World of Genomics: Germany

Original piece written by Shannon Gunn, 2021. Updated by Lyndsey Fletcher, 2023.

In this week’s World of Genomics entry, we explore Deutschland, known more commonly as Germany. Despite the strength of basic science within Germany, it got off to a late start in genetics-related research. However, more recently, Germany has been a key figure in advancing science and contributing to successes within medical genetics. Germany is also home to some amazing scientists and Nobel Prize winners!

The population of Germany  

Germany is a country in Central Europe, and the second-most populous country in Europe (after Russia). Ancient humans were present in Germany at least 600,000 years ago. The first people to inhabit the region now called Germany were Celts. They were gradually displaced by Germanic tribes moving down from the north. The Federal Republic of Germany, the current German government and constitution were established in 1949. Germany has a complex history, including the Weimar Republic, Nazi Germany, East Germany and the reunification of Germany. Germany has a strong economy and is a global leader in several industries, including science and technology.

Geographic and demographic information

Summary statistics:

• Land area: 357,022 km²
• Gross domestic product (GDP):
  • Total: $4.26 trillion (2021)
  • Per capita: $51,203 (2021)

Population statistics

• Population size: 83.2 million (2021)
• Birth rate: 9 per 1,000 (2020)
• Death rate: 12 per 1,000 (2020)
• Infant mortality rate: 3 per 1,000 (2021)
• Average life expectancy: 81 (2020)
  • Male: 79 (2020)
  • Female: 83 (2020)
• Ethnicity: German (88.2%), Turkish (3.4%), Italian (1.0%), Greek (0.7%), Serb (0.7%), Russian (0.6%), Other (5.5%).

Healthcare system

Germany was the first country in the world to establish a nationwide social health insurance system, in 1883. Health insurance is mandatory in Germany. They have adopted a multi-payer healthcare system paid for by a combination of statutory health insurance and private health insurance. This ‘all for one and one for all’ approach (or ‘solidarity principle’) ensures that everyone gets the same treatment. The public health system provides extensive in- and out-patient care.

All workers contribute about 7.3% of their salary into the public health insurance pool, which is matched by employers. For those who contribute to the public health scheme, all dependents living at their address are covered by their insurance. The higher you earn, the more you pay, up to a limit of €4,425 a year. If you earn above this threshold, you will not be charged higher fees, but you can opt to take out private health insurance. Others who can opt for private insurance include those who earn under €450 per month, students between the ages of 23-30, self-employed individuals and civil servants. Germany’s spending on healthcare is relatively high, just over 12.8% of its budget.

All German individuals must also be enrolled onto the long-term nursing care scheme. The contribution is 2.8% of one’s salary, up to a limit of €123 per month, and is also split between employee and employer.

With an expanding population and inflation of medical costs, health insurance costs are increasing. In addition, many doctors in Germany earn less than in some other countries, meaning many doctors migrate to other places. This has meant that the German healthcare system has strongly relied on recruiting foreign qualified doctors.

Health priorities

The most common cause of death in Germany is cardiovascular disease, accounting for 35.3% of all deaths in 2019. The second most common cause is cancer, accounting for a quarter of all deaths. Diseases of the respiratory system are also one of the main causes of death. There are several prominent risk factors in Germany. In 2014, 21% of adults smoked tobacco every day. To address this issue, in 2021 the ‘Strategy for a Tobacco Free Germany 2040’ was published, which details plans to decrease the number of smokers to less than 2% of the population within the next two decades. While smoking and alcohol consumption have generally declined, binge drinking remains problematic (and is the fifth highest in the EU). Another growing concern is obesity, with a quarter of adults in Germany being obese.

In addition, along with many other countries, a major issue is the ageing population. An ageing population not only puts additional pressure on the healthcare system, but it also increases the prevalence of chronic and age-related conditions, like dementia.

Surprisingly, in recent years, scabies has been diagnosed more frequently. The number of prescriptions against scabies increased from 38,000 in 2016 to 61,000 in 2017. In 2022, the incidence of scabies was around 52.6 per 100,000 individuals. It is currently unclear why the prevalence is rising.

Genomic medicine capabilities

Due to restrictive regulations, Germany has lagged behind other countries in genetic diagnostic capabilities. This has meant that meaningful diagnostic tests were not being offered to the majority of patients. For example, doctors were only allowed to invoice the health insurance companies for sequencing up to 25,000 of the three billion base pair of the human genome. This is equivalent to about four genes. Some conditions, like mental disabilities, have as many as 1,000 genes known to be involved. Fortunately, in 2021 Germany removed the prior authorisation requirement for sequencing analysis by public health insurers. This means that the entire population now has better access to diagnostic approaches. Also in 2021, Illumina announced an agreement with the Institute of Medical Genetics and Applied Genomics at the University Hospital of Tübingen to assess the value of whole-genome sequencing (WGS) as a first-line diagnostic test for patients with genetic diseases and familial cancer syndromes. The project, called Ge-Med Project, uses the data to generate polygenic risk scores which will help identify individuals that may benefit from personalised medicine. The Institute is the first laboratory in Germany accredited to perform clinical WGS.

Germany has placed bans on the cultivation and sale of GMOs. They also have strong restrictive regulations that ban direct-to-consumer testing, with only a medically qualified practitioner being able to request genetic testing.

The nationwide newborn screening program in Germany was established in 2005. It includes diagnosis of hypothyroidism, congenital adrenal hyperplasia, biotinidase deficiency, galactosemia and phenylketonuria (PKU). The costs of this program are covered by public health insurance. As of 2022, 19 diseases were screened for as standard. Apparent increases in the prevalence of these diseases over the last two decades are likely due to increased testing.

Despite advances in the field, a remaining knowledge gap, uncertainty regarding test reimbursement and physicians’ lack of awareness of existing pharmacogenomic clinical support systems mean that there is still a way to go in implementing genomic medicine in clinical practice.

Notable projects

• genomDE: genome DE is a national genome initiative that aims to improve the prevention, diagnosis and treatment of diseases by scaling access of genomic data, as well as linking it to clinical and phenotypic data.
• 1+Million Genomes Initiative: In 2020, Germany signed the Declaration, “Towards access to at least 1 million sequenced genomes in the EU by 2022”. This collaboration aims to improve disease prevention, allow for more personalised treatment and enable clinically impactful research.
• The German Human Genome-Phenome Archive (GHGA): The GHGA is an omics data infrastructure that hopes to bridge the gap between research and healthcare whilst keeping data safe and secure.

Notable organisations and companies

• Max Planck Institute for Molecular Genetics: Max Planck Institute for Molecular Genetics is a research institute for molecular genetics based in Berlin. The Max Planck Society was founded in 1911.
• The German Cancer Researcher Center: The German Cancer Research Center is a national cancer research centre founded in 1964.
• Merck: Founded in 1668, Merck is a multinational science and technology company operating across healthcare, life science and performance materials.
• BioNTech: BioNTech, short for Biopharmaceutical New Technologies, is a German biotechnology company founded in 2008 that develops and manufactures active immunotherapies. It develops pharmaceutical candidates based on mRNA.
• EMBL: European Molecular Biology Laboratory (EMBL) was created in 1974 to support molecular biology research. The headquarters is based in Heidelberg.
• Several pharmaceutical companies were founded in Germany, including Bayer and Boehringer Ingelheim.

Notable individuals

• Charlotte Auerbach (1899-1994): Auerbach was a German geneticist who contributed to founding the science of mutagenesis. She discovered that mustard gas could cause mutations in fruit flies.
• Christiane Nüsslein-Volhard (1942-): Nüsslein-Volhard is a German developmental biologist and 1995 Nobel Prize-winner. She is known for her work on protein-DNA interactions. She won her Nobel Prize for her research on the genetic control of embryonic development.
• Franz Josef Kallmann (1897-1965): Kallmann was a German-born American psychiatrist. He fled Germany in 1936 for the United States, because he was of Jewish heritage. He was one of the pioneers in the study of the genetic basis of psychiatric disorders. He also developed the use of twin studies in assessing the role of heredity and environment in psychiatric disease.
• Jan Korbel: Korbel is a researcher at EMBL, who focuses on genomic structural variations and their impact on human health.
• Klaus Pantel (1960-): Pantel is the Chairman of the Institute of Tumour Biology at The University Medical Centre Hamburg-Eppendorf. Alongside Catherine Alix-Panabières, Pantel coined the term ‘liquid biopsy’ and is a major player in this field.
• Klaus Patau (1908-1975): Patau was a German-born American geneticist. He reported the extra chromosome in trisomy 13 in 1960 (also called Patau syndrome).
• Rolf Apweiler: Apweiler is a director at EMBL-EBI. His work has focused on creating efficient, automated ways to annotate proteins.
• Rudolf Jaenisch (1942-): Jaenisch is a Professor of Biology at MIT and a founding member of the Whitehead Institute for Biomedical Research. He is also a pioneer of transgenic science.
• Walther Flemming (1843-1905): Flemming was a German biologist and a founder of cytogenetics.

Future Genomics Landscape

Despite a slow start, the value of advanced genomic technologies has become increasingly apparent in Germany. In order to ensure the successful integration of genomic medicine into the healthcare system, several challenges still remain, including the need for a more specialised workforce. In addition, Germany’s healthcare system is decentralised, making it difficult to establish uniformed quality standards. Developing standardised quality assurance standards is important, particularly in laboratories. Furthermore, experts have emphasised the importance of storing data in a central database to support seamless cooperation between researchers and healthcare.

Despite having to play catch up with other nations, continued collaborations and regulatory reviews will help with the implementation of genomic medicine in Germany, ultimately improving patients’ lives.

References:

Britannica. Germany. Available at: https://www.britannica.com/place/Germany

World Banks. Indicators. Available at: https://data.worldbank.org/indicator

Academics.com. Health Insurance Germany. Available at: https://www.academics.com/guide/health-insurance-germany#subnav_public_health_insurance_how_much_does_it_cost

The Commonwealth Fund. 2020. International Health System Profiles. Germany. Available at: https://www.commonwealthfund.org/international-health-policy-center/countries/germany