## Neurociencia | Neuroscience

#### Neuroscience

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### Video

0:12 - Can we, as adults, grow new nerve cells? There's still some confusion about that question, as this is a fairly new field of research. For example, I was talking to one of my colleagues, Robert, who is an oncologist, and he was telling me, "Sandrine, this is puzzling. Some of my patients that have been told they are cured of their cancer still develop symptoms of depression." And I responded to him, "Well, from my point of view that makes sense. The drug you give to your patients that stops the cancer cells multiplying also stops the newborn neurons being generated in their brain." And then Robert looked at me like I was crazy and said, "But Sandrine, these are adult patients -- adults do not grow new nerve cells." And much to his surprise, I said, "Well actually, we do." And this is a phenomenon that we call neurogenesis.

1:12 - [Neurogenesis]

1:14 - Now Robert is not a neuroscientist, and when he went to medical school he was not taught what we know now -- that the adult brain can generate new nerve cells. So Robert, you know, being the good doctor that he is, wanted to come to my lab to understand the topic a little bit better. And I took him for a tour of one of the most exciting parts of the brain when it comes to neurogenesis -- and this is the hippocampus. So this is this gray structure in the center of the brain. And what we've known already for very long, is that this is important for learning, memory, mood and emotion. However, what we have learned more recently is that this is one of the unique structures of the adult brain where new neurons can be generated. And if we slice through the hippocampus and zoom in, what you actually see here in blue is a newborn neuron in an adult mouse brain. So when it comes to the human brain -- my colleague Jonas Frisén from the Karolinska Institutet, has estimated that we produce 700 new neurons per day in the hippocampus. You might think this is not much, compared to the billions of neurons we have. But by the time we turn 50, we will have all exchanged the neurons we were born with in that structure with adult-born neurons.

2:54 - So why are these new neurons important and what are their functions? First, we know that they're important for learning and memory. And in the lab we have shown that if we block the ability of the adult brain to produce new neurons in the hippocampus, then we block certain memory abilities. And this is especially new and true for spatial recognition -- so like, how you navigate your way in the city.

3:25 - We are still learning a lot, and [neurons] are not only important for memory capacity, but also for the quality of the memory. And they will have been helpful to add time to our memory and they will help differentiate very similar memories, like: how do you find your bike that you park at the station every day in the same area, but in a slightly different position?

3:51 - And more interesting to my colleague Robert, is the research we have been doing on neurogenesis and depression. So in an animal model of depression, we have seen that we have a lower level of neurogenesis. And if we give antidepressants, then we increase the production of these newborn neurons, and we decrease the symptoms of depression, establishing a clear link between neurogenesis and depression. But moreover, if you just block neurogenesis, then you block the efficacy of the antidepressant. So by then, Robert had understood that very likely his patients were suffering from depression even after being cured of their cancer, because the cancer drug had stopped newborn neurons from being generated. And it will take time to generate new neurons that reach normal functions.

4:48 - So, collectively, now we think we have enough evidence to say that neurogenesis is a target of choice if we want to improve memory formation or mood, or even prevent the decline associated with aging, or associated with stress.

5:07 - So the next question is: can we control neurogenesis? The answer is yes. And we are now going to do a little quiz. I'm going to give you a set of behaviors and activities, and you tell me if you think they will increase neurogenesis or if they will decrease neurogenesis. Are we ready? OK, let's go.

5:31 - So what about learning? Increasing? Yes. Learning will increase the production of these new neurons.

5:39 - How about stress? Yes, stress will decrease the production of new neurons in the hippocampus.

5:47 - How about sleep deprivation? Indeed, it will decrease neurogenesis.

5:53 - How about sex? Oh, wow!

5:56 - (Laughter)

5:57 - Yes, you are right, it will increase the production of new neurons. However, it's all about balance here. We don't want to fall in a situation --

6:06 - (Laughter)

6:10 - (Laughter)

6:13 - How about getting older? So the neurogenesis rate will decrease as we get older, but it is still occurring.

6:25 - And then finally, how about running? I will let you judge that one by yourself.

6:32 - So this is one of the first studies that was carried out by one of my mentors, Rusty Gage from the Salk Institute, showing that the environment can have an impact on the production of new neurons. And here you see a section of the hippocampus of a mouse that had no running wheel in its cage. And the little black dots you see are actually newborn neurons-to-be. And now, you see a section of the hippocampus of a mouse that had a running wheel in its cage. So you see the massive increase of the black dots representing the new neurons-to-be.

7:07 - So activity impacts neurogenesis, but that's not all. What you eat will have an effect on the production of new neurons in the hippocampus. So here we have a sample of diet -- of nutrients that have been shown to have efficacy. And I'm just going to point a few out to you: Calorie restriction of 20 to 30 percent will increase neurogenesis. Intermittent fasting -- spacing the time between your meals -- will increase neurogenesis. Intake of flavonoids, which are contained in dark chocolate or blueberries, will increase neurogenesis. Omega-3 fatty acids, present in fatty fish, like salmon, will increase the production of these new neurons. Conversely, a diet rich in high saturated fat will have a negative impact on neurogenesis. Ethanol -- intake of alcohol -- will decrease neurogenesis. However, not everything is lost; resveratrol, which is contained in red wine, has been shown to promote the survival of these new neurons. So next time you are at a dinner party, you might want to reach for this possibly "neurogenesis-neutral" drink.

8:20 - (Laughter)

8:23 - And then finally, let me point out the last one -- a quirky one. So Japanese groups are fascinated with food textures, and they have shown that actually soft diet impairs neurogenesis, as opposed to food that requires mastication -- chewing -- or crunchy food.

8:41 - So all of this data, where we need to look at the cellular level, has been generated using animal models. But this diet has also been given to human participants, and what we could see is that the diet modulates memory and mood in the same direction as it modulates neurogenesis, such as: calorie restriction will improve memory capacity, whereas a high-fat diet will exacerbate symptoms of depression -- as opposed to omega-3 fatty acids, which increase neurogenesis, and also help to decrease the symptoms of depression. So we think that the effect of diet on mental health, on memory and mood, is actually mediated by the production of the new neurons in the hippocampus. And it's not only what you eat, but it's also the texture of the food, when you eat it, and how much of it you eat.

9:44 - On our side -- neuroscientists interested in neurogenesis -- we need to understand better the function of these new neurons, and how we can control their survival and their production. We also need to find a way to protect the neurogenesis of Robert's patients. And on your side -- I leave you in charge of your neurogenesis.

10:06 - Thank you.

10:07 - (Applause)

10:13 - Margaret Heffernan: Fantastic research, Sandrine. Now, I told you you changed my life -- I now eat a lot of blueberries.

10:20 - Sandrine Thuret: Very good.

10:22 - MH: I'm really interested in the running thing. Do I have to run? Or is it really just about aerobic exercise, getting oxygen to the brain? Could it be any kind of vigorous exercise?

10:35 - ST: So for the moment, we can't really say if it's just the running itself, but we think that anything that indeed will increase the production -- or moving the blood flow to the brain, should be beneficial.

10:50 - MH: So I don't have to get a running wheel in my office?

10:53 - ST: No, you don't!

10:54 - MH: Oh, what a relief! That's wonderful. Sandrine Thuret, thank you so much.

10:58 - ST: Thank you, Margaret.

10:59 - (Applause)

 Palabra(s) clave: new brain cells

### Your DNA Is Nothing Special

#### It’s time to relax about genetic testing

DNA testing has become very popular among genealogists. The birth certificates, census records, and other documents they usually rely on can be wrong. DNA is never wrong. It can’t be altered, or forged, and you can’t misfile it. You can’t even always destroy it: DNA has been recovered from a frozen, 5,000-year-old corpse and used to identify his living descendants.2 Genetics do not uncover everyday family secrets such as the fact your great-great-grandfather owned slaves (unless he fathered children with some of them) or that a great uncle flunked out of West Point—it reveals the family secret, from whence you came, your begat. And your tree very likely has some invasive branches. As you look further up the tree, the chances of a non-paternal event rise exponentially. After 10 generations, you have 1,024 ancestors—I’m telling you, someone strayed. That’s why it’s prudent to trace families, not pedigrees.

You read these alarming stories once in a while about men who were first enthused about testing but then troubled when they discovered they aren’t who they thought they were, at least biologically, or that they have a half-brother they didn’t know about, or that an unsuspecting, elderly uncle doesn’t match any other male in the family (do you break it to him?). A hyperventilating, cautionary report posted last year at Vox.com trumpeted that genetic testing can unexpectedly tear families apart with revelations that are especially painful “when users aren’t looking for them in the first place.” As the databases at testing sites such as 23andMe grow, it warned, “there will be more and more family reunions, many of them by users who have no idea they are coming and aren’t prepared for them.”3 The article was accompanied by an essay by a reproductive biologist who had submitted his Y-DNA and that of his father for analysis. After the samples were processed, “George Doe” and his father both opted to see close matches. As George recounted, a user identified only as Thomas was shown to be a 50 percent match to George’s father—a son. George’s father professed to know nothing about Thomas, but George said the revelation unleashed “years of repressed memories and emotions,” presumably because Thomas had been conceived during an affair.4

If a child is found to have a higher risk of skin cancer, can a parent be compelled to keep the child away from the beach?

The Vox report irritated Blaine Bettinger, who blogs as The Genetic Genealogist. He argued it unfairly castigated DNA as a home wrecker. After all, Bettinger pointed out, census records, birth certificates, wills, and many other records also have the same potential. Bettinger discovered this himself when a state census revealed his great-grandmother was adopted, a fact that affected more than 60 living descendents. (Should he have been warned by the census bureau that the data he was requesting was dangerous?) Further, most people are not devastated but overjoyed to discover lost siblings, or birth parents, or re-connect with children given up for adoption.5Startling tales of discovery are also extremely rare: while Vox reported that some 7,000 users at 23AndMe “have discovered that their parents weren’t who they thought they were, or that they had siblings they never knew existed,” a 23andMe spokesman told me that calculation was based on a guess that about 1 percent of its then-700,000 users had discovered a relative they didn’t know about, and that discovering distant cousins was far more common than anything about parents or siblings. The lost relative must also be a member of the site, which makes a match all that more unlikely.

Genetic Surprises

• The comedian and director Tyler Perry was originally named Emmitt Perry, after his father, although his father was so abusive Tyler wondered about the relationship. His mother reassured him, but after her death, Perry tested his Y-DNA and found it did not match his brother’s. He confirmed the family secret when his father was tested and matched Tyler’s brother but not him. He is now searching for his biological father.
• A Pennsylvania doctor named Mark Hudson discovered in 2005 through Y-DNA testing that his 12-year-old son was not his. Hudson left his wife but was ordered to pay $1,400 a month in child support. “I still feel like he’s my son,” he told a reporter. “But I think it’s wrong to enrich the person who committed the fraud. The child deserves the truth.” • Alan Cumming, best known for his role in the X-Men films, had a troubled relationship with his father. They had not spoken for 16 years when his father revealed that Alan wasn’t his son. He said Alan’s mother had cheated with a family friend, whose name he provided. Cumming was devastated but also wary, so he had Y-DNA tests done that proved he was, in fact, his father’s son. “Whatever the results of the DNA test, even before that, I didn’t think I was my father’s son,” Cummings has said. “I marvel at the fact I am related to this person.” Bettinger labeled Vox’s sky-is-falling approach as an example of “genetic exceptionalism.” The term caught my eye because I hadn’t seen it in a long while, and never in relation to genealogy, only medicine. It was coined in 1997 by a bioethicist named Thomas Murray to describe the fallacy that our genetic code is so powerful it deserves special protection beyond that given to other kinds of personal information.6 The phrase is a play on the earlier idea of “HIV exceptionalism”—that HIV status needed to be locked behind two steel doors because of the enormous potential for discrimination. While geneticists generally don’t subscribe to the notion that genetic information is exceptional (unless hyping their own research to secure more funding, perhaps), the public is another story. According to public opinion surveys, we vastly overestimate the predictive power of genetics. For instance, in a 1990 survey, 55 percent of respondents believed incorrectly that genetic testing could be used to “predict whether or not a person will have a heart attack.”7 Even as late as 2010, half felt “all children will be tested at a young age to find out what disease they get at a later age.” Further, 38 percent believed a class system would soon develop between those with “good” and “bad” genetic dispositions.8 The public frets especially that employers and insurance companies will use genetic tests to fire them, or hike their rates, or deny coverage. They fear insurers and employers will embrace the power of genetics and use it against them, because those groups believe in the same power—an infinite loop of ignorance. James Evans, a geneticist at the University of North Carolina, specializes in public policy and attitudes toward genetics. Genetics are indeed powerful, he told me, in that they are “at the heart of our most profound relationships.” (Genealogists would agree.) But too many people believe they define who we are by “determining” our personality, intelligence, appearance, behavior, and health. C. Thomas Caskey, a doctor at the department of Molecular Genetics at Baylor College of Medicine recalls one example. A young patient visiting his clinic was found to have mutations inBCRA1 that are associated with a fast-growing type of breast and ovarian cancer. The woman had an elderly aunt who had survived breast cancer, and the doctor suggested the aunt be tested forBRCA1. The aunt refused, saying she didn’t want to know because if she had the gene, she might have to tell her daughters they were at risk. Caskey found that attitude unfortunate but not surprising. The aunt may have associated telling her daughters about BRCA1 as the equivalent of a diagnosis of cancer, yet most women with these mutations in BCRA1 never develop breast cancer. The gene is not a death sentence. The idea that genetic testing somehow reveals dark, infallible secrets about the future puts pressure on politicians to do something about it. Although genetic testing is protected, like medical data, by privacy laws, many states have passed laws that treat genetic test results as super-double-special secret. Congress brought them all together in the Genetic Information Nondiscrimination Act of 2008, which is aimed specifically at employers and insurers. (Notably, long-term disability and life insurance are not covered by the law, so those providers test you for whatever they want. There are also no laws protecting your genealogical data, although sites that provide these services all have privacy policies, however binding those may be.) Ironically, genetic privacy laws discriminate in their own way by singling out people whose diseases can be tied to genetic risks. As two Georgetown law professors wrote in 1999 about state laws: “Why, for example, should medical information about a woman who has developed breast cancer of genetic origin … be given greater protection than a woman who has developed breast cancer because of environmental or behavioral factors (e.g., smoking)?”9 Besides, the professors added, genetic test results usually tell a doctor far less about future risk than a patient’s sex, age, race, occupation, financial status, employment status, and family history—all of which receive only “ordinary” protection from prying eyes. Scientists deserve some blame for these misconceptions about the power of DNA. “Since the 1950s at least, molecular biologists have been prone to talk of DNA … ascontaining genetic information,” the British bioethicist Neil Manson has written. “But this is to use ‘information’ in a causal sense: … specific DNA sequences (in the right context) will cause those traits or bring about the production of those proteins.”10 In other words, genes don’t operate in a vacuum; environmental influences play a huge role. (It’s worth noting that epigenetics, which studies heritable trait changes not caused by changes in genes, has its own exceptionalist discussion.11) But that’s not always what you hear. James Watson, one of the discoverers of the double helix, said, “We used to think our fate was in the stars. Now we know in large measure, our fate is in our genes.” In 1993 George Annas, a health lawyer at Boston University, described our genes as a “future diary.”12 That shorthand got him in trouble, he told me recently, with some colleagues accusing him of coming off as a “determinist,” which is a geneticist’s way of calling someone a simpleton. Annas was and is deeply concerned about the potential bureaucratic abuse of genetic markers, and contributed to the 2008 federal privacy law.13 If a child is found by a child protection agency to have a higher risk of skin cancer, he asked in 1993, can a parent be compelled to keep their child away from the beach? Or, as the cost of sequencing an individual’s genome drops (it’s now less than$1,000), will universities ask for samples to check applicants for markers of sufficient intelligence? How about those that point to early death, since so much is being invested in the person’s education? And what about our obligations and responsibilities when it comes to sharing genetic data? Annas told me he believes parents should be prohibited from testing their fetus or child for genetic markers unless there is a way to prevent or cure the disease before the child turns 18. Otherwise, it’s nobody’s business but our own. (Annas concedes, given the legal power parents have over their children, this prohibition is unlikely to happen.)

That’s like saying that because a woman is born with eggs in her ovaries she has a pre-existing pregnancy.

The problem with this line of thinking is a simple one: As the geneticist Eric Juengst has written, genetic testing is not fortune telling, but a weather map, a fallible tool.14 I’m sure health insurers would love to codify genetic exceptionalism and treat specific genes as “pre-existing conditions,” but that’s like saying that because a woman is born with eggs in her ovaries she has a pre-existing pregnancy. “The identification of a risk marker is not a disease,” Caskey explains. “Everyone has five to 10 recessive traits, including some that are potentially very severe.” Further, studies have shown that even if you combine several risk factors for any particular illness, it can’t tell you or a doctor what will happen. As Evans pointed out in one study: “The lifetime risk for an individual in the United States to develop Crohn’s disease is about 1 in 1,000. How helpful is it for clinicians and patients if that risk shifts to 1 in 500 or 1 in 2,000?”15 There is also no evidence that knowing you have a genetic marker (or a lack of one) changes behavior. Finding out their genetics suggest a decreased risk for diabetes doesn’t send most people on a sugar binge.

ACTING LIKE A PARENT: Actor Tyler Perry used a Y-DNA test to determine that the man who raised him was not his biological father. Jeff Kravitz / contributor

Further, there is no “gene for Alzheimer’s” or “gene for breast cancer.” Researchers were focused on single genes early on but have shifted focus to arrays of genes and how they conspire with each other and the environment, rather than scanning for lone assassins in the crowd. For example, the suspicion now is that some people who have a gene associated with a certain disease but never develop it may have other genes that suppress the first one. Gene mutations have been found that prevent HIV from entering cells, reduce the amount of bad cholesterol, or offer partial protection against heart disease and Type 2 diabetes. One effort to find healthy people with genes that increase their propensity for fatal diseases is called The Resilience Project. The researchers analyzed the genetic code of 500,000 test subjects and found 20 people who seem to fit the criteria. One example is Doug Whitney of Port Orchard, Washington, who has a genetic mutation associated with Alzheimer’s. That disease killed his mother and nine of her 13 siblings, most of whom had died by their mid-50s. Whitney is 65 and healthy—and quite popular with geneticists.

You also can’t ignore the role of chance. Earlier this year researchers at Johns Hopkins University School of Medicine concluded in a paper published in Science that random mutations in otherwise healthy stem cells may account for two-thirds of the risk in whether a person gets the deadliest types of cancer. (Notably, the study did not look at breast or prostate cancers.)16 “If you go to the American Cancer Society website and you check what are the causes of cancer, you will find a list of either inherited or environmental things,” the lead researcher, Cristian Tomasetti, told Science. “We are saying two-thirds is neither of them.” The researchers said they hoped the results would help people calm down about whether every little lifestyle choice was going to give them a tumor. On the other side of that coin, the fact that so much cancer occurs because of random mutations may mean you can’t do anything to prevent it. Sometimes you’re just unlucky.

It’s been just 12 years since scientists finished sequencing the 3 billion DNA letters in the human genome. It is going to take more time for the public to gain a more nuanced view of what genes are and do—and this includes me. Recently I noticed a store greeter dancing and singing and being generally peppy and optimistic, in distinction to my own default state, which is glum resolve. Yet even after having spent a few days talking with geneticists, after which I should have known better, I thought to myself, “He must have happy genes.”

Chip Rowe is a writer based in New York.

References

• 1. Anderson, K.G. How well does paternity confidence match actual paternity? Evidence from worldwide nonpaternity rates. Current Anthropology 47, 513-520 (2006).
• 2. Ermini, L., et al. Complete mitochondrial genome sequence of the Tryolean Iceman. Current Biology18, 1687-1693, (2008).
• 3. Belluz, J. Genetic Testing Brings Families Together—And Sometimes Tears Them Apart. Vox.com (2014).
• 4. Doe, G. With Genetic Testing, I Gave My Parents the Gift of Divorce. Vox.com (2014).
• 5. Bettinger, B. A Response to the Genetic Testing Article in Vox. Thegeneticgenealogist.com (2014).
• 6. Murray, T.H. Genetic Exceptionalism and “Future Diaries”: Is Genetic Information Different From Other Medical Information? In Genetic Secrets: Protecting Privacy and Confidentiality in the Genetic Era Yale University Press, New Haven, CT (1997).
• 7. Singer, E. Public attitudes toward genetic testing, Population Research and Policy Review10, 235-255 (1991).
• 8. Henneman, L., et al. Public attitudes towards genetic testing revisited: comparing opinions between 2002 and 2010. European Journal of Human Genetics21, 793-799 (2013).
• 9. Gostin, L.O. & Hodge J.G. Genetic privacy and the law: an end to genetics exceptionalism.Jurimetrics40, 21-58 (1999).
• 10. Manson, N.C. How not to think about genetic information. The Hastings Center Report35, 3 (2005).
• 11. Rothstein, M.A. Epigenetic exceptionalism. Journal of Law, Medicine & Ethics41, 733-736 (2013).
• 12. Annas, G.J. Privacy rules for DNA databanks: Protecting coded “Future Diaries.” Journal of the American Medical Association270, 2346-2350 (1993).
• 13. Annas, G.J. Drafting the Genetic Privacy Act: policy, and practical considerations. Journal of Law, Medicine & Ethics23, 360-366 (1995).
• 14. Juengst, E.T. FACE facts: Why human genetics will always provoke bioethics. Journal of Law, Medicine & Ethics32, 267-275 (2004).
• 15. Evans, J.P., Meslin, E.M., Marteau, T.M., & Caulfield, T. Deflating the genomic bubble. Science331, 861-862 (2011).
• 16. Tomasetti, C. & Vogelstein. B. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science347, 78-81 (2015).

 Palabra(s) clave: DNANothing Special

### Your Robot Replacement Has Arrived

#### Robotic process automation can help companies operate more frugally and efficiently, though potentially at the expense of human workers.

When is a robot not a robot? When it's robotic process automation, or RPA.

In a new research paper, "The IT Function and Robotic Process Automation," the Outsourcing Unit at London School of Economics finds that RPA can provide a variety of business benefits, and it anticipates accelerated deployment in the years to come. The paper followed three case studies of customers of RPA-provider Blue Prism. In addition, Blue Prism partly funded the paper.

RPA is similar to business process management, but it doesn't require developers to create code. It's software.

As implemented by firms such as Automation Anywhere or Blue Prism, RPA allows people to generate code through a menu-driven drag-and-drop visual interface. That code can then handle structured, repetitive tasks like onboarding employees at a large company. Think of it as software that can be trained to operate the business applications a human would use for routine clerical or administrative work.

(Image: Blue Prism)

As the paper explains:

RPA software is ideally suited to replace humans for so called "swivel chair" processes; processes where humans take inputs from one set of systems (for example, email), process those inputs using rules, and then enter the outputs into systems of record (for example, Enterprise Resource Planning (ERP) systems).

Implemented correctly, RPA can make routine human resources work, for example, more efficient and affordable by taking people out of the loop. The report concedes this could reduce the need for human resources employees.

"There would be fewer HR specialists needed overall if the volume of work was constant, but those HR specialists remaining should have more challenging work," the paper says.

This acknowledgement underscores the angst surrounding advancements in automation and artificial intelligence: Technology may allow people to focus on higher-value, less easily automated work, but it's not clear whether there will be enough of these improved jobs to go around. Nor is it obvious that what cannot be automated today will remain the province of people tomorrow.

RPA occupies a middle ground between shadow IT -- tools deployed without the oversight of IT -- and traditional IT. The paper characterizes it as "lightweight IT" in the sense that it can be begin as a project that doesn't require IT involvement, but may need IT support as it spreads through an organization. Though it tends to be business-led, it's clearly an option that IT should evaluate.

[See the real-world application of RPA. Read Using RPA in Banking to Streamline Development.]

Despite its employment implications, there's little doubt that companies can find value in RPA. The paper notes that some companies surveyed have automated more than 35% of their back-office transactions. The benefits include reduced costs, greater process efficiency and accuracy, and improved customer satisfaction.

Having analyzed the financial impact of RPA deployments at Telefonica O2, Xchanging, and an unnamed major utility, the paper cites ROI figures of 650% to 800% over three years for Telefonica OS, 30% per process (14 automated) for Xchanging, and 200% over one year for the utility.

However, the paper doesn't explore the challenge of asking people to train their computers to replace them.

Thomas Claburn has been writing about business and technology since 1996, for publications such as New Architect, PC Computing, InformationWeek, Salon, Wired, and Ziff Davis Smart Business. Before that, he worked in film and television, having earned a not particularly useful ...View Full Bio

 Palabra(s) clave: Robot Replacement

### You’d never know it wasn’t Bach (or even human)

By Eric Gershon and Jim Shelton

In her spare time, when she can find any, Donya Quick composes music, typically jazz, generally on the six-foot baby grand piano that dominates her apartment’s living room. A baby grand isn’t an all-hours option in a multi-unit building, so she also keeps a Yamaha silent guitar on hand, for the days when inspiration strikes late in the evening.

“I like to compose at 11 p.m.,” says Quick, a lecturer in computer science at Yale. “I have been able to use that piano so little, the keys are starting to get sticky.”

For most of the last two years, Quick, who is originally from Virginia, largely subordinated her compositional impulse to the demands of another type of musical project: The fine tuning of a computer program she developed to create music for her — original, never-before-heard music that sophisticated listeners have mistaken for the fruit of a sublime human sensibility.

Donya Quick

In two separate tests, each involving more than 100 human subjects of varied musical experience, participants listened to 40 short musical phrases, some written by humans, others by computer programs, including Quick’s, which she calls Kulitta. The subjects were asked to rate the musical phrases on a seven-point scale ranging from “absolutely human” to “absolutely computer.” In both tests, Kulitta’s compositions rated, on average, on the human side of the scale.

The late Paul Hudak, Quick’s dissertation adviser at Yale, organized a separate series of informal public demonstrations where he juxtaposed a musical phrase composed by Kulitta with a phrase by J.S. Bach, the 17th-century German musical genius famous for his cello suites, fugues and chorales. Hudak then challenged audience members to identify which was which; invariably, even some music sophisticates confused Kulitta’s phrase for work by Bach.

“It really does work, and that judgment isn’t just based on a few people listening to a few of the pieces that have been produced,” says Holly Rushmeier, a Yale computer science professor who has seen the system in action. “I was impressed with the user study that verified how effective the system is. Kulitta produces wonderfully sophisticated compositions.”

### Unnerving automation

Automation unnerves some people, and the automation of art has a special power to offend humanity’s view of itself as soulful: How could a thing without psychological or emotional states express itself with the spirit and feeling seemingly necessary for making music? “Before I encountered any of this stuff, I probably would have had a similar reaction,” Quick says. “It’s an adverse reaction to novelty, the same way people first reacted to synthesizers.”

Konrad Kaczmarek, a composer and assistant professor in the Department of Music, says Kulitta and other new technologies are likely to change the way composers write, perform, and listen to music. But the fundamental elements of composition will remain the same, he explains.

“Whether it’s someone with a computer or a guy strumming a guitar, it’s always an algorithmic process,” Kaczmarek says. “You begin with an unlimited palette, and then apply different rules and decision-making strategies to filter it all down. Adding a computer to the equation, with an analysis of every Bach chorale ever written as a data set, influences the entire process in exciting and powerful ways.”

Quick does not want to put human composers out of business. Indeed, she thinks computer music generators can serve as a fresh source of ideas for musicians and as a tool for studying how humans actually experience music. She also thinks programs like Kulitta could allow people without advanced musical skills to engage in composition at a fairly high level — “sort of like being the director of a movie rather than the scriptwriter,” she says.

Viewed this way, programs like Kulitta are a help to human musicians, not a threat. “They’re another tool in the toolbox,” Quick says. “People can use this to do what they already were doing, but better.”

By several accounts, Kulitta is one of the most versatile automated musical composition programs developed to date, surpassing well-known predecessors in its ability to blend dissimilar musical styles to pleasing effect. Even David Cope, the celebrated composer and computer music innovator, was impressed by the demonstration Quick gave him during a visit to Yale. “He was very positive when he heard the Kulitta woodwind piece,” she said.

To be sure, Quick is not the first to create computer programs to write music. Cope, one of Quick’s role models, did it decades ago. His programs “Emily Howell” and “Emmy” have written thousands of classical compositions, from sonatas and concertos to chamber orchestra opuses and pieces for multiple pianos. The programs also helped him complete an opera he began but couldn’t seem to finish. Cope remains a towering figure in the field of computer music. But as Hudak, the Yale computer scientist, saw it, Quick has gone a step further than Cope: With Kulitta, Hudak once said, “You can create sounds that no one’s ever heard before.”

### “Top down” approach

It was Hudak, in fact, who suggested that Quick call her program “Kulitta” after a female musician from Hittite mythology. Like existing automated composition systems, Kulitta has the ability tolearn musical properties, such as abstract rules for harmony and pitch mapping, from a corpus of existing compositions (in this case, Bach chorales primarily). Kulitta also has the ability to write music with a “top-down” approach that composes by eliminating musical elements it does not want to use.

The Kulitta software was named after a female musician from Hittite mythology.

“As soon as I heard about it, I decided I had to take it and planned my schedule around it, although I really had no idea what to expect beyond the idea that it somehow involved two things I liked a lot: programming and music,” Quick says. “The subject was intriguing to me, but also completely mysterious at the time. I haven’t looked back.”

Indeed not. She envisioned, developed, and began refining Kulitta, which became the subject of her dissertation in 2014. At the heart of Kulitta is a four-module process that transforms human directives into musical dialogue.

The first module establishes musical properties. In computer programming terms, it would look something like this: p=learn(corpus). The second module produces an abstract musical structure: a=generate(p); the third module creates musical chords: c=harmony(a,h); and the fourth module puts everything into a specific musical framework: music=style(c,chorale).

“Kulitta can produce a piece of music incredibly fast,” Quick says. “For something that would take at least a day for a human, Kulitta can do it in a few seconds or less.”

### Metallica and Mozart

Quick’s ambitions for Kulitta will take a bit more time. Now that she’s produced mergers of classical and jazz, she’d like to do something even bolder. “The one I want to try is Metallica and Mozart,” she says. “I’d like Kulitta to do a rock symphony, at some point. That’s my pie-in-the-sky.”

In May, as a tribute to her late mentor, Quick played a Kulitta composition at a memorial service for Hudak. “I found it quite moving,” said Dana Angluin, a Yale computer science professor who attended the service, and who has worked with Quick.

Quick also has allowed a number of Yale students to work with Kulitta for term projects in a class she taught.

Such uses speak to one of the main ways Kulitta can be of service, according to Quick. Kulitta can quickly test a compositional idea for a classical concerto or a jazz harmony and spark an intellectual or emotional response. Not only can Kulitta accomplish this sort of test quickly, it can produce many variations on the same, specific musical idea and tailor them to the physical dimensions of the musician’s hands.

As to what Kulitta cannot do, says Quick, it cannot beat Bach at his own musical game. To say Kulitta composes music that has been confused for works generated by the mind of Bach is not to say the computer is as good a composer as Bach, she notes. “It’s kind of hard to match the gold standard. Bach defined a style, with specific rules. Kulitta will have mistakes, by that definition.”

Kulitta also will evolve. Quick says that if people like what they hear from Kulitta now, they’ll like version 2.0 better. She continues to expand Kulitta’s musical vocabulary and refine its understanding of compositional nuances. She is planning another listening test and has had an academic paper accepted for an international computer music conference.

Someday, Kulitta may even sing.

“This is a life’s work,” Quick says. “I would like to keep building a bigger, better, more proficient Kulitta.”

But Kulitta differs from other composition systems in important ways. Above all, there is its versatility. Where Cope’s justly celebrated programs can produce realistic, enjoyable music that largely works within established styles (using information about chorales to produce more chorales), Kulitta can use the structures of different musical forms and combine them to create music that sounds distinctly like something else altogether.

Firing up a laptop computer in the Euterpea Studio at Yale’s Watson Hall, surrounded by silent guitars, synthesizers, and drum kits, Quick demonstrates the process. She asks Kulitta to compose a 30-second piece in the style of a Bach chorale, but with a middle block that incorporates a jazz harmony. The jazzy block is then run back through the chorale parameters. The result takes less than 10 seconds.

“That wasn’t bad,” Quick says, after human ears have heard the piece for the first time. “I’m going to save that one. You can think of it as, ‘This might be what Bach would have done if he knew about jazz.’”

### Beyond bioinformatics

Quick came to Yale from Southern Methodist University, where she received bachelor’s and master’s degrees in computer science (and a second bachelor’s degree in environmental studies). In 2008, as she anticipated her doctoral studies in New Haven, she planned to continue with the bioinformatics research she’d begun in Texas, which involved analyzing the DNA of nematode worms.

She was interested in computers as a source of music, but had little exposure to it. “I was completely unaware of the potential that existed for automated composition, since the only algorithmic compositions I’d come across were really quite awful sounding,” she says.

In August 2008, she and her husband, a graduate student in psychology at the University of Connecticut, drove from Texas to Connecticut with their load of musical instruments, including three guitars, a keyboard, a theremin, and some other stringed instruments, including an oud and bouzouki. Soon after arriving she saw that Hudak was offering a course in computer music, "Fundamentals of Computer Music: Algorithmic and Heuristic Composition."

Donya Quick performs a piece composed using the Kulitta software.

“As soon as I heard about it, I decided I had to take it and planned my schedule around it, although I really had no idea what to expect beyond the idea that it somehow involved two things I liked a lot: programming and music,” Quick says. “The subject was intriguing to me, but also completely mysterious at the time. I haven’t looked back.”

Indeed not. She envisioned, developed, and began refining Kulitta, which became the subject of her dissertation in 2014. At the heart of Kulitta is a four-module process that transforms human directives into musical dialogue.

The first module establishes musical properties. In computer programming terms, it would look something like this: p=learn(corpus). The second module produces an abstract musical structure: a=generate(p); the third module creates musical chords: c=harmony(a,h); and the fourth module puts everything into a specific musical framework: music=style(c,chorale).

“Kulitta can produce a piece of music incredibly fast,” Quick says. “For something that would take at least a day for a human, Kulitta can do it in a few seconds or less.”

### Metallica and Mozart

Quick’s ambitions for Kulitta will take a bit more time. Now that she’s produced mergers of classical and jazz, she’d like to do something even bolder. “The one I want to try is Metallica and Mozart,” she says. “I’d like Kulitta to do a rock symphony, at some point. That’s my pie-in-the-sky.”

In May, as a tribute to her late mentor, Quick played a Kulitta composition at a memorial service for Hudak. “I found it quite moving,” said Dana Angluin, a Yale computer science professor who attended the service, and who has worked with Quick.

Quick also has allowed a number of Yale students to work with Kulitta for term projects in a class she taught.

Such uses speak to one of the main ways Kulitta can be of service, according to Quick. Kulitta can quickly test a compositional idea for a classical concerto or a jazz harmony and spark an intellectual or emotional response. Not only can Kulitta accomplish this sort of test quickly, it can produce many variations on the same, specific musical idea and tailor them to the physical dimensions of the musician’s hands.

As to what Kulitta cannot do, says Quick, it cannot beat Bach at his own musical game. To say Kulitta composes music that has been confused for works generated by the mind of Bach is not to say the computer is as good a composer as Bach, she notes. “It’s kind of hard to match the gold standard. Bach defined a style, with specific rules. Kulitta will have mistakes, by that definition.”

Kulitta also will evolve. Quick says that if people like what they hear from Kulitta now, they’ll like version 2.0 better. She continues to expand Kulitta’s musical vocabulary and refine its understanding of compositional nuances. She is planning another listening test and has had an academic paper accepted for an international computer music conference.

Someday, Kulitta may even sing.

“This is a life’s work,” Quick says. “I would like to keep building a bigger, better, more proficient Kulitta.”