Tag Archives: Medicine

October 24, 1632

Anton Van Leeuwenhoek

On this date, the Dutch microscopist Antony van Leeuwenhoek was born.  He made some of the most important discoveries in the history of biology.  During his lifetime, Leeuwenhoek ground over 500 optical lenses and created over 400 different types of microscopes, only nine of which still exist today.  Leeuwenhoek was the first person to see bacteria, free-living and parasitic microscopic protists, sperm cells, blood cells, microscopic nematodes and rotifers, and much more. His researches on lower animals refuted the doctrine of spontaneous generation, and his observations helped lay the foundations for microbiology.

It is worth noting that Leeuwenhoek’s early discoveries in the field of microbiology are analogous to Galileo’s early discoveries in the field of astronomy. Both men used the newly improved optical technologies of their day to make major discoveries that entirely overturned traditional beliefs and theories in their respective fields, and both men were initially met with strong skepticism and resistance to the inevitable conclusions to which their discoveries led. Ultimately, Leeuwenhoek was more fortunate than Galileo in that his discoveries were eventually widely accepted and applauded in his lifetime, whereas Galileo’s were not. In addition, Leeuwenhoek’s main opposition was from the scientific community, not the religious community, because Holland was freer of religious persecution than many other European nations at the time. Galileo, for example, faced strong religious persecution.

October 19, 1932 (a Wednesday)

Depression-era U.S. poster advocating early syphilis treatment. Although treatments were available, participants in the study did not receive them.

On this date, Dr. Raymond A. Vonderlehr arrived in Montgomery, Alabama, following a rainy drive from Washington, DC. After meeting Dr. Oliver C. Wenger, both men drove down to Tuskegee, checking into the only hotel for whites in town – the Carr Hotel. Here they intended to spread the word to Macon County’s black population that a new syphilis control demonstration was about to begin. In actuality, this was the beginning of what was to become the notorious Tuskegee Syphilis Study, a non-therapeutic, observational study of the effects of untreated sexually-transmitted syphilis in poor, rural black men who thought they were receiving free health care from the U.S. government.

Investigators enrolled in the study a total of 600 impoverished, African-American sharecroppers from Macon County, Alabama; 399 who had previously contracted syphilis before the study began, and 201 without the disease. For participating in the study, the men were given free medical care, meals, and free burial insurance. They were never told they had syphilis, nor were they ever treated for it. According to the Centers for Disease Control, the men were told they were being treated for “bad blood,” a local term used to describe several illnesses, including syphilis, anemia and fatigue.

The 40-year study was controversial for reasons related to ethical standards, primarily because researchers knowingly failed to treat patients appropriately after the 1940s validation of penicillin as an effective cure for the disease they were studying. Choices available to the doctors involved in the study might have included treating all syphilitic subjects and closing the study, or splitting off a control group for testing with penicillin. Instead, the Tuskegee scientists continued the study without treating any participants and withholding penicillin and information about it from the patients. In addition, scientists prevented participants from accessing syphilis treatment programs available to others in the area. The study continued under numerous U.S. Public Health Service supervisors until 1972, when a leak to the press by Peter Buxtun, a PHS venereal disease investigator, eventually resulted in its termination.

The Tuskegee Syphilis Study has been called “arguably the most infamous biomedical research study in U.S. history.”

References:

  • James H. Jones. Bad Blood (Simon & Schuster, 1992) pp. 113-114.

October 9, 1676

Anton Van Leeuwenhoek

In 1673 Regnier de Graaf, a brilliant young physician in Delft, Holland, wrote a letter of introduction about Anton Van Leeuwenhoek to Henry Oldenburg, Secretary of the Royal Society in London. De Graaf said that Leeuwenhoek had devised microscopes that were far superior to any then known.  Accompanying De Graaf’s letter was the first letter to the Royal Society written by Leeuwenhoek, which dealt with observations on the structure of mold, as well as the structure of the bee and the louse.  Leeuwenhoek’s letter was published in Philosophical Transactions of the Society, and Oldenburg wrote to the author requesting further communications. Over the next fifty years, Leeuwenhoek wrote more than three hundred letters to the Royal Society.

On today’s date, Anton Van Leeuwenhoek wrote his most famous letter to the Royal Society, communicating the results of a series of experiments on water infused with pepper. Leeuwenhoek began by examining some snow-water that he had kept sealed for three years. He noted no creatures. He then added some peppercorns to the solution in what might have been an attempt to discover “the cause of the hotness or power whereby pepper affects the tongue.” Three weeks later, on 24 April 1676, Leeuwenhoek discovered the sudden appearance of a tremendous number of “very little animals.” Judging by his calculations of their number and size, historians have surmised that Leeuwenhoek had become the first person to see bacteria. Leeuwenhoek wrote:

The 31th of May, I perceived in the same water more of those Animals, as also some that were somewhat bigger. And I imagine, that [ten hundred thousand] of these little Creatures do not equal an ordinary grain of Sand in bigness: And comparing them with a Cheese-mite (which may be seen to move with the naked eye) I make the proportion of one of these small Water-creatures to a Cheese-mite, to be like that of a Bee to a Horse: For, the circumference of one of these little Animals in water, is not so big as the thickness of a hair in a Cheese-mite.

Previously, the existence of single-celled organisms was entirely unknown. Thus, even with his established reputation with the Royal Society as a reliable observer, his observations of microscopic life were initially met with skepticism. Eventually, in the face of Van Leeuwenhoek’s insistence, the Royal Society arranged to send an English vicar as well as a team of respected jurists and doctors to Delft to determine whether it was in fact Van Leeuwenhoek’s ability to observe and reason clearly, or perhaps the Royal Society’s theories of life itself that might require reform.

Finally, in 1680, Van Leeuwenhoek’s observations were fully vindicated by the Society. Although he neither lectured nor wrote formal scientific papers, he was recognized as an original scientist and was admitted as a Fellow to the Royal Society. Given contemporary medical theories, it did not occur to Leeuwenhoek that what he saw with his microscope was in any way connected to disease, but his observations laid a foundation on which further investigations were born.

References:

  • Letter to H. Oldenburg, 9 Oct 1676. In The Collected Letters of Antoni van Leeuwenhoek (1957), Vol. 2, 75.

September 13, 1848 (a Wednesday)

Phineas Gage skull diagram 1868 (left) and skull (right).

Phineas Gage (1823-1860) is one of the earliest documented cases of severe brain injury. He is the index case of an individual who suffered major personality changes after brain trauma. As such, Gage is a legend in the annals of neurology, which is largely based on the study of brain-damaged patients.

On this date, 25-year-old Phineas Gage and his crew were working on the Rutland and Burlington Railroad near Cavendish, Vermont. Gage was preparing for an explosion by compacting a bore with explosive powder using a tamping iron. While he was doing this, a spark from the tamping iron ignited the powder, causing the iron to be propelled at high speed straight through his skull. It entered under the left cheek bone and exited through the top of the head, and was later recovered some 30 yards from the site of the accident.

Gage recovered almost entirely from his physical disabilities, except for loss of sight in one eye. It is surprising, of course, that Gage survived such a traumatic event at all, but more surprising is the fact that his personality was completely changed as a result of the accident. Gage’s doctor describes how “the equilibrium or balance, so to speak, between his intellectual faculty and animal propensities” had been destroyed. The changes became apparent as soon as the acute phase of brain injury subsided. He was now “fitful, irreverent, indulging at times in the grossest profanity which was not previously his custom, manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times perniciously obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned. . . .” .

These new personality traits contrasted sharply with the “temperate habits” and “considerable energy of character” Phineas Gage was known to have possessed before the accident. Previously, he had “a well balanced mind and was looked upon by those who knew him as a shrewd, small businessman, very energetic and persistent in executing all his plans of action.” So radical was the change in him that friends and acquaintances could hardly recognize the man. They noted sadly that he was “no longer Gage.”  In fact, he was so different that his employers had to let him go shortly after he returned to work. The problem was not lack of physical ability or skill – it was his new character.

References:

  • Damasio, Antonio R. Descartes Error: Emotion, Reason and the Human Brain, New York: Avon, 1994.

Location of the Mind Remains a Mystery

ResearchBlogging.orgWhere does the mind reside? It’s a question that has occupied the best brains for thousands of years, including the Buddha’s.

Recent advances in functional magnetic resonance neuroimaging, a technique that measures brain activity in the hope of finding correlations between mental functions and specific regions of the brain, have led to a wealth of studies that map particular functions onto regions. Self-awareness is defined as being aware of oneself, including one’s traits, feelings, and behaviors. Previous neuroimaging studies had suggested that self-awareness (SA), which is central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). This proposal predicts that damage to these regions should disrupt or even abolish SA — an afflicted individual should be like a zombie, according to David Rudrauf, a neurologist at the University of Iowa in Iowa City.

University of Iowa researchers studied the brain of a patient with damage to three regions long considered integral to self-awareness — left to right, the insular cortex, anterior cingulate cortex, and medial prefrontal cortex. Image credit: UI Department of Neurology.

So when Rudrauf and his team heard about patient R, they immediately thought he could help set the record straight. Patient R is a 57-year-old man whose brain was damaged in 1980 following a severe episode of herpes simplex encephalitis. His brain damage is bilateral, more extensive on the right, and encompasses the target regions mentioned above: the insular cortex, the ACC, and the mPFC. Rudrauf et al reasoned that if any of the structures that are damaged in this patient are indeed critical for the different aspects of SA implicated by the hypothesis described above — i.e., insula, ACC, mPFC — the patient should show clear disruptions of the corresponding functions. Conversely, if these structures are not critical, R should show largely preserved SA.

In fact, R displays a strong concept of selfhood. Rudrauf’s team confirmed this by checking whether he could recognize himself in photographs and by performing the tickle test — based on the observation that you can’t tickle yourself. They concluded that many aspects of R‘s self-awareness remained unaffected. “Having interacted with him it was clear from the get go that there was no way that [the theories based on neuroimaging] could be true,” says Rudrauf. R also has an IQ within the normal range, although he does have severe amnesia, which prevents him from learning new information, and he struggles with social interaction.

The UI researchers estimate that R has ten percent of tissue remaining in his insula and one percent of tissue remaining in his anterior cingulate cortex. Some had seized upon the presence of tissue to question whether those regions were in fact being used for self-awareness. But neuroimaging results presented in the current study reveal that R’s remaining tissue is highly abnormal and largely disconnected from the rest of the brain.

The authors of the report conclude that:

R is a conscious, self-aware, and sentient human being despite the widespread destruction of cortical regions purported to play a critical role in SA, namely the insula, anterior cingulate cortex, and medial prefrontal cortex.

“Self-awareness corresponds to a brain process that cannot be localized to a single region of the brain,” says Rudrauf. “In all likelihood, self-awareness emerges from much more distributed interactions among networks of brain regions.”

Patient R demonstrates that the mind remains as elusive as ever.

References:

  • Philippi CL, Feinstein JS, Khalsa SS, Damasio A, Tranel D, & et al. (2012). Preserved Self-Awareness following Extensive Bilateral Brain Damage to the Insula, Anterior Cingulate, and Medial Prefrontal Cortices Plos ONE, 7 (8) DOI: 10.1371/journal.pone.0038413

At the Intersection of Science and Human Rights

Inmates sew at a compulsory drug rehabilitation centre in Kunming.

A study by Xue et al, published in Science‘s 13 April 2012 issue, tested an experimental treatment for addiction on 66 former heroin users confined at two detention centers in Beijing.

According to Reuters:

Studies published by Science must have approval from an ethics board; the Chinese scientists say their study had such approval from Peking University.

BUT…

Again quoting Reuters:

Joseph Amon, director of the health and human rights division at Human Rights Watch, charged in [a] letter that in both [detention centers] addicts are ‘detained without due process’ and, he told Reuters, ‘held in a closed institution where monitoring of human rights abuses is not allowed.’ It is not clear from the study whether the addicts ‘were voluntary patients’ at the facilities or forcibly held, Amon said in his letter.

Mr. Amon, who is also an associate in the department of epidemiology at the Bloomberg School of Public Health at Johns Hopkins University and a lecturer in public and international affairs at Princeton University, is correct. Arrest for illegal drug use in China can lead to compulsory treatment (for a minimum of 2 years) at detention centers that function as de facto penal colonies where inmates are fed substandard food and denied basic medical care. The detentions are enforced by police, where the drug user has no opportunity to have a trial, face a judge, or raise an appeal. When a drug user leaves detention, the problems do not end there: their having been arrested for drug use is noted on their national identification card, making future employment difficult and leaving them vulnerable to frequent and humiliating searches by police.

This is not a rare phenomenon: according to a May 2009 report by the Joint United Nations Programme on HIV/AIDS (UNAIDS), half a million people are confined in drug detention centers in China at any given time. Most reports indicate that “treatment” during detention looks like punishment, exploitation, or merely lame, consisting of unpaid labor in chicken farms or shoe factories, or in the form of untested “therapies” like sandbox play, art, or boxing.

The study by Xue et al was conducted at Beijing Ankang and Tiantanghe Drug Rehabilitation Centers, but these are two of the facilities that have raised concerns about human rights violations over the past years.

‘The journal is not an investigative body,’ a spokeswoman for Science told Reuters. ‘On the basis of the authors’ response as well as (the editors’) own internal review, which included a science ethicist, the concerns about human rights seem to have been addressed, and the paper remains in good standing at this time.’

Daniel Wikler, a bioethicist at the Harvard School of Public Health in Boston, publicly commented:

Human Rights Watch has published valuable reports on inhumane treatment of drug addicts in many lands, including both China and the United States…But why brand the experiment by Xue et al as unethical?… Mr. Amon’s objections to the Xue et al study do not amount to much. He seems to be using the publication of the study as a means of drawing attention to wrongs in China’s treatment of addicts… it would be a shame if Mr. Amon’s letter tarnished the reputation of Chinese and U.S. scientists who seem to have conducted an innocuous (but valuable) experiment… [emphasis added]

Wikler is a frequent lecturer on ethics and health in the PRC and Hong Kong and holds honorary appointments at two Beijing research institutions, but he is no expert on the Chinese government’s attitude toward human rights and the rule of law. It seems at least equally plausible that Mr. Amon is using the wrongs in China’s treatment of addicts as a means of drawing attention to the unethical nature of the Xue et al experiment.

Inmates take an oath to resist drugs at a mandatory rehab center in Wuhan, China. (Stringer Shanghai/Reuters).

The authors of the study included 11 scientists at Peking University, led by Yan-Xue Xue, and two scientists, David Epstein and Yavin Shaham, at the National Institute on Drug Abuse (NIDA), which is part of the U.S. National Institutes of Health. The NIDA declined to allow the two U.S. scientists to speak about the study. And the two NIDA researchers did not sign the response, nor did three of the Beijing University scientists. So the response to Amon’s letter published by Science in their 3 August 2012 issue was actually signed by only eight authors, all from Peking University, out of the total of 13.

In the authors’ response, the scientists explain that their work used subjects who they say were “court mandated” — but as noted before, drug users are usually sent to detention centers without any formal trial, never seeing the inside of a courtroom, because drug abuse in China isn’t considered a criminal offense. They dismiss Amon’s charges by stating, “The human rights violations mentioned by Amon would have violated China’s new National Narcotics Control Law and Chinese law in general…Patients who work are always paid. This provision has been put into effect for many years, and recently has been written in the National Narcotics Control Law, which bans forced labor.” This sounds like something written by the Chinese Communist Party (CCP). Such naivete about China’s respect for fundamental freedoms and human rights is disturbing. Chinese laws hardly justify confidence in the humane treatment of their study subjects.

There is a well-known saying in China that makes despotic officials (such as those staffing detention centers) happy: “the heaven is high and the emperor, far away”; therefore even if the central government is good and has formulated good laws, regulations, rules, codes, policies, etc., a despotic official may still do whatever he wants. China is too large and the central government is too far away to be aware of their malpractices; while the God who always upholds justice, is too high away to meddle.

In institutional settings, where conformity and compliance are rewarded, people may not feel that they have a real choice. Prisoners are aware that behavior is continuously monitored and assessed, and that this can have very real consequences.

As a scientist, I am appalled at the glib way the AAAS addresses human rights concerns. With drug user detainees in such circumstances in China, is voluntary informed consent of participants really possible? Are researchers who conduct research in these facilities complicit in the ill-treatment of drug users at the hands of Chinese authorities? I believe so.

Although the NIDA didn’t provide direct funding for the study, it did contribute financial support for the paper by paying the salaries of Epstein and Shaham. In a statement released to the Associated Press on April 22, the NIDA explained that its scientists “advised on the experimental design of the preclinical studies, and were involved in the data analyses and in the preparation of the manuscript.” Science magazine’s guidelines, as well as the NIDA’s code of conduct and standard scientific protocol, state that all co-authors are responsible for the sum total of any article published in its pages. By allowing their names to be published on the study, Epstein and Shaham took responsibility for the entire contents of the report, including the ethics of the research. Since these two scientists were significant enough contributors to the research to warrant authorship, should the study have also been reviewed under the (rather stringent) U.S. regulations governing prisoner research? I believe so. If it had been, would it have passed muster? I believe not. For one thing, under American law, federally funded research on inmates must be approved by a panel that includes at least one prisoner who volunteers to serve (see Title 45 CFR Part 46.304(b)).

I strongly urge Science magazine to retract this study for not adhering to standards protective of human subjects; verification of compliance with human rights standards should be obtained from third-party sources, not affiliated in any way with the CCP (which includes Peking University), as a matter of policy whenever considering publication of such studies from China.

References:

July 27, 1921 (a Wednesday)

On this date at the University of Toronto, Canadian scientists Frederick Banting and Charles Best successfully isolated insulin from canine test subjects — a hormone they believed could prevent diabetes — for the first time. On November 14, following successful trials on diabetic dogs, the discovery was announced to the world.

At that time, the only way to treat the fatal disease was through a diet low in carbohydrates and sugar and high in fat and protein. Instead of dying shortly after diagnosis, this diet allowed diabetics to live — for about a year.

On 11 January 1922, Banting and Best gave 14-year-old Leonard Thompson an injection of a reasonably pure extract of insulin from the pancreases of cattle from slaughterhouses. His blood sugar levels dropped significantly, but an abscess developed at the injection site making him acutely ill. A refined extract was again administered on 23 January, causing a drop in blood sugar levels from 520 mg/dl to 120 mg/dl within 24 hours. Leonard lived for 13 years, taking doses of insulin, before dying of pneumonia (another disease for which no cure was available in those days).

Within a year of isolating the hormone, the first human sufferers of diabetes were receiving insulin treatments, and eventually countless lives were saved from what was previously regarded as a fatal disease. By early 1923, insulin had become widely available, and Banting and Macleod were awarded the Nobel Prize in Physiology or Medicine for that year.

References:

June 6, 1822 (a Thursday)

Alexis St. Martin with his wife in his later years.

Alexis St. Martin with his wife in his later years.

On this date, Alexis St. Martin was working at a fur-trading post in Mackinac Island in Lake Huron when he was accidentally shot with a gun at close range. The charge of the gunshot blew a fist-sized hole through his side and into his stomach. The following account from Gurdon S. Hubbard is the only eyewitness description of the incident.

This St. Martin was at the time one of the American Fur Company’s engages, who, with quite a number of others, was in the store. One of the party was holding a shotgun (not a musket) which was accidentally discharged, the whole charge entered St. Martins body. The muzzle was not over three feet from him — I think not over two. The wadding entered, was well as pieces of his clothing; his shirt took fire; he fell, as we supposed, dead.

William Beaumont, a US Army surgeon stationed at a nearby army post, treated the wound. Although St. Martin was a healthy 28-year-old [1], he was not expected to recover due to the severity of his wound. Nevertheless, he did so under Beaumont’s care, and when the wound healed itself, the edge of the hole in the stomach had attached itself to the edge of the hole in the skin, creating a permanent gastric fistula. The strong stomach acid essentially disinfected the wound from the inside out, making it safe to not sew it up.

The trading post where St. Martin was shot still stands today in Michigan.

The trading post where St. Martin was shot still stands today in Michigan.

Beaumont recognized the wonderful opportunity he had in St. Martin to investigate the mysterious process of digestion. For centuries, the stomach was thought to produce heat that somehow cooked foods. Alternatively, the stomach was imagined to be like a mill, a fermenting vat, or a stew pan. Beaumont performed two kinds of experiments on the digestive processes from 1825 to 1833. First, he observed the fluids discharged by the stomach when different foods were eaten (in vivo). Second, he extracted samples of the stomach’s content and put them into glass tubes to determine the time required for “external” digestion (in vitro).

Expressing his dislike for his role, St. Martin periodically disappeared. In 1832, to secure his experimental subject, Beaumont signed St. Martin to a 1-year contract. Per the contract, St. Martin was to “obey, suffer and comply with all reasonable and proper orders or experiments” for $150 and room, board, and clothing. In 1833, St. Martin went home to Canada, never to return to Beaumont’s care. The difference in social status and wealth makes Beaumont’s use of St. Martin ethically questionable.

Beaumont published the first results of his experiments on St. Martin in the Philadelphia Medical Recorder for January 1825, and full details in 1838 as Experiments and Observations on the Gastric Juice, and the Physiology of Digestion. He ended his treatise with a list of fifty-one inferences based on his 238 separate experiments. Although working away from the centers of medicine, Beaumont used findings from Spallanzini, Carminiti, Viridet, Vauquelin, Tiedemann and Gmelin, Leuret and Lassaigne, Montegre, and Prout. Even with their information, he still obeyed the scientific method, basing all his inferences on direct experimentation.

Beaumont proved once and for all that digestion in the stomach was chemical — a product (mostly) of the gastric juice itself which Beaumont surmised, correctly, was composed largely of hydrochloric acid. Beaumont’s important experiments quickly reached an international audience. In the United States, Dunglison’s 1844 second edition of Human Health included a 3-page appendix of Beaumont’s “…time required for the stomachal digestion of different alimentary substances,” and Cutter’s popular Anatomy and Physiology Designed for Academies and Families (1848) included Beaumont’s results for the mean times for digesting foods. In France, Claude Bernard cited Beaumont’s work in his 1865 Introduction to the Study of Experimental Medicine.

Beaumont’s accomplishment is even more remarkable because the United States, unlike England, France, and Germany, provided no research facilities for experimental medicine. Beaumont, a “backwoods physiologist,” inspired future studies of gastric emptying, intestinal absorption, electrolyte balance, rehydration, and nutritional supplementation with so-called sports drinks.

[1] For some reason, St. Martin’s age at the time was given by Beaumont as 18 years, and the error was not corrected until the Canadian Physiological Society marked his grave in 1962. Often referring to his patient as a “lad,” the doctor was actually just nine years his senior. It is possible that Alexis for some reason falsified his age throughout his dealings with Beaumont, or even that someone else stated the age and the wounded man was never actually asked. On the other hand, others think that it was not an error. “I doubt that Beaumont, who showed himself to be a notoriously accurate observer, would not have noticed the difference between a youth of 18 and a grown man of 28,” said Sylvio Leblond, MD. “I do not believe that Alexis had any reason to state that he was ten years younger than his correct age, and I feel certain that the thought would never have occurred to him…It is reasonable to conclude, then, that he was…18 or 19 in 1822.”

References:

May 25, 1769

Jan Ingen-Housz

On this date, the Dutch physician and scientist Jan Ingen-Housz was elected to the Royal Society of London. He is best known today for showing that light is essential to photosynthesis and thus having discovered photosynthesis. He also discovered that plants, like animals, have cellular respiration.

In the summer of 1771, Joseph Priestley had carried out experiments with air and jars, noting that a closed jar would eventually kill a mouse and extinguish a candle, but vegetation (he used mint) would allow the mouse to live and the candle to burn. Although he did not have the official names of the “types” of air he was observing, Priestly had discovered that mice and candles need something (oxygen), and plants are capable of using other things in the air (carbon dioxide) to produce that something. In short, plants restore to the air whatever breathing animals and burning candles remove.  However, Priestly and others were unable to reproducibly demonstrate oxygen production by plants because they were unaware of the requirement for light in photosynthesis.

Probably motivated by Priestley’s publications on the subject, Ingen-Housz obtained a short leave of absence in 1779 from his post in Vienna, Austria in order to do research in England on plants during the summer months. He performed more than 500 experiments trying to determine why plants restore bad air and described the results in his exceptional book entitled Experiments Upon Vegetables, Discovering Their Great Power of Purifying the Common Air in the Sunshine and of Injuring it in the Shade and at Night, published in October 1779.

Underwater plants producing bubbles of oxygen.

In some of his experiments, Ingen-Housz placed plants underwater in a transparent container.  He found they gave off bubbles of gas only when placed in sunlight and that the bubbles gradually ceased when the plants were placed in darkness. He determined that it is not because of the warmth of the sun, and it is not the sun acting on its own, but the light of the sun reacting with the green parts (stalks and leaves) of the plants.

Once he realized a gas was being produced in the presence of light, Ingen-Housz collected it and conducted a series of tests to determine its identity. He eventually discovered that a smoldering candle would relight when it was exposed to the unknown gas. This showed that it was oxygen (known at that time as ‘dephlogisticated’ or ‘vital’ air).

In another experiment, Ingen-Housz put a plant and a candle into a transparent closed space. He allowed the system to stand in sunlight for two or three days. This assured that the air inside was pure enough to support a candle flame. But he did not light the candle. Then, he covered the closed space with a black cloth and let it remain covered for several days. When he tried to light the candle it would not light. Ingen-Housz concluded that somehow the plant must have acted in darkness like an animal. It must have breathed, fouling the air. Ingen-Housz quickly printed his book in London, allowing him to take along copies when he returned to Vienna.

The biochemistry of photosynthesis.

So why is Priestley until today a well-known name in the history of science, while Ingen-Housz is virtually unknown , except for a few historians of chemistry and botany? Ingen-Housz was a humble person, not interested in fame, pomp, or circumstance. Low-key and introverted, enjoying friendships, shying away from stardom, he stood in contrast to some of his fellow researchers of that time. For example, Priestley admitted in private that Ingen-Housz indeed had been the first to describe the beneficial power of plants in a letter to Giovanni Fabroni from 1779:

I have just read and am much pleased with Dr. Ingenhousz’ work. The things of most value that he hit upon and I missed are that leaves without the rest of the plants will produce pure air and that the difference between day and night is so considerable.

Priestley promised Ingen-Housz that he would rectify the situation in a later publication. But the attribution never appeared in print; Ingen-Housz was not even mentioned by Priestley. In the meantime, Priestley repeatedly claimed in public to have observed and published before Ingen-Housz and kept repeating this until 1800. In fact, never did Priestley give an accurate reference to Ingen-Housz’ work, never did Ingen-Housz’ name appear in the index of Priestey’s works. On the other hand, Ingen-Housz systematically referred to Priestley, with much respect.  Ingen-Housz refrained from disputing the claims of his rival colleagues, but they continued as they did, obfuscating Ingen-Housz’ rightful place in science as the discoverer of photosynthesis in the eyes of the historians and the public.

References:

April 10, 1901 (a Wednesday)

On this date, Duncan MacDougall, MD, performed his first experiment to test a hypothesis, to wit, “If personal continuity after the event of death is a fact, if the psychic functions continue to exist as a separate individuality after the death of brain and body, then it must exist as a substantial material entity.” This implies that this entity should have mass, so MacDougall asked himself, “Why not weigh on accurate scales a man at the very moment of death?”

The following is an extract of a letter written by Dr. MacDougall to a Richard Hodgson, MD and dated 10 November 1901, describing MacDougall’s first experiment. The letter was published in May 1907, along with a report of his subsequent experiments, in the Journal of the American Society for Psychical Research:

duncan_macdougall_1907_-_21pp_page_13-14

Interestingly, in a commentary published with the report, the editor of the Journal wrote that he “does not share the hopes which many entertain regarding the possibility of ‘weighing a soul,’ but this does not preclude his [MacDougall’s] recognition of the value of experiment, whatever its outcome. The main point is to have a definite conclusion established, whether it be negative or affirmative.”

According to The New York Times, MacDougall was a “reputable physician” and “at the head of a Research Society which for six years has been experimenting in this field.”

References:

Lead, Violence, and Society

Big Business conducted a Big Experiment with America's youth you never knew about.

Big Business conducted a Big Experiment with America’s youth you never knew about.

When Rudy Giuliani ran for mayor of New York City in 1993, he campaigned on a platform of bringing down crime and making the city safe again. It was a comfortable position for a former federal prosecutor with a tough-guy image, but it was more than mere posturing. Since 1960, rape rates had nearly quadrupled, murder had quintupled, and robbery had grown fourteenfold. New Yorkers felt like they lived in a city under siege.

Giuliani won the election and selected Boston police chief Bill Bratton as the NYPD’s new commissioner. Bratton aggressively cracked down on small crimes, believing bigger crimes would drop as well. And they did.

But in fact, violent crime had actually peaked in New York City in 1990, four years before the Giuliani-Bratton era. By the time they took office, it had already dropped 12 percent. And it continued to drop. And drop. And drop. By 2010, violent crime rates in New York City had plunged 75 percent from their peak in the early ’90s.

It’s not just New York that saw a big drop in crime. In city after city, violent crime peaked in the early ’90s and then began a steady and spectacular decline. Washington, DC, didn’t have either Giuliani or Bratton, but its violent crime rate dropped 58 percent since its peak. Dallas’ fell 70 percent. Newark: 74 percent. Los Angeles: 78 percent.

The disappearance of lead from gas and paint is one of the most compelling hypotheses to explain the decline of violent crime in America, especially in cities — big cities, with their density and traffic, were particularly vulnerable to airborne lead.

It’s the only hypothesis that persuasively explains both the rise of crime in the ’60s and ’70s and its fall beginning in the ’90s. Two other hypotheses — the baby boom demographic bulge and the drug explosion of the ’60s — at least have the potential to explain both, but neither one fully fits the known data. Only gasoline lead, with its dramatic rise and fall following World War II, can explain the equally dramatic rise and fall in violent crime. In fact, gasoline lead may explain as much as 90 percent of the rise and fall of violent crime over the past half century.

Having said that, it’s important to note that the evidence so far is not conclusive in favor of any of the hypotheses.

References:

January 21, 1799 (a Monday)

James Gillray's caricature in 1802 of Dr. Jenner administering a smallpox vaccination to an unnerved woman. The cows emerging from the bodies of those inoculated point to the fear of the new vaccination, created from cowpox.(Library of Congress).

Until Edward Jenner came along, the only way to prevent smallpox was through a procedure called variolation (from variolae, Latin for “smallpox”) — the deliberate infection of an individual with smallpox. While in Constantinople in 1717, Lady Mary Wortley Montagu, the wife of the British ambassador, had learned about variolation, which had originally been developed in Asia. In 1721, at the urging of Montagu and the Princess of Wales, several prisoners and abandoned children were inoculated by having smallpox scabs from a recent victim inserted under the skin. As expected, they then contracted a mild form of the disease. Several months later, the children and prisoners were deliberately exposed to smallpox. When none contracted the disease, the procedure was deemed safe and members of the royal family were inoculated. The procedure then became fashionable in Europe. Between 1% to 2% of those variolated died as compared to 30% who died when they contracted the disease naturally.

However, variolation was never risk-free. Not only could the patient die from the procedure but the mild form of the disease which the patient contracted could spread, causing an epidemic. Victims of variolation could be found at all levels of society; King George III lost a son to the procedure as did many others. Edward Jenner was himself variolated while at school. He was “prepared” by being starved, purged and bled; then locked up in a stable with other artificially infected boys until the disease had run its course. He suffered particularly badly. It was an experience he would never forget.

Edward Jenner, a rural English doctor, is shown injecting his first patient, James Phipps, in 1796, using fluid obtained from one of the blisters on the hand of dairymaid Sarah Nelmes, standing behind him.

Jenner, an English physician, used folk knowledge to find an alternative to variolation. Recognizing that dairymaids infected with cowpox were immune to smallpox, he deliberately infected James Phipps, an eight year old boy, with cowpox on 14 May 1796 by placing fluid from a victim’s sore into two small incisions on the boy’s arm. A week later, Phipps developed the symptoms of cowpox, including infected sores, chills, head and body aches, and loss of appetite. The child recovered quickly. On 1 July 1796, Jenner variolated Phipps using fluid from smallpox pustules, and he had no reaction. Jenner inoculated the boy several more times in this manner with the same results. After repeating the experiment on other children, including his own son, Jenner concluded that this procedure, later named vaccination (from vacca, Latin for “cow”) by Louis Pasteur, provided immunity to smallpox without the risks of variolation. Jenner rejected the suggestion that he could become personally wealthy from his new smallpox vaccination, and he planned to share it with all of England and the world.

In late 1796, Jenner submitted a paper to be considered for publication in Philosophical Transactions of the Royal Society, England’s premier scientific journal. However, the Council of the Royal Society rejected the article and berated Jenner in scathing terms, characterizing his findings as unbelievable and “in variance with established knowledge”. It advised him that advancing such wild notions would destroy his professional reputation.

In June of 1798, Jenner independently published the findings from all of his research to date, including reports of the cases from his first manuscript and nine other patients he had vaccinated beside Phipps. This seventy-five-page book was titled An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease Discovered in Some of the Western Counties of England, Particularly Gloucestershire, and Known by the Name of The Cow Pox. Again, the London medical establishment was extremely negative toward his findings. Some prominent physicians questioned the validity of his findings. Others, who were profiting handsomely from variolation, attacked Jenner for fear of losing their lucrative monopoly on protecting the public from smallpox.

After the publication of his book, Jenner tried for three months to find people who would agree to be vaccinated in order to demonstrate the effectiveness of the procedure. He did not find a single volunteer because of the public attacks on his professional competence. Instead, Jenner pursued his goal of popularizing vaccination indirectly, through London physicians to whom he provided vaccine.

And so, on this date, Dr. William Woodville, a physician at the London Smallpox and Inoculation Hospital in England, first began inoculating the general public with Jenner’s vaccine. The results over the next four months were largely favorable to the new practice but contradicted several of Jenner’s claims, since approximately 60% of patients developed generalized pustular eruptions and were thought to be infectious. Jenner argued that Woodville’s vaccines had become contaminated with smallpox. Woodville ultimately accepted that this was the case. (Cowpox samples often became contaminated with smallpox itself because those handling it worked in smallpox hospitals or carried out variolation.) Nevertheless, despite the calumnies of the skeptics and confusion among its supporters, cowpox inoculation spread remarkably quickly in Britain, in the rest of Europe, and in other parts of the world.

References:

  • Murray Dworetzky, Sheldon Cohen, and David Mullin, “Prometheus in Gloucestershire: Edward Jenner”, The Journal of Allergy and Clinical Immunology Vol. 112, Issue 4, pp. 810-814 (October 2003)
  • John M. Hull, The philanthropic repertory of plans and suggestions for improving the condition of the labouring poor, (Sold by Suter, Cheapside, and by Snow, 1841) p. 72.
  • John Powell (ed.), Great Events from History: The 18th Century, 1701-1800 (Hackensack, NJ: Salem Press Inc., 2006).
  • History of Medicine Division/U.S. National Library of Medicine/National Institutes of Health, “Smallpox: A Great and Terrible Scourge” last updated 9 Dec 2011, accessed 23 Jan 2012.

December 27, 1822 (a Friday)

Louis Pasteur

On this date, the chemist and microbiologist Louis Pasteur was born in Dole in the Jura region of France.

From the time of the ancient Romans, through the Middle Ages, and until the late nineteenth century, it was generally accepted that some life forms arose spontaneously from nonliving matter. Such “spontaneous generation” appeared to occur primarily in decaying matter. For example, a seventeenth century recipe for the spontaneous production of mice required placing sweaty underwear and husks of wheat in an open-mouthed jar, then waiting for about 21 days, during which time it was alleged that the sweat from the underwear would penetrate the husks of wheat, changing them into mice. Likewise, the spontaneous generation hypothesis was proposed by scientists to explain the origin of the “animalcules” observed by Antoni van Leeuwenhoek in his magnifying lenses and had received wide acceptance all over Europe. Although such a concept may seem laughable today, it was consistent with the other widely held cultural and religious beliefs of the time.

It wasn’t until Louis Pasteur that this fallacy was finally disproved. In 1859, the French Academy of Science offered the Alhumbert Prize of 2500 francs to whoever could shed “new light on the question of so-called spontaneous generation”. Young Pasteur’s award winning experiment was a clever variation of earlier experiments performed by John Needham (1713-1781) and Lazzaro Spallanzani (1729-1799). Pasteur filled a long necked flask with meat broth. He then heated the glass neck and bent it into an “S” shape. Air could reach the broth, but gravity acted to trap airborne microorganisms in the curve of the neck. He then boiled the broth. After a time, no microorganisms had formed in the broth. When the flask was tipped so that the broth reached the microorganisms trapped in the neck, the broth quickly became cloudy with microscopic life.

Pasteur filled a flask with medium, heated it to kill all life, and then drew out the neck of the flask into a long S. This prevented microorganisms in the air from entering the flask, yet allowed air to flow freely. If the swan neck was broken, microbes could enter the flask and grow.

Thus, Pasteur disproved spontaneous generation. Furthermore, Pasteur proved that some microorganisms are airborne. “There is no known circumstance in which it can be confirmed that microscopic beings came into the world without germs, without parents similar to themselves,” he concluded in 1864. His experiment also supported germ theory. Germ theory states that specific microscopic organisms are the cause of specific diseases. While Pasteur was not the first to propose germ theory (Girolamo Fracastoro, Agostino Bassi, Friedrich Henle and others had suggested it earlier), he developed it and conducted other experiments that clearly indicated its correctness, thereby managing to convince most of Europe it was true.

Despite what creationists and proponents of “intelligent design” may insist, Pasteur’s research on spontaneous generation did not demonstrate the impossibility of life arising in simple form from nonliving matter under conditions vastly different from those today and by means of a long and propitious series of chemical steps/selections. In particular, he did not show that life cannot arise once, and then evolve. Neither Pasteur, nor any other post-Darwin researcher in this field, denied the age of Earth or the fact of evolution. What Louis Pasteur and the others who denied spontaneous generation did demonstrate is that life does not currently spontaneously (i.e., within a matter of weeks) arise in complex form from nonlife in nature.

Memorable Quote:

One does not ask of one who suffers: What is your country and what is your religion? One merely says: You suffer, this is enough for me: you belong to me and I shall help you.

— quoted in Louis Pasteur, Free Lance of Science (1950) by René Jules Dubos, p. 85

Is evolutionary biology useful in medicine?

medicalsymbol4David Hillis at The University of Texas in Austin sent an e-mail that answers this question to Jerry Coyne, who has posted the message on his website. David’s e-mail, although brief, is very specific, includes citations from the scientific literature, and is persuasive!