HOW TO SAVE LIVES

Vaccine mandates are controversial. They’re also an effective way to save lives.

By David Leonhardt and Ian Prasad Philbrick | The New York Times
July 23, 2021

How to save lives
Vaccine mandates are controversial. They’re also effective.

• Before Houston Methodist became one of the first hospital systems in the U.S. to mandate Covid-19 vaccines, about 85 percent of its employees were vaccinated. After the mandate, the share rose to about 98 percent, with the remaining 2 percent receiving exemptions for medical or religious reasons, Bloomberg’s Carey Goldberg reported. Only about 0.6 percent of employees quit or were fired.


• Schools — including Indiana University and many private colleges — that require students and workers to get vaccinated have reported extremely high uptake.


• A recent Kaiser Family Foundation survey of Americans who had been opposed to getting vaccinated and later changed their minds found that mandates — or restrictions on the unvaccinated — were one common reason. One 51-year-old man told Kaiser that he began to feel as if he had “limited options without it.”


• The French government will soon require that people show proof of vaccination or a recent negative test to eat at a restaurant, attend a movie or participate in many other activities. After President Emmanuel Macron announced the policy last week, the number of vaccine appointments surged. Italy announced a similar policy yesterday, The Times’s Marc Santora explains.

It’s true that these mandates often generate intense criticism. In France, more than 100,000 people marched to protest Macron’s policy. In the U.S., critics sued, unsuccessfully so far, to stop Indiana University’s mandate. Some Republican politicians have also tried to stop mandates, including Gov. Ron DeSantis of Florida and Gov. Mike DeWine of Ohio.

The mandates are also not 100 percent effective. Some people will receive exemptions, as was the case at Houston Methodist. A small number may forge vaccine records. And some vaccinated people will still contract mild versions of Covid, through so-called breakthrough infections.

But even with the opposition and the exceptions, mandates can play a major role in reducing the spread of Covid and saving lives. That’s especially true now that the Delta variant is fueling a rise in cases. “The takeaway message remains, if you’re vaccinated, you are protected,” Dr. Céline Gounder, an infectious disease specialist, told our colleague Apoorva Mandavilli. “You are not going to end up with severe disease, hospitalization or death.”

A ‘staggering’ success

Covid is a new disease, and the debates over Covid policy can seem new, as well. But they’re often not wholly new. They instead echo longstanding debates. Vaccine mandates fall into this category.

Throughout history, societies have struggled with when and how to require vaccines. Opponents of mandates have argued that individuals should be allowed to make their own health decisions — and bear the consequences: What, they ask, is more personal than deciding whether to inject a medicine into one’s body? Supporters of mandates have replied that society has a duty to protect its citizens, including those who cannot be inoculated (like young children and some immunocompromised people, in the case of Covid) and are therefore put at risk by people who voluntarily refuse vaccines.

For these reasons, vaccine mandates cause intense disputes. But when supporters win the argument, public health has often benefited. Guy Nicolette, an administrator at the University of California, Berkeley, pointed out to The Washington Post that colleges have long required other vaccines, like the one for measles. “It’s staggering how well a mandate works on a college campus,” he said.

Dr. Aaron Carroll, Indiana University’s chief health officer, has noted that the country’s victories over many diseases — including smallpox, polio, mumps, rubella and diphtheria — have depended on vaccine mandates by states or local governments. “That’s how the country achieves real herd immunity,” Carroll wrote in The Times. (In the U.S., a national mandate may be unconstitutional.)

When states and school districts have opted not to require vaccines, a disease can often spread needlessly, Carroll explained. That has been the case with human papillomavirus, a sexually transmitted disease known as HPV that can cause cancer. It’s also been the case with influenza, which kills about 35,000 Americans in a typical flu season.

Covid now seems certain to join influenza and HPV as diseases that American society chooses to accept. But it is a choice. Companies, schools and communities that decide to enact vaccine mandates will almost certainly save American lives by doing so.

Mark Barnes, a former health official in New York City, told Bloomberg that he expected the number of these mandates to grow in coming months. “We’re going to see more vaccine mandates by large organizations of all kinds,” he predicted.

Link to original article:

https://www.nytimes.com/live/2021/07/23/world/covid-variant-vaccine-updates#vaccine-mandates-are-controversial-theyre-also-effective

"40 years ago, the first cases of AIDS were reported in the US"

As a gay man who was 18 when the AIDS pandemic started, this article and the anniversary itself brought back a lot of memories and sadness and anger. And our recent COVID pandemic strongly resonated for me, and reminded me of the fear that was in the air in my community for a decade and more. I feel like I held my breath from anxiety for about fifteen years, from 1981 until the mid-90s, so it is comical for me to see how people this last year kicked and screamed for having to wear a mask and practice physical distancing, while I have a living memory of all of us in my community having to alter our behavior, and wear something that was uncomfortable that we did not want to wear, and live with fear while not knowing exactly how the virus was spread in the early days, and watch as scores of wonderful, talented, valuable men died horribly. Please, I've done this exercise already. A mask is nothing.

40 years ago, the first cases of AIDS were reported in the US

By Harmeet Kaur, CNN

Updated 1:01 PM ET, Sat June 5, 2021

(CNN) On June 5, 1981, a curious report appeared in the Center for Disease Control's weekly public health digest: Five young, gay men across Los Angeles had been diagnosed with an unusual lung infection known as Pneumocystis carinii pneumonia (PCP) -- and two of them had died.

It was the first time that acquired immunodeficiency syndrome (AIDS) -- the devastating advanced-stage of HIV infection that would go on to claim the lives of more than 32 million people globally -- was reported in the US.

Days after the initial report hit the newspapers, the CDC learned of many more such cases in gay men. Not only did those men have PCP, they also had other secondary infections, among them a rare and aggressive cancer known as Kaposi's sarcoma (KS).

Saturday marks the 40th anniversary of the nation's first reported cases of AIDS. More than 700,000 people in the US have died of the disease since then -- and though medical advancements have drastically changed the prognosis for HIV/AIDS patients, there remains to this day no cure.

President Joe Biden released a statement marking the anniversary and noting the work the US has done to combat the illness at home and around the globe.

About a month after that first report, the write-up in the CDC's Morbidity and Mortality Weekly Report counted 26 gay men across New York and California with those diagnoses -- a number that would increase exponentially.

He said he's asked Congress to provide $670 million to fight new HIV cases by increasing treatment, expanding the use of preexposure prophylaxis and ensuring equitable access to treatment.

"In honor of all those we have lost and all those living with the virus -- and the selfless caregivers, advocates, and loved ones who have helped carry the burden of this crisis -- we must rededicate ourselves to reducing HIV infections and AIDS-related deaths," the President said in the statement.

"We must continue empowering researchers, scientists, and health care providers to ensure equitable access to prevention, care, and treatment in every community -- particularly for communities of color and the LGBTQ+ community."

Here's a look back at how the AIDS epidemic unfolded.

Activists drove the early response

The early years of the AIDS epidemic were an uncertain and unsettling time.

LGBTQ communities were losing friends and loved ones to the disease, one after another -- with little idea as to how or why. All the while, it seemed society had turned a blind eye.

"Can you imagine what it must be like if you had lost 20 of your friends in the last 18 months?" Larry Kramer, famed AIDS activist and co-founder of the Gay Men's Health Crisis, said in a 1983 interview with the "Today" show.

"No cause, no cure, people in hospitals. It's a very angry community."

Gary Walsch, who was living with AIDS, leans on a friend's shoulder before a candlelight vigil in San Francisco in 1983.
The vigil was held to bring attention to the AIDS crisis affecting the gay community.

President Ronald Reagan's administration paid little attention to the epidemic, with four years going by before Reagan made a public mention of AIDS.

Exchanges between Reagan's press secretary and reporters in 1982 and 1983 indicate that the nation's top officials and mainstream society viewed the disease as a joke, and not an issue of great concern.

That stemmed from the perception of AIDS as a "gay plague" -- a condition thought to be tied to the lifestyles and behaviors of gay men, even though cases had also been reported in women, infants, those with hemophilia and people who injected drugs.

In a recently published interview with the New England Journal of Medicine, AIDS researcher Alexandra Levine spoke of "the horror of watching as society as a whole turned its back on this suffering, the horror of watching as many of my own colleagues refused to help, refused to care, refused to act as the professionals they were supposed to be."

Demonstrators in New York in 1987 hold hands during a moment of silence
while demanding more government action in the fight against AIDS.

As politicians and government entities proved slow to act, activists took matters into their own hands, doing what they could to combat homophobia and stigma and make sure their communities received the public health information they needed.

Among those efforts was the 1982 pamphlet titled, "How to Have Sex in an Epidemic: One Approach."

Created by Michael Callen and Richard Berkowitz, it was one of the first times that gay men were advised to use condoms during sex with other men, according to an exhibit by the National Library of Medicine. Though the two are widely considered to be pioneers of safe sex, many in the gay community at the time criticized their work as "sex negative."

Black gay and lesbian organizations, meanwhile, fought back through poster campaigns against misconceptions that AIDS primarily affected White gay men.

Scientists struggled to understand AIDS

In the early '80s, HIV/AIDS was considered a death sentence.

Scientists and physicians were struggling to understand what caused the disease and how it spread -- making the process of finding a treatment all the more challenging.

Dr. Anthony Fauci, who became director of the National Institute of Allergy and Infectious Diseases at the height of the AIDS epidemic, refers to that period of his career as the "dark years."

"I went from a person who was seeing patients with other diseases and developing cures and adequate therapies for them in the early part of my career, to every day taking care of people who inevitably were going to die, usually within a short period of time," he said in a recent interview with CNN.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases,
talks to his team about HIV/AIDS during a meeting in 1990.

It was an experience shared by many clinicians who cared for early AIDS patients: Feeling as though there was nothing they could do to stop the suffering.

"You were really putting Band-Aids on hemorrhages for a while," Fauci added.

In the absence of viable treatments, Gerald Friedland, who worked on early AIDS cases at Montefiore Medical Center in the Bronx, recalled how he focused on empathy.

"The onslaught of death and dying of young men and women was beyond 'usual professional commitments' and terribly hard," he said in a recently published interview with the New England Journal of Medicine. "But I learned how to become skilled at providing people with a 'decent death.'"

Therapies came in the late '80s and '90s

The tide started to turn in the late '80s and '90s, as more effective therapies became available and transformed what it meant for an individual to live with HIV.

On March 19, 1987, the Food and Drug Administration approved an antiretroviral drug known as AZT to treat HIV infection.

Another important change also happened that year.

After pressure from activists fighting for their community's survival, the FDA issued new regulations around clinical drug trials -- making it possible for patients to access experimental, potentially life-saving therapies without having to wait years for official agency approval.

Princess Diana visited patients with AIDS at a hospital in Rio de Janeiro on April 25, 1991.
Her advocacy and compassion for people with HIV/AIDS helped destigmatize the disease and change public perception.

By the late '80s and '90s, public perception of HIV/AIDS was also starting to shift -- thanks in part to high-profile activists and celebrities.

One of those activists was Ryan White, an Indiana teenager who contracted AIDS in 1984 through contaminated needles while being treated for hemophilia. He experienced discrimination in his community after his diagnosis, even being denied entry to his middle school. As White spoke publicly about his experiences and his family challenged his treatment in court, he became one of the early public faces of the disease.

Princess Diana was also instrumental in shattering stigmas and myths around the illness, famously photographed visiting HIV/AIDS patients in hospital wards and shaking hands with them without gloves.

And in 1991, NBA star Earvin "Magic" Johnson revealed he had been diagnosed with HIV -- his identity as a straight, Black man helped demonstrate that anyone could contract the disease.

Another scientific breakthrough came in 1996, when the FDA approved the first protease inhibitors. That development brought into use what's known as highly active antiretroviral therapy (HAART), turning HIV/AIDS from a fatal diagnosis to a controllable condition.

"We now are giving drugs to people who are living with HIV -- not only do these save their lives and give them essentially a normal lifespan, but you can prevent them from infecting other people," Fauci told CNN on June 1.

Richard Chaisson, a physician who helped lead the fight against AIDS at Johns Hopkins University Hospital in the late '80s and '90s, described the feeling to the New England Journal of Medicine.

"Desperation changed to hope. Hope changed to belief, and belief changed to joy," he recalled. "So many patients returned home from the ship of the doomed and went back to living near-normal lives."

Visitors and volunteers walk on the 21,000-panel AIDS Memorial Quilt on October 10, 1992 in Washington.

In 2010, researchers announced yet another exciting development: A study had found that taking a daily dose of HIV drugs reduced the risk of infection for men who had sex with other men. In 2012, the FDA approved the use of pre-exposure prophylaxis (PrEP) for adults at high risk of infection -- one of the most significant milestones of the epidemic.

As new treatments for HIV/AIDS have made the diagnosis more manageable and even help prevent infection, public health challenges remain.

About 1.2 million people in the US were living with HIV at the end of 2018, according to the CDC.

There are disparities in access to treatment, and Black and Hispanic Americans are disproportionately affected by HIV. Resistance to HIV/AIDS medications has also become increasingly common.

Some researchers and clinicians began to shift their attention and efforts elsewhere after the toll of the early years, according to the New England Journal of Medicine. And despite the US setting a goal in 1997 to find an HIV vaccine within 10 years, four decades later, there is still no vaccine or cure.

Link to original article: 

https://www.cnn.com/2021/06/05/health/aids-40-anniversary-first-reported-cases-trnd/index.html

Why you can't compare Covid-19 vaccines: What a vaccine's "efficacy rate" actually means

Nicely and clearly explained: why all the vaccines will work...if people will just take them!

https://www.vox.com/

Reasons To Be Optimistic About The Vaccine

We explain why the vaccine news is better than you may think.

by David Leonhardt
January 18, 2021 for New York Times

‘We’re underselling the vaccine’
Early in the pandemic, many health experts — in the U.S. and around the world — decided that the public could not be trusted to hear the truth about masks. Instead, the experts spread a misleading message, discouraging the use of masks.

Their motivation was mostly good. It sprung from a concern that people would rush to buy high-grade medical masks, leaving too few for doctors and nurses. The experts were also unsure how much ordinary masks would help.

But the message was still a mistake.

It confused people. (If masks weren’t effective, why did doctors and nurses need them?) It delayed the widespread use of masks (even though there was good reason to believe they could help). And it damaged the credibility of public health experts.

“When people feel as though they may not be getting the full truth from the authorities, snake-oil sellers and price gougers have an easier time,” the sociologist Zeynep Tufekci wrote early last year.

Now a version of the mask story is repeating itself — this time involving the vaccines. Once again, the experts don’t seem to trust the public to hear the full truth.

This issue is important and complex enough that I’m going to make today’s newsletter a bit longer than usual. If you still have questions, don’t hesitate to email me at themorning@nytimes.com.

‘Ridiculously encouraging’ 

Right now, public discussion of the vaccines is full of warnings about their limitations: They’re not 100 percent effective. Even vaccinated people may be able to spread the virus. And people shouldn’t change their behavior once they get their shots.

These warnings have a basis in truth, just as it’s true that masks are imperfect. But the sum total of the warnings is misleading, as I heard from multiple doctors and epidemiologists last week.

“It’s driving me a little bit crazy,” Dr. Ashish Jha, dean of the Brown School of Public Health, told me.

“We’re underselling the vaccine,” Dr. Aaron Richterman, an infectious-disease specialist at the University of Pennsylvania, said.

“It’s going to save your life — that’s where the emphasis has to be right now,” Dr. Peter Hotez of the Baylor College of Medicine said.

The Moderna and Pfizer vaccines are “essentially 100 percent effective against serious disease,” Dr. Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia, said. “It’s ridiculously encouraging.”

The details

Here’s my best attempt at summarizing what we know:

*The Moderna and Pfizer vaccines — the only two approved in the U.S. — are among the best vaccines ever created, with effectiveness rates of about 95 percent after two doses. That’s on par with the vaccines for chickenpox and measles. And a vaccine doesn’t even need to be so effective to reduce cases sharply and crush a pandemic.

*If anything, the 95 percent number understates the effectiveness, because it counts anyone who came down with a mild case of Covid-19 as a failure. But turning Covid into a typical flu — as the vaccines evidently did for most of the remaining 5 percent — is actually a success. Of the 32,000 people who received the Moderna or Pfizer vaccine in a research trial, do you want to guess how many contracted a severe Covid case? One.

*Although no rigorous study has yet analyzed whether vaccinated people can spread the virus, it would be surprising if they did. “If there is an example of a vaccine in widespread clinical use that has this selective effect — prevents disease but not infection — I can’t think of one!” Dr. Paul Sax of Harvard has written in The New England Journal of Medicine. (And, no, exclamation points are not common in medical journals.) On Twitter, Dr. Monica Gandhi of the University of California, San Francisco, argued: “Please be assured that YOU ARE SAFE after vaccine from what matters — disease and spreading.”

*The risks for vaccinated people are still not zero, because almost nothing in the real world is zero risk. A tiny percentage of people may have allergic reactions. And I’ll be eager to see what the studies on post-vaccination spread eventually show. But the evidence so far suggests that the vaccines are akin to a cure.

Offit told me we should be greeting them with the same enthusiasm that greeted the polio vaccine: “It should be this rallying cry.”

The costs of negativity

Why are many experts conveying a more negative message?

Again, their motivations are mostly good. As academic researchers, they are instinctively cautious, prone to emphasizing any uncertainty. Many may also be nervous that vaccinated people will stop wearing masks and social distancing, which in turn could cause unvaccinated people to stop as well. If that happens, deaths would soar even higher.

But the best way to persuade people to behave safely usually involves telling them the truth. “Not being completely open because you want to achieve some sort of behavioral public health goal — people will see through that eventually,” Richterman said. The current approach also feeds anti-vaccine skepticism and conspiracy theories.

After asking Richterman and others what a better public message might sound like, I was left thinking about something like this:

We should immediately be more aggressive about mask-wearing and social distancing because of the new virus variants. We should vaccinate people as rapidly as possible — which will require approving other Covid vaccines when the data justifies it.

People who have received both of their vaccine shots, and have waited until they take effect, will be able to do things that unvaccinated people cannot — like having meals together and hugging their grandchildren. But until the pandemic is defeated, all Americans should wear masks in public, help unvaccinated people stay safe and contribute to a shared national project of saving every possible life.

Link to original article:
https://www.nytimes.com/2021/01/18/briefing/donald-trump-pardon-phil-spector-coronavirus-deaths.html

New Study Suggests Connections Between Homophobia And Mental Disorders

Just can't resist posting this article about an Italian study on homophobia. I couldn't agree with it more. We have always known this to be true, but it is nice to now have scientific proof to back it up.


New Study Suggests Connections Between Homophobia And Mental Disorders
BY ZACK FORD SEP 11, 2015 3:17PM

Homosexuality was long derided as a mental disorder — and being transgender often still is — but a new study suggests that it might be more likely that it’s actually homophobia that is a sign of mental disorder.

Researchers working with the Italian Society of Andrology and Sexual Medicine evaluated the mental health of 560 Italian University students to see what connections could be found between their psychological traits and their propensity for homophobia. Indeed, they found that aspects of psychoticism and immature defense mechanisms were significant predictors for homophobic attitudes.

“We found that psychoticism represented an important risk factor for homophobia, demonstrating that pathologic personality traits are involved in homophobic attitudes,” the study explains. Psychoticism embodies various characteristics, but above all, “severe psychopathologic conditions, such as delusion, isolation, and interpersonal alienation, but also hostility and anger.” Homophobia could be partially linked by “pathologic trait of personality,” meaning that various disorders of relationship and thought could be predictive of homophobia.

Immature defense mechanisms similarly predicted homophobic attitudes. These are coping mechanisms activated during states of distress and anxiety and include behaviors like projection, acting out, isolation, denial, passive aggressiveness, and displacement. “Our data revealed that immature defense mechanisms predict homophobia, highlighting that a negative attitude toward homosexuals is influenced once again by dysfunctional aspects of personality.”

While these aggressive personality traits were linked with homophobia, depression had the opposite effect. “Subjects with depression have a lower risk to develop homophobic behavior,” in part because it seems they were less likely to “perceive external reality as a threat and project their anger.”

The study also found that gender was a significant predictor of homophobia. “Men are more homophobic than women,” and in particular, they demonstrated a tendency toward more negative attitudes and “a major risk of aggressive behavior or acting out toward homosexuals.”

Speaking to Medical Daily, lead researcher Dr. Emmanuele A. Jannini suggested, “After discussing for centuries if homosexuality is to be considered a disease, for the first time we demonstrated that the real disease to be cured is homophobia, associated with potentially severe psychopathologies.”

Homophobic attitudes have previously been linked to unacknowledged same-sex attractions and dying younger.


Link to original article on Think Progress:
http://thinkprogress.org/lgbt/2015/09/11/3700857/homophobia-mental-disorder/

Antibiotic Breakthrough

Oh, by the way, did you see this story about a new breakthrough in antibiotics? For a while now, we have been hearing from the scientific community about how antibiotics were abused over these last many decades and as a result, many classes of the drug no longer work on new, resistant bacteria. This very important discovery could change everything and it is great news!

From BBC:

Antibiotics: US discovery labelled 'game-changer' for medicine
By James Gallagher
Health editor, BBC News website

The decades-long drought in antibiotic discovery could be over after a breakthrough by US scientists.

Their novel method for growing bacteria has yielded 25 new antibiotics, with one deemed "very promising". The last new class of antibiotics to make it to clinic was discovered nearly three decades ago.

The study, in the journal Nature, has been described as a "game-changer" and experts believe the antibiotic haul is just the "tip of the iceberg".

The heyday of antibiotic discovery was in the 1950s and 1960s, but nothing found since 1987 has made it into doctor's hands. Since then microbes have become incredibly resistant. Extensively drug-resistant tuberculosis ignores nearly everything medicine can throw at it.

The researchers, at the Northeastern University in Boston, Massachusetts, turned to the source of nearly all antibiotics - soil. This is teeming with microbes, but only 1% can be grown in the laboratory. The team created a "subterranean hotel" for bacteria. One bacterium was placed in each "room" and the whole device was buried in soil. It allowed the unique chemistry of soil to permeate the room, but kept the bacteria in place for study.

The scientists involved believe they can grow nearly half of all soil bacteria. Chemicals produced by the microbes, dug up from one researcher's back yard, were then tested for antimicrobial properties.

The lead scientist, Prof Kim Lewis, said: "So far 25 new antibiotics have been discovered using this method and teixobactin is the latest and most promising one.

"[The study shows] uncultured bacteria do harbour novel chemistry that we have not seen before. That is a promising source of new antimicrobials and will hopefully help revive the field of antibiotic discovery."

Tests on teixobactin showed it was toxic to bacteria, but not mammalian tissues, and could clear a deadly dose of MRSA in tests on mice.

The researchers also believe that bacteria are unlikely to develop resistance to teixobactin. It targets fats which are essential for building the bacterial cell wall, and the scientists argue it would be difficult to evolve resistance. "Here is an antibiotic that essentially evolved to be free of resistance," said Prof Lewis. "We haven't seen that before. "It has several independent different tricks that minimise resistance development."

There are limits to the discovery of the antibiotic teixobactin, which has yet to be tested in people. It works on only Gram-positive bacteria; this includes MRSA and mycobacterium tuberculosis. It cannot penetrate the extra layer of protection in Gram-negative bacteria such as E. coli. But even if their method does mark a new era of antibiotic discovery there are big questions. Sir Alexander Fleming, who discovered penicillin, warned of the dangers of resistance back in his Nobel prize speech in 1945. Yet even now prescriptions in England are rising, with half deemed "inappropriate" and contributing to the problem.

But can we be trusted with new antibiotics? Or will we make the same mistakes again?

http://www.bbc.com/news/health-30657486

Bio-Computers!

This reminds me of the David Cronenberg film "eXistenZ"...

This incredible piece of scientific news yesterday comes from Stanford School of Medicine. The possibilities are mind-boggling.

Biological transistor enables computing within living cells, study says
BY ANDREW MYERS

When Charles Babbage prototyped the first computing machine in the 19th century, he imagined using mechanical gears and latches to control information. ENIAC, the first modern computer developed in the 1940s, used vacuum tubes and electricity. Today, computers use transistors made from highly engineered semiconducting materials to carry out their logical operations.

And now a team of Stanford University bioengineers has taken computing beyond mechanics and electronics into the living realm of biology. In a paper published March 28 in Science, the team details a biological transistor made from genetic material — DNA and RNA — in place of gears or electrons. The team calls its biological transistor the “transcriptor."

“Transcriptors are the key component behind amplifying genetic logic — akin to the transistor and electronics,” said Jerome Bonnet, PhD, a postdoctoral scholar in bioengineering and the paper’s lead author.

The creation of the transcriptor allows engineers to compute inside living cells to record, for instance, when cells have been exposed to certain external stimuli or environmental factors, or even to turn on and off cell reproduction as needed.

“Biological computers can be used to study and reprogram living systems, monitor environments and improve cellular therapeutics,” said Drew Endy, PhD, assistant professor of bioengineering and the paper’s senior author.

In electronics, a transistor controls the flow of electrons along a circuit. Similarly, in biologics, a transcriptor controls the flow of a specific protein, RNA polymerase, as it travels along a strand of DNA.

“We have repurposed a group of natural proteins, called integrases, to realize digital control over the flow of RNA polymerase along DNA, which in turn allowed us to engineer amplifying genetic logic,” said Endy.

Using transcriptors, the team has created what are known in electrical engineering as logic gates that can derive true-false answers to virtually any biochemical question that might be posed within a cell.

They refer to their transcriptor-based logic gates as “Boolean Integrase Logic,” or “BIL gates” for short.

Transcriptor-based gates alone do not constitute a computer, but they are the third and final component of a biological computer that could operate within individual living cells.

Despite their outward differences, all modern computers, from ENIAC to Apple, share three basic functions: storing, transmitting and performing logical operations on information.

Last year, Endy and his team made news in delivering the other two core components of a fully functional genetic computer. The first was a type of rewritable digital data storage within DNA. They also developed a mechanism for transmitting genetic information from cell to cell, a sort of biological Internet.

It all adds up to creating a computer inside a living cell.

Digital logic is often referred to as “Boolean logic,” after George Boole, the mathematician who proposed the system in 1854. Today, Boolean logic typically takes the form of 1s and 0s within a computer. Answer true, gate open; answer false, gate closed. Open. Closed. On. Off. 1. 0. It’s that basic. But it turns out that with just these simple tools and ways of thinking you can accomplish quite a lot.

“AND” and “OR” are just two of the most basic Boolean logic gates. An “AND” gate, for instance, is “true” when both of its inputs are true — when “a” and “b” are true. An “OR” gate, on the other hand, is true when either or both of its inputs are true.

In a biological setting, the possibilities for logic are as limitless as in electronics, Bonnet explained. “You could test whether a given cell had been exposed to any number of external stimuli — the presence of glucose and caffeine, for instance. BIL gates would allow you to make that determination and to store that information so you could easily identify those which had been exposed and which had not,” he said.

By the same token, you could tell the cell to start or stop reproducing if certain factors were present. And, by coupling BIL gates with the team’s biological Internet, it is possible to communicate genetic information from cell to cell to orchestrate the behavior of a group of cells.

“The potential applications are limited only by the imagination of the researcher,” said co-author Monica Ortiz, a PhD candidate in bioengineering who demonstrated autonomous cell-to-cell communication of DNA encoding various BIL gates.

To create transcriptors and logic gates, the team used carefully calibrated combinations of enzymes — the integrases mentioned earlier — that control the flow of RNA polymerase along strands of DNA. If this were electronics, DNA is the wire and RNA polymerase is the electron.

“The choice of enzymes is important,” Bonnet said. “We have been careful to select enzymes that function in bacteria, fungi, plants and animals, so that bio-computers can be engineered within a variety of organisms.”

On the technical side, the transcriptor achieves a key similarity between the biological transistor and its semiconducting cousin: signal amplification.

With transcriptors, a very small change in the expression of an integrase can create a very large change in the expression of any two other genes.

To understand the importance of amplification, consider that the transistor was first conceived as a way to replace expensive, inefficient and unreliable vacuum tubes in the amplification of telephone signals for transcontinental phone calls. Electrical signals traveling along wires get weaker the farther they travel, but if you put an amplifier every so often along the way, you can relay the signal across a great distance. The same would hold in biological systems as signals get transmitted among a group of cells.

“It is a concept similar to transistor radios,” said Pakpoom Subsoontorn, a PhD candidate in bioengineering and co-author of the study who developed theoretical models to predict the behavior of BIL gates. “Relatively weak radio waves traveling through the air can get amplified into sound.”

To bring the age of the biological computer to a much speedier reality, Endy and his team have contributed all of BIL gates to the public domain so that others can immediately harness and improve upon the tools.

“Most of biotechnology has not yet been imagined, let alone made true. By freely sharing important basic tools everyone can work better together,” Bonnet said.

The research was funded by the National Science Foundation and the Townshend Lamarre Foundation.

Information about Stanford’s Department of Bioengineering, which also supported the work, is available at http://bioengineering.stanford.edu. The department is jointly operated by the School of Engineering and the School of Medicine.

Original story at Stanford Medicine website:
http://med.stanford.edu/ism/2013/march/bil-gates.html