When we talk about the glory of science everywhere, we used to oversee failures, struggles, and even trickeries involved in it. Yeah...! After all, scientists are also people like us, and we, humans, are prone to make mistakes. Unfortunately, the selfishness of a few will never seize, and the wound they create remains as a scar forever. Here, I am going to tell you about one of the rare frauds that happened in scientific research, more than a decade ago.
As the title conveys this write up is about stem cells, which are, kind of, primary cells in our body from which all types of other cells such as blood cells, neurons, skin cells etc., originate. In 2005, a South Korean researcher named Woo Suk Hwang and his twenty-four co-workers published a research paper related to stem cells in the Science Journal. In that article, they claimed that they successfully created human embryonic stem cells, a remarkable advancement in the field of therapeutic cloning. But this 'Nobel-deserving' discovery didn't bring laurels but ten years of imprisonment for Hwang. What went wrong? Before jumping into it, let me give some details about stem cells and its therapeutic potential.
What are stem cells?
A cell is the basic functional unit of life. Tissues that make-up our organs consist of different types of cells. A cell in the brain is different from a cell in the muscles; A blood cell is very much different from a pancreatic cell. All these cells show variations in their appearance as wells as the tasks they perform. Have you ever thought how a single cell called 'zygote' formed by fertilisation of an egg with a sperm divides and create a diverse array of cells that organise to build the human body?
To answer this, one should understand what is known as cell potency. The ability of a cell to divide and differentiate into other types is called its potency. The potency of a stem cell is directly proportional to the number of cell types to which it can differentiate. A cell that can form an entire organism by differentiating into all the cell types is called a 'totipotent' stem cell. Zygote and the cells formed from it after first few divisions (till the 'morula' stage) are totipotent. As the cell division continues to reach the 'blastula' stage, the cells separate to 'inner cell mass' and 'trophoblast'. Inner cell mass develops to form the embryo and trophoblast are the precursors of the placenta. Cells of inner cell mass are called 'pluripotent' as they can differentiate into all cell types but cannot create the embryo. A 'multipotent stem cell' is a generous term dedicated to denote stem cells that can generate multiple types of cells. Hematopoietic stem cells in bone marrow, from which blood cells originate, are multipotent. A stem cell that can form a few types of cells is called 'oligopotent', and a stem cell that is the progenitor for a single type is called 'unipotent'.
What determines the potency of a stem cell?
Figure schematically represents how a stem cell differentiates into a neuronal cell. Epigenetic markers (read the text) act as activation switch for a specific set of genes. (Image source: Pixabay)
The genetic composition (The composition of DNA molecules) of every cell in our body is the same. DNA decides almost all the cellular functions by serving as the template for the synthesis of proteins which are the workhorses of a cell. Then how different stem cells and their daughter cells show a wide variety of structural and functional characteristics?
DNA molecules work in the form of genes. Genes are functional units within the DNA which 'code for' RNAs (RNA is also a 'nucleic acid' like DNA, but there are some variations in the composition, structure and function. A specific type of RNA called the messenger RNA codes for proteins. Check the reference session for more about this (de)coding mechanism which generates proteins using DNAs as templates). There exist several marks in genes, called the epigenetic marks, which determine whether a gene shall act or not. Epigenetic marks are chemical modifications over DNA or 'histones' (histones are proteins that help DNA to stay in a compact form). Such modifications act as regulators of earlier mentioned activities of DNA.
Cells achieve these regulatory actions by recruiting certain proteins known as transcription factors that bind to DNA according to the marks present. As the above-said mechanism also regulates the production of these factors, the activities of every gene are depended on the availability of appropriate transcription factors.
Epigenetic marks on the embryonic stem cells are different from that of non-embryonic daughter cells (daughter cells are also called adult cells). For example, the primary function of beta cells of the pancreas is to keep the genes for the insulin pathway active; these genes are not essential for heart muscle cells where genes required for generating proteins involved in contractile activities are prime. Presence of suppressing epigenetic marks make insulin-related genes inactive in muscle cells. These marks and the availability of correct transcription factors determine the potency of stem cells also.
Other than the earlier mentioned hematopoietic stem cells, the adult human body also contains additional stem cells, which are intestinal stems cells, mesenchymal stem cells, neural stem cells etc. Unlike in the case of embryonic stem cell, there are no ethical issues while dealing with such non-embryonic stem cells. Due to this, adult stem cells are valuable in therapy such as bone marrow transplantation for leukaemia (blood cancer) treatment.
Need for research in Stem cell biology
Like in bone marrow transplantation, stem cells in the umbilical code blood are used for treating blood cancer and anaemia. Studies using animal model suggest that stem cells have the potential to cure brain and spinal cord injury, blindness, infertility, diabetes and heart-related diseases. Scientists have succeeded in culturing human organs partially or fully using stem cells in laboratories.
In therapeutic cloning, the nucleus of an egg cell (ovum) is replaced with the nucleus of an adult cell. But this kind of studies is restricted to animal models due to the ethical issues in using human ova. Chance of destruction of embryos and fear of human cloning made this topic controversial since the advent of it.
About the fraud
In 2005, Woo Suk Hwang of Seoul University of South Korea forged the result and published a paper in the Science journal. The method that he claimed to be successful for developing human embryonic stem cells was not reproducible at all. The source of egg cells that he used in experiments was either his graduate students or the black market! And this made him a criminal and an international fraud.
Constructing stem cells other than from embryonic sources is highly valuable as we can get away from the controversies and ethical issues. That is the reason why a Nobel Prize in physiology or medicine was awarded to John B. Gurdon and Shinya Yamanaka "for the discovery that mature cells can be reprogrammed to become pluripotent" in 2012. Yamanaka played a crucial role in discovering the reprogramming factors that can convert adult cells into induced pluripotent stem cells.
According to Roger Pedersen, a professor of regenerative medicine at Cambridge University, stem cells have the potential to replace the conventional medication for the cure of several diseases. Possibility of converting adult cells into pluripotent stem cells paves the way for patient-specific stem cells and hence patient-specific medicines. It is fantastic if we can use the blood cells or skin cells of a patient to treat his/her medical conditions, sometimes, problems as complicated as a spinal cord injury!
Although we look forward to the extraordinary capabilities of stem cells, the infancy of the field is worrisome. Overhyping of the good things about stem cells may lead to unauthorised trials and treatments. Regulatory authorities should take extreme caution in the clinical usage of stem cells, and effective stem cell therapies require extensive research and trials.
References and suggested readings
- Fraudulent Human Embryonic Stem Cell Research in South Korea: Lessons Learned
- Stem-cell therapy
- Induced pluripotent stem cell
- Epigenetic Marks
- Stem Cell Transcription Factors and Regulators
- DNA to RNA to Protein
- Somatic cell nuclear transfer
- Are Stem Cells The Future Of Medicine?
PS: If you like my post, please follow me for more such contents.
As I was reading this I recalled a blog I wrote a while back about genomic imprinting. I guess you're saying essentially the same thing...cloning doesn't work because while we can duplicate a gene we can't duplicate all those instructions that come along with a gene and actually determine its expression.
Your article also reminded me of another issue that interests me...researchers who are so hungry for credit, they claim stuff that isn't true. Not just dishonorable, but dangerous. And in Woo Suk Hwang's case, stupid--because if the experiment couldn't be duplicated the fraud would be discovered.
Good piece :)
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