Nobel Prizes in Functional Medicine
In 2009 the Nobel Prize in Medicine was awarded to 3 scientists who solved a major problem in biology.
“How chromosomes can replicate during cell divisions and how can they be protected against degradation and destruction.”
The solution is to be found in the ends of the chromosomes, the Telomeres, and the enzyme that forms them, Telomerase.
The long, thread-like DNA molecules that carry our genes are packed into chromosomes, and telomeres are the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence, telomeres, protects the chromosomes from degradation.
Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that enhances telomere DNA synthesis. These discoveries explain that the ends of the chromosomes are protected by the telomeres and that they have been built by telomerase.
When telomeres are shortened, cells age.
Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed.
This is the case in cancer cells, which have the characteristic of “immortality”.
Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells.
The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies.
Thus an important piece in the puzzle was found regarding human ageing, cancer, and stem cells.
These discoveries had a major impact within the International Scientific Community.
Scientists believe that telomere shortening is the cause of Ageing, not only in individual cells, but also in the organism as a whole.
However, the Ageing process (i.e. the accumulation of Diseases) has turned out to be complex. It is thought to depend on several different factors
The telomere is one of them. Research in this area remains intense.
Most normal cells do not divide frequently, therefore their chromosomes are not at risk of shortening and they do not require high telomerase activity.
In contrast, cancer cells have the ability to divide constantly, infinitely, and yet preserve their telomeres.
So how do they age?
One explanation became apparent based on the finding that cancer cells often have increased telomerase activity.
Therefore, it was proposed that cancer could be treated by eradicating telomerase of its cells.
Several studies are underway in this area, including clinical trials evaluating vaccines directed against cells with elevated telomerase activity.
Certain inherited diseases are now known to be caused by telomerase defects. For example, some forms of congenital aplastic anemia, in which insufficient cell divisions in the stem cells of the bone marrow lead to severe anemia. Certain inherited diseases of the skin and the lungs are also caused by telomerase defects.
In conclusion, the discoveries of Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostakby Blackburn have added a new dimension to cell understanding.
They have shed light on disease mechanisms, and stimulated the development of new therapies.
The Nobel Prize in Medicine 2011 was divided.
One half jointly to Bruce A. Beutler and Jules A. Hoffmann “for their discoveries concerning the activation of innate immunity”, and the other half to Ralph M. Steinman “for his discovery of the dendritic cells and their role in adaptive immunity”.
The work of these three scientists has been proven to be vital for the development of new, improved vaccines that fight infectious diseases and the innovative approach in combating cancer.
Their research has helped in setting the foundation for a new type of “therapeutic vaccines” that stimulate the immune system so that to attack cancer tumors.
A better understanding of our immune system’s complexity has also provided data for the treatment of inflammatory diseases, such as rheumatoid arthritis.
Immune System: the Protector of the organism.
Both humans and other species actually live together with microorganisms. Most of these are either beneficial or neutral.
For the small minority of those that are life-threatening, our organism has developed a series of defense mechanisms, among which the immune system has a leading role.
Non-specific immunity (innate immunity), which is the first line of defense of the human organism and evolutionarily is the older defense strategy. It is also the immunity of plants, insects and fungi. Immune system’s cells that are involved in innate immunity can block the assaults of microorganisms. This type of immunity does not offer long-term protection against each individual microorganism from which we have been infected.
Specific immunity (adaptive immunity) is the next line of defense of our organism. It develops with the help of cells involved in non-specific immunity, which also presene to the immune system the antigens of the microorganisms that attack us,in order to develop specific antibodies. Adaptic immunity allows long-term protection against the organisms that attack us.
Overall, the three Laureates opened the way for the development of effective vaccines, as well as new type vaccines.
These vaccines are developed in order to direct our immune system against cancer tumors.
They also allowed the better understanding of Inflammatory Diseases. Steinman’s touching story reveals the capabilities of dendritic cell applications. According to an announcement of Rockefeller University, Steinman was diagnosed with pancreatic cancer 4 years ago and extended his life with a dendritic cell vaccine, designed and manufactured by himself.
Nobel Prize in Medicine 2012
It was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka for their discovery that “when cells mature they can be reprogrammed to become pluripotent”.
Where life begins.
All of us went through this stage, but nobody remembers it.
It is actually the first moment of our personal history. The moment when the sperm of our father fertilized the egg of our mother and triggered procedures that led to our birth.
Which forces drive the fertilized egg to be divided so that to produce the first cells?
And how is it possible from these first cells that are similar to each other to finally produce highly specialized cells, such as nerve or muscle or liver cells?
More than four decades passed, until light was shed on these important questions of developmental biology, by the two Laureates of the Nobel Prize in Medicine 2012.
He was born in 1933 in Dippenhall, United Kingdom. He was a university student when he attempted to provide answers to the great questions.
It was only a few years after the elucidation of DNA structure, and the scientific community ignored almost everything about the molecule of heredity.
Thus, the fact that specialized cells were so different from each other had led to the hypothesis that in order for each cell to adopt its identity, it selected to keep those parts of the DNA it needed while excepting the other cells.
Gurdon worked with frog ovaries, which are abundant and large, and also have the added benefit that they can be fertilized outside the body, something that gives immediacy to the monitoring of the experiment, to establish whether this hypothesis is true.
Thus, he first removed the cell nucleus of a frog’s egg, and replaced the egg’s nucleus with a nucleus from a specialized intestinal cell taken from amphibia.
The birth of tadpoles from these eggs showed to the young student that his hypothesis was not right.
The specialized cells kept all their genetic material, despite the fact that they used only a part of it.
At the same time it was established that the egg had a life-giving force, capable of making the specialized cell nucleus to “forget” the commands it had and return to its original state, in which all the DNA is available.
All these happened in the end of the ‘50s and the beginning of the ‘60s.
And while Gurdon and his colleagues studied (successfully!) the factors determining cells’ identity in the developing embryo, it was thought, for many reasons that, contrary to amphibia, the nuclei of mammalian cells would not be as receptive to egg commands.
The above viewpoint was proven incorrect when Dolly, the first cloned mammal, was born on the 5th of July, 1996.
It paved the way for the work of the other 2012 Laureate, Shinya Yamanaka.
Born in Osaka, Japan, Yamanaka wanted to find all those life-giving forces that make the first (primitive) embryonic cells to become Stem cells.
Stem is cells are, capable to remain undifferentiated in that situation, allowing them both to act as a source of cells and on the other hand, under certain circumstances, to differentiate into all cell types.
While working with mice, Yamanaka found in 2006 the four genes that ensure stem cells’ ability to “grow”.
The researcher from Japan together with his co-workers introduced the four genes in fibroblasts (differentiated cells from connective tissue).
They found that they lost their differentiation and became Stem cells.
Yamanaka’s undifferentiated cells were called iPS cells (induced Pluripotent Stem cells) and their establishment was considered a major scientific breakthrough.
Not without reason, as these are the base to implement the boldest scientific dream since the beginning of Medicine.
Indeed, scientists hope that they will be able to cure diseases with the use of these cells.
Organs and tissues for transplantations will be produced from these cells.
Needless to say that these organs and tissues produced by the cells of the patient will not be rejected (autologous transplantation).
As far as the time that all these will be the usual clinical practice is concerned, nobody can be certain. Nevertheless, the progress during the past years and the large number of researchers focusing on this field, show that we will experience soon the Medical Revolution.
These discoveries changed radically our understanding about organisms’ development.
They created new scientific disciplines.
Thanks to these, researchers hope that in the near future many diseases will be treated with the help of Cellular Therapies.
I wish all the best
Dr. Kyriakos Tigkas, M.D.
Surgeon Gynecologist – Obstetrician
Specialization in: Functional Medicine
Biomimetic Hormone Replacement Therapy for Women
Surgical Gynecologic Oncology, Breast Surgery