Genome Sequencing Quotes

Our ability to read out this sequence of our own genome has the makings of a philosophical paradox. Can an intelligent being comprehend the instructions to make itself? —John Sulston Scholars

There was never a better illustration of the validity of the Enlightenment dream – that order can emerge where nobody is in charge. The genome, now sequenced, stands as emphatic evidence that there can be order and complexity without any management.

The beauty in the genome is of course that it's so small. The human genome is only on the order of a gigabyte of data...which is a tiny little database. If you take the entire living biosphere, that's the assemblage of 20 million species or so that constitute all the living creatures on the planet, and you have a genome for every species the total is still about one petabyte, that's a million gigabytes - that's still very small compared with Google or the Wikipedia and it's a database that you can easily put in a small room, easily transmit from one place to another. And somehow mother nature manages to create this incredible biosphere, to create this incredibly rich environment of animals and plants with this amazingly small amount of data.

S. Schiffels and R. Durbin, “Inferring Human Population Size and Separation History from Multiple Genome Sequences,” Nature Genetics 46 (2014): 919–25.

Creating a PCR test for a new pathogen is a pretty easy task once you’ve sequenced its genome. Because you already know what its genes look like, you can create the special substances, dye, and other necessary products very quickly—which is why researchers were able to establish PCR tests for COVID just twelve days after the first genome sequences were published.

A DNA sequence for the genome of bacteriophage ΦX174 of approximately 5,375 nucleotides has been determined using the rapid and simple 'plus and minus' method. The sequence identifies many of the features responsible for the production of the proteins of the nine known genes of the organism, including initiation and termination sites for the proteins and RNAs. Two pairs of genes are coded by the same region of DNA using different reading frames.

took ten years and $5 billion to sequence the first human genome, and now it takes less than twenty-four hours and costs less than $1,500.5

This genome was so well-preserved that it has provided DNA sequences as reliable as those from a living human. This certainly makes the Denisovans worthy of a tale.

Our ability to read out this sequence of our own genome has the makings of a philosophical paradox. Can an intelligent being comprehend the instructions to make itself? —John Sulston

Surprisingly, palindromes appear not just in witty word games but also in the structure of the male-defining Y chromosome. The Y's full genome sequencing was completed only in 2003. This was the crowning achievement of a heroic effort, and it revealed that the powers of preservation of this sex chromosome have been grossly underestimated. Other human chromosome pairs fight damaging mutations by swapping genes. Because the Y lacks a partner, genome biologists had previously estimated that its cargo was about to dwindle away in perhaps as little as five million years. To their amazement, however, the researchers on the sequencing team discovered that the chromosome fights withering with palindromes. About six million of its fifty million DNA letters form palindromic sequences-sequences that read the same forward and backward on the two strands of the double helix. These copies not only provide backups in case of bad mutations, but also allow the chromosome, to some extent, to have sex with itself-arms can swap position and genes are shuffled. As team leader David Page of MIT has put it, "The Y chromosome is a hall of mirrors.

If your personal genome sequence was written out longhand, it would be a three-billion-word book. The King James Version of the Bible has 783,137 words, so your genetic code is the equivalent of nearly four thousand Bibles. And if your personal genome sequence were an audio book and you were read at a rate of one double helix per second, it would take nearly a century to put you into words!

As the leader of the international Human Genome Project, which had labored mightily over more than a decade to reveal this DNA sequence, I stood beside President Bill Clinton in the East Room of the White House... Clinton's speech began by comparing this human sequence map to the map that Meriwether Lewis had unfolded in front of President Thomas Jefferson in that very room nearly two hundred years earlier. Clinton said, "Without a doubt, this is the most important, most wondrous map ever produced by humankind." But the part of his speech that most attracted public attention jumped from the scientific perspective to the spiritual. "Today," he said, "we are learning the language in which God created life. We are gaining ever more awe for the complexity, the beauty, and the wonder of God's most divine and sacred gift." Was I, a rigorously trained scientist, taken aback at such a blatantly religious reference by the leader of the free world at a moment such as this? Was I tempted to scowl or look at the floor in embarrassment? No, not at all. In fact I had worked closely with the president's speechwriter in the frantic days just prior to this announcement, and had strongly endorsed the inclusion of this paragraph. When it came time for me to add a few words of my own, I echoed this sentiment: "It's a happy day for the world. It is humbling for me, and awe-inspiring, to realize that we have caught the first glimpse of our own instruction book, previously known only to God." What was going on here? Why would a president and a scientist, charged with announcing a milestone in biology and medicine, feel compelled to invoke a connection with God? Aren't the scientific and spiritual worldviews antithetical, or shouldn't they at least avoid appearing in the East Room together? What were the reasons for invoking God in these two speeches? Was this poetry? Hypocrisy? A cynical attempt to curry favor from believers, or to disarm those who might criticize this study of the human genome as reducing humankind to machinery? No. Not for me. Quite the contrary, for me the experience of sequencing the human genome, and uncovering this most remarkable of all texts, was both a stunning scientific achievement and an occasion of worship.

In 1977, when Fred Sanger had sequenced the genome of the phiX virus, with 5,386 bases of DNA, that number represented the outer limit of gene-sequencing capability. The human genome contains 3,095,677,412 base pairs-representing a scale shift of 574,000-fold.

The Human Genome Project, the full sequence of the normal human genome, was completed in 2003. In its wake comes a far less publicized but vastly more complex project: fully sequencing the genomes of several human cancer cells. Once completed, this effort, called the Cancer Genome Atlas, will dwarf the Human Genome Project in its scope. The sequencing effort involves dozens of teams of researchers across the world. The initial list of cancers to be sequenced includes brain, lung, pancreatic, and ovarian cancer. The Human Genome Project will provide the normal genome, against which cancer’s abnormal genome can be juxtaposed and contrasted. The result, as Francis Collins, the leader of the Human Genome Project describes it, will be a “colossal atlas” of cancer—a compendium of every gene mutated in the most common forms of cancer: “When applied to the 50 most common types of cancer, this effort could ultimately prove to be the equivalent of more than 10,000 Human Genome Projects in terms of the sheer volume of DNA to be sequenced.

They would certainly have been simpler than the earliest known microbial mats, but somewhere in your genome there will be sequences of DNA that have been faithfully passed down across the great sweep of geological time, and if you have children, you’ll pass these four-billion-year-old messages on to them.

Scientists were able to replicate this process—successfully replacing a viral sequence with other types of DNA and inserting that DNA in the target cell—making “genomic surgery” possible. CRISPR rapidly replaced older methods of genetic engineering, making gene editing cleaner, more accurate, and much faster.

Introns are not the exception in human genes; they are the rule. Human introns are often enormous-spanning several hundreds of thousands of bases of DNA. And genes themselves are separated from each other by long stretches of intervening DNA, called intergenic DNA. Intergenic DNA and introns-spaces between genes and stuffers within genes-are though to have sequences that allow genes to be regulated in context. To return to our analogy; these regions might be described as long ellipses scattered with occasional punctuation marks. The human genome can thus be visualized as: This......is............the......(...)...s...truc...ture......of......your......gen...om...e; The words represent genes. The long ellipses between the words represent the stretches of intergenic DNA. The shorter ellipses within the words (gen...ome...e) are introns. The parentheses and semicolons-punctuation marks-are regions of DNA that regulate genes.

Our prototypical behavior has occurred. How was it influenced by events when the egg and sperm that formed that person joined, creating their genome—the chromosomes, the sequences of DNA—destined to be duplicated in every cell in that future person’s body? What role did those genes play in causing that behavior?

An arcane microbial defense, devised by microbes, discovered by yogurt engineers, and reprogrammed by RNA biologists, has created a trapdoor to the transformative technology that geneticists had sought so longingly for decades: a method to achieve directed, efficient, and sequence-specific modification of the human genome.

The structure of the human genome can thus be likened to a sentence that reads- This......is the......str...uc......ture...,,,...of...your...(...gen...ome...)... - where the words correspond to the genes, the ellipses correspond to the spacers and stuffers, and the occasional punctuation marks demarcate the regulatory sequence of genes.

The best way to figure out what Perl is used for is to look at the ... Comprehensive Perl Archive Network (the CPAN, for short). ... [Y]ou'll get the impression that Perl has interfaces to almost everything in the world. With a little thought, you may figure out the reason Perl has interfaces to everything is not so much so Perl itself can talk to everything, but so Perl can get everything in the world talking to everything else in the world. The combinatorics are staggering. The very first issue of The Perl Journal ... contained an article entitled 'How Perl Saved the Human Genome Project'. It explains how all the different genome sequencing laboratories used different databases with different formats, and how Perl was used to massage the data into a cohesive whole.

In the above examples, a sample of the tumor (e.g., biopsy) is tested to determine the molecular signature. Testing may be by genetic sequence tests (e.g., for BCR-ABL, mutated EGFR, or HER2 gene amplification) or tissue protein stains (e.g., for the presence of ER/PR receptors or HER2 protein overexpression). The results of the testing will guide the choice of treatment—it will be personalized for the individual.

Oxytocin and vasopressin are chemically similar hormones; the DNA sequences that constitute their genes are similar, and the two genes occur close to each other on the same chromosome. There was a single ancestral gene that, a few hundred million years ago, was accidentally “duplicated” in the genome, and the DNA sequences in the two copies of the gene drifted independently, evolving into two closely related genes

How does the body push the comparatively tiny genome so far? Many researchers want to put the weight on learning and experience, apparently believing that the contribution of the genes is relatively unimportant. But though the ability to learn is clearly one of the genome's most important products, such views overemphasize learning and significantly underestimate the extent to which the genome can in fact guide the construction of enormous complexity. If the tools of biological self-assembly are powerful enough to build the intricacies of the circulatory system or the eye without requiring lessons from the outside world, they are also powerful enough to build the initial complexity of the nervous system without relying on external lessons. The discrepancy melts away as we appreciate the true power of the genome. We could start by considering the fact that the currently accepted figure of 30,000 could well prove to be too low. Thirty thousand (or thereabouts) is, at press time, the best estimate for how many protein-coding genes are in the human genome. But not all genes code for proteins; some, not counted in the 30,000 estimate, code for small pieces of RNA that are not converted into proteins (called microRNA), of "pseudogenes," stretches of DNA, apparently relics of evolution, that do not properly encode proteins. Neither entity is fully understood, but recent reports (from 2002 and 2003) suggest that both may play some role in the all-important process of regulating the IFS that control whether or not genes are expressed. Since the "gene-finding" programs that search the human genome sequence for genes are not attuned to such things-we don't yet know how to identify them reliably-it is quite possible that the genome contains more buried treasure.

(...) to think that worms and slugs are neurologically simple is another blunder of contemporary, scientifically uninformed philosophy. To take as an example the current “superstar” nematode worm --superstar, because it was the first multicellular organism to have its genome completely sequenced, by 1998, and is widely used as a model organism-- the 1 mm long Caenorhabditis elegans, it exhibits a nervous system of 302 neurons and a sensorimotor system with very complex connectivity patterns.

Should we consider allowing parents to fully sequence their children’s genomes and potentially terminate pregnancies with such known devastating genetic mutations? We would certainly eliminate Erika’s mutation from the human gene pool—but we would eliminate Erika as well. I will not minimize the enormity of Erika’s suffering, or that of her family—but there is, indubitably, a deep loss in that. To fail to acknowledge the depth of Erika’s anguish is to reveal a flaw in our empathy. But to refuse to acknowledge the price to be paid in this trade-off is to reveal, conversely, a flaw in our humanity.

Despite the advancements of systematic experimental pipelines, literature-curated protein-interaction data continue to be the primary data for investigation of focused biological mechanisms. Notwithstanding the variable quality of curated interactions available in public databases, the impact of inspection bias on the ability of literature maps to provide insightful information remains equivocal. The problems posed by inspection bias extend beyond mapping of protein interactions to the development of pharmacological agents and other aspects of modern biomedicine. Essentially the same 10% of the proteome is being investigated today as was being investigated before the announcement of completion of the reference genome sequence. One way forward, at least with regard to interactome mapping, is to continue the transition toward systematic and relatively unbiased experimental interactome mapping. With continued advancement of systematic protein-interaction mapping efforts, the expectation is that interactome 'deserts', the zones of the interactome space where biomedical knowledge researchers simply do not look for interactions owing to the lack of prior knowledge, might eventually become more populated. Efforts at mapping protein interactions will continue to be instrumental for furthering biomedical research.

In 2006, the Vogelstein team revealed the first landmark sequencing effort by analyzing thirteen thousand genes in eleven breast and colon cancers. (Although the human genome contains about twenty thousand genes in total, Vogelstein’s team initially had tools to assess only thirteen thousand.) In 2008, both Vogelstein’s group and the Cancer Genome Atlas consortium extended this effort by sequencing hundreds of genes of several dozen specimens of brain tumors. As of 2009, the genomes of ovarian cancer, pancreatic cancer, melanoma, lung cancer, and several forms of leukemia have been sequenced, revealing the full catalog of mutations in each tumor type. Perhaps

It is dynamic. In some cells, it reshuffles its own sequence to make novel variants of itself. Cells of the immune system secrete "anti-bodies"-missilelike proteins designed to attach themselves to invading pathogens. But since pathogens are constantly evolving, antibodies must also be capable of changing; an evolving pathogen demands an evolving host. The genome accomplishes this counter-evolution by reshuffling its genetic elements-thereby achieving astounding diversity)s...tru...c...t...ure and g...en...ome can be reshuffled to form an entirely new word c...ome...t). The reshuffled genes generate the diversity of antibodies. In these cells, every genome is capable of giving rise to an entirely different genome.

These chunks of DNA are highly informative. For example, we can use their length to date the time of interbreeding. This relies on the fact that over time, long lengths of genome are chopped and swapped by recombination. The longer the intact sequence, the fewer generations undergone since interbreeding—the effect has been confirmed by looking at ancient DNA from Siberian contemporaries of the Neanderthals: modern-looking Homo sapiens sapiens, for whom Neanderthal interbreeding must have been a recent thing. These true Moderns have significantly longer Neanderthal regions in their genome. Such considerations put our Neanderthal hybridisation suggestively close to our recent African exodus, between 50,000 and 60,000 years ago.*

If I sequenced my own genome and showed it to a geneticist, she would be able to say approximately where on the planet I or my ancestors came from by matching variants in my genome with the geographic patterns of variants across the globe. She would not, however, be  able to tell whether I was smart or dumb, tall or short, or almost anything else that matters with respect to how I function as a human being. Indeed, despite the fact that most efforts to understand the genome have sprung from efforts to combat disease, for the vast majority of diseases, such as Alzheimer’s, cancer, diabetes, or heart disease, our current understanding allows us only to assign vague probabilities to the likelihood that an individual will develop them.

It was a fascinating hint that flu might have a heritable component, but other studies failed to replicate the finding. Then in January 2011, in the midst of the annual flu season in France, a two-year-old girl was admitted to the intensive care unit of the Necker Hospital for Sick Children in Paris, suffering from ARDS (acute respiratory distress syndrome). Doctors saved her life, and one of them, Jean-Laurent Casanova, sequenced her genome. He wanted to know if it held the key to why an otherwise healthy child had nearly died of a disease that most children shrug off. It turned out that the girl had inherited a genetic defect that meant she was unable to produce interferon, that all-important first-line defence against viruses. As a result, her besieged immune system went straight to plan B: a massive inflammatory response similar to the one pathologists saw in 1918.

There is no real reason why Disney should not buy up the human genome, which is currently being sequenced, to turn it into a genetic attraction. Why not cryogenize the whole planet, exactly as Walt Disney had himself cryogenized in liquid nitrogen, with a view to some kind of resurrection or other in the real world? But there no longer is a real world, and there won’t be one – not even for Walt Disney: if he wakes up one day he’ll get the shock of his life. In the meantime, from the depths of his liquid nitrogen he goes on annexing the world – both imaginary and real – subsuming it into the spectral universe of virtual reality in which we have all become extras. The difference is that, as we slip on our data suits or our sensors, or tap away at our keyboards, we are moving into living spectrality, whereas he, the brilliant precursor, has moved into the virtual reality of death.

the disparity between Eastern and Western spirituality resembles that found between Eastern and Western medicine—with the arrow of embarrassment pointing in the opposite direction. Humanity did not understand the biology of cancer, develop antibiotics and vaccines, or sequence the human genome under an Eastern sun. Consequently, real medicine is almost entirely a product of Western science. Insofar as specific techniques of Eastern medicine actually work, they must conform, whether by design or by happenstance, to the principles of biology as we have come to know them in the West. This is not to say that Western medicine is complete. In a few decades, many of our current practices will seem barbaric. One need only ponder the list of side effects that accompany most medications to appreciate that these are terribly blunt instruments. Nevertheless, most of our knowledge about the human body—and about the physical universe generally—emerged in the West. The rest is instinct, folklore, bewilderment, and untimely death.

The bacterial defense system was soon found to involve at least two critical components. The first piece was the "seeker"-an RNA encoded in the bacterial genome that matched and recognized the DNA of the viruses. The principle for the recognition, yet again, was binding: the RNA "seeker" was able to find and recognize the DNA of an invading virus because it was a mirror image of that DNA-the yin to its yang. It was like carrying a permanent image of your enemy in your pocket-or, in the bacteria's case, an inverted photograph, etched indelibly into its genome. The second element of the defense system was the "hitman." Once the viral DNA had been recognized and matched as foreign (by its reverse-image), a bacterial protein named Cas9 was deployed to deliver the lethal gash to the viral gene. The "seeker" and the "hitman" worked in concert: the Cas9 protein delivered its cuts to the genome only after the sequence had been matched by the recognition element. It was a classic combination of collaborators-spotter and executor, drone and rocket, Bonnie and Clyde.

The trends speak to an unavoidable truth. Society's future will be challenged by zoonotic viruses, a quite natural prediction, not least because humanity is a potent agent of change, which is the essential fuel of evolution. Notwithstanding these assertions, I began with the intention of leaving the reader with a broader appreciation of viruses: they are not simply life's pathogens. They are life's obligate partners and a formidable force in nature on our planet. As you contemplate the ocean under a setting sun, consider the multitude of virus particles in each milliliter of seawater: flying over wilderness forestry, consider the collective viromes of its living inhabitants. The stunnig number and diversity of viruses in our environment should engender in us greater awe that we are safe among these multitudes than fear that they will harm us. Personalized medicine will soon become a reality and medical practice will routinely catalogue and weigh a patient's genome sequence. Not long thereafter one might expect this data to be joined by the patient's viral and bacterial metagenomes: the patient's collective genetic identity will be recorded in one printout. We will doubtless discover some of our viral passengers are harmful to our health, while others are protective. But the appreciation of viruses that I hope you have gained from these pages is not about an exercise in accounting. The balancing of benefit versus threat to humanity is a fruitless task. The viral metagenome will contain new and useful gene functionalities for biomedicine: viruses may become essential biomedical tools and phages will continue to optimize may also accelerate the development of antibiotic drug resistance in the post-antibiotic era and emerging viruses may threaten our complacency and challenge our society economically and socially. Simply comparing these pros and cons, however, does not do justice to viruses and acknowledge their rightful place in nature. Life and viruses are inseparable. Viruses are life's complement, sometimes dangerous but always beautiful in design. All autonomous self-sustaining replicating systems that generate their own energy will foster parasites. Viruses are the inescapable by-products of life's success on the planet. We owe our own evolution to them; the fossils of many are recognizable in ERVs and EVEs that were certainly powerful influences in the evolution of our ancestors. Like viruses and prokaryotes, we are also a patchwork of genes, acquired by inheritance and horizontal gene transfer during our evolution from the primitive RNA-based world. It is a common saying that 'beauty is in the eye of the beholder.' It is a natural response to a visual queue: a sunset, the drape of a designer dress, or the pattern of a silk tie, but it can also be found in a line of poetry, a particularly effective kitchen implement, or even the ruthless efficiency of a firearm. The latter are uniquely human acknowledgments of beauty in design. It is humanity that allows us to recognize the beauty in the evolutionary design of viruses. They are unique products of evolution, the inevitable consequence of life, infectious egotistical genetic information that taps into life and the laws of nature to fuel evolutionary invention.

Although we fully understand the genetic code-i.e., how the information in a single gene is used to build a protein-we comprehend virtually nothing of the genomic code-i.e., how multiple genes spread across the human genome coordinate gene expression in space and time to build, maintain, and repair a human organism. The genetic code is simple: DNA is used to build RNA, and RNA is used to build a protein. A triplet of bases in DNA specifies one amino acid in the protein. The genomic code is complex: appended to a gene are sequences of DNA that carry information on when and where to express the gene. We do not know why certain genes are located in particular geographic locations in the genome, and how the tracts of DNA that lie between genes regulate and coordinate gene physiology. There are codes beyond codes, like mountains beyond mountains.

This is not a book about the Human Genome Project — about mapping and sequencing techniques - but a book about what that project has found. Some time in the year 2000, we shall probably have a rough first draft of the complete human genome. In just a few short years we will have moved from knowing almost nothing about our genes to knowing everything. I genuinely believe that we are living through the greatest intellectual moment in history. Bar none. Some may protest that the human being is more than his genes. I do not deny it. There is much, much more to each of us than a genetic code. But until now human genes were an almost complete mystery. We will be the first generation to penetrate that mystery. We stand on the brink of great new answers but, even more, of great new questions. This is what I have tried to convey in this book.

We have sequenced each of your genomes from the blood samples you provided and have determined that—as expected—a disproportionate number of you share what’s known as the ‘wanderlust gene,’ DRD4-7R. This gene is highly correlated with a desire for novel experiences. Many of the world’s greatest explorers, adventurers, and entrepreneurs have this gene. Its

problems.” “There might be more than a small group of people, Nancy. If the technology can now be applied commercially, it means it’s been around for longer.” “What’s your point, Jasper?” “We’ve had our own government genome projects investigating DNA sequencing, composition, replication, repair and gene therapy for decades.

Such then is the nature of quasispecies : the density of the sequence cloud at any point in sequence space is determined by the relative fitness of the sequence; regions of the cloud representing sequences of lesser fitness will be less densely populated and those with higher fitness, most populated. Here lies the most powerful quality of viral quasispecies: the density distribution of fitness variants dictates that sequences are represented at frequencies in relation to their relative fitness. Genomes with lower fitness will replicate poorly, or not at all, and the fittest genomes will replicate most efficiently. It therefore follows that there is a large bias toward the production of well-adapted genotypes: there are more of them, and they undergo most replicative cycles. This can permit viruses to experience evolutionary adaptation at rates that are orders of magnitude higher than those that could be achieved by truly random unbiased mutation. Sequences rapidly condense around the fittest area of the sequence space. Should the environment change, and, therefore, selective pressures change, a quasispecies can opportunistically exploits its inherent adaptive potential. Genotypes rapidly and ever-faster gravitate toward the cloud's new notational center of gravity. Changes in the fitness landscape of the sequence space that is occupied by a quasispecies are the natural consequence of altered selective pressures operating on the virus population. Such alterations may be the consequence of changed immunologic pressures exerted by the host, the application of antiviral drug therapy, or even cross-species transmission requiring the virus to adapt to a new host. Genotypes that once occupied the 'central' space, reserved for the fittest genotypes, are reduced in frequency and now occupy the more sparsely populated fringes of the fitness landscape; the very edge of the sequence cloud if you will. Here too lies an advantage for a quasispecies: it has a memory. The once best-adapted genotypes, now at a fitness disadvantage, can persist in the quasispecies as minor sequence variants. Under circumstances of fluctuating selective pressures, the ability of the population to recall an 'old' genome variant is a great asset. The quasispecies can rapidly respond and adapt by plucking out a preexisting variant and quickly coalescing around it to recreate an optimal fitness landscape.

Collectively, the veritable zoo of mobile genetic elements comprises a remarkable 40 percent of our genome. The retroviral sequences littered across all vertebrate genomes are termed endogenous retroviral elements (ERVs). Endogenous retroviral sequences themselves are so plentiful that they take up more space in our genomes than genes encoding human proteins. Their existence is evidence of waves of retroviral infection and germline infiltration throughout vertebrate evolution. We have only recently begun to realize the powerful influence that retroviruses wielded over the evolution of vertebrate genomes and the identity of our species. They were catalysts of genetic instability that fueled evolutionary change; today they are vestiges of their former selves, fossils of viruses that once preyed on vertebrate hosts. Their remains are evidence of pyrrhic victories of sorts in many wars and arms races that have taken place between retroviruses and hosts. Most endogenous retroviruses have long been silenced by host cell restriction mechanisms. Associated with no phenotype, and under no selective pressure they become nonviable after millions of years of mutational drift, resulting in the accumulation of mutations and deletions in their coding sequences and control elements.

After a handful of geeks sequenced the Neanderthal genome and found a 2% match, they opened the flood gates to hundreds of geneticists that now make a living telling you what diseases you inherited from an extinct Arctic ape.

The litter of ERVs across vertebrate genomes, mainly in the form of defective and deleted proviruses, mutationally inactivated proteins coding sequences, and isolated LTRs, confirms that the vast majority of endogenized retroviral genones decay to nonfunctional sequences. If they have been silenced by cellular regulatory mechanisms or if their gene products are not under purifying or positive selective pressures, their DNA sequences will be under no selective pressure to retain their functionality. Over time, they accumulate random mutations and their sequences drift without consequence to the host. That ERVs mostly become such inconsequential DNA is a topic of hot debate; it is, however, an easy matter to pick several examples that illustrate how hosts can benefit from their ERVs. As for all matters of evolution, we bear witness only to the successful events that are now fixed in genomes. Evolutionary failures, no matter they far outnumber the successes, go unrecorded, rapidly purged from the gene pool.

Krause and his team unearthed the evolution of Yersinia pestis, and the genomic tracks of its terrible journey. An earlier study had shown that, just like the Plague of Justinian, the Black Death in the 1340s had also originated in China. With a publicly available database of the full sequence, the history and the genetics can be aligned. Over a five-year period we can track a course from Russia to Constantinople, to Messina, to Genoa, Marseille, Bordeaux, and finally London. All these ports acted as points from which radiation of the plague could crawl inland. En route, it claimed the lives of some 5 million people.

The rediscovery of Mendel's laws of heredity in the opening weeks of the 20th century sparked a scientific quest to understand the nature and content of genetic information that has propelled biology for the last hundred years. The scientific progress made [since that time] falls naturally into four main phases, corresponding roughly to the four quarters of the century." "The first established the cellular basis of heredity: the chromosomes. The second defined the molecular basis of heredity: the DNA double helix. The third unlocked the informational basis of heredity [i.e. the genetic code], with the discovery of the biological mechanism by which cells read the information contained in genes, and with the invention of the recombinant DNA technologies of cloning and sequencing by which scientists can do the same." The sequence of the human genome, the project asserted, marked the starting point of the "fourth phase" of genetics. This was the era of "genomics" - the assessment of the entire genomes of organisms, including humans. There is an old conundrum in philosophy that asks if an intelligent machine can ever decipher its own instruction manual. For humans, the manual was now complete. Deciphering it, reading it, and understanding it would be quite another matter.

To remind you, the Human Genome Project took about a decade to sequence a single human genome, completed in April of 2003 at an approximate cost of nearly $3 billion. Today Illumina’s latest generation sequencer has the potential to sequence your genome in an hour and for $100—or 87,600 times faster and 30 million times cheaper.

Second, “this work provides a proof of principle for producing cells based on genome sequences designed in the computer. DNA sequencing of a cellular genome allows storage of the genetic instructions of life as a digital file.” The reduction of genetic instructions to a digital file delivered a knockout second blow to vitalism.

While the first genomic sequencing cost $3 billion and took fifteen years to complete, today a whole human genome can be sequenced in an afternoon for about $200.

It was one thing to get the sequence of one little piece of mtDNA that looked interesting from the Neanderthal fossil, but it would be quite another to convince ourselves, let alone the rest of the world,

I myself had often suggested that extraordinary claims about DNA sequences from ancient bones require extraordinary evidence—namely, repetition of the results in another lab, an unusual step in a typically competitive scientific field.

The era of digital DNA (if there ends up being one) is still a long way off. Million-fold improvements in the scale and speed of DNA synthesis are needed if it is to become a viable solution to the world’s growing data storage problem. But it is worth considering that the cost of DNA sequencing has dropped two-million-fold since 2003, a pace that exceeds Moore’s Law. And consider this: at a theoretical maximum density of 2 bits per nucleotide, all of the world’s data could be stored in a mere kilogram of DNA. That’s a lot of DNA—it’s also a lot of data! It is not difficult to envision a future in which the world’s data archiving centres are full of DNA chips instead of computer hard drives.

Genomics has transformed the biological sciences. From epidemiology and medicine to evolution and forensics, the ability to determine an organism’s complete genetic makeup has changed the way science is done and the questions that can be asked of it. Far and away the most celebrated achievement of genomics is the Human Genome Project, a technologically challenging endeavour that took thousands of scientists around the world thirteen years and ~US$3 billion to complete. In 2000, American President William Clinton referred to the resulting genome sequence as ‘the most important, most wondrous map ever produced by humankind.’ Important though it was, this ‘map’ was a low-resolution first pass—a beginning not an endpoint. As of this writing, thousands of human genomes have been sequenced, the primary goals being to better understand our biology in health and disease, and to ‘personalize’ medicine. Sequencing a human genome now takes only a few days and costs as little as US$1,000. The genomes of simple bacteria and viruses can be sequenced in a matter of hours on a device that fits in the palm of your hand. The information is being used in ways unimaginable only a few years ago.

approximately 80 percent of the final sequence of the Human Genome Project comes from a library known as RPCI-11, containing the DNA of an African American, while the rest comes from RPCI-13, a library made from Pieter’s own DNA.

The problem was a crazy problem. It wasn’t going to have a non-crazy solution. Still, she’d sort of shocked herself. She’d never had the slightest interest in business. But if she wanted to save the country, she’d need to become an entrepreneur, and create a company—though in business, she quickly learned, she couldn’t talk like that. When she said she wanted to build a tool “to save the country,” people just smiled and thought she was goofy in the head. But when she said things like “I’m going to create a data-based tool for disease prevention that companies can use to secure their supply chains,” serious business types nodded. “Five smart people have replied with confusion when I said the company was to save the world and protect our country,” said Charity, after her first attempts to explain her vague idea. “Then when I said, ‘We’re going to do private government operations, like Blackwater,’ their eyes lit up and they said, ‘Oh wow, you could take over the world.’ ” She’d entered the private sector with the bizarre ambition to use it to create an institution that might be used by the public sector. She’d already hired twenty people, among them public-health nurses and some of the team at the Chan Zuckerberg Biohub responsible for genomic sequencing, including Josh Batson and David Dynerman. Joe DeRisi had signed on as an adviser; Carter Mecher was about to. She’d raised millions of dollars in capital. Venrock, a leading health care venture capitalist, had taken a stake in the new company. As a local health officer, she hadn’t been able to get the tens of thousands of dollars she needed for some new disease-stopping machine. In the private sector, people would throw tens of millions at an idea: if she failed, it wouldn’t be because investors wouldn’t give her the money to try. The Public Health Company, she’d called it.

Humans are 99.9 percent identical in their haploid DNA/genome sequence of approximately 3.2 billion base pairs. However, while we all have roughly the same genes, there are polymorphisms—small differences in the sequence of these genes—that lead to changes in expression levels, and even alter a gene’s function.

I think there’s a huge misconception about how much science is actually going on. In the back corner of George Church’s lab [at Harvard] they have a few people who are using a tiny amount of resources that are available to them to attempt to swap out genes in elephant cells which are growing in culture in a dish in a lab. I have a student who’s trying to convince me that it’s a good idea to bring passenger pigeons back to life. There’s a group in Australia who are thinking about the gastric-brooding frog but are stuck because they can’t cause the cells to actually grow up. There’s a group in New Zealand that is thinking about bringing a Moa [an extinct bird] back to life and are working on sequencing the moa genome, which is not de-extinction, in itself. There’s a Spanish group that’s thinking about the bucardo [a subspecies of Spanish ibex that went extinct in 2000], and there’s the backbreeding group for the aurochs [an extinct species of wild cattle] in Holland. That’s it. That’s everything that’s going on in the world right now.

They sequenced the Neanderthal genome way back in 2010—the guy who did it won a Nobel Prize.

You may discover that a certain sequence of letters in your autosomal DNA is typically found in someone with Finnish heritage or Korean ancestry. Only a few years ago the world of science was turned upside down when it was discovered that in ancient times two nonhuman species contributed to the human genome.

The individual links of the chain are small molecules called nucleotides, which come in four types denoted by the letters A, C, G, and T. Your genome is the entire sequence of nucleotides in your DNA, or equivalently a long string of letters drawn from this four-letter

Only 2 per cent of our genome codes for proteins. A massive 42 per cent is composed of retrotransposons. These are very odd sequences of DNA, which probably originated from viruses in our evolutionary past. Some retrotransposons are transcribed to produce RNA and this can affect the expression of neighbouring genes. This can have serious consequences for cells. If it drives up expression of genes that cause cells to proliferate too aggressively, for example, this may nudge cells towards becoming cancerous.

An increasing number of devices allow people to collect data about themselves: blood sugar levels, the number of steps taken each day, and sleep cycles. It won’t be long before checking blood work will only require a relatively inexpensive device that plugs into a smartphone, not a visit to the doctor’s office. The cost of sequencing the genome continues to drop, and soon it will be as unremarkable as taking a fingerprint.

Open the "book of life" and you will see a "text" of about 3 billion letters, filling about 10,000 copies of the new York Times Sunday edition. Each line looks something like this: TCTAGAAACA ATTGCCATTG TTTCTTCTCA TTTTCTTTTC ACGGGCAGCC These letters, abbreviations of the molecules making up the DNA, could easily mean that the anonymous donor whose genome has been sequenced will be bald by the age of fifty. Or they could reveal that he will develop Alzheimer's disease by seventy. We are repeatedly told that everything from our personality to future medical history is encoded in this book. Can you read it? I doubt it. Let me share a secret with you: Neither can biologists or doctors.

did you know that way back in the 1980s some scientists proposed an ambitious effort called the Human Protein Project to map all human proteins? It never happened. Instead, the NIH backed the Human Genome Project for one big reason: Proteins were tough to study, while genes were far easier to sequence. The tools dictate the science.

Unlike some other immune-system gene families, whose genes are all clustered together on one chromosome, the 10 human TLR genes are distributed between five chromosomes. This reflects the ancient, invertebrate origin of the Toll-like receptors, which were present before the two genome-wide duplications that occurred during the early evolution of the vertebrates around 500 million years ago. On the basis of sequence similarities, the Toll-like receptors form four evolutionary lineages (I, II, III, and IV) that are descendants of the four Toll-like receptor loci formed by these two ancient genome duplications.

The high degree of intertumoral heterogeneity revealed by TCGA shocked everyone. No single mutation could be identified that was required for the disease to start. No combination of mutations that initiated the disease could be found. Other than a few commonly mutated oncogenes, there was a frightening degree of randomness. The studies sequenced the tumors from eleven individuals with breast cancer and eleven individuals with colon cancer. Over eighteen thousand genes were sequenced, almost forty times the number in the initial studies and the most exhaustive sequencing to date. Vogelstein was stunned by the seeming random nature of the cancer genome seen two years into the project. He posed the question on everybody’s mind: “Is it possible to make sense out of this complexity?

When Hamiltonella's genome was sequenced, the real reason behind the bacterium's protective powers became apparent: about half of its DNA actually belonged to a virus. It was a phage - one of those spindly-legged, mucus-loving viruses that we met before. They typically kill bacteria by reproducing inside them and bursting fatally outward. But they can also opt for a more passive lifestyle, where they integrate their DNA into a bacterium's genome and stay there for many generations. Dozens of these phages now hide within Hamiltonella. The viruses are Hamiltonella's fists; they give the bacterial bodyguard its punch. Oliver showed that when Hamiltonella carries a particular phage strain, it renders aphids almost totally wasp-proof. If the virus disappeared, the same bacterium became useless, and almost all of its aphid hosts succumbed to their parasites. Without the phage, Hamiltonella might as well have been completely absent for all the good it did. The phages could be poisoning the wasps directly: they certainly mass-produce toxins that can attack animal cells, but don't seem to harm the aphids. Alternatively, they could split Hamiltonella apart, causing the bacteria's own toxins to spill onto the wasps. Or maybe the viral and bacterial chemicals are working together. Whatever the case, it is clear that an insect, a bacterium, and a virus have formed an evolutionary alliance against a parasitic wasp that threatens them all.

Our ability to read out this sequence of our own genome has the makings of a philosophical paradox. Can an intelligent being comprehend the instructions to make itself? —John Sulston

It is common today to hear techno-futurists and billionaire trans-humanists muse about the potential of technology to help mankind—or least the extremely wealthy—slip the surly bonds of aging and even death by “uploading” memories to a digital cloud and using AI to recreate consciousness. Billionaire investor and entrepreneur Balaji Srinivasan, who sees “the vector of our civilization” in terms of a choice between “anarcho-primitivism or optimalism/transhumanism,” has talked about “life extension” technologies that could make possible what he calls “genomic reincarnation,” in which a person’s sequenced DNA could in theory be synthesized and printed out into a new body, “like a clone, but it is you in a different time.”23 And of course there are the billionaire enthusiasts like Elon Musk who see a future in which technology is fused with human biology in some kind of brain-machine interface, or Mark Zuckerberg, who dreams of replacing physical society with a virtual “Metaverse.

It took thirteen years after its discovery to sequence full-length genome of HIV in 1996, and only thirty-one days to sequence the SARS virus in 2003, and we can now sequence many biological viruses in a single day.

The heritability of bipolar disorder or schizophrenia surpassed the heritability of cancer, diabetes, and hypertension. In identical twins who share all their DNA, the concordance of schizophrenia is 50 percent, fifty times higher than the general population and ten times higher than nonidentical twins. How could genomics fail to identify individual risk or subtypes? Surely DNA sequences could help us cut nature at the joints.

Although Sanger Sequencing is still used, it is now increasingly being replaced by newer technologies that are developing at an astounding pace. These technologies, collectively referred to as next-generation or high-throughput sequencing, allow DNA to be sequenced much more quickly and cheaply. The Human Genome Project, which used Sanger sequencing, took ten years to sequence and cost 3 billion US dollars. Using high-throughput sequencing, the entire human genome can now be sequenced in a few days at a cost of 3,000 US dollars. These costs are continuing to fall, making it more feasible to sequence whole genomes.

What’s good for you isn’t necessarily good for others—and vice versa. Consider this story: In 1985, a discovery by a major U.S. pharma firm led to a significant success in breast cancer treatment in two animal species. The phase I human trials showed no major safety concerns, but the study failed in phase II. The problem was with the cohort that was used. Half the patients had a gene that failed to metabolize the drug and they developed toxicity; the other half had a gene that metabolized the drug so quickly that it had no effect. When this problem was finally discovered in 2010 after gene sequencing of humans and of their tumors became more common, researchers realized that this beneficial drug had not helped the hundreds of thousands it could have since 1985. The point: The Human Genome Project has led to a better understanding of why something can be bad for some but good for others. That has led to scientific progress that is letting us live younger for longer.

This knowledge all stems from the Human Genome Project work that defined what makes you you. Four chemicals—represented by the four letters A, C, G, and T—come in base pairs to determine everything about you, from hair color to disease predisposition. Your individual sequence? About 3.2 billion letters in those 22,500 genes. That’s your individual code. That code is housed in 23 pairs of chromosomes—one of each pair from each parent. Each chromosome contains hundreds to thousands of genes that contain code that directs the manufacture of proteins and controls cell growth, function, and survival.

As strange as it sounds, it is no longer possible to determine how many human genomes have been sequenced. At present the strategy of choice is whole-genome re-sequencing (Chapter 3) whereby next-generation sequence data are mapped onto a reference genome. The results have been breathtaking. The recently concluded (and aptly named) 1000 Genomes Project Consortium catalogued ~85 million SNPs, 3.6 million short insertions/deletions, and 60,000 larger structural variants in a global sampling of human genetic diversity. These data are catalysing research in expected and unexpected ways. Beyond providing a rich source of data for GWA-type studies focused on disease, scientists are also using the 1000 Genomes Project data to learn about our basic biology, something that proved surprisingly difficult when only a pair of genomes was available. For example, a recent GWAS taking advantage of the 1000 Genomes Project data identified ten genes associated with kidney development and function, genes that had previously not been linked to this critical aspect of human physiology. In 2016, Craig Venter’s team reported the sequencing of 10,545 human genomes. Beyond the impressively low cost (US$1,000–2,000 per genome) and high quality (30–40× coverage), the study was significant in hinting at the depths of human genome diversity yet to be discovered. More than 150 million genetic variants were identified in both coding and non-coding regions of the genome; each sequenced genome had on average ~8,600 novel variants. Furthermore, each new genome was found to contain 0.7 Mbp of sequence that is not contained in the reference genome. This underscores the need for methods development in the area of structure variation detection in personal genome data. Overall, however, the authors concluded that ‘the data generated by deep genome sequencing is of the quality necessary for clinical use’.

RNA viruses mutate relatively quickly, and many, like influenza, are able to undergo a process known as antigenic drift, by which the virus is able to alter the surface antigens that are the targets of our antibodies—thus evading our existing immunity. Some viruses, like measles, cannot change their genomic sequence in ways that substantially alter enough of their surface proteins, so measles remains susceptible to our vaccines or the immunity that we get from prior infection. However, for viruses like influenza, as their surface proteins undergo change, the virus is able to dodge the protective antibodies that we’ve developed from past infection or vaccination

genomic sequencing,

Like most children of her era, she’d been taught to believe that the genome—the sequence of base pairs expressed in the chromosomes in every nucleus of the body—said everything there was to say about the genetic destiny of an organism. A small minority of those DNA sequences had clearly defined functions. The remainder seemed to do nothing, and so were dismissed as “junk DNA.” But that picture had changed during the first part of the twenty-first century, as more sophisticated analysis had revealed that much of that so-called junk actually performed important “roles in the functioning of cells by regulating the expression of genes. Even simple organisms, it turned out, possessed many genes that were suppressed, or silenced altogether, by such mechanisms. The central promise of genomics—that by knowing an organism’s genome, scientists could know the organism—had fallen far short as it had become obvious that the phenotype (the actual creature that met the biologist’s eye, with all of its observable traits and behaviors) was a function not only of its genotype (its DNA sequences) but also of countless nanodecisions being made from moment to moment within the organism’s cells by the regulatory mechanisms that determined which genes to express and which to silence. Those regulatory mechanisms were of several types, and many were unfathomably complex. Had it not been for the sudden intervention of the Agent, the biologists of Old Earth would have devoted at least the “remaining decades of the century to cataloging these mechanisms and understanding their effects—a then-new science called epigenetics. Instead of which, on Cleft, in the hands of Eve Moira and the generations of biologists she reared, it became a tool. (...) Thousands of years later, epigenetics was sufficiently well understood to be programmed into the DNA of some of the newly created species that would be let loose on the surface of New Earth. And one of the planks in the Get It Done platform was to use epigenetics for all it was worth. So rather than trying to sequence and breed a new subspecies of coyote that was optimized for, and that would breed true in, a particular environment, the GID approach was to produce a race of canines that would, over the course of only a few generations, become coyotes or wolves or dogs—or something that didn’t fit into any of those categories—depending on what happened to work best. They would all start with a similar genetic code, but different parts of it would end up being expressed or suppressed depending on circumstances. And no particular effort would be made by humans to choose and plan those outcomes. They would seed New Earth and see what happened. If an ecosystem failed to “take” in a particular area, they “they would just try something else. In the decades since such species had been seeded onto New Earth, this had been going on all the time. Epigenetic transformation had been rampant. Still, when it led to results that humans saw, and happened to find surprising, it was known as “going epi.

18. Elaine T. Ostrander, “Genetics and the Shape of Dogs: Studying the new sequence of the canine genome shows how tiny genetic changes can create enormous variation within a single species,” American Scientist (Sept.–Oct. 2007). 19.

What else can he do?” Talbot reached forward to queue up another video.  “A lot.  But reaching most of the genes, even using a genome sequencing process like CRISPR, takes a long time.  Too long for your schedule.” She stared at Bullman.  “What we need…is that sample.

The first solar photovoltaic panel built by Bell Labs in 1954 cost $1,000 per watt of power it could produce.128 In 2008, modules used in solar arrays cost $3.49 per watt; by 2018, they cost 40 cents per watt.129 According to a pattern known as Swanson’s Law, the price of solar photovoltaic modules tends to fall by 20 percent for every doubling of cumulative shipped volume. The full price of solar electricity (including land, labor to deploy the solar panels, and other equipment required) falls by about 15 percent with every doubling. The amount of solar-generated power has been doubling every two years or less for the past forty years—as costs have been falling.130 At this rate, solar power is only five doublings—or less than twelve years—away from being able to meet 100 percent of today’s energy needs. Power usage will keep increasing, so this is a moving target. Taking that into account, inexpensive renewable sources can potentially provide more power than the world needs in less than twenty years. This is happening because of the momentum that solar has already gained and the constant refinements to the underlying technologies, which are advancing on exponential curves. What Ray Kurzweil said about Craig Venter’s progress when he had just sequenced 1 percent of the human genome—that Venter was actually halfway to 100 percent because on an exponential curve, the time required to get from 0.01 percent to 1 percent is equal to the time required to get from 1 percent to 100 percent—applies to solar capture too.

We are in an exciting new era of biomedical research. Scientists can now read the entire sequence of someone’s genome, all 4.6 billion letters spread across the forty-six chromosomes, in a process that takes just a couple of weeks and costs about a thousand dollars. (The first complete sequencing of a human genome took over a decade to finish and cost nearly three hundred million dollars.)

Our ability to read out this sequence of our own genome has the makings of a philosophical paradox. Can an intelligent being comprehend the instructions to make itself

Through genetic sequencing, scientists have discovered that the axolotl has the largest genome ever seen to date - ten times larger than the base pairs of human DNA; these salamanders have 32 billion base pairs of DNA, while humans have only three billion! Researchers believe that in this DNA is contained the secret of this super-regeneration.

I can trace her bloodline right back to Arabians on Earth from the mid-nineteenth century. She’s as pure as they come. Not an artificial sequence in her whole genome;

registered email address and went global in 2007. Twitter split off onto its own platform and went global in 2007. Airbnb was born in 2007. In 2007, VMware—the technology that enabled any operating system to work on any computer, which enabled cloud computing—went public, which is why the cloud really only took off in 2007. Hadoop software—which enabled a million computers to work together as if they were one, giving us “Big Data”—was launched in 2007. Amazon launched the Kindle e-book reader in 2007. IBM launched Watson, the world's first cognitive computer, in 2007. The essay launching Bitcoin was written in 2006. Netflix streamed its first video in 2007. IBM introduced nonsilicon materials into its microchips to extend Moore's Law in 2007. The Internet crossed one billion users in late 2006, which seems to have been a tipping point. The price of sequencing a human genome collapsed in 2007. Solar energy took off in 2007, as did a process for extracting natural gas from tight shale, called fracking. Github, the world's largest repository of open source software, was launched in 2007. Lyft, the first ride-sharing site, delivered its first passenger in 2007. Michael Dell, the founder of Dell, retired in 2005. In 2007, he decided he'd better come back to work—because in 2007, the world started to get really fast. It was a real turning point. Today, we have taken another

Literary agent John Brockman points out another angle on the news from science: Through science we create technology and in using our new tools we recreate ourselves. But until very recently in our history, no democratic populace, no legislative body, ever indicated by choice, by vote, how this process should play out. Nobody ever voted for printing. Nobody ever voted for electricity. Nobody ever voted for radio, the telephone, the automobile, the airplane, television. Nobody ever voted for space travel. Nobody ever voted for nuclear power, the personal computer, the Internet, email, the Web, Google, cloning, the sequencing of the entire human genome

Everybody’s genome is like a book with 23 chapters,” he told them. “You have two copies of each chapter, one from your dad and one from your mom. Whole genome sequencing looks for everything. It looks for missing chapters, missing paragraphs, every misspelled word.

Perhaps even more amazing was the rapid development of not just one but several effective vaccines against COVID-19, not even a year after the pandemic took hold in early 2020. The virus genome was sequenced within weeks of the first deaths, allowing the speedy formulation of vaccines that specifically target its surface proteins. Progress with COVID treatments has also been remarkable, yielding multiple types of antiviral drugs within less than two years. This represents Medicine 2.0 at its absolute finest.

The map was a giant DNA stone, and appeared to represent Triplet DNA, which is also the shape of a pyramid. Triplet DNA refers to the sequence of amino acids in the human genome in which a protein determines its structure and function. The DNA code is a triplet code.

Gene sequences that code for proteins compose less than 2 percent of the human genome. That leaves some 98 percent with no genes at all in it. Genes are but islands in a sea of DNA.

growing crop of biometric tools—sleep measurement apps, fitness monitors, the thumbprint reader introduced on Apple’s iPhone 5S, the gene-sequencing service 23andme.com—means that corporations are set to know us at the physical, even genomic level. (“Your DNA will be your data,” says one particularly creepy HSBC ad spotted at JFK airport.)

But this is not to say that the whole project was irredeemably flawed. Later scientists, using better tools and larger data sets, would succeed in deriving statistically meaningful information from biometric information, and with the sequencing of the human genome, the role of biological evidence in the search for answers about human history would leap to the fore.

Today, I can read an entire human genome of 25,000 genes in a few days for less than a hundred dollars on a candy bar–sized DNA sequencer called a MinION that I plug into my laptop. And that’s for a fairly complete readout of a human genome, plus the DNA methyl marks that tell you your biological age.

If the genome of human beings is sequenced, then their genomic data is going to fall on spectrums.

Hundreds of oncogenes that promote prostate cancer, breast cancer, colon cancer, and other conditions were switched off in only three months. We published this research with Dr. J. Craig Venter (the first person to sequence a human genome) in the Proceedings of the National Academy of Sciences.

Viable offspring capable of reproduction resulted from all these liaisons and in August 2018, Denisova Cave obliged yet again by yielding up a bone fragment, more than 50,000 years old and in sufficiently good condition for genome sequencing. It turned out to have belonged to a female, about 13 years of age, who had a Neanderthal mother and a Denisovan father.57

My jaw nearly hit the floor. My inner voice sought clarification. So let me get this straight: This is 2010, and you sequenced your whole family? And you and your daughter have been working on the analysis? And you wondered if we could help? And, to clarify, you are talking about your seventeen-year-old daughter, and this is her high school science project?

Take Human Longevity Inc. (HLI), one of the companies Peter cofounded. HLI offers a service called “Health Nucleus,” an annual, three-hour health scan consisting of whole genome sequencing, whole body MRI, heart and lung CT, electrocardiogram, echocardiogram, and a slew of clinical blood tests—essentially the most complete picture of health currently available.

By probing the full sequence of the London plague for the very first time, geneticist Johannes Krause and his team unearthed the evolution of Yersinia pestis [the Plague microbe], and the genomic tracks of its terrible journey. An earlier study had shown that, just like the Plague of Justinian, the Black Death in the 1340s had also originated in China. With a publicly available database of the full sequence, the history and the genetics can be aligned. Over a five-year period we can track a course from Russia to Constantinople, to Messina, to Genoa, Marseille, Bordeaux, and finally London. All these ports acted as points from which radiation of the plague could crawl inland. En route, it claimed the lives of some 5 million people. Just as in the Byzantine Empire 600 years earlier, wave after wave of outbreak crashed into Britain’s population in the centuries after the fourteenth, and it was only after the Great Fire of London in 1666 that this pandemic was crushed. Krause’s work also shows that it never really went away. The pandemic might have ended, but the strains of Yersinia that cause bubonic plague outbreaks to this day are identical.