Searching for Missing Genomes

Enormous strides have been made to unravel the secrets of the human genome, so why are we missing the genetic information of most of the planet?

In the summer of 2020, a 63-year-old African American woman with colon cancer was treated with a common chemotherapy known as fluoropyrimidines at the National Institutes of Health (NIH) Clinical Centre in Bethesda, Maryland. But over the coming weeks, she began to develop a severe side-effect known as pancytopenia – a rapid and sudden decrease of red and white blood cells and platelets – causing her to be rushed into intensive care.

This kind of reaction is surprisingly common. Around 38,000 cancer patients in England and approximately 154,000 patients in the US are initiated on fluoropyrimidine-based treatments every year. While fluoropyrimidines help save lives, between 20% and 30% of the people who receive these drugs require lower doses, because their bodies struggle to process them. If given the standard dose, they experience reactions which can vary from severe to fatal.

Like many adverse drug reactions, this is thought to be at least in part due to variations in the human genome, the strings of billions of letters or chemical bases which comprise our DNA. But while all humans share 99.9% of our genome, the remaining 0.1% varies markedly from one individual to another, or between ethnic groups. Differences in the underlying sequence behind a particular gene – which can be anything from a few hundred to several million bases – can have profound and far-reaching consequences for our health.

In recent years, genetic-sequencing studies have started to get to the bottom of why some people react so badly to fluoropyrimidines, pinpointing four different variations of a gene called DPYD which is involved in metabolism, as the likely cause. Healthcare systems around the world have now begun sequencing the DNA of certain cancer patients and screening for each of these four variants before determining their chemotherapy dose.

The only problem is that these studies were done entirely on white people, or as geneticists say, "individuals of European ancestry". While different variants of DPYD may serve as warning signs for people of other ethnicities, we do not have enough data to be sure of which variants are most applicable to different ethnic groups. "Ethnic minority patients will usually be given conventional doses of the drugs," says Munir Pirmohamed, a pharmacologist at the University of Liverpool in the UK. "Some of these patients will carry other ethnic-specific variants which also affect their ability to metabolise these drugs, but we do not currently genotype for those, largely because we do not know."  READ MORE...

Cloning Humans

There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments.

Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. 

The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits.

Chimpanzees are the closest relatives of Homo sapiens, our species. There is a precise correspondence bone by bone between the skeletons of a chimpanzee and a human. Humans bear young like apes and other mammals. Humans have organs and limbs similar to birds, reptiles, and amphibians; these similarities reflect the common evolutionary origin of vertebrates. 

However, it does not take much reflection to notice the distinct uniqueness of our species. Conspicuous anatomical differences between humans and apes include bipedal gait and an enlarged brain. Much more conspicuous than the anatomical differences are the distinct behaviors and institutions. 

Humans have symbolic language, elaborate social and political institutions, codes of law, literature and art, ethics, and religion; humans build roads and cities, travel by motorcars, ships, and airplanes, and communicate by means of telephones, computers, and televisions.

Human Origins
The hominin lineage diverged from the chimpanzee lineage 6–7 Ma, and it evolved exclusively in the African continent until the emergence of Homo erectus, somewhat before 1.8 Ma. Shortly after its emergence in tropical or subtropical Africa, H. erectus spread to other continents. 

Fossil remains of H. erectus (sensu lato) are known from Africa, Indonesia (Java), China, the Middle East, and Europe. H. erectus fossils from Java have been dated at 1.81 ± 0.04 and 1.66 ± 0.04 Ma and from Georgia at 1.6–1.8 Ma (1). Anatomically distinctive H. erectus fossils have been found in Spain, deposited before 780,000 y ago, the oldest in southern Europe (2).

The transition from H. erectus to H. sapiens occurred around 400,000 y ago, although this date is not well determined owing to uncertainty as to whether some fossils are erectus or archaic forms of sapiens. H. erectus persisted for some time in Asia, until 250,000 y ago in China and perhaps until 100,000 ago in Java, and thus was contemporary with early members of its descendant species, H. sapiens. 

Fossil remains of Neandertal hominids (Homo neanderthalensis), with brains as large as those of H. sapiens, appeared in Europe earlier than 200,000 y ago and persisted until 30,000 or 40,000 y ago (3, 4).  READ MORE...