Genetic medicine

A new technique to help cure mitochondrial diseases should be permitted by the law

In September Britain’s Human Fertilisation and Embryology Authority launched a public consultation on what sounds like a crackpot idea: to create children with three genetic parents. Yet this could be a way to eliminate a set of rare but nasty diseases caused by problems with pieces of cellular machinery called mitochondria. According to research published this week (see article), the basic technique of substituting problem-free mitochondria has now been tested in a laboratory and the researchers seem confident that, given the green light, they could bring a healthy child into the world.

Most of a child’s genes would come from the couple it would learn to call mum and dad. A tiny fraction of the DNA, however, would come from a female donor who would provide part of the egg from which the child grew. At present the law in Britain, like that in most other places, prohibits any genetic modification of embryos. It should be changed.

An in-gene-ious idea

Mitochondria turn the energy in sugar into a form a cell can use, so if they go wrong the consequences are dire. The brain, the nerves and the muscles, all huge consumers of energy, are the organs that suffer most. Mitochondria are also special, because they contain their own genes, completely separate from those in the cell nucleus, which are thus transmitted from mother to child in the egg.

Some mitochondrial disease is caused by mutations in these genes and is thus also inherited solely from the mother. Such diseases affect one person in 5,000 during his or her lifetime. But the separateness of mitochondrial genes means that by moving the nucleus from an afflicted egg into a healthy one, the mutated, disease-causing genes can be left behind. In effect, the nucleus would receive a mitochondrial transplant.

This incorporation of the DNA of two women might be seen by the nervous as a step down the slippery slope towards the genetic engineering of people. But that is unlikely.

The principal worry about genetic engineering is that it will lead to “designer babies” with customised DNA. But mitochondrial transplants involve no tinkering with the DNA itself. Though on a microscopic scale, the process is quite like a heart, liver or kidney transplant, with the caveat that the transplant will be passed on to the recipient’s children, if she is female. Any organ transplant introduces new genes into the body. Mitochondrial genes are ubiquitous, it is true, but this difference is one of degree, not kind.

Another reason not to worry is that the mitochondria carry only 37 genes, compared with about 20,000 in the cell nucleus, and these genes are exclusively concerned with energy metabolism. Pushy parents will not be picking mitochondrial donors on the basis of looks, personality or intelligence.

Non-biological objections are sometimes raised as well. Some worry, for instance, that a person with three genetic parents might suffer an identity crisis. But that seems less likely than in the case of people conceived by in vitro fertilisation using sperm donated by strangers who have contributed half of their offspring’s genes, not a paltry three dozen. And for that reason mitochondrial donors are even less likely than sperm donors to want to be involved with bringing up children in whom they have but a fractional genetic interest.

But is the process safe? Doing the experiment is the only way of finding out. It should be preceded by a lot of tests in Petri dishes and laboratory animals. But in the end, you just have to try it and see.

First published as a Leader in The Economist. Also available in audio hereThis editorial also had an accompanying article with it.

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Stay sharper for longer

With the advent of old age, incidences of misplaced keys and embarrassing moments of forgotten names occur more often. As you inch closer to becoming a senior citizen, certain cognitive skills start to decline and others improve. But you can still find some 70-year-olds who can beat those at 50 on a memory test. How do they retain such abilities and how can that knowledge be used to our advantage? Results emerging from unique studies show that there might indeed be ways to slow down the inevitable slide.

Stay sharper for longereu:sci, Autumn 2012 issue.

A list of main references here. Free image from here.

Stay sharper for longer

Fighting cognitive decline can be simple but needs an early start 

With the advent of old age, incidences of misplaced keys and embarrassing moments of forgotten names occur more often. As you inch closer to becoming a senior citizen, certain cognitive skills start to decline and others improve. But you can still find some 70-year-olds who can beat those at 50 on a memory test. How do they retain such abilities and how can that knowledge be used to our advantage?

Results emerging from a unique study titled “Midlife in the United States” (or Midus) have shown that there might indeed be ways to slow down the inevitable slide. Margie Lachman, psychologist at Brandeis University and principal investigator for Midus, found education to be the most essential element of mental fitness. For middle-agers, a university degree obtained in younger days can slow the brain’s aging process by up to a decade.

Intelligence can be viewed as a composite of cognitive skills. Those skills that decline with age are categorised as fluid intelligence (pattern recognition, working memory and abstract thinking), while those that improve are called crystallised intelligence (verbal ability, inductive reasoning and judgment). Critically, it is fluid intelligence in the younger generation that gives them an advantage over the older.

Midus researchers found a robust correlation between senior citizens with the strongest cognitive skills and those who exercised frequently, engaged in social activities, coped well with stress and felt more in control of their lives. To probe into ways of delaying the decline in fluid intelligence, Dr Lachman and colleagues reviewed results from Midus studies. They were surprised to find that even into middle age and beyond, people could improve their fluid intelligence enough to make up for a lack of formal education.

To understand the factors that enabled this cognitive leap, Dr Lachman tested thousands of Midus participants for memory, calculation and reasoning. It involved reciting 15 common words and then recalling them after a 90-second delay, a check for verbal memory; counting as many digits as possible backwards from 100 in 30 seconds to assess processing speed; and, for numerical reasoning, completing a series of numbers, for instance, determining the next number in the series 1, 4, 9, 16.

Results from this study, that were published in the American Journal of Geriatric Psychiatry, indicate that being regularly exercising the brain with activities such as reading, writing, attending lectures or completing word puzzles help maintain fluid intelligence to a similar extent as younger people (<40 years of age). Such simple habits seemed to even compensate for the intellectual stimulation offered by formal university education.

A closely related study titled “Whitehall II”, conducted in Britain, indicates that cognitive decline begins at 45 years, which is much earlier than previously thought. The study, which spanned a period of 24 years and involved thousands of civil servants, has brought into question the widely accepted results of two smaller American studies which put the onset of cognitive decline at 55 years. The Whitehall II study began in 1985, and recorded responses from 7500 men and women. Archana Singh-Manoux, lead author of the study and research director at the French National Institute of Health and Medical Research in Paris, also found that health practices that are good for our heart are good for our brain, too. A lifestyle that reduces the risk of cardiovascular diseases, such as regular exercise and balanced diet, seems to also slow down cognitive decline. Well-directed clinical practices and public health policies may enable better cardiovascular care and hope to preserve our fluid intelligence.

Edinburgh University’s Centre for Cognitive Ageing and Cognitive Epidemiology has also published a number of studies about factors that can mitigate cognitive decline. One such study published in Psychology and Aging in June this year found that those who were more open to new experiences were more likely to preserve their fluid intelligence.

As the western economies face an increased aging population and signs of cognitive decline appear at an earlier age, continued development from such studies could aid older generations to stay at their peak performance for longer. At an individual level though, starting to incorporate simple habits today could turn misplaced keys and forgotten names into distant memories.

This article was first published in the Autumn 2012 issue of eu:sci, Edinburgh University’s science magazine.

References:

  1. Lachman et al., American Journal of Geriatric Psychiatry, 2010
  2. Whitehall II study
  3. Hogan et al., Psychology and Aging, 2012

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