients.
The project involves the construction of a state-of-the-art facility at the premises of the National Hospital Colombo. The project’s location within the premises of the National Hospital underscores its importance and relevance to the healthcare infrastructure of the nation.
This facility will include a cardiology building and a tertiary care center, equipped with the latest technology to handle and treat all types of heart-related conditions and surgeries.
Securing funding was a major milestone for this initiative. Minister Pathirana successfully obtained approval for a $40 billion loan from the Asian Development Bank. With the funding in place, the foundation stone is scheduled to be laid in September this year, and construction will begin in January 2025.
This project guarantees a consistent and uninterrupted supply of stents and related medications for heart patients. As a result, patients will have timely access to essential medical supplies during their treatment and recovery. By securing these critical resources, the project aims to enhance patient outcomes, minimize treatment delays, and maintain the highest standards of cardiac care.
Upon its fruition, this monumental building will serve as a beacon of hope and healing, symbolizing the unwavering dedication to improving patient outcomes and fostering a healthier society.We anticipate a future marked by significant progress and positive outcomes in Sri Lanka’s cardiovascular treatment landscape within the foreseeable timeframe.
by Fr. Emmanuel Fernando, OMI
Jesuit Fr. Aloysius Pieris (affectionately called Fr. Aloy) celebrated his 90th birthday on April 9, 2024 and I, as the editor of our Oblate Journal, THE MISSIONARY OBLATE had gone to press by that time. Immediately I decided to publish an article, appreciating the untiring selfless services he continues to offer for inter-Faith dialogue, the renewal of the Catholic Church, his concern for the poor and the suffering Sri Lankan masses and to me, the present writer.
It was in 1988, when I was appointed Director of the Oblate Scholastics at Ampitiya by the then Oblate Provincial Fr. Anselm Silva, that I came to know Fr. Aloy more closely. Knowing well his expertise in matters spiritual, theological, Indological and pastoral, and with the collaborative spirit of my companion-formators, our Oblate Scholastics were sent to Tulana, the Research and Encounter Centre, Kelaniya, of which he is the Founder-Director, for ‘exposure-programmes’ on matters spiritual, biblical, theological and pastoral. Some of these dimensions according to my view and that of my companion-formators, were not available at the National Seminary, Ampitiya.
Ever since that time, our Oblate formators/ accompaniers at the Oblate Scholasticate, Ampitiya , have continued to send our Oblate Scholastics to Tulana Centre for deepening their insights and convictions regarding matters needed to serve the people in today’s context. Fr. Aloy also had tried very enthusiastically with the Oblate team headed by Frs. Oswald Firth and Clement Waidyasekara to begin a Theologate, directed by the Religious Congregations in Sri Lanka, for the contextual formation/ accompaniment of their members. It should very well be a desired goal of the Leaders / Provincials of the Religious Congregations.
Besides being a formator/accompanier at the Oblate Scholasticate, I was entrusted also with the task of editing and publishing our Oblate journal, ‘The Missionary Oblate’. To maintain the quality of the journal I continue to depend on Fr. Aloy for his thought-provoking and stimulating articles on Biblical Spirituality, Biblical Theology and Ecclesiology. I am very grateful to him for his generous assistance. Of late, his writings on renewal of the Church, initiated by Pope St. John XX111 and continued by Pope Francis through the Synodal path, published in our Oblate journal, enable our readers to focus their attention also on the needed renewal in the Catholic Church in Sri Lanka. Fr. Aloy appreciated very much the Synodal path adopted by the Jesuit Pope Francis for the renewal of the Church, rooted very much on prayerful discernment. In my Religious and presbyteral life, Fr.Aloy continues to be my spiritual animator / guide and ongoing formator / acccompanier.
Fr. Aloysius Pieris, BA Hons (Lond), LPh (SHC, India), STL (PFT, Naples), PhD (SLU/VC), ThD (Tilburg), D.Ltt (KU), has been one of the eminent Asian theologians well recognized internationally and one who has lectured and held visiting chairs in many universities both in the West and in the East. Many members of Religious Congregations from Asian countries have benefited from his lectures and guidance in the East Asian Pastoral Institute (EAPI) in Manila, Philippines. He had been a Theologian consulted by the Federation of Asian Bishops’ Conferences for many years. During his professorship at the Gregorian University in Rome, he was called to be a member of a special group of advisers on other religions consulted by Pope Paul VI.
Fr. Aloy is the author of more than 30 books and well over 500 Research Papers. Some of his books and articles have been translated and published in several countries. Among those books, one can find the following: 1) The Genesis of an Asian Theology of Liberation (An Autobiographical Excursus on the Art of Theologising in Asia, 2) An Asian Theology of Liberation, 3) Providential Timeliness of Vatican 11 (a long-overdue halt to a scandalous millennium, 4) Give Vatican 11 a chance, 5) Leadership in the Church, 6) Relishing our faith in working for justice (Themes for study and discussion), 7) A Message meant mainly, not exclusively for Jesuits (Background information necessary for helping Francis renew the Church), 8) Lent in Lanka (Reflections and Resolutions, 9) Love meets wisdom (A Christian Experience of Buddhism, 10) Fire and Water 11) God’s Reign for God’s poor, 12) Our Unhiddden Agenda (How we Jesuits work, pray and form our men). He is also the Editor of two journals, Vagdevi, Journal of Religious Reflection and Dialogue, New Series.
Fr. Aloy has a BA in Pali and Sanskrit from the University of London and a Ph.D in Buddhist Philosophy from the University of Sri Lankan, Vidyodaya Campus. On Nov. 23, 2019, he was awarded the prestigious honorary Doctorate of Literature (D.Litt) by the Chancellor of the University of Kelaniya, the Most Venerable Welamitiyawe Dharmakirthi Sri Kusala Dhamma Thera.
Fr. Aloy continues to be a promoter of Gospel values and virtues. Justice as a constitutive dimension of love and social concern for the downtrodden masses are very much noted in his life and work. He had very much appreciated the commitment of the late Fr. Joseph (Joe) Fernando, the National Director of the Social and Economic Centre (SEDEC) for the poor.
In Sri Lanka, a few religious Congregations – the Good Shepherd Sisters, the Christian Brothers, the Marist Brothers and the Oblates – have invited him to animate their members especially during their Provincial Congresses, Chapters and International Conferences. The mainline Christian Churches also have sought his advice and followed his seminars. I, for one, regret very much, that the Sri Lankan authorities of the Catholic Church –today’s Hierarchy—- have not sought Fr.
Aloy’s expertise for the renewal of the Catholic Church in Sri Lanka and thus have not benefited from the immense store of wisdom and insight that he can offer to our local Church while the Sri Lankan bishops who governed the Catholic church in the immediate aftermath of the Second Vatican Council (Edmund Fernando OMI, Anthony de Saram, Leo Nanayakkara OSB, Frank Marcus Fernando, Paul Perera,) visited him and consulted him on many matters. Among the Tamil Bishops, Bishop Rayappu Joseph was keeping close contact with him and Bishop J. Deogupillai hosted him and his team visiting him after the horrible Black July massacre of Tamils.
Sri Lanka-Singapore Free Trade Agreement
By Gomi Senadhira
senadhiragomi@gmail.com
“You might tell fairy tales, but the progress of a country cannot be achieved through such narratives. A country cannot be developed by making false promises. The country moved backward because of the electoral promises made by political parties throughout time. We have witnessed that the ultimate result of this is the country becoming bankrupt. Unfortunately, many segments of the population have not come to realize this yet.” – President Ranil Wickremesinghe, 2024 Budget speech
Any Sri Lankan would agree with the above words of President Wickremesinghe on the false promises our politicians and officials make and the fairy tales they narrate which bankrupted this country. So, to understand this, let’s look at one such fairy tale with lots of false promises; Ranil Wickremesinghe’s greatest achievement in the area of international trade and investment promotion during the Yahapalana period, Sri Lanka-Singapore Free Trade Agreement (SLSFTA).
It is appropriate and timely to do it now as Finance Minister Wickremesinghe has just presented to parliament a bill on the National Policy on Economic Transformation which includes the establishment of an Office for International Trade and the Sri Lanka Institute of Economics and International Trade.
Was SLSFTA a “Cleverly negotiated Free Trade Agreement” as stated by the (former) Minister of Development Strategies and International Trade Malik Samarawickrama during the Parliamentary Debate on the SLSFTA in July 2018, or a colossal blunder covered up with lies, false promises, and fairy tales? After SLSFTA was signed there were a number of fairy tales published on this agreement by the Ministry of Development Strategies and International, Institute of Policy Studies, and others.
However, for this article, I would like to limit my comments to the speech by Minister Samarawickrama during the Parliamentary Debate, and the two most important areas in the agreement which were covered up with lies, fairy tales, and false promises, namely: revenue loss for Sri Lanka and Investment from Singapore. On the other important area, “Waste products dumping” I do not want to comment here as I have written extensively on the issue.
1. The revenue loss
During the Parliamentary Debate in July 2018, Minister Samarawickrama stated “…. let me reiterate that this FTA with Singapore has been very cleverly negotiated by us…. The liberalisation programme under this FTA has been carefully designed to have the least impact on domestic industry and revenue collection. We have included all revenue sensitive items in the negative list of items which will not be subject to removal of tariff. Therefore, 97.8% revenue from Customs duty is protected. Our tariff liberalisation will take place over a period of 12-15 years! In fact, the revenue earned through tariffs on goods imported from Singapore last year was Rs. 35 billion.
The revenue loss for over the next 15 years due to the FTA is only Rs. 733 million– which when annualised, on average, is just Rs. 51 million. That is just 0.14% per year! So anyone who claims the Singapore FTA causes revenue loss to the Government cannot do basic arithmetic! Mr. Speaker, in conclusion, I call on my fellow members of this House – don’t mislead the public with baseless criticism that is not grounded in facts. Don’t look at petty politics and use these issues for your own political survival.”
I was surprised to read the minister’s speech because an article published in January 2018 in “The Straits Times“, based on information released by the Singaporean Negotiators stated, “…. With the FTA, tariff savings for Singapore exports are estimated to hit $10 million annually“.
As the annual tariff savings (that is the revenue loss for Sri Lanka) calculated by the Singaporean Negotiators, Singaporean $ 10 million (Sri Lankan rupees 1,200 million in 2018) was way above the rupees’ 733 million revenue loss for 15 years estimated by the Sri Lankan negotiators, it was clear to any observer that one of the parties to the agreement had not done the basic arithmetic!
Six years later, according to a report published by “The Morning” newspaper, speaking at the Committee on Public Finance (COPF) on 7th May 2024, Mr Samarawickrama’s chief trade negotiator K.J. Weerasinghehad had admitted “…. that forecasted revenue loss for the Government of Sri Lanka through the Singapore FTA is Rs. 450 million in 2023 and Rs. 1.3 billion in 2024.”
If these numbers are correct, as tariff liberalisation under the SLSFTA has just started, we will pass Rs 2 billion very soon. Then, the question is how Sri Lanka’s trade negotiators made such a colossal blunder. Didn’t they do their basic arithmetic? If they didn’t know how to do basic arithmetic they should have at least done their basic readings. For example, the headline of the article published in The Straits Times in January 2018 was “Singapore, Sri Lanka sign FTA, annual savings of $10m expected”.
Anyway, as Sri Lanka’s chief negotiator reiterated at the COPF meeting that “…. since 99% of the tariffs in Singapore have zero rates of duty, Sri Lanka has agreed on 80% tariff liberalisation over a period of 15 years while expecting Singapore investments to address the imbalance in trade,” let’s turn towards investment.
Investment from Singapore
In July 2018, speaking during the Parliamentary Debate on the FTA this is what Minister Malik Samarawickrama stated on investment from Singapore, “Already, thanks to this FTA, in just the past two-and-a-half months since the agreement came into effect we have received a proposal from Singapore for investment amounting to $ 14.8 billion in an oil refinery for export of petroleum products. In addition, we have proposals for a steel manufacturing plant for exports ($ 1 billion investment), flour milling plant ($ 50 million), sugar refinery ($ 200 million). This adds up to more than $ 16.05 billion in the pipeline on these projects alone.
And all of these projects will create thousands of more jobs for our people. In principle approval has already been granted by the BOI and the investors are awaiting the release of land the environmental approvals to commence the project.
I request the Opposition and those with vested interests to change their narrow-minded thinking and join us to develop our country. We must always look at what is best for the whole community, not just the few who may oppose. We owe it to our people to courageously take decisions that will change their lives for the better.”
According to the media report I quoted earlier, speaking at the Committee on Public Finance (COPF) Chief Negotiator Weerasinghe has admitted that Sri Lanka was not happy with overall Singapore investments that have come in the past few years in return for the trade liberalisation under the Singapore-Sri Lanka Free Trade Agreement. He has added that between 2021 and 2023 the total investment from Singapore had been around $162 million!
What happened to those projects worth $16 billion negotiated, thanks to the SLSFTA, in just the two-and-a-half months after the agreement came into effect and approved by the BOI? I do not know about the steel manufacturing plant for exports ($ 1 billion investment), flour milling plant ($ 50 million) and sugar refinery ($ 200 million).
However, story of the multibillion-dollar investment in the Petroleum Refinery unfolded in a manner that would qualify it as the best fairy tale with false promises presented by our politicians and the officials, prior to 2019 elections.
Though many Sri Lankans got to know, through the media which repeatedly highlighted a plethora of issues surrounding the project and the questionable credentials of the Singaporean investor, the construction work on the Mirrijiwela Oil Refinery along with the cement factory began on the24th of March 2019 with a bang and Minister Ranil Wickremesinghe and his ministers along with the foreign and local dignitaries laid the foundation stones.
That was few months before the 2019 Presidential elections. Inaugurating the construction work Prime Minister Ranil Wickremesinghe said the projects will create thousands of job opportunities in the area and surrounding districts.
The oil refinery, which was to be built over 200 acres of land, with the capacity to refine 200,000 barrels of crude oil per day, was to generate US$7 billion of exports and create 1,500 direct and 3,000 indirect jobs. The construction of the refinery was to be completed in 44 months. Four years later, in August 2023 the Cabinet of Ministers approved the proposal presented by President Ranil Wickremesinghe to cancel the agreement with the investors of the refinery as the project has not been implemented! Can they explain to the country how much money was wasted to produce that fairy tale?
It is obvious that the President, ministers, and officials had made huge blunders and had deliberately misled the public and the parliament on the revenue loss and potential investment from SLSFTA with fairy tales and false promises.
As the president himself said, a country cannot be developed by making false promises or with fairy tales and these false promises and fairy tales had bankrupted the country. “Unfortunately, many segments of the population have not come to realize this yet”.
(The writer, a specialist and an activist on trade and development issues . )
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