By Don C. Reed
One day I did a thousand sit-ups; I don’t know why.
I was in the eleventh grade, and just started doing them in PE class, going for a hundred at first, then continuing on and on. The person holding my ankles got bored and quit; somebody else harassed me by tossing a paper cupful of water on the floor where my lower back kept touching. But I was on a mission and could not be dissuaded. I just kept on and on, a skinny teenager doing situps…
I wore a patch of skin the size of a silver dollar off my tailbone area. It was raw and itched for a couple of days and then healed without complication.
Which is important for the story.
Because what if the skin could not stay together?
Try this. Take your right index finger and run it roughly across your left forearm.
Nothing happens, right? The skin ripples, then springs back as before.
But if you had a skin disease called Epidermolysis Bullosa (EB), that small touch might scrape off skin.
When you first see the video of John Hudson Dilgen, the “Boy with Butterfly Skin”, he appears to be wearing white sweats. He is smiling and talking, a regular kid, the athletic type who would be running around like crazy at the school playground, and be last to come in from recess.
It takes a moment to realize the “white sweats” are bandages — over wounds.
There are four different types of EB, but the title “Butterfly skin” comes because EB skin is fragile as a butterfly’s wing. In a healthy body, the layers of skin stick together by the body’s natural glue, collagen. In EB, the collagen gene does not work right, and layers of skin can break away.
When John was born, his feet were bleeding from just the strain of childbirth. As he grew, more terrors developed.
“Bath time”, said his mother, “was heartbreaking, with relentless fear and screaming…”
He loved potato chips, but just swallowing something rough can be deadly for a child with EB, doing damage to the inside of the throat.
Today, John Delgin is a teenager, but the disease is still with him. If he rubs his eyes, the damage may require him to spend several days in a dark room.
EB is rare, an “orphan disease”. This is good news/bad news: we do not want it common, because no child should have to suffer like that — but a small number of patients also means fewer customers, less profit for the big corporations.
Less profit, of course, means less incentive for private enterprise to put money into research for cure.
This is another reason for continuing the California stem cell program — research projects it supports do not have to make an immediate profit. For CIRM, the California Institute for Regenerative Medicine, it is enough that we should do it.
There are practical reasons to support “orphan disease” research. Other skin problems are similar: improvements for one may help another. EB is rare, but skin disease is common, affecting 2% of the population.
Wound healing problems affect more than eight million Americans.
And last, research on EB may accelerate cure for cancer. EB sufferers often die of a deadly cancer called squamous cell carcinoma. Studying the skin of an EB patient may determine the triggerpoint of many kinds of cancer — exactly when and how it begins potentially benefiting millions.
“… treating rare diseases is the first step toward achieving…(the) personalized medicine that the Obama Administration has highlighted as a priority.” — Julia Jenkins, Executive Director, Every Life Foundation for Rare Diseases personal communication.
Stanford University is heavily invested in this effort, with a superb dermatology (skin science) lab. More recently they have started a whole program to develop tissue and cell manufacturing technologies called the Center for Definitive and Curative Medicine.
Here are two top Stanford scientists , working on the problem right now.
They are: Anthony Oro, Primary Investigator (PI) and a skin genetics and development expert, who is not only attempting to do the impossible with the invisible in medical research, but can even explain it in peopletalk; and Marius Wernig, stem cell authority, who once came to a formal science event wearing white tennis shoes with his tuxedo.
The two are codirecting the project with a talented team including Project Manager and EB physician Jean Tang; Stanford Good Manufacturing Process Director David Digiusto; the head of the EB group and the University of Colorado, Dennis Roop; and the head of the EB effort at Columbia University, Angela Christiano.
How will they try to defeat this currently incurable disease?
One weapon they may use is Induced Pluripotent Stem cells (iPS), the micromanipulation of skin cells which won Shinya Yamanaka the Nobel prize.
Here is my layman’s interpretation of what they plan to do:
1. Take a tiny skin sample from the patient;
2. Make personalized stem cells from the patient;
3. Correct the defective genes;
4. Do quality control on the lines to remove those with genetic abnormalities;
5. Make new cells (with the corrected genes);
6. Make the healthy new skin and graft it onto the patient’s wounds.
The stakes? “There are over 200 genetic skin diseases that could in principle be treated with this approach. Similar therapeutic reprogramming studies are being developed for other tissues like heart, brain, pancreas, liver and cornea.” — Anthony Oro, Personal Communication.
Have they won? Not yet.
Like a series of advancing waves, science moves forward, every effort benefiting from what went before.
Will the Oro/Wernig approach be the one that succeeds? We cannot know. But the fact that these talented individuals are fighting on gives me hope.
“Stanford…will soon move forward with an expanded patient study… We are hopefully years, not decades, away from meaningful therapies and potential cures.” — Jessica Schneer, Epidermolysis Bullosa Research Partnership Executive Director, personal communication.
Want to follow the research to fight “butterfly skin”? Watch for grant number TRAN110416, called “Genetically Corrected, Induced Pluripotent CellDerived Epithelial Sheets for Definitive Treatment of Dystrophic Epidermolysis Bullosa ”.
I love those two words: “Definitive Treatment”….
P.S. Dr. Anthony Oro’s work continues — as I understand it, small patches of skin will be removed from an EB patient, genetically altered (fixing the weakness) and then put back, where they will grow as sheets of normal healthy tissue.
AND — news just in from Italy, Dr. Michele De Luca and Reggio Emilia of the University of Modena have used another stem cell approach to regrow skin on an EB sufferer; and Dr. DeLuca was named “Stem Cell Person of the Year” by Dr. Paul Knoepfler for his work on EB!
If the idea of saving lives and easing suffering appeals to you, VOTE YES! on Proposition 14: the California Stem Cell Research, Treatments and Cures Initiative of 2020. Proposition 14 will renew funding for the California stem cell program, so that chronic diseases, like EB, cancer, paralysis, Parkinson’s, Alzheimer’s. arthritis, Spinal Muscular Atrophy, COVID-17, heart disease, multiple sclerosis and many more may be defeated.
Vote YES! On Prop 14!!
Don C. Reed is the author of “STEM CELL BATTLES” from World Science Publishing, Inc., and other books on regenerative medicine.