Archive for September, 2011
You have to wonder what's going on in the DNA of Harvard genetics professor George Church.
About 30 years ago, Prof Church was one of a handful of people who dreamed up the idea of sequencing the entire human genome – every letter in the code that separates us from fruit flies as well as our parents. His lab was the first to come up with a machine to break that code, and he's been working to improve it ever since.
"There used to be this attitude: here's your genetic destiny, get used to it," Prof Church says. "Now the attitude is: genetics is really about the environmental changes you can make to change your destiny."
Standing at 1.93m, with a bushy reddish-grey beard, George Church is hard not to notice. The 57-year-old is both imposing and unassuming. There's an awkwardness to Church, like an 8th grade boy after a summer growth spurt, and an openness that makes him easy to like. His manner is the same with a Harvard faculty colleague as with the technician operating a machine he helped design.
This democratic instinct comes through in his science. Church advises 20 of the 30-or-so advanced genomics companies in the United States, but his heart is clearly in academia, doing basic science that helps everyone.
As he pushes for the mapping of more and more complete genomes, he also pushes to make those genomes public, so researchers can learn about medical conditions by comparing them. He's put 11 up on the web already, including his own, and is aiming for 100,000 more.
Once thousands of people with diverse backgrounds have made their genomes and health status public, researchers will be able to delve into a wide range of diseases and disorders, from schizophrenia to heart disease, diabetes to learning disabilities, looking for patterns.
"You bring down the price and many blossoms bloom," he says.
Prof Church doesn't want to make these discoveries himself. The pace of that kind of science is too slow for him, and not driven by technology.
There's a climate-controlled room in the middle of Church's generous lab space, where a small tray shakes back and forth, jostling pellets of E. coli DNA.
In a four-hour production process, researchers can turn on or off a single base pair of that DNA, or whole regions of genes to see what happens. The goal is to find a way to improve production of industrial chemicals or medications, or to test viral resistance.
"You could think of this as driving evolution to very rapid rates," Church said. "Sort of evolution on steroids."
The machine is a second-generation Multiplex Automated Genome Engineering (MAGE) machine, built with help from industry; the first one, which sits across the street not far from Church's corner office was a doctoral student's PhD thesis. Another thesis project sits just on the other side of the wall from new MAGE. Called the Polonator, this open-source genome-sequencing machine can read and write a billion base pairs at a time.
These two machines put Church's lab at the forefront of synthetic biology, a burgeoning new field that aims to make things Mother Nature never thought of, like high efficiency, non-polluting fuels, and viruses that can carry cancer drugs safely to a tumour.
With these machines, Prof Church is doing to synthetic biology what he's already done to personalised genomics: making it cheaper, faster and available to everyone.
"He's beginning to transform synthetic biology to a larger scale," says James J. Collins, a professor at Boston University and Prof Church's colleague at the Wyss Institute for Biologically Inspired Engineering at Harvard.
Prof Collins acknowledges that some people will have ethical concerns about scientists writing genetic codes. But, he said, the reality of synthetic biology is nowhere near as scary as the hype. No one is creating doomsday species or humanoids. They're just barely able to create a single new cell, says Prof Collins.
"I think we as a community have a need and a role and responsibility to educate the public as well as to take precautionary safeguards to make sure we're not introducing something that's problematic," says James Collins, who builds his cells with programmable kill switches, so they self-destruct before reproducing or mutating.
George Annas, chairman of the department of health law, bioethics and human rights at Boston University, agrees that it's too early to be troubled by the ethics of synthetic biology. "At this point, we don't know how synthetic biology will turn out or even if it will work at all," he says.
Of the possible fears about new life forms: "I think we're in the realm of science fiction right now," Mr Annas says.
Prof Church's optimism about the power of reading and writing DNA is contagious, but not irresistible.
"You need George's imagination and his vision if you're going to do make any progress at all. But you've got to be foolish to think you're going to make as much progress as he [imagines]," Mr Annas says.
American medical care is going broke as it is, he said. Adding more personalised treatment is only going to drive up the cost. And medicine may be able to add years to someone's life, but the quality of those years is unlikely to be good, warns Mr Annas.
Chad Nussbaum agrees.
"There's a statistical chance of being hit by a truck that's going to make it hard to live to 150 no matter how healthy you are," says Mr Nussbaum, co-director of the genome sequencing and analysis program at the Broad Institute of Harvard and MIT, a genetics research institute, where Church is an associate member.
Extreme aging isn't all about genetics, Mr Nussbaum says, it's basic engineering: parts just wear out over time. "It's wonderfully naive to think all we have to do is learn all the genetics and we'll live to be 150."
But Chad Nussbaum says he still admires Prof Church's vision and his "genius."
"It's a great thing to think big and try to do crazy things," says Mr Nussbaum. "If you don't try to do things that are impossible, we'll never accomplish the things that are nearly impossible."
September 25 2011 | Health | Comments Off
“Take Two” is an ongoing series about new business owners over 50.
After two decades as the co-owner of a landscape materials yard in northern California, 57-year-old Debbie Hannan didn’t just retire: She divorced her business partner. Though amicable, the split led to a drawn-out legal battle over the terms of a settlement. The divorce, begun in August 2007, took nearly a year to finally close.
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More than 1 million husband-and-wife teams run businesses together, according to the National Federation of Independent Business, and as with most businesses, the recession has put an economic strain on the ventures. At the same time, marriages remain rocky: In spite of data that suggests that married couples postponed divorce for economic reasons during the recession, the divorce rate stayed basically flat from 2005 to 2008, at about 17 per 1,000 married women. And while no one tracks the number of business-owning couples who split, or the number of divorces that also result in the dissolution of a family-owned business, when a business-owning couple splits, the complications are more than Judge Toler can handle.
The risks — and options — become especially stark as a divorcing couple gets older, experts say. As retirement grows closer, any retirement savings takes on added importance; that pot of money is considered marital property, and once the divorce is final, so is the distribution of assets. For business partners, the best way forward after a divorce depends on the nature of the venture and industry sector, as well as an ability to get along, if only at the workplace.
Gregg Herman, a family law attorney based in Milwaukee, says a common approach is to let one partner buy out the other. There are many ways to do that — all at once or over time, as a 50-50 split or in some other proportion — but good accountants can help value the business, which is critical, he says. “But what’s really important is to do this in a co-operative way, since the business is the goose that lays the golden egg and you don’t want to kill it.” That kind of transition becomes more difficult if the couple shared crucial roles in the business, such as day-to-day operations, or key points of contact with customers and suppliers — the “vital organs” of a company that can’t be so easily separated without hurting sales, he says. That’s especially worrisome now, when access to capital is still tight, which can make it harder to bridge a lag in sales with credit.
If that can’t be solved, the couple might consider dividing their business in two. Herman recently helped a pair of dentists who divorced after sharing an office for years. Since each had their own patients, they opted to split the practice down the middle, and continue to work together in the same office without any trouble.
Perhaps the riskiest approach is to continue running the business together even after the marriage ends. To keep the peace over the years to come, Otis Baskin, a consultant with the Chicago-based Family Business Consulting Group Inc., suggests setting up a board of directors to ensure key decisions are based on a business perspective, rather than a personal grudge. “You don’t need million-dollar directors,” he says. “You just need people with good business judgment who don’t have a dog in the race.” And, he notes, this works only if the couple has established a strong working relationship that’s separate from a soured personal relationship.
When all else fails, most lawyers will advise selling the business and splitting the assets — a risky proposition, since only about 30% of small businesses on the market sell, industry figures show. In the end, Hannan’s ex-husband bought out her share of the landscaping yard for more than $500,000 and continues to run the business today. She was satisfied with that arrangement, she says, but remained frustrated by the drawn-out legal battle that seemed driven more by lawyers than by Hannan and her ex. In response, Hannan and her 36-year-old daughter, Becky Shook-Wotzka, launched the first U.S. outlet of Fairway Divorce Solutions, a Canadian franchise that offers independently negotiated divorce settlements through mediators, rather than lawyers, with an eye to financial planning. Based in Sacramento, they now have four employees and are on pace to hit 120 clients and more than $100,000 in revenue by the end of the year.
September 20 2011 | Uncategorized | Comments Off
Portland, Oregon (CNN) — There was cake at one of the last birthdays Robert John Kreitner Jr. would have at the nursing home in Pennsylvania, but the guest of honor didn’t open his eyes to see it.
His wife propped him up at the end of the table. Their son Phil couldn’t help thinking the scene macabre.
Phil Kreitner’s father, a self-taught engineer, was firm-minded and hated to concede a point. Only once in the last 12 years of his life had Robert Kreitner admitted he had trouble remembering things. Now that his son is having memory problems of his own, he vows he’ll never end up in a nursing home like his father, but won’t deny what’s happening to his brain.
"It’s helpful to me that my father had Alzheimer’s, because it makes it much easier for me to accept the existence of it, the reality of it, and the personalization of it, and the finality of it," says Kreitner, 71, of Portland, Oregon.
Kreitner has mild cognitive impairment, an early stage of dementia that researchers consider a prime window of opportunity to try potential treatments to stop the progression of memory loss and cognitive decline. A person with mild cognitive impairment has a measurable memory problem, but no language or general thinking difficulties and is still able to function, says Dr. Joseph Quinn, researcher at Oregon Health & Sciences University and Portland VA Medical Center.
Not everyone who has mild cognitive impairment will worsen and develop Alzheimer’s disease, but there are certain signatures in the brain — plaques formed from a protein called beta-amyloid — that indicate a high likelihood of Alzheimer’s in patients who are already having memory problems. The plaques can be identified through MRI and PET scans.
"My memory is a jigsaw puzzle and it’s just been dumped out of the box," Kreitner says. "If I were to have to reconstruct that puzzle, I couldn’t do it."
Insulin may help treat Alzheimer’s disease
Kreitner believes it’s his duty to humankind join the effort to fight Alzheimer’s, the disease that ultimately took his father’s life. The condition affects about 5.4 million people in the United States and is projected to affect 16 million by 2050.
That’s why Kreitner is participating in a clinical trial that is investigating a drug in patients with mild cognitive impairment.
"My father was very militaristic, so I’ve had this stuff beat into my head my whole life: You have a responsibility to the collectivity, however the collectivity is defined. No man is an island," Kreitner says.
Getting patients into trials
Alzheimer’s researchers wish they found more people with Kreitner’s attitude, but in practice it’s hard to get patients into clinical trials for Alzheimer’s and dementia.
One problem is that some people want to join a trial only if they know for certain they will be trying an experimental drug. But scientifically valid medical studies are "double-blind," meaning neither the researchers nor the participants know who’s getting real medicine or and who’s getting a fake treatment called a placebo.
That is the strongest way to demonstrate that taking a drug works better than doing nothing. It also means that some participants will go through the entire trial process without trying the experimental treatment. Even some physicians try to get their patients in the drug treatment groups, but it goes against the standard method of trials for the experimenters to know who is getting what treatment, says William Thies, chief medical and scientific officer at the Alzheimer’s Association.
There are also practical issues with elderly patients’ participation, such as transportation and coordinating with caregivers. In the early stages of dementia, patients are still able to make decisions about joining trials. For later-stage patients, the caregiver has the burden of finding a study and taking the patient through the process.
It is especially challenging to recruit for mild cognitive impairment trials because people are more reluctant to come forward with mild problems, Quinn says. Also, some people don’t want to take on the potential risks of an experimental drug.
The Alzheimer’s Association’s TrialMatch website, which launched last year, aims to help people find appropriate trials that are convenient to them. The website lists more than 120 trials. So far, almost 12,000 people have completed profiles on the website; the Alzheimer’s Association is in the process of helping them find appropriate trials.
"Without trial volunteers, we actually won’t have the next new medication. If everybody actually understood how critical their participation might be in making a better future, probably we’d have many more people volunteering for trials," Thies says.
An experimental drug
Kreitner is taking part in a phase II drug trial sponsored by Bristol-Myers Squibb. Quinn is the principal investigator for the portion of the trial at Oregon Health & Sciences University, one of dozens of sites across the country.
The drug in question is a gamma secretase inhibitor, a class of drug that is supposed to interfere with the formation of plaques of beta-amyloid proteins in the brain.
The news around gamma secretase inhibitors hasn’t been good so far — at least in patients with Alzheimer’s. Last year, Eli Lilly announced it would halt the development of semagacestat, a gamma secretase inhibitor, because two ongoing long-term phase III studies indicated that it didn’t slow the progression of Alzheimer’s; researchers found an association with worsening of cognitive symptoms, too.
But Quinn and colleagues are hoping that a drug of the same type will work in patients with mild cognitive impairment, given that their brains have not built up as much pathology.
Documented risks of this drug include increased incidence of relatively benign skin cancer, gastrointestinal problems and brain swelling, he says.
So far, Kreitner says he has felt no side effects. Every two or three months, he gets brain scans and spinal taps so researchers can check for the biomarkers associated with dementia. He doesn’t mind the process, not even when they stick a needle into his spinal column.
"It’s my personal feeling that I’m making literally no sacrifice except to force myself to remember to take these capsules every day," he says.
Life in the shadow of Alzheimer’s
Kreitner has had myriad careers: naval officer, adjunct professor, massage therapist, environmentalist and demographer, among other things. He’s also a master at the rowing machine and logs 90 minutes a week. He snagged second place at the World Indoor Rowing Championship in Boston in his age group this year.
You can tell he has done a lot of thinking about society’s failings, and admits he has always felt a general dissatisfaction with the world and himself. He’s always been someone who self-assesses, striving to stay in good shape; these days, that includes monitoring his own mental functioning.
His wife, Sherril Gelmon, professor of public health at Portland State University, noticed Kreitner’s forgetfulness about two years ago. Kreitner himself became aware of small lapses; he would find himself in a room and forget his purpose for being there, for example. The two began to get edgier with each other, which is uncommon in their 13 years of marriage.
She went with Kreitner to the Layton Aging and Alzheimer’s Disease Center at Oregon Health & Sciences University. The couple wanted to know if Kreitner would be eligible for any treatments, and learned about the Bristol-Myers Squibb trial. Quinn told them Kreitner could be eligible, and after an official screening, Kreitner joined the study.
After Gelmon recounts this history, Kreitner smiles and says that he wouldn’t have been able to give all those details himself.
"I’m at the stage where everything that Sherril just said rings a bell," he says. "If you were to ask me, ‘What’s happened in the past couple of years relating to this?’ I couldn’t have given you 10% of that."
Members of both sides of Gelmon’s family have had dementia. Her father died in 2009 and her mother is in the advanced stages, so she’s also familiar with the realities of the condition. She monitors her own mental state, but doesn’t wake up afraid of it. She and Kreitner talk regularly about how they might need to adjust their lifestyle, if at all, if Phil’s condition were to worsen.
"It’s hard when you’re not as good at what you’re doing as you used to be. I wouldn’t say we’re depressed; I would say frustrated, upset. Since both of us have watched parents go through it, we’ve already done a certain level of coping," Gelmon says.
Toward the end
Before his death, Kreitner’s current goal is to write a book — and if he can’t get there, a 1,500-word article — about how he views the world. He says it’s an "an adjuration to my fellow humans to start thinking like a species; my hypothesis is that we’re on an individual, class, ethnic, national, racial self-destruction trip, and we’re taking the planet down in the struggle."
Remembering how his mother suffered trying to take care of his father at home, and visiting him in the nursing home, Kreitner doesn’t want to burden Gelmon in the same way, nor does he see himself in a nursing home.
But if he gets to a point that he deems too far along, he’s resolved, even though it is not legal, to find a way to "check out" of life.
"I will give proper notice. It will not be specific but it will be implicit that I feel that the time is now or never. I will bear complete responsibility for any actions that result in my death. I will not make a mess," he says.
Gelmon shows no anguish when her husband speaks this way; she is calm and matter-of-fact when she says: "My expectation is that if and when we get to that point, we will have discussed it at length and it will not be a surprise. It will still make me very sad, but if we’re communicating well and early, then it should not come as a surprise and it should be something I’m as informed about as he’s willing to inform me."
In the meantime, Kreitner continues to follow the regimen of gray capsules prescribed by the clinical trial. He relies on notes, a lot of them, to remember to keep appointments, and often waits for memories to make their way up through the mud in his mind.
"We’ve got way more human beings on this planet than it could sustain, even if we were sane. Who the hell am I? When my effectiveness is gone, I’m gone," he says. "Lead, follow, or get out of the way."
September 17 2011 | Health | Comments Off
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September 05 2011 | Alternative Health | Comments Off
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