Edexcel Biology Gcse - Making Medicines Part 2

Relating to medicines and drugs, their production, sale and use.

He discovered the antibiotic penicillin from the penicillium mould. By chance, he discovered that where an agar plate of bacteria had been contaminated by a mould, the bacteria had been killed.

Historically drugs have come from nature, as parts of plants and microorganisms have been extracted.

Certain drugs can be extracted from natural sources, and have been known about for a long time. For example, willow bark was used by the ancient Greeks to help cure fevers and pains. It was later discovered that the active ingredient was salicylic acid. This was modified by chemists into the substance we call aspirin, which is less irritating to the stomach than salicylic acid. Another example is the heart drug, digitalis which is extracted from foxgloves.

Plants are still important today, but most drugs are now created in a laboratory by scientists at pharmaceutical companies. These companies now have synthetic versions of the plant extracts, and use these as the starting point to develop new drugs.

• Safety
  This is important as some drugs are toxic, and have other side effects that might be harmful to people.

• Effectiveness
  This is also known as efficacy, and checks how well the drug cures the disease, or improves symptoms.

• Dosage
  This varies, and has to closely controlled, as too high a concentration might be toxic.

1) Preclinical drug trials
2) Animal trials
3) Human clinical trials

The drugs are tested using computer models and human cells grown in the laboratory. This allows the efficacy and possible side effects to be tested. Many substances fail this test because they damage cells or do not seem to work.

Drugs that pass the first stage are tested on animals. In the UK, new medicines have to undergo these tests. But it is illegal to test cosmetics and tobacco products on animals. A typical test involves giving a known amount of the substance to the animals, then monitoring them carefully for any side-effects.

Drugs that have passed animal tests are used in clinical trials. They are tested on healthy volunteers to check that they are safe. The substances are then tested on people with the illness to ensure that they are safe and that they work. Low doses of the drug are used initially, and if this is safe the dosage increases until the optimum dosage is identified.

Thalidomide is a medical drug that caused unexpected and serious damage to unborn babies in the 1950s and 1960s. Thalidomide was developed as a sleeping pill, but it was also thought to be useful for easing morning sickness in pregnant women. Unfortunately, it had not been tested for use in this way.

Birth defects
By 1960, thalidomide was found to damage the development of unborn babies, especially if it had been taken in the first four to eight weeks of pregnancy. The drug led to the arms or legs of the babies being very short or incompletely formed. More than 10,000 babies were affected around the world. As a result of this disaster, thalidomide was banned. Drug testing was also made more rigorous than before.

Thalidomide today
Thalidomide is now used as a treatment for leprosy and bone cancer. Its use is heavily regulated, however, to prevent a repeat of the problems it caused in the last century.

Antibodies are proteins produced by a type of white blood called lymphocytes. Pathogens have proteins on their surface called antigens. When a pathogen infects the body, the lymphocytes recognise these antigens as foreign and attack them by producing antibodies.

Antibodies bind to specific antigens on pathogens. This means that only one type of antibody will bind to a matching antigen. Scientists discovered that we could make antibodies to bind to antigens on other substances, and not just those on pathogens. Once bound the antigens - and the substances they are found on - are merged tightly together. This makes them easier to identify and deal with.

1) An antigen is injected into a mouse.
2) The mouse naturally produces lymphocytes, which produce antibodies specific to the antigen. Lymphocytes can no longer divide once it has started to make antibodies.
3) Spleen cells which produce the lymphocytes are removed during a small operation.
4) The spleen cells are fused with human cancerous white blood cells called myeloma cells to form hybridoma cells. Cancerous cells divide indefinitely.
4) These hybridoma cells divide and produce millions of monoclonal antibodies specific to the original antigen. The hybridoma cells have the characteristics of both the lymphocyte in producing antibodies and the cancerous cell in the ability to divide over and over again.

1) A mouse is vaccinated to start the formation of antibodies.
2) Spleen cells that form antibodies are collected from the mouse in a operation.
3) These are fused with tumour cells called myeloma cells.
4) This forms hybridoma cells.
5) These are grown in a laboratory and those that produce antibodies are separated.
6) Antibodies are collected.

Pregnancy test kits use monoclonal antibodies. These have been designed to bind with a hormone called HCG which is found only in the urine of pregnant women. Monoclonal antibodies are attached to the end of a pregnancy test stick onto which a woman urinates. If she is pregnant, HCG will be present in her urine and will bind to the monoclonal antibodies on the test stick. This will cause a change in colour or pattern which will indicate pregnancy. These specific monoclonal antibodies in the pregnancy test will only bind with HCG.

Cancerous cells have antigens on their surface. Monoclonal antibodies can be designed to bind specifically with these antigens. When injected into a person's body, the monoclonal antibodies will bind with these cancer cells and clump them together. This makes it easier to identify a cancerous tumour, which can then be treated or removed. The antibodies can be made slightly radioactive to allow the cancerous cells to be detected in the body, for example using a PET scanner.

• Carrying drugs that have been attached to them, to the tumour. This means that the drugs specifically target the cancer cells and can allow smaller doses of chemotherapy drugs to be used. This can reduce the side effects and reduce risk to healthy cells.

• Encouraging your immune system to attack the cancer cells directly.

Monoclonal antibodies can be made to bind to antigens on blood clots. The monoclonal antibodies can be attached to dyes that will glow fluorescently under UV light or attached to radioactive elements which can be detected with special cameras. This can make locating the clot much easier and can help to speed up how quickly a patient is treated.

Monoclonal antibodies can be designed to bind to, and identify, almost any substance. They are used to test for pregnancy by detecting HCG hormones in urine, as well as detecting other hormones in the blood, and diseases such as HIV and AIDS, herpes and chlamydia. They can also be used to treat conditions like cancer by carrying drugs directly to the tumour cells, and helping the immune system attack them. Making monoclonal antibodies for the first time can be time consuming. When they have been made, they can then be produced quickly.

The human body is very complicated. Scientists originally thought that monoclonal antibodies would be a 'magic bullet' and would be able to identify and treat many medical conditions. Tests have revealed, however, that this is not the case. The interactions in the human body have resulted in some unwanted side effects. This means they are not as widely used by doctors as originally thought.

Monoclonal antibodies are also very expensive to produce.

An ethical issue is one in which people disagree for religious or other moral reasons. The first step in making a monoclonal antibody is to inject a mouse with an antigen. After it has produced antibodies, a small operation removes spleen cells, which then continue make the antibodies. Some people disagree with this use of animals to produce monoclonal antibodies.

In 2006 a drug trial involving humans and using monoclonal antibodies to treat conditions such as arthritis and leukaemia went wrong. The individuals involved in the trial did not die, but despite monoclonal antibodies being given in very low doses, this resulted in organ failure. The monoclonal antibodies had been safely used in other animal trials before being used in human trials and the side effects were unexpected. This is an example of how careful we must be during drug development.

The factor causes the disease.

A link between a factor and a corresponding disease.

Antigens

Antigens

Cancerous white blood cells

The first step is to inject a mouse with an antigen.

Spleen cells

A spleen cell and a myeloma cell