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Bioengineering, Genetics, History, Immunology, Stanford News

Leonard Herzenberg, FACS developer and Stanford professor, dies

HerzenbergIt’s a huge responsibility (and a privilege) to write about someone’s life after they have died; I inevitably come away wishing I had known the subject personally. That’s how I felt when writing about Leonard Herzenberg, PhD, who died last week. He was a scientific giant and a passionate advocate for those less fortunate than himself, and he and his wife of 60 years, Leonore Herzenberg, collaborated scientifically at Stanford for five decades.

From the obituary:

“Len was a valuable and treasured member of our Stanford Medicine community for more than 50 years,” said Lloyd Minor, MD, dean of the medical school. “He was a kind, thoughtful and just person eager to share scientific discoveries and opportunities with his friends and colleagues, and to improve access to education and career-advancement opportunities to women and disadvantaged youth. FACS technology made possible the birth of modern immunology, stem cell research and proteomics, and significantly advanced the clinical care of people with diseases such as cancer and HIV infection. Len’s scientific accomplishments are prodigious. But it is his commitment to helping others that will be his enduring legacy.”

Over and over again I heard words like “warm,” “welcoming” and “remarkable” while writing this article. And, although I had worked with Len Herzenberg in the past (most notably in 2006 when he was awarded the Kyoto Prize), I didn’t realize the extent of his sense of fairness and responsibility to others. From the article:

Herzenberg was well known for his pursuit of social justice, his desire to help those less fortunate then himself and his warm and welcoming demeanor. He donated the money accompanying his Kyoto Prize to nonprofit organizations working to improve health, human rights and education.

And:

[The Herzenbergs] encouraged minority teenagers to pursue a college education by establishing a program to bring high school students from East Palo Alto to Stanford to learn about medicine, biology and the multiple benefits of higher education. In addition, from the 1960s onward, Leonard Herzenberg conducted a behind-the-scenes campaign to expand career advancement opportunities for women in immunology and in science in general.

Please feel free to leave your thoughts and remembrances about Len Herzenberg, or messages to his family, on our online guestbook. The family requests that, in lieu of flowers, donations in Len’s memory be made to the Len and Lee Herzenberg endowed fund at the Stanford School of Medicine. Gifts may be sent to Stanford Medical Center Development, 3172 Porter Drive, Suite 210, Palo Alto, CA. 94304, or made online. Plans for a memorial service will be announced at a later date.

Photo by Steve Gladfelter

Evolution, Genetics, History, Research, Science, Stanford News

On the hunt for ancient DNA, Stanford researchers improve the odds

On the hunt for ancient DNA, Stanford researchers improve the odds

110427-N-YY9999-002On the surface, it’s perfect Halloween fodder: Ancient Peruvian mummies, Bronze and Iron Age human teeth from Bulgaria and a thousands-of-years old hair sample from Denmark. In fact, one attendee of Stanford geneticist Carlos Bustamante’s talk this morning at the annual conference of the American Society of Human Genetics in Boston quipped that his introduction sounded like “the start of a joke.”

But really old human DNA (we’re talking thousands of years) holds amazing secrets about our distant past. What did we look like? Where did our ancestors come from? What diseases may we have had? Unfortunately, it’s much more difficult than it seems to unlock these mysteries.

Stanford postdoctoral scholar Meredith Carpenter, PhD, explained the problem in an e-mail to me yesterday:

From Neandertals to mammoths to Otzi the Iceman, discoveries in ancient DNA sequencing have been making headlines.  But what you might not realize is that most of the ancient genomes sequenced to date have come from exceptionally well-preserved specimens – Otzi, for example, was literally frozen in ice for 5000 years.

Ancient DNA specimens from temperate environments, in contrast, are much trickier to sequence because they contain high levels of environmental contamination, primarily derived from bacteria and other microbes inhabiting the ancient bone. This contamination often makes it too expensive to sequence the tiny amounts of endogenous DNA (which degrades over the years due to exposure to the elements) remaining in a sample.

Now, Carpenter and Bustamante, PhD, and their colleagues have hit upon a way to enrich, or increase the proportion of ancient human DNA in an environmental sample from about 1.2 percent to nearly 60 percent–rendering it vastly easier to sequence and analyze. They do so by exposing the sample to a genome-wide panel of human-specific RNA molecules to which the degraded DNA in the sample can bind. The effect is somewhat like stirring a pile of iron-rich dirt with a powerful magnet to isolate the metal from the soil.

This isn’t Bustamante’s first foray into the secrets of ancient DNA. Last year he published very interesting results showing that the ancestors of the famous Iceman likely came not from mainland Italy, as previously thought, but instead from the islands of Corsica or Sardinia. This new technique should enable researchers to learn even more about our ancestors, including those oh-so-intriguing mummies.

According to Carpenter:

We hope that this new method will enable ancient DNA researchers to more cheaply sequence a larger number of specimens, providing broader insight into historical populations rather than just a few well-preserved individuals.

The research is published online today in the American Journal of Human Genetics. If you’re interested in following tweets from the conference, which goes through tomorrow, you can do so by following hashtag #ASHG2013.

Previously: Iceman’s origins discovered at Stanford, Stanford study investigates our most-recent common ancestors  and Recent shared ancestry between Southern Europe and North Africa identified by Stanford researchers.
Photo by Official US Navy Imagery

History, Humor, Medicine and Literature, Science, Technology

Half-century climb in computer’s competence colloquially captured by Nobelist Michael Levitt

Half-century climb in computer's competence colloquially captured by Nobelist Michael Levitt

ancient computerOn October 9, the day Stanford macromolecule-modeling maven Michael Levitt, PhD, won his Nobel Prize, I wrote him a note of congratulations.

He wrote back six days later: “Thanks so much. It has been one wild ride! It will be good for the field, though, and I will learn to disappear and still have time for myself.” It’s a wonder he got back to me as soon as he did, crushed as he must feel by the cheering throngs dogging him at every turn since Nobel day. But he has made a point of replying quickly and gracefully to not only well-wishers but deadline-driven reporters.

Although his Nobel was for chemistry, the lab Levitt operates in is stocked with shelves full of ones and zeroes. His expertise lies in the field of computer science, a field of which Alfred Nobel had no inkling when he created the awards in his final will, written in 1895.

As we all know, Nobel made his millions in the explosives field. No explosion he could have imagined in 1895 has been more profound, in recent decades, than the explosion in computing power pithily encapsulated in Moore’s law. In the late 1960s, Levitt began constructing his increasingly detailed simulations of the giant biomolecules that animate our cells and, in a sense, our souls as well, by pumping punchcards into what was then among the world’s most potent computers (dubbed Golem in memory of a powerful, soulless giant of medieval Jewish folklore) at Israel’s Weizmann Institute.

Since those seminal days, the ones-and-zeroes game has picked up speed. Responding to an e-mailed query from science writer Lisa Krieger of the San Jose Mercury News, Levitt put it this way:

The computer that I used in 1968 allowed me 300 [kilobytes] of memory, or about 1/10,000th of the memory on a smart phone. [An extremely complex,  fifty-step computation] took 18 minutes on the Golem computer… for a cost of about five million 1965 U.S. dollars ($35 million today). The same calculation takes 0.18 seconds on an Apple MacMook PRO laptop costing $3,500. This means that the calculation is… 6,000 times faster on a computer costing… 10,000 times less.

If cars had changed in the same way, Levitt drolly noted, “a 1965 Cadillac that cost $6,000 in 1965 dollars ($40,000 today) would actually cost just four dollars. More amazingly, it would have a top speed of 600,000 miles an hour and be able to carry 50,000 people.”

Makes me wonder: Just how long will it be before we can no longer tell our computers from ourselves?

Previously: But is it news? How the Nobel Prize transformed noteworthy into newsworthy, Nobel winner Michael Levitt’s work animates biological processes, No average morning for Nobel winner Michael Levitt and Stanford’s Michael Levitt wins 2013 Nobel Prize in Chemistry
Photo by kalleboo

Genetics, History, Medicine and Society, Research, Stanford News

The dawn of DNA cloning: Reflections on the 40th anniversary

The dawn of DNA cloning: Reflections on the 40th anniversary

DNA for Cohen blogAs you might guess, I write a lot about science for my job. And it’s always great fun to hear about all the newest findings – some of which appear to have the potential to be genuinely groundbreaking in their field. But I rarely stop to contemplate how science, like every other human endeavor, has a very real, very important history that echoes through the papers I write about today.

In today’s Online Early Edition of the Proceedings of the National Academies of Science, Stanford geneticist Stanley N. Cohen, MD, reflects on his role, together with that of Herbert Boyer, PhD, (then at the University of California, San Francisco), in a series of events 40 years ago that led to the first instances of “DNA cloning” and an explosion in the fields of genetics, biotechnology and medicine.

The article is a fascinating read that clearly took a great deal of effort. When I asked Cohen why he felt it was important to accept the invitation to write such an article, here’s what he told me:

DNA cloning has now become such an integral part of the biological sciences that it is sometimes difficult for students and other young scientists to imagine that there was once uncertainty about whether genes could be propagated and cloned in a foreign host.   The invitation from the PNAS provided an opportunity for me to write a first-person account of the science and events that led to successful DNA cloning 40 years ago.  It also provided a format to explain the scientific logic underlying the crucial experiments, describe some of the personal interactions involved, and point out the scientific and political consequences of the findings. I’ve tried to combine my personal perspective with careful documentation of the history – while communicating the sense of scientific excitement that existed at the time.  Not the least of my intents was to remind people – at a time when public support of basic research is decreasing – that the invention of DNA cloning, which has had important practical applications in addition to contributing to knowledge about the workings of genes and cells in health and disease, resulted from the pursuit of fundamental questions about biological phenomena.

I highly encourage scientists (and science writers!) at all stages of their careers to take a look. If you’re interested in learning more about the history of science in the early days of biotechnology, you should check out the Regional Oral History collection at U. C. Berkeley’s Bancroft Library, which includes interviews with Cohen and Boyer as well as Stanford’s Paul Berg, PhD, and Niels Reimers. Reimers founded Stanford’s Office of Technology Licensing, which obtained the patent on the recombinant DNA technology.

Previously: Why basic research is the venture capital of the biomedical world and First U.S. heart transplant among the top 50 breakthroughs in science
Photo by Christian Guthier

History, Infectious Disease, Microbiology, Public Health, Research, Stanford News

Did microbes mess with Typhoid Mary’s macrophages?

Did microbes mess with Typhoid Mary's macrophages?

macrophage with salmonella insideMary Mallon (a.k.a. “Typhoid Mary“) didn’t mean any harm to anybody. An Irish immigrant, she made her living for several years about a century ago by cooking for better-off families in the New York City area. Strangely, the people she cooked for kept on coming down with typhoid fever – but not Mary.

Mallon, alas, turned out to be a chronic asymptomatic carrier of Salmonella typhi, the bacterial strain that causes typhoid fever. Typhoid is a deadly disease that, while no longer a huge problem in the United States, infects tens of millions – and kills hundreds of thousands – of people around the world every year.

“She didn’t know she had it,” says Stanford microbiologist Denise Monack, PhD. “To all outward appearances, she was perfectly healthy.”

Salmonella strains, including one called S. typhimurium, also cause food poisoning in people and pets, taking an annual human toll of 150,000 globally. While S. typhi infects only humans, closely related S. typhimurium can infect lots of mammals.

Between 1 and 6 percent of people infected with S. typhi become chronic, asymptomatic typhoid fever carriers. Nobody has known why this happens, but it’s a serious public-health issue. To address this, Monack has developed an experimental mouse model that mimicks asymptomatic typhoid carriers. In a new study published in Cell Host & Microbe, she and her colleagues put that model to good effect, showing that Salmonella has a sophisticated way of messing with our immune systems. The bacteria set up house inside voracious attack cells called macrophages (from the Greek words for “big eater”). Macrophages, are known for their ability to engulf and digest pathogens and are called to the front lines of an immune assault against invading microbes. Ornery critters that they are, macrophages would seem like the last thing bacteria bent on long-term survival would want to meet.

But, as I wrote in my release about this study, a macrophage has two faces, depending on its biochemical environment:

“Early in the course of an infection,” [Monack] said, “inflammatory substances secreted by other immune cells stir macrophages into an antimicrobial frenzy. If you’re not a good pathogen, you’ll be wiped out after several days of causing symptoms.” But salmonella is one tough bug. And our bodies can’t tolerate lots of inflammation. So, after several days of inflammatory overdrive, the immune system starts switching to the secretion of anti-inflammatory factors. This shifts macrophages into a kinder, gentler mode. Thus defanged, anti-inflammatory macrophages are more suited to peaceful activities, such as wound healing, than to devouring microbes.

And, sure enough, Monack and her colleagues showed that salmonella germs have a way (still mysterious, but stay tuned) of taming macrophages, flipping an intercellular switch inside of these thug-like cells that not only expedites their champ-to-chump shift but induces them to pump out tons of glucose, the bug’s favorite food. What better place to hide than in the belly of the beast?
Previously: TB organism’s secret life revealed in a hail of systems-biology measurements
Photo by AJC1

Cancer, History, In the News, Science

Some resolution for the immortal cells of Henrietta Lacks

Some resolution for the immortal cells of Henrietta Lacks

We’ve written quite a bit here about Henrietta Lacks, the poor black woman who died in 1951 of cervical cancer, and whose cancer cells – taken without her knowledge – led to great advances in biomedical research. (Lacks’ story was told in the award-winning The Immortal Life of Henrietta Lacks.) Lacks’ family, in the words of Smithsonian blogger Rachel Nuwer, have “harbored a deep discontent about their relative’s stolen cells;” “they were never informed that Lacks’ cells were taken; they never received any royalties from the HeLa line; and researchers often ignored Lacks’ great personal legacy.”

Today, there’s big news about Lacks, with Nature reporting that the family reached a deal with the National Institutes of Health regarding access to the so-called HeLa cells. Ewen Callaway explains how the agreement came to be and also addresses the issue of financial compensation:

Some Lacks family members raised the possibility of [it],[NIH director Francis] Collins says. Directly paying the family was not on the table, but he and his advisers tried to think of other ways the family could benefit, such as patenting a genetic test for cancer based on HeLa-cell mutations. They could not think of any. But they could at least reassure the family that others would not make a quick buck from their grandmother’s genome, because the US Supreme Court had this year ruled that unmodified genes could not be patented. [Henrietta’s granddaughter Jeri] Lacks-Whye says that the family does not want to dwell on money — and that her father has often said he “feels compensated by knowing what his mother has been doing for the world.”

Previously: Do you have a ‘HeLa’ story? Share it with Rebecca Skloot, Will Henrietta Lacks now get her due?, Image of the Week: HeLa cells and Immortal cells: Henrietta Lacks lives on and on

Health Costs, Health Policy, History, Stanford News

The history of U.S. health care in about 1,000 words

The history of U.S. health care in about 1,000 words

“All men are created equal” may be the guiding legal principle for citizens of the United States, but not when it comes to health care coverage and outcomes, says Victor Fuchs, PhD, one of the nation’s foremost health economists and the Henry J. Kaiser Jr. Professor, Emeritus, at Stanford.

In a Viewpoint published today in the Journal of the American Medical Association, Fuchs provides a history lesson on how and why the U.S. health care system spends more than double on per-person health expenditures than other advanced nations, and he offers some strategies for controlling future costs.

“This is the best short piece on U.S. health care that I’ve ever seen,” Howard Bauchner, MD, editor-in-chief of JAMA, told me.

Beginning today, the Affordable Care Act expands the number of Americans receiving preventive care, providing new federal funding to state Medicaid programs that choose to cover preventive services. It also requires that states pay primary care physicians no less than 100 percent of Medicare payment rates for primary care services.

While the health-care reforms mandated in the act include some provisions to motivate health-care providers to become more efficient, less fragmented and more accountable, it doesn’t include revenue sources for all its new services. Fuchs says, “More comprehensive reforms are necessary to avoid financial disaster.”

According to Fuchs, there are three fundamental differences in the U.S. system — driven by its history — that make it difficult for the U.S. to adopt a less costly government-financed health care system. There is a distrust of large government that began when America broke away from the strong-armed British Empire. There is a reluctance to redistribute wealth across all citizens, in part because of the country’s cultural diversity. And there are “choke points” in the U.S. political system — such as the cost of election campaigns and the Senate filibuster — that give deep-pocketed special interest groups the upper hand in preventing sweeping reforms.

As a new Congress returns to work with health care reform high on its new year’s resolutions, Fuchs’ editorial provides a starting point, grounded in history, for a new round of negotiations.

Previously: Study: If Americans better understood the Affordable Care Act, they would like it more, Does the Affordable Care Act address our health-cost problem?, Stanford economist Victor Fuchs: Affordable Care Act “just a start” and An expert’s historical view of health care costs

From Dec. 24 to Jan. 7, Scope will be on a limited holiday publishing schedule. During that time, it may also take longer than usual for comments to be approved.

History, Medicine and Literature

Top medical reads of 2012 from Stanford Medicine’s editor

As the editor of Stanford Medicine, I think a lot about new research, new discoveries, new treatments. So it’s no wonder I find stories of long ago a refreshing change when I’m reading for pleasure. A look at my 10 favorites this year shows my predilection, though there’s lots of new here too. History fan or not, if you read just one, read about the immortal jellyfish! I can’t stop thinking about them.

Undead: The rabies virus remains a medical mystery, by Monica Murphy and Bill Wasik, Wired
An account of a modern attempt to cure rabies, with lots of history woven in.

Can a jellyfish unlock the secret of immortality? by Nathaniel Rich, New York Times Magazine
Including wondrous jellyfish that grow younger and a researcher who breaks the mold, and it’s told with humor and lyricism.

Two hundred years of surgery, by Atul Gawande, New England Journal of Medicine
For gems like this: “Liston operated so fast that he once accidentally amputated an assistant’s fingers along with a patient’s leg, according to Hollingham. The patient and the assistant both died of sepsis, and a spectator reportedly died of shock, resulting in the only known procedure with a 300% mortality.”

Post-Prozac nation: The science and history of treating depression, by Siddhartha Mukherjee, New York Times
Everything we knew about antidepressants like Prozac was wrong. But that’s OK.

The nature of the Knight Bus, by Chris Gunter, Story Collider
A look behind the scenes at top science journal Nature from one of the journal’s editors.

The island where people forget to die, by Dan Buettner, New York Times Magazine
On mellowing out on a Greek island to live to 100. It got me thinking about how to bring more mellowness into my life.

Fear fans flames for chemical makers, by Patricia Callahan and Sam Roe, Chicago Tribune
A great investigation into a chemical industry-funded front group’s deceptive campaign that fueled demand for flame retardants in furniture, electronics and baby products among many other items. The whole four-part series is worth reading. It also explains that the chemicals have been linked to cancer, neurological deficits, developmental problems and impaired fertility — and not only that, but they don’t work.

The measured man, by Mark Bowden, The Atlantic
On one man’s effort to use big data as a tool to guide him to better health. This is either insane, the future, or both.

A family learns the true meaning of the vow ‘in sickness and in health’, Washington Post Magazine
A heartrending, inspiring read for me, though not for all – as evident by the comments.

Previously: My top medical reads of 2011 (aside from those I edited)

From Dec. 24 to Jan. 7, Scope will be on a limited holiday publishing schedule. During that time, it may also take longer than usual for comments to be approved.

History, Medical Education, Medicine and Literature, Medicine and Society, Technology

From the archives: A 1949 satirical prediction of medical education and life in 2000

From the archives: A 1949 satirical prediction of medical education and life in 2000

Throughout history, mankind has been making predictions about what the future will hold. While many of us only think a few years ahead, two enterprising interns working in 1949 at STAT, a publication from the Stanford School of Nursing (which no longer exists), daydreamed what life would be like at the start of the new millennium.

A colleague of mine stumbled upon the authors’ fun and satiric article (.pdf) not long ago, and I decided to take a moment to compare their predictions with reality. The story is set in the year 2000, where everything is done on screens and the world runs on the latest technologies of a fictitious technology conglomerate named Tele-Tele Inc.

While the story presents a lot of far-fetched and comical ideas of life in 2000, the imagined world of Tele-Tele Inc. actually has a few similarities to modern-day life. In one part of the story, the narrator explores how the School of Medicine has changed:

…I decided to take a look at the old Med School. Surely, this would not be changed by Tele-Med. But to my utter amazement, I found only a large Tele-Transmitter, which I was to learn later, would be used to send Tele-Lectures to the New Tele-Med Students. I was also to learn that these Tele-Lectures could only be received on specially built ceiling screens, designed to put the students in an obviously comfortable position.

Could this have been an early prediction of YouTube and Skype as a way for students to follow lectures?

The article also foretells the impact that advancements in technology would have on patient health care. I spoke about this with article co-author Eldon Ellis, a 90-year-old retired surgeon, who told me:

It’s really important to not let the relationship between doctor and patient get lost in all the technology. Unfortunately, the good features of technical changes sometimes get overwhelmed, and the first thing someone gets is a batch of X-rays and lab studies. What we really need to do is look at the patient and talk to the patient.

The full article is worth a read.

Cancer, History, Public Health

Cigarettes and chronographs: How tobacco industry marketing targeted racing enthusiasts

Hot on the heels of reading about the tobacco industry’s connection to the Olympics, I’ve just come across a post on Hodinkee (a great watch blog) detailing a surprising relationship between Swiss watch manufacturer Uhrenmanufaktur Heuer AG (now TAG Heuer) and Brown & Williamson. According to Jeff Stein, the relationship arose out of a need to better position Viceroy cigarettes:

For years, Viceroy’s advertising theme had been balance–”not too strong, not too light, Viceroy’s got the taste that’s right.” A normal ad might depict a woman offering her companion one of her cigarettes, and he, surprisingly, enjoys the taste. The Viceroy was “less masculine than its key competition,” and the brand had a “feminine orientation,” according to internal documents. While the Viceroy couple shopped for flowers, the Marlboro man rode his horse straight into more market share.

The solution, Stein writes, was to make Viceroy the brand of the “auto racer.” To help shape that perception, Brown & Williamson partnered with Heuer to offer a discounted chronograph wristwatch ($88!) with the purchase of a carton of Viceroy cigarettes:

Brown & Williamson contacted Heuer in late 1971 with the idea of offering the Heuer Autavia in a Viceroy promotion. Throughout the 1960s, Heuer was a dominant presence at the racetrack. Its stopwatches, handheld chronographs, dashboard timers, and timing systems were the gold standards in their respective categories.

I don’t want to spoil the rest of the entry, so head over to Hodinkee if you’d like to see another example of how the tobacco industry has, in Jackler’s words, “affiliated its products with cherished and admired cultural icons.”

Previously: A discussion of the tobacco industry’s exploitation of “smoke-free” Olympic Games

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