This article was published in Scientific American’s former blog network and reflects the views of the author, not necessarily those of Scientific American
From medicine to science
When I was about 3 or 4 years old, I got very sick. I stayed in bed for many weeks and every day a nurse would come to give me a penicillin shot. The pain from shots turned into fear, in time fear turned into a plan for revenge. When I got better I demanded to have my own syringe and cruelly treated all teddy bears and dolls. If they didn’t look sick I made them sick, just to perform surgeries, sew wounds and give shots. I even offered my service to family members; unfortunately, they stubbornly kept on being healthy.
As I grew up, my feelings for medicine didn’t get any warmer and I decided I would rather learn about the universe and its contents at the molecular level. I spent over 20 years working in many scientific laboratories, focused mostly on interactions between proteins. It was important to know that deficiency of a certain protein (Factor 8) causes hemophilia but it was much more interesting to express this protein in a cow, so it could be produced in milk in massive amounts. A cup of this milk per day could supply enough substitute to keep hemophilia under control.
On supporting science journalism
If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.
At that time I was thinking that disease provided conditions where certain phenomena did not occur the way they should have. As such, I perceived illness only as an occasion to verify and to strengthen precise scientific laws. Once we found out how to transfer and express a human gene in an animal mammary gland and really got the resulting functional protein, we could apply scientific findings in medicine. We would publish results and patent the idea, then move forward to another problem. Not to another patient.
But all that was about to change once I attended a certain panel discussion.
From science to medicine
One a cold November day I attended a conference on lung diseases at Johns Hopkins University in Baltimore. At the end of a series of presentations there was a panel discussion with participation of physicians, nurses and a patient suffering from pulmonary fibrosis. He was a middle aged college teacher, handsome, with a charming smile. I’ll call him Harry. Harry said that when he had heard the diagnosis, treatment options, and possible outcome, he asked his doctor if he would be able to play the violin. "Yes," the doctor answered. So he smiled and said: "Well, then, I need to start learning how to play it".
I was stunned. I already knew that he is one of over half a million patients in the United States with the disease, of which 40,000 die every year. It predominantly affects people in the seventh to eighth decade of life, yet here in front of me was an example of the increasing trend of this disease afflicting younger individuals.
I knew that the main feature of pulmonary fibrosis is an irreversible replacement of normal air sacs with inflexible fibrotic scar. And I knew that the cause of fibrosis is not identified in 60% of cases. If causes of fibrosis are not known, it means there is no effective treatment. Expected survival time is 2-3 years.
I came back to my lab thinking that Harry didn’t have much time to learn how to play the violin. Was there anything I could do to change it? Thankfully, his physician was my boss who had hired me to help her with an animal model of the disease.
Harry had completely changed my focus: This wasn’t just another scientific problem. This time the patient and his disease were the center of my attention. I couldn’t give him shots as I did to my teddy bears, but his physician could, if only we had any idea of what to inject. For this, I needed to find out what went wrong in Harry’s lungs.
Left: Human lung with advanced fibrotic foci
Digging in literature and discussions with pulmonologists at Johns Hopkins helped us design an approach that, we’re hoping, should shed some light on the pathogenesis of lung fibrosis. In our research plan we focused on blood vessels in the lung.
In 1963 an important observation was made that at the very beginning of the disease new very tiny blood vessels appear in the lung. They grow rapidly to some point, then gradually disappear, and in their place scar tissue forms. When we compared this observation with what we knew about other lung diseases, we found significant differences. For instance, in the lungs of patients suffering from emphysema there is a loss of lung blood vessels from the very beginning of the disease. But, in yet another lung disease, in pulmonary hypertension, appearance of new blood vessels is observed, similarly as it is happening at the beginning of fibrosis, but these do not vanish at all!
Why do blood vessels behave differently in each of these diseases? What is the force that makes them grow rapidly then die, or grow endlessly? Is it something coming from the environment that affects them, or is it something within the blood vessels that makes them act in a wrong way?
We decided to check on blood vessels first, so we took a closer look at the components of the circulation system in the lung. Every blood vessel in the body is lined by a tight layer of endothelial cells. These cells can "sense" the environment and when a new vessel is needed, they grow and form the new vessel. The same cells can decide to die, then the vessel vanishes.
Left: Endothelial cells derived from a healthy lung stained for VE-cadherin (green) and nuclei (blue)
We designed a study that asks the question what goes wrong with endothelial cells in fibrotic lungs that makes them grow rapidly, then equally rapidly, vanish? We decided to address this problem by comparing thee groups of endothelial cells -- ones derived from lungs affected with fibrosis, with hypertension, and with emphysema. We’re going to check on what genes are actively working and what are not working at all in each cell line. We’re going to compare gene patterns specific to the disease to the ones taken from a healthy lung. Thus, we should be able to define differences between each type of the sick cells and between the sick and healthy cells. Once we identify genes and proteins behind the differences, we should be able to link them with the disease. This will be helpful in designing potential therapies.
So far we have derived 12 endothelial cells lines out of 19 tissues. The lung is the only internal tissue directly exposed to environment. Therefore it’s often affected with mold, bacteria, or air pollutants. Cells that show signs of such a contamination cannot be used in our study. Once we achieve the number of 20 (4 cell lines per each disease plus healthy control) we’ll be ready to start real tests and experiments.
We continue to work on this research question. We use samples from excess lung tissue of human origin, biopsy specimens, and tissues from donors.
I’m not a physician, but I consider donors my patients. I won’t be able to help those who give their tissue samples. But others, including Harry, may have a better chance to be cured or at least to survive more than 2-3 years. Maybe even long enough to learn how to play a violin.
Images: by Iwona Fijalkowska
About the Author: Iwona Fijalkowska, Ph.D is a faculty member in the Pulmonary and Critical Care Division of the Johns Hopkins School of Medicine where she researches vascular components in the pathogenesis of fibrosis, hypertension, and emphysema. Her passion for exploring new areas extends beyond science: she likes traveling and modern jazz.
The views expressed are those of the author and are not necessarily those of Scientific American.