The incredible achievements in medicine over the last 100 years has done wonders to extend the human lifespan. Advances like medical imaging, antibiotics, vaccination, and others have allowed people today to live roughly three decades longer than they did in 1900.
Now, with the advent of precision treatments and genome editing, we are on the brink of another revolution in medicine. Two Nobel Laureates in Chemistry, Aaron Ciechanover and Ben L. Feringa, discussed the next wave of technologies for treating patients during their Agora Talk on Monday, the second day of the 70th Lindau Nobel Laureate Meeting.
A New Revolution in Medicine
“Personalised medicine is going to be a suit-like medicine, tailored to our genetic make-up,” said Ciechanover, who received the 2004 Nobel Prize in Chemistry for the discovery of ubiquitin-mediated protein degradation. “Rather than just treating a disease, we are treating a disease within the context of a patient.”
When he was studying medicine, the tools for investigating the underlying molecular mechanisms of a specific patient’s disease did not yet exist. If a patient had a tumor, for instance, doctors would use medical imaging such as X-ray or computed tomography (CT) to determine whether surgery could extract the mass.
“If the tumor was not resectable because it was too big or touching essential organs, then you try to decrease its size by chemotherapy or radiation… which are like shooting a fly with a cannon,” he said. “They are not discriminating between healthy tissue and sick tissue.”
In the early 2000s, the first human genome sequences were published in nearly complete draft form, which marked the beginning of a new era in medicine. In the twenty years that have passed since that pivotal discovery, researchers have made enormous progress in leveraging that knowledge of our genetic makeup towards improving the precision and personalization of medicine.
Many patients with cancer today are no longer subjected to a one-size-fits-all treatment regimen that comes with adverse side effects and damage to healthy tissue. Instead, tumor sequencing performs analysis at the molecular level in order to identify genetic mutations that drive their particular disease. By knowing the underlying mechanism, the cancer can then be treated with targeted therapies that often work more efficiently and with less side effects than chemotherapy and radiation therapy.
“With the new revolution of personalised medicine, we are going to change dramatically the basic three fundamental definitions upon which medicine is standing: disease, patient, and treatment,” he said.
In other words, with the refinement of genome editing techniques like CRISPR/Cas9, the disease might be found in the sperm or egg through genetic screening and edited out before it can even manifest in a human being. Such advances would represent a complete paradigm shift for medicine that has the potential to eliminate the burden of disease and extend the human lifespan to its limits.
Improving the Precision of Pharmaceuticals with Light
Feringa took less of a big-picture approach to his Agora Talk and focused on one particular aspect of precision medicine, a budding field known as photopharmacology. Pharmaceutical development has gone through various stages throughout history, from drugs being discovered purely by accident to high-throughput screening of small molecule compounds. Today, the more sophisticated approach involves looking at the genome to find specific disease targets where naturally occurring or man-made molecules can interfere.
However, he believes that researchers in the field can go a step further by incorporating light-dependent controls into pharmaceuticals in order to boost their precision.
“Photopharmacology is a development that you see now around the world of people building light switches into the molecule,” said Feringa, who received the 2016 Nobel Prize in Chemistry for the design and synthesis of molecular machines. “You switch your computer on and off, and you switch your smartphone on and off. Here you take advantage of new developments in physics, chemistry, and molecular biology to switch on the activity of a drug on the spot.”
These smart pharmaceuticals, as he calls them, would add a level of spatiotemporal specificity to treatment with drugs that does not currently exist. Two main areas of application include photocontrolled antibiotics and precision chemotherapy. For example, take the situation of a patient given a broad-spectrum antibiotic modified with a light-dependent molecular switch. Exposure to light would activate the antibiotic only in the part of the body with the infection, and only for a controlled amount of time, which prevents resistance build-up. Or imagine an photocontrollable anti-tumor drug that is given to a patient. Doctors would only illuminate the cancer tissue to switch on the drug, while healthy tissue is kept in the dark and spared.