Eric Kumah asked:


TECHNOLOGY AND COMMUNITY DEVELOPMENT

KUMAH ERIC JUNIOR

MARCH 2009

ABSTRACT:

In today’s world, technology has invaded many aspects of human life. From its gigantic influence on our education and professional development, to the more subtle presence of little gadgets littering our homes, technology is almost everywhere.

The reasons for such pervasiveness would boil down to some characteristics that technology by itself possesses. One such characteristic, which is of major interest to many scholars, is the seeming lack of barriers to the spread of technology. It easily penetrates societies and even to remote communities, and once it reaches its destination and catches on, it becomes seemingly difficult to stop its spread. As a result of this, consumer technology like cellular phones, computers, PDAs, radios and televisions have become commonplace in places like Africa, even with all the barriers one would have envisaged.

Sadly, it does not need much analysis to realize that even though technology usage is growing rapidly in Africa, we still have numerous developmental problems in our continent. This is a situation where advanced technology is coexisting with underdevelopment in Africa. With all the power that technology wields, it will be a useful exercise to study the ways in which it can be used to solve some of those very problems it has come to meet. In essence, using our little gadgets to solve our big problems.

This is the background against which this study is undertaken. Asking whether our problems can be solved at all, then enumerating instances where development projects that utilize technology have been put to work, and concluding by examining the cases and drawing lessons from them.

CHAPTER. 1.

INTRODUCTION

The limits to what the human mind can conceive and achieve are increasing. More discoveries have been made, more things have been created, more theories have been proved and disproved, more machines have been made and more problems have been created. Scientific technology has been the driving force behind all these. Science has indeed proved to be a powerful tool which has touched many people and has shaped many communities.

According to the Concise Oxford dictionary 10th edition, technology is the application of scientific knowledge for practical purposes. Clearly from this definition we can see that scientific knowledge may exist theoretically but it only becomes technology when it is used in practical settings. For example we may say the knowledge of the rules of up-thrust and buoyancy is theoretical, however practical utilization of these rules to manufacture airplanes could be termed aircraft technology.

Again according to the Concise Oxford dictionary 10th edition, a community is the people of an area considered collectively, while development is explained to mean to grow or cause to grow and become larger or more advanced. By deduction, community development could be explained to be the growth or advancement of a group of people.

Today, the world has become highly technological, and things which in the seventies would have passed for science fiction are now so commonplace that they have almost become necessities. From every corner of the world, technology has global acceptance, it is ubiquitous and has the ability to dramatically change situations.

Any attempt to ascribe reasons for this pervasiveness of technology will have many suggestions, some of which are that machines have been proven more efficient than humans at some tasks, machines are less error prone, impartial and never get tired like humans. Another could be the increased sophistication of humans and the attendant need for equally complicated messengers to help us perform many tasks, which is linked to the interesting nature of technology that once a more advanced way of doing something is found, it becomes almost unthinkable to try to do it by "old fashioned" means.

With such large scale interplay of these and many more factors, there is little reason to be surprised by the sudden emergence of automatic machines to handle the little tasks of old; cleaning floors, washing clothes, cutting bread, mixing cake etc. the list goes on and on.

And that is far from all and the list of innovative possibilities is endless. In truth, some of these innovations have shaped the world and there are many examples to cite. The discovery of electricity and the radio wave both changed the world. Today, computers are changing the world even faster. Now with cellular phones, new opportunities have come and our imagination has become the only limiting factor. We can only wait for the next big thing to be created and who knows what it will be?

The picture of technological advancement is not a completely rosy one. Indeed, there are some minuses to science as well, such as the introduction of new forms of danger which come as a consequence of innovative forms of technology, for example the nuclear bomb came from nuclear technology, unforeseen genetic mutations are as the result of genetic engineering, and the numerous and little talked about chemicals which can destroy the ozone or warm the planet.

The seriousness of the disadvantages of technology have prompted some people to argue that technological advancement, which is an example of scientific development, is making us more of advanced entities but less of humans. In other words, we have become better scientists, bankers and professionals and worse human beings. Martin Luther King puts this argument succinctly when he said "Our scientific power has outrun our spiritual power, we have guided missiles and misguided men."

The disadvantages that technology brings are issues which require serious examination to ascertain what can be done to eliminate them or at least minimize their effects since technology has definitely come to stay, and it would be to our advantage to learn how to work with it in ways that will be the most beneficial to us.

But despite the disadvantages listed here and the many more unnamed, we have seen that we can still derive many benefits from science and given that we live in, or at least come from, a part of the world where development is still a big headache, we should be the first to start a serious study of this phenomenon and see how best we can use it to our advantage. We may be surprised to see that there is a great viability in using our little gadgets to solve our big problems.

Let us make it clear that the aim of this paper is not to present technology as the magic cure that will clear our multitude of problems in a whiff, technology alone will not solve Africa’s problems because our problems are too complex, too deep and too overwhelming for any simplistic scheme to be successful. We can only achieve success when if have a more comprehensive approach to the problem, to include solid commitment to serious research, establishment of the appropriate structures, and the taking of required initiatives. It will be incorrect to assume that technology in itself is inherently good, and just implementing it alone will be enough to achieve any good result3. Though technology may be able to do anything, people must have the vision to drive it in the right direction.

Only with this knowledge can we make any meaningful gains in the development agenda.

In our particular context, Africa has proved that advanced technology could coexist with underdevelopment. People have satellite televisions whilst there are no teachers in the classrooms, we have mobile devices and pocket PCs and devices but our streets are still not named properly, there is still a large number of illiterates among the people who own and use cell phones, spreading of healthcare information is still a challenge even though a lot of people have access to radio and TV. This sorry list is endless.





























CHAPTER 2:

CAN TECHNOLOGY REALLY ADDRESS OUR PROBLEMS?



From healthcare, access to water and life expectancy, to governance, industrialization and even the quality of human life, there are numerous problems confronting African communities.

Today we are said to be living in the information age, an era where access to information is the new driving force of the world. The proliferation of the Internet and World Wide Web has reduced the whole world to a massive audience with unprecedented access to vast quantities of information. This communication is unencumbered and the formation of alliances is unhindered by physical distance, national or political borders4. With all the dynamics that this modernity brings, technology stands tall as a favourite to achieve any meaningful sustainable development for many reasons.

Principal among such reasons is the fact that there is improved awareness of underdevelopment among Africans themselves, which could be due to the information age, and an improved belief that our situations can be turned around. This is markedly different from decades ago when there was a lot of resignation and despair among black professionals. Evidence to support this would be the observation that much more thought is being directed at the Africa integration agenda and greater attention being paid to the Economic partnership agreements (EU- ECOWAS).

Another positive indicator is the growing number of trained and competent technological professionals on the face of the continent. Granted, the improved numbers by themselves will not be a good indicator, but with the holistic approach talked about earlier, one can see a sign of hope which shows that there is very high potential for success in a well though out scheme to utilize technology to solve our developmental problems.

Another good point is the individual work that is being carried out by different groups using different approaches (studies of the indigenous chieftaincy system for e.g.) at trying to solve the same problems. This is clear evidence to state that beyond the level of commitment, there have been actual attempts at problem solving. Even if some of such attempts have not been successful due to the numerous challenges in the way, the experiences have been gained and lessons have been drawn from them which would be utilized for future use.

Finally there are areas where major strides have already been made in Africa. Statistics show for example that there have been remarkable improvements in girl student enrollments in places like Nigeria, Kenya and Zambia5. This is definitely a feather in our cap and such areas may serve as boosters to face the remaining dark spots.

All these imply that we might be closer than ever to solving our problems, and all that may be left will be a few giant pushes forward.

This is where technology comes into the picture. It is the one thing that seems to know no barriers, catches on easily and has the power to transform even the most remotely inaccessible locations on earth to budding business towns. It is ubiquitous. Its innovations accelerate by the month. As a result, it is the most probable tool to achieve anything meaningful.

In the early 90’s, scholars described Africa as being left in a technological apartheid 6. Today however, with increased globalization perhaps a slightly better picture can be painted. Even though Africa is not in the league of the innovators of the most novel initiatives and we may not be making as good use of technologies as we ought to, or as some others are, we would still have something positive to report. For example, in some cases, Africa actually has comparable human and hardware resources. Therefore, "apartheid" would no longer be a precise definition of the situation as it stands.

As stated earlier in this paper, technology alone will not solve our problems. But with very serious considerations using active participation, a comprehensive and well though out scheme that incorporates technology will be a very viable solution.

However taking a look at all the attempts made so far and their attendant challenges and effects if any, one may say confidently that will all the proper accompanying compliments, technology will made very significant gains in spurring the development agenda on.











CHAPTER 3:

HOW IS TECHNOLOGY BEING USED TO SOLVE PROBLEMS?

Across many countries around the world, people have made serious strides at utilizing technological knowledge to solve all manner of problems. Many issues have arisen out of such attempts, and below are very brief summaries of some of those places where practical scientific knowledge has been utilized for the growth of the community.





3.1 ELECTIONS

In Africa’s recent governance history, elections have always been a challenge. It is hard to find a totally free and fair voting exercise, whilst contested elections, unfair processes, non transparent irregularities and simple ineffectiveness are commonplace. With a background of poverty, it is not too difficult to understand why the stakes are so high in African politics and why power is very lucrative in this part of the world.  This not withstanding however, there is a good number of unrests that could have been avoided if any election is proven to be fair, free and transparent to an appreciable degree.

Attaining this ideal degree has proved difficult for reasons of the complex interplay of some factors including, a government founded electoral commission, a winner takes all setting, and no motivation to commit to the right virtues. Knowing that power is so lucrative when you come from this winner takes all setting, it is really hard to let go of control of the electoral process. This is one motivation for the dishonourable acts that unfortunately we see quite often.

Because elections are highly involving and they require elaborate programs that span a series of locations (from a voter’s home to the polling station, the collation center, the electoral commission headquarters, the public domain and back to the voter’s home), It follows that unless you are trying to make public exhibition of your nefarious activity, you would need to be tactical to be successful at such dishonorable acts. The tactics employed may vary but they invariably entail series of acts that are designed to prevent information from getting into the public domain. So that for example, figures could be changed anytime so long as the original and authentic ones do not get into the hands of the public.

If democratic leadership were genuinely understood, there will be no attempt at election rigging. But since we are currently not in that ideal stage, election monitoring is one tool we can exploit to at least cut the ability for cheating.

Mobile phone technology is being used in election monitoring in some African countries under a new system of election monitoring called "parallel reporting". Parallel reporting is simply an approach to election monitoring whereby independent observers spread news of the votes counted at the basic level, which is the polling station. The figures are then relayed to an independent center where they are collated and cross checked with official figures announced by the electoral commission.

One advantage of this scheme is seen that it will make it increasingly difficult for an electoral commission to attempt to fraudulently sway the results in the favour of any of the contesting parties. The spreading or relaying of the results figures are done largely with mobile phones. Senegal is an example of a country where this project has been successful.

3.2       HEALTHCARE

The statistics obtained from healthcare research are interesting. Figures show that a large number of the world’s HIVAIDS afflicted people live in Africa. At the same time, one of the growing markets for consumer electronics such as mobile devices, handheld PC etc may be found here in Africa. This represents a population overlap, and it is only prudent that some amount of research has been directed towards attempting to find ways to incorporating technology in the treatment of the numerous diseases on the face of the continent7.

Tuberculosis (TB) has long been known to be one of the deadliest diseases known to man. Apart from the threat that this highly infectious bacterial disease presents to human life, it also enjoys some additional notoriety for lowering the sufferer’s immune system to make it easy for other diseases, which may have various degrees of harmfulness, to attack the sufferer.

As if that were not enough, TB has a deadly habit of mutating at the least case of drug non adherence. Therefore any TB caregiver knows that a patient who demonstrates non compliance with drug rules is clearly not interested in getting healed. As a result of this, over the years, ways to enforce religious adherence of medication have been tried but success has largely eluded caregivers.

In South Africa, there is a very laudable project, the SimPill’s award-winning Adherence System project, which uses a real-time management system to increase adherence to medications prescribed to treat chronic illnesses – particularly tuberculosis, which is a significant cause of death of people living with HIV.

3.3       SOCIAL ISSUES

Serious projects that utilize technology to address social issues have been implemented in South Africa. One such idea named Fahamu’s Umn Yango (meaning ‘doorway’ in isiZulu) has been implemented to curb domestic violence by equipping people with cell phones as tools to monitor and report abuse. Under this scheme, victims use cell phones to call a predefined and popular number and give details of the abuse.

The fear of being victimized has always made it difficult for victims, witnesses or relatives to step up and lodge complaints to the relevant authorities. There are examples of places where people had reported abuses and had been picked upon by the abuser. We have had friends of a victim reporting an abuse of their friend only to go home to be abused themselves by their spouses as punishment for "poking their noses in other people’s business". These good citizens were made to pay the price for exposing a wrong thing.  

This fear has been totally eliminated under this project because of the provision of anonymity, the telephone call could be made in secret, and even the details of the reporter are not always required. This is a sharp contrast to the situation in the past where victims, neighbours, or witnesses were required to walk into a police station to make a formal report.

Apart from successes chalked in the number of reports that are received, there has also been a reduction in the numbers of abuse cases. This may be partly due to the deterring feeling among would-be abusers that, any passerby holding a mobile phone might just make sure they get a visit from a police detective for spouse battering.

3.4       ANIMAL FARMING

Technology has also been put to good use in farming.

Farmers who rear cattle in small herds, over time, develop a personal relationship with the animals, the farmer knows all of them and can notice a missing animal or a sick one with just a glance. However, because it takes months of careful observation of the behaviour of every cow to know every animal well enough to take note when there is an infection or when an animal does not ruminate properly, this task would be ineffective if it were performed by a human shepherd with a large herd.

To remedy this situation, the technology of vocal tags has been developed in Europe. This project employs a tag, which is a belt fitted with sensors and worn around each animal’s neck. These sensors monitor several indicators such as the animal’s rate of rumination, voice clarity, digestion and breathing and send the data collected to a central computer.

Over time the computer knows what is normal for every cow and will notify the shepherd when something goes wrong with a cow.

The advantage of this project is that a farmer can take quick and specific action like giving treatment to the particular animal involved. This removes the need to give general treatments to the whole herd, which is both time and money wasting.

These are some of the ways that technology is being used towards increased development.

CHAPTER  4

WHAT LESSONS HAVE BEEN LEARNT?

No matter how promising an idea or project sounds, there are bound to be problems encountered in the deployment of the project. In achieving the above projects, following are some of the problems one is likely to be faced with:

In the election monitoring program, misinformation has been identified to be one of the problems starring the program in the face. It is true that when all the information is not localized in the hands of government, then a lot more transparency will be achieved, but it is also true that mass misinformation remains an unpleasant possibility.

Another problem could arise when there is a situation where people do not necessarily trust the degree of independence of the so called independent observers. It may lead to a problem where parties could cast a slur on the reputation of the observers so as to use the resulting mistrust to set the stage for a possible rejection of the results.

Overall this is a laudable idea and if a means of verification were added, the figures would mean much more to a lot of people.

Whilst celebrating the successes chalked, it is important to note that a number of other factors needed to progress before a state could move towards a more democratic model of governance. According to African political expert, Sheldon Gellar, these changes include: strengthening independent media, growing and ensuring freedom of civil society, decentralizing power, ceding more control to local governments, empowering women and improving judicial systems to ensure independence and power to punish.

Governance is one area that is set to reap some benefits of this phenomenon when used judiciously, unilateral rule and arbitrary action may be reduced towards a more participatory approach to leadership in Ghana

Technology could help achieve those goals to some extent, as communication was the key to overcoming oppression.

In some of the cases, such as the election monitoring or domestic violence reporting, the internet could be used to provide communities with means to communicate, to organize and obtain good information which is not controlled by the government. However, this is not practical in Africa since only a tiny percentage of Africans have affordable access to internet.

In the healthcare project, basic mismanagement has been identified as one of the reasons why many projects seem to skid to halt after being piloted. Needed funds are not always available to those who need them.

Another problem observed was that the people who will be using the project are not always consulted in the designing and planning of the ideas, so there is a lack of communication between beneficiaries, health professionals, technologists, and managers.

Another problem was the theft of cell phones. Although cell phones are a relatively low-cost technology, they still hold considerable value in poverty-stricken areas, and are commonly stolen. And, such theft is likely to rise as these devices become more and more complex. However this is quite debatable since some analysts argue that losing a cell phone to a thief is less of a financial loss than losing a more costly machine.

In the domestic violence project one stumbling block was the communication gap between the various parties involved in the system. Feedback was largely missing and people could not tell whether their input was useful – or received, and in some cases, police officers who receive messages reporting violence against women may not be prepared to respond.

Another problem was the unfortunate situation where some unscrupulous people made the work more difficult for the authorities by raising false alarms. This could be addressed by education and the incorporation of punitive measures.

However to use effective punitive measures, even more advanced technology will be required, for example to pinpoint a particular cell phone subscriber, and take action against them like blocking their Subscriber Identity Module (SIM) Cards etc.

And the usual problem of financing in many projects is ever present as well, and it is the more predominant one in the animal rearing project.

CHAPTER  5

CONCLUSION

Granted, there are challenges that exist in using technology to achieve development goals, but such efforts still hold great potential and the costs of any obstacle will not stand in comparison to the threat of underdevelopment and poverty. So we can only strive to work harder at such solutions.

Our development attempts and efforts should think more seriously about sustainability and scalability. One important consideration in this direction is the affordability of the programmes we plan and develop. The more affordable options have a higher chance of success, so the fact that most of the development projects do not require any extraordinarily complex or new gadgets is indeed pleasant to note.

Also throughout the creation and deploying of any project, enough consultation should be carried out to ensure that there is a general buy-in into the idea from the creators to the beneficiaries. This will make an idea command a common sense of ownership.

The quality of the management should also be improved and measures should be put in place to ensure the right things are done.

Identifying the problem is half the solution. We already now have greater awareness and we have made some attempts at solving them. Putting our acts together to draw the lessons and re-strategizing with a new approach -technology, is definitely the way to go. I am confident of the viability of this new approach.

CITED REFERENCES

1         Steere M. Cell phones promise fairer elections in Africa. Cable News Network [Online]2009. Available from edition.cnn.com/europe. Accessed 2009 Feb 6.

2         Wikipedia. Technology.Wikipedia.org[online]2009.

Available from en.wikipedia.org/wiki/Technology. Assesed 2009 March 27

3         Macha N. Will Technology solve Africa’s problems?. Global Voices Online[Online]2009. Available from globalvoicesonline.com/ Accessed 2009 Feb 6.

4         Finnis A.J. Learning in the Information Age.Twinisles[Online]2009.

Available from dev.twinisles.com/research/learninfoage.htm. Accessed 2009 March 27

5 Kitetu, C. Gender in Education: An overview of developing trends in Africa.

Available from www.ling.lancs.ac.uk/groups/crile/docs/crile54kitetu.pdf. Accessed 2009 March 27

6 Castells M. Information Technology Globalization and Social Development.[Abstract]. In UNRISD Discussion Paper No. 114.September 1999.p11.



7 Walvaren K. Did you say cell phones for development? Association for Progressive Communications.[Online]2007.Available from www.acp.org/en/home. Accessed 2009 Feb 6.

keegan asked:


And now for the perhaps shocking news: there are times when Viagra, Cialis and Levitra are of no help at all for treating erectile dysfunction. You have all been persuaded to believe that Viagra and the other PDE-5 inhibitors will always be able to help, even if only a little. Unfortunately, that’s not true. There are times when the degree of damage is too great for a “natural” solution. And let’s be clear. In relative terms, the use of Viagra and the others allows the body to respond to sexual stimulation as it was designed to do. Viagra simply removes a physical barrier to a natural ********.

This means we are into the surgical options. The first to mention is vascular reconstructive surgery. In a small number of cases, the surgeon may be able to reconstruct the arteries so that blood will flow more freely into the corpus cavernosum. Alternatively, surgery may help those suffering from venous leakages. When the blood inflates the corpus cavernosum, it compresses the veins that allow the blood to drain out of the *****. If the compression is inadequate, the blood will not be retained inside the corpus and the ******** will deflate. Unfortunately, the surgical theories have mostly failed in practice. Only about 5% of those having reconstructive surgery have found improved performance. This surgery is expensive. It is a long and difficult operation, and any incision can cause nerve damage. So it is not often used today.

Thus, when all else has failed or is not acceptable for some reason, we come to the somewhat radical solution of implanting a penile prosthesis.

How does this work?

There are three tubes in the penile shaft. Running along the bottom of the penis, the urethra drains the urine from the bladder out of the body through the *****. Along the top of the penis, the two more substantial tubes run side-by-side. They are designed to work in much the same way as the tyre on a car, i.e. with an inner and outer tube. So when the inner tubes fill with blood, they push against the outer tubes and, as the volume of blood increases, lift the ***** into an erect position.

Since the 1930s, medical researchers have been experimenting with implants to mimic this process of inflation and create the effect of an ********. We therefore have more than seventy years of experience among more than one million men to draw on. Two different approaches have come to dominate. One range of implants remains semi-rigid. These devices are easy to implant and very rarely fail mechanically. The problem, however, is that they produce a permanent ******** which can be difficult to conceal. Although they may be flexed up and down, most have limited mobility. The Dura II manufactured by American Medical Systems (AMS) has a more sophisticated system relying on interlocking disks strung on a central cable under tension which offers greater control over positioning, but may have an increased risk of mechanical failure.

The others are hydraulic, e.g. Dynaflex and CXM, and inflate, relying on a pump contained inside the ******* to transfer fluid (almost always water) from a reservoir inside the abdomen. These devices may have:

1.one, rod-like inflatable chamber which is hinged;

2.a two chamber system, e.g. the Ambicor; or

3.a three chamber system. All these systems replace the original corpa cavernosa. Today’s three-piece inflatable devices produced by AMS and Mentor Corporation offer flaccidity and ********* that approach the natural state. Whichever system you opt for, you should expect some pain and discomfort for five or six weeks following surgery. And, once installed, the implants cannot replace the “real thing”. Thus, if you have already lost your libido, it will not return. Similarly, if the nerve damage had caused a loss of sensation, or you were unable to achieve ****** or ejaculation, prosthetics will not restore those functions.So what are the advantages of this technology? Well, when the oral medications such as Viagra, Cialis and Levitra have failed, the convenience factors of the alternatives become important. Implants are safe and work no matter what the original cause of the ED. They are particularly useful to treat cases of damage following priapism and Peyronie’s Disease, fibrosis after injections, and to restore function after surgery for prostate cancer. So long as the partners are counselled on the strengths and weaknesses of the systems available, they provide satisfaction in more than 90% of all cases. Once installed, there are no further costs and they require no further maintenance (only about 3% of all installed devices ever need attention). From a psychological point of view, there is no external equipment to distract — as in the case of injections and vacuum devices. Equally, there is no need to remember to bring the Viagra, Cialis or Levitra along. If you are in the mood, you can simply act without having to wait for the medication to take effect.

Nevertheless, there are disadvantages to consider. This is a once-and-for-all procedure. Once the implant has been installed, it is no longer possible for a natural ******** to occur. It is always possible that, as science develops, different non-invasive procedures may become available. One may solve the ED problem you have. If your view is that a more natural form of treatment is better, then you may decide to wait. On the issue of informed consent, there are always risks in surgery involving an anaesthetic. In particular and despite a coating of antibiotics to modern implants, you will learn there is a small risk of infection following the surgery. This is relatively rare, but if it does occur and irrigation fails, the only response is to remove the prosthesis. However, once installed, there are three more general complaints.

1.Because the ******** is not being caused “naturally”, the systems only produce hardness in the body of the *****. Neither system affects the head of the ***** which remains soft. This can feel unsatisfactory and make *********** uncomfortable.

2.The body of the ***** does not warm as in the natural ******** which can feel strange to your partner.

3.The surgery can sometimes produce a shorter ***** which you and your partner may find unsatisfactory.

Finally, let’s dispose of one more general worry that some of you may have. There have been a number of problems with the safety of some silicone implants, e.g. in ****** enhancements. None of the inflatable prostheses use any form of silicone as the fluid.

Niels Grønning Rasmussen asked:


Preface

 

A growing industrial demand for high throughput screening of new molecular entities (NME) has spurred great advances in various divisions of scientific development. Researchers has begun to combine various scientific methods to meet the competitive demands in modern drug development, and as a consequence optimized individual phases of drug development.

 

Technological improvements should ensure high quality expeditious drug development and a as a consequence a modern “fast track” from drug discovery to marketed product.

 

These scientific advances should however be viewed in sharp contrast to the increased economical expenditures observed in pharmaceutical companies worldwide. The price from discovery phase to actual marketing is estimated to be in the region of 0.8 billion to 1.7 billion dollars (11) and research has shown that investments in NME’s has increased 55 % over the last five year (12). These economical prospects are paradoxically followed by the fact that there has been observed a mere 7% increase in FDA-approved NME’s from 1993 to 2003. These combined factors are inherently linked to a new paradigm shift in drug development where technological advances outrun the collaborative marketing of new drugs.

 

This project will present the reader with three established analytical methods in drug development and link these methods with nine analytical properties proposed by M. Valcárel and A. Rios (2). Implementation of these methods in drug development and individual quality standards and guidelines will be presented and discussed and the project will be summarised with concluding remarks.

 

The nine analytical properties

The analytical properties proposed by M. Valcárel and A. Rios (2) should be regarded as a framework which efficiently introduces the students to the various aspects of analytical chemistry. They are a means of providing a hierarchical approach toward the analytical chemistry curriculum and should ensure an organized introduction to analytical chemistry.

 

The significance of introducing analytical properties hierarchically to students can be described in terms of the following three groups proposed by the authors. The most important group is the top or capital group. This group is defined by the need for accurate and representative data which in turn is the sole contributor towards the quality of the results.

 

The second group, the basic properties, ensure the quality of the analytical process and cover the more practical aspects of analytical chemistry. They include such properties as selectivity, precision, sensitivity and proper sampling. They are properties which during the course of an analytical approach can prove contradictory and could lead to a great deal of decision making in the process. The decisions which are made could alter the quality of the analytical processes and in turn influence the quality of the results. The scientist must reflect on these basic properties and establish a standard by which the analytical processes are conducted in order to facilitate high quality analytical processes. The various analytical factors their complementary and contradictory relationships (2) fig. 4) should be evaluated and the analytical research should be conducted accordingly.

 

The quality of the analytical process and the quality of the results are thus highly dependent on one another, and it should become apparent that the capital properties and the basic properties have a mutual relationship in obtaining high quality results meeting external quality standards. The accuracy and representativeness defined by the capital properties is only relevant if we ensure strict precision, sensitivity, selectivity and proper sampling in the laboratory.

 

The last group of properties, the accessory properties, are interesting in respects to their mutual influence and relationship with the basic properties. The accessory properties are represented by expeditiousness, cost-effectiveness and personnel safety and comfort. These are properties reflecting the competitive aspects of analytical chemistry and are mutually dependent on the basic properties. Thus, compromises regarding sensitivity, precision and selectivity could yield greater expeditiousness and improved productivity compared to competing companies or laboratories. There are however contradictory aspects of the accessory properties and reducing the basic properties could potentially influence various accessory properties thus leading to further challenges in the productivity and competitiveness.

 

The properties proposed by M. Valcárel and A. Rios should be thought of as a way to hierarchically introduce analytical chemistry. Each group represents a significant part of analytical chemistry and should be dealt with thoroughly by the teacher in order to facilitate a correct understanding by the individual student. The individual groups thus represent the framework by which we can introduce the student to analytical chemistry and rightfully cover the curriculum. It also reflects contradictory relationships in analytical chemistry and proposes some interesting aspects concerning competitiveness, expeditiousness and sensitivity in the laboratory. In industrial context the properties illustrate the paradox observed then assessing various pharmaceutical projects and they are an excellent way to graphically present various dilemmas in drug development.

 

Analytical techniques in drug design and discovery

Current initiatives in analytical chemistry propose some interesting aspects by combining various division of science towards high yield quality data. Some of these methods are successfully implemented in various phases of drug development and aid in shortening the timeline from lead compound to marketed drug. A collection of these methods are presented below and they should present the reader with a quick overview on some industrially applied analytical techniques. These methods equally show promising results towards scientific advances in analytical chemistry and they demonstrate the implementation of “lean” strategic guidelines in modern drug development and discovery.

 

“Development of a Ubiquitin Transfer Assay for High Throughput Screening by Fluorescence Resonance Energy Transfer” (3).

 

Boiscalir et. al (3) propose a new assay based on fluorescence resonance energy transfer (FRET) which successfully could lead to high throughput real time screening of the ubiquitination process in vitro. They furthermore challenge the novel DELFIA assay and suggest that the FRET assay shows lower data variability and due the simplicity of the FRET analysis, the tedious washing, binding and incubation steps in DELFIA are avoided.

 

Protein degradation by means of ubiquitination involves three enzymatic steps (E1 to E3). Each of these enzymes contributes to the ubiquitination process which leads to the covalent attachment of ubiquitin with ?-aminoacid lysine residues on the target protein (6). The binding of ubiquitin targets the protein for degradation by the proteasomes.

 

The suggested assay measures the transfer of ubiquitin between the E2 enzyme (Ubc4) and Rsc (human HECT protein). By coupling the Rsc protein to glutathione-S-transferase (GST) and using an anti-GST antibody labelled with Eu3+ it is possible to pre-label the Rsc-GST fusion protein.

 

The assay exploits the fact that the upon excitation of the compounds, the flourophores Eu3+ and APC exhibits energy transfer and the emission experienced is directly measurable at 665 nm (APC) and 615 nm (Eu3+). To introduce the APC flourophore, the authors have created an ubiquitin-biotin-Streptavidin-Apc complex. Eu3+ acts as the energy donor while APC acts as the energy acceptor, when these are in close proximity (less then 100 Å) to one another, emission is observed from Eu3+ at 615 nm and at 665 nm with APC. The signal intensity presents a means to quantify the ubiquitination process real-time.

 

The results presented in the paper and the sophisticated experimental set-up revels promising real time data acquisition of biological processes and the method could become a valuable tool in either lead optimization or could successfully be implemented in future HTS assays.

 

“Drug screening of pharmaceutical discovery compounds by micro-size exclusion chromatography/mass spectrometry” (4).

 

Paul A. Wabnits and Joseph A. Loo propose a new method which successfully could improve the screening of active ligands in molecular binding studies. Micro-size exclusion chromatography offers a fast and simple way to separate the free ligand from the bound protein-ligand complex. Coupled with liquid chromatography and mass spectrometry the authors present a quick and efficient assay which potentially could lead to high throughput molecular binding quantification.

 

The metalloenzyme peptide deformylase (PDF) was chosen as the target protein, but in order to achieve sufficient spectroscopic data, the authors exchanged the native Fe2+ with the spectroscopically active Co2+. The binding assay was performed on PDF with several suspected inhibitory drugs (the complete structure was only revealed for actinonin due to commercial reasons).

 

Various ligands were incubated with PDF, and by means of micro-size exclusion chromatography and mass spectrometry, it was possible to obtain mass spectrums revealing the presence or absence of free ligands. The presence of free ligand should indicate weak/no binding and by performing this with various combinations of drugs the researchers where able to establish the binding rank order of the drugs ((4) table 3).

 

These data suggest the rank by which various drugs show inhibition of the PDF enzyme, and furthermore introduces a method which could yield fast screening of therapeutic leads towards potential macromolecular targets. The procedure shows high sensitivity and enables researcher to perform fast efficient binding studies of various protein and ligand combinations.

 

The proposed micro-size exclusion principle is furthermore a great example of the simplicity observed in recent advances in drug development and discovery.  

 

“In vitro identification using fast gradient high performance liquid chromatography combined with tandem mass spectrometry” (5).

 

In order to perform quick efficient separation of novel drugs and their metabolites, a growing need for optimization of already established analytical techniques is required. A reduction in the time by which researchers can assess potential drugs and their metabolites could be proven valuable in the lead optimization stage of drug design. Even a small reduction in the identification time is of great interest economically and professionally, and could lead to an enhancement in this important phase of drug design.

 

Coupling fast gradient high liquid chromatography with tandem mass spectrometry could reduce the bottleneck observed in the lead optimization stage as proposed by Cornelis et. al.

 

The authors present a fast and efficient way to separate and identify isomeric drug metabolites as well as the parent compound, by use of already established analytical processes. Microsomal incubation of the novel drugs produces the suspected metabolites which by means of fast gradient high liquid chromatography are successfully separated. The separation process is proven by coupling the chromatographic process with tandem mass spectrometry. This enables the researcher to establish the presence or absence of various metabolites and indicates the metabolic fate of the investigated drug.

 

By reducing analysis time researchers could reduce this step and Cornelis et. al propose a technique which successfully could separate metabolites from parent compound in less than 2 minutes. Optimal conditions were obtained upon increasing the flow rate to 2000 µL/min, and enabled successful chromatographic separation of the metabolites and the pure compound ((6) fig. 2+3).

 

The method is thus of industrial significance due to the time reduction observed in the process and the relatively easy experimental set-up.

 

 

Lead discovery and optimization

 

High throughput screening (HTS)

Industrial high throughput screening (HTS) presents a multidisciplinary science protruding various scientific fields of study. HTS has become a standard in modern drug development signified by a new paradigm shift toward automatization in the lead discovery phase. It is no longer unusual, that pharmaceutical companies have huge screening libraries containing between 500.000 and 1.000.000 compounds (8), controlled by robotics and computational devices. These libraries provide an extensive database containing valuable compound information which linked to recombinant “humanized” in vitro tests could improve expeditiousness and thus as a consequence improve the drug development and discovery process. The libraries should however not be perceived as a clear cut improvement in the lead discovery phase. The expeditiousness of a lead finding is highly dependent on the development of independent assays modelled towards the suspected target. This could potentially produce a bottleneck in discovery phase and should thoroughly be debated in project decision making.

 

 Criteria’s in HTS

The dawn of these enormous screening libraries has sequestered a demand for assays which are able to successfully screen thousands of compounds and furthermore provide sustainable data fast and efficient. This has forced researchers to optimize existing analytical techniques and implement various branches of natural science towards the creation of assays which fulfil specific standards.

 

The ideal HTS assay should exhibit the following properties (8):

High signal to background ratio (S/B) or signal to noise (S/N) High z´-factor (9) (values >0,5 represent a good assay) Fast screening time Low coefficient of variation (CV %) Large Stokes Shift



These properties are quantifiable measures aiding the researcher in producing high quality HTS assays modelled towards the proposed target. These criteria thus impose boundaries and guidelines which if followed properly optimistically results in ideal screening methods for future implementation in the drug development phases. Even the smallest improvement in one of the parameters could result in higher expeditiousness and potentially a shortening of the individual developmental phases.

 

As stated above, efficient screening of compounds is essential in locating the perfect lead candidate for future studies. Observing the parameters, it is evident that there are colliding interests between various aspects of analytical chemistry and economical interests. HTS could be grouped with the above mentioned accessory properties in the nine analytical properties (1,2), reflecting upon the balance between expeditiousness and cost effectiveness in terms of economical profitability. It stands in sharp contrast to the basic properties ensuring high precision, sensitivity and selectivity.

 

There is a fine balance between producing high throughput data and obtaining the adequate precision needed to produce quality results which live up to internal/external standards. As a consequence, the decisions we choose in these two groups highly reflect the accuracy and representativeness found in the capital properties and thus the quality of the results. These conflicting properties should be evaluated in the early drug development phases and it is the research and development team’s job in collaboration with the financial team to define internal standards for which they both can agree upon.

 

Implementation of quantitative techniques in drug development

 

HTS assays implemented in the early discovery phase are a powerful tool in establishing the lead compounds interaction with a suspected biological target. Once a suitable lead has been found quantitative studies are needed to further elucidate the leads biological and chemical characteristics. Quantitative studies following these screening assays provide direct quantifiable data concerning the leads metabolic, pharmacokinetic and toxicological fate. These studies provide valuable information concerning the leads biological properties, and the data obtained in the quantitative studies informs the researchers about potential problems such as toxicology, absorption, distribution excretion, pharmacodynamics and metabolism. Quantitative studies are thus often observed in lead optimization studies where they provide important experimental data.  

 

These studies rely on analytical methods with great precision, expeditiousness, sensitivity and they inherit some of the same criteria as HTS assays (se above). Deviations to the above mentioned criteria’s exist and they include the following:

The need for an adequate internal standard Heightened Precision (of great importance in e.g. toxicological studies) High Selectivity Low matrix interference



When conducting these quantitative studies it is of great importance that the data obtained reflects the precise action of the drug and that the methods inherently refrains from producing false positives. It is obvious that quantification of a seemingly unknown drug is difficult. Purification and the construction of an internal standard is alone a tedious task which requires a great deal of experimental work. Introduction of the lead drug into the lead optimization stage furthermore requires the development of specific modelled analytical techniques which potentially could resolve in a bottleneck in the specific phase.

 

As stated above there is a clear cut difference between the quantitative studies and the screening methods employed upon implementing assays and procedures in drug design and development. Screening has obvious advantages in the lead discovery phase, and is a strong tool which efficiently and swiftly screens numerous compounds for desired characteristics. The screening assays are however restricted upon relying on a great deal of compound information concerning the proposed target and lead compounds. Structural information concerning pKa, lipphilicity, LogP and LogD is needed to develop an assay that follows the above mentioned success criteria. However, once developed, a successful assay generates valuable data for further use and is imperative when evaluating potential lead candidates in the lead discovery phase.   

 

The quantitative study presented by Cornelis et. al (5) is an excellent example of a procedure which could be deployed in the lead optimization stage of drug development. The metabolic fate of the lead compound can be evaluated and quantification is possible in specific ADME/Tox studies. However, the procedure is dependent on extensive knowledge of the mass and structure of the metabolite or drug compound in order to adequately ascertain that we quantify the correct entity.

 

In conclusion

 

The drug development and discovery phases introduce some interesting possibilities for various implantation strategies in respects to scientific collaborations and technological advances. One recent advance in liquid chromatography is the dawn of ultra performance liquid chromatography (UPLC) which shows promising results toward quantitative studies (14). The current trends thus reveal great potential in implementation of these new analytical techniques and future studies may contribute to heightened quality in the lead discovery and optimization phases.

 

The increased governmental requirements for quantitative ADME/Tox studies has forced pharmaceutical companies to invest enormous amounts of money in order to fulfil requirements suggested by the FDA or other local medicines agencies. This has prolonged the development from lead compound to marketed drug and I suggest that this indeed has faltered a paradigm shift in modern drug development. New biotech companies and scientific entrepreneurs are now faced with tough decisions regarding financial aspects in order to ***** the sustainability of a suspected leads and they should rightfully evaluate the various properties presented by M. Valcárel and A. Rios. We are positioned in a technological vacuum where technological advances greatly exceed the introduction of new drugs towards patients and the industrial drug development is faced with exciting challenges for the future which successfully may increase the amount of drugs marketed per year.

 

References 

1. Valcárcel M. A modern definition of analytical chemistry. Trends in Analytical Chemistry. 1997. 16. pp 124-131 

2. Varcárcel M and Rios A. Teaching analytical properties. Fresenius Journal of Analytical Chemistry. 1997. 354. 202-205. 

3. Michael D. Boisclair, Christopher McClure, Serene Josiah, Susan Glass, Steve Bottomley, Shubi Kamerkar and Ilkka Hemmilä. Development of a Ubiquitin Transfer Assay for High Throughput Screening by Fluorescence Resonance Energy Transfer. Journal of Biomolecular Screening, Vol. 5, 2000, pp. 328. 

4. Paul A. Wabnitz and Joseph A. Loo. Drug Screening of pharmaceutical discovery compounds by micro-size exclusion chromatography/mass spectrometry. Rapid communications in mass spectrometry, Vol. 16, 2002, pp. 85-91. 

5. Cornelis E. C. A. Hop, Phillip R. Tiller and Leslie Romanyshyn. In vitro metabolite identification using fast gradient high performance liquid chromatography combined with tandem mass spectrometry. Rapid communications in mass spectrometry, Vol. 16, 2002, pp. 212-219. 

6. Jeremy M. Berg, John L. Tymoczko, Lubert Stryer. Biochemistry 5th edition. W. H. Freeman and Company. 

7. György M. Keser? and Gergely M. Makara. Hit discovery and hit-to-lead approaches. Drug Discovery Today. Volume 5, Issue 7, 1 July 2000, Pages 286-293.

8. H P Rang. Drug Discovery and Development. Churchill Livingstone, Elsevier. 2006. 

10. Alfonso Espada, Manuel Molina-Martin, Jeffrey Dage2 and Ming-Shang Kuo. Application of LC/MS and related techniques to high-throughput drug discovery. Drug Discovery Today. Volume 13, issue 9-10, May 2008, Page 417-423.

11. Tufts Center for the Study of Drug Development, Backgrounder: How New Drugs Move Through the Development and Approval Process, Boston: November 2001

12. Windhover’s In Vivo: The Business of Medicine Report, Bain drug economics model, 2003 

13.