Ernest McCulloch: Hematologist and Stem Cell Research

• McCulloch and Till's combination of skills in cellular biology and biophysics proved powerful.
• In 1961, while researching bone marrow cells, McCulloch and Till discovered the first clue to the existence of stem cells.
• Stem cells have a unique potential to become other, specialized types of cells, and can also self-renew and multiply.
• McCulloch described the discovery as a case study in "the importance of serendipity in scientific research."
• McCulloch was interested in the medical potential of nuclear radiation and wanted to explore its effects on cancer cells.
• McCulloch's project involved irradiating mice.
• McCulloch, a medical doctor, needed Till, a physicist, with the necessary expertise in radiation.
• The two began measuring the radiation sensitivity of the mice's bone marrow cells.
• Mice were exposed to lethal radiation and then had their bone marrow cells replaced with donor cells.
• Bone marrow transplantation was a new treatment known to replenish crucial blood cells.
• Till and McCulloch exposed the donor marrow in their transplants to varying doses of radiation.
• The scientists measured how many donor cells survived the radiation doses by monitoring the mice’s response.
• The team repeated the experiment and carried out autopsies on the mice 10 days after the transplants.
• One Sunday morning, McCulloch assessed tissue samples from the autopsies.
• McCulloch saw a number of small bumps on the dead mice’s spleens.
• The number of spleen bumps, or nodules, was in direct proportion to the number of live marrow cells the mice had received.
• Till and McCulloch needed to find out whether each of these nodules had grown from a single cell or from many cells.
• Till and McCulloch, with Till's PhD student Andrew Becker, irradiated the donor cells to create a marker or trace.
• Radiation caused small changes to the chromosomes in a few of the irradiated donor cells.
• Altered chromosomes acted as a marker, present in any new cells that had grown from them.
• After isolating and examining hundreds of cells from a new set of spleen nodules, the team found that each nodule had grown from a single cell, meaning they were clones.
• Till and McCulloch referred to the original cells as "colony-forming units."
• The colonies of cells in each nodule were a mixture of those that develop into the three types of blood cells: red cells, white cells, and platelets.
• Till and McCulloch published their findings in 1961 in a paper that referred to the "radiation sensitivity of normal mouse bone marrow cells," which was largely ignored.
• In 1963, Till, McCulloch, and Becker published further results in Nature, which gained attention.
• Subsequent studies showed that bone marrow contains special cells that can reproduce and develop into other types of cells, with specialized functions.
• Adult stem cells exist in many organs and tissues and help the body heal or regenerate damaged tissue.
• Discovery was a vital advance in biological science and has huge potential for treating disease.
• After the marrow transplants, the mice were examined for 10 to 11 days.
• Each mouse spleen nodule corresponded to 10,000 bone marrow cells.
• Stem cell research accelerated the development of bone marrow transplants.

Shinya Yamanaka

• Yamanaka reprogrammed mature cells and was able to turn them back into stem cells.
• In 2006, Yamanaka introduced 24 specific genes into adult skin cells in mice, reverting them to an immature stem-cell state.
• Yamanaka showed that these cells were pluripotent, meaning they can become any type of cell.
• Previously, it was thought that only embryonic stem cells were pluripotent.
• Yamanaka jointly received the Nobel Prize in Physiology or Medicine in 2012 for his work.