In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery. A new approach has been developed to understand how disease and infection are controlled at the molecular and physiological level and to target specific entities based on this knowledge.
The process of drug discovery involves the identification of candidates, synthesis, characterization, screening, and assays for therapeutic efficacy. Once a compound has shown its value in these tests, it will begin the process of drug development prior to clinical trials.
Despite advances in technology and understanding of biological systems, drug discovery is still a lengthy, expensive, difficult, and inefficient process with low rate of new therapeutic discovery.
Structure of Drugs
Despite the rise of combinatorial chemistry as an integral part of lead discovery process, natural products still play a major role as starting material for drug discovery. Natural products may be useful as a source of new chemical structures for modern techniques of development of antibacterial therapies. Despite the implied potential, only a fraction of Earth's living species has been tested for bioactivity.
Prior to Paracelsus, the vast majority of traditionally used crude drugs in Western medicine were plant-derived extracts. This has resulted in a pool of information about the potential of plant species to be used as an important source of starting material for drug discovery. A different set of metabolites is sometimes produced in the different anatomical parts of the plant (e.g. root, leaves and flower), and botanical knowledge is crucial also for the correct identification of bioactive plant materials.
Also microbes are the main source of antimicrobial drugs. Streptomyces species have been a source of antibiotics. The classical example of an antibiotic discovered as a defense mechanism against another microbe is the discovery of penicillin in bacterial cultures contaminated by Penicillium fungi in 1928.
It's interesting that marine environments are potential sources for new bioactive agents. However, it was 2004 when the first marine-derived drug was approved. The cone snail toxin Ziconotide, also known as Prialt, was approved by the Food and Drug Administration to treat severe neuropathic pain. Several other marine-derived agents are now in clinical trials for indications such as cancer, anti-inflammatory use and pain. One class of these agents are bryostatin-like compounds under investigation as anti-cancer therapy.
Preclinical and Clinical Trials
Considering the discovery of drugs it’s necessary to mention pre- and clinical developments. Pre-clinical development is a stage of research that begins before clinical trials (testing in humans), and during which important feasibility, iterative testing and safety data are collected. The main goals of pre-clinical studies (also named nonclinical studies) are to determine a product's ultimate safety profile. Products may include new or iterated or like-kind medical devices, drug. Each class of product may undergo different types of pre-clinical research. For example, drugs may undergo toxicity testing through animal testing. These data allow researchers to estimate a safe starting dose of the drug for clinical trials in humans. Most pre-clinical studies must adhere to Good Laboratory Practices (the abbreviation is GLP). The information collected from these studies is vital so that safe human testing can begin.
Typically, in drug development studies animal testing involves two species. The most common models to be used are murine and canine, although primate and porcine are also used. The choice of species is based on which will give the best correlation to human trials. But rodents cannot act as models for antibiotic drugs. Most studies are performed in larger species such as dogs, pigs and sheep which allow for testing in a similar sized model as that of a human. Animal testing in the research-based pharmaceutical industry has been reduced in recent years both for ethical and cost reasons. However, most research will still involve animal based testing for the need of similarity in anatomy and physiology that is required for diverse product development.
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety (or more specifically, information about adverse drug reactions and adverse effects of other treatments) and efficacy data to be collected for health interventions (e.g., drugs, diagnostics, devices, therapy protocols). Depending on the type of product and the stage of its development, investigators enroll healthy volunteers and/or patients into small pilot studies initially, followed by larger scale studies in patients that often compare the new product with the currently prescribed treatment. As positive safety and efficacy data are gathered, the number of patients is typically increased. Clinical trials can vary in size from a single center in one country to multicenter trials in multiple countries. Clinical trials often involve patients with specific health conditions who then benefit from receiving otherwise unavailable treatments.
During the clinical trial, the investigators: recruit patients with the predetermined characteristics, administer the treatment(s), and collect data on the patients' health for a defined time period. These patients are volunteers and they are not paid for participating in clinical trials. These data include measurements like vital signs, concentration of the study drug in the blood, and whether the patient's health improves or not. The researchers send the data to the trial sponsor who then analyzes the pooled data using statistical tests. The most commonly performed clinical trials evaluate new drugs, medical devices, biology, psychological therapies or other interventions.
The Role of Drugs
Drugs in modern medicine act a very important role. They are a powerful weapon in the struggle with a variety of diseases, in the conduct of preventive measures. Medications are used in almost all areas of medical practice. We make wide use of drugs, such as therapy in the treatment of cardiovascular diseases, tuberculosis, diarrheal diseases, influenza, etc., in dermatology for the treatment of skin diseases, in surgery, pain management, and in ophthalmology at infectious diseases. A number of drugs are used for disinfection.
Great achievements of modern medicine, the development of powerful chemical and pharmaceutical industry, the synthesis of drugs, a broad study of domestic medicinal plants led to the creation of new highly efficient drugs such as antibiotics, sulfa drugs and hormones which further increased the role and value of drugs and expanded the range of applications.
Ex. 1. Match the expressions in the left-hand column with their definitions in the right-hand column. The expressions appear in the text you have just read.
1. serendipitous discovery
a. follow the requirements
2. implied potential
b. related to nervous disease
3. diarrheal disease
c. symptoms, signs
4. cardiovascular disease
d. repeated, recurrent checking
5. administer treatment
e. summed up, total, general information
f. hidden, unrevealed opportunities
7. iterative testing
g. finding based on intuition, guided by intuition
8. assays for therapeutic efficacy
h. prescribe medications, perform, conduct medication
i. related to heart and blood vessels illnesses
10. enroll/recruit volunteers
j. the basic indicators of a body condition
11. pooled data
k. tests for evaluation of the therapeutic power of a drug, medication
12. adhere to
l. realizability, ability for being put into effect
m. involve patients into clinical trials on their own free will
14. vital signs
n. related to digestive disorder
Ex. 2. Mark the following statements as True or False.
1. Drug discovery is a highly efficient process with a high coefficient of new therapeutic effects.
2. Before Paracelsus extracts produced from plants constituted the main part of traditionally used raw medications in Western medicine.
3. Ziconotide is a toxic substance extracted from plant species to treat nervous disease.
4. The main objectives of pre-clinical studies are to find out if the product to be tested is safe as much as possible.
5. Preclinical trials include tests in humans.
6. In recent years animal testing has expanded.
7. Murine, canine, porcine models are related to rats/mice, dogs and pigs respectively.
8. Patients are involved into clinical trial against their own free will.
9. The number of patients taking part in clinical trials is always the same.
10. Patients are not paid for participating in clinical trials.
Ex. 3. Consult the text above and complete the following sentences.
1. A source of antibiotics has been … .
2. An important source of … material for … discovery were plant… .
3. A different set of … is sometimes produced in the different anatomical parts of the plant.
4. Microbes are the main source of …drugs.
5. Sea is a potential … for new … … .
6. Each type of products may … different types of preclinical … .
7. The … send the data to the … … who then analyzes the … … using … … .
8. Drugs are …weapon in the … with a variety of … , in the conduct of … … .
Ex. 4. Arrange the sentences in the logical order using the part of text A under the heading Pre-clinical and Clinical Trials.
1. The total data are analyzed by statistical tests.
2. Clinical trials are intended to collect information on negative drug reactions and negative as well as positive consequences of other treatments to carry out further investigations on patients.
3. Testing in human can begin after the safety information has been available.
4. The most commonly performed clinical trials evaluate new drugs, medical devices, psychological therapies or other interventions.
5. During the clinical trial data on the patients’ health for a definite period of time are collected.
6. Pre-clinical development of drugs is a stage of research that begins before Clinical Trials.
7. Pre-clinical studies are aimed at determining the maximum possible safety of a drug or medical device to be tested in humans.
8. The choice of animal species is based on the similarity in anatomy and physiology with humans.
9. Drug discovery process suggests animal testing.
Ex. 5. Answer the following questions.
1. What do you know about the ways of discovering drug in the past and nowadays?
2. What does the process of drug discovery involve?
3. Name the sources of starting materials for drug discovery. Could you provide any examples?
4. Why does the correct identification of bioactive plant materials imply botanical knowledge?
5. What kind of information is collected during the pre-clinical development stage of research?
6. What are the most common models used for animal testing?
7. Could you comment on the following statement: the choice of species is based on those which will give the best correlation to human trials?
8. Rodents cannot act as models for antibiotic drug, can they? Why?
9. What procedures are conducted by investigators during clinical trials?
10. What do data collected on the patients’ health for a definite period of time after administering the treatment include?
Ex. 6. Make your own research and report on the role of drugs in modern medicine. Consider the following issues:
1. Drugs are powerful weapon in the struggle with a variety of diseases, in the conduct of preventive measures.
2. Creation of new highly effective drugs and their application.
3. The role of natural products in drug discovery.
THE INFINITIVE (revision)
Ex. 1. Study the forms of the Infinitive and remember their meanings.
(simultaneous with the predicate)
to be visited
(in process, simultaneous with the predicate)
to be visiting
(prior to the predicate)
to have visited
to have been visited
(in process, prior to the predicate)
to have been visiting
I am glad to visit you ß ðàä ïîñåòèòü âàñ
to have visited you ,÷òî ïîñåòèë âàñ
to be visited by you ,÷òî âû ïîñåùàåòå ìåíÿ
to be visiting you ,÷òî ïîñåùàþ âàñ
to have been visited by you ,÷òî âû ïîñåòèëè ìåíÿ
to have been visiting you ,÷òî ïîñåùàþ âàñ óæå íåêîòîðîå âðåìÿ
Ex. 2. Point out the forms of the Infinitive which express the simultaneous or future actions relative to the action expressed by the finite verb.
To establish, to be accompanying, to have accomplished, to have been considered, to substitute, to have discovered, to be emitted, to have been produced, to be determined, to have carried out.
Ex. 3. Change these sentences according to the models. Mind the forms of the Infinitive:
a) Perfect Active
I am happy that I obtained satisfactory results so quickly. –
I am happy to have obtained satisfactory results so quickly. –
1. He is sorry that he has given up the University.
2. I am lucky that I have studied high-level programming languages before.
3. He was sorry that he had lost his chance to get the job.
4. I am glad that I had the opportunity to observe the experiment myself.
5. He was happy that he had improved the design of the device.
6. She is lucky that she has followed this technique in her research work.
7. I am proud that I have made about ten discoveries which play a very important role in chemistry.
I am lucky that I was sent abroad to continue my studies. –
I am lucky to have been sent abroad to continue my studies. –
1. I am glad that I was paid due attention.
2. They are pleased that they were shown a new laboratory of inorganic chemistry.
3. I am happy that I was told about that apparatus.
4. I am lucky that I was informed of the situation.
5. He is sorry that he was interrupted.
6. She was angered that she was not given time to think.
7. I am terribly sorry that I was misunderstood.
8. He was proud that he was offered an interesting job.
9. We were pleased that we were met by him.
Ex. 4. Pay attention to the translation of the sentences below in which the infinitive is used:
a) as a subject
1. To vaporize means to change a solid into a vapor by heating it. 2. It is quite possible to have a solution of a gas in a liquid, or in a solid, or in another gas. 3. To do it accurately was the main problem. 4. To give a true picture of the surrounding matter is the task of natural science.
b) as a predicative
1. Two liquids which mix with the absorption of heat may limit solubility in each other. 2. Our present concern is to analyze the information obtained during the experiment. 3. His problem is to determine equivalent weights. 4. You should remember that the yield in this reaction is good only if it goes to completion.
c) as an object
1) to such verbs as: to agree, to want, to wish, to prefer, to ask, to decide, to intend, to cause, to begin, to try, to attempt, etc.
1. He intended to find out the required element. 2. They decided to use an old apparatus because the new one was out of order. 3. When heated sulphur begins to darken. 4. He claims to be an expert on the subject.
2) to such adjectives as: difficult, sure, important, hard, interesting, sorry, etc.
1. Equations for redox reactions involving complex ions are more difficult to balance. 2. They were ready to use this new invention for peaceful purposes. 3. They are sorry to be late.
d) as an adverbial modifier of
1. An aqueous solution of bromium is used in analytical work to absorb carbon dioxide. 3. In order to test for a sulphate, we add a little hydrochloric acid, followed by barium chloride solution. 4. Concentrated sulphuric acid was used so as to maintain a moisture free atmosphere inside the desiccator.
2) result or consequence
1. At this temperature aluminium is brittle enough to be ground to a powder. 2. This dioxide dissolves sparingly in water to give a slightly acidic solution. 3. In the reaction of displacement an element reacts with a compound to liberate another element.
e) as an attribute.
1. It is just the article to be discussed in class. 2. The substance to be extracted should be more soluble in the extracting solvent than in the initial solution. 3. He is the man to rely on. 4. She was the first to agree that the best methods were the electrolysis of water and the fractional distillation of liquid air. 5. There are still many problems to solve in organic chemistry. 6. The substance to be dissolved is called the solute.
Ex. 5. Complete the following sentences by selecting the proper form of the Infinitive.
1. It is difficult to give a definition which tells clearly and briefly how solutions differ from mixtures and compounds, in spite of the fact that solutions are among the most familiar substances … in nature.
a) to find b) to be found c) to have found
2. The solution prepared was sufficiently saturated … in this case.
a) to use b) to be used c) to be using
3. Such a substance has properties and composition which might be described as either inhomogeneous or homogeneous depending on the experiment … .
a) to be doing b) to do c) to be done
4. … the thorium from iron, this precipitate is dissolved in hydrochloric acid.
a) To be separated b) To have been separated c) To separate
5. In his publication D.I. Mendeleyev used the periodic character … the properties of the elements … later as those of scandium, gallium and germanium.
a) to have predicted b) to be predicted c) to predict
a) to be described b) to be describing c) to have been described
6. He is happy to … you for a week.
a) to visit b) to have been visiting c) to have been visited
Ex. 6. Translate the sentences into Russian. Pay attention to the functions of the Infinitive.
1. The purpose of these experiments was to observe the properties of the element involved.
2. If the temperature is raised, a small amount of phenol must be added in order to produce the separation of a liquid.
3. The results of several methods to be described later are in satisfactory agreement.
4. A new approach was developed to target specific entities.
5. This is the condition for everybody to observe.
6. The substances used to specify the composition of a solution are known as components.
7. In studying the properties of a substance it is desirable to know its composition.
8. You are not allowed to work in the laboratory without learning the safety instruction.
9. This drug may be given to reduce the risk of the death of cardiac tissue.
10. The main goals of pre-clinical studies are to determine a product’s ultimate safety profile.