ISSUE

No.4
August-September 2019

Health&
Medicine
Plus:
DOES THE
PULLOUT
METHOD WORK
TO PREVENT
PREGNANCY?

The
CANCER RISKS
OF SOME
ANTIAGING

Satisfaction
PRODUCTS

ONE STEP

Diet
FOODS THAT ARE ESPECIALLY SATIATING CAN DECREASE
CLOSER TO A
UNIVERSAL
FLU VACCINE
WITH COVERAGE FROM

HUNGER, REDUCE BODY FAT AND LOWER BLOOD SUGAR

FROM
THE Health&
EDITOR Medicine
Your Opinion
Matters!
Help shape the future
of this digital magazine.
Let us know what you
think of the stories within
these pages by emailing us:
[email protected].
LIZ TORMES

In Search of Satisfaction
In 1944 researchers recognized that millions of people were at risk of famine as a result of the ravages of World War II.
To investigate the impact of food deprivation on the human body, 36 healthy men volunteered to endure a six-month
semistarvation diet and be observed by scientists and doctors. The result? Hunger made the men obsessed with food.
They would dream and fantasize about eating. They reported fatigue, irritability and depression, along with decreased
concentration, comprehension and judgment. Interestingly enough, the subjects were allowed about 1,500 calories a
day, substantially more than many fad diets endured today. It’s no wonder that diets based on restricting food are unsus-
tainable—according to some studies, approximately 95 percent of diets fail over the long term. As Shirin Panahi reports,
researchers are now exploring whether a diet that centers on satisfying foods—healthy foods that make the eater happy
(imagine that!)--might be the key to maintaining body weight after all (see “Have We Found a Diet That Truly Works?”).
What a fulfilling prospect.

Elsewhere in this issue Jen Schwartz takes a compelling look at the science of the withdrawal tactic for preventing preg-
nancy (see “Can You Prevent Pregnancy with the Pullout Method?”), and Helen Shen covers a wave of research on how
boosting the molecule nicotinamide adenine dinucleotide (NAD) might stave off the aging process. The trend is alarming
some critics who worry about that molecule’s association with cancer (see “Cancer Research Points to Key Unknowns On the Cover
about Popular ‘Antiaging’ Supplements”). As always, enjoy this issue! Foods that are especially
satiating can decrease
Andrea Gawrylewski

CHRIS GASH
hunger, reduce body fat and
Senior Editor, Collections lower blood sugar.
[email protected]

2
WHAT’S August-
September 2019

INSIDE
Volume 1 • Number 4

OPINION
27.
The Next Wave of
Immuno-Oncology
A cutting-edge therapy
currently used for blood
cancers is now being
adapted to fight solid
tumors
29.
A New Approach to
GETTY IMAGES

Addiction Treatment
We need to create
learning laboratories
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NEWS where researchers interact

GETTY IMAGES
4. directly with patients
Brain-Controlled 31.
Hearing Aids Could The Case for
Cut through Crowd 8. 11. FEATURES Collaborative Care
Noise Cannabis Compound New Finding 15. It produces better patient
A prototype detects Eases Anxiety and Advances the Search Have We Found a Diet That Truly Works? outcomes. Here’s why it
whom you are listening Cravings of Heroin for a Universal Flu The so-called satiating diet seems to help people works and how it can be
to and amplifies only that Addiction Vaccine manage weight and good health without going to effectively deployed
speaker’s voice; a Cannabidiol reduces Antibodies to a portion extremes 33.
potential solution to the levels of stress hormone of the influenza virus that 17. The Polycystic
“cocktail party problem” and blunts urge to use varies relatively little from Can You Prevent Pregnancy with the Sisterhood
6. opioids strain to strain may Pullout Method? Infertility is on the rise,
How to Kill HIV: 9. provide flu protection in An investigation into one of the biggest but one major cause—
Target Its Mole Rat Pain humans misconceptions in male fertility polycystic ovarian
“Influencers” Resistance Could 13. 24. syndrome—gets too
Applying network theory Point the Way to New The Human Body Is a Cancer Research Points to Key Unknowns little attention
to HIV’s structure has Analgesics Mosaic of Different about Popular “Antiaging” Supplements
revealed the most A novel mechanism has Genomes The health promises of boosting an important
valuable—and been discovered in the Survey finds that metabolic molecule may be clouded by its possible
vulnerable—parts of bucktoothed rodents’ “normal” human tissues role in promoting cancer cell growth
the virus ability to withstand hurt are riddled with
mutations

3
NEWS

Brain-Controlled
Hearing Aids
Could Cut through
Crowd Noise
A prototype detects whom you are
listening to and amplifies only that
speaker’s voice—a potential solution
to the “cocktail party problem”

AT A CROWDED PARTY or a noisy

restaurant, most of us do something
that is remarkable. Out of all the
voices surrounding us, our brains
pick out the one we want to hear
and focus on what that person has or mushes them together so they are and limited the solutions they have to revealed an experimental technology
to say. People with hearing loss are indistinguishable. offer. But researchers have just taken that could lead to a brain-controlled
not so fortunate. Noisy situations are The question of how the brain a major step forward toward helping hearing aid. Their proof-of-concept
especially difficult for them, and manages the trick of hearing in noise people hear in noise. In a paper device uses artificial intelligence to

GETTY IMAGES
hearing aids and cochlear implants is known as the “cocktail party published on May 15 in Science separate voices and compare them
do not help much. Such technology problem.” It is a puzzle that has bedev- Advances, engineers from Columbia with a listener’s brain waves to
generally either amplifies all voices iled auditory scientists for decades University’s Zuckerman Institute identify and amplify the speaker to

4
 NEWS

whom that listener is paying closest field closer to a practical application, distinct streams of sound. Graphically
attention. but it’s not there yet.”
“We are not trying to represented, the paper shows two
Nima Mesgarani of Columbia What Mesgarani and his colleagues simulate the brain. combined voices as a haze of red and
University’s Zuckerman Institute, the have created is an algorithm, and they We are just trying to blue dots. Once separated, one voice
senior author on the paper, has been have tested it only in epilepsy patients solve the cocktail is a cluster of red dots, the other blue.
working on aspects of the same undergoing brain surgery. Such party problem.” There is still an element of mystery in
problem since 2012 when he first patients provide a rare opportunity for how exactly the algorithm does this.
discovered it was possible to figure scientists to put electrodes directly
—Nima Mesgarani “Our guess is that it uses the spectral
out which voice a listener was focused into human brains. From a loudspeak- and temporal information, common
on by monitoring brain waves. er in front of the participants, Mesga- onsets and offsets [speech charac-
In 2017, he developed technology rani and his colleagues played two time. Such neural network models, teristics], and harmonic structures,”
that could pull one voice from many, voices (one male, one female) developed within the last four years, Mesgarani says. “We tell it that this
but only if the system was trained to speaking simultaneously. They look for statistical regularities in cloud of red and blue should become
recognize that particular speaker—a instructed participants to focus first increasingly complex layers of separable. It figures out somehow
severe limitation in real-world com- on one and then the other. The computations to determine which magically this transformation, and
munication. Now Mesgarani and his Columbia engineers fed the sound of parts of a sound mixture belong suddenly you have two clouds.”
colleagues have achieved a signifi- the voices and the electrical signals together. “Deep learning is the secret Considerable challenges remain
cant step forward by using brain from the patients’ brains into their sauce that made [this] possible,” before this technology can be used in
waves to decode whom you are algorithm, which sorted the sounds, Mesgarani says. an actual hearing aid. Mesgarani
listening to and then separating the amplified the attended voice and It doesn’t matter that neuroscien- estimates it will be at least another
interlocutor’s voice without the need attenuated the other. “These two tists still haven’t fully worked out how five years. Of course, a marketable
for training. “To remove that barrier,” inputs go inside this box, and what the brain hears in noise. “We are not device requires a noninvasive tech-
he says, “is a pretty big breakthrough.” comes out of it is the modified audio trying to simulate the brain,” Mesgara- nique for generating EEG recordings
“It’s a beautiful piece of work,” says in which the target speaker is louder,” ni says. “We are just trying to solve of brain waves. Several scientists,
auditory neuroscientist Barbara Mesgarani says. the cocktail party problem.” They including Mesgarani, have shown that
Shinn-Cunningham, director of the Although using brain waves to trained the algorithm with far more in-the-ear or around-the-ear hearing
Neuroscience Institute at Carne- follow auditory attention is an impres- examples of human speech than any aids with electrodes can work,
gie-Mellon University, who was not sive achievement, the real advance person would hear in a lifetime. Then although they generate a far less
involved in the research. Auditory has to do with the algorithm. It uses a they gave it the task of analyzing the precise signal. And while powerful,
neuroscientist Andrew Oxenham of sophisticated form of artificial detailed, often overlapping informa- the algorithm is still not yet success-
the University of Minnesota, who has intelligence known as a deep attrac- tion in the spectrograms, or acoustic ful 100 percent of the time.
studied the cocktail party problem for tor network to separate unknown signatures, created by multiple speak- In all probability, the first devices to
years, says, “This brings the whole speakers automatically and in real ers’ voices and separating them into use this technology will help people

5
 NEWS

with mild to moderate hearing loss.

“You probably need some residual How to Kill HIV:
hearing,” Mesgarani says. “As long as
you can track the ups and downs of
Target Its
[one] voice, that would be the kind of “Influencers”
signature that this technology would Applying network theory to HIV’s
look for.” structure has revealed the most
The talker separation algorithm valuable—and vulnerable—parts
alone could prove helpful without of the virus
monitoring brain waves at all, says
electrical engineer Mario Svirsky of
New York University’s Langone IN JUST ABOUT ANY system or
Medical Center. “I envision a smart- group, elements with a larger num-
phone app that talks to your hearing ber of connections tend to have
aid,” he says. “The app shows you more clout than others. Think of
icons for different talkers. If you Instagram “influencers,” for exam-
click an icon, then that talker is ple—or the chief executive officers
preferentially amplified and the of companies.
others attenuated.” Even within a virus, some structural
As for a true brain-controlled components—in this case, parts of
hearing aid, Svirsky fears that the proteins—have more links to one
costs may outweigh the benefit and another than others do. And coaching
is skeptical one will ever be imple- the immune system to recognize and mutation that makes people natural- focused on buttressing a person’s
mented. But he remains enthusiastic destroy such influencers is an ly resistant to HIV; in effect, the immune system. The new study
about Mesgarani’s work. “The whole efficient way to kill HIV, suggests a procedure replaced the patient’s turns that approach on its head by
idea of having a mind-reading hearing new study published in May in immune system with a new, resistant looking for the most critical parts of
aid is fascinating,” Svirsky says. “It’s Science. one. But bone marrow transplants the virus itself.

KATERYNA KON GETTY IMAGES

not just science fiction. This research There has been a lot of excite- are risky and invasive, and many For the new study, the researchers
has shown that it is at least a plausi- ment in the HIV field following the experts believe a practical cure for focused on “elite controllers”—people
ble possibility.” news in March that a second person, the roughly 37 million HIV-infected whose bodies control the virus
Related Video often called the “London patient,” people worldwide is more likely to without the aid of any drugs, and who
Related Video was cured after a bone marrow come from smart molecular work. are estimated to number about one in
—Lydia Denworth transplant. The donor carried a Most HIV-cure research has so far every 300 infected individuals. It

6
 NEWS

made sense that investigating how lose-lose situation: it ends up de- and the virus within it. There are
their immune systems kill HIV might
“If you take a highly stroyed whether it mutates or not. thousands of HLA types, some more
point the way to a cure, says Bruce networked [amino Walker’s team found that elite common than others, and some
Walker, senior author of the paper acid] and mutate it, controllers’ immune systems tend to better at controlling certain infections.
and director of the Ragon Institute of the virus basically selectively target these influencer Among these, B*57 is thought to be
Massachusetts General Hospital, the falls apart. It amino acids; in most other infected particularly potent against HIV. But
Massachusetts Institute of Technolo- people, immune systems instead scientists have been puzzled by the
gy and Harvard University. “There are
dramatically loses mount futile attacks on other, less fact that not everyone with B*57 is an
not two people who are cured of HIV fitness.” important parts of the virus. elite controller—nor do all elite
infection, in my view,” Walker says. —Bruce Walker “This is impressive and important controllers carry B*57. The new paper
“There are thousands—and a lot of work,” says Andrew McMichael, an suggests that what is key is not so
them who control [the virus] on their emeritus professor of molecular much B*57 itself, but the influencer
own. We, as a field, need to pursue branchlike structures that cause them medicine at the University of Oxford, amino acids it targets.
this with the highest priority.” to interact with many other amino who co-wrote a commentary accom- B*57 “is the major determinant of
Walker and his colleagues found acids. These branched amino acids panying the paper but was not progression or nonprogression [of
that elite controllers’ immune systems have a high “network score,” Walker involved in the new research. “It HIV infection], but it’s not totally
target the most influential regions in says, and are thus the most important explores why some [immune re- flawless,” McMichael says, adding that
the virus. The researchers made this to HIV’s integrity. HIV can mutate in a sponses] are effective and why some the new paper “goes some way
discovery by applying network theory, defensive response to a drug that are less effective.” toward explaining why that may be.”
a type of analysis frequently used in targets a specific part of its struc- The new research may also resolve Walker and others have studied
mathematics to chart relationships ture. But the amino acids with high some previously inconsistent findings elite controllers for decades. One
between objects. They employed the network scores are so important about an immune molecule called such patient, Loreen Willenberg, now
theory to map connections between that the virus cannot vary them B*57—which has been suggested as 65 years old, was diagnosed in 1992
amino acids, the building blocks of without great cost to itself: if those a magic weapon that elite controllers and has since donated hundreds of
proteins, in three-dimensional amino acids change, the connec- wield against HIV. B*57 is a subtype samples for research. Willenberg, who
molecular structures of HIV proteins. tions are lost. of molecules called human leukocyte says she has “an amazing immune
(They used the 3-D structures “If you take a highly networked antigens (HLAs), which make up a system,” is invulnerable to dozens of
because two amino acids that appear [amino acid] and mutate it, the virus key part of the immune system. HLAs pathogens, including HIV. Tests that
far apart in a protein’s linear se- basically falls apart,” Walker says. “It carry fragments of viruses to an measure her immune response to
quence may be much closer—and dramatically loses fitness.” This infected cell’s surface so that killer HIV still come back positive, but no
connected—in three dimensions.) finding makes such amino acids immune cells circulating in the blood test can detect the virus itself. “I’ve
The researchers found that some attractive targets for therapy, because can recognize the flagged cell as never measured a viral load, ever. It’s
amino acids tend to have numerous attacking them puts the virus in a infected, and destroy both that cell always been undetectable,” Willen-

7
 NEWS

berg says. targeting the same pathways that

Walker has studied Willenberg for opioids use. Although these drugs
about 15 years. But this time, instead can ease physical need, they don’t
of focusing on the aspects of her quiet the anxiety that environmental
genetics that protect her from HIV, cues can trigger, leaving open a door
the team homed in on which parts of to addiction reentry.
HIV her system attacks. “Here, we The cannabis compound cannabidi-
don’t take into account host genetics ol (CBD), a nonpsychoactive compo-
at all,” Walker says. Yet the study still nent of cannabis, might be the key to
explains what makes her immune keeping that door locked. Research-
system so remarkable: it selectively ers report that among people with
attacks the amino acids with the opioid addiction, CBD dampens
highest network scores. “She fit the cue-triggered cravings and anxiety,
pattern perfectly,” he says. along with reducing stress hormone
With this confirmation of the levels and heart rate. The results were
importance of these influential amino published May 21 in the American
acids, Walker says he hopes to Journal of Psychiatry.
develop a “therapeutic vaccine” that to avoid resurrecting their addiction “These findings provide support for
can be given to people already Cannabis Compound also must grapple with reminders of an effect of cannabidiol on this
infected with HIV. The vaccine would it: the sights, sounds and people process,” says Kathryn McHugh,
contain about 30 of the viral parts
Eases Anxiety and who were part of their addictive be- assistant professor in the department
with the highest network scores. The Cravings of Heroin haviors. These cues can trigger a of psychiatry at Harvard Medical
hope is that it would prime an Addiction craving for the drug, creating anxiety School’s Division of Alcohol and Drug
infected person’s immune system to Cannabidiol reduces levels of that steers them straight back into Abuse, who was not involved in the
recognize and then go after these stress hormone and blunts urge addiction for relief. study. However, she cautions, the
key targets, and destroy the virus. to use opioids The opioid epidemic in the United results are preliminary, and behavioral
“We believe we can redirect the States has taken more than 300,000 therapies are also quite effective at

JAN ENKELMANN GETTY IMAGES

immune response,” Walker says. “We lives, and support for people working dimming the signal from cues.
don’t know whether this will work, AS ANYONE WHO’S DEALT with sub- to keep these drugs out of their orbit The anxiety reduction isn’t specific
but there’s a very strong rationale stance addiction can tell you, break- has become crucial. Methadone and to opioid-related cues and could
for it to.” ing the physical intimacy with the buprenorphine, the current medical generalize to other situations, says
—Apoorva Mandavilli drug isn’t always the most challeng- treatment options, help break the neuroscientist Yasmin Hurd, first
ing part of treatment. People trying physical craving for opioids by author on the study and director of

8
 NEWS

the Addiction Institute at the Icahn College London. Pointing to another Species related to the naked
mole rat (Heterocephalus
School of Medicine at Mount Sinai. study showing that a dose of 400 mg glaber) share some of its
“It’s just that this particular anxiety of CBD reduced anxiety about public pain-resistant abilities.
leads someone to take a drug that speaking, she says that in both cases,
can cause them death, and anything something triggers the anxiety, rather
we can do to decrease that means than its being chronic and general-
increasing the precious chance of ized. “The system on which CBD acts
preventing relapse and saving their works to bring the body down to a
lives.” steady state during acute anxiety,”
Hurd and her colleagues conducted Hindocha says, so CBD may have its
a randomized, controlled, double-blind effects by speeding up that process.
trial of 42 drug-abstinent people with Pinning down the just-right CBD
a heroin-use disorder. The partici- dose may be tricky, says Gustavo
pants took either 400 or 800 milli- González Cuevas, an associate
grams of CBD or placebo at different professor and coordinator in the
intervals so that researchers could department of psychology at the
assess the immediate and lon- European University of Madrid School
ger-term effects of the compound. of Biomedical and Health Sciences,
Those in the CBD groups exhibited who was not involved in the study.

BUFFENSTEIN BARSHOP INSTITUTE AND UTHSCSA FLICKR (CC BY 2.0)

reduced anxiety and craving in “Sometimes lower doses of CBD
response to drug-related cues such have been proven to be more effec-
as videos showing drug paraphernalia. tive than higher doses,” he says.
They also had reduced levels of the Dose-finding is a next step, says
stress hormone cortisol in their saliva Hurd, in addition to figuring out the THE NAKED MOLE RAT became an
and lower heart rates. These effects best route, oral or inhaled, for admin- Mole Rat Pain unlikely media star in 2008 when
of CBD lasted a week after the last istering a CBD-based drug. One thing Resistance Could researchers showed it is highly resis-
dose, when little to no CBD would be is for sure, says Hurd: using commer- tant to certain types of pain. Physiol-
expected to remain in the body. cially available “edibles” or smoking Point the Way to ogist Gary Lewin of the Max Del-
The antianxiety effects look promis- cannabis won’t be the best choice New Analgesics brück Center for Molecular Medicine
ing, but whether or not they will because these options offer little A novel mechanism has been disco- in Berlin, biologist Thomas Park of
generalize is unclear, says Chandni dosage control. ­ vered in the bucktoothed rodents’ the University of Illinois at Chicago
Hindocha, a research fellow in the —Emily Willingham ability to withstand hurt and their colleagues found that the
division of psychiatry at University odd-looking creatures are insensitive

9
 NEWS

to acid and capsaicin, the substance researchers injected the substances class of pain relievers. “Our findings been found that doesn’t avoid AITC,”
that gives chilies their burn. Lewin’s in one of the animals’ paws, those could lead to a drug-discovery Lewin says. The channel activated by
team has now investigated a range that experienced pain would lick or program to try and make molecules AITC is called TRPA1, and when the
of mole rat relatives, revealing that flick their limb. In addition to the that increase the function of this researchers examined the Trpa1
the naked variety is not the only one naked mole rat, two other species channel,” Lewin says. gene in Highveld mole rats, they
resistant to pain. The study uncovers (the Cape mole rat and East African The researchers set out to dissect found a mutation that reduces the
a previously unknown trick for shut- root rat) were resistant to acid, and the genetic and molecular mecha- channel’s sensitivity to the spicy
ting down the sensation, which could one other (the Natal mole rat) was nisms underlying this striking varia- chemical. But they also saw this
lead to the development of new resistant to capsaicin. The Highveld tion. They took tissue samples from mutation in three other species that
pain-relieving drugs. mole rat, named after the eastern the spinal cords and dorsal root do not have the Highveld mole rat’s
The naked mole rat is the original South African region where it lives, ganglia (bundles of spinal cord immunity. Also, these rodents are not
mole rat species, from which numer- was the only species impervious to neurons that transmit pain informa- just resistant, they seem utterly
ous others evolved in various parts of AITC. “It’s absolutely remarkable that tion) of all the species and measured impervious: increasing the concentra-
Africa, Lewin says. This diversity five of the [species studied] turned the activity of nearly 7,000 genes. The tion of AITC from 0.75 to 100
across habitats makes mole rats an out to have evolved distinct sensory scientists found evidence of a normal percent still failed to trouble the
ideal group of animals to study. “As deficits,” says neurobiologist Jorg complement of neurons for detecting critters, which is difficult to explain
they populated Africa, they probably Grandl of Duke University, who was painful stimuli in each species. And purely in terms of reduced sensitivity.
came into contact with all kinds of not involved in the study. specialized proteins called ion “In four different species, the channel
different environments,” Lewin says. The researchers conducted a series channels, activated by capsaicin or had the same insensitivity, but only
“We wanted to know, ‘Are these of experiments in the Highveld mole AITC, were present at similar levels in one species was completely behav-
special properties of the naked mole rat to probe its resistance to AITC. all species—suggesting pain resis- iorally insensitive,” Lewin says. “So
rat something all African mole rats Their findings revealed a previously tance is not simply a case of lacking there had to be something else.”
have, or are they something to do unknown mechanism for suppressing the relevant detectors. There were The one gene whose activity was
with the environment they’re con- pain, involving a single gene coding differences, however. For instance, significantly different in Highveld
fronted with?’” for an ion channel that, when highly the three acid-resistant species had mole rats codes for a channel called
In a study published online in May active, prevents pain-sensing neurons altered activity in 41 genes, almost all NALCN, which was more than six
in Science, the team assessed the from firing. This activity gives the of which are likely expressed, or times as active as in other species.
responses of eight kinds of mole rats animal a very specific resistance, turned on, in sensory neurons, and a The team investigated NALCN’s
and two other rodent species to presumably because it is restricted to few of which are known to encode function in laboratory-grown cells
three substances that normally elicit cells that sense AITC. But research- acid-sensing channels. and found that it acts as a kind of
pain: acid, capsaicin and allyl isothio- ers could target this channel in The team then focused on High- “short circuit” that leaks current,
cyanate (AITC), the substance that general, anywhere they find it, veld mole rats’ unique resistance. preventing neurons from firing even
gives wasabi its fiery heat. When potentially opening up a whole new “This is the only animal that's ever when sensing the chemical that

10
 NEWS

normally activates them. The re- NALCN abolished the resistance.

searchers then injected Highveld “This is a fascinating dissection of
mole rats with a drug that blocks the molecular machinery that senses
NALCN, making them sensitive to noxious substances and how it
AITC. The effect disappeared as the evolved,” Grandl says.
drug wore off, strongly supporting The findings show that nature
NALCN’s role in the species’ particu- harbors more pain-perception
lar superpower. “The researchers mechanisms than previously appreci-
used an impressive range of tech- ated. “The study suggests the
niques, in multiple species, to look response to noxious substances and
beyond variation in the genetic code the molecular basis controlling these
and instead identify changes in levels are not as conserved as previously
of gene activity that appear critical thought,” Davies says. “The results
for one species’ pain resistance,” says could have implications for our
evolutionary biologist Kalina Davies understanding of controlling pain.” shown that targeting a specific
of Queen Mary University of London, Humans also possess the Nalcn New Finding portion of the flu virus that varies rela-
who was not involved in the study. gene so the implications for develop-
The researchers think these pain ing novel analgesics are fairly
Advances the Search tively little from strain to strain offers
protection in humans. The study was
resistances are evolutionary adapta- straightforward. “It’s the same gene for a Universal Flu published in the June 3 issue of
tions. AITC and other irritants are we have, except it’s massively more Vaccine Nature Medicine.
present in roots, one of mole rats’ expressed in the sensory neurons [of Antibodies to a portion of the influ- “If you have a universal flu vaccine
main food sources, so reduced Highveld mole rats] than in any other enza virus that varies relatively litt- you would take off the table the need
sensitivity would be generally benefi- species,” Lewin says. “It’s a standard le from strain to strain may provide to have to vaccinate persons every
cial. Zoologist and team member procedure in the pharmaceutical flu protection in humans single year, and change the vaccine
Daniel Hart of the University of industry to make a channel opener: a every year,” says Anthony Fauci,
Pretoria in South Africa discovered small molecule that would open the director of the National Institute of
that Highveld mole rats often share channel. And we’d predict that could THE QUEST FOR A universal flu vac- Allergy and Infectious Diseases

JUSTIN SULLIVAN GETTY IMAGES

their burrows with an aggressive, have very powerful analgesic proper- cine, one that provides long-lasting (NIAID). Each year in the U.S.,
venomous ant species, the Natal ties, because it would shut down pain protection from multiple types of seasonal influenza, or flu, kills more
droptail. Experiments using venom receptors,” he explains. “With modern influenza, even those that might than 36,000 people and hospitalizes
from the ants showed that these methods, we can really discover how cause a pandemic, has moved a 200,000 more. Worldwide, influenza
mole rats were the only species evolution solved a problem.” step closer. causes 650,000 deaths annually.
resistant to it and that blocking —Simon Makin For the first time, scientists have Your yearly flu vaccine targets

11
 NEWS

hemagglutinin, one of the two types infection and disease.”

of proteins that cover the influenza Gordon and her team have been
“If you have a universal flu vaccine you
virus. The protein resembles a tracking household flu transmission in would take off the table the need to have to
mushroom, made up of a cap (head) a cohort in Managua, Nicaragua, vaccinate persons every single year,
and a stem (stalk). since 2007. For this specific research, and change the vaccine every year.”
Current flu vaccines induce the they focused on the 2013 and 2015 —Anthony Fauci
production of antibodies that recog- flu seasons. “We wanted to do two
nize the hemagglutinin head and seasons to make sure that whatever
inhibit its ability to mediate viral entry we were seeing wasn’t specific to
into a cell. However, this portion of one season,” she says.
the protein undergoes rapid mutation In collaboration with the local Florian Krammer, a study co-author showed that a rise of four times in
to escape the antibodies, making it health center, the scientists were who is a professor in the department the stalk antibody levels correlated
necessary to develop a new flu alerted when someone tested of microbiology at the Icahn School of with a 42 percent reduction in
vaccine every year. positive for influenza. They took that Medicine at Mount Sinai in New York. influenza infection, and about a 50
In contrast, the hemagglutinin stalk case and enrolled in the study the Krammer used a novel assay to percent reduction in symptomatic
is far more resistant to mutations, afflicted individual’s entire house- measure the hemagglutinin stalk influenza.
providing a target for antibodies that hold, getting blood samples and antibodies. It was built from a mole- The study, Fauci says, “provides a
block its activity—the reason it may be following them for three to five cule containing the stalk of the H1N1 proof of concept that if we can
a candidate for a universal flu weeks. The study tracked a total of virus—the influenza strain that was induce [hemagglutinin] stem antibod-
vaccine. Several studies have shown 300 household members who lived the subject of this research—and the ies we may be able to have what we
that antibodies against the hemag- with the 88 individuals with con- head of an avian influenza virus call an important step toward a
glutinin stem confer protection in firmed influenza. “You’re basically (H6N1) that is not present in humans. universal flu vaccine. The people
animals, but their role in human getting a population of people who “This construct allows us to mea- pursuing this line of research will be
infections were unknown until now. are going to naturally be exposed to sure antibodies for the stalk only,” much more energized about doing it.”
“We have shown that stalk antibodies influenza,” Gordon explains, “and you Krammer explains, adding: “We Work has already begun on vaccine
correlate with protection in humans,” see who gets sick, and then you can developed it here, and we have used development. At NIAID’s Vaccine
says Aubree Gordon, a professor of compare the antibody levels of it for the last two or three years to Research Center, Barney Graham
epidemiology at University of Michi- those who got the flu and those who measure immune response in and his team have already started an
gan’s School of Public Health and didn't get the flu to see if specific animals.” However, they didn’t have a early-stage (phase I) trial of a vaccine
co-author of the study. “We’ve seen antibodies or antibody groups are study that could allow them to test it that aims to induce hemagglutinin
an association between having higher correlating with protection.” in humans. “It was with Aubree stem antibodies. “His approach is to
levels of stalk antibodies and being To measure those antibodies, the Gordon’s cohorts in Nicaragua that take the stem part of the hemaggluti-
protected from both influenza blood samples were sent to the lab of this was possible,” he says. The tests nin and put it onto a nanoparticle that

12
 NEWS
Skin has a high level
of mosaicism
compared to other
tissues in the body.

induces a very good immune re-

sponse,” Fauci says, adding: “Peter The Human Body
Palese at the Icahn School of Medi-
cine at Mount Sinai is looking at what
Is a Mosaic of
happens when you shave off the Different Genomes
head of the hemagglutinin molecule Survey finds that “normal” human
and only present the stalk to the tissues are riddled with mutations
body, can you get good antibodies?
Those are two laboratories that are
looking at the approach of selectively THE HUMAN BODY IS a complex
making antibodies against the stalk.” mosaic made up of clusters of cells
Krammer points out a few caveats with different genomes—and many
for the Nicaraguan study. Influenza A of these clusters bear mutations that
viruses can be categorized into two could contribute to cancer, according
phylogenetic groups (group 1 and to a sweeping survey of 29 different
group 2). H1N1, the virus that was types of tissue.
studied, belongs to group 1. The It is the largest such study to date,
research, already underway in and compiles data from thousands of
Nicaragua, must now be replicated samples collected from about 500
with group 2 viruses to determine if people. The results, published in June
hemagglutinin stalk antibodies also in Science, could help scientists to
offer protection. better understand how cancer starts,
Also, what was measured in the and how to detect it earlier.
initial study provided protection “We now appreciate that we are division, or because of exposure to were typically gleaned from sequenc-
induced by natural infection. “We mosaics, and that a substantial environmental factors such as ing specific genes in microscopic
don’t know if induced antibodies number of cells in our body already ultraviolet light or cigarette smoke. tissue samples.
through vaccination are as good. We carry cancer mutations,” says Iñigo When a skin cell with a given muta-
need to look into that,” he says. The Martincorena, a geneticist at the tion divides, it can create a patch of COMPLEX PATTERNS
next few years should reveal whether Wellcome Sanger Institute in Hinxton, skin that is genetically different from These studies caught the eye of Gad
this promising finding will turn into a U.K. “These are the seeds of cancer.” its neighbors. Getz, a computational biologist at

GETTY IMAGES
genuine prospect for a long-sought Tissue mosaics arise as cells Previous studies have found high Massachusetts General Hospital in
universal flu vaccine. accumulate mutations—from DNA levels of mosaicism in the skin, Boston. Getz and his team decided to
—Debbie Ponchner errors that creep in during cell esophagus and blood. Those results take a different tack: rather than

13
 NEWS

sequencing DNA from minute wide array of tissues. may become cancer.”
samples, they would mine a Tissues with a high rate of cell Researchers now need to find
database of RNA-sequence data division, such as those that makeways to sort out which of those
from the Genotype-Tissue up the skin and esophagus, cells will become tumors and
Expression (GTEx) project. tended to have more mosaicism which are “normal,” says Cristian
Because the body uses DNA as a than tissues with lower rates of Tomasetti, an applied mathemati-
template for making RNA se- cell division. Mosaicism also cian at Johns Hopkins Medicine
quences, mutations in DNA are increased with age, and was in Baltimore, Maryland. That could
sometimes reflected in RNA. be crucial for improving efforts to
particularly prevalent in the lungs
The decision to study RNA gave and skin—tissues that are ex- detect cancers early.
Getz and his colleagues quick posed to environmental factors Tomasetti has developed
access to data from 6,700 that can damage DNA. methods for detecting tumor
samples taken from 29 tissues in DNA circulating in the blood,
about 500 people. But their SUBTLE SIGNALS which researchers hope could
approach has its drawbacks. Not A gene called TP53—which one day be used to find early
all DNA codes for RNA, so not helps to repair DNA damage signs of cancer. But he says that
every DNA mutation will be and is known as the guardian of his team was initially surprised to
evident in RNA sequences. And the genome—was one of the find that some of the mutations in
because the samples used for the most common mutation sites. their results—which are associat-
GTEx project are relatively large, Certain changes in TP53 are ed with cancer, and so could have
the DNA signature from small associated with cancer, but it indicated the presence of a
clusters of cells with unique might take additional mutations tumor—were from a group of
genomes might be drowned out in other genes before cells give normal blood cells.
by the far larger numbers of other rise to tumors. “This messy situation is the new
cells. “What we’re seeing are some normal,” Tomasetti says. “The
Overall, the study found fewer of the earliest precancerous challenge is now to figure out up
examples of mosaicism in some changes that are then going to to what point we call something
types of tissue than would be accumulate more mutations,” normal.”
expected on the basis of previous says Erin Pleasance, who —Heidi Ledford
research. But the key, says studies cancer genomics at the This article is reproduced with
Martincorena, is that the latest British Columbia Cancer Agency permission and was first pub-
analysis demonstrated that in Vancouver, Canada. “Eventual- lished in Nature on June 6, 2019.
mosaicism is present across a ly a small proportion of these

14
Have We
Found a Diet
That Truly
Works?
The so-called satiating
diet seems to help
people manage weight
and good health without
going to extremes
By Shirin Panahi

CHRIS GASH
15
E
Shirin Panahi is a postdoctoral researcher in
the departments of physical education and
kinesiology at Université Laval in Quebec City,
Canada. Her goal is to design programs and
interventions that promote healthy eating and
lifestyle strategies that support health.

“EAT LESS AND MOVE MORE.” healthy foods that are especially satiating; that is, foods er there, I have spent years trying to understand how
Oh, such simple advice, but is maintaining a healthy that create feelings of fullness and satisfaction. Nutrition what we eat affects appetite, body weight and metabolic
weight really that simple? We live in an era of nutritional researchers have discovered many such foods, which health over the life span. We took foods containing most
misinformation and opinions galore. These days, it seems improve appetite control and decrease food intake, condi- of these components and created what we called a “high-
that everyone feels qualified to offer expert advice on diet, tions necessary for sustained weight loss. A satiating diet ly satiating diet.”
exercise and weight loss. With rising obesity rates all includes foods that are high in protein (such as fish), high In a 2017 study, 34 obese men were placed on this regi-
around the world, we are constantly searching for in fiber (whole grains, for example) and high in fruits and men, which was 20 to 25 percent protein, for 16 weeks.
approaches to better manage our weight and our health. vegetables. It contains healthy fats, such as the polyunsat- Another 35 obese men followed a standard diet: 10 to 15
For decades, the main strategy for losing weight has urated fats found in avocados, and includes dairy prod- percent protein, and based on Canadian national guide-
been to cut back on calories: what nutritionists call an ucts such as yogurt. Perhaps surprisingly, it might also lines for healthy eating. The men who followed the highly
“energy-restricted diet.” Although this often works in the include capsaicin, the substance that makes jalapenos and satiating diet significantly reduced their weight and body
short term, it rarely produces long-term success. It back- other peppers so hot. fat and had greater feelings of fullness compared to men
fires because it can lead to greater feelings of hunger after What’s so special about these foods is that each of them who followed the standard diet. They were also better able
the weight is lost, more obsessive thoughts about food possesses specific characteristics that benefit our health to stick to the highly satiating diet: only 8.6 percent quit
and eating, and a greater risk of overeating due to nega- either by decreasing hunger, reducing body fat, lowering the diet, compared to 44.1 percent of the men following
tive emotions and stress. These complicate the bodily blood sugar, improving blood pressure or increasing the standard diet.
mechanisms that control appetite and partly explain why metabolism. For instance, yogurt contains protein, calcium These are very promising findings, but is it possible to
most people regain the weight in the long term. and lactic acid bacteria, which are the live and active bac- maintain the weight lost over the long term with this
Other types of restrictive diets, such as the popular teria that help with the growth of good bacteria in the gut. strategy? What about metabolic and mental health; can
high-fat, no-carbohydrate ketogenic regimen, have some A healthy gut microbiome has been found to help control it prevent cravings and negative emotions? What about
of the same problems. Like low-calorie diets, they are body weight and improve other aspects of health. In some the role of other lifestyle factors on body weight such as
difficult to follow over a long period of time, which can specific populations, such as people with obesity or type 2 sleep, physical activity and prolonged sitting? We don’t
lead to feelings of frustration and failure. The challenge diabetes, these food components have been found to help have the answers yet, but we are planning further stud-
for researchers has been to find a strategy that is not control appetite and positively impact overall health. ies that we hope will address these questions. If the high-
restrictive and that can reduce feelings of hunger and But what if we took all of these key components and ly satiating diet proves to have the benefits we saw in
improve eating habits and overall health without caus- combined them into one diet as an approach to manage our study and if it proves to be sustainable, it could be a
ing some of these negative side effects. weight? That’s exactly what our team did at Université realistic and potentially powerful dietary solution to the
The answer, it turns out, may be a diet constructed from Laval in Quebec City, Canada. As a nutritional research- problem of weight control.

16
 Can You Prevent
Pregnancy with the
Pullout Method?
An investigation into one of the biggest
misconceptions in male fertility

CHRISTOPH BURGSTEDT GETTY IMAGES

By Jen Schwartz

17
 Jen Schwartz is a senior editor at Scientific American who writes about
the intersection of science, technology and society.

It starts with an age-old question: But real life is rarely perfect. Some males cannot reli-
ably perceive the imminence of ejaculation and with-
draw too late. Others might emit semen intermittently
If a man pulls out before ejaculating, or over a long period of time instead of as a single event,
according to a 1970 family-planning manual. A lot of

can a woman still get pregnant? men don’t realize that the highest concentration of
sperm occurs in the first spurt of semen—which can be
especially problematic if getting drunk slows down their
In bedrooms, basements and the backs of cars world- white goo, you’re likely to get an answer to a different reaction time. Still others don’t pull out in time because
wide, millions of sexually active humans make choices question—that is, a declaration that pulling out is a ter- their pleasure takes precedence over a woman’s health
(or regret them) based on what should be foundational rible form of birth control. and well-being. For reasons such as these, the “typical
fertility knowledge. Most trusted sources say the answer “When we’re talking about what’s in preejaculate, use” failure rate of coitus interruptus jumps to between
is yes—it is unlikely but possible that pregnancy will that’s not really the point,” said Michael Eisenberg, 20 and 30 percent.
occur, so don’t risk it. director of male reproductive medicine and surgery at People in the reproductive-health field largely dismiss
Dig deeper, though, and it quickly becomes unclear Stanford University School of Medicine, after I’d asked the pullout method because they don’t believe men have
exactly where the risk is coming from. Instead of evi- him the fertilizing-power question in various ways. “We the ability and willpower to withdraw at the correct
dence-based education, you’ll encounter some of the know that pulling out is not effective at preventing time, every time. Meanwhile there is a shocking lack of
most durable misconceptions in sexual and reproduc- pregnancy.” research on whether or not viable sperm are actually
tive health. When researchers analyzed a year’s worth of The pullout method—alternatively known as “with- present in preejaculate.
questions that were submitted to an emergency contra- drawing” or “pull and pray” and formally christened in The best way to synthesize the answers I collected
ception Web site, they found that almost half of the ques- Latin as “coitus interruptus”—is an ancient form of con- from physicians, peer-reviewed journals and education-
tions that involved sexual acts “express fear about the traception. The Talmud refers to it as “threshing inside al institutions is this: Preejaculate itself does not con-
pregnancy risk posed by pre-ejaculatory fluid.” and winnowing outside.” Globally, it is still one of the tain sperm—or maybe it does occasionally, but perhaps
Preejaculate—which pretty much everyone calls pre- most commonly used forms of birth control, particular- it gets contaminated with sperm that has “leaked” from
cum—is the lubricative secretion that is emitted, invol- ly in regions without access to modern methods. When elsewhere. Plus, there’s leftover sperm from previous
untarily, from the Cowper’s gland in the penis during performed perfectly every time, it actually has a failure ejaculation. And anyway, Eisenberg says, we should
sexual arousal. Its job is to create a hospitable ride for rate that isn’t much higher than that of condoms: 4 per- assume that preejaculate “usually has some sperm,
sperm that ultimately pass through the urethra during cent versus 2 percent, respectively. That means about which can lead to [contraception] failure.”
ejaculation. But whether you query the Internet or an four out of 100 women who rely on the pullout method It is obvious to blame inadequate sex education for our
andrology expert about the fertilizing power of that egg- exclusively will become pregnant during one year of use. collective confusion. But ironically, write the authors of a

18
2009 Contraception paper, “the notion that pre-ejaculato-
ry fluid can cause pregnancy ... seems to have been intro-
In textbooks and the media, sperm are “often
duced by the medical profession itself.” anthropomorphized as masculine, forceful,
DISPELLING A MYTH?
competitive, and single-mindedly determined to
Where did the fertile prowess of preejaculate originate? fertilize the egg against all obstacles.”
Perhaps it was in 1931, when Abraham Stone—a physi-
cian and colleague of Planned Parenthood founder Mar-
garet Sanger—wondered how it was even possible for the Wagner’s “Ride of the Valkyries.” Additionally, girls often set out to more rigorously investigate the fertilizing
withdrawal method to fail: Sperm are made in the testi- learn to be terrified of sperm yet aren’t taught how their potential of preejaculate, noting that “no study has found
cles and don’t route through the Cowper’s gland on their own body works: A recent survey of 1,000 American motile sperm in the pre-ejaculate.” Their paper, pub-
way out. Stone asked some buddies with microscopes to women of reproductive age found that 80 percent of lished in Human Fertility in 2011, analyzed 40 samples
examine their preejaculate for sperm. Among the 24 sam- them were not able to correctly answer how many days of preejaculate from 27 volunteers. Ten of the volunteers
ples from 18 men, only four contained many or a few of each cycle they are fertile. (37 percent) produced samples that included “a reason-
sperm. In a 1938 book, Practical Birth-Control Methods, Since Stone’s experiment, there has been little incen- able proportion” of motile sperm.
Stone wrote that these figures were insignificant. Regard- tive to research coitus interruptus at all, partly because Because some of the men gave samples on multiple sep-
less, a “myth” that a handful of sperm in preejaculate unlike condoms or intrauterine devices (IUDs), there’s arate occasions, an intriguing pattern emerged: sperm
makes coitus interruptus unreliable took off, and it was no contraceptive product to sell. While the pregnancy was present in either all of an individual’s samples or in
“copied uncritically from one textbook another,” accord- risk of preejaculate has only been investigated a handful none of them. “It would appear from our study,” the
ing to the 1994 edition of the book Fertility Control. of times, the results challenge popular assumptions and authors wrote, “that some men repeatedly leak sperm in
This myth was popularized by the classic 1966 text- raise new questions. their pre-ejaculatory fluid while others do not.”
book Human Sexual Response, by William H. Masters Here’s what the literature tells us: In the early 1990s, They therefore concluded, “it is tempting to speculate
and Virginia E. Johnson, according to the Contraception a study examined the preejaculate of HIV-positive men that the use of withdrawal as a means of contraception
paper. These pioneering sex researchers “warned of the to determine if the virus was present. (It was.) An ancil- might be more successful in some men because they are
possibility of pregnancy from withdrawal due to the lary but “more significant” finding described in Contra- less likely to release sperm with their pre-ejaculate.”
presence of sperm in secretions of the Cowper’s gland”—a ceptive Technology Update was that “most pre ejaculate Then, in 2016, a larger study of 42 healthy Thai men
statement that “was apparently not evidence-based but samples did not contain any sperm and those that did reported that “actively mobile sperm” were found in only
subsequently repeated,” the authors write. had only small clumps of a very small amount of sperm 16.7 percent of the subjects. Unfortunately, the researchers
The Contraception paper’s authors also speculate on which seemed to be immobile.” If a larger study con- did not collect preejaculate samples on multiple
why sperm seem to have “extraordinary potency” in the firmed the results, the article said, it “may dispel the occasions.
eyes of the public. In textbooks and the media, sperm are myth that pre ejaculate fluid contains sperm.” To make sense of these conflicting data, I called John
“often anthropomorphized as masculine, forceful, com- Only tiny studies have taken place since. In a 2003 exper- Amory, a physician and professor at the University of
petitive, and single-mindedly determined to fertilize the iment with 12 Israeli men who gave at least two samples of Washington, who is known for his research on male
egg against all obstacles,” they write. Indeed, the memo- preejaculate each, scientists examined the secretions infertility and novel forms of contraception. I asked him
rable 1989 educational film The Making of Me features under a microscope and found that none of them con- about the plausibility of this “two groups” concept: the
cartoon sperm “men” in a literal race for a sexualized tained sperm. Another small study also found no sperm. idea that men might either always have sperm in their
egg “woman,” set to a soundtrack that includes Richard Several years ago, researchers in England and the U.S. preejaculate or never have it.

19
 Amory responded with surprise. “See, I didn’t even
know that,” he said about the studies. “We were taught
[in medical training] that sperm were left over from the
last ejaculate.” This is a popular theory. Planned Parent-
hood similarly says that preejaculate “may pick up sperm
from a previous ejaculation as it passes through a man’s
urethra.” Wikipedia promotes a familiar fix: just urinate
before intercourse, the logic goes, and you’ll flush out lin-
gering sperm.
Though the acidity of urine does harm sperm, I could
not find any evidence to prove that this strategy is solid. In
fact, researchers in the 2011 Human Fertility paper wrote
that the volunteers giving samples had, of course, gone to
the bathroom several times since their last ejaculation.
Therefore, every time the authors observed sperm in pree-
jaculate, the contamination “must have taken place imme-
diately prior to ejaculation.” Clearly, there are consequenc-
es to misunderstanding this facet of male fertility.

“FERTILITY IS A TEAM SPORT”

Because we know so little about sperm in preejaculate,
the failure rate of pulling out is really more of an “educat-
ed guess” and a topic of controversy among experts in the
field. The reality is that lots of people in the U.S. use this
method to avoid pregnancy. So, do males approach with-
drawal as a serious form of contraception and take
responsibility for learning how to maximize its efficacy?
While plenty of men feel confident discussing the minu-
tia of abortion and female reproductive parts they tend
to be quite ignorant of their own fertility.
Greg Sommer discovered just how few males under-
stand their contribution to pregnancy when he launched

ED WHITE GETTY IMAGES

an at-home sperm-testing kit called Trak. In 2017, he
brought his product to the Consumer Electronics Show
in Las Vegas. “We had a demo kit at our booth, and I can’t
tell you how many guys came up and said, ‘So, what, I pee
in the cup?’”Sommer recalls. “And we had to tell them,

20
‘No, there’s no sperm in your urine.’”
Sperm awareness got a boost in 2017, when a meta-anal-
“We had a demo kit at our booth, and I can’t tell you
ysis showed that sperm counts of men from the U.S., how many guys came up and said, ‘So, what, I pee in
Europe, Australia and New Zealand had dropped by
more than 50 percent in less than 40 years. “Men are
the cup?’ And we had to tell them, ‘No, there’s no
responsible for nearly half of infertility cases but take sperm in your urine.’ ” —Greg Sommer
way too long to get a semen analysis when they are not
conceiving naturally,” Sommer says. The study was wide- “Done with condoms? Join the fight for male birth con-
ly framed as a potential crisis in male fertility, sparking trol,” it reads, followed by the hashtag #LoveWithoutThe-
some men to consider their sperm functionality more Glove. It seems to be working: A major clinical trial for a
deeply—or just consider it at all. hormonal gel began late last year.
Whereas women have long shouldered the burden of It sounds woefully apropos that scientists and entre-
both preventing pregnancy (with drugs) and causing preneurs are convincing guys to learn about reproduc-
pregnancy (with assisted-reproduction technologies tive responsibility by appealing to their sexual pleasure—
such as egg freezing), “there is a growing understanding particularly at a time when some U.S. lawmakers want to
that fertility is a team sport,” Eisenberg says. “We need to investigate the “criminality” of miscarriages and classify
understand more about the male side.” treatment for ectopic pregnancy as an “abortion.”
Recent population surveys have shown that many men Yet more options and knowledge for preventing preg-
do want more birth-control options. Without contracep- nancy are good things for everyone. After all, nearly half
tion methods beyond condoms, vasectomy and with- of all pregnancies in the U.S. are unintended, and the
drawal, some guys are already doing “all sorts of crazy lack of access to birth control and health care providers
and potentially dangerous things to make themselves is not the only problem. Nearly 40 percent of women are
less fertile to avoid pregnancy,” Sommer says. not satisfied with the birth-control method they are cur-
In discussion forums on Trak’s infertility education rently using, according to the Guttmacher Institute.
Web site at www.dontcookyourballs.com Sommer found When people dislike their contraception for whatever
that some men “are biohacking themselves” by using pre- reason—including health side effects from the pill or the
scription steroid creams to intentionally squash sperm tactile compromises of condoms—they are less likely to
count. Others sit in a hot tub every day. One guy wrote use it correctly and consistently.
about his “hacked-up underwear heater-type device with One day, if the pharmaceutical industry decides to

PATRICK LLEWELYN-DAVIES GETTY IMAGES

a little battery pack,” Sommer says. “Don’t underestimate reverse course and fund the development of innovative
men’s drive and creativity when it comes to having a bet- birth control, we could get genetic tests and other tech-
ter sex life”—meaning men will indeed make efforts and nologies to help people of both sexes figure out what kind
take risks to have sex without condoms. of contraception might work best for our individual phys-
The Center for Male Contraceptive Research & Devel- iologies and ways of life. In addition to hormones and
opment even exploits this incentive to solicit volunteers IUDs, researchers could investigate “proteins, enzymes
for clinical drug trials. One image on the center’s Insta- and genes involved in the reproductive process that
gram account features a boxer with a punching bag. could be targeted to prevent pregnancy in both women

21
and men—and potentially do so in more precise ways,”
wrote journalist Maya Dusenbery in the May issue of Sci-
“What if the male partner is willing to take on some of
entific American. the risks and side effects to lower the risks and side
With a personalized-medicine approach, imagine if
birth control could be catered to the specific needs and
effects of his female partner? No one has really talked
priorities of an individual. In some cases, the task of pre- about the idea of reframing risk paradigms.”
venting pregnancy could be truly shared between a cou- —John Amory
ple. “What if the male partner is willing to take on some of
the risks and side effects to lower the risks and side effects
of his female partner?” Amory says. “No one has really FOR SCIENCE! nancy tests while awaiting the results. A white column in
talked about the idea of reframing risk paradigms.” The Trak test, while approved by the Food and Drug the prop reached above the 55 M/mL mark, signaling
Until this equitable future arrives, understanding the Administration, is not designed for testing preejaculate. that his sperm concentration made it into the “optimal”
fertilizing potential of an individual’s preejaculate could Nor is it intended to be used as form of pregnancy pre- range for conception. After another 48 hours of abstain-
give some men another way to participate in the respon- vention. But according to Sommer, it is sensitive enough ing from ejaculation (“for consistent science,” I insisted),
sibility of contraception. Let’s say that males do fall into to pick up on sperm concentration as low as one million it was time to test his preejaculate.
two groups, as the Human Fertility study speculates. What per milliliter (M/mL). While that sounds like a lot, “the “I think accurately testing just precum might be a chal-
if a man—my boyfriend, for instance—could undergo a chance of pregnancy is extremely low,” Amory says. “In lenge,” Sommer wrote when I informed him of my plans
preejaculate sperm evaluation? fertility settings, we take care of a lot of men with those to use his test for off-label endeavors. “Collecting a sam-
If so, my boyfriend and I might scientifically resolve counts who never conceive spontaneously.” The World ple via masturbation might have different discharge
the final variable in our birth-control efficacy. We use Health Organization has determined that suppressing dynamics than during intercourse.”
coitus interruptus1 during my fertile window, the week- sperm counts to this threshold appears to decrease the The hallowed pages of Scientific American are not
long span during which his sperm can potentially fertil- chances of conception to less than 1 percent per year. the place to describe how we collected a full milliliter
ize my egg. (An egg is only viable for fertilization for up I ordered a Trak fertility kit and recruited one study of unadulterated preejaculate. I will say that our meth-
to 24 hours per menstrual cycle, and sperm can survive participant: after assuring my boyfriend that his genetic odology was informed by the science of arousal, a com-
in the female body for up to five days.) I determine this material wouldn’t be sent off to a lab and end up in a mitment to rigorous research standards and an abun-
window using a technique called the symptothermal database (Trak isn’t connected to the Internet), he gave dance of humor.
method, a means of avoiding pregnancy that involves me his informed consent. Per the discussions of methodology in the academic
meticulously tracking changes in cervical fluid and bas- First, we did a control test to get a sense of his sperm studies, we knew it was critical to collect only preejacu-
al-body temperature in order to predict, and then con- baseline. After 48 hours of abstinence (the minimum late. The authors of the Thai paper wrote that study vol-
firm, when ovulation occurs.2 length of time for proper semen analysis, according to unteers might have smeared semen on the collection
We devised this contraception strategy based on our the WHO), he proffered a five-milliliter ejaculation sam- slides instead of preejaculate, which could mean the
personal risk-benefit analysis and combined physiolo- ple. Per the instructions, we let it sit for 30 minutes to liq- number of preejaculate samples that were found to con-
gies—and it has worked for us so far. But I’d prefer to uefy, gave it a good swirl, then deposited a pipette’s worth tain sperm was artificially high. In other words, the sub-
empirically validate the absence (or problematic pres- of fluid into a test prop. That went into the Trak “engine,” jects might have been sloppy, leading to false positives.
ence) of sperm in my boyfriend’s preejaculate. Frustrat- an adorably sized, battery-powered centrifuge. (Anecdotally, appealing to male pride created a strong
ed by the paltry research, I decided to conduct an exper- My boyfriend stared down the engine until it beeped to motivation for my volunteer to endure the 30-ish min-
iment myself. signal its finish, recalling the way women glare at preg- utes it took to retrieve enough volume of pure preejacu-

22
late to run the Trak test. “Wow, look at how much you’re After all, contraceptive use in the real world is more
producing,” I cheered about halfway through. By com- varied and circumstantial than the behavioral patterns
parison, the academic study subjects were likely mastur- that determine “failure rates.” Few people use only one
bating, presumably alone, in a lab, and I humbly hypoth- method in the same exact way every time they have sex.
esize that they may have gotten bored. The authors of the Recent surveys suggest that coitus interruptus is actual-
2011 Human Fertility study even suggested that subjects ly employed more frequently than previous research
might have knowingly handed over samples of ejaculate suggests and often in conjunction with other methods.
fluid because they were embarrassed they couldn’t pro- If some men do consistently have viable sperm in their
duce sufficient preejaculate.) preejaculate, it might help explain the 4 percent failure
We ran the preejaculate test just as with my boy- rate of the withdrawal method despite “perfect” use. It
friend’s ejaculate: a full pipette of well-mixed fluid went would not be the first time the medical field was wrong
into the prop, followed by a six-minute spin in the cen- to blame contraceptive failure on user error instead of
trifuge. Then we peered into the measuring strip under physiological variation.
bright light and couldn’t find even a speck of white. If At the least, researching the mechanisms of preejacu-
there was sperm present, the concentration was likely late and pregnancy risk could add evidence-based
below one million per milliliter, which means my boy- nuance to sex education. As Amory told me after review-
friend’s preejaculate sample could be considered infer- ing the studies on preejaculate, “I think this is an exam-
tile by WHO standards. ple of when you drill down on a ‘truth,’ one finds it’s not
Though promising, one at-home test doesn’t confirm based on much.”
anything. We would need to replicate this experiment sev-
1
eral more times. Sperm count in semen changes over time We could use condoms during my “fertile window,”
and is affected by health factors, so perhaps the same is but their failure rate over time is not significantly low-
true for preejaculate. Because Trak is not intended for er than coitus interruptus. Given the best available sci-
such diagnostics, it would be best to compare the results ence and our personal considerations, we chose to be in
of our experiments with lab tests at a fertility clinic (if control over preventing user error rather than risk the
they’d even indulge such a request). uncertainty of product failure. ↩
2
Larger questions abound: Even if there are sperm in The symptothermal method should not be confused
preejaculate, can they swim? Are all of their parts intact? with the rhythm method or similar counting tech-
And if the sperm present in preejaculate aren’t simply niques. With perfect use, it can be just as effective as the
“left over” from the last ejaculation, then from where pill at preventing pregnancy. While I chart my data in
might they be “leaking,” as the literature suggests? a cycle-tracking app, I do not consult predictive algo-
Filling these knowledge gaps has the potential to fine- rithms to determine when I am fertile. Like all contra-

ED WHITE GETTY IMAGES

tune the math of pregnancy risk. Imagine if males were ceptive methods, the symptothermal method is certain-
able to better gauge whether the pullout method is a use- ly not right for everyone. It can, however, be used as an
ful tool in their contraception arsenal or, more critically, excellent educational tool for learning about fertility
whether it is too risky even when the act itself is per- and reproductive health.
formed correctly every time.

23
Cancer Research
Points to Key
Unknowns about
Popular “Antiaging”
Supplements

The health promises of

boosting an important
metabolic molecule
may be clouded by its
possible role in
promoting cancer
cell growth

DMITRI OTIS GETTY IMAGES

By Helen Shen

24
 Helen Shen is a science writer based in Sunnyvale, Calif. She has
contributed to Nature, Science and the Boston Globe.

A
s the world’s aging population grows rapidly, so has its appetite for health tips, NR supplement is also the subject of many clinical trials,
tricks and products that could help guard against the ravages of time. Among with the company recently sponsoring a study of its effects
countless dietary supplements—vitamins, minerals and other products—some on cognitive function, mood and sleep in people older
people have pinned their hopes on a molecule called nicotinamide adenine than 55.
dinucleotide (NAD), a key player in the cellular production of energy. Often For very different reasons, NAD+ has also attracted a
written as NAD+, the name of its oxidized form, the molecule participates in a wave of attention from cancer researchers. Recent studies
host of metabolic pathways and is involved in other important processes, such suggest that cancer cells of many types depend on NAD+
+
as DNA repair. NAD levels naturally decline as people and animals age, and this loss has been to sustain their rapid growth and that cutting off the NAD+
supply could be an effective strategy for killing certain
proposed as contributing to the underlying physiology of aging.
cancers. The data from these studies paint a more compli-
Studies show that boosting NAD+ levels can extend life attracted their share of criticism as well. Unlike drugs, cated picture of NAD+ and raise new questions about the
span in yeast, worms and mice. Animal research also indi- dietary supplements are lightly regulated by U.S. authori- diverse ways taking an NAD+-boosting supplement might
cates NAD+’s promise for improving several aspects of ties, allowing them to be sold before research confirms influence health. “It might still slow down the aging part,
health. Raising levels of the molecule in old mice appears their safety and effectiveness in humans. Recent clinical but it might fuel the cancer part,” says Versha Banerji, a
to rejuvenate mitochondria—the cell’s energy factories, trials funded by ChromaDex and Elysium show that adults clinician-scientist at the University of Manitoba. “We just
which falter over time. Other mouse studies have demon- taking NR-containing supplements for six to eight weeks need to figure out more about the biology of both of those
strated benefits such as improved cardiovascular function, experience increased levels of NAD+ in their blood with- processes, to figure out how we can make people age well
enhanced muscle regeneration and better glucose metab- out serious side effects. But researchers are still working and also not get cancer.”
olism with NAD+ supplementation. to prove that NR can actually improve human health—a In a Nature Cell Biology study in February scientists
Banking on such results, multiple companies currently sticking point for critics and an issue acknowledged by the reported a newly discovered role for NAD+ metabolism at
sell dietary supplements containing NAD+ precursors companies themselves. the intersection of cellular aging and cancer—specifically,
such as nicotinamide riboside (NR) or nicotinamide “Not everything that works in mice works in humans, in a process called cellular senescence. Senescence occurs
mononucleotide (NMN). NR supplements, in particular, which is why it’s critical to do the rigorous human trials,” when aging, damaged cells stop dividing. The process can
have attracted buzz for the scientific star power associat- says Leonard Guarente, a co-founder of Elysium and its help suppress cancer, but it leads cells to produce inflam-
ed with two major suppliers, ChromaDex and Elysium chief scientist. The company is studying the effectiveness matory molecules that can also promote cancer growth
Health. The companies’ research advisers hail from insti- of its NR-containing supplement for a number of condi- under certain conditions. In the Nature Cell Biology study,
tutions such as Stanford, Harvard and Columbia Univer- tions in people, including kidney injury and fatty liver. Rugang Zhang of the Wistar Institute and his colleagues
sity. Elysium’s scientific advisory board currently boasts Early this year, Elysium published a small trial showing found that in cells entering senescence, rising levels of
eight Nobel laureates. that its product could potentially slow the neurodegener- NAMPT (a major NAD+-producing enzyme in mammals)
But the NR business and some scientists involved have ative disease amyotrophic lateral sclerosis. ChromaDex’s encourage the release of inflammatory and potentially

25
protumor molecules. Consistent with those findings, mice These emerging questions are not ruffling makers of The answer may not be a single or straightforward one.
genetically predisposed toward pancreatic cancer devel- NR supplements. “I’m not losing sleep over this,” says NAD+ is a ubiquitous and fundamental molecule, involved
oped more precancerous and cancerous growths when Charles Brenner, chief scientific adviser for ChromaDex. in many biological pathways and cellular operations. Its
they consumed the NAD+ precursor NMN. Zhang says Reports of higher-than-normal NAMPT levels in many ingestion could lead to a mix of positive and negative out-
more research is needed to fully understand the role of cancers do not prove that high NAD+ levels actually pro- comes, the balance of which might depend on context.
NAD+ in cancer, but he adds that “we should be cautious mote cancer growth, he notes. He contends that studies NAD+ precursors, consumed orally, may be taken up by
and bear in mind the potential downside of NAD+ supple-
mentation as a dietary approach for antiaging.” “There is tremendous interest in the NAD+ field right now. And I’m
Zhang’s work is part of a growing body of research
that has drawn attention to NAD+ metabolism in cancer, pretty sure sooner or later, we will have the evidence to answer this.”
particularly involving NAMPT. Compared with healthy —Shashi Gujar
tissues, elevated NAMPT levels have been reported in
several human cancers, including; colorectal, ovarian, that kill cancer cells by suppressing the NAD+-produc- some tissues more than others. And different cell types are
breast and prostate cancers. In studies in animals and ing enzyme also do not properly address the issue. known to employ distinct metabolic programs, which
cells, drugs that inhibit NAMPT have shown promise in “Whether low NAD+ would block cancer and whether could lead to tissue-specific responses to NAD+.
killing cancer cells or enhancing the effectiveness of oth- high NAD+ would promote cancer are two separate ques- Like the tissues from which they arise, cancers are
er cancer therapies. tions,” he says. diverse in their cellular ways—and at least some run
In 2016 researchers at Washington University School Indeed, Zhang’s study is one of the first to directly counter to the “cancer fuel” hypothesis of NAD+. A 2014
of Medicine in St. Louis found that among people with show that providing supplemental NAD+, via the precur- study, for instance, reported that in a mouse model of
glioblastoma—an aggressive form of brain cancer— sor NMN, was associated with increased cancerous liver cancer, inhibiting NAD+ production was a key step
tumors with higher NAMPT levels correlated with short- growths in mice. But Elysium’s Guarente is skeptical of by which an errant gene caused DNA damage and tumor
er survival times. When human glioblastoma cells were the data, arguing that Zhang’s study showed a small formation. In this case, feeding NR to the mice actually
implanted in mice, the cells proliferated and established effect in a small number of animals and that it has yet to helped protect against these harmful effects.
new tumors. But when researchers suppressed NAMPT be replicated by other groups. “I don’t think the evidence Together these findings do not necessarily point to
in these cells before implantation, they later saw reduced is there at all to say that raising NAD+ levels would favor ready answers for consumers interested in NR or NMN
brain-tumor formation and increased survival in the cancer,” Guarente says. supplements, so much as they highlight questions for
mice—suggesting that glioblastoma cells depend on At the moment, the idea that elevating NAD+ levels scientists to address in the coming years. “I would say
NAMPT and NAD+ to thrive. could fuel cancer growth remains a hypothesis, but it is that given that many people are taking these supple-
What might this result say about NAD+-boosting sup- one that has attracted considerable attention. Cancer ments for health benefits, a study of what these do to
plements? “There’s a lot of buzz about taking NAD+ pre- cells have high metabolic needs, including processes cancer risk or existing cancer biology is warranted,” says
cursors for their antiaging effects, which is based on a lot requiring NAD+. And many types of cancer cells boost Matthew Vander Heiden, a clinician-scientist at the Mas-
of great science,” said Albert Kim, senior author of the NAD+-making enzymes and then die when those sachusetts Institute of Technology’s Koch Institute for
2016 study, in a School of Medicine press release “I don’t enzymes are blocked by drugs. “We know that they like Integrative Cancer Research.
know if taking NAD+ precursors makes existing tumors NAD+, but it’s too early to say, if you add NAD+, whether The need for more evidence is a sentiment that is shared
grow faster, but one implication of our work is that we they will grow really fast,” says Shashi Gujar, a cancer by others. “There is tremendous interest in the NAD+ field
don’t yet fully understand all of the consequences of immunologist at Dalhousie University. “Many labs are right now,” Gujar says. “And I’m pretty sure sooner or lat-
enhancing NAD+ levels.” working to figure that out.” er, we will have the evidence to answer this.”

26
 Rafael Amado is president of research
and development at Adaptimmune.
Opinion

OBSERVATIONS

The Next Wave of

Immuno-Oncology
A cutting-edge therapy currently used
for blood cancers is now being adapted to
fight solid tumors

I
n 2017, the first immuno-oncology cell thera-
pies, known as chimeric antigen receptor T cells,
or CAR T, were approved by the U.S. Food and
Drug Administration. Immuno-oncology cell thera-
py is a field that leverages the immune system by
modifying, and thereby enhancing, immune cells to
target cancer. It accomplishes this by interdicting
pathways that maintain checks and balances on
cellular elements of the immune system, thereby
disrupting the tolerance of the body to the growth
and spread of cancer.
CAR T therapies have had an unprecedented

JUAN GAERTNER GETTY IMAGES

success in blood cancers, such as certain leukemias
and lymphomas. They have shown high response rates
and redefined the treatment of patients who have
exhausted other options. The therapeutic success
relies on an antibody fragment that binds to a surface
Illustration of CAR T cell cancer
protein on leukemias and lymphomas; the protein is immunotherapy in action.

27
 Opinion

known as CD19. The antibody fragment is linked to Patients in dire need of novel treatment options are the
stimulatory and signaling molecules that fire upon
binding of the antibody with the CD19 molecule,
driving force behind the impetus of Adaptimmune and many
thereby activating the T cells and making them destroy companies in the life sciences industry to continue the quest
the cancer cell. to eradicate metastatic cancer.
SOLID TUMOR CHALLENGES
CAR T therapies have shown limited success in solid However, cancer cells have proteins that look similar (specific peptide enhanced affinity receptor) T cell
tumors, since they do not typically express a molecule to the body’s own, not like foreign proteins, which platform to engineer TCRs so that they can recog-
on their surface that is unique to the solid tumor and creates an ability to evade the immune system. This nize cancer proteins on solid tumors. Adaptimmune’s
not to normal tissue. This, coupled with the complex makes it difficult to effectively target tumors with our SPEAR T cell therapy targeting a protein called
matrix in which cancer cells grow, makes it challenging body’s own naturally occurring TCRs. When cancer NY-ESO, now transitioned to GlaxoSmithKline, has
to develop cellular therapies for solid tumors. cells develop mutations, they may present novel shown efficacy in two unique sarcoma types—both
One way to overcome this challenge is to target aberrant peptides, but often the malignant cell and very difficult-to-treat solid tumors.
proteins expressed inside the cell rather than large cell other elements of the tumor dampen the T cell
surface proteins. This sort of immune response response by interfering with the molecular network FUTURE IMMUNO-ONCOLOGY
involves the activation of T cells against a portion of an that regulates how the T cell functions. The unraveling There is still more to come from the immuno-oncology
internal protein that the T cell sees as foreign. These of some of the proteins that regulate T cell function cell therapy field with respect to utilizing TCRs, since
protein fragments, known as peptides, dock with against tumor cells resulted in two scientists sharing many solid tumors recur and become incurable. This is
protein structures known as major histocompatibility the 2018 Nobel Prize in Physiology or Medicine. why Adaptimmune is conducting clinical trials with
antigens (MHC) on the cell surface, which is the multiple engineered TCRs across a broad range of
cellular network that governs the presentation of self THE POTENTIAL OF ENHANCED RECEPTORS solid tumors. The company is also investigating
versus nonself peptides and lets T cells distinguish Companies are now exploring how to enhance the next-generation TCRs armed with molecules to further
friend from foe. body’s naturally occurring TCRs to target solid improve the engineered T cells’ ability to target and
T cells are some of the “surveyors and assassins” of tumors. Engineering TCRs to have optimal affinity to destroy solid tumors. These enhanced approaches will
the immune system. They have T cell receptors (TCRs) the docking peptide enables the receptors to more likely lead to longer-lasting antitumor responses.
on their surface, and they circulate through the body, easily identify proteins from cancer cells that would Patients in dire need of novel treatment options are
binding foreign peptides on the surface of cells that have otherwise not be recognized as foreign. the driving force behind the impetus of Adaptimmune
are infected by foreign organisms such as viruses and These engineered TCRs can be put into a pa- and many companies in the life sciences industry to
bacteria. When a cell is infected, bits of that organism’s tient’s own T cells and then returned to the patient. continue the quest to eradicate metastatic cancer. The
protein make it to the surface, docking with the right These newly enhanced T cells can kill tumors, field has come a long way, and its potential appears
MHC. Surveying T cells can see these proteins multiply and attack more cancer cells than a boundless as scientists unravel the intricate interplay
through their TCRs and kill them to prevent propaga- patient’s naturally occurring T cells. between cancer and anticancer immunity.
tion of the infection. At Adaptimmune, we utilize our unique SPEAR Related Video

28
 Jon Morgenstern is an internationally recognized expert on the Opinion
treatment of substance use disorders. He leads addiction research at
Wellbridge Addiction Treatment and Research and serves as assistant
vice president of addiction services at Northwell Health.

OBSERVATIONS

A New Approach
to Addiction
Treatment
We need to create learning laboratories where
researchers interact directly with patients

T
he nation’s growing addiction crisis has am-
plified the urgent and long-standing need
for integrating research into the substance
abuse treatment and recovery process. While
there has been an increase in research activity
focused on addiction issues, the challenge is
that it often takes a decade or more before im-
portant clinical findings can be implemented into
real-world care delivery.
How can the industry address this problem and actionable treatment methodologies that can be this knowledge in ongoing care regimens. For
make continuous quality improvement a corner- shared with and help advance the work of example, most programs offer a variety of
stone of substance abuse treatment? I believe addiction professionals nationwide. different treatments, but there is no research on
we need to create addiction treatment learning the impact of these multicomponent programs or
laboratories that are embedded into, and coexist WHY NOW how to tailor care to the unique problems of

GETTY IMAGES
with, treatment and recovery centers. While research has generated evidence of individual patients.
The goal of this approach is to accelerate the treatment efficacy in highly controlled settings, Additionally, because there is little knowledge of
translation of basic science discoveries into there is limited understanding of how to apply how best to measure progress in treatment, it can

29
 Opinion

be very difficult to make critical decisions about Drug addiction has now become the deadliest
when to extend care or introduce a new treatment.
As a result, the current standard of substance use
public health crisis in recent U.S. history.
disorder (SUD) treatment too often provides a To address this major epidemic, it is imperative to find new
one-size-fits-all set of services, or if treatment is and innovative approaches to treatment.
personalized, it is based on clinical intuition without
the benefit of research.
AFFILIATIONS AND COLLABORATIONS is why integrating research into the treatment
CRITICAL DATA Establishing strong affiliations with the nation’s process creates a tremendous opportunity to
Compared to other areas of health care, the leading health care providers and building identify more precise markers for determining how
addiction field lags behind in the use and analysis collaborative relationships with major research a specific patient responds to specific treatments.
of data. Certainly, the human element can’t be institutions will play an important role in accelerat- Affiliations and collaborations can also help
replaced, but collecting and analyzing data in a ing the integration of research into the substance create opportunities to study large cohorts of
manner that is actionable will help more patients. abuse treatment and recovery process. patients, support continuum of care by tracking
The need is for real-time data collection to A good example of this is how Northwell Health, patients’ recovery, and explore new options for
enable care that is tailored to the individual and the largest health care provider in New York, and staying in touch with patients over extended
how he or she changes over time. Engel Burman, a leading developer of assisted-liv- periods of time.
For the most part, current SUD treatment ing facilities, have engaged in a joint venture with Key to all of this will be the ability to leverage the
programs do not have this capacity as part of Wellbridge Addiction Treatment and Research. This intersection of health care and technology (i.e.,
routine operations. Consequently, the industry unique venture will approach addiction in a modern “connected health”) and apply it to addiction
must now begin to work toward developing way by aligning best practices in a manner similar treatment. For example, many of the techniques
state-of-the-art clinical informatic platforms that to how Northwell addresses other illnesses like found effective for other chronic diseases can also
can collect research quality data on every patient diabetes and cancer. be used to promote better management of addic-
at admission, during treatment and for several A key advantage of this venture will be having tion care.
years following discharge. access to the necessary resources to explore Drug addiction has now become the deadliest
The goal is for researchers to be able to some of the more promising areas of addiction public health crisis in recent U.S. history. To
identify treatment outcomes and patterns, and in treatment, including mapping genetic profiles address this major epidemic, it is imperative to
doing so understand the interventions that work directly to optimize addiction treatment, as well as find new and innovative approaches to treatment.
best for individual patients. Once best practices expanding research on how genetic biomarkers While having patients down the hall from re-
along the continuum are identified, clinicians can can inform the use of medications. searchers is very rare in addiction treatment
then integrate them into everyday clinical care. Other important areas of study might include centers, it is now absolutely necessary to study,
Bottom line: Being able to see if outcomes imaging, neuroscience, precision medicine and properly treat and ultimately overcome this
improve as treatment is modified will be a comparative effectiveness. There are huge differ- devastating disease.
significant advancement in the addiction field. ences in how patients respond to treatment, which

30
 Rick Hohner is senior integrated care Opinion
manager at NeuroFlow.

OBSERVATIONS

The Case for

Collaborative Care
It produces better patient outcomes. Here’s why
it works and how it can be effectively deployed

S
everal years ago, a patient of mine was suf-
fering from intrusive thoughts and associat-
ed rituals stemming from a case of obses-
sive compulsive disorder (OCD). One day, she took
a significant risk and shared her distress with her
primary care provider, who realized that she need-
ed a behavioral health clinician (BHC). Fortunately,
one was “embedded” at the same health care pro-
vider where I work—a concept that is gaining in collaborative care model (also called integrated depression and anxiety.
popularity. care or health homes), the opportunity for patients When psychological problems lead to or exacer-
Soon, she eliminated 90 percent of her ritualized to receive comprehensive care for all of their bate physical symptoms in a traditional “compart-
behaviors and regained control. If she had not physical and behavioral health needs is greatly mentalized care” setting, it is more likely that the
spoken up, and her primary care provider was not enhanced. patient’s overall health (mind and body) will be
equipped to input data and integrate with a BHC, Untreated behavioral health issues can have impacted by disconnected treatment. Cardiologists
the story might have ended differently. significant downstream repercussions on physical are not skilled psychiatrists, and vice versa, but by
Every day, patients visit a health care provider or health, and can occasionally cause an alteration to coming together in a collaborative care model, they

GETTY IMAGES
hospital in order to discuss one or more physical treatment protocols. Whether it is heart disease or can each be more confident in knowing that their
symptoms, when in reality what they may really cancer or psoriasis, physical ailments are closely patient is receiving holistic treatment.
need is to talk about their mental health. In a connected to mental health conditions such as The collaborative care team may include a

31
 Opinion

primary care physician, a mental health specialist One case study, tracking the impact of collabora-
(social workers, psychiatric nurse practitioners, tive care in a hospital system, demonstrated a 57
counselors, psychologists, and psychiatrists), and percent reduction in depression among primary
other physical medicine specialists who may be care patients. Results like these can nudge other
treating the patient. All team members agree to health care systems and leaders to adopt technol-
hold each other accountable and to work in ogies and software that facilitate the collaborative
sharing their knowledge of the patient with the care approach.
overall goal of using this information to ensure the
best possible outcome. THE ROAD AHEAD
Each team member is expected to set goals with The benefits of patient-centered collaborative care
the patient that are aligned with and supportive of go beyond better physical and mental health. This
those from other team members. This model approach takes into account the patient’s values,
implies that team members share ideas, outcomes beliefs and preferences while encouraging him or
(positive or otherwise) and recommendations with her to actively participate in an individualized
each other in a respectful and supportive manner. treatment plan. Additionally, the economic benefits
Finally, the team evaluates the outcomes using of collaborative care must not be overlooked.
validated measures and makes adjustments to the Depression costs employers an estimated $44
collaborative plan accordingly. billion annually in lost productivity.
Across all disciplines, we need to find ways to
GAINING TRACTION integrate our knowledge and skills so that every-
Research around collaborative and integrated care one can engage in such a dynamic and effective
models began in the 1970s, so this is not a new mode of care. Despite the positive results from
idea, but adoption has been tepid. Fortunately, with collaborative care models, there is still work to be
more than 80 trials completed, there is greater done to successfully adopt these practices across
acceptance of this approach as a well-supported our health care landscape. I recently joined Neuro-
model of care. In true collaborative fashion, many of Flow, a health care technology company whose
these trials involved multiple specialties, including goal is to bridge the gap between mental and
OB-GYN, pediatrics and pain management, and physical health in all care settings. But currently,
studied patients with a range of complex needs. As fewer than 3 percent of psychiatrists and psychiat-
recently as 2016, the American Psychiatric ric nurse practitioners work with primary care
Association and the Academy of Psychosomatic physicians in designing and implementing treat-
Medicine (since renamed the Academy of Consul- ment plans for their shared patients. Increasing
tation-Liaison Psychiatry) issued a report and a that percentage would allow many more patients to
public statement recommending collaborative care. reap the benefits.

32
 Abigail Meola is a student at Stevens Institute of Technology in Opinion
Hoboken, New Jersey. She studies science communications
and writes for the school's newspaper The Stute.

OBSERVATIONS

The Polycystic
Sisterhood
Infertility is on the rise, but one major
cause—polycystic ovarian syndrome—gets too
little attention

A
sk anyone in a sorority and they will tell you
that sisterhood is priceless. I’m not in a so-
rority, but I am not a stranger to the con-
cept. I have two biological sisters of my own and
recently joined another sisterhood inadvertently:
the women suffering from polycystic ovarian syn-
drome (PCOS).
Sure, it’s not your typical social club. It is certain-
ly not as much fun. But women with PCOS have a
bond as close as you would find in any sorority. We swings. I had my thyroid levels checked more the U.S. is as high as 15 percent and climbing.
are a scientific cysterhood, you might say. times than I can count. But as common as it is, it is equally confusing.
I first caught a glimpse of my emerging PCOS Polycystic ovarian syndrome is a common but The name of the disorder suggests multiple
when I gained close to 40 pounds in six months. I complex endocrine disorder affecting a woman’s cysts in the ovaries, which is only partially true.
was in my second year of college, and though I hormones, metabolism and reproductive capabili- You do not need to have any cysts to be diag-

GETTY IMAGES
was well aware of the “freshman 15,” I was ties. It is the leading cause of infertility among nosed with the syndrome. To add even more
doubtful that a “sophomore 60” was another rite women. Some 5 to 10 percent of women suffer ambiguity, the “cysts” associated with the disor-
of passage. I had low energy and extreme mood from the disorder worldwide, and the number in der are more accurately categorized as “follicles,”

33
 Opinion

since they are not lined or fluid-filled, and are day, bawling my eyes out to Coldplay songs. I fertility, thus minimizing reproductive success.
significantly smaller than the typical cyst. The took inositol, an alternative to synthetic proges- Many people have posed explanations for this
National Institutes of Health’s PCOS workshop terone. I drank turmeric and cinnamon. And I confusing genetic inheritance, such as the idea
panel even moved to rebrand the syndrome, ended up taking metformin, a diabetes drug and from Sabine Eggers and her colleagues that
since the current name “causes confusion and is common off-label treatment for PCOS sufferers childless women have inclusive fitness because
a barrier to effective education.” with insulin resistance. they help raise other women’s children. I am
Misnomers aside, the syndrome has some These are all accepted treatments for PCOS, unconvinced.
characteristic symptoms that wreak havoc on the along with the inevitable recommendations about In 2017, another theory started gaining traction
body. One of the hallmarks of PCOS is hyperan- diet and exercise. None of them are perfect when a study led by Paolo Giacobini claimed to
drogenemia, or extremely elevated levels of male remedies, and thus there is no official cure for identify both the cause and the cure for PCOS. In
hormones (testosterone, DHEA and more). the syndrome. Doctors constantly emphasize the experiments on mice, Giacobini’s team traced
Hormone imbalance by itself can cause many importance of lowering weight and body fat, but elevated levels of two hormones, anti-Mullerian
side effects—excess body hair, mood swings, weight loss is nearly impossible because of the hormone (AMH) and gonadotropin-releasing
anxiety and depression, insulin resistance, and unique hormonal and metabolic challenges of hormone (GnRH), that when present in the womb
uncontrolled weight gain, to name a few. In PCOS. caused fetuses to develop PCOS. GnRH is
addition, PCOS women usually have irregular As for the cause of PCOS, the story gets even inhibited by various well-known cancer medica-
ovulation, which can make it hard to get pregnant more convoluted. The syndrome was first de- tions, so by treating adult women doctors could,
regardless of whether the mother is otherwise scribed over 80 years ago by the gynecologists in theory, prevent future generations from
fertile. Irving Stein and Michael Leventhal, yet research- developing PCOS. Researchers and patients
On top of the day-to-day challenges, women ers today are not much closer to figuring out the were temporarily abuzz, but with a big caveat. The
with PCOS are at much higher risk of life-threat- root of the problem. potential cure was only viable for PCOS mice
ening diseases. According to the advocacy group At the Endocrine Society’s annual meeting in without excess body fat, meaning it is not appli-
PCOS Challenge, polycystic ovarian syndrome San Diego this past March, experts brought up cable to most cases of the syndrome.
makes a woman more likely to develop cardio- plastic as a potential aggravator of PCOS. Even with theories like these swirling around
vascular disease or type 2 diabetes. In fact, the Microplastics get into the body from food and the scientific community, there is still no cure, no
NIH predicts that over half of women with PCOS water. Once there, plastic is a major endocrine comprehensive treatment and no definitive cause
will have diabetes or prediabetes by the age of disruptor because it mimics hormones in the for PCOS.
40. These women are also two to four times bloodstream. The Endocrine Society’s official Doctors often fail to diagnose people with this
more likely to develop some types of reproductive scientific statement notes that chemicals found condition—so often that 50 percent of women with
cancers such as endometrial or breast cancer. in common household plastics have been linked PCOS do not know they have it. In a survey
Once I finally learned that I had PCOS, I tried with PCOS in both rats and humans. published in the Journal of Clinical Endocrinology
numerous unsuccessful treatments. I started The fact that genes underlying the syndrome & Metabolism, nearly half of women visited three or
wearing an estrogen patch, which made me so continue to be passed on in such high volume is more doctors and a third of them took more than
depressed that I was lying in bed for most of the puzzling for scientists because PCOS decreases two years before receiving a PCOS diagnosis.

34
 Opinion

The general public and scientific community saying, ‘No way! Me too!’” She decided to make
are equally slow on the uptake. Even though an Instagram page (@pcos_sisterhood) where
more than 10 million American women might suf- she accepts the stories, advice and questions of
fer from PCOS, the NIH research budget is other “PCOS warriors.”
significantly lower for PCOS than other promi- Support groups have been working tirelessly to
nent women’s health issues. gain awareness for the syndrome. The organiza-
Why? For one, PCOS is extremely complicated, tion PCOS Challenge met on Capitol Hill in
possibly without much payoff for big pharmaceu- March for a PCOS Advocacy Day, with Lauren
tical companies. There have been fewer than Ash joining the group to speak to lawmakers. The
1,000 clinical trials ever conducted on PCOS PCOS Awareness Association recently estab-
patients, and only about 10 percent of these lished September as PCOS Awareness Month.
were done by industry. Although there have yet to be major strides in
Likewise, polycystic ovarian syndrome involves a funding and discovery, patients have been active
complex network of scientists, physicians and in making incremental changes and providing
patients. The breadth of different disciplines support to one another. The countless social
involved makes knowledge sharing difficult. The media pages dedicated to PCOS have actually
field is ill defined, and scientists have barely even been able to contribute to the knowledge base
come to a consensus about what the syndrome is. by aggregating data from women with the
PCOS affects women only, yet without the syndrome. For instance, women have uncovered
celebrity status of other women’s health issues a high incidence of PCOS-related binge-eating
like breast cancer. But if the #MeToo movement disorders and have helped to reveal the ineffica-
or International Women’s Day are indicators, cy of some formerly accepted treatment plans.
today’s women are not willing to sit idle. Enter the PCOS is on the rise worldwide and is especially
PCOS sisterhood. problematic in the U.S., where there is an existing
Women from all walks of life are banding infertility crisis. We need to prioritize PCOS
together on social media to support each other research. It significantly impacts every woman
and learn more about their PCOS. Actress and who endures it. If you suffer from polycystic
comedian Lauren Ash, famous for her role in the ovarian syndrome, take this chance to become
NBC show Superstore, accidentally became an part of the sisterhood—and know that you are
activist for PCOS when she announced her not, so to speak, ovary-acting.
diagnosis on Twitter. “It was one of the best
things I ever did,” she said in an interview with
Women’s Health. “Within hours I had thousands
of replies and messages from other women

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