Recombinant human insulin produced in Poland has been saving lives at home and abroad for several years. This medication has brought many benefits to both the manufacturer and the government's budget. It is just as effective as its foreign counterparts, but much cheaper.

In the mid-1990s human insulin was among the leading drugs reimbursed by the government in Poland. Scientists from the Institute of Biotechnology and Antibiotics (IAB) in Warsaw decided to try to obtain this hormone in their laboratories. Usually, developing and launching the production of a new biotechnological medication with well-known effects, like human recombinant insulin, takes six to nine years on average. The project began in 1996, and just four years later the production technology was ready. The drug was registered in December 2000, and it went on sale at pharmacies on May 4, 2001. This fast-track procedure was made possible by the commitment of a large number of specialists. "At times, there were about 100 people working on the project simultaneously," says Dr. Piotr Borowicz, the IAB's director and one of the creators of the Polish insulin.

How they succeeded
Producing human insulin is one of the most complicated biochemical processes. Scientists have gotten Escherichia coli bacteria to do the work. These microorganisms dangerous to human health can be used to good purpose in laboratory projects due to the great possibilities they offer. Like most living organisms, E.coli bacteria contain genetic material. It is formed by a combination of genes tailored precisely to their owner's needs. As biotechnology developed, researchers began using these bacteria to produce different biological substances. To this end, they introduced into their genome some genes that code the desired proteins (this is called gene recombination), such as human insulin. The bacteria are "tricked" into becoming a factory of the human hormone. The hormone produced by E.coli is purified and then used to make medication.

The hormones made by different companies differ mainly in the technology used. The Polish insulin, as Borowicz says, is "a different structure, different idea and different implementation." He says the technology developed at the IAB is exceptionally high-yielding. "The bacteria produce insulin like mad," he says.

Money problems
Polish biotechnologists can make almost anything in their laboratories. Problems start when it comes to putting such products to practical use. Borowicz recalls the moment when the IAB asked the government to support the insulin project financially. "In the 1990s, when the idea to produce insulin emerged, it turned out that moving from the laboratory, where you are making a fraction of a milligram of protein of unspecified purity, to industrial production of hundreds of kilograms of the same protein of almost ideal purity (over 99.5 percent), was inconceivable to decision-makers," he says. "The Committee for Scientific Research (KBN), which disbursed government funds for science at the time, did not want to give us any supplementary funding, saying the product was very good, but the project unworkable. In the end, though, the government forked out zl.8 million, which covered just one-tenth of the total cost of the project," Borowicz says.

Persuading companies to invest in the project was no less difficult. The necessary funds were finally found thanks to Bioton, a company that the IAB had taken over in the first half of the 1990s, and its main shareholder Prokom Investments S.A., owned by Ryszard Krauze, one of Poland's wealthiest businessmen. From the start, it was assumed that the medication would be produced by Bioton, not the institute.

Work on the insulin project allowed the company to be launched on the Warsaw Stock Exchange in 2005. By the time the Polish insulin appeared on the market, under the brand name Gensulin, more than zl.80 million had been spent on the project. "Seeking funding was a hugely stressful, new experience. The investors simply did not believe the project could succeed. What could I promise them apart from my own absolute faith that we would be successful?" says Borowicz.

The researchers also had to win the trust of doctors from specialist hospitals. "They, too, could not believe that this was actually our product," Borowicz says. "A leading biotechnologist whom I finally brought to see the almost completed factory, almost fainted with surprise. He told me later that he had been unable to imagine that some company he had never heard of before could implement the project of his dreams."

Going international
Despite all these problems, the project was launched quickly. Today there are just a few producers of human insulin in the world. Before the launch of Gensulin, the Polish market was dominated by foreign companies, mainly Novo Nordisk and Eli Lilly, followed by Sanofi Aventis.

Last year Gensulin's share of the Polish market was about 25 percent. The Polish drug is also expanding to foreign markets; it is already available in 17 countries, including both Eastern Europe and nations such as Egypt, India, Pakistan, Jordan and Vietnam. Bioton says another 30 countries, including Argentina and Cuba, may soon register the medication.

Global annual production of insulin stands at about 6 tonnes, of which 200-300 kilograms is made at a factory in Macierzysz near Warsaw.

Borowicz says he and his colleagues have been extremely lucky in their work. "We just kept moving forward without hesitation, going out of our way to reach our goal," he says. But luck would not have helped much had it not been for the extensive knowledge, skills and experience of the whole team-not to mention the money, without which the project would have remained a pipe dream.

Work on recombinant human insulin gave the researchers not only theoretical but also practical knowledge that they could later use in work on producing human growth hormone (used in treatment for dwarfism and other growth disorders) and alpha interferon (used in treating hepatitis, for example).

The insulin project has shown that, contrary to popular belief, one can make money from science in Poland. Bioton reports that its net sales from insulin products stood at about zl.200 million in the first five years of production. In 2005 alone, this was about zl.82 million. The company has been employing more people year by year, starting from under 50 in 1993, up to over 520 in 2006.

For patients, Gensulin means a choice of one more pure insulin, and better access to treatment. Doctors admit that in terms of its effectiveness, the Polish hormone is no different from its foreign equivalents. From a technical viewpoint, if a synthetic protein is built correctly and is just as pure as natural protein, it is considered to be identical to the latter.

"The insulin made by Bioton is very good. There have been no complaints so far," says Andrzej Bauman, president of the Polish Diabetes Association.

Czesława Kicińska, a 60-year-old diabetic, switched from an imported product to the Polish insulin in September 2005. "I feel just as well as I did before," she says. "My doctor recommended the change, but the financial side of the deal was also important. Foreign insulin cost me about zl.60 per month. Now I use a fully reimbursed drug that costs a symbolic 1 grosz," Kicińska adds.

Market competition has forced producers to reduce their prices. It has also lowered the costs of reimbursing patients for insulin. The government's savings run into hundreds of millions of zlotys.
Anna Zdolińska


Diabetes in Poland
Some two million diabetics have been diagnosed in Poland. According to the Polish Diabetes Association, a further two million people may either be in a pre-diabetic state, or simply unaware that they have the disease. There are more than 230 million diabetics worldwide, including 25 million in Europe. Experts warn that this figure could reach 350 million within the next 20 years.

Diabetics are a special category of patient who need insulin throughout their lives and who will die without it. There are two main types of diabetes. Type I diabetes mainly occurs in children and adolescents and causes a deficiency of insulin in the pancreas. Type II occurs in older people, especially those who suffer from obesity or arterial hypertension. In Type II diabetes, cells fail to react to insulin. This inhibits their normal functioning as insulin regulates all the body's metabolic processes. Insulin ensures a constant supply of nutrients to all the cells in the body, both before and between meals, and irrespective of how long the interval lasts. Food is converted into the energy that enables you to function thanks to insulin. From this viewpoint, diabetes may be compared with a power grid failure in a large country. The disease can lead to serious metabolic and energy production disorders. For the rest of their lives, diabetics have to take either insulin or drugs to normalize blood sugar levels. Before human insulin was successfully synthesized, diabetics had been administered bovine or porcine pancreas extract. Taking this preparation over a long time, however, sometimes resulted in complications such as allergies and could lower the body's sensitivity to hormone action.