Nathaniel Martin is an expert in antibiotic research and a professor of biological chemistry at Leiden University. He is also a member of the NCOH Executive Board. Learn more about his domain of expertise, the challenges he faces, his role in NCOH and his personal motivation as a scientist.
What type of research do you do?
As bio-organic chemists, we use chemistry to make new and better antibiotic molecules. One of the most successful approaches for doing so is via a technique known as semisynthesis, where you start from an antibiotic molecule that is known to exist in nature and make it better. Many of the antibiotics we use in the clinic are actually natural products or are derived from natural products. Often microorganisms make an antibiotic to give themselves a competitive advantage against other bacteria. Of course, nature has not optimized these antibiotics for use in humans. Semisynthesis offers the possibility of taking nature’s antibiotics and making them better medicines.
How can you turn these natural compounds into an antibiotic for humans?
Microorganisms that produce these antibiotics generally live in environments like the soil, certainly not the bloodstream of a human. Some high-level chemistry is needed to improve these molecules to make them better drugs in the human body. That’s really fun. You can make them more active as an antibiotic or reduce their toxicity. And once we’ve synthesised new antibiotics, we also have the expertise in the lab to assess how well these molecules work as antibiotics. We also collaborate with other groups to see what these new antibiotics do in animal models. In recent years, we’ve taken a number of new compounds to the stage of testing to see how well they cure infections in animals, this primarily mouse infection models.
For an antibiotic molecule, what is the biggest difference between the bloodstream and the soil?
The bloodstream of a human represents a really challenging environment for a molecule to exist in, because our bodies are very well adapted to get rid of foreign molecules. A big challenge in drug development is to make a molecule that is stable enough in the bloodstream or in the gut to cure the disease. So it’s quite amazing how many antibiotics from soil dwelling organisms are even able to work in a human body.
Is it easier to develop a vaccine rather than a new antibiotic?
If we consider the most recent successes in vaccine development, so the development of COVID-19 vaccines, we can see that if you have enough financial backing and an urgent enough medical need, things can happen very quickly. I think if we as a society were faced with a doomsday bacterium that was resistant to all of our antibiotics, we would be surprised how quickly we could develop an antibiotic against it. So I wouldn’t say it’s easier to develop a vaccine compared to an antibiotic. It’s more a matter of having financial backing and a real urgency.
How will things look in the future?
Antibiotic resistance is rising quickly. Some predictions suggest that by 2050 up to 10 million deaths will be caused by drug resistance, mostly in developing countries. Then we will have more people dying of antibiotic resistance than of cancer. That’s unbelievable. In many cases the infections that are killing people, so the drug-resistant infections, could have been prevented and cured with an available antibiotic thirty years ago. So, we are actually moving backwards in terms of the global healthcare system.
The science is already very good at understanding the opportunities we have for developing antibiotics. But we also need the industry. There are a number of small businesses working on the problem, but it’s almost impossible for them to earn enough money because of the financial hurdles they face. It’s not a money maker for the industry, but with a strong push from the government we could quickly put some new antibiotics to the market. I’m an optimist.
What is your role in NCOH, besides principle investigator?
I’m a member of the NCOH Executive Board. So we meet regularly to discuss the different initiatives, plans and visions the NCOH has for future research, not only in antibiotic resistance of course, but in all sectors of human health that have a One Health element.
What benefits do you think NCOH has?
I think it pools the strength of Dutch research institutions together into one focused body. It can also help to connect researchers more rapidly, make people aware of what others are doing, identify the opportunities and maybe prevent redundancy in certain activities. It’s an important and useful collective.
The next NCOH Science Café will be organised in Leiden. The topic is Antibiotics and beyond. What can we expect?
We want to have a broad discussion about the opportunities of developing antibacterial agents for future therapeutics. There’s a lot of exciting science from the last decade on next generation therapies that haven’t been exploited in treating bacterial infections. This may involve antibody therapy or maybe the use of viruses that target bacteria, but don’t harm human cells. To explore the topic, we have some excellent speakers from UMC Utrecht, TU Delft and Naturalis.
What do you do in your free time?
I go running two or three times a week and that gives me a great opportunity to clear my mind and come up with new ideas. My wife and I have two young kids which makes for a busy but fun life away from the lab. Travelling is something else I enjoy and is part of the job that can provide opportunity for new experiences. Attending conferences or visiting other universities often means meeting interesting people and seeing other parts of the world.
What do you get out of bed for?
This morning it was easy to get out of bed because I had to give a 9:00 AM lecture to students on a topic I am very enthusiastic about. In my experience as a teacher, students are most engaged when they can appreciate why you think what you do is exiting. I also get a great boost from seeing the new and exciting results generated by the PhDs and postdocs working in the lab.
That is a great feeling to get out of bed for, but still work-related. Do you also have a guilty pleasure?
I’m from Canada and I really love North American sports, I like watching and playing baseball and ice hockey. I also enjoy a good whiskey, I wouldn’t call that a guilty pleasure though – it’s a good pleasure!
Update from the NCOH Executive Board
Last year we eagerly prepared the discussions on the continuation of NCOH after its first funding period. In June we celebrated the first 5 years of NCOH, and NCOH will now continue for at least 5 more years until 2027! The Executive and Supervisory Board members were involved to shape the new contours and have committed for this time. Currently, the Executive Board is preparing an application for the National Growth Fund, aimed at increasing the national preparedness for infectious disease outbreaks.
On the 1st of July 2022, the University of Groningen entered into partnership with NCOH. NCOH is very pleased to welcome its new Partner! Please read more about the accession of our new Partner in this newsletter.
Last but not least, we would like to thank prof. Geert de Snoo (KNAW, NIOO) for his commitment as the Chair of the NCOH Supervisory Board during the last three years. He was very much involved and guided through the new term of NCOH. We would also hereby like to take the opportunity to welcome the new Chair of the Supervisory Board, Pancras Hogendoorn (LUMC). We are very pleased he has accepted the position of the chair and look forward working with him.