Embryo Project Encyclopedia

Ovism was one of two models of preformationism, a theory of generation prevalent in the late seventeenth through the end of the eighteenth century. Contrary to the competing theory of epigenesis (gradual emergence of form), preformationism held that the unborn offspring existed fully formed in the eggs or sperm of its parents prior to conception. The ovist model held that the maternal egg was the location of this preformed embryo, while the other preformationism model known as spermism preferred the paternal germ cell, as the name implies.

This embryology image is a pencil sketch by Nicolaas Hartsoeker, published as part of his 1694 French-language paper entitled Essai de Dioptrique, a semi-speculative work describing the sorts of new scientific observations that could be done using magnifying lenses. Dioptrique was published in Paris by the publishing house of Jean Anisson. The image depicts a curled up infant-like human, now referred to as a homunculus, inside the head of a sperm cell. This sketch is important to embryology because it is one of the most illustrative examples of preformationism, a theory of generation stating that each future member of any given species exists, fully formed though miniscule, within the gametic cells (sperm or eggs) of its parents. This theory was popular among naturalists in the eighteenth century.

Nicolaas Hartsoeker, a Dutch astronomer, optics manufacturer, and naturalist, was born 26 March 1656 in Gouda, Netherlands, and died 10 December 1725. His mother was Anna van der Mey and his father was Christiaan Hartsoeker, a prominent evangelical minister. His major contribution to embryology was his observations of human sperm cells, which he claimed to be the first to see under a microscope. His sketch of the homunculus, a tiny preformed human he believed to exist in the head of spermatazoa, is his lasting scientific legacy in the field of embryology. This sketch was only a minor part of his first publication, Essai de Dioptrique (1694), which dealt primarily with the use of optical lenses in science. In subsequent years the sketch became iconic of the theory of embryological development known now as preformationism. Hartsoeker himself was a vocal adherent of spermist preformationism and is often cited as the originator of the idea.

Preformationism was a theory of embryological development used in the late seventeenth through the late eighteenth centuries. This theory held that the generation of offspring occurs as a result of an unfolding and growth of preformed parts. There were two competing models of preformationism: the ovism model, in which the location of these preformed parts prior to gestation was the maternal egg, and the spermism model, in which a preformed individual or homunculus was thought to exist in the head of each sperm. Preformationism was a widely-held theory by Enlightenment-era scientists, but by the early 1800s, most scientists had abandoned it, in part because higher magnification in microscopes enabled them to see the very earliest stages of embryos as small collections of cells. Prior to preformationism, naturalists who studied embryo development favored the theory of spontaneous generation in lower animals, such as flies, which appeared to arise from manure. In higher animals, however, scientists used the theory of epigenesis put forth by Aristotle, who said that maternal and paternal fluids came together in the uterus and solidified during early gestation into a fetus. Preformationism was the first theory of generation and development that applied to all organisms in the plant and animal kingdoms.

In 2012, Jennifer Doudna, Emmanuelle Charpentier from the University of California, Berkeley, in Berkeley, California, and Umeå University in Umeå, Sweden, along with their colleagues discovered how bacteria use the CRISPR/cas 9 system to protect themselves from viruses. The researchers also proposed the idea of using the CRISPR/cas 9 system as a genome editing tool. In bacteria and archaea, researchers had found that CRISPR, which stands for clustered regularly interspaced short palindromic repeats, and CRISPR associated proteins, or cas, helped organisms recognize and silence the genetic material of viruses that have infected the cell before. In their experiment, Doudna, Charpentier, and their colleagues found how the specific molecules in bacteria can recognize and cut specific DNA sequences of invading viruses. Doudna, Charpentier, and their colleagues’ discovery of the CRISPR/cas 9 mechanism and proposal of using CRISPR/cas 9 for genetic editing led to the successful engineering of CRISPR/cas 9 as a novel method of editing genomes.

In 2013, George Church and his colleagues at Harvard University in Cambridge, Massachusetts published RNA-Guided Human Genome Engineering via Cas 9, in which they detailed their use of RNA-guided Cas 9 to genetically modify genes in human cells. Researchers use RNA-guided Cas 9 technology to modify the genetic information of organisms, DNA, by targeting specific sequences of DNA and subsequently replacing those targeted sequences with different DNA sequences. Church and his team used RNA-guided Cas 9 technology to edit the genetic information in human cells. Church and his colleagues also created a database that identified 190,000 unique guide RNAs for targeting almost half of the human genome that codes for proteins. In RNA-Guided Human Genome Engineering via Cas 9, the authors demonstrated that RNA-guided Cas 9 was a robust and simple tool for genetic engineering, which has enabled scientists to more easily manipulate genomes for the study of biological processes and genetic diseases.

Mary-Claire King studied genetics in the US in the twenty-first century. King identified two genes associated with the occurrence of breast cancer, breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2). King showed that mutated BRCA1 and BRCA2 genes cause two types of reproductive cancer, breast and ovarian cancer. Because of King’s discovery, doctors can screen women for the inheritance of mutated BRCA1 and BRCA2 genes to evaluate their risks for breast and ovarian cancer. King also demonstrated the genetic similarities between chimpanzees and humans and helped to identify victims of human rights abuses using genetics. King's identification of the BRCA genes and their relationship to breast and ovarian cancer, both reproductive cancers, has allowed physicians to screen thousands of women for the genes and for those women to choose to undergo preventative cancer treatment to lower their risk of cancer.

Robert Guthrie developed a method to test infants for phenylketonuria (PKU) in the United States during the twentieth century. PKU is an inherited condition that causes an amino acid called phenylalanine to build to toxic levels in the blood. Untreated, PKU causes mental disabilities. Before Guthrie’s test, physicians rarely tested infants for PKU and struggled to diagnosis it. Guthrie’s test enabled newborns to be quickly and cheaply screened at birth and then treated for PKU if necessary, preventing irreversible neurological damage. After developing the test, Guthrie traveled the world to advocate for mass screening for PKU in newborns. Along with his PKU test, Guthrie developed newborn screens for maple syrup urine disease and for galactosemia. Guthrie’s test for PKU and campaign for newborn screening led to the early diagnoses of PKU in thousands of infants, preventing those infants from developing mental disabilities.

In 2015, Junjiu Huang and his colleagues reported their attempt to enable CRISPR/cas 9-mediated gene editing in nonviable human zygotes for the first time at Sun Yat-Sen University in Guangzhou, China. Their article, CRISPR /Cas9-mediated Gene Editing in Human Tripronuclear Zygotes, was published in Protein and Cell. Nonviable zygotes are sperm-fertilized eggs that cannot develop into a fetus. Researchers previously developed the CRISPR/cas 9 gene editing tool, which is a system that originated from bacteria as a defense mechanism against viruses. In their article, Huang and his team demonstrate that CRISPR/cas-9 gene editing can be used to correct a mutation in zygotes, or sperm-fertilized egg cells. However, they report that using CRISPR/cas 9 to edit those nonviable human zygotes led to off-target changes and, therefore, to unintended mutations in the human genome. Before Huang and his colleagues' experiment, CRISPR/cas 9 had never been used on human zygotes. In their article, Huang and his colleagues demonstrated the need to improve CRISPR/cas 9 gene editing accuracy before using it for gene therapy to treat and correct genetic diseases in humans.

David Baltimore studied viruses and the immune system in the US during the twentieth century. In 1975, Baltimore was awarded the Nobel Prize in Physiology or Medicine for discovering reverse transcriptase, the enzyme used to transfer information from RNA to DNA. The discovery of reverse transcriptase contradicted the central dogma of biology at the time, which stated that the transfer of information was unidirectional from DNA, RNA, to protein. Baltimore’s research on reverse transcriptase led to the discovery of retroviruses, which accelerated the development of treatments for human immunodeficiency virus or HIV and cancer vaccines. Baltimore also influenced public policy and opinion on genetic engineering. In 1975, he helped organize the Asilomar Conference in Pacific Grove, California, which discussed the regulation of recombinant DNA or the DNA created using multiple sources of genetic material. Baltimore’s research demonstrated how retroviruses replicate and infect cells, and his influence on the Asilomar Conference on Recombinant DNA has guided discussions about regulating biotechnology.