From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench

From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench From academia to entrepreneur chapter 3 taking academic biomedical research beyond the lab bench

Taking Academic Biomedical Research Beyond the Lab Bench

3

C H A P T E R

3.2.1 Interacting with Clinical Staff 49

3.3.1 Biomaterials: Building Blocks for Medical Devices 51 3.3.2 Shortlisting a Biomaterial for Applied Research 52

3.6.3.2 Glaucoma Drainage Device (GDD) 65

3.7 INTO the Real World 67

3.7.2 Safety and Performance Testing 69

O U T L I N E

3.1 FROM THE PATIENT TO THE LAB BENCH

The issues to work through for an academic contemplating the preneur route while in academia were introduced in the previous chap-

entre-ter In order to expedite academic research results to become a runway

enterprise reality, a lot of the preparative work can be completed while

in academia To illustrate how this can be carried out, this chapter utilizes some of my NUS research activities in biomaterials development and

information can only serve as an example, and is not meant to encompass all facets of biomed research that is overwhelmingly diverse and varied

in complexity It is hoped that the reader can obtain a sense of the many, seldom-mentioned or formally taught topics conveyed here and assimi-late into their arsenal of practices in carrying out their own undertakings

A biomaterial according to the ESB (European Society for

intended to interface with biological systems to evaluate, treat, ment or replace any tissue, organ or function of the body” The journal

aug-Biomaterials defines a biomaterial “as a substance that has been neered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living sys-tems, the course of any therapeutic or diagnostic procedure” Both defi-nitions are acceptable since the “use purpose” is stated, i.e a material/substance becomes a biomaterial when the use is defined

engi-The science of biomaterials has progressed steadily since the 1960s

I settled on a material called chitin, isolated primarily from the shells of

crabs and shrimps I was fascinated that this material, being obtained from nature, should be more acceptable by biological entities such

3.2 mEDICAL INTERvENTION: sCIENCE AND TECHNOLOGy’s ROLE 47

as the human body My first encounter with chitin was using a cal variant, chitosan, to assist a botany colleague to develop an artificial

biomate-rial, I settled to investigating the use of chitin for several conceived medical device applications such as bone substitutes and wound heal-ing that were popular in the 1980s among the chitin research commu-nity Publications in the 1990s and early 2000s reflect this bias Taking the research results into product development proved fruitless until, by

a gradual refinement process, the needs-driven clinician-centered applied

research evolved For me, the start point in using this method to turn biomaterials into medical devices is not research excellence, but the patient

The human body is a unique biological entity that is extremely plex, highly organized, efficient, self-sustaining and self-regulating, functioning within a well-defined and restricted tolerance range For example, the average body temperature is 37°C at 1 atmosphere pres-

problems set in The extent of problems depends on the individual, since

no two persons are identical Thankfully for most humans, divergences from normal fall within known statistically accepted limits that permit standard responses to be developed to bring the body back to a healthy state In other words, when the human body breaks down or is damaged, the body turns into a patient that requires medical intervention

3.2 MEDICAL INTERVENTION: SCIENCE AND

TECHNOLOGY’S ROLE

Medical intervention can be described as all manners of treatment,

be they pharmaceuticals, invasive procedures, etc to relieve illness and injury in attempts to bring the body back to its normal state In the con-text of this chapter, the issue is how to go about participating in medical intervention from the perspective of an academic engineer or scientist in

the needs-driven clinician-centered applied research manner once the

medi-cal need is identified It has already been made clear that interacting with

a clinician is a necessity (Chapter  2) Equipping oneself with the lingua

franca of the medical world, and an overview knowledge of how the human body is organized and works, should precede this This would better facilitate communication and understanding to be initiated and grow when you start working with the clinician While you do not have

to become an expert, basic comprehension of disciplines such as omy, biochemistry, immunology, pathology, physiology and structural

anat-ii 2°C is used, as there is normally no doubt that problems exist at this deviation.

biology, provide a vital background Once you have a grasp of the mentals, secondary factors such as patient age, ethnicity and size should slowly creep into your thoughts whenever you ponder conceived solu-tions for clinician-posed problems worthy of developing into medical devices And remember, while physicians are the principal parties you will interact with, do not forget their nursing staff, EMT (emergency medical technician), and those involved directly with patient care who may offer you a different but related insight A surgeon can show you how she does her surgery, but her surgical nurse in charge ensures every-thing else is in order in the OR/OT (operating room/theater) and can

medicine to science and engineering You handle the job at the lab bench level.

Consider the process of developing an implant device The surgeon from experience identifies the limitations of existing devices, and has a

wish list of preferences that she would like in a new design Better still

if she has an original design to solve a need she has but has not been satisfactorily addressed, you have a rare opportunity Your role as the sci-ence and technology component is to provide a technological solution for

the problem at hand, i.e to satisfy the wish list as best you can A

gen-eral background in the medical topics listed above will assist you as you

go about defining the applied research Take for example that you want

to develop an implant such as a sub-5-mm blood vessel for heart bypass

its location in the body, normally referred to as the target site This gives

you an idea of the challenges confronting you, such as blood tions with biomaterials that you select and similar matters You will also take into account in your deliberations whether the implant is address-ing a critical and/or life-threatening situation, the accessibility of the tar-get site, the complexity of the replacement procedure, and affordability

interac-of the intended device For the first three points, you will doubtless be guided by your surgeon, while the last point you will most likely have to figure out for yourself

It may appear to many as being cold and calculating, insensitive, bordering on inhumane, wanting to address this affordability ques-tion But if no one can, or is willing to pay for what you intend to cre-ate, it is unlikely to become a business Let’s take as an example that

iii Much like in the military where an officer (platoon commander) is more focused

on command and the mission, while the platoon sergeant runs the platoon Be

forewarned, from personal observation, you underestimate the senior nurse’s

influence on your surgeon to your own peril.

iv In this instance, refers to the heart’s size in proportion to the body, not the literal size

of the heart in an infant, child or adult.

3.2 mEDICAL INTERvENTION: sCIENCE AND TECHNOLOGy’s ROLE 49

you can conceive a totally implantable artificial kidney that will work near perfectly to address kidney failure, an illness that afflicts millions

of people globally The cost to the patient per device is estimated to be US$100,000.00, an exaggerated sum for elucidatory purpose Is it realis-tic that the average patient can pay for it? You know the answer with-out doing the math, which is of course very unlikely The real purpose

of taking note of affordability for you, the academic applied researcher,

is to work on possible solutions that may better the artificial kidney lyzers presently in existence) and yet will not overwhelm the patient

contribute for developing potential biomed products before it transcends the academia–business divide Research, as the term implies, is for you to try out the options that provide choices from which the best compromise (and it will always be a compromise) can be selected to take into product development Academia is more flexible in resource utilization towards such exploratory efforts compared to industry

There is one important detail to note using the needs-driven

clinician-centered method sponsored in this book Science and engineering is ondary when the practical aspects of implant surgery come into play The decision to use or not to use a particular implant is the surgeon’s, and the surgeon will choose accordingly The surgeon also performs the procedure and the success of the implant depends to a fair extent on the surgeon’s skill and care in implant handling and placement, and post-surgery monitoring to ensure the favorable performance of the implant The success of an implant (or any biomed product that is the outcome of this process) by default relies on the clinician Therefore, while the scien-tist and engineer have equally important roles in this collaborative effort,

avenue available to cross this chasm is going back to university and ting a medical degree An MD/PhD combination together with the requi-site specialist training provides the holder with the necessary credentials

get-minus the capability limitations to carry out the needs-driven clinician-

centered method

3.2.1 Interacting with Clinical Staff

Working with a clinician is similar to interacting with any sional Depending on their clinical specialty, the demand on their time differs The cardiothoracic surgeon I worked with in my first applied project was frequently busy, called to perform many emergency pro-cedures that resulted in my meetings with him either being delayed or

profes-v And by extension, includes the manufacturer, entrepreneur, investors and regulator that commence beyond academia.

re-scheduled.vi This was more about the number of cardiothoracic geons available at the time having its consequences I subsequently worked with an orthopedic surgeon and an eye surgeon, episodes that will be recounted later in this chapter Again many meetings with both were delayed as clinics and surgery take priority However, in these lat-ter projects, more than 10 years had elapsed and experience enabled me

sur-to ensure work progressed at a steadier rate between progress meetings.Choose your clinical contact carefully I have worked with a senior world-recognized authority, established surgeons, and up and com-ing younger surgeons I find that it does not matter what their positions

or reputations are, but how well you get  along with the clinician you work with

By far my best association and from whom I learnt the most, was

my pathologist colleague, who was always on time or made time for

valve that required the use of a rat animal model I sought the tance of a pathologist in interpreting histology results and from then

assis-on, a good professional relationship developed that lasted more than 10 years She was very patient, explaining everything including how best

to retrieve tissue samples from the explant site, process the tissue and of course comprehending the histological results She continued with my research group when we moved on to bone materials and wound heal-ing The other gem of a colleague was the university’s vet who taught

me how to handle and treat laboratory animals, perform procedures and investigative studies the proper way The point I make here is that work-ing with clinicians is more than interacting with the clinical specialty of interest; you should gain as much insight from as many varied perspec-tives as possible An animal study or histology interpretation can impact the final understanding of a research study, and it should not be trivi-

alized just because you don’t get the prestige factor you expect since in

yours eyes, it may be less glamorous Naturally, an experienced gist sees things you do not see in a histology slide, and a vet can provide you with a different insight into animal model selection that may be bet-

vii A hospital pathologist’s role in the healthcare system should never be underrated.

viii There are many ways and many animal models you can select for a particular study.

vi Never cancelled Secretaries or PAs (personal assistants) are your best buddies in achieving this, i.e do not underestimate the authority of personnel without titles before, or alphabets after their name.

3.3 FROm THE LAB BENCH BACk TO THE PATIENT 513.3 FROM THE LAB BENCH BACK TO THE PATIENT

After understanding the needs of the clinician, the first step in ing back to the patient is to settle on an applied research project, plan and secure the necessary funding for it This entails conceiving, for example, an implant medical device based on your proposed solution

head-to the clinical need, utilizing biomaterials The traditional als have been metals, ceramics and polymers Let’s take a closer look at biomaterials

biomateri-3.3.1 Biomaterials: Building Blocks for Medical Devices

Metals as biomaterials usually (but not exclusively) mean stainless steel and titanium Their primary roles are in load-bearing situations or where rigidity is required such as the shaft of a hip implant, knee joint replacements and skull plates For non-implant Class 2 devices, they are used as syringe needles and surgical instruments The shape and contours of the body can limit metal implant design and, consequently, utilization Magnetic beads are a more recent innovation in this class of materials gaining a presence in diagnostics applications

Ceramics as biomaterials can be crystalline or amorphous, the most common being alumina Similar to metals, alumina-based ceramics in various compositions are employed where load-bearing and rigidity are required, for example, the ball head of a hip replacement joint There are other types of ceramics that are created to be surface reactive and bio-resorbable, used as coatings on metal implants to promote better adhe-sion between the implant and bone A constraint for ceramics is their brittleness

Polymers span a wide range from flexible to rigid, and are the most versatile of materials used as biomaterials They can be synthetic (made from petroleum) or natural (isolated or extracted from biological mate-rials) Traditionally, polymers are prepared to perform in various non-degradable, usually non-load-bearing situations Polymers useful as matrices for controlled delivery such as pharmaceuticals and biolog-ics have been fabricated to degrade by dissolution in body fluids or by action of enzymes in the body The main role of biomaterials for drug delivery and gene delivery is to maintain integrity of the pharmaceuti-cal or biological agent as they are introduced and transit the circulatory system Polymer choice depends on the type of delivery: oral, nasal, sys-temic; whether the drug is encapsulated or chemically bonded to the car-rier matrix; the mechanism and ease of drug loading; the drug release mechanism; and, the kinetics and how the biomaterials are degraded

by, and discharged from, the body New medical device possibilities are in tissue engineering, components of micro-machines, forming 3-D

cell-cultures and as hydrogels Research in the use of polymers in these applications include developing scaffolds and other structures for cell colonization, growth, proliferation, micro-fabrication, as temporary or permanent biomaterials and as various gel types: thixotropic, self-assem-bly and responsive Polymer design includes tailoring to suit the appli-cation sought Finally, polymers are used extensively in packaging of medical devices and other medical products.

Therefore, there exist a wide variety of materials that can be selected for use as biomaterials Most material’s chemical, physical and engineer-ing properties are known, including their advantages and disadvantages Research on improving material attributes by manipulating character-istics such as chemistry, microstructure and processing methods are of course on-going More often, it is the creativity in deriving a solution to

a conceived application, rather than the material, that will be a constraint

in their selection Last, there is no need to strive towards getting the mate solution that does not exist If you have a 95% fit you are already well ahead of the curve Know that the body can compensate for minor imperfections

ulti-3.3.2 Shortlisting a Biomaterial for Applied Research

In selecting a potential biomaterial for a given end use, it is useful to have a procedure such as the following

previously mentioned clinician’s wish list You will likely have many

predecessors (other devices for the intended application), and that

is a good place to start because you have a reference More often, incremental improvements are the rule of the day It is more a matter

of alleviating the existing shortcomings Revolutionary innovations are harder to realize

properties match There is such a flood of information in the scientific and technical literature about metals, ceramics and polymers available that you should be able to find a material that meets most of your

requirements Try and use known biomaterials, i.e materials that have

been used in other medical devices The rest is about studying the fit

to reach a good compromise

exhaustive evaluation to rule out the selection of known materials

should developing a NEW biomaterial be considered The same goes

developing a new material just because you have the resources to do

so In this era of ever increasing demands on regulatory compliance,

3.3 FROm THE LAB BENCH BACk TO THE PATIENT 53

existing materials will face a more amenable regulatory scrutiny

A new material will be subject to strict evaluation for approval,

an expensive and timely process At times materials study can be totally circumvented, as described in Section 3.6.3.2 In this instance bypassing the materials study outlined next and proceeding to proof

of concept is pragmatic

academic goals, i.e the target should at least be one patent and several academic research publications This is because you are still the recipient

of research grant awards and those commitments have to be met After all, there is no guarantee the applied research will definitely yield

something useful and keeping your options open at this stage is astute

3.3.3 Material Characteristics

The bulk properties of the biomaterial are manifested in their physical and mechanical characteristics that relate to functional integrity and sta-bility of the biomaterial Using polymers as example, some of the mate-rial’s physical and mechanical attributes that may be considered are the ultimate strength, the fatigue strength, the yield elasticity, toughness, hardness, wear resistance and time dependent deformations (e.g creep) Again there is so much information available for first performance approximations to be made Applied research to support and refine these estimations may involve studying dimensional stability, load effects and in-use stresses that may arise Both computer modeling and measure-ments taken on the physical models will provide information as to the suitability of the material for the intended use

The chemical make-up of the biomaterial governs the potential cal reactions and biological interactions the biomaterial may undergo

chemi-in the body Primarily, this is through the surface (geometry also exerts

an influence) of the biomaterial The body, probably the ultimate hostile environment, does not like foreign material and will respond The scien-tific knowledge of what occurs and how to arrive at harmony between biomaterials and body tissues and fluids is prevalent Again, tailored research for the conceived application has to be performed Studies using simulated body fluids, cell culture and comparative sciences models are popular ways of defining the biomaterial’s choice

In investigating the physical, engineering, chemical and biological characteristics, what is being established at this stage is the suitability

of the selected material for the intended application There is a lot more

to do once the project leaves academia, but the groundwork put in here provides the confidence of materials choice for downstream processes and the usefulness of the device to maintain functionality throughout the period of use

3.4 AT THE ACADEMIC LAB BENCH

As the applied research progresses, there comes a point where you will find difficulty in delineating where research stops and product development begins The recommendation is always to do as much in academia, especially in answering most of the scientific questions Two case studies will illustrate this involved process a little later For now it is useful to discuss three factors that can be limitations for commercializa-tion and are best dealt with early These are refining the science, scalabil-ity and sterilization

3.4.1 Refining the Science

Preliminary research results may be good and encouraging, but require further fine-tuning You need to corroborate the science by first confirming that it really works and second, to make it robust for an industrial setting

Confirming the scientific results is about ensuring there is no operator

prejudice; but if present, it is removed Ridiculous as it sounds, researchers:

the blanks based on a keyword that represents perhaps 10 steps in a procedure

media attention) Do distort results

Disagree with these assertions? Try the following exercise Pick out any published paper in any journal in your field Go to the experimen-tal section Try repeating the experiment as per the description in the article The probability you can duplicate the experiment successfully based on what is written in the few sentences is very low As a journal referee, I paid attention to this section and even when a better descrip-tion was provided after the manuscript was revised, I maintain it would

be difficult for someone skilled in the art to replicate that experiment well

Therefore, confirming the work independently (by more than the person doing the work, and outside the research group if possible) is a necessity

to remove any reservations about the results Second, ensure ity on a constant basis, again by several individuals followed by groups This will give you the confidence that practically anyone with the right background given the proper training and information can do what is required

repeatabil-3.4 AT THE ACADEmIC LAB BENCH 55

The other aspect of refining the science is to make the science robust Research typically utilizes expensive and/or customized equipment to perform the experiments, with much of the data obtained using sophis-ticated expensive scientific instruments You now have to duplicate this process with cheaper and less sophisticated equipment and instruments, but with the same or better reliability This is because generally in indus-try, multi-million dollars’ worth of equipment for routine use is a luxury Industry’s preference is to have cost-effective processes, easily calibrated and maintainable equipment and instruments to verify the science

at specific points in the manufacturing process Your present task is to break up the science into well-defined parts, ensure that each component

is workable, verifiable and when re-assembled, the end result matches your original exploratory effort

3.4.2 Scalability

Scalability is about authenticating that the science can transit to a product or service, since the problem-solving format of the academic research lab bench is not readily converted into an industrial configu-ration Experiments conducted at the research lab level use microgram

or gram quantities or are performed one at a time These experiments seldom work well when the capacity increases to the kilogram and ton level, or have to be carried out repeatedly

In small experiments the microenvironment can be controlled sonably well by careful manipulation of the settings such as tempera-ture, stirring speed, sequence of component additions, etc arrived at most likely by trial and error, and by one operative patiently spending weeks or months at the task When you scale-up to 1000 times the origi-nal amount of a substance, the environment is of course no longer micro, and factors such as diffusion rates of reactants, viscosity and heat dissi-pation effectiveness, influence the course of the experiment For example, conducting experiments with 10 times the original quantities used and seeing if shifts in the product quality, or reaction efficiency as deduced from yield, can be small steps to guide you to sort out this issue

rea-Assays are subject to operator skill Regardless of standardization and practice, some people may do a defined task differently compared to oth-ers Time and further work will have to be expanded to determine how

to remove such operator prejudices

And while in the end this may be achievable experimentally, it may not be at a cost that is acceptable This is because when you do a large quantity or volume, the process no longer utilizes the same approach as

a single experiment Tooling-up, automation and remote monitoring, for example, are all necessary on an industrial scale, issues that you do not deal with at the lab bench level It is important therefore to be guardedly

optimistic when results on a small-scale prove promising Until the bility of scaling-up is confirmed (execution as well as costs), and this is usually addressed outside of academia, it is premature to declare you have a true winner Therefore, confirm the scientific aspects as much as possible.

via-3.4.3 Sterilization

As a referee for scientific journals in my latter years at NUS, one topic that my attention was drawn to for manuscripts sent for my review

containing cell culture and/or comparative sciences model studies, was

the sterilization method of test samples Admittedly, this tion came about as a consequence of my involvement in BRASS (refer

me wondering if the authors realized the difference between sterilization and disinfection Furthermore, regardless of the sterilization method, I found myself searching for the follow-up comments on how sterility was verified using specific sterility tests that were not included

The ability for biomaterials and medical devices to be sterilized is important, and should not be casually treated during applied research This is because many lab scale sterilization methods may have no bear-ing on whether medical devices made from these materials would sur-vive unscathed when subjected to the more rigorous commercial setting This normally means exposure to ethylene oxide (EtO) gas at elevated temperatures or gamma irradiation under very strict conditions that

placement in a particular spot in the sterilization chamber can affect

is gaining popularity for small volume sterilization may also warrant consideration

The researcher should be aware of this sterilization factor need and ensure their materials and/or devices can endure and remain unchanged

by the industrial processes There is no sense in carrying out applied research that will never meet industry requirements Devise a proper sterilization investigation program that explores the sterilization method fit for the material or device during development to cover all your bases

ix Sterility is a complex subject Although it is supposed to be either yes or no, it is not that straightforward You are urged to know this topic thoroughly if you are going to

do this as a biomed entrepreneur.

x There are other methods used for commercial sterilization EtO and gamma are presently the most popular.

3.5 IP AND LICENsING 57

To complete Section 3.4, it is relevant to comment from the standpoint

of a potential fund evaluator or sponsor When a prospect proposes a start-up biomed business, ask to peruse her publications If some of the elements listed in this section are reported in her publications, the indica-tion is good that the prospect has thought about some of the aspects of commercialization She may not have it all, but she will probably be able

to work through issues that pop up along the way This is another plus factor in the checklist on her to tick

3.5 IP AND LICENSING

When the scientific results are original and promising enough, there

is a need to legally safeguard this intellectual property (IP) in order for these research results to have value This legal safeguard can be in the

com-mon The legal protections accorded are:

Each institution has its own process of evaluating the IP to make sions on whether to pursue legal protection or not If the decision is to proceed, the PI is usually involved in drafting the patent and providing input during the patent examination process If the institution’s decision

deci-is to drop, you as the PI can pick it up and utilize with no restrictions

or prejudice to the institution There are plenty of sources available to enlighten you on the patent process I also recommend that you engage legal counsel when you plan to patent your IP What will be expanded here is how this impacts your potential enterprise

First, you have to license the IP from the institution exclusively to your

start-up business entity If non-exclusive, you must define the territory

or types of products that are covered in the license This is always tough and not a favorable situation you should settle for, and I recommend you walk away from these types of deals For exclusive license, the terms are pretty standard and there is not much to negotiate except the percent-age of the royalty based on gross profit and the number of years in force Most institutions also require the payment of an upfront fee to formal-ize the licensing agreement Often an accommodation can be reached

to defer this fee, but it is unlikely to extend until you make your first

xi You should seek legal counsel on this matter All I can tell you is that you have to pay; not once, but on a continual basis, and it is not cheap.

profit So delay as long as possible, because near your launch date, you probably would have raised the funds to pay for the initial fees for the license You have to settle licensing since the patent is normally a stan-

dard requirement by potential investors, the so-called value proposition

Conversely, it is also your leveraging tool during funding negotiations The license to you must be in force before you launch your product.Second, you have to reasonably determine whether what you intend

to do will encroach on existing patents and other IP This is not forward, as conflicts are not obvious by looking at the titles of patents based on searches using keywords What is written in the invention descriptions and claims are more relevant to determine infringement

straight-Again, legal assistance is recommended to comprehend the legalese and

this will be money well spent as it may prevent you from paying more for litigation down the road In the circumstance when you are the aggrieved party, know that protecting your patent is only as good as your financial war chest, and stamina to prosecute in a jurisdiction that will

cost-effective way to handle disputes in territories where your patent is filed and the rule of law enforced fairly, but be aware it is not a cure all.Third, know that a patent is not a guarantee of success The hard work commences from here on, as you attempt to turn a promise into a tech-nology and, eventually, a product

3.6 PROOF OF CONCEPT

Encouraging research results indicate a potential that has been onstrated workable only at the lab scale, the preliminary promise There are technical questions to be answered Refining the science, scalability and sterilization have already been discussed The corresponding scien-tific questions regarding the physical, engineering, chemical and biologi-cal characteristics of the selected material have also been answered and should be favorable But again, regardless of the sophistication of scien-tific investigations, they only provide a measure of confidence There is a need now to answer all these questions from a commercial perspective

dem-You have to do a prototype of the proposed device to investigate whether the prototype device can perform the required device functions and be

sterilized successfully by evaluating the materials’ properties sterilization This is the proof of concept phase Again, where possible this should be within the confines of academia In addition, everything

post-xii There are still places in this world where the barrel of a gun still rule, and others where corruption can negate or at least frustrate any legal discourse.