By Elof Axel Carlson

Elof Axel Carlson

Science is a way of interpreting the universe in the era in which we live. One of the realities of our lives is that we do not know how much of the world we think we know is really incomplete.

Think of it this way — If you grew up when the American Revolutionary War was being fought, you would not know a lot. You would not know your body is composed of cells. You would not know that heredity is transmitted by genes located on chromosomes present in nuclei of cells because no one knew there were nuclei, chromosomes or genes.

You would also not know there are biochemical pathways that carry out your metabolism in cell organelles because no one then knew there was such a thing as metabolism, biochemical pathways or cell organelles. And you would not know that infectious diseases are associated with bacterial and viral infections nor would you know that your body is regulated by hormones. If you created a time line of scientific findings in the life sciences, the cell theory was introduced in 1838. Cells were named in 1665, but Robert Hooke thought they accounted for the buoyancy of cork bark. He drew them as empty boxes.

When Schleiden and Schwann described cells, they were filled with fluid; and Schwann thought nuclei were crystallizing baby cells being formed in a cell. The cell doctrine (all cells arise from pre-existing cells) did not come until Remak and Virchow presented evidence for it. Mitosis, or cell division, was not worked out until the late 1870s; and meiosis of reproductive cells (sperm and eggs) was not worked out until the 1990s.

Fertilization involving one sperm and one egg was first seen in 1876, while most cell organelles were worked out for their functions and structure after the invention of the electron microscope in the 1930s. There was no organic chemistry before Wöhler synthesized molecules like urea in 1823, and biochemical pathways were not worked out until the 1940s.

DNA was not known to be the chemical composition of genes until 1944, the structure of DNA was worked out in 1953, molecular biology was not named until 1938 and the germ theory was worked out in the 1870s and 1880s by Pasteur and by Koch, who both demonstrated bacteria specific for infectious diseases. Embryology was worked out in 1759 by Wolff, while hormones were first named and found in 1903 by Bayliss and Starling.

What the history of the life sciences reveals is how dependent science is on new tools to investigate life. Microscopes up to 30 power came from Hooke’s efforts in 1665. A better microscope by Leeuwenhoek distinguished living organisms (“animalcules”) at up to 500 power.

It was not until the 1830s that microscopes were able to overcome optical aberrations and not until the 1860s that a stain technology developed to see the contents of cells. This boosted observation to 2000 power. For the mid-20th century, cell fractionation made use of centrifuges and chromatography to separate organelles from their cells and work out their functions.

Experimental biology began in England with Harvey’s study in 1628 of the pumping action of the heart. Harvey was educated in Padua, Italy, where experimental science had been stressed by Galileo and his students who began applying it to the motion of the body relating bones and muscles to their functions. No one alive in 1750 (or earlier) could have predicted DNA, oxidative phosphorylation, the production of oxygen by plants, Mendel’s laws of heredity or the role of insulin in diabetes.

But what about the present? How complete is our knowledge of life processes? Are there major findings in the centuries to come that will make our present understanding look as quaint as reading the scientific literature in the 1700s?

We can describe what we would like to know based on our knowledge of the present and likely to be achievable. We cannot predict what may turn out to be new functions or structures in cells. At best (using what we do know) we can hope to create a synthetic cell that will be indistinguishable from the living cell from which it was chemically constructed. But that assumes the 300 or so genes in a synthetic cell will account for all the activities of the vague cytoplasm in which metabolism takes place.

For the level of viruses there are no such barriers and the polio virus has been synthesized artificially in cell-free test tubes in 2002 (an accomplishment of Eckard Wimmer at Stony Brook University).

Within a few years ongoing studies of bacteria and of yeast cells with artificial chromosomes, may resolve that question for the genome of a eukaryotic cell. I hope that an artificial cytoplasm will be worked out in that effort. That might be more of a challenge than presently assumed.