Manufacturing Human Insulin

Insulin is a hormone that controls the level of glucose (sugar) in the blood. People with diabetes cannot make enough insulin of their own, so many of them need to inject insulin to stay healthy.

The problem is supply: huge numbers of people need insulin, so we must be able to make large quantities of it. In the past, insulin was taken from the pancreas of animals such as pigs and cattle. Today, almost all insulin is made by genetic engineering using bacteria.

The big idea of this topic is this: we can move the human insulin gene into a bacterium, then grow those bacteria in huge numbers so they make human insulin for us. Because bacteria reproduce very quickly, this lets us produce large amounts of insulin that is identical to human insulin.

Exam tip. Be ready to state that insulin is used to treat diabetes, and that GM bacteria let us make large quantities of human insulin. These are common one-mark points.

Genetic engineering uses two special enzymes to move the gene. You should know what each enzyme does.

Step 1 — Cut out the gene. A restriction enzyme is used to cut out the human insulin gene from human DNA. A restriction enzyme acts like 'molecular scissors' — it cuts DNA at a specific place.

Step 2 — Cut open the plasmid. A plasmid is a small circular piece of DNA found in bacteria. The same restriction enzyme is used to cut the plasmid open. Because the same enzyme is used, the cut ends of the gene and the plasmid match each other (they have matching 'sticky ends').

Step 3 — Join the gene into the plasmid. The enzyme ligase is then used to join (stick) the insulin gene into the plasmid. The plasmid now carries the human insulin gene and is called a vector (something that carries the gene into the bacterium).

You can picture the sequence like this:

Exam tip. Examiners want the right enzyme for the right job: restriction enzyme = cuts, ligase = joins (sticks together). Mixing these up is a very common error.

Once the plasmid carries the human insulin gene, it is put back into a bacterium. The bacterium has now had a gene from a different species (a human) added to it, so it is genetically modified (GM) — also called transgenic or genetically engineered.

Two ideas matter here:

1. The plasmid acts as a vector — it carries the human insulin gene into the bacterium.
2. Because the bacterium now contains the human insulin gene, it can read that gene and make human insulin, just as a human cell would.

So a single bacterium now has the instructions to produce human insulin. The next stage is to grow enormous numbers of these GM bacteria so they make insulin in large amounts.

Exam tip. Use the correct phrase: the plasmid (vector) is put back into / taken up by a bacterium, which becomes genetically modified. Saying the bacterium 'now contains the human insulin gene' scores well.

To make large amounts of insulin, the GM bacteria are grown in a fermenter — a large container (tank) used to grow microorganisms in ideal conditions.

Inside the fermenter the bacteria are given everything they need to grow and reproduce quickly:

• Nutrients (a food/sugar supply) so they can grow.
• The right temperature, kept steady so the bacteria grow fast but their enzymes are not denatured.
• The right pH for growth.
• Often oxygen (stirred or bubbled in) for respiration.

In these ideal conditions the GM bacteria multiply (reproduce) very quickly, so there are soon billions of bacteria, all carrying the human insulin gene and all making human insulin.

Finally, the insulin is extracted (separated) from the fermenter and purified so that it is pure enough to be used as a medicine. This purified human insulin is then used to treat people with diabetes.

Exam tip. A full-mark sequence is: GM bacteria placed in a fermenter → given nutrients, correct temperature and pH (ideal conditions) → bacteria multiply/reproduce → they make human insulin → insulin extracted and purified.

Before genetic engineering, insulin was taken from the pancreases of animals such as pigs and cattle. Insulin made from GM bacteria has several advantages over animal insulin:

• It is identical to human insulin (animal insulin is slightly different), so it works better.
• Because it is identical to human insulin, it is less likely to be rejected or cause an allergic reaction.
• It can be made in very large quantities to meet the high demand.
• It is usually cheaper to produce than extracting insulin from animals.
• It avoids animal welfare and ethical issues — no animals need to be killed to obtain it. This also suits people whose religion or beliefs mean they do not want animal (e.g. pig) products.
• Production can be scaled up quickly because bacteria reproduce so fast.

Exam tip. If asked for advantages, give clear, separate points: identical to human insulin, less rejection, large quantities, cheaper, and no animal welfare/ethical problems. Vague answers like 'it is better' score nothing — name the actual advantage.