Nicholas Lydon
(February 27, 1957-      )
Born in England
Years of Discovery: 1990s

Lydon1280px Nicholas LydonGleevec is Cause for Glee for Leukemia Patients

Cancer doctors witnessed the results with awe and amazement.  Their patients who teetered near death, previously without hope, were leaving the hospital, feeling well, full of new optimism, after being dosed with a new drug.  Gleevec is the “Magic Bullet” drug that attacks only the molecule which causes a form of leukemia (chronic myelogenous leukemia - CML), a ray of hope from teams of scientific minds led by Nicholas Lydon and Brian Druker. 

CML is one of the four main types of leukemia and begins with a change to a single stem cell.  The American Cancer Society predicts that in 2021 over 9,000 adults in the United States are expected to be diagnosed with CML.  Prior to 2001 when Gleevec was approved, CML was treated by chemotherapy, radiotherapy and bone marrow transplants.  Over 52% of patients diagnosed with CML died.  Today, over 90% of patients diagnosed with CML will survive beyond 5 years. Gleevac has switched CML from a fatal cancer to a manageable chronic condition.

Nicholas Lydon began his scientific journey at the University of Leeds in England where he received his bachelor’s degree in biochemistry.  He went on to complete his PhD in biochemistry at the University of Dundee in Scotland.  From 1982 to 1997 Lydon researched interferon, originally in Paris then in Basel, Switzerland. Lydon was recruited by Alex Matter to become the leader of the protein kinase inhibitor program at Ciba-Geigy Corporation, which would later become Novartis. A kinase is a type of enzyme that transfers phosphate groups in human cells. Kinases, of which more than 500 have been identified, transmit signals and control complex processes in cells.

In the late 1980s Lydon was introduced to oncologist Brian Druker.  At this time Druker was expanding his expertise in tyrosine kinases and Lydon was interested in developing tyrosine kinase inhibitors. Inhibitors are tiny molecules that fit themselves between two puzzle-like pieces of kinases, blocking the phosphate messages they are trying to send to each other. It turns out that in order for leukemia (CML) cells to grow they need a specific protein - BCR-ABL associated with tyrosine kinase. Stop it and maybe the cancer will stop. When Druker began looking for a tyrosine kinase inhibitor his very first call was to Lydon, who was anxious to begin testing several inhibitors he thought might be promising.

“My vision was to come up with a small molecule drug that would specifically bind to this protein, and not to other proteins in the body that use the same mechanism,” explained Dr Lydon.  Druker screened Lydon’s compounds in human bone marrow cells, and one named STI571 stood out. STI571 targeted a section of the BCR/Able protein and it excelled at killing CML cells, leaving surrounding healthy cells unaffected.   “At that point I knew we had a potential drug,” says Druker.  Finally in 1996 the two scientists were successful in accomplishing development of the drug at Novartis. It was named Gleevec.

Over the next years they tested the drug. Usually with new drug trials, even promising drugs only improve a few more patients than other drugs, and then only marginally. But 53 of the 54 patients in the first drug trial with Gleevec markedly improved. Given the great results, they expanded the trial.  Knowing that it was working for patients in the chronic or stable phase of the disease, they offered it to patients in “blast crisis,” the name given to the late stage eruption of cancer.  That is when the most remarkable thing happened.  Patients who were at death’s door, were up and about and leaving the hospital within a week of their first dose. Less than 3 years after the first clinical study, in 2001 the US Food and Drug Administration approved the drug. Now, the five year survival rate for CML patients is close to 90%. 

Another remarkable feature of the Gleevec story is that it is a new type of attack on cancer that has revolutionized drug development. Rather than trying to kill the cancer cells without killing other cells, which is the chemotherapy approach, Lydon and Druker targeted specific molecules inside the cancer cells. Already there are more than 500 drugs in development based on this new approach. According to Lydon, "The approval of Gleevec in 2001 represented a breakthrough in the treatment of cancer, yet we are really just starting to see the full promise of small molecule kinase inhibitors as targeted therapies for cancer and other important diseases." Gleevec is currently used for CML, gastrointestinal stromal tumors, and five other cancers.

In October of 2009 Lydon won the Lasker DeBakey Award, one of the highest honors in American science. Lydon was nominated for the Lasker Award by Professor Sir Philip Cohen, a leading biochemist from the University of Dundee, where Lydon received his PhD.  The Lasker award is shared with colleagues Brian Druker and Charles Sawyer. Sawyers’ work designed a second-generation inhibitor when resistance to Gleevec developed in some patients.  

Lydon currently leads Granite Biopharma LLC, a consulting company he formed in Jackson Hole, Wyoming.

Written by science writer, April Ingram


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Snippets
Nicholas Lydon Quotes
We were constantly bombarded with criticism at the time. The view then was that cancer was far more complicated and people didn’t believe that targeting a single genetic abnormality would be sufficient.

Our most optimistic expectations were exceeded beyond our wildest dreams.

Do-developer Brian Druker on Nick Lydon
Breakthroughs don’t come about without lots of different areas of investigation converging. We shared a common vision — to get a tyrosine kinase inhibitor into the clinic. Nick was always willing to share data and was a true scientific collaborator.


Charles Sawyer, Brian Druker, and Nicholas Lydon
Receiving the Lasker Award for Medical Innovation
LydonLaskerAwards2009


Key Contributors
Nicholas Lydon 
Brian Druker 
Charles Sawyers 


Links to Information on the Scientist and Science
Journal of Clinical Investigation
https://www.jci.org/articles/view/41141/pdf
Nicholas Lydon's Wikipedia page
https://en.wikipedia.org/wiki/Nicholas_Lydon