Twenty Tiny Fingers

“Twenty tiny fingers, Twenty tiny toes
Two angel faces, Each with a turned up nose
One looks like Mommy, With a cute little curl on top
And the other one’s got, A big bald spot
Exactly like his Pop…”

Alma Cogan

Like many people, I have pet cats. My two cats are called Marvel and Oba. I look after them and they look after me. I am devoted to my cats and, as far as I can tell, my feelings are reciprocated. Even the idea that they wouldn’t be around one day fills me with grief. I am quite certain that millions of people throughout the world feel exactly the same way about their cats, dogs, bunnies, hamsters and the numerous other types of animals that share their lives. But obviously there is nothing one can do to prevent the death of a beloved companion—or is there?

A recent news story described events in China concerning a man named Huang Yu and his cat, a British shorthair named Garlic. Huang and Garlic were deeply attached to one another. But then Garlic developed a urinary tract infection and died. To begin with, Mr. Yu buried Garlic in a park near his home, but then he had another idea. He had read an article about the possibility of cloning pets and, as he was a well-off business man, he decided to give it a shot. So, he contacted a cloning company named the Sinogene Biotechnology Company. Following Sinogene’s instructions, Huang exhumed Garlic’s corpse, wrapped it carefully in a towel and placed it in his refrigerator. He then waited for a Sinogene employee to arrive from Beijing to extract skin cells from Garlic and deep freeze them while Huang decided what to do. About a month after Garlic’s death, Huang decided to take the plunge and to go through with the procedure for cloning Garlic for a fee of around $40,000. Sixty six days later, Garlic junior was successfully born to a surrogate mother—he was the first cat to have been cloned in China. Stringent biochemical tests confirmed that Garlic Jr. was in fact genetically identical to Garlic Sr. However, as things turned out, baby Garlic didn’t really look all that much like his “parent.” For example, Garlic Sr. had a very marked black spot in the middle of his face and baby Garlic didn’t. Nevertheless, Garlic junior is a really adorable kitten, and perhaps he may one day develop behaviors that will remind Mr. Yu of his beloved forebear.

Garlic Sr.
Garlic Jr.

The fact that Garlic junior didn’t actually look much like his clone parent isn’t all that surprising given previous experience with cat clones. The first cloned cat was produced on December 22, 2001, when scientists at Texas A&M University, in collaboration with the pioneering pet cloning company Genetic Savings and Clone, announced the birth of the world’s first cloned cat which they named “Copy Cat” or “CC.” CC’s clone mother was a calico cat named Rainbow. Rainbow’s coat was made up of a mixture of orange, black and white patches, whereas CC was a tiger tabby—a completely different coat pattern. Again, biochemical tests confirmed that Rainbow and CC had exactly the same genes. But if all their genes are identical, why don’t cloned cats like CC or Garlic Jr. resemble their clone parents? Let’s consider how the cloning procedure actually works.

Rainbow, left, nuzzles the ear of her clone, named “CC,” on a table at Texas A&M University a little more than a year after CC’s birth. Even though the cats share the same DNA, each uses it differently, leaving them with different markings and personalities.

Now remember Dolly the sheep? Dolly was an example of a cloned animal and, as she was cloned from an adult mammalian cell, she was the first of her kind. How exactly does this work? Consider that all animals arise from a single fertilized egg through a developmental program which is directed by their genes. The first few cells in a dividing embryo are pretty much the same. However, they gradually become more “restricted” in their properties as different tissues develop. Genes are made of large strings of the biochemical polymer, DNA. With a few exceptions (known as mitochondrial genes), the DNA that directs the development of an animal is localized in the nucleus of each cell. During development, certain genes get turned on or off resulting in the development of different tissues. However, the nucleus of virtually every cell in the body still contains the full complement of an animal’s DNA, although in each tissue only certain genes that are specific for that tissue are activated. The idea of cloning, then, is to take an animal’s cell, remove the nucleus (which contains all of its genes), and coax it to develop into a new animal—a “clone” of the original animal. The cell could be taken from the skin of the animal or some other convenient source. How exactly can this be done, considering that—although this nucleus has all of the required genes—many of them have been turned off? To obtain a cloned animal, these genes need to be turned on again. This is achieved by taking an egg cell from the same species. The nucleus of that egg cell is then removed and the nucleus derived from the clone parent’s cell is inserted in its place. Under the right circumstances, the nucleus becomes “reprogrammed” to return to its original embryonic state. Now, the newly reconstituted egg cell is electrically zapped and begins to divide just like a zygote—an egg cell that has been fertilized by a sperm. The developing embryo is now implanted into a surrogate mother who will carry it to term if all goes well. As the DNA of the original animal and the clone are identical, the two should resemble each other exactly. Or at least, that’s the theory. The entire procedure is known as Somatic Cell Nuclear Transfer (SCNT). Development of this process by the scientist John Gurdon won him the Nobel Prize.

SCNT was the method used to clone Dolly. The original cloning of Dolly was a tour de force and represented a positive result obtained in the midst of innumerable failures. Since the cloning of Dolly, animal cloning has become much more efficient and reproducible and is now considered to be a part of agricultural science where it is applied to the production of livestock. In addition, a vast array of other animals including deer, horses, rabbits, cats, rats, mice, dogs and monkeys have also been successfully cloned. Yes, monkeys—indicating that cloning humans isn’t going to be far behind if somebody actually wants to go down that path. Indeed, human embryos have been cloned, but just never implanted into surrogate mothers and brought to term. Cloning people’s pets is an interesting offshoot of animal cloning science, and companies that perform these procedures are hoping to find a niche in the pet market. At the moment, cloning pets is very expensive—maybe somewhere in the region of $20,000–$50,000—so the number of people who are in a position to do it is relatively small and restricted to wealthy businessmen like Mr. Yu, or superstars. Indeed, another recent example that was widely discussed in the media concerned the famous singer Barbra Streisand. For many years, Ms. Streisand had a dear pet dog—a Coton de Tulear called Samantha or “Sammie.” Eventually, Sammie passed away, leaving Ms. Streisand distraught with grief. She had a friend who had cloned her pet and who was very satisfied with the results, and so Ms. Streisand decided to do the same thing. In an interview, Ms. Streisand said that when she saw her beloved pet dying she realized she “couldn’t bear to lose her” and so decided to attempt cloning. “I think any pet lover will really understand this,” added Ms. Streisand. One cannot help but agree with her. Among the offspring were two beautiful dogs that looked exactly like Sammie, their clone parent. Ms. Streisand named these dogs Miss Violet and Miss Scarlett. However, in spite of the fact that they certainly resemble their forebear, Ms. Streisand reported that their personalities were quite different and that they did not display the degree of “wisdom” associated with their clone parent. Nevertheless, she said she was hopeful that this trait might emerge with age.

Miss Violet and Miss Scarlett (left and right ) with their cousin Fanny in the center, visiting Samantha’s grave.

Why is it, then, that in the case of the cats we have discussed, the cloned progeny look so different from their clone parents? And furthermore, why is it that even in the case of Ms. Streisand’s two cloned dogs, their personalities are different from that of their clone parent, even though they closely resemble her? If their genes are the same, which they certainly are, how can they be different? The fact is that our genes are rather like a recipe. They give you the basic instructions and ingredients for baking a cake but, as we know, things will turn out differently depending on who is doing the baking. There are actually a whole host of mechanisms which are known as “epigenetic” effects which may result in a clone being different from its parent. Epigenetic effects operate by altering the way gene products are expressed. They are mechanisms that can affect how an animal develops (its phenotype) that are not due to changes in the DNA sequences of genes per se. Among other things, such mechanisms can allow a developing animal to respond to changes in its environment, either in utero or once it is born. How does this happen? There are enzymes that can chemically modify DNA, for example by adding methyl groups to cytosine bases resulting in changes in gene transcription. Moreover, the histone proteins that wrap themselves around DNA and control the way genes are turned on and off can also be modified by methylation or acetylation, and this can also alter their activity. The activity of genes is also controlled by proteins called transcription factors which can respond to environmental influences. Overall, therefore, there are numerous ways that the expression of genes in two identical organisms (clones or identical twins) can be modified by environmental influences and lead to identical twins or cloned progeny who begin to differ from each other or their clone parent as they develop.

As we have seen, neither Garlic Jr. nor CC looked like their clone parent. In fact, the coat color of a cat is also an interesting example of epigenetic influence. There are several different genes that determine the coat pattern of a cat. One gene, named O/o, is found on the X chromosome. “O” determines whether there will be any orange tones in the fur color due to the synthesis of the pigment phaeomelanin. Its variant—or “allele,” to use genetic terminology—“o” produces the non-orange pigmentation eumelanin (black or brown). Because males have just one copy of the X chromosome, they can carry only one of the alleles of this gene—either O or o. If they carry the allele O, they will be red, orange or creamy (depending on the variation), otherwise, they won’t have any orange tones to their fur. Females have two X chromosomes which means they will carry two alleles of the gene. However, in cells from a female, one X chromosome is always inactivated and this is a random process. Hence, in a cat who is O/o, the O- or o-containing chromosome is randomly inactivated in some clusters of skin cells and activated in others. When O is activated, the skin cells produce orange fur and when inactivated they produce black fur. This process usually results in a mosaic of orange and black or what is known as a tortoiseshell pattern. Another gene called “white spotting” can also play a role in determining coat pattern. During fetal development, melanocytes, the pigment-producing cells in the skin, migrate across the skin starting from the back and moving towards the belly. If the melanocytes get a late start on their migration, which is what happens when white spotting is active, they pull up short, leaving the cat with a white non-colored pattern primarily on their underside and legs. When this gene comes into play, the female cat can be tricolor or calico rather than just tortoiseshell. The mechanism for expression of the white spotting gene is also random, meaning that even clones of say a simple black and white tuxedo cat could exhibit patterns with noticeable variations. Of course, it is not only coat color that can result from processes such as this. Interactions with the environment in utero can have a pronounced effect on epigenetic processes. Consider that the womb of a surrogate mother is not the same as the womb where the clone parent developed. Following birth, many factors including nutrition, nursing and stress may affect the activity of enzymes that place epigenetic tags on histones and regulate development in different ways. Hence, there are numerous reasons why a cloned pet may vary from its parent. Indeed, it is difficult to see how a cloned pet could ever be exactly like its clone parent.

Although the idea of people cloning pets has its charms and the idea of cloning cattle might be important for agricultural reasons, the entire idea of cloning animals has a dark side, even if we dismiss the idea of cloned humans. We need to give the entire subject some careful consideration as to what things should or should not be done. Where do we draw a line in the sand, why or when would we cross some ethical Rubicon? Consider an important story earlier this year resulting from work going on in China. The report described the cloning of a group of genetically modified monkeys. These weren’t the first monkeys to be cloned using the SCNT method. This event took place in 2018 when a paper in the journal Cell described the cloning, also in China, of two long-tailed macaques named Zhong Zhong and Hua Hua. One American scientist commented, “Working with cloned animals greatly reduces the variability of the genetic background, so fewer animals are needed,” something that could be true if the entire procedure is considered purely from a practical point of view. The story that broke earlier this year was an extension of these events. In this case, scientists at the Institute of Neuroscience in Shanghai reported that they had used gene editing to disable the gene BMAL-1, which is involved in regulation of the sleep/wake cycle in macaque monkeys, humans and other animals. The scientists then produced 5 clones of this monkey. This is the first time that scientists have cloned gene-edited monkeys which, in this case, have severely disrupted sleep patterns. This is what the scientists responsible call a “proof of principle” experiment, indicating what can potentially be achieved. As far as the future is concerned, the leader of the group has stated that as monkeys are much closer to humans than any other animal, in the future they will “revolutionize research” by being able to make monkeys with genes that give rise to complicated human diseases like schizophrenia and other disorders which involve higher cognitive functions. Dr. Poo, who leads the group, opined that this is much better than trying to study these diseases in mice which don’t resemble humans in most respects. Dr. Poo thinks that schizophrenic mice simply don’t do the job.

How should we feel about the work of the Chinese scientists? It is certainly quite true that genetically modified cloned monkeys may help people investigate scientific questions. But hold on a minute. The cloned monkeys, and those that are in the planning stages, are being created to have terrible diseases. Monkeys are very sophisticated animals and can certainly experience emotions of many types. They can certainly suffer, as can any sophisticated animal with a terrible disease. It is interesting to note that the creators of these monkeys spend a lot of time explaining how accurately the cloned monkeys will model the diseases that they carry. Conveniently, there is no discussion of the emotional toll of these diseases, which are certainly major components of each syndrome. In other words, apart from anything else, what the scientists are creating are a group of animals that are designed to suffer throughout their lives. Of course, science makes use of animal models very extensively, especially mice. There has been considerable discussion about the ethical appropriateness of doing such experiments and it might be argued that such considerations are particularly relevant in the case of monkeys. When one thinks about the complete spectrum of biological consequences of making genetically modified cloned monkeys that are destined to carry horrible diseases, I think that the appropriate reaction is one of revulsion and horror. It really isn’t a question of whether we can potentially obtain useful scientific information from these creatures. This fact is trumped by the sheer inhumanity of the entire enterprise. We shouldn’t do such things, and that is that.

Whatever we think about the cloning and modifying of animals to be used in scientific research, it will be clear that pet cloning has arrived to stay. At this particular time, it is very expensive and so access to these procedures is restricted. However, like all techniques in the burgeoning field of molecular genetics and cell biology, the prices will fall rapidly in coming years. Even in such situations, should one do it? People who criticize the technique, I think, fail to understand its appeal. Even if your cloned cat doesn’t look or behave exactly like its parent, one imagines that it will be imbued with aspects of the “spirit” of the dearly departed and that is something that people recognize and want to hang on to. Nevertheless, there are probably better alternatives. While researching this article, I found several companies online that will synthesize an artificial cloned pet for you. This is prepared from photographs of your pet taken from different angles which are then analyzed to provide a design that is then used as a basis for making an artificial animal. The results can certainly be very striking.

Which is which? Pet cat and its “cuddle clone”

Moreover, these artificial animals really do look like your original pet. Of course, given the fact that they aren’t actually alive, some aspects of your pet will clearly be missing. I should also point out that there are millions of beautiful stray cats and dogs living in animal shelters all over the world who need a good home with loving owners. So, perhaps even if you are tempted to clone Fluffy or Rover, adoption of a stray and generally participating in animal welfare is the way to go.

The Church of Woodstock

Woodstock poster

A story that has received considerable attention in the media over the past few weeks celebrates the 50th anniversary of what was originally advertised as the “Woodstock Music and Art Fair” in upstate New York. In keeping with the 1960s counter cultural aim of establishing an “Age of Aquarius,” the festival was billed as “An Aquarian Exposition” and “3 Days of Peace and Music.” As I was working in New York City at the time, it was not difficult for me to attend the festival, which I did. The story of what happened is well known and has been widely discussed. What was supposed to be an audience optimistically estimated at perhaps 50,000 people turned into a gathering of some 400,000 who came together to hear music performed by many of the cutting-edge artists of the time. The overall mood of the audience was one of cooperation and realization of mutual aims devoted to opposing racism and war and promoting love and peace. In spite of the sometimes chaotic organization of the entire affair, there was virtually no violence. The vast group of young people and the temporary city that grew up around the festival stage showed the world that perhaps a different kind of society was indeed possible, free from the economic and social assumptions that plagued the world.

Psychotropic drugs, and hallucinogenic drugs like LSD and mescaline in particular, played an important role in promoting the quasi-religious atmosphere that prevailed at the festival. Indeed, the connection between hallucinatory thinking and religious experience is a close one going back to the very beginnings of human culture. The word “hallucination” was a neologism coined by the great Sir Thomas Browne in a chapter of his Pseudodoxia Epidemica (1646) in which he discussed the proposition, apparently current at the time, that all moles are blind. He thought not. In the article entitled “Of Moles,” he considered several kinds of visual problems to which he assigned different names. For example, he wrote that if vision is “depraved and receive[s] its objects erroneously—hallucination.” Of course hallucinations had been described for hundreds of years even if, prior to Browne, they were not named as such. The occurrence of a hallucination in an individual was always interpreted in a religious context. More often than not, the victim was thought to be possessed by a devil or evil spirit. But this wasn’t always the case. Indeed, many great religious leaders have experienced hallucinations and they have been interpreted as the receipt of important information from a deity.

One can see how this played out historically, and how it was eventually closely associated with the development of the Age of Aquarius in the 1960s. In the last four centuries, for example, there were several important religious figures who experienced marked hallucinations and used them as part of their religious message. This was certainly true of the influential 17th century theosophist Jacob Boehme and of the mystical leader Emanuel Swedenborg in the 18th century. Of course the figure who was widely appropriated by the 1960s counter culture movement was that of William Blake. Blake suffered from hallucinations throughout his life—of angels sitting in the trees, for example. Moreover, his revolutionary technical advances in print making were inspired by visions of his deceased younger brother who provided him with technical information. The kind of mystical world inhabited by Blake was a powerful contrast to the burgeoning Enlightenment by which he was surrounded. This is certainly clear in his art—which can obviously be seen by comparing a picture by Blake to one painted by the great portraitist Sir Joshua Reynolds, who was his contemporary.

Joshua Reynolds: Mrs. Abington as Miss Prue in “Love for Love” by William Congreve (1771)
William Blake (1757–1827): The Great Red Dragon and the Woman Clothed in Sun

But things go a lot deeper than that. Blake completely rejected the intellectual underpinnings of the Enlightenment saying things such as “I must not reason and compare: my business is to create.” Blake had no time for science which he thought was a force that constrained the mind and reduced human creativity. Blake took issue with important Enlightenment figures such as Newton and Locke, satirizing them in his mythical universe as Urizen—a character who pedantically stifled creativity through the rule of law and rational thinking. Blake famously portrayed Newton situated in a cave where, as in Plato’s Republic, he was only aware of the shadows of reality.

William Blake: Newton (1795)

Mystical thinkers like Blake, Swedenborg and Boehme were part of an entire intellectual history which has been called the Western Esoteric Tradition, which, as opposed to science, deals much more with myth and mysticism as an explanation for the world. The fact that this tradition has gone from strength to strength over the years in the face of extraordinary advances in our scientific understanding of Nature speaks to what must surely be some important advantages it must have for human society. Indeed, thinkers such as CG Jung strongly believed that mystical thinking and beliefs were actually hard-wired into the human psyche and had important functions for human cognition. Although present throughout history, organizations that encouraged non-rationalist thinking underwent a strong resurgence during the 19th century, particularly in association with the establishment of the Theosophical society by Helena Petrovna Blavatsky. The actual factual basis for Madame Blavatsky’s religion as detailed in her books Isis Unveiled and the Secret Doctrine,that she received information telepathically from Tibetan adepts living in the Himalayas which engendered her theory of human evolution and her ideas about contact with the spiritual world,would clearly seem like complete nonsense to anybody with modern scientific training. Nevertheless, in spite of this, Blavatsky’s ideas have proven to be enormously influential with people who are not invested in a scientific outlook of the world and are receptive to ideas of a mystical nature. For example, the Theosophical notion that thoughts actually had shapes and colors, as detailed by Blavatsky’s successors Annie Besant and William Leadbetter in their book Thought-Forms, provided a powerful stimulus to people like Hilma af Klint, Piet Mondrian and Wassily Kandinsky who were all committed Theosophists and developed non-representational modern painting.

Annie Besant and CW Leadbetter: The Music of Gounod in Thought-Forms” (1901)
Wassily Kandinsky: Untitled (1910)

It is this type of thinking that can be enabled in individuals by hallucinogenic drugs like LSD. As Blake said, “If the doors of perception were cleansed everything would appear to man as it is, Infinite. For man has closed himself up till he sees all things through narrow chinks in his cavern.” Many others, including Aldous Huxley in his study of mescaline use, have subsequently used “The Doors of Perception” as an allusion to the use of hallucinogenic drugs, allowing imaginative and creative thought that is not shackled by rational thinking.

Indeed, hallucinogenic drugs have always been associated with religious thinking. When the Spaniards first conquered Mexico in the 16th century, they quickly became aware that the religions of the indigenous peoples relied to a great extent on the use of hallucinogens in the ceremonies. Great scholars like the marrano priest Bernardino de Sahagun—who produced the 16th century Florentine Codex, an anthropological text describing the societies of the indigenous Mexican populations—described the use of hallucinogenic psilocybin mushrooms, ergot alkaloid-containing morning glory seeds, and mescaline-containing hallucinogenic cacti such as peyote (Lophophora Williamsi) by shamans when they conducted religious ceremonies. Many of these practices disappeared from plain view following the Spanish conquests, although they continued to be practiced in small villages out of the direct view of the conquistadors. However, this wasn’t the end of things. They were rediscovered in the 20th century by people such as Gordon Wasson who wrote about his findings in widely distributed articles such as his influential 1957 article “Seeking the magic mushroom” in Life Magazine.

One of the people that read the article was a young faculty member in the Psychology department at Harvard university named Timothy Leary. Leary journeyed to Mexico and sampled some psilocybin mushrooms. The experience had a profound effect on him and he returned to Harvard determined to investigate drug-induced experiences and how they might benefit modern Western societies. He performed several studies using university students as subjects. However, these were deemed unethical by the authorities and eventually Leary and some of his closest colleagues were dismissed. However, his activities had attracted the attention of numerous influential people including the heirs to the Mellon family fortune who now bankrolled Leary so that he could set up a private research institution which he named the Castilia Foundation (in reference to Herman Hesse’s “The Glass Bead Game”) in a mansion in Millbrook, NY where he continued to carry out experiments with hallucinogens, particularly LSD. Leary did a great deal to popularize the use of LSD for personal improvement and for use in radical politics, telling young people to “Turn on, tune in and drop out.” Interestingly, the ceremonies carried out at the Castilia Foundation were based on the Tibetan book of the dead, thereby reviving once again the mystical traditions of 19th century theosophy. Whatever value was associated with Leary’s LSD-fueled therapies, it is certainly true to say that the fascinating effects produced by drugs like LSD were taken very seriously by psychiatrists in the two decades between 1950 and 1970 when thousands of bona fide research articles were published on the potential use of these drugs in the treatment of numerous psychiatric disorders.

Psychedelic drugs also found their way to the West Coast courtesy of the CIA. American intelligence had been investigating the potential of psychedelic drugs as brainwashing agents to be used as weapons in the Cold War. One of the people on whom they tested LSD was Ken Kesey, then a creative writing student at Stanford, who went on to write the bestselling novel “One Flew Over the Cuckoo’s Nest.” Like Leary, Kesey rapidly became convinced in the power of hallucinogenic drugs to change humanity for the better, and with his group of acolytes, the Merry Pranksters, began to distribute LSD widely throughout the Bay Area and beyond. Hallucinogenic drug use fueled the San Francisco counter culture “hippie” movement, resulting in an entirely new day-glo aesthetic which characterized the psychedelic hallucinatory experience. This was particularly manifest in poster art sometimes paying homage to Helena Blavatsky and William Blake, obviously strong influences on the movement.

Poster for Big Brother and the Holding Company featuring Madame Blavatsky—Stanley Mouse and Anton Kelley (1966)

The 1960s counter culture had many of the characteristics of a religion with shamans like Leary and Kesey. The enormous music festivals like Woodstock and Monterey were akin to religious gatherings fueled, as in ancient times, by the use of hallucinogens. This kind of behavior was anathema to the majority of middle-class Americans who became seriously frightened by what was going on, and President Nixon and his government passed the Controlled Substances Act that completely banned the possession and use of hallucinogens. Drugs like LSD (and cannabis) were categorized as Schedule 1 under the new law, which meant that they were deemed to be extremely dangerous and have no medical utility whatsoever. However, it should be noted that this move was entirely motivated by politics and not for bona fide medical reasons. In fact, it might be argued that drugs like LSD, which are not addictive, are useful in allowing humans access to a mystical psychological realm which could be extremely helpful to them. Nevertheless, with the passage of the Act, drugs like LSD completely disappeared from the arena of medical research.

The total eclipse of hallucinogens lasted for several decades. However, scientific interest in drugs that produced such interesting cognitive effects and had obvious psychotherapeutic potential was bound to resurface at some point. Over the last decade, there has been a clear revival of interest in the scientific underpinnings of hallucinogenic drug action, something that has been enabled by the use of powerful brain imaging techniques that were not available in the 1960s. It has been understood for many years that hallucinogens act as agonists at 5-HT2A receptors in the brain, but how this biochemical effect produced such profound changes in cognition was not known.

The detailed effects of drugs like LSD and psilocybin on the active, conscious human brain can be observed by using brain imaging techniques like functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Not surprisingly, drugs like LSD produce widespread changes in the activity of the brain. One of the most interesting things that has been consistently observed are changes in what is known as the Default Mode Network (DMN) of the brain. The DMN is an interconnected group of brain structures that seems to be particularly active when the brain is “at rest,” that is thinking without any explicit goal in mind. In other words, it is the state one is in when one is not actively engaged in a particular task and one’s mind is more focused on oneself. Indeed, it is considered likely that such self-reflective mental activity may constitute important aspects of our sense of self—or what we might call our ego.

Drugs like psilocybin and LSD decrease activity of brain structures within the DMN, while simultaneously increasing functional connectivity between various other brain regions—something that has been described by workers in the field as an increase in “entropy” of the connectivity of the brain. Perhaps not surprisingly, many of the areas where major changes in connectivity or rhythmic activity occur express high concentrations of 5HT2A receptors for which the hallucinogenic drugs act as agonists. Taken together, these results indicate that hallucinogens enhance global and between-module communication while diminishing the integrity of individual modules like the DMN, and that this effect is mediated by the brain’s key integration centers such as those that are rich in 5-HT2A receptors. How are such changes in the activity of the brain to be interpreted? We know that drugs like LSD produce extraordinarily profound changes in mood, the quality of thought and sensory perceptions, frequently leading to synesthesia, hallucinations and delusions, alterations in an individual’s experience of time and space, and an individual’s experience of self. In particular, hallucinogenic drugs cause a loosening of an individual’s sense of ego—a phenomenon sometimes called “ego dissolution” or “ego death.” The way that such changes in the perception of self are interpreted will depend on the individual and the setting. They could be associated with a sense of henosis, oneness and bliss or they might lead to more negative interpretations, including fear and paranoid ideation associated with experiences of the loss of one’s ego. Of great interest is the fact that the LSD-induced changes to the DMN observed in imaging studies are closely correlated with the subjects reported sense of ego dissolution.

The connectome of the human brain on LSD

Because we are now starting to develop a more sophisticated picture of how hallucinogenic drugs alter the activity of the brain, we might ask whether such changes also occur in individuals who report mystical thinking. It is obviously the case that in many respects, LSD intoxication and mysticism represent very different mental states. Nevertheless, because they seem to overlap significantly, it is a reasonable question to ask what the neural correlates might be that define these areas of commonality? Certainly, not all experiences induced by hallucinogens are of the mystical type. However, with the proper setting, preparation, support, and dose, mystical experiences are occasioned with a high frequency. We know this very well because hallucinogenic drugs have been used by shamans and witch doctors for producing these very effects for thousands of years. Questionnaires supplied to subjects undergoing imaging studies with hallucinogenic drugs report a high incidence of mystical thinking. One of the most famous “experiments” carried out by Timothy Leary and his colleagues back in the 1960s was the Marsh Chapel experiment in which individuals participating in a Good Friday religious service were given psilocybin or a placebo and asked to rate their spiritual experience. Participants who had received psilocybin overwhelmingly reported that their experience during the service had been more spiritually meaningful. This same experiment has now been repeated a number of times and the results are always the same.

It appears, therefore, that humans have evolved an extremely ancient and deeply encoded capacity for mystical thinking, something that one might speculate is related to a need for humans to make spiritual connections with other individuals, the biosphere and the universe in general. In modern times, mystical thinking is often something that relates to an individual’s struggle for meaning in the face of a world which is increasingly “explained” by rational, material and scientific approaches which, in many respects, have sought to displace the mystical side of human existence. Mystical thinking can be accessed by meditative procedures, ecstatic religious practices, the use of hallucinogenic drugs, and is sometimes present as an aspect of psychopathology. Brain imaging studies have started to provide us with an understanding of the neural substrates that may underlie this mode of thinking. Because mystical thinking is quintessentially irrational, it is not bound by the rules that normally govern much of conventional thinking, allowing an escape into a state of mind that is more “outside the box” and in many respects representative of a sort of creativity that can lead to original artistic and philosophical insights. It is perhaps not surprising, therefore, that since the earliest times, humans have found great utility in the use of naturally occurring hallucinogenic substances that help them to access mystical states. The modern world has attempted to legislate these substances out of the mainstream of human existence. But this is surely shortsighted, as it seems that they help us to address a fundamental human need. It is only when humanity fully appreciates both the rational and irrational sides of the human psyche that it will attain its full potential. Current research on hallucinogens has suggested that the personal insights afforded by such drugs may be therapeutically useful in the context of some psychiatric disorders such as depression.

The Woodstock festival was really a “religious” gathering in many respects. The aims of the young people who gathered there were admirable. But over the last 50 years, the influence of the 60s counter cultural movement has waned. Now, as science and society are becoming interested in the potential of hallucinogenic drugs once again, perhaps it is time to re-examine some of the goals of the Woodstock generation as a guide to healing a planet that is quickly succumbing to malevolent forces that are spinning out of control.