Biotechnology: Molecules, Technique and Therapies (Part 1)

by Wiebke Heiss / MEDICA.de

Detergents, plants resistant to bugs, drugs - chemistry, physics, biology – in the country, at sea or in the air. Biotechnology is everywhere since it is one of the most interdisciplinary branches of research – and helps medicine to combat diseases formerly known as not being treatable.15/11/2008

The concept is always the same: Scientists observe biological processes, analyze mechanisms and substances involved and try to mimic, produce, use the products with the help of current technologies. Quite a colourful affair since biotechnology is classified into white, blue or green categories depending upon its use for industrial processes, in the sea or agriculture.

Experts use the phrase red biotechnology when medical issues are being addressed and talk about products and technologies such as proteins, antibodies, enzymes, stem cells, cell and tissue cultures or gene therapy. One of the most famous examples that is being produced with biotechnological techniques is the hormone insulin. Many decades the hormones was extracted from the pancreas of cattle and pigs with the side effect of having to kill many animals and causing immune responses of diabetics due to the animal origin of insulin. When scientists discovered the gene for insulin in humans thanks to genetic engineering they were capable of transferring it into bacteria or yeast resulting in the production of human insulin by microorganisms.

Medicine from the deep of the sea

Wanting to combat diseases such as cancer, multiple sclerosis, rheumatism or Alzheimer's with biotechnology demands the discovery of new substances from nature. That is way scientists started to take a close look at the world's oceans. „Life is much more abundant at sea than ashore, biodiversity is much higher, bacteria and viruses are plentiful“, Professor Werner Müller from the University of Mainz, Germany explains. The reason: liquids are denser than air creating more living space and more evolutionary potential. „Sea creatures are more versatile“, the molecular biologist adds. Since they virtually live in abeyance they can divert into many imaginable appearances. Sea animals only need little skeletal support.

Sponges, for example, sit around on cliffs, rocks and reefs all over the world, filter water all day long through their soft bodies and comprise family members from only a few millimeters up to three meters in size. "Up to six billion bacteria are being filtered through a large sponge's body", Müller explains. This fact calls for a very efficient immune system that combats myriads of bugs. And indeed, sponges produce chemical substances that have not been heard of ashore in addition to repellents from microorganisms living in symbiosis with sponges in the need of defense against toxic bacteria and fungi.

Therefore, sponges offer plenty of potential as a biotech resource. Research in blue biotechnology is advancing in Germany in order to produce medicine made by the sea. The results so far: A drug that inhibits herpes viruses, a painkiller and potential agents against cancer.

Biochips in order to suss out diseases

However, biotechnological procedures are not just important in the development of new drugs. They also help in the diagnosis of diseases with biochips being one of the great advancements. A small plate not larger than a fingernail serves as the platform for accomplishing a few dozen tests simultaneously. So called gene chips assist with the detection of DNA and RNA fragments, protein chips fulfill the same purpose with proteins and help to learn more about a patient's problems.

A current example is a new chip that helps in the diagnosis of Morbus Wilson. Hartmut Schmidt works at the University of Münster in Germany and wants to more easily detect this hereditary disease. „An effective therapy for Morbus Wilson exists that enables patients to live without any restraints“, the director of Experimental Transplantation and Hepatology says. „The disease needs to be diagnosed in an early stage, though. Otherwise those affected are going to die.“ Usually between the age of 12 and 16. Morbus Wilson is a mutation and affects copper metabolism: The body is not able to get rid off copper leading to an accumulation of the metal in liver cells which are destroyed subsequently.

Fluorescence as the chip language
© Schmidt

Until recently it has been quite difficult and also dangerous to diagnose Morbus Wilson since samples had to be taken from the liver increasing the risk of bleedings. After that a variety of tests had to take place. In contrary: A simple blood sample would suffice when detecting the illness with a gene chip. The development of such a chip requires a lot of genetic information, though. Knowledge that has been collected by Schmidt: „We have plenty of information about Morbus Wilson that others do not have.“ Stored in a data base comprising 1,730 DNA samples from patients from all around the globe - from Germany to China, Iran and Canada.

This data base has been the basis for identifying about 200 genetic traits that make up the docking stations on the gene chip. „If you apply a patient sample to the chip it starts to fluoresce when the docking stations score a hit“, Schmidt explains. A software registers the signal matrix and assesses whether Morbus Wilson is exsitent or not. That works for patients all around the world. „Our chip is a worldwide chip“, says Schmidt. This is important, since mutations connected to Morbus Wilson differ between countries and continents – even between Germany and Poland.

- Part 1: Molecules, Technique and Therapies
- Part 2: Monoclonal antibodies - specific attack on the bad ones

Part 2: Monoclonal antibodies - specific attack on the bad ones


„Please ask your physician or pharmacist about the risks and side effects“ - with the help of something called drug delivery the risks when taking drugs are going to be diminished. Biotechnology is supposed to help in the development of processes that directs medicine to its target where it can unfold its real potential without harming tissues and organs on its way. One big helper in this matter: monoclonal antibodies - immunological proteins that are being produced in the lab and that can find targets extremely specific.

Gerhard Moldenhauer has been developing such molecules for the last 30 years to be used in the diagnosis and therapies of diseases. „The future is going to be very bright. Three to five hundred types of monoclonal antibodies are being investigated in clinical studies at the moment. They are going to flood the market soon," the director of the Department Translational Immunology of the German Cancer Research Center predicts. The goal: Therapies against cancer, rheumatoid arthritis, allergic asthma and more.

When an antigen – a bacterium, a virus or foreign protein – gets into the body cells belonging to the immune system start producing different antibodies that attack the invader at different sites. The total of these different antibodies are called polyclonal. Scientists however want monoclonal antibodies – one and the same type in great numbers. The reason: Monoclonal antibodies made up of just one type identify collectively a predetermined target. A target defined by researchers beforehand.

Hat man seinen bestimmten Typ Antikörper, geht eine Heerschar von ihnen im Körper auf Suche und bindet sich. So können sie zum Beipiel auf Rezeptoren von Wachstumsfaktoren setzen und diese blockieren. „Tumoren werden quasi ausgehungert, da sie nicht mehr zum Teilen angeregt werden können“, sagt Moldenhauer. „Es ist aber auch möglich mit monoklonalen Antikörpern eine antikörperabhängige zellvermittelte Cytotoxizität auszulösen.“ Kurz: Die Antikörper docken an bestimmte Tumormarker und locken natürliche Killerzellen an, die die Geschwulst dann angreifen.

After having developed a specific type of monoclonal antibody, they deploy and search for their bodily target. They can, for example, block receptors for certain growth factors. „Tumours can be starved to death that way since they do not receive the signal to grow anymore," Moldenhauer explains. „It is also possible to initiate an antibody dependent cell cytotoxicity with monoclonal antibodies.“ That means: The immunological active proteins attract natural killer cells after having bound to a tumour.

Antibodies - proteins with potential

However, monoclonal antibodies are also of use in drug delivery: medicine, toxins, radioactive elements can be carried piggyback by the antibodies to a specific target. They dock to certain surface properties of a tumour, the passengers take care of the rest. „A lot of development takes place in this area," Moldenhauer says. The advantages are obvious: Chemotherapy puts a strain on the whole body, whereas monoclonal antibodies ensure that toxins only act on location. „Side effects with monoclonal antibodies are much less when compared to chemotherapy," Moldenhauer says. „Often it is best to use the therapies in combination, though.“

The production of monoclonal antibodies represents an important milestone in biotechnology. The market for these proteins is the fastest growing segment of the pharmaceutical industry. In 2007, more than 26 billion US dollars had been earned with them - mostly in the form of therapies against cancer and autoimmune diseases.

The next milestone is already in sight: „The next breakthrough for monoclonal antibodies will be their use against tumour stem cells," Moldenhauer believes. These cells are the reason why cancer sometimes reappears out of the blue. These cells are the real bad ones and only make up a very small amount of all cancerous cells. They seem to hide somewhere in the body - ready to strike again as researchers have observed with breast and pancreatic cancer: „You need to inject a million normal cancer cells in order to provoke the development of a tumour. With cancer stem cells one percent suffices.“ If it is possible to identify special markers carried by these cancer stem cells it would one day be possible to send out monoclonal antibodies in order to find them in their hiding places.

- Part 1: Molecules, Technique and Therapies
- Part 2: Monoclonal antibodies - specific attack on the bad ones