Showing posts with label cancer. Show all posts
Showing posts with label cancer. Show all posts

Tuesday, August 16, 2016

Our Genes




In the Mahabharata epic, there is a poignant exchange that takes place after the Great War, between the eldest of the Pandava princes, Yudhistira, and a forest spirit. A quiz in metaphysics is the price demanded by the Spirit for reviving Yudhistira's siblings who have died of thirst and poisoning.

One of the questions is: 'What is the greatest wonder in the world?'
And Yudhistira's reply is : "People die everyday and those who are alive go on as though they will live for ever!"

Siddhartha Mukherjee's books seems to capture this profound irony in his first book, "Emperor of All Maladies" and then again, in his latest book, "The Gene". A 'normal' healthy body and mind is something most of us take for granted - even as an entitlement - until something happens to us, or to our own close friends or relatives that brings us face to face with the fragility of life itself.

The great advances in science & technology lull us into a false sense of security - until raconteurs like Mukherjee tell us about the heroic efforts, pain and serendipity that underpin each and every invention that mark our progress, as well as the huge lacunae in our own understanding of the world around us, and within us.

Here are a couple of shockers that hit me while reading "The Gene"

There are more than 2500 different genetic defects that have been recorded to date. Most of them are like simple spelling mistakes that end up destroying lives, across generations.

Take the case of Sickle Cell Anemia. It is the result of a single change in one triplet in our DNA. The sequence GAG gets changed to GTG. This results in the substitution of one amino acid for another: glutamate gets switched to valine, thus altering the folding of the hemoglobin protein chain. As a result protein debris gets accumulated in string like clumps in our red cells; they are unable to glide smoothly through our blood capillaries, and get jammed into microscopic clots throughout the body, interrupting the flow of blood, and resulting in excruciating pain, like corkscrews being drilled into our bones.

Then there is Huntington's Chorea. It is the "opposite of a dance, a joyless pathological caricature, the ominous manifestation of dysregulated brain function".

In 1992 researchers tracked the disease down to one gene called “interesting transcript 15” (IT15). This gene was found to encode an enormous protein - a biochemical behemoth containing 3,144 amino acids, larger than any protein in the human body (insulin has a mere 51 amino acids). And yet, beyond the fact that this protein is found is our neurons and testicular tissue, we know nothing about its actual role in our bodies, let alone why it causes a debilitating disease...

The Gene puts the Spirit's question and Yudhistira's answer into completely new perspectives.


Thursday, March 12, 2015

Yella's Discoveries




One of the simple pleasures of life is to find an Indian-sounding name in a piece of work that touches excellence. Quite often, I find myself waiting for the credits to roll at the end of a great movie, or flipping through the 'acknowledgements' section of a book, or a computer app, just to take delight at the number of such names that turn up.

Yesterday, I started on a book that had such a name right on the front-cover: Siddhartha Mukherjee's "The Emperor of All Maladies". It won the Pulitzer Prize in 2011 but, until now, I had put it away, assuming that it was a work of fiction that was somehow connected to Jumpa Lahiri's "Interpreter of Maladies". Never have I been so wrong about titles!

The book actually combines three things that I would never tire of -- history, science and technology. It is a biography of a disease we all dread - Cancer.

Right at the beginning of the story, amid 20th century scientists of Europe and USA struggling to understand this strange disease, an Indian name pops up in the most unlikely place and time - Yellapragada Subbarow at Harvard Medical School, 1923. Yella was a product of Madras Medical College, but his degree was not recognized, so he started all over again at Harvard as a biochemist, supporting himself by working as a part-time janitor, cleaning halls and toilet-bowls.

Down the road, he went on to discover the role of phosphocreatine, adenosine triphosphate (ATP) as an energy source in the cell, and developed methotrexate for the treatment of cancer. He discovered polymyxin widely used even today in cattle-feed and aureomycin (the first broad-spectrum antibiotic), and the first of tetracycline antibiotics. SubbaRow and his team of organic and biological chemists isolated folic acid from liver and a microbial source and then synthesized it in 1945. As Director of Research at Lederle, he  found in Hetrazan  (diethylcarbamazine (DEC), the cure for filariasis. The method for estimating phosphorous is called the Fiske-SubbaRow Method.

According to Banerjee, "Any one of these achievements should have been enough to guarantee him a professorship at Harvard. But Subbarow was a foreigner, a reclusive, nocturnal, heavily accented vegetarian who lived in a one-room apartment downtown, befriended only by other nocturnal recluses".

How is it that we never heard about him in our own school science textbooks?

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LINKS
  • Mukherjee, Siddhartha (2011): EMPEROR OF ALL MALADIES - A BIOGRAPHY OF CANCER, Scribner, 2011 -- url -- http://www.amazon.in/The-Emperor-All-Maladies-Biography/dp/1439170916 
  • Indian Academy of Clinical Medicine -- http://medind.nic.in/jac/t01/i1/jact01i1p96.pdf
  • Wiki - http://en.wikipedia.org/wiki/The_Emperor_of_All_Maladies
  • Yellapragada Subbarow (12 January 1895 – 9 August 1948) -- http://en.wikipedia.org/wiki/Yellapragada_Subbarow
  • Miracle Man of Miracle Drugs -- http://www.ysubbarow.info/ 



Sunday, May 18, 2014

Behind that Yummy Crust

Is there a connection between Asparagus, the golden-brown crust on breads, and... cancer?

Its amazing how our understanding of organic chemistry can change the way look at the most ordinary things in life.

Among the 20 most commonly found amino-acids (the 'bricks' that make proteins) is one called Asparagine. It was the first AA to be isolated and it was originally found in - no prizes for guessing here - Asparagus juice. Since then asparagine has been found in many places - especially in starchy foods.

When starchy substances are baked or fried, asparagine undergoes a process called Maillard Reaction, responsible for giving baked/roasted/fried foods their brown color, crust and toasty flavor. Unfortunately the reaction also produces carcinogens like Acryamide and some heterocyclic amines.

How does one deal with this problem? Apparently, if you add an enzyme (Asparaginase) to break down Asparagine in the starchy substances,  the amount of Acryamide can be reduced by 90% without any change in food taste, color or 'crustiness'!

The problem is that food-grade Asparaginase does not come cheap.

Until public-awareness matches with buying power, perhaps we will all continue to consume carcinogens with each bite into a crusy morsel!


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LINKS / REFERENCES

*
- Mannitol - sugar derivatie used to prodce medicine - http://en.wikipedia.org/wiki/Mannitol
- Tumor cells too cannot make their own Asparagine, a non-essential  amino acid. L-A removes it from the blood and starves tumors to death!
- Present marketshare of for therapeutic recombinant proteins is around $200 billion
- Erythropoietin - A glycopptotein hormone / cytokine (protein signalling molecule) that controls RBC production (erythropoiesis). Mkt leader - Amgen ($2.15b)
- http://en.wikipedia.org/wiki/Potentilla
- http://en.wikipedia.org/wiki/Asparagine


- http://en.wikipedia.org/wiki/Advanced_glycation_end-product

An enzyme in India -

* Mohan, Vishwa (2014): Unique enzyme discovered by CSIR institution to increase shelf life of fruits and vegetables, ToI, 11May2014
- CSIR-Institute of Himalayan Bio-resource Technology (CSIR-IHBT), Palampur has signed a MoU with its industry partner— Phyto Biotech, Kolkata, to formalize technology transfer for production of unique enzyme which may be used in developing anti-ageing cream.
- enzyme — Super Oxide Dismutase (SOD) — may also be used in food and pharmaceutical industries for end applications like extending shelf life of fruits and vegetables.
- Medicinal plant based research, discovery of APIs and related molecules
- enzyme — Super Oxide Dismutase (SOD) — may also be used in food and pharmaceutical industries for end applications like extending shelf life of fruits and vegetables.
- Source - 10,000 feet in the Western Himalayan region from Potentila astrosangunia, plant growing under snow cover
- work over the years has resulted in the isolation of the SOD gene -  a protocol was developed for cloning of the gene in E Coli.
- stability and functionality ranging from sub-zero to high temperature (above 40°C) with varying specific activity



Saturday, January 18, 2014

Battle of Clones


Yesterday, Biocon India launched a 'new', cheaper breast cancer drug called CANMab

In India, breast cancer is the second-most common form of cancer after cervical cancer with 150,000 patients being diagnosed every year. The new drug, CANMAb, is priced about 25% lower than Roche's Herceptin.

For all practical purposes, this seems to be a copycat drug. Like Heceptin, CANMAb too disrupts HER2 protein production and is being marketed as a 'Biosimilar' to a monoclonal antibody called Transtuzumab.

So what does this mean in plain English?

An antibody is a "Y" shaped protein used by our body to identify and kill intruders like bacteria and viruses. Like matching pieces of a jigsaw puzzle, a part of the Y-shaped protein identifies and 'locks' on to a unique part of a foreign target (called antigen). An intruder thus marked can then be destroyed by the immune system. Monoclonal antibodies are produced by identical immune cells and are exact replica's (clones) of the parent cell.

Biosimilars are substances derived from a living organism by techniques that use recombinant-DNA or controlled gene expression methods.

So Biocon India has essentially found a better, commercially more competitive method of producing monoclonal antibodies (MAb's), to take bite of the Swiss MNCs lobal market share ($6.4b globally and $21m in India), for an existing anti-cancer drug.

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LINKS & REFERENCES

Heceptin from Roche - http://www.herceptin.com/

Biocon Press Release - http://www.biocon.com/docs/PR_Biocon_CANMAb_18Jan2014.pdf?subLink=news&Fileid=467

http://en.wikipedia.org/wiki/Antibodies
http://en.wikipedia.org/wiki/Monoclonal_antibodies