Scientists Make Progress in Growing Organs From Stem Cells

Liver buds and brain organoids are among this year's life-saving advances in growing spare human parts.

Liver Buds to the Rescue

Some 16,000 ailing Americans are waiting to receive a liver transplant. But due to a shortage of viable livers, it’s likely that fewer than 7,000 transplants will be performed in 2013. In Japan, where the shortage is worse, the number of people in need of new livers is 10 times as great as the number of deceased donors who could provide one. 

That gap motivated stem cell biologist Takanori Takebe and his colleagues at the Department of Regenerative Medicine at Yokohama City University in Japan to find an alternate solution. This year they succeeded in generating mini-livers, or liver buds, from stem cells that were taken from human skin and reprogrammed to an embryonic state. (Embryonic stem cells are notable because they can morph into virtually any cell type in the body.) 

When mixed with two other types of cells, the fabricated primitive liver cells organized themselves into three-dimensional structures, complete with blood vessels. In effect, Takebe’s team re-created the process by which a human embryo begins to form a functioning liver. 

Transplanted into a mouse, the human liver buds, about 5 millimeters long, exhibited many functions of the mature organ, such as metabolizing sugars and drugs. When the scientists disabled the mouse’s own liver, the human buds kept the animal alive for two months. A person with liver failure would require an infusion of “tens of thousands” of liver buds, Takebe says. 

Until the buds can be generated from the skin of each individual patient, recipients will have to rely on immune-suppressing drugs to avoid rejection, just as they would with the transplant of an entire organ. Replacement liver buds might be available to human patients in a decade or less. — Jeff Wheelwright

Growing Brain Organoids

Scientists can’t yet grow spare parts of the human brain to fix neurological injuries or defects, but they have recently used stem cells to create brain organoids, formations of cells that mimic some of the brain’s regions. A team led by neuroscientist Jürgen Knoblich of Austria’s Institute of Molecular Biotechnology developed the organoids to help them simulate disease. 

Two types of stem cells were used to produce the mini-brains: embryonic cells and adult cells that had been reprogrammed to a starter state. The cells were put into a special culture and then suspended in a gel and stimulated by nutrients, all geared to turn them into neurons like those found in the cortex. 

The neurons literally “self-organized,” according to Knoblich, and after several weeks formed three-dimensional structures about one-tenth of an inch in diameter.

“If you zoom out and look at the whole, it’s not a brain,” Knoblich says. “But our cultures contain individual brain regions that have a functional relationship with one another.” Besides the dorsal cortex, researchers were able to grow, among other regions, parts of the ventral forebrain, which makes neurons that connect to the cortex, and the choroid plexus, which generates spinal fluid. 

In their most impressive experiment, the scientists derived organoids from the skin cells of a person affected by microcephaly. This genetic disorder causes a drastic reduction in brain size and stature. The microcephalic organoids were smaller than the organoids grown from healthy people, apparently because the patient’s stem cells had divided too early and became depleted. 

“What our organoids are good for is to model the development of the brain and to study anything that causes a defect in development,” Knoblich says. For example, by taking neural stem cells from a patient with schizophrenia, researchers might turn back the clock and track the onset of the condition in an organoid. Knowing how schizophrenia starts might help prevent it. — Jeff Wheelwright

Human Stem Cells Made From Eggs

It was 1996 when biologists first fused a mammalian skin cell with an egg cell, cloning Dolly the sheep. That was the start of the race to make a human embryo the same way. The method, called somatic cell nuclear transfer (SCNT), replaces the DNA in an egg cell’s nucleus with the genetic material from the nucleus of a skin cell, then tricks the egg cell to start dividing as if it had been fertilized with sperm. 

The result: an embryo that is an almost perfect genetic copy of the skin cell donor. In humans, the goal of SCNT is “nonreproductive cloning” — making embryos, then removing stem cells from the embryo and cultivating them to grow into tissues that could cure diseases, replace organs and heal injuries.

But getting eggs to act like embryos turned out to be far more difficult in humans than in sheep. It wasn’t until 2013 that Shoukhrat Mitalipov of the Oregon Health and Science University finally made SCNT work in humans, through careful tweaking and fine-tuning based on experiments with more than 1,000 rhesus monkey eggs. His final protocol requires a few dozen steps. 

“It’s a very complex procedure,” he says. Among Mitalipov’s secrets: stimulating reprogramming activity by priming the eggs with caffeine and by precisely dosing them with chemicals that coil and uncoil DNA’s twisted strands, and applying a gentle electric jolt to get the egg to begin dividing. (An embryo created this way will not develop into a fetus.) 

There are now other methods to make stem cells, but those made via SCNT have unique value because they are genetic copies of the living person who donated the skin cells (other methods either use foreign cells or involve genetic reprogramming). Thus, replacement tissues made from them shouldn’t trigger the immune system rejection that dooms many transplants. 

Making purpose-built tissues may be far in the future, because figuring out the exact recipes to turn cells into functioning bone, heart or spinal cord will take time. But Mitalipov’s triumph has big near-term benefits in giving researchers a new tool to understand all the details of how stem cells grow, divide and differentiate, says Larry Goldstein, director of the University of California San Diego Stem Cell Program: “It’s great science.” — Kat McGowan

Edward Snowden, the NSA, and the Never-Ending End of Privacy

The unprecedented government surveillance that surfaced in the summer brought the perennial clash between technology and privacy to a new level.

Samuel Warren and Louis Brandeis, writing in the Harvard Law Review, expressed concern over privacy infringements threatened by new technology: “Recent inventions and business methods call attention to the next step which must be taken for the protection of the person, and for securing to the individual . . . the right ‘to be let alone,’ ” they wrote. 

The year was 1890, and the inventions Warren and Brandeis cited were “instantaneous photographs” and devices for “reproducing scenes or sounds.” Those innovations now sound quaint, but the concerns they raised are fresher than ever. 

In 2013, former National Security Agency contractor Edward Snowden created an international firestorm when he leaked top-secret documents detailing the U.S. government’s surveillance activities. In addition to providing details on foreign eavesdropping of private citizens and leaders, the government effort has included PRISM, a massive data surveillance program that gathers Internet communications from open sources and a variety of private companies to track people’s connections. 

Americans still have legal protection for their most private communications — what they say and write to other American citizens — but how important is that protection in light of the government’s vast ability to collect data about almost every aspect of people’s daily activities?

As the scope of Snowden’s revelations expands by the day, the picture looks increasingly ominous: The NSA collects records of phone calls going back years. It patrols Internet cloud services. Your Facebook chats, your Skype calls, your Gmail messages can all be monitored.

The ironies are rich. Warren and Brandeis fretted over a shutterbug snapping pictures of an unsuspecting woman, while Sprint’s recent iPhone 5 commercial touts a “billion roaming photojournalists uploading the human experience.”

The introduction of Google Glass, the wearable computer with a head-mounted display that lets users record everything, may make personal surveillance nearly ubiquitous.

Technology has long driven fears. In the mid-1970s, Congress held a hearing to discuss ARPANET, a Pentagon project that some considered a frightening assault on privacy because it could create vast files on individuals by networking computers. Those concerns were soon eclipsed by public support for ARPANET’s successor: the Internet.

In 2002, the Pentagon took heat over the Total Information Awareness program, which New York Times columnist William Safire called a “supersnoop’s dream” that would create a “computerized dossier on your private life” based traffic and has access to most of the major email, chat and on commercial and government information. 

When the program was canceled, the public largely lost interest despite reports that it merely moved to the covert world. But while data mining a decade ago was concerned about cross-matching, say, travel reservations with immigration records, what Snowden revealed in 2013 was something far more ambitious. 

The documents demonstrated the NSA can and often does decrypt, hack and access almost any device or service used by private citizens.

What has enabled the government’s increasing ability to monitor our lives is not exotic spy technology but commercial technology embraced by Americans. We upload pictures to Instagram, provide information about friends and family to Facebook and store private letters on Gmail.

Even those who don’t broadcast their thoughts on Twitter provide reams of data mopped up by commercial companies. News read online is logged, purchases are tracked, and website visits are recorded. 

There is, thanks to the spread of Internet access and smartphones, more information on our daily lives than could have been imagined even a decade ago: We Google our aches and pains and stalk our former lovers, leaving a virtual trail of our daily movements simply by carrying a cell phone.

That data, recorded by commercial companies — be they cell phone and Internet service providers or your favorite social media — can be intercepted, hacked or secretly requested by the government. People may think they have control over personal information by, say, disabling location services on an app, but that’s not always the case, says Kalev Leetaru, a fellow in residence at Georgetown University and an expert in big data. 

“We never really think about it with a cell phone,” says Leetaru, pointing to the ability to trace a user’s location by tracking cell towers, essentially “leaving digital bread crumbs wherever you go.”

Today’s surveillance issues emerge from a clash of technology and policy. Companies encourage us to store our music, pictures and email in the cloud, but most people aren’t aware of what this means for privacy. A letter sitting in your home is covered by the Fourth Amendment protection against unreasonable search and seizure, but that same letter in your Gmail, if sent and read over six months ago, is not afforded the same protection.

Similarly, even when the content of our communication is protected by law, Snowden has demonstrated that metadata — the who, what, where and when of communications, encoded in our messages, calls and online activity — is fair game. 

The NSA may not be allowed by law to listen to your call to a friend, but the government can collect information about how many times you called that friend, how long the calls lasted and on which dates. And then they can use data mining to cross-match the relationship to your friend’s friends, essentially tracking your entire social network, like an involuntary version of Facebook.

One of the problems, says Paul Rosenzweig, a former Department of Homeland Security official and expert in data mining issues, is that people focus on content — what they actually say on the phone or in an email. What Snowden has brought to public debate is that as technology has expanded the amount of metadata being generated, the debate itself may need to change. 

“Metadata is more robust and detailed than content,” says Rosenzweig. “It may be we’re reaching a point where metadata is content. That would be a very big sea change.”