Let's Synthesize Our Drugs
Every year, in the early portions of my fourth year medicinal chemistry class, I have had to correct a popular misconception that has gained traction with the Ghanaian public. The misconception is that we “make” our own drugs here in Ghana and my students literally shout it out from the rooftops beaming with nationalistic pride. When I reply forcefully that we don’t “make” our own drugs, irritated and patriotic-sounding students proceed to list the seemingly endless catalog of Ghanaian pharmaceutical companies that have trademarked drugs. “There are many Pharmaceutical companies in Ghana and you’re wrong; we make our own drugs!” they will lecture me sternly.
“No we don’t, I will counter and this “accusation and defence routine” will go on for some time. Eventually I will implore them to just hear me out. So let’s clear this confusion up right from the start. If by “make” you are referring to formulation of the active ingredients as syrup, as tablets, as tinctures, as portions, as sprays or as ointments, then yes, we “make” our own drugs. But if the “make” is in reference to the synthesis of the active ingredient itself - that drug component that makes the tablet or the syrup a drug - then I am afraid we don’t “make” our drugs here in Ghana. We import our drugs because the most critical bioactive ingredient – the active ingredient – without which a drug is not really a drug is an import.
What is an active ingredient? This is known information in the public domain but it is couched in a technical language. Let me attempt to strip this issue of its technical jargons and put it in general terms with a less dense language. The medicinal action of any drug resides in the structural framework of its active ingredient putatively and/or chemically termed the “bioactive agent.” The mechanistic interaction of this bioactive agent - compound/substance/chemical - at specific physiological targets within the body (proteins-enzymes and transcription factors, DNA, RNA and other miscellaneous biomolecules) evokes a physiological response in the body that gives rise to the drug’s action or the drug’s efficacy (cure, treatment, relieve). Off-target interactions (when the drug is unable, incapable of interacting with its intended target and instead interacts with other spurious targets) of the compound/substance/chemical trigger undesirable side effects (nausea, headache, fainting and others). By far, the bioactive compound (active ingredient) is the most important component of a drug accounting for 99.9 % of the drug’s activity.
But from where do we source the active ingredients? From India, China, South Korea, Pakistan, Malaysia. Vietnam, Thailand. Your surprise will probably be as strong as mine if you factor in the fact that some of these out-sourced/supply countries were our peers at independence (in fact our collective lot was better than some of them). A sociological analyses of what has happened to get us that far behind them in the sheer volume and public health impact of the scientific output of the nation-specific scientific communities will be the topic of a thesis of a social scientist in the near future. But sometime between then (1957) and now (2020), we lost our thirst, our drive, our zeal and our foresight for true independence and instead settled for quick money making in a collective national catharsis that was enthusiastically supported by easy political platitudes and advertised with empty slogans.
Synthetic chemical methods represent a cornerstone technology of the burgeoning drug biotechnology industry. In synthesis, a scientist starts with available simple reagents and proceeds on through sequential addition of other readily available simple reagents to create a new previously unavailable molecule with a complex architecture using defined reaction routes. Synthesizing new compound with medicinal properties (the active ingredient) is arguable the toughest part of the drug manufacturing process. By contrast, its formulation as tincture, portions, tablets, as syrups is easy with straight forward methodology and protocols and with instrumentational aids the process is rather too formulaic to excite even the enthusiast. Together with natural product research (herbal medicine), organic synthesis will be the critical first step towards making state-of-the-art drug development accessible and affordable to KNUST faculty and to Ghanaians. Organic synthesis complements herbal medicine because bioactive compounds in our many efficacious herbal medicines will have to be synthesized to pave the way for detailed biochemical tests on the mechanism of its drug-action.
Let me quote the 1990 Nobel Laureate in Chemistry, the synthesis guru EJ Corey (his award was on pioneering work in organic synthesis). “It is not easy to find an area of scientific work that encompasses so many interesting elements. I shall name just a few: great complexity and variety; challenge verging on impossibility; demand for both mental and manipulative rigor, and for dedication, persistence and hard work; never-ending frontiers for discovery and never-ending advances in sophistication; unlimited opportunities for intellectual excitement and satisfaction; strong coupling not only with all areas of chemistry, but also with biology and medicine; relevance, at a very fundamental level to human well-being, health, and education.”
Since drugs are a vital modality in our national healthcare system it remains crucial that the research, development and manufacture of active pharmaceutical ingredients remain a top priority in our national agenda. And this agenda starts with synthesis. As daunting as it sounds, synthesis is not an impossible endeavour for us. It can be done here and it can be done by KNUST trained Ghanaians and it can be done now.
Conceptually, how can synthesizing our own drugs over buying it form others help us? In diverse ways, every single minutiae of an “in-house” local self-synthesis will advance multiple points on our collective inclusive national development program:
- Saving foreign exchange through use of our “in-house” methods for synthesis of bioactive compounds.
- Creating much-needed upper end jobs for our trained scientists-including but not limited to chemists, biologists, biochemist, pharmacist, molecular biologist and lawyers. Yes, lawyers are included. It means developing new academic fields like “patent attorneys” who will handle the judiciary wing of the litigious processes involved in drug discovery and drug manufacture. Patent Attorneys have at least a basic degree in any of the sciences together with a law degree-in fact they are the vexatious litigants of science whose tenacious involvement in conflict resolution concentrates on the originality of a scientific idea. Who was first to propose that idea and how much financial reward does he deserve from other workers who intend to surreptitiously use his/her concepts.
This effort will be of relevance not only to synthetic, medicinal, and pharmaceutical chemists and scientists but will be of relevance to many ancillary workers in related fields both in industry and academia.
- Forestalling drug shortages-“In-house” synthesis will ensure that Ghanaians have immediate access to all brands of their medications when they need them. Refer to the delays of shipments and other unanticipated bottlenecks that happened during COVID-19 lockdown when global supply chains were disrupted and the need becomes pressing.
- Earning foreign exchange through sale of our synthesized compounds to countries in the sub-region.
And so on and so forth. You can add your own list of benefits to this short-list.
How can we do it? The solutions are just basic and actually unoriginal. The neglect of the obvious that got us here has in it a silver lining-we are endowed with the mental capacity to know what to do and when and how to do it now.
- Establishment of a synthesis lab and provision of an infrastructure/administrative support
This effort calls for radical changes. Let our researchers throw away moderation with our leaders and insist that establishing a state-of-the-art synthesis lab equipped with all the modern nuts-and-bolts for local research and development will yield both economic benefits and nationalistic pride. No, not with political platitudes and slogans but with actionable policy. Establishment of a synthesis lab should become a national priority with the slogan “synthesize your own drugs.”
The patent for some of the common medications in regular use have expired and its accompanying variety of synthetic routes are in the scientific literature. So why buy from somewhere when you can, conceptually and realistically and practically, synthesize it yourself.
KNUST management has to move past the point of “subtlety” with political leaders - we have to get to the “damn it all” stage and let all our collective frustration with inaction “hang out there in the open.”
It is true that successive governments of all ideologies have struggled to figure out how to balance “bread and butter” politics with aspirational endeavors like ours. We can make the equation work if as a first start, our politicians don’t give the electrorate all the promises in the Bible as we so often do. Promises in the Bible are yea and Amen through God who has all the resources to fulfil them to the letter. But on synthesis science, by all means please make lofty promises and back it up with action. Its privation isn’t a national dilemma but an existential threat.
Government support and local administrative support also means funding universities and sciences in a proportion comparable to our total GDP. It means taking good care of the lab-bench workers and tending very well to its ancillary scientific community including the technical staff.
- Provide training to undergraduate and graduate students in the laboratory methods of synthetic organic chemistry.
We already have the taught course in synthesis in our course syllabi. Practically, students will have to be trained in state of the art organic and organometallic synthesis including training in experimental design and experimental execution, reaction product purification and reaction product identification and reaction product characterization via spectroscopic means (NMR, IR, UV-VIS, MS and many others). The outcome will not only be to speed up related drug discovery researches, but most critically, will be to provide the foundational edifice of highly trained lab-bench workers knowledgeable in state-of-the-art methods of synthetic organic chemistry for ready employment by the nascent drug manufacturing industry.
It’s not an immensely expensive project. Just starting small with undergraduate lab and moving incrementally to postgraduate research can help establish a cadre of “synthesis buffs” clad in sweaty T-shirts and dirty jeans who see organic reaction mechanisms in innocuous gestures.
Multi-national drug companies desire to set-up subsidiaries in Ghana is contingent on the availability of infrastructure, the prompt availability of essential services and most pressingly on a highly trained and skilled synthetic workforce. But whether companies are local or international, a workforce of tremendous skills is a required necessity and that is where KNUST must establish and sustain her supremacy.
But our training of students in organic synthesis leaves much to be desired. The practical lab training, for all intents and purposes, is off the table for obvious reasons while the theoretical course work limbs along suffering from the familiar students disinterest and its subsidiary students complaints that it is too difficult.
Other predictable snafus have contributed to the demise of organic synthesis labs. Since I want you to feel guilty about this abysmal state of our labs, I will take you on a guilt-trip. Take a guided tour of our undergraduate labs with me and you will see 8-10 students huddled around a single pipette. One student performs the experiment and the others do whatever they damned well feel led to do. One can get a BSc degree in Chemistry in today’s Ghana without ever touching or holding a test-tube or a beaker during one’s 4-year training. That’s absurd! It’s even sad that just 2 or 3 of the SUV our politicians ride in can buy enough glassware to enable each Chemistry first year student get to use one pipette without the need to share with 10 others.
Development of innovative therapies should be a priority area of research in our national agenda and such drug development efforts require specialized expertise in synthetic organic chemistry, an area that our students lack expertise. We can change the end of this story.
- Cross-discipline research.
Synthetic training of undergraduate students can then be integrated into an inter-disciplinary research effort that offers exposure to Medicinal Chemistry, Protein Biochemistry, Structural Biology, Nucleic acid chemistry/biology (DNA and RNA and genomic and proteomic science), Carbohydrate biochemistry and Metagenomics and Computational Studies including Rational Drug Design.
KNUST faculty research programs can incorporate organic synthesis into a cross-discipline covering a broad swath of topics at the chemistry/biology interface and at the chemistry/engineering interface (e.g. glycobiology, metabolic engineering, DNA repair, RNA modification, Protein translation, photoreception, photosynthesis, cancer therapeutics, drug metabolism, metabolomics, molecular imaging, solar cells and genome editing) using an extensive range of approaches (e.g. genetics, genomics, x-ray crystallography, NMR spectroscopy, EPR spectroscopy, mass spectrometry, combinatorial chemistry, high throughput screening, computational modeling, and enzymology).
Financially rich Ghanaians can respond to the clarion call and invest in synthesis labs to complement the efforts of government. The pay-off in real profit terms is big! Bigger than operating a grocery store at every corner to sell the same goods that are on offer in every other corner store!
There are two major ways out of this neglect-driven synthetic lab unavailability: investment of great personal wealth by individuals desirous in making profit or an astute politician using his influence to shake things up. With projected increases in population growth, increases in longevity and exponential growth in health-care needs, Ghanaians will soon find out just how expensive their drugs will be and just how unaffordable their health-care cost will be when we don’t have either great personal wealth to weather the storm or an astute politician to make the pressing but immediate politically inexpedient call.
Let’s make synthesis of our drugs the centrepiece of this election cycle. This particular blog is not just an aspirational appeal; it’s a call to action NOW. This issue matters to the nation because the threat posed by the lack of it is existential. The appeal should command almost universal assent within and among Ghanaians of all persuasions.
Let’s not postpone it and hope that it will be dealt with by others tomorrow. "In the fullness of time we will make a better tomorrow tomorrow" won’t work this time. A shift in public opinion towards synthesizing our drugs is a necessity. Yes, we need an optimistic view on Ghana’s drive towards self-sustenance but let us not engage in blind nationalistic posturing to accomplish this objective. Let’s just show in tone and content that there is nothing more pressing to talk about than synthesizing our drugs “in-house”.
Whether the end-goal is for academic or industrial research the development of new methodologies and novel pharmaceutically useful organic transformation for the synthesis of drugs and for the manufacture of its scaffolds is needed. That means interested students will have to receive rigorous novel practical training in the theory, the methods and the strategies of organic synthesis (taught in the lab with hands-on training at a bench, not in the class room by rote-memorization). Using multiple approaches students will understand the value and the power of synthesis to address national health issue, ultimately improving the health and the welfare of Ghanaians.