Introduction
You want to understand the terrifying world of extreme science, but traditional accounts feel distant and sterile. Richard Preston solves this problem through total journalistic immersion, placing you directly inside high-containment laboratories, dense tropical forests, and advanced mathematical workshops.
You can explore the most extreme frontiers of science, from high-containment lethal viruses and transcendental mathematics to rare genetic disorders and disappearing ecosystems, by immersing yourself in the visceral reality of human discovery.
The book guides you through adventures in dangerous biological containment, supercomputing calculations of pi, invasive ecological collapses, lethal viral outbreaks, and high-throughput genomics.
You will find answers to questions such as:
- How do scientists survive inside Level 4 maximum-containment labs?
- What drives researchers to spend years computing the infinite digits of pi?
- How do deadly hemorrhagic fevers emerge from isolated ecosystems?
- What secrets do ancient forests and rapid gene sequencing reveal about life?
1. Adventures in Nonfiction Writing and Containment
To capture the terrifying reality of high-containment science, you must fully immerse yourself in the physical environments, equipment, and emotional states of your subjects.
Quoting mathematician Oliver Heaviside, Richard Preston notes that to understand soup, you must climb into the pot and be boiled. By experiencing the same physical environments, dangers, and equipment as your subjects, you capture the visceral reality and psychological state of the characters.
Preston visited USAMRIID at Fort Detrick and gained access to a Biosafety Level 4 hot suite to observe researchers working with an Unknown virus sample.
Biosafety Level 4 Containment
Biosafety Level 4 represents the highest biosecurity tier, requiring pressurized full-body suits and strict airlock decontamination to handle lethal agents without cures. BL-4 facilities are sealed environments accessible through air locks equipped with chemical decontamination showers. Researchers wear blue pressurized space suits supplied with air via overhead hoses to prevent inhalation of aerosolized pathogens.
Army scientists at USAMRIID store frozen viral samples in hot freezers kept at 95 degrees below zero Fahrenheit.
The 2001 anthrax mailings dramatically increased biosecurity at facilities like USAMRIID, ending the era of informal journalistic access to high-containment labs. Following the Amerithrax terror events where 5 people died after inhaling anthrax spores, security at Army medical research facilities became extremely tight, making it impossible for reporters to enter space-suit labs. Former USAMRIID researcher Steven Jay Hatfill was named a person of interest by the Department of Justice, though he was never charged.
Journalism Techniques
Comprehensive reporting requires taking deep notes that record the complete sensory and emotional reality of a person and scene. You should record sights, smells, sounds, and the emotional aura of the scene.
When you practice deep notes methodology, you follow these steps:
- Jot down observations on any and all details of a person and a scene
- Include sights, smells, sounds, and the emotional aura of the scene
- Note details of how people move their bodies, what they wear, and what tics and gestures they display
- Observe the color of a person's eyes and their hands when possible
Preston closely examined Army scientist Lieutenant Colonel Nancy Jaax's hands, noticing a knuckle scar from a childhood goat bite in Kansas.
The delayed note technique allows you to capture verbatim statements without making an interviewee self-conscious by postponing writing until a distraction occurs.
When you use the delayed note technique, you follow these steps:
- Stop writing and put down the notebook when someone says something powerful
- Assume a neutral expression to avoid drawing attention
- Memorize exactly what the person is saying until short-term memory is full
- Change the subject and ask a question that results in a dull answer
- Jot down delayed notes in the notebook while the person gives the dull answer
Narrative nonfiction writers must fact-check descriptions of a character's interior thoughts directly with the subject to ensure emotional and factual accuracy.
When you verify an interior monologue, you follow these steps:
- Ask people what they were thinking or were thinking during key events
- Read drafted interior monologue passages aloud to the person, usually on the telephone
- Ask if the sentences accurately reflect their recollection of their thoughts at that moment
- Incorporate corrections made by the person to align the narrative with their memory
When Preston asked Nancy Jaax if she thought she would die with Ebola blood in her suit, she replied that she was actually worried about paying her babysitter.
2. Supercomputing and the Infinite Mystery of Pi
Mathematics operates as an objective cathedral of the intellect where dedicated researchers build custom machines to probe the infinite depths of transcendental numbers. You can explore this domain through the eccentric world of modern number theory.
Mathematics exists independently of the human mind, waiting to be discovered by those with the patience to probe its infinite depths.
The Chudnovsky Brothers
Gregory and David Chudnovsky built a powerful general-purpose supercomputer named m zero out of mail-order parts inside a Manhattan apartment. The brothers spent around 70,000 dollars on parts to build m zero, which ran day and night and burned 2,000 watts of power. It utilized a web of high-speed processors and was used to perform complex algebra, analyze stock market fluctuations, and process medical imaging data.
The supercomputer heated Gregory's apartment to over a hundred degrees Fahrenheit in the summer, causing circuit boards to smell of cooking silicon and requiring dozens of fans and a meat thermometer to monitor hot spots. Gregory Chudnovsky suffered from severe myasthenia gravis while living and working in a cramped, paper-filled Manhattan apartment alongside his brother David. Gregory was confined mostly to a bed surrounded by a ton of working papers and books, unable to breathe city air or tolerate direct light.
Despite their monumental contributions to number theory, the Chudnovsky brothers faced severe institutional neglect and lack of permanent academic positions due to Gregory's disability and unconventional working methods. Major academic institutions refused to offer them stable tenure-track positions because Gregory could not teach conventional classes and the brothers insisted on being hired as a single entity. Topologist Samuel Eilenberg expressed open disdain for their supercomputer-based digit computation, comparing it to going to the beach and counting grains of sand.
The Nature of Pi
Pi is a transcendental number whose decimal expansion goes on forever without repeating periodically, making it impossible to express completely in any finite form. Transcendental numbers transcend the power of algebra to display them in their totality. Although generated by a simple geometric ratio of a circle's circumference to its diameter, the digits of pi appear completely random and unpredictable, presenting an infinite nonrepeating sequence.
German mathematician Ferdinand von Lindemann proved the transcendence of pi in 1882, demonstrating that a piece of paper as big as the universe would not be large enough to hold even the tiniest droplet of pi. The Chudnovsky brothers repeatedly broke world records by computing billions of digits of pi using supercomputers to test their machines and probe for hidden mathematical structure. The Chudnovsky brothers eventually pushed their calculations past a billion digits, achieving a world record of 2,260,321,336 decimal places before moving on to other mathematical projects.
Working mathematicians often hold Platonist views, believing that numbers and mathematical objects possess an independent, eternal reality separate from the physical world. Gregory Chudnovsky viewed observing pi as a form of experimental physics, asserting that mathematical objects exist whether human minds or computers are aware of them. Captain O.C. Fox derived pi to two decimal places during the American Civil War by tossing fine steel wire onto a wooden board ruled with parallel lines 1,100 times.
3. Invasive Species and Ecosystem Collapse
Global trade and human movement drive biological upheavals that spread invasive parasites and destroy ancient temperate rain forests.
Human movement and global trade drive a biological upheaval by spreading invasive species that escape their natural predators, causing functional extinction across diverse North American tree species. Parasites moving into new habitats through trans-species jumps often find hosts with no built-in resistance, resulting in massive die-offs. This phenomenon mirrors viral leaps like HIV and Ebola, while devastating native flora such as chestnuts, elms, and Fraser firs.
A fungal disease called chestnut blight killed almost every American chestnut tree after appearing in 1904, and the balsam woolly adelgid killed 70 to 90 percent of mature wild Fraser firs in the southern Appalachians.
The hemlock woolly adelgid, an invasive Asian insect parasite, is systematically wiping out eastern hemlock trees in North America because native trees lack resistance and the insect lacks natural predators. The adelgid reproduces through female clones without needing males, with a single female capable of generating up to ninety thousand copies in a year. They suck nutrients out of tree needles, inducing a deadly cycle of shock and defoliation that kills mature trees within two to six years.
In 1951, an entomologist discovered the hemlock woolly adelgid near Maymont Park in Richmond, Virginia, where it likely originated from evergreens planted by Sallie Dooley in 1911. By the late eighties, entomologist Tim Tigner found that 90 percent of ancient hemlocks in a grove on the York River were dead.
The Hemlock Woolly Adelgid
The southern Appalachian coves contain ancient temperate rain forests featuring some of the largest and oldest eastern hemlocks on earth, representing an irreplaceable ecological epicenter. Eastern hemlocks create a distinctive, cool, and dark habitat by casting deep shade and covering the ground with beds of needles. The Cataloochee Valley in Great Smoky Mountains National Park holds the highest average tree height of any watershed in eastern North America.
Arborist Will Blozan discovered the world's tallest eastern hemlock in the Cataloochee Valley in January 2007, measuring it at 173.1 feet and naming it Usis, which is Cherokee for antler.
Conservation and Treatment
Saving infected hemlocks in wilderness areas requires intensive chemical treatments or biological controls, effectively placing the surviving old-growth forest on permanent medical life support.
Because oil sprays are impractical for vast wilderness areas, foresters deploy a chemical insecticide called imidacloprid via soil injection or root pills, and release imported lady beetles that consume adelgids. Treated trees must be continually retreated, turning the forest into a system dependent on ongoing drug management.
Will Blozan and his company, Appalachian Arborists, were hired to climb trees, sample foliage, and treat individual hemlocks, including saving thousands of sick hemlocks at Reverend Billy Graham's religious training center.
You can manage individual trees using specific field techniques:
- Collect water from creeks in jugs and put the jugs in backpacks.
- Mix the insecticide imidacloprid with water and inject it into the soil around the root system of a hemlock.
- Climb the tree using ropes, harnesses, and ascenders to take foliage samples and monitor chemical movement.
- Ascend to the tree canopy using a spider lanyard by flinging alternating ends over overhead branches while suspended.
Faced with the imminent extinction of old-growth hemlocks, independent arborists launched a dedicated documentation project to measure and record the giant trees before they completely disappear. Will Blozan and his partners founded the Tsuga Search Project, investing their own funds to locate, climb, and record the dimensions of the largest eastern hemlocks. Even when finding iconic trees already dead, they climbed the skeletons to gather data for future science.
In October 2007, Will Blozan and Jason Childs went into a Cataloochee cove to check on Usis, the world's tallest hemlock that Blozan had previously treated with chemicals, only to find that the tree had died.
4. Epidemiology and the Ghost of Ebola
Deadly hemorrhagic viruses emerge from transitional forest ecotones to overwhelm local medical systems while evading detection in their natural animal reservoirs.
Patient Zero in Kikwit
The 1995 Ebola outbreak in Kikwit started with a man named G.M. who worked as a charcoal maker in a transitional forest fragment called Mbwambala. G.M. commuted daily by bicycle to the Mbwambala forest, an ecotone where two different ecosystems meet, which are typically rich in biodiversity. He engaged in clearing trees, digging pits for charcoal, and setting traps, which likely exposed him to an undiscovered animal host or vector carrying the Ebola virus before he fell ill and died at Kikwit General Hospital.
G.M. was 42 years old at the time of his death. The Mbwambala forest fragment was 3 miles long and 0.5 miles wide. Kikwit sits 250 miles east of Kinshasa. The charcoal pits dug by G.M. were 5 feet deep.
G.M. lived in Kikwit in a wattle hut, rode his bicycle five miles to Mbwambala, dug a two-foot hole near tree roots, and later died on January 13 from what locals called la diarrhée rouge. The virus caused disseminated intravascular coagulation (DIC).
Hospital Collapse and Medical History
Ebola infiltrated the Kikwit Maternity Hospital and General Hospital, causing catastrophic mortality among pregnant women and medical personnel due to a lack of basic supplies. The virus caused severe hemorrhagic symptoms, immediate termination and fatality for all fetuses, and extreme vulnerability in medical staff who operated without proper protective gear. Surgeons operating on an infected technician became systematically infected through contact with homogenized, non-coagulating blood, leading to the collapse of the local health system.
Sister Floralba Rondi and two surgeons operated on the Maternity Technician without gloves, expecting bacterial peritonitis; nearly every member of the surgical team subsequently died of Ebola. Pavilion Three held 30 patients in the isolation ward. Laboratories in Belgium and the CDC received 14 tubes of blood.
During past Ebola outbreaks, doctors performed high-risk emergency obstetric procedures without anesthesia and experienced extreme accidental exposures to bodily fluids. Because Ebola universally causes pregnant women to hemorrhage and abort, doctors in extreme conditions had to deliver obstructed fetuses using emergency surgical methods that split the pelvic bone. In multiple documented historical cases, doctors and nurses performed mouth-to-mouth resuscitation or wiped away bloody tears, risking their lives through direct fluid contact.
- split the cartilage at the pubic symphysis with a scalpel until the bones go pop and the pelvis springs open
- spread the mother's legs to open the pelvis and facilitate the passage of the fetus
- reach inside, turn the fetus around, and deliver it bottom-first
Dr. Jean-François Ruppol performed the Zarate procedure without anesthetics on an infected woman in Yambuku in 1976 and gave mouth-to-mouth resuscitation to the newborn baby, miraculously escaping infection. The first Ebola outbreak in Yambuku occurred in 1976. Jean-François Ruppol survived for 30 years after his potential exposure.
International scientific teams from the CDC, WHO, and European institutions investigated the outbreaks in Congo and Ivory Coast but failed to identify the natural animal host. Researchers analyzed blood samples in Biosafety Level 4 hot zones, identifying a new strain named Ebola Kikwit, while parallel teams trapped thousands of mammals and tens of thousands of arthropods in the wild. None of the collected animal or insect specimens tested positive for Ebola, leaving the mystery of the natural reservoir unsolved.
A team led by ecologist Herwig Leirs collected over three thousand animal specimens around Kikwit, while Paul Reiter's team collected thirty-five thousand arthropods, finding zero traces of Ebola. The Danish team collected 3000 specimens, of which 10 percent were bird specimens.
5. Genomics and the Race for the Human Code
The human genome consists of a massive amount of genetic code structured into chromosomes and containing a vast majority of non-coding DNA. You find that the human genome contains at least 3.2 billion letters of genetic code. This amount is comparable to the number of letters in three thousand copies of Moby-Dick. Approximately three percent of this code consists of genes that hold recipes for proteins. Much of the rest is categorized as junk DNA.
High-throughput industrial sequencing transforms molecular biology, opening new frontiers in metagenomics and synthetic life.
Hamilton Smith demonstrated the physical properties of human DNA to the author by showing clear, syrupy liquid containing unbroken DNA extracted from white blood cells. A typical set contains 23 chromosomes, with two sets totaling 46 chromosomes per human cell. Researchers estimate there are 25,000 genes in the human genome.
Celera Genomics revolutionized DNA sequencing by treating it as an automated, high-throughput industrial manufacturing process rather than a slow manual procedure. Celera used hundreds of ABI Prism sequencing machines operating twenty-four hours a day. Powerful supercomputers and whole-genome shotgun sequencing drove the process to break DNA into random overlapping fragments and reassemble them via software.
Craig Venter showed the author Celera's facility in Rockville, Maryland, housing 150 Prism machines worth forty-five million dollars. Just three people operated these machines. Celera maintained a burn rate of 150 million dollars a year while running 150 Prism DNA-sequencing machines in its main decoding factory. Each Prism machine cost 300 thousand dollars.
The race to sequence the human genome triggered intense political and personal conflict between the private enterprise Celera and the publicly funded Human Genome Project over data openness and patenting. The public project projected a cost of 3 billion dollars, while Celera's sequencing effort cost an estimated 200 million dollars. While the public project insisted on making all human genetic code immediately available free of charge on GenBank, Celera pursued information subscription models and provisional patents on gene fragments. This approach caused severe acrimony among leading scientists.
James Watson publicly disparaged Craig Venter's methods at a Senate hearing, suggesting his machines could be run by monkeys. He later compared Venter to Hitler during a contentious meeting at Cold Spring Harbor Laboratory.
Industrial Sequencing
Celera's commercial rise coincided with the Internet stock bubble, causing extreme volatility and massive paper wealth for its employees before crashing in a broader tech bear market. As investors realized Celera was successfully decoding the genome and filing gene patents, its stock surged dramatically. Enthusiastic retail investing and media attention drove the stock before it collapsed when the dot-com bubble burst and data-sharing clashes escalated.
During a trading halt at 101 dollars a share, employees across Celera checked Yahoo! quotes as their paper wealth multiplied into millions within minutes. The stock started trading at 7 dollars a share during the summer and reached an all-time high of 276 dollars a share after a split. This surge pushed Celera's peak stock-market value to 20 billion dollars.
Synthetic Biology
Sampling seawater and sequencing its environmental DNA revealed an uncharted universe of previously unknown microorganisms and viral diversity. Using his yacht Sorcerer II, Craig Venter collected seawater samples every two hundred miles during a global expedition. He ran the extracted DNA through sequencing machines to uncover millions of novel microbial and viral species.
The Sorcerer II sailed 33,000 miles on a circumnavigation expedition modeled after the HMS Challenger. The expedition discovered that oceans contain immense numbers of unrecorded viruses and bacteria, including an estimated 100 million different kinds of viruses in the earth's oceans.
Following genome mapping, Venter and Hamilton Smith shifted focus to synthetic biology, aiming to construct artificial life and engineered bacteria to produce alternative fuels. The researchers began creating artificial genes in the laboratory to build synthetic microbes capable of converting plant cellulose, carbon dioxide, and coal into clean energy sources like ethanol, methane, and jet fuel. Synthetic Genomics established commercial partnerships, such as a major deal with BP to develop synthetic bacteria that metabolize coal into natural gas.
Craig Venter eventually published a complete, highly accurate diploid version of his own personal genome containing both sets of chromosomes. In the fall of 2007, Venter published his superaccurate diploid human genome and made his entire DNA code available for free on the Internet. Unlike the initial public draft, Venter's personal genome sequence included two sets of chromosomes for a total of 6 billion letters. This release provided the most detailed individual human genetic blueprint published to date.
10 Key Ideas
- To capture the terrifying reality of high-containment science, you must fully immerse yourself in the physical environments, equipment, and emotional states of your subjects.
- The delayed note technique allows you to capture verbatim statements without making an interviewee self-conscious by postponing writing until a distraction occurs.
- Mathematics exists independently of the human mind, waiting to be discovered by those with the patience to probe its infinite depths.
- Working mathematicians often hold Platonist views, believing that numbers and mathematical objects possess an independent, eternal reality separate from the physical world.
- Global trade and human movement drive biological upheavals that spread invasive parasites and destroy ancient temperate rain forests.
- Saving infected hemlocks in wilderness areas requires intensive chemical treatments or biological controls, effectively placing the surviving old-growth forest on permanent medical life support.
- Deadly hemorrhagic viruses emerge from transitional forest ecotones to overwhelm local medical systems while evading detection in their natural animal reservoirs.
- High-throughput industrial sequencing transforms molecular biology, opening new frontiers in metagenomics and synthetic life.
- Art conservation technology utilizes advanced scientific methods, such as non-destructive imaging and chemical analysis, to preserve priceless historical artifacts and paintings.
- The genetic basis of Lesch-Nyhan syndrome stems from a rare metabolic disorder caused by a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase.