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Applied Biotechnology, Ethics, Fertility, Genetics, Medicine and Society, Parenting

Medical practice, patents, and “custom children”: A look at the future of reproductive medicine

Medical practice, patents, and "custom children": A look at the future of reproductive medicine

black and white baby

Recently, 23andMe, the direct-to-consumer genetic diagnostic company, announced it had been issued a patent for a system of applying genetic testing – and, consequently, genetic screening – to egg and sperm banks. (Full disclosure: I am a 23andMe consumer.) In brief, 23andMe’s system involves receiving information from would-be parents about which traits they’d like their children to possess, and then determining which egg or sperm donations would be the best genetic fit to create those children. While egg and sperm banks currently allow would-be parents to sort through the traits of egg and sperm donors – such as race, height, athleticism, and even SAT scores – 23andMe’s patent envisions applying statistics to the genetic profiles of both donors and recipients to create something of a “custom child.”

To be clear, 23andMe’s patent is just that: a patent. There’s no indication that 23andMe has put its system into implementation or even made a serious business attempt to do so. Nonetheless, others have discussed the ethics behind 23andMe’s system, the propriety of the patent, and 23andMe’s ultimate plans with its intellectual property. But one question I’m particularly intrigued by is: Assuming 23andMe’s vision comes to pass – one easily within our technological if not cultural grasp – what will the future of reproductive medicine look like?

First, it would be a tremendous boon to the medical care of those “custom children,” as it would likely eliminate many common gene variants responsible for disease. These range from simple, single-gene diseases, such as Marfan syndrome, spinal muscular atrophy, and Huntington’s disease, to complex multi-gene diseases, such as breast and ovarian cancer, for which certain gene variants play a significantly large etiological role. And, as is demonstrated by the list above, these diseases need not be limited to the traditional fatal-in-childhood diseases, such as Tay-Sachs or Niemann-Pick syndrome, that are currently screened for. Rather, as is the case with Huntington’s disease, which only afflicts its sufferers in mid-life, the method could quash those genetic variants that cause disease through all stages of life.

Second, the robustness of the technology behind the 23andMe patent may spur demand for  in vitro fertilization. Few couples capable of conceiving without technological intervention undergo IVF today. But some of that is ultimately a matter of choice: that there are few benefits to be had through IVF relative to natural conception. The possibilities for customization described in the 23andMe patent – choosing a child possessing hundreds of hand-picked traits, from curly hair down to caffeine metabolism – may, at least for some, change that calculus. The potential for customization drives demand in other enterprises – smartphones, cheeseburgers, insurance policies, even house paint. It’s culturally naïve to think it will have no effect on reproductive technology.

And lastly, I suppose it also means that reproductive medicine will increasingly come within the ambit of patent law. Since its inception in the 1970s, IVF has largely been free of the destructive and costly patent litigation seen in other industries, such as smartphones. If 23andMe’s patent is indicative of a future norm, reproductive medicine may very well operate in a world controlled by licensing agreements and cowered by threats of litigation. Whether one is entitled to a particular genetic screening method may have little to do with the quality of the institution – as it generally does now – but more with whether an institution has agreed to pay the appropriate royalties. At least this aspect of reproductive medicine is not so futuristic: The current set of patent infringement lawsuits among Verinata, Sequenom, Natera, and Ariosa has held up much non-invasive, prenatal screening for Down’s syndrome.

These issues are both fascinating and complex, and the larger concerns raised by the system described in the 23andMe patent only touch a small fraction of the ethical and practical quandaries involved. For a discussion of the remainder, Stanford’s own Hank Greely, JD, will attempt to address them in his upcoming book, “The End of Sex“. Let us at least hope that that institution’s end is not because of patents.

Jake Sherkow, JD, is a fellow at Stanford Law School’s Center for Law and the Biosciences. His current research focuses on the intersection of patent law, biotechnology, and agency regulation.

Previously: Whole-genome fetal sequencing recognized as one of the year’s “10 Breakthrough Technologies”Stanford bioethicists discuss pros, cons of biotech patents, The end of sex? Maybe not just yet, New techniques to diagnose disease in a fetus, and Sex without babies, and vice versa: Stanford panel explores issues surrounding reproductive technologies
Photo by Lisa Williams

Applied Biotechnology, In the News, Science

The history of biotech in seven bite-sized chunks

Yesterday, an absolute gem appeared on Smithsonian.com’s blog Around the Mall: an assemblage of objects that neatly summarizes the progression and history of biotechnology. Before you stifle a yawn, remember these are the same people who made a paper bag exciting.

Through these seven photos of seven objects the Smithsonian masterfully tells the story of how the first synthetic insulin, Humalin, came to be and how technology used for genetic research advanced in the process. These objects, acquired from the San Francisco company Genentech, can be viewed at the American History Museum in an exhibit called “The Birth of Biotech.”

From the blog:

Genentech’s work began with a discovery made in the 1970s by a pair of Bay Area scientists, Herbert Boyer [PhD] of UC San Francisco and Stanley Cohen, MD, of Stanford: Genes from multi-cellular organisms, including humans, could be implanted into bacteria and still function normally. Soon afterward, they teamed with venture capitalist Robert Swanson to form the company, with the hope of using genetic engineering to create a commercially viable product.

One of their first achievements was synthetically building the human insulin gene in the lab, a single genetic base pair at a time. In order to check the accuracy of their sequence, they used a technique called gel electrophoresis, in which electricity forces the DNA through a gel. Because larger pieces of DNA migrate more slowly than smaller pieces, the process effectively filters the genetic material by size, allowing researchers to pick out the pieces they want, one of the key steps in early genetic sequencing methods.

Holly MacCormick is a writing intern in the medical school’s Office of Communication & Public Affairs. She is a graduate student in ecology and evolutionary biology at University of California-Santa Cruz. 

Previously: The dawn of DNA cloning: Reflections on the 40th anniversaryGenetic basis for anthrax susceptibility in humans discovered by Stanford scientists and Potential therapeutic target for Huntington’s disease discovered by researchers in Taiwan, Stanford

Applied Biotechnology, Bioengineering, Immunology, Research, Stanford News, Stem Cells

Alchemy: From liposuction fluid to new liver cells

Alchemy: From liposuction fluid to new liver cells

alchemyHow’s this for modern-day medical alchemy: A team led by Stanford’s Gary Peltz, MD, PhD, has found a fast, cheap, efficient way for regenerating liver tissue from a patient’s own fat cells. Let it be immediately said that the “patients” in this endeavor (described in a just-published study in Cell Transplantation) were mice. But the fat cells that Peltz’s team used as starter materials and the liver tissue that grew inside the mice (replacing their own organs, which had experienced severe poisoning not unlike that caused by a Tylenol overdose) were completely human.

The liver – the body’s chemistry set – builds complex biomolecules we need and filters and breaks down waste products and toxic substances we need to get rid of. Unlike most organs, a healthy liver can regenerate itself to a significant extent. But this ability is no match for acute liver poisoning or damage from chronic alcoholism or viral hepatitis. Acute liver failure from acetaminophen (Tylenol) alone takes a toll of about 500 lives every year and accounts for upwards of 60,000 emergency-room visits annually.

That begets an ongoing, life-threatening liver shortage. From my release on the study:

Some 6,300 liver transplants are performed annually in the United States, with another 16,000 patients on the waiting list. Every year, more than 1,400 people die before a suitable liver can be found for them. While it can save lives, liver transplantation is complicated, risky and, even when successful, fraught with aftereffects. Typically, the recipient is consigned to a lifetime of taking immunosuppressant drugs to prevent organ rejection.

Making new livers out of a patient’s own readily retrieved fat tissue could help plug the gap between the number of available donor livers for transplantation and the number of people in dire need of that procedure. It might also go a long way to alleviating the requirement for lifelong immunosuppressant therapy afterward.

Peltz’s team obtained adipose stem cells, which ordinarily grow up to be fat cells, from fat-filled fluid removed during routine liposuction procedures. The team then put these cells through a series of biochemical hoops that caused them to change their minds and decide to be liver cells instead.

That’s not easy. (“We had to work hard to convert them to liver cells,” Peltz told me.) But it’s been done before. The problem was that previous fat-to-liver methods took longer than a patient with acute liver failure can survive, and were inefficient and expensive to boot. Using a new technique, Peltz’s group was able to get enough good liver cells for the next regenerative step – injecting the cells into mice’s liver cavities – within seven or eight days. A month later the mice exhibited healthy human liver formation and activity. Importantly, inspection at two months out showed no signs of tumor formation, which is a big obstacle to the alternative use of human embryonic stem cells or induced pluripotent stem cells for this purpose.

Peltz hopes to see the new technology enter clinical trials within a couple of years.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, Free database of drugs associated with liver injury available from NIH and Hepatitis C virus’s Achilles heel
Photo by Abode of Chaos

Applied Biotechnology, Genetics, Research, Stanford News, Technology

Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using

Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using

caught catA new technique promises to provide huge amounts of information about which genes in a cell are hard at work and which are sleeping.  This, in turn,could pay off in dozens of different ways.

From my news release on the advance, which was just published in Nature Methods:

Genes are recipes for the production of proteins, which do almost all the work in every living cell. The biological field of genomics focuses on describing which genes an organism has. The newer field of epigenomics aims to discern which genes are actually used by various tissues within an organism — or, in the case of disease, misused… Virtually every cell in a person’s body contains essentially the same genes. Yet cells from different tissues — liver, skin, muscle, blood — do very different things because they use different genes, as do otherwise identical cells in different biochemical environments, developmental stages or states of health.

Geneticists Howard Chang, MD, PhD, and Will Greenleaf, PhD, of Stanford have teamed up to produce a method of mapping the epigenome – the on/off status of each of the 22,000-odd genes in virtually every human cell - in as little as 10 hours, using off-the-shelf instrumentation and easily available reagents, and requiring only the amount of cells that can be obtained in a single blood draw or needle biopsy.

That’s a major leap. Current epigenome-mapping methods are costly, time-consuming and difficult – and understandably so. The real estate occupied by the roughly 22,000 protein-coding genes in a human cell’s genome is dwarfed by the vast stretches of regulatory DNA regions that control the timing of, and degree to which, these genes are “switched on” (engaged in the production of proteins) or “shut down” (prevented in one way or another from being actively put to use use in protein generation.)

All the DNA in a human cell – which if stretched out would be about six feet long – is scrunched into the cell’s nucleus, which measures about 1/50,000 inch in diameter, Greenleaf told me. This is like bunching up a telephone line that stretches from New York City to Los Angeles and stuffing it into a two-bedroom house, he said.

Chang told me that as advance word of their new study’s publication has leaked out, dozens of labs around the world are already putting the new method to work in research applications. The technique’s speed, low cost, tiny sample-size requirement and ease of use also radically reduce the barriers to widespread and even clinical use. Remember: Which genes a tissue is using, and to what extent, tells a ton about that tissue’s health status.

Previously: Night of the living dead gene: Pseudogene wakes up, puts chill on inflammation, Red light, green light: Simultaneous stop and go signals on stem cells’ genes may enable fast activation, provide aging clock and New job description for RNA, oldest professional molecule
Photo by Mel B.

Applied Biotechnology, Bioengineering, In the News, Stanford News, Technology

Project demonstration today: Stanford’s bioengineering boot camp for high schoolers

Project demonstration today: Stanford's bioengineering boot camp for high schoolers

Flanked by 18-year-old Zoe Nuyens (left) and 17-year-old Justine Sun, Alex Lee, also 17, demonstrates a system for detecting surgical gauze that was designed by local high school students. The trio were among the 26 students who attended at a bioengineering "boot camp" held at Stanford University.This summer, a group of 26 high-school students participated in Stanford’s first bioengineering boot camp. Based on the story in yesterday’s Stanford Report, I think it’s safe to say these students have a pretty enviable response to the age-old question, “What did you do in school today?”

For starters, they invented a way to help surgeons track and retrieve the gauze placed inside of patients during medical procedures.

Tom Abate describes the origins of “smart gauze” and the new boot camp here:

“Surgical sponges are the most common item left behind in surgeries and they’re very difficult to detect,” said [17-year-old Alex] Lee, who was one of 26 participants in a free, six-week bioengineering boot camp for high school students organized by Stanford undergraduate Stephanie Young.

Young, a bioengineering student who grew up in San Mateo, Calif., said she got the idea for the boot camp last year after talking with a friend who had gone through a similar intensive summer program in the law.

The boot camp employed the learning-by-building approach honed by Stanford’s Product Realization Lab, a teaching environment that offers design and prototyping facilities in support of student product creation. The high school students were presented with a series of real-world challenges and grouped into teams to devise solutions, which they then fashioned in the lab.

The camp’s high school students will demonstrate their designs today from 2 to 5 p.m. at the medical school’s Li Ka Shing Center for Learning and Knowledge. This special presentation is open to the public.

Holly MacCormick is a writing intern in the medical school’s Office of Communication & Public Affairs. She is a graduate student in ecology and evolutionary biology at University of California-Santa Cruz.

Previously: Image of the Week: CIRM intern Christina Bui’s summer project and Image of the Week: CIRM intern Brian Woo’s summer project
Photo, of students demonstrating a system for detecting surgical gauze, by Steve Castillo

Applied Biotechnology, Research, Stanford News

Stanford researchers develop solar-powered, wireless retinal implant

Stanford researchers develop solar-powered, wireless retinal implant

Researchers at Stanford have created a solar-powered retinal implant capable of transmitting visual signals to the brains of rats. A Medical Daily story offers more details about the study (subscription required), which appears today in Nature Communications:

To address [the] shortcomings of bionic implants, [Daniel Palanker, PhD, an associate professor ophthalmology at Stanford, and his colleagues developed a solar-powered microchip that could be inserted into the sub-retinal layers of the eye.

This device was placed adjacent to the neurons that send visual information to the brain, which should stimulate a more “natural” pattern of neural activity. Their retinal prosthetic is wireless, so its special set of video eyeglasses beams images directly into the microchip.

In this study, Palanker’s team from the Hansen Experimental Physics Laboratory placed these second-generation implants into the retinas of rats with or without macular degeneration. The researchers found that the new bionic retinas could transmit images into the minds of rats, which was observed by measuring brain activity in the visual centers of the rodents’ brains.

Brain activity returned to normal in rats with eye disease that were given these retinal implants.

Previously: Australian scientists implant early prototype of a “bionic eye” into a patient, Stanford-developed retinal prosthesis uses near-infrared light to transmit images and Developing a prosthetic eye to treat blindness

Applied Biotechnology, Neuroscience, Research, Stanford News, Stem Cells

You’ve got a lot of nerve! Industrial-scale procedure for generating plenty of personalized nerve cells

You've got a lot of nerve! Industrial-scale procedure for generating plenty of personalized nerve cells

Embryonic stem cells (or ESCs) and their younger cousins the induced pluripotent stem cells (iPSCs) are prized because they can, alternatively, replicate themselves indefinitely in a dish or differentiate into every cell type in the body. This makes them potentially valuable tools for regenerative medicine.

And because iPSCs can be made from a person’s skin cells, manipulating their differentiated progeny lets investigators study disease processes at the cellular level, in a dish and in a personalized way. By custom-producing, for example, a given individual’s nerve cells,  researchers can study the specific defects of those cells in a dish, without having to first perform the ethically unthinkable – and, therefore, purely hypothetical – act of slicing chunks of tissue out of that person’s brain in order to do so. The researchers can, further, toss thousands of different compounds into thousands of tiny “wells” containing these nerve cells to see which ones might restore those cells’ proper function. (Different drugs are likely to work better with different individuals’ defective cells, depending on the nature of the cell’s defining defect.)

Scientists have successfully coaxed both ESCs and iPSCs down the developmental pathway to become nerve cells. They’ve even generated nerve cells directly from skin cells. But up to now, the procedures they’ve used have been plagued by two problems. First, quality assurance: The extent to which nerve cells generated by these methods actually look and act like nerve cells are supposed to look and act varies a lot, depending on which particular ESC line, or which iPSC line, was used to generate them. Second, the process is slow and the yield is low (it typically takes months to get from the beginning to the end, and many of the “starter” ESCs or iPSCs don’t successfully convert to decently functioning nerve cells).

But in a recently published paper in Neuron,  a team under the direction of Stanford cell physiologist and neuroscientist Tom Sudhof, PhD, has showed that just boosting the level, in human ESCs or iPSCs, of one single substance (a type known as a transcription factor) results in an abundant and quite pure population of nerve cells within as little as two weeks. And unlike previous methods, this one seems to generate nerve cells of equally high functional quality regardless of which “starter” cell line was used to get the process underway.

Clearly, if you’re doing regenerative medicine for a stroke or brain-trauma victim etc., you’re going to need a lot of nerve cells, and time is of the essence. So the new method represents a major forward step toward the realization of the dream of personalized regenerative medicine.

Previously: Revealed: the likely role of Parkinson’s protein in the healthy brain, Nervous breakdown: Preventing demolition of faulty proteins counters neurodegeneration in lab mice and Human neurons from skin cells without pluripotency?
Photo by Crystalline Radical

Applied Biotechnology, Cardiovascular Medicine, Research, Stanford News

Ultra-thin flexible device offers non-invasive method of monitoring heart health, blood pressure

Ultra-thin flexible device offers non-invasive method of monitoring heart health, blood pressure

Tiny, bendable biosensors hold the promise of allowing health-care providers to track patients’ vital signs without them having to be tethered to bulky machines. But the difficulty of squeezing sophisticated circuitry onto surfaces no wider than a postage stamp makes designing such devices especially tricky.

To overcome this challenge, Zhenan Bao, PhD, a professor of chemical engineering at Stanford, and colleagues combined layers of flexible materials into pressure sensors to create a small skin-like heart monitor that can be attached to the wrist with a regular-sized adhesive bandage. A Stanford news release offers more details about the device and its potential uses in health care:

When the sensor is placed on someone’s wrist using an adhesive bandage, the sensor can measure that person’s pulse wave as it reverberates through the body.

The device is so sensitive that it can detect more than just the two peaks of a pulse wave. When engineers looked at the wave drawn by their device, they noticed small bumps in the tail of the pulse wave invisible to conventional sensors. Bao said she believes these fluctuations could potentially be used for more detailed diagnostics in the future.

Doctors already use similar, albeit much bulkier, sensors to keep track of a patient’s heart health during surgery or when taking a new medication. But in the future Bao’s device could help keep track of another vital sign.

“In theory, this kind of sensor can be used to measure blood pressure,” said [Gregor Schwartz, a post-doctoral fellow and a physicist for the project]. “Once you have it calibrated, you can use the signal of your pulse to calculate your blood pressure.”

This non-invasive method of monitoring heart health could replace devices inserted directly into an artery, called intravascular catheters. These catheters create a high risk of infection, making them impractical for newborns and high-risk patients. Thus, an external monitor like Bao’s could provide doctors a safer way to gather information about the heart, especially during infant surgeries.

The team’s work is described in paper published today in Nature Communications.

Previously: Touch-sensitive, self-healing synthetic skin could yield smarter prosthetics, Beetle wing design inspires ultra-sensitive electronic skin, Stanford researchers develop transparent, stretchable skin-like sensor and Stretchable solar cells could power electronic ‘super skin’

Applied Biotechnology, Chronic Disease, Pediatrics, Research, Stanford News

Visible symptoms: Muscular-dystrophy mouse model’s muscles glow like fireflies as they break down

Visible symptoms: Muscular-dystrophy mouse model's muscles glow like fireflies as they break down

A luminescent lab mouse, genetically engineered to produce the same protein that makes fireflies’ tails light up, may accelerate progress in coming up with treatments for muscular dystrophy. This bioengineered mouse also has a genetic defect that, like its counterpart gene defect in people, causes the disease.

The luminescence happens only in damaged muscle tissue, and its intensity is in direct proportion to the amount of damage sustained in that tissue. So each glowing mouse muscle gives researchers an accurate real-time readout of just how much the disease has progressed and where.

It adds up to vastly expedited drug research. Tom Rando, MD, PhD, director of Stanford’s Glenn Laboratories for the Biology of Aging and founding director of Stanford’s Muscular Dystrophy Association Clinic, told me. As I wrote in my release about his new report in the Journal of Clinical Investigation about the Rando lab’s invention:

No truly effective treatments for muscular dystrophy exist. “Drug therapies now available for muscular dystrophy can reduce symptoms a bit, but do nothing to prevent or slow disease progression,” said Rando. Testing a drug’s ability to slow or arrest muscular dystrophy in one of the existing mouse models means sacrificing a few of them every couple of weeks and conducting labor-intensive, time-consuming microscopic and biochemical examinations of muscle-tissue samples taken from them, he said.

With an eye to vastly speeding up drug testing while simultaneously dropping its cost, Rando and his colleagues developed the new experimental strain whose glow (you see it through the skin) gives investigators an instantaneous, accurate reflection of what’s going on inside a mouse’s muscles, well before the degenerative changes could have been observed using standard detection techniques  - without any need to kill the mouse in order to get the results.

Trivia point: The word “muscle” comes from the Latin musculus, meaning “little mouse.” More than mere coincidence?

Okay, probably not. But I thought it was worth mentioning.

Previously: Aging research comes of age, Can we reset the aging clock, one cell at a time? and Mouse model of muscular dystrophy points finger at stem cells
Photo by Goldring

Applied Biotechnology, Ethics, Genetics, In the News, Medicine and Society, Stanford News

Whole-genome fetal sequencing recognized as one of the year’s “10 Breakthrough Technologies”

Whole-genome fetal sequencing recognized as one of the year's "10 Breakthrough Technologies"

A million years ago (all the way back in 2006!) I wrote an article for Stanford Medicine magazine about genetic technologies and the eugenics movement in this country during the first part of the 1900s. I still remember it as one of the most fascinating of my articles to research, demanding as it did that I speak with a variety of geneticists and ethicists about the increasing control that humans have over their genetic destiny.

When, last year, I had the privilege of writing about Stanford biophysicist Stephen Quake, PhD, and his work on whole-genome sequencing of fetuses before birth, I couldn’t help but remember that article of yore. What are we getting ourselves into?

Now MIT Technology Review has recognized whole-genome fetal sequencing as one of its “10 Breakthrough Technologies 2013.” Accompanying the designation is an in-depth review of the technology and its implications – which are far more complex than I could have imagined six years ago. The article contains comments from several experts, including Stanford law professor and bioethicist Hank Greely, JD, and Quake:

Quake says proving that a full genome readout is possible was the “logical extension” of the underlying technology. Yet what’s much less clear to Quake and others is whether a universal DNA test will ever become important or routine in medicine, as the more targeted test for Down syndrome has become. “We did it as an academic exercise, just for the hell of it,” he says. “But if you ask me, ‘Are we going to know the genomes of children at birth?’ I’d ask you, ‘Why?’ I get stuck on the why.” Quake says he’s now refining the technology so that it could be used to inexpensively pull out information on just the most medically important genes.

In my opinion, experts are right to consider the impact of this type of technology before it becomes commonplace. The ethical implications of parents learning their child’s genome sequence within a few weeks of conception – and of possibly using that information to make decisions about the pregnancy’s outcome – are substantial. Thankfully, some really smart people have been asking these questions in one form or another for years, even though the answers seem to end up more grey than black and white. From that ancient article I wrote six years ago:

For example, even though sex selection of embryos fertilized in vitro has many people up in arms, there’s no evidence that it’s on track to alter the gender balance in this country: Boys and girls are nearly equally sought after, says [medical geneticist and associate chair of pediatrics Eugene Hoyme, MD]. And although some parents will terminate a pregnancy if the fetus has a genetic or developmental problem that they feel isn’t compatible with a meaningful life, different families draw this line at dramatically different points in the sand. For some, it’s too much to consider having a child with Down syndrome. For others it’s important to sustain life as long as possible regardless of the severity of the condition. Still others might choose to have a child as similar to them as possible, down to sharing disabilities such as deafness.

“Eugenics is here now,” says Stanford bioethicist David Magnus, PhD. “So what? We allow parents to have virtually unlimited control over what school their child attends, what church they go to and how much exercise they get. All of these things have a much bigger impact on a child’s future than the limited genetic choices available to us now. As long as these are safe and effective, why not give parents this option as well?”

Previously: New techniques to diagnose disease in a fetus, Better know a bioengineer: Stephen Quake and Stanford bioethicists discuss pro, cons of biotech patents
Photo by paparutzi

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