Going back, To the future

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Nostalgia is perhaps the easiest forms of time travel. The allure of the past clouded with quirks of one’s memories effects emotions strong enough that they transport us to happier (or sadder) times. Looking back in time can also serve as a corrective measure for individuals and societies. We have all had that one instance where an upset stomach has lead to a mental reconstruction of past meals. Similarly, we compare contemporary events to historical happenings to get a sense of impending events.

It is a principle doctors often use to understand the progression of diseases. An unsteady gait can indicate neurological dysfunction in cases like Huntington’s or amyotrophic lateral sclerosis. Excessive weight-loss and lack of strength are commonly seen in people going on to develop cancer. This ability to foretell and diagnose can be immensely useful in treating complex disorders. However, so far, such telltale signs are not specific and the ones known are seen too late to inform treatment.

The possibility of peeping back into time, until 2006, was thought to be the promise of the future. That is until a Japanese researcher changed it all. Prof. Shinya Yamanaka’s research had for long focused on genes that were responsible for maintaining a pluripotent state in stem cells. During his research Prof. Yamanaka shortlisted 24 genes that were important for maintaining the nature of a stem cell. Then, by the use of computer algorithms and tedious permutation experiments, along with Kazutoshi Takahashi, he narrowed it down to 4 crucial genes that when introduced into any mature cell type (such as skin cells) could ‘reprogram’ it to look and behave exactly like a stem cell. These genes (called Yamanaka factors) are now routinely used in research labs across the world to ‘reprogram’ skin, blood and even epithelial cells purified from urine of certain patients. For this work, Prof. Yamanaka went on to share the Nobel Prize for Physiology and Medicine with Prof. John Gurdon in 2012.

Pluripotent: or pluripotency: The ability of a cell to give rise to cells of an entire organism

While this means that the scientific community has jumped over the ethical hurdle of using stem cells derived from donor eggs, it has also strengthened research into several disorders of the blood (hemophilia), brain (autism, schizophrenia, Alzheimer), pancreas (diabetes) and others.

The idea behind all of these is rather a simple one. A scientist can obtain skin cells from individuals suffering from specific illnesses and to convert these to stem cells (or more specifically to induced pluripotent stem cells). These stem cells can be culture indefinitely in laboratory conditions and under specific chemical instructions be coaxed to become cells of specific organs. Several defined recipes have been developed that can generate neurons, cartilage, blood and even sperm from these patient-specific stem cells.

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Having made the cell-type of choice, researchers can now compare them to cells from healthy individuals and identify errors in cell behaviour that occur much before critical stages of illness. Owing to the self-renewing properties of stem cells, it becomes possible to grow large batches of cells and treat them with libraries of drug compounds.

While it will take years to see the fruits of this labour, it cannot be overlooked that stem cell research is already changing our appreciation of patient differences. Scientists can now understand why two individuals with bipolar disorder respond to different drugs. In doing so, it also allows them to practice a patient specific approach rather than one size fits all. Combined with advances in fields of gene editing and microscopy, scientists can model disorders more intricately in the laboratory.

The adage that we must learn from history is often applied to politics. It might however, be equally relevant to biomedical research. Only time will tell.

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