Herceptin- A case of Perseverance in Drug Development

From concept to commercialisation,  drug development takes decades.  The process demands a concerted, multi-disciplinary approach involving several agencies.  The time span is too long for   people and management  to remain committed to the cause. That almost happened to  Herceptin,  the best drug now available  in the market for HER2 positive  breast cancer.  Now in living tissues   HER-2 protein is the  biochemical signal for  cells to grow and multiply.   When the levels of   HER-2, become abnormally high, cells are  provoked  to  mushroom at an alarming rate and that is cancer. This type of cancer is also referred to  as HER2 positive.  Herceptin moieties  attach themselves to HER2 receptors and suppress them. The uniqueness of  herceptin  is that it doesn't have the debilitating side effects of either chemotherapy or radiotherapy. 

Herceptin,  has the generic name Trastuzumab which in WHO nomenclature is loaded with information. While Tras is a euphonic prefix,  tu stands for miscellaneous tumours, zu for   humanised and mab for   monoclonal antibody.  This drug was  developed jointly by  scientists at the biotech company  Genentech and the University of California,Los Angeles.  Axel Ullrich of Genentech and Dennis Slamon of UCLA were at the helm in the beginning. When Ullrich moved to Max Planck Institute of Biochemistry, it fell on Slamon to see the project through.  In retrospect, the timeline presents a hazzle free smooth roadmap, as easy as connecting the dots: for example  the seventies provided  the concept of monoclonal antibodies; by the eighties  the HER2 gene was cloned  and its role in   breast cancer  established; beginning of  nineties saw the  design and creation of herceptin and by 1998 the FDA approval was in place.  But it wasn't a smooth sail at all.  Science journalist Robert Bazell tells the story in great detail in  his book  Her-2 :The making of Herceptin, a revolutionary treatment for breast cancer. Scientific hurdles apart, there were parties with vested interests. 

New England Journal of Medicine in its review described the book  as  the story of the triumph of an inspired clinician against great opposition, which included his own colleagues, grant-awarding agencies, and pharmaceutical companies. Robin M. Henig , wrote      in    The New York Times     : Populated with single-minded scientists, clueless biotech company executives and women stricken with a particularly vicious form of breast cancer -- one that rages so fiercely that it can erupt along the fault lines of a mastectomy incision even before the scar heals -- ''Her-2'' is about the making and marketing of an entirely new kind of cancer therapy. 
Later the book was made into a telefilm " Living Proof" 

REFERENCES:

1. Genentech Her2 Story

2. HER-2: The making of Herceptin, a Revolutionary Treatment for  Breast cancer by Robert Bazell, Random House 1988 ISBN 13: 978-0812991840

Lights off please, let them work !

Time to time NASA releases images of Earth at night. These are  night maps of human activity.  In these snapshots  Mother Earth seems  like a diamond studded field.  Eastern US , Western Europe and Japan are the most glittering areas in the map with Africa remaining true to its name:  Dark Continent-  leading to   rather confusing trend  of equating a nation's development index to its energy consumption.  NASA's  nighttime images have multiple objectives- to collect  climatic & meteorological  data, to spot oceanic activities such as  unregulated fishing  and  of course they could serve as surveillance maps- monitor ing clandestine activities in war zones.  

Earth at Night  Courtesy NASA

But there are others who strongly believe that  such images  can be used as powerful tools to monitor Light Pollution and take necessary steps to protect  endangered and fragile ecosystems.  Light Pollution? Are we waking up to a new threat?   Not exactly. We have been unconsciously aware of this issue for quite some time now but didn't take it seriously. For example when did we last spot  the glow of fireflies in our garden?  Scientists have attempted to quantify the danger of depleting nocturnal visitors.  In a research  article published in the 10th August issue of Nature,  Eva Knop and coworkers alert us to the dangers of  ALAN (Artificial Light At Night).     Knop et al provide data on how ALAN  adversely affects the habitats of nocturnal species consequently how  their population has registered  a global decline. Nocturnal pollinators (insects and animals) are essential for sustaining Nature's biodiversity.   The research team is  apprehensive that dwindling   nocturnal pollinator population will eventually affect   the well-being of  diurnal pollinators too because  decreased pollen transport means reduced food availability. In their detailed study, which covered  14 wild meadows ( 7 test fields, and 7 controls), the team  monitored  interactions between flowers(plants)  and their nocturnal visitors. They recorded  that in illuminated fields,  nocturnal visitors  flocked towards the light source,  totally  neglecting the flowers with the result that  pollinator -flower contacts were  reduced by 62%.  

Several earlier studies highlight the issue and provide detailed  cost-benefit analyses of artificial nighttime  lighting on the environment. Perhaps for our part we could switch off our porch  and garden lights and thus encourage   fireflies to visit us.  But there a lurking dangers-  a house wrapped in darkness might attract burglers and thieves too. 

Tailpiece:

Day and Night is a 6 minute animated film (2010) in which an exuberant guy  Day, encounters  Night who is forever a gloomy.  The initial  intense dislike between them soon turns into a unique friendship when each realises that  that they are just two sides of the same coin. 

REFERENCES:

1. Artificial light at night as a new threat to pollination.Knop et al, Nature 548 p.206-9 2017

2. The dark side of street lighting : impacts on moths and  evidence for the disruption of 
    nocturnal pollen transport  Macgregor et al  Glob.Change Biol. 23, 697-707 2017

3. Ecological consequences of Artificial Night Lighting: edited by Catherine Rich and 
     Travis Longcore, Island Press 2013