Trends in biotechnology, Nr.18 1/00, Charles R. Cantor, page 6
Biotechnology in the 21st century
Although the future is unpredictable, it is highly likely that biotechnology will play a much more visible and significant role in the 21st century than it did in the 20th century. The number and kinds of drugs provided by biotechnology will expand markedly and biotechnology will stand at the center of the oncoming revolution in bioinformatics.
Attempts to predict the future are certain to contain serious errors of omission.
However, as long as the basic laws of physics remain intact, it is relatively safe to
envisage certain short-term trends. A wise soul, in 1900, might have predicted the current
explosion of the use of cellular telephones, but who could have predicted the power of
today's laptop computers? In this article, I will separate notions that I consider to be
relatively safe bets from those that strike me as plausible but totally speculative.
Some of the techniques that fueled the development of biotechnology in the 20th century
will continue to be important in the foreseeable future. These have brought us several
protein-based therapeutics produced by recombinant-DNA methods and more are likely to
follow. Combinatorial chemistry and automated tools for high-throughput screening have
improved the prospects for finding novel drugs; it is likely that these methods will be
further developed and more-generally applied.
The human genome sequence will appear at the beginning of the 21st century and this will
provide a plethora of drug targets. Intelligent use of the sequence is encompassed in a
newly named field, functional genomics, which will narrow the choice of therapeutic
targets to a practical range. There will also be a vast acceleration in the rate of
protein-structure determination, by a method known as structural genomics1.
This will lead to the knowledge of all protein folds, and so structural modeling by
homology will provide an instant view of the likely structure of any protein sequence. The
availability of such encyclopedic structural information will greatly facilitate rational
drug design because it will enable screening not just for good ligands but also for
ligands without unwanted targets.
Personalized medicine
It seems certain that a major focus of biotechnology over the next two decades will be
on the area of pharmacogenetics and pharmacogenomics, or 'individualized medicine'. The
notion is simple. Normal genetic variations in genes responsible for drug metabolism or
receptors of various ligands become medically significant when drugs are applied. By
determining the particular variations carried by each individual, a more rational choice
can be made of particular drugs to be used and the levels to be administered. Even though
the task of screening for potentially thousands of variations in the global population
seems daunting with current technology, industry is rushing to fulfill this large, unmet
need.
Various chip-based2,3 or mass-spectrometric (http:// www.sequenom.com)
approaches are likely to be scaleable and ready when needed. This will produce a win-win
situation for all the participants: patients will receive better care; pharmaceutical
companies will see the costs of clinical trials reduced; the success rates of clinical
trials will be increased because the trial population can be segmented intelligently;
diagnostic companies will vastly increase their business; and medicalcare insurers will
see lower medical-care costs because they will not have to pay for medication that is
either ineffective or has adverse side effects.
Keeping up appearances
The concept of medication will expand during the 21st century and this will increase
the types of target and product that industry will focus on. Already, we can see a trend
towards a concern with wellbeing rather than sickness. These factors will become much more
pervasive and will include the control of weight and body fat, the reduction of stress and
compensation for, or control of, unwanted environmental effects, even jet lag.
It is easy to think of attractive commercial targets. A drug enabling the rapid removal of
all blood alcohol on demand would please many. Viagra is surely just the beginning of
drugs that address lifestyle, rather than conventional views of illness. There is hardly a
soul who is not concerned with aging. The young would like to speed it up; the old would
like to retard it or, at least, hide its effects. This poorly understood area of biology
may take on major prominence. What some have called 'vanity genetics' will thrive and we
will see therapy for wrinkles, adipose deposits, male-pattern baldness, bad breath and
perhaps even monotony or decreased pheromone output.
Nutraceuticals
The notion of what a drug is and how it is delivered will change. Genetically
engineered plants and other foodstuffs, termed nutraceuticals, will become the norm.
Already, a canola oil has been developed with vastly increased levels of beneficial
antioxidants4, and this may be just the tip of the iceberg.
As the genomics tidal wave expands to plants and animals of commercial importance, it will
become much easier to use the tools of genetic engineering to create the desired
modifications. Consumer resistance to such notions will evaporate as consumers become
educated about the benefits and as they begin to taste products with improved flavors.
Disadvantages of biotechnology
As Wally Lamb so poignantly said, 'I know this much is true'5. What follows
is much more uncertain. Biotechnology can do good, but it also has the potential to do
great harm. In the wrong hands, genetic engineering could be used to create an
increasingly complex set of pathogens targeted at humans, Plants or animals. The popular
press is full of such stories and Richard Preston's The Cobra Event is particularly
compelling6.
Although we cannot predict the exact course that biotechnology will take, we can predict
that some people will try to use any future advances malevolently. Thus, an unceasing
effort has been mandated to develop defensive tools or preventative measures against the
use of biotechnology in the making of weapons. In the USA, this issue is already the
target of a major research program, 'Unconventional Pathogen Countermeasures', which is
funded by the Defense Advanced Research Projects Agency (http://www.darpa.mil/dso/rd.upc).
Directed evolution
Another area that is destined to play a major role in 21st-century biotechnology is
directed evolution. I discuss it here in the 'blue sky' category because I feel that it
has an almost limitless perspective. Macromolecular combinatorics (e.g. shuffling7,
RNA aptamers8 or mRNA-protein fusions9) when combined with either
high-throughput screening methods Or, better yet, intelligent selection schemes, will
allow proteins and nucleic acids with a vast array of novel properties to be produced.
Whole organisms can be subjected to similar rapid evolution. Where this will ultimately
take us might surpass our imagination. It also raises a number of important ethical and
legal issues. The more I reflect on it, the more I am forced to conclude that the next
step in humankind's evolution is our acquisition of the power to control the evolution of
our own species and all others on this planet. I can only hope we use this power wisely.
If it is not impossible, for some reason I cannot fathom, we should be able to use
directed evolution to create plants that walk, animals that can carry out photosynthesis
and other unlikely chimeras.
Computer communication
The area of computational biology or bioinformatics is already an active component of
biotechnology, as reflected by the successes of companies such as Incyte and LION. Its
placement in the 'blue sky' category occurs because the upside is almost too vast to
contemplate.
The power of available computation continues to expand exponentially. The next revolution,
a dramatic increase in user-friendliness, is just beginning. Soon, we will use sound
rather than fingertips for most computer communication. Thus, we will be able to maintain
contact with the network whatever else we may be doing. Is it only a matter of time before
the barrier between our brain and the computer is bridged directly?
Although the detailed path this 'will take is not predictable, I would be astounded if, by
the end of the 21st century, the distinction between organisms and computers was not
blurred. This will require some kind of interface whether it be electronic or chemical,
but it will happen, and it will change our way of life more dramatically than the current
computers have changed life in the 20th century.
Developing improved interfaces between organisms and computers may come about by a
generalization of the DNA and protein chips already in production. Such chips, although
capable of parallel processing, are actually rather unintelligent devices because they
require cumbersome readout. Integration of the readout directly with computer-readable
electronics has been achieved, but apparently not with the sensitivity or reliability
needed for general use. This will come, and the readout might be coupled through the
electronic, mechanical or chemical properties of the biological targets themselves,
whether these are molecules, cells or organisms. Nathan Lewis et al.10 have
described a remarkably effective chemical nose, based on very simple hardware analysed by
very sophisticated software.
As we learn more about our own sensory systems, the principles used by nature to design
these, sharpened by eons of evolution, may be used to improve the specificity of such
communication. As our ability to speed up evolution matures, we should be able to go
beyond, in human-computer communication, anything we can remotely conceive of at present.
Suffice to say for certain that, in 2099, biotechnologists will not be reading hard-copy
journals as some of the readers of this article have just done.